TpUB05, a Homologue of the Immunodominant Plasmodium falciparum Protein UB05, Is a Marker of Protective Immune Responses in Cattle Experimentally Vaccinated against East Coast Fever.

PubMed

Dinga, Jerome Nyhalah; Wamalwa, Mark; Njimoh, Dieudonné Lemuh; Njahira, Moses N; Djikeng, Appolinaire; Skilton, Rob; Titanji, Vincent Pryde Kehdingha; Pellé, Roger

2015-01-01

East Coast fever, a devastating disease of cattle, can be controlled partially by vaccination with live T. parva sporozoites. The antigens responsible for conferring immunity are not fully characterized. Recently it was shown that the P. falciparum immunodominant protein UB05 is highly conserved in T. parva, the causative agent of East Coast fever. The aim of the present investigation was to determine the role of the homologue TpUB05 in protective immunity to East Coast fever. The cloning, sequencing and expression of TpUB05 were done according to standard protocols. Bioinformatics analysis of TpUB05 gene was carried out using algorithms found in the public domain. Polyclonal antiserum against recombinant TpUB05 were raised in rabbits and used for further analysis by Western blotting, ELISA, immunolocalization and in vitro infection neutralization assay. The ability of recombinant TpUB05 (r-TpUB05) to stimulate bovine PBMCs ex-vivo to produce IFN-γ or to proliferate was tested using ELISpot and [3H]-thymidine incorporation assays, respectively. All the 20 cattle immunised by the infection and treatment method (ITM) developed significantly higher levels of TpUB05 specific antibodies (p<0.0001) compared to the non-vaccinated ones. Similarly, r-TpUB05 highly stimulated bovine PMBCs from 8/12 (67%) of ITM-immunized cattle tested to produce IFN-γ and proliferate (p< 0.029) as compared to the 04 naїve cattle included as controls. Polyclonal TpUB05 antiserum raised against r-TpUB05 also marginally inhibited infection (p < 0.046) of bovine PBMCs by T. parva sporozoites. In further experiments RT-PCR showed that the TpUB05 gene is expressed by the parasite. This was confirmed by immunolocalization studies which revealed TpUB05 expression by schizonts and piroplasms. Bioinformatics analysis also revealed that this antigen possesses two transmembrane domains, a N-glycosylation site and several O-glycosylation sites. It was concluded that TpUB05 is a potential marker of protective immunity in ECF worth investigating further.

Ubiquitin chain specificities of E6AP E3 ligase and its HECT domain.

PubMed

Kobayashi, Fuminori; Nishiuchi, Takumi; Takaki, Kento; Konno, Hiroki

2018-02-05

Ubiquitination of target proteins is accomplished by isopeptide bond formation between the carboxy group of the C-terminal glycine (Gly) residue of ubiquitin (Ub) and the ɛ-amino group of lysine (Lys) on the target proteins. The formation of an isopeptide bond between Ubs that gives rise to a poly-Ub chain on the target proteins and the types of poly-Ub chains formed depend on which of the seven Lys residues or N-terminal methionine (Met) residue on Ub is used for chain elongation. To understand the linkage specificity mechanism of Ub chains on E3, the previous study established an assay to monitor the formation of a free diubiquitin chain (Ub 2 chain synthesis assay) by HECT type E3 ligase. In this study, we investigated Ub 2 chain specificity using E6AP HECT domain. We here demonstrate the importance of the N-terminal domain of full length E6AP for Ub 2 chain specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung diseases*

PubMed Central

Yamada, Tsutomu; Kawabata, Yoshinori

2015-01-01

Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs). Histological markers of pneumocyte injury and inflammation include pneumocyte necrosis, erosion, hyaline membrane and fibrin exudation with subsequent intraluminal granulation tissue formation. We found that intracytoplasmic inclusions in pneumocytes are ubiquitin-positive (Ub+) and that the number of Ub+ pneumocytes shows positive correlation with the extent of diffuse alveolar damage (DAD). To determine the role of Ub+ pneumocytes and inclusions in IPs, we studied their relationship with pathological and clinical features of DAD, usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including airspace enlargement with fibrosis (AEF). We analysed Ub+ pneumocytes, inclusions, erosions and intraluminal granulation tissue in relation to pneumocyte injury. The numbers of immunohistochemically identified Ub+ inclusions in each IP were higher than the number of inclusions detected by light microscopy. The inclusions detected by Ub+ immunostaining were identical to the inclusions observed by light microscopy. UIP and DAD had many Ub+ inclusions, while OP and AEF had fewer Ub+ inclusions. These results suggest that the extent of Ub+ inclusions reflects the severity of pneumocyte injury among IPs. Thus, Ub+ inclusions are a histological marker of pneumocyte injury that may be helpful in determining the severity and prognosis of IPs. PMID:25123224

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

PubMed

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

2017-02-16

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

77 FR 68834 - Proposed Exemptions From Certain Prohibited Transaction Restrictions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

...This document contains notices of pendency before the Department of Labor (the Department) of proposed exemptions from certain of the prohibited transaction restrictions of the Employee Retirement Income Security Act of 1974 (ERISA or the Act) and/or the Internal Revenue Code of 1986 (the Code). This notice includes the following proposed exemptions: D-11610, UBS Financial Services, Inc. D- 11666, Central Pacific Bank 401(k) Retirement and Savings Plan (the Plan); D-11672, Studley, Inc. Section 401(k) Plan Profit Sharing Plan (the Plan); and D-11724, EquiLend Holdings LLC (EquiLend).

Differential T-cell responses to a chimeric Plasmodium falciparum antigen; UB05-09, correlates with acquired immunity to malaria.

PubMed

Dinga, J N; Njimoh, D L; Kiawa, B; Djikeng, A; Nyasa, R B; Nkuo-Akenji, T; Pellé, R; Titanji, V P K

2016-05-01

The development of a sterilizing and cost-effective vaccine against malaria remains a major problem despite recent advances. In this study, it is demonstrated that two antigens of P. falciparum UB05, UB09 and their chimera UB05-09 can serve as protective immunity markers by eliciting higher T-cell responses in malaria semi-immune subjects (SIS) than in frequently sick subjects (FSS) and could be used to distinguish these two groups. UB05, UB09 and UB05-09 were cloned, expressed in E. coli, purified and used to stimulate PBMCs isolated from 63 subjects in a malaria endemic area, for IFN-γ production, which was measured by the ELISpot assay. The polymorphism of UB09 gene in the malaria infected population was also studied by PCR/sequencing of the gene in P. falciparum field isolates. All three antigens were preferentially recognized by PBMCs from SIS. IFN-γ production induced by these antigens correlated with the absence of fever and parasitaemia. UB09 was shown to be relatively well-conserved in nature. It is concluded that UB05, UB09 and the chimera UB05-09 posses T-cell epitopes that are associated with protection against malaria and could thus be used to distinguish SIS from FSS eventhough acute infection with malaria has been shown to reduce cytokine production in some studies. Further investigations of these antigens as potential diagnostic and/or vaccine candidates for malaria are indicated. © 2016 John Wiley & Sons Ltd.

Sequential Poly-ubiquitylation by Specialized Conjugating Enzymes Expands the Versatility of a Quality Control Ubiquitin Ligase.

PubMed

Weber, Annika; Cohen, Itamar; Popp, Oliver; Dittmar, Gunnar; Reiss, Yuval; Sommer, Thomas; Ravid, Tommer; Jarosch, Ernst

2016-09-01

The Doa10 quality control ubiquitin (Ub) ligase labels proteins with uniform lysine 48-linked poly-Ub (K48-pUB) chains for proteasomal degradation. Processing of Doa10 substrates requires the activity of two Ub conjugating enzymes. Here we show that the non-canonical conjugating enzyme Ubc6 attaches single Ub molecules not only to lysines but also to hydroxylated amino acids. These Ub moieties serve as primers for subsequent poly-ubiquitylation by Ubc7. We propose that the evolutionary conserved propensity of Ubc6 to mount Ub on diverse amino acids augments the number of ubiquitylation sites within a substrate and thereby increases the target range of Doa10. Our work provides new insights on how the consecutive activity of two specialized conjugating enzymes facilitates the attachment of poly-Ub to very heterogeneous client molecules. Such stepwise ubiquitylation reactions most likely represent a more general cellular phenomenon that extends the versatility yet sustains the specificity of the Ub conjugation system. Copyright © 2016 Elsevier Inc. All rights reserved.

Ubiquitin--conserved protein or selfish gene?

PubMed

Catic, André; Ploegh, Hidde L

2005-11-01

The posttranslational modifier ubiquitin is encoded by a multigene family containing three primary members, which yield the precursor protein polyubiquitin and two ubiquitin moieties, Ub(L40) and Ub(S27), that are fused to the ribosomal proteins L40 and S27, respectively. The gene encoding polyubiquitin is highly conserved and, until now, those encoding Ub(L40) and Ub(S27) have been generally considered to be equally invariant. The evolution of the ribosomal ubiquitin moieties is, however, proving to be more dynamic. It seems that the genes encoding Ub(L40) and Ub(S27) are actively maintained by homologous recombination with the invariant polyubiquitin locus. Failure to recombine leads to deterioration of the sequence of the ribosomal ubiquitin moieties in several phyla, although this deterioration is evidently constrained by the structural requirements of the ubiquitin fold. Only a few amino acids in ubiquitin are vital for its function, and we propose that conservation of all three ubiquitin genes is driven not only by functional properties of the ubiquitin protein, but also by the propensity of the polyubiquitin locus to act as a 'selfish gene'.

SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme.

PubMed

Békés, Miklós; Rut, Wioletta; Kasperkiewicz, Paulina; Mulder, Monique P C; Ovaa, Huib; Drag, Marcin; Lima, Christopher D; Huang, Tony T

2015-06-01

Ubiquitin (Ub) and the Ub-like (Ubl) modifier interferon-stimulated gene 15 (ISG15) participate in the host defence of viral infections. Viruses, including the severe acute respiratory syndrome human coronavirus (SARS hCoV), have co-opted Ub-ISG15 conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub-ISG15-conjugated host proteins. In the present study, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle East respiratory syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that, similar to SARS PLpro, MERS PLpro is both a deubiquitinating (DUB) and a deISGylating enzyme. Further analysis of the intrinsic DUB activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, whereas SARS PLpro prefers to cleave Lys48-linked polyUb chains. Secondly, MERS PLpro cleaves polyUb chains in a 'mono-distributive' manner (one Ub at a time) and SARS PLpro prefers to cleave Lys48-linked polyUb chains by sensing a di-Ub moiety as a minimal recognition element using a 'di-distributive' cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP (Ub-specific protease)-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help to identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses.

Structure of an E3:E2~Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases

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

Pruneda, Jonathan N.; Littlefield, Peter J.; Soss, Sarah E.

2012-09-28

Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanismby which this class of enzymes facilitates Ub transfer remains enigmatic. Here, we present a structural model for a RING/U-box E3:E2~Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2~Ub ensembles toward closed conformations with enhanced reactivity for substrate lysines. We identify a key hydrogen bond between a highly conserved E3 side chain and an E2 backbone carbonyl, observed in all structures of active RING/ U-Box E3/E2 pairs, as the linchpin for allosteric activation of E2~Ub. The conformationalmore » biasing mechanism is generalizable across diverse E2s and RING/U-box E3s, but is not shared by HECT-type E3s. The results provide a structural model for a RING/ U-box E3:E2~Ub ligase complex and identify the long sought-after source of allostery for RING/UBox activation of E2~Ub conjugates.« less

Saturation scanning of ubiquitin variants reveals a common hot spot for binding to USP2 and USP21.

PubMed

Leung, Isabel; Dekel, Ayelet; Shifman, Julia M; Sidhu, Sachdev S

2016-08-02

A detailed understanding of the molecular mechanisms whereby ubiquitin (Ub) recognizes enzymes in the Ub proteasome system is crucial for understanding the biological function of Ub. Many structures of Ub complexes have been solved and, in most cases, reveal a large structural epitope on a common face of the Ub molecule. However, owing to the generally weak nature of these interactions, it has been difficult to map in detail the functional contributions of individual Ub side chains to affinity and specificity. Here we took advantage of Ub variants (Ubvs) that bind tightly to particular Ub-specific proteases (USPs) and used phage display and saturation scanning mutagenesis to comprehensively map functional epitopes within the structural epitopes. We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or "hot spot," consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences. The Ubv core functional epitope contacts residues that are conserved in the human USP family, and thus it is likely important for the interactions of Ub across many family members.

78 FR 12372 - UBS AG, et al.; Notice of Application and Temporary Order

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

... financial planning and wealth management consulting, asset-based and advisory services and transaction-based... Limited (``ESC GP''); UBS Financial Services Inc. (``UBSFS''); UBS Alternative and Quantitative... Switzerland, is a Swiss-based global financial services firm. UBS AG and its subsidiaries provide global...

A comparison of RUL ultrabrief pulse (0.3 ms) ECT and standard RUL ECT.

PubMed

Loo, Colleen K; Sainsbury, Kirby; Sheehan, Patrick; Lyndon, Bill

2008-11-01

An important goal in electroconvulsive therapy (ECT) research is to minimize associated cognitive side-effects while maintaining its high efficacy. This study explored the use of a novel approach, right unilateral (RUL) ECT with an ultrabrief pulsewidth (0.3 ms) (RUL-UB), in comparison with standard RUL ECT. Seventy-four depressed in-patients received RUL-UB ECT at six times seizure threshold, and 22 patients received standard RUL ECT (1.0 ms pulsewidth) at five times seizure threshold. Formal, prospective evaluations of mood and cognitive functioning over the treatment course were done by a rater blinded to treatment condition. Efficacy was maintained using the ultrabrief pulsewidth, with equivalent numbers of responders and remitters to the standard RUL ECT group, although the speed of response was slower. Cognitive outcomes were superior in the RUL-UB ECT group, particularly in the retention of verbal and visual information, as well as in retrograde autobiographical memory.

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

Pham, Grace H.; Rana, Ambar S. J. B.; Korkmaz, E. Nihal

Ubiquitin (Ub) chains regulate a wide range of biological processes, and Ub chain connectivity is a critical determinant of the many regulatory roles that this post-translational modification plays in cells. To understand how distinct Ub chains orchestrate different biochemical events, we and other investigators have developed enzymatic and non-enzymatic methods to synthesize Ub chains of well-defined length and connectivity. A number of chemical approaches have been used to generate Ub oligomers connected by non-native linkages; however, few studies have examined the extent to which non-native linkages recapitulate the structural and functional properties associated with native isopeptide bonds. Here, we comparemore » the structure and function of Ub dimers bearing native and non-native linkages. Using small-angle X-ray scattering (SAXS) analysis, we show that scattering profiles for the two types of dimers are similar. Moreover, using an experimental structural library and atomistic simulations to fit the experimental SAXS profiles, we find that the two types of Ub dimers can be matched to analogous structures. An important application of non-native Ub oligomers is to probe the activity and selectivity of deubiquitinases. Through steady-state kinetic analyses, we demonstrate that different families of deubiquitinases hydrolyze native and non-native isopeptide linkages with comparable efficiency and selectivity. Considering the significant challenges associated with building topologically diverse native Ub chains, our results illustrate that chains harboring non-native linkages can serve as surrogate substrates for explorations of Ub function.« less

Enhanced acquired antibodies to a chimeric Plasmodium falciparum antigen; UB05-09 is associated with protective immunity against malaria.

PubMed

Dinga, J N; Gamua, S D; Titanji, V P K

2017-08-01

It has been shown that covalently linking two antigens could enhance the immunogenicity of the chimeric construct. To prioritize such a chimera for malaria vaccine development, it is necessary to demonstrate that naturally acquired antibodies against the chimera are associated with protection from malaria. Here, we probe the ability of a chimeric construct of UB05 and UB09 antigens (UB05-09) to better differentiate between acquired immune protection and susceptibility to malaria. In a cross-sectional study, recombinant UB05-09 chimera and the constituent antigens were used to probe for specific antibodies in the plasma from children and adults resident in a malaria-endemic zone, using the enzyme-linked immunosorbent assay (ELISA). Anti-UB05-09 antibody levels doubled that of its constituent antigens, UB09 and UB05, and this correlated with protection against malaria. The presence of enhanced UB05-09-specific antibody correlated with the absence of fever and parasitaemia, which are the main symptoms of malaria infection. The chimera is more effective in detecting and distinguishing acquired protective immunity against malaria than any of its constituents taken alone. Online B-cell epitope prediction tools confirmed the presence of B-cell epitopes in the study antigens. UB05-09 chimera is a marker of protective immunity against malaria that needs to be studied further. © 2017 John Wiley & Sons Ltd.

76 FR 20045 - The Ubs Group, a Division Of Ubs Ag, Also Known as Ubs Financial Services, Inc. and/or Ubs-Glb...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

... Known as Brinson Partners, Inc., Corporate Center Division; Group Technology Infrastructure Services... Division, Group Technology Infrastructure Services, Distributed Systems and Storage Group, Chicago... Infrastructure Services, Distributed Systems and Storage Group have their wages reported under a separate...

77 FR 37016 - Applications for New Awards: Upward Bound Math and Science Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... DEPARTMENT OF EDUCATION Applications for New Awards: Upward Bound Math and Science Program AGENCY... Bound Math and Science Program. Notice inviting applications for new awards for fiscal year (FY) 2012.... There are three types of grants under the UB Program: regular UB grants, Veterans UB grants, and UB Math...

Atypical binding of the Swa2p UBA domain to ubiquitin.

PubMed

Matta-Camacho, Edna; Kozlov, Guennadi; Trempe, Jean-François; Gehring, Kalle

2009-02-20

Swa2p is an auxilin-like yeast protein that is involved in vesicular transport and required for uncoating of clathrin-coated vesicles. Swa2p contains a ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin (Ub)-mediated processes. We have determined a structural model of the Swa2p UBA domain in complex with Ub using NMR spectroscopy and molecular docking. Ub recognition occurs predominantly through an atypical interaction in which UBA helix alpha1 and the N-terminal part of helix alpha2 bind to Ub. Mutation of Ala148, a key residue in helix alpha1, to polar residues greatly reduced the affinity of the UBA domain for Ub and revealed a second low-affinity Ub-binding site located on the surface formed by helices alpha1 and alpha3. Surface plasmon resonance showed that the Swa2p UBA domain binds K48- and K63-linked di-Ub in a non-linkage-specific manner. These results reveal convergent evolution of a Ub-binding site on helix alpha1 of UBA domains involved in membrane protein trafficking.

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

PubMed Central

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

2017-01-01

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

Protein misfolding specifies recruitment to cytoplasmic inclusion bodies.

PubMed

Bersuker, Kirill; Brandeis, Michael; Kopito, Ron R

2016-04-25

Inclusion bodies (IBs) containing aggregated disease-associated proteins and polyubiquitin (poly-Ub) conjugates are universal histopathological features of neurodegenerative diseases. Ub has been proposed to target proteins to IBs for degradation via autophagy, but the mechanisms that govern recruitment of ubiquitylated proteins to IBs are not well understood. In this paper, we use conditionally destabilized reporters that undergo misfolding and ubiquitylation upon removal of a stabilizing ligand to examine the role of Ub conjugation in targeting proteins to IBs that are composed of an N-terminal fragment of mutant huntingtin, the causative protein of Huntington's disease. We show that reporters are excluded from IBs in the presence of the stabilizing ligand but are recruited to IBs after ligand washout. However, we find that Ub conjugation is not necessary to target reporters to IBs. We also report that forced Ub conjugation by the Ub fusion degradation pathway is not sufficient for recruitment to IBs. Finally, we find that reporters and Ub conjugates are stable at IBs. These data indicate that compromised folding states, rather than conjugation to Ub, can specify recruitment to IBs. © 2016 Bersuker et al.

UbMES and UbFluor: Novel probes for ring-between-ring (RBR) E3 ubiquitin ligase PARKIN.

PubMed

Park, Sungjin; Foote, Peter K; Krist, David T; Rice, Sarah E; Statsyuk, Alexander V

2017-10-06

Ring-between-ring (RBR) E3 ligases have been implicated in autoimmune disorders and neurodegenerative diseases. The functions of many RBR E3s are poorly defined, and their regulation is complex, involving post-translational modifications and allosteric regulation with other protein partners. The functional complexity of RBRs, coupled with the complexity of the native ubiquitination reaction that requires ATP and E1 and E2 enzymes, makes it difficult to study these ligases for basic research and therapeutic purposes. To address this challenge, we developed novel chemical probes, ubiquitin C-terminal fluorescein thioesters UbMES and UbFluor, to qualitatively and quantitatively assess the activity of the RBR E3 ligase PARKIN in a simple experimental setup and in real time using fluorescence polarization. First, we confirmed that PARKIN does not require an E2 enzyme for substrate ubiquitination, lysine selection, and polyubiquitin chain formation. Second, we confirmed that UbFluor quantitatively detects naturally occurring activation states of PARKIN caused by Ser 65 phosphorylation (pPARKIN) and phosphorylated ubiquitin (pUb). Third, we showed that both pUb and the ubiquitin-accepting substrate contribute to maximal pPARKIN ubiquitin conjugation turnover. pUb enhances the transthiolation step, whereas the substrate clears the pPARKIN∼Ub thioester intermediate. Finally, we established that UbFluor can quantify activation or inhibition of PARKIN by structural mutations. These results demonstrate the feasibility of using UbFluor for quantitative studies of the biochemistry of RBR E3s and for high-throughput screening of small-molecule activators or inhibitors of PARKIN and other RBR E3 ligases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Optimization of isolation of the concentrate of stem cells from the umbilical blood].

PubMed

Tiumina, O V; Savchenko, V G; Gusarova, G I; Pavlov, V V; Zharkov, M N; Volchkov, S E; Rossiev, V A; Gridasov, G N

2005-01-01

To study correlations between body mass and height of the newborn, Apgar scale estimates, gestation time, volume of the obtained umbilical blood (UB), number of nucleated cells (NC); to compare manual and automatic modes of UB processing. 330 procurements of UB were made, 230 (69.7%) samples were frozen. Comparison of 2 techniques of UB processing was made in 73 cases of double centrifugation with hydroxyethylstarch (HES) and 47 cases of using separator Sepax (Biosafe, Switzerland). Blood cell count before and after UB processing and number of CD34+ cells were estimated. A correlation analysis was made of dependence of the volume of 102 samples of UB on the weight (r = 0.268, p < 0.01) and height of the fetus (r = 0.203, p < 0.05), estimation by Apgar scale (r = -0.092, p < 0.1) and gestation term (r = -0.003, p > 0.1); analysis of the number of NC dependence on the volume of UB (r = 0.102 p < 0.1), mass (r = 0.073 p > 0.1) and fetus height (r = 0.121 p > 0.1), gestation time (r = 0.159 p > 0.1), Apgar scale assessment (r = -0.174 p > 0.1). In manual UB management NC yield made up 71.9 +/- 6.7%, in automatic--81 +/- 8.0% (p < 0.05). Percent of erythrocytes removal was 73 +/- 5.7% and 80.5 +/- 6.1% (p < 0.05), respectively. A weak correlation was found between UB volume, mass and height of the fetus. The number of NC in UB depends on none of the parameters. Automatic processing of UB provides a greater release of NC and better elimination of erythrocytes in minimal risk of contamination.

The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like β-grasp domains

PubMed Central

Iyer, Lakshminarayan M; Burroughs, A Maxwell; Aravind, L

2006-01-01

Background Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear. Results We systematically analyzed prokaryotic Ub-related β-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages. Conclusion These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to function together in signaling systems just as in eukaryotes. PMID:16859499

Ubiquitin S65 phosphorylation engenders a pH-sensitive conformational switch

PubMed Central

Dong, Xu; Gong, Zhou; Lu, Yun-Bi; Liu, Kan; Qin, Ling-Yun; Ran, Meng-Lin; Zhang, Chang-Li; Liu, Zhu; Zhang, Wei-Ping

2017-01-01

Ubiquitin (Ub) is an important signaling protein. Recent studies have shown that Ub can be enzymatically phosphorylated at S65, and that the resulting pUb exhibits two conformational states—a relaxed state and a retracted state. However, crystallization efforts have yielded only the structure for the relaxed state, which was found similar to that of unmodified Ub. Here we present the solution structures of pUb in both states obtained through refinement against state-specific NMR restraints. We show that the retracted state differs from the relaxed state by the retraction of the last β-strand and by the extension of the second α-helix. Further, we show that at 7.2, the pKa value for the phosphoryl group in the relaxed state is higher by 1.4 units than that in the retracted state. Consequently, pUb exists in equilibrium between protonated and deprotonated forms and between retracted and relaxed states, with protonated/relaxed species enriched at slightly acidic pH and deprotonated/retracted species enriched at slightly basic pH. The heterogeneity of pUb explains the inability of phosphomimetic mutants to fully mimic pUb. The pH-sensitive conformational switch is likely preserved for polyubiquitin, as single-molecule FRET data indicate that pH change leads to quaternary rearrangement of a phosphorylated K63-linked diubiquitin. Because cellular pH varies among compartments and changes upon pathophysiological insults, our finding suggests that pH and Ub phosphorylation confer additional target specificities and enable an additional layer of modulation for Ub signals. PMID:28611216

TRIM5α requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription

PubMed Central

Fletcher, Adam J; Christensen, Devin E; Nelson, Chad; Tan, Choon Ping; Schaller, Torsten; Lehner, Paul J; Sundquist, Wesley I; Towers, Greg J

2015-01-01

TRIM5α is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that assembles on incoming retroviral capsids and induces their premature dissociation. It inhibits reverse transcription of the viral genome and can also synthesize unanchored polyubiquitin (polyUb) chains to stimulate innate immune responses. Here, we show that TRIM5α employs the E2 Ub-conjugating enzyme Ube2W to anchor the Lys63-linked polyUb chains in a process of TRIM5α auto-ubiquitination. Chain anchoring is initiated, in cells and in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5α. This modification serves as a substrate for the elongation of anchored Lys63-linked polyUb chains, catalyzed by the heterodimeric E2 enzyme Ube2N/Ube2V2. Ube2W targets multiple TRIM5α internal lysines with Ub especially lysines 45 and 50, rather than modifying the N-terminal amino group, which is instead αN-acetylated in cells. E2 depletion or Ub mutation inhibits TRIM5α ubiquitination in cells and restores restricted viral reverse transcription, but not infection. Our data indicate that the stepwise formation of anchored Lys63-linked polyUb is a critical early step in the TRIM5α restriction mechanism and identify the E2 Ub-conjugating cofactors involved. PMID:26101372

Chemical ubiquitination for decrypting a cellular code.

PubMed

Stanley, Mathew; Virdee, Satpal

2016-05-15

The modification of proteins with ubiquitin (Ub) is an important regulator of eukaryotic biology and deleterious perturbation of this process is widely linked to the onset of various diseases. The regulatory capacity of the Ub signal is high and, in part, arises from the capability of Ub to be enzymatically polymerised to form polyubiquitin (polyUb) chains of eight different linkage types. These distinct polyUb topologies can then be site-specifically conjugated to substrate proteins to elicit a number of cellular outcomes. Therefore, to further elucidate the biological significance of substrate ubiquitination, methodologies that allow the production of defined polyUb species, and substrate proteins that are site-specifically modified with them, are essential to progress our understanding. Many chemically inspired methods have recently emerged which fulfil many of the criteria necessary for achieving deeper insight into Ub biology. With a view to providing immediate impact in traditional biology research labs, the aim of this review is to provide an overview of the techniques that are available for preparing Ub conjugates and polyUb chains with focus on approaches that use recombinant protein building blocks. These approaches either produce a native isopeptide, or analogue thereof, that can be hydrolysable or non-hydrolysable by deubiquitinases. The most significant biological insights that have already been garnered using such approaches will also be summarized. © 2016 Authors; published by Portland Press Limited.

E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

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

Pruneda, Jonathan N.; Smith, F. Donelson; Daurie, Angela

Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A cocrystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes anmore » active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.« less

Structural basis of ubiquitin modification by the Legionella effector SdeA.

PubMed

Dong, Yanan; Mu, Yajuan; Xie, Yongchao; Zhang, Yupeng; Han, Youyou; Zhou, Yu; Wang, Wenhe; Liu, Zihe; Wu, Mei; Wang, Hao; Pan, Man; Xu, Ning; Xu, Cong-Qiao; Yang, Maojun; Fan, Shilong; Deng, Haiteng; Tan, Tianwei; Liu, Xiaoyun; Liu, Lei; Li, Jun; Wang, Jiawei; Fang, Xianyang; Feng, Yue

2018-05-01

Protein ubiquitination is a multifaceted post-translational modification that controls almost every process in eukaryotic cells. Recently, the Legionella effector SdeA was reported to mediate a unique phosphoribosyl-linked ubiquitination through successive modifications of the Arg42 of ubiquitin (Ub) by its mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains. However, the mechanisms of SdeA-mediated Ub modification and phosphoribosyl-linked ubiquitination remain unknown. Here we report the structures of SdeA in its ligand-free, Ub-bound and Ub-NADH-bound states. The structures reveal that the mART and PDE domains of SdeA form a catalytic domain over its C-terminal region. Upon Ub binding, the canonical ADP-ribosyltransferase toxin turn-turn (ARTT) and phosphate-nicotinamide (PN) loops in the mART domain of SdeA undergo marked conformational changes. The Ub Arg72 might act as a 'probe' that interacts with the mART domain first, and then movements may occur in the side chains of Arg72 and Arg42 during the ADP-ribosylation of Ub. Our study reveals the mechanism of SdeA-mediated Ub modification and provides a framework for further investigations into the phosphoribosyl-linked ubiquitination process.

Preparation of ubiquitin-conjugated proteins using an insect cell-free protein synthesis system.

PubMed

Suzuki, Takashi; Ezure, Toru; Ando, Eiji; Nishimura, Osamu; Utsumi, Toshihiko; Tsunasawa, Susumu

2010-01-01

Ubiquitination is one of the most significant posttranslational modifications (PTMs). To evaluate the ability of an insect cell-free protein synthesis system to carry out ubiquitin (Ub) conjugation to in vitro translated proteins, poly-Ub chain formation was studied in an insect cell-free protein synthesis system. Poly-Ub was generated in the presence of Ub aldehyde (UA), a de-ubiquitinating enzyme inhibitor. In vitro ubiquitination of the p53 tumor suppressor protein was also analyzed, and p53 was poly-ubiquitinated when Ub, UA, and Mdm2, an E3 Ub ligase (E3) for p53, were added to the in vitro reaction mixture. These results suggest that the insect cell-free protein synthesis system contains enzymatic activities capable of carrying out ubiquitination. CBB-detectable ubiquitinated p53 was easily purified from the insect cell-free protein synthesis system, allowing analysis of the Ub-conjugated proteins by mass spectrometry (MS). Lys 305 of p53 was identified as one of the Ub acceptor sites using this strategy. Thus, we conclude that the insect cell-free protein synthesis system is a powerful tool for studying various PTMs of eukaryotic proteins including ubiqutination presented here.

AIRUSE-LIFE+: a harmonized PM speciation and source apportionment in 5 Southern European cities

NASA Astrophysics Data System (ADS)

Amato, F.; Alastuey, A.; Karanasiou, A.; Lucarelli, F.; Nava, S.; Calzolai, G.; Severi, M.; Becagli, S.; Gianelle, V. L.; Colombi, C.; Alves, C.; Custódio, D.; Nunes, T.; Cerqueira, M.; Pio, C.; Eleftheriadis, K.; Diapouli, E.; Reche, C.; Minguillón, M. C.; Manousakas, M.; Maggos, T.; Vratolis, S.; Harrison, R. M.; Querol, X.

2015-09-01

The AIRUSE-LIFE+ project aims at characterising similarities and heterogeneities in PM sources and contributions in urban areas from the Southern Europe. Once the main PMx sources are identified, AIRUSE aims at developing and testing the efficiency of specific and non-specific measures to improve urban air quality. This article reports the results of the source apportionment of PM10 and PM2.5 conducted at three urban background sites (Barcelona, Florence and Milan, BCN-UB, FI-UB, MLN-UB) one sub-urban background site (Athens, ATH-SUB) and one traffic site (Porto, POR-TR). After collecting 1047 PM10 and 1116 PM2.5 24 h samples from January 2013 to February 2014 simultaneously at the 5 cities, these were analysed for the contents of OC, EC, anions, cations, major and trace elements and levoglucosan. The USEPA PMF5 receptor model was applied to these datasets in a harmonised way for each city. The sum of vehicle exhaust and non-exhaust contributes within 3.9-10.8 μg m-3 (16-32 %) to PM10 and 2.3-9.4 μg m-3 (15-36 %) to PM2.5, although a fraction of secondary nitrate is also traffic-related but could not be estimated. Important contributions arise from secondary particles (nitrate, sulphate and organics) in PM2.5 (37-82 %) but also in PM10 (40-71 %) mostly at background sites, revealing the importance of abating gaseous precursors in designing air quality plans. Biomass burning (BB) contributions vary widely, from 14-24 % of PM10 in POR-TR, MLN-UB and FI-UB, 7 % in ATH-SUB to < 2 % in BCN-UB. In PM2.5, BB is the second most important source in MLN-UB (21 %) and in POR-TR (18 %), the third one in FI-UB (21 %) and ATH-SUB (11 %), but again negligible (< 2 %) in BCN-UB. This large variability among cities is mostly due to the degree of penetration of biomass for residential heating. In Barcelona natural gas is very well supplied across the city and used as fuel in 96 % of homes, while, in other cities, PM levels increase on an annual basis by 1-9 μg m-3 due to this source. Other significant sources are: - Local dust, 7-12 % of PM10 at SUB and UB sites and 19 % at the TR site, revealing a contribution from road dust resuspension. In PM2.5 percentages decrease to 2-7 % at SUB-UB sites and 15 % at the TR site. - Industries, mainly metallurgy, contributing 4-11 % of PM10 (5-12 % in PM2.5), but only at BCN-UB, POR-TR and MLN-UB. No clear impact of industrial emissions was found in FI-UB and ATH-SUB. - Natural contributions from sea salt (13 % of PM10 in POR-TR but only 2-7 % in the other cities) and Saharan dust (14 % in ATH-SUB), but less than 4 % in the other cities. During high pollution days, the largest specific source (i.e. excluding SSO and SNI) of PM10 and PM2.5 are: VEX+NEX in BCN-UB (27-22 %) and POR-TR (31-33 %), BB in FI-UB (30-33 %) and MLN-UB (35-26 %) and Saharan dust in ATH-SUB (52-45 %) During those days, there are also quite important Industrial contributions in BCN-UB (17-18 %) and Local dust in POR-TR (28-20 %).

AIRUSE-LIFE+: a harmonized PM speciation and source apportionment in five southern European cities

NASA Astrophysics Data System (ADS)

Amato, Fulvio; Alastuey, Andrés; Karanasiou, Angeliki; Lucarelli, Franco; Nava, Silvia; Calzolai, Giulia; Severi, Mirko; Becagli, Silvia; Gianelle, Vorne L.; Colombi, Cristina; Alves, Celia; Custódio, Danilo; Nunes, Teresa; Cerqueira, Mario; Pio, Casimiro; Eleftheriadis, Konstantinos; Diapouli, Evangelia; Reche, Cristina; Cruz Minguillón, María; Manousakas, Manousos-Ioannis; Maggos, Thomas; Vratolis, Stergios; Harrison, Roy M.; Querol, Xavier

2016-03-01

The AIRUSE-LIFE+ project aims at characterizing similarities and heterogeneities in particulate matter (PM) sources and contributions in urban areas from southern Europe. Once the main PMx sources are identified, AIRUSE aims at developing and testing the efficiency of specific and non-specific measures to improve urban air quality. This article reports the results of the source apportionment of PM10 and PM2.5 conducted at three urban background sites (Barcelona, Florence and Milan, BCN-UB, FI-UB and MLN-UB), one suburban background site (Athens, ATH-SUB) and one traffic site (Porto, POR-TR). After collecting 1047 PM10 and 1116 PM2.5 24 h samples during 12 months (from January 2013 on) simultaneously at the five cities, these were analysed for the contents of OC, EC, anions, cations, major and trace elements and levoglucosan. The USEPA PMF5 receptor model was applied to these data sets in a harmonized way for each city. The sum of vehicle exhaust (VEX) and non-exhaust (NEX) contributes between 3.9 and 10.8 µg m-3 (16-32 %) to PM10 and 2.3 and 9.4 µg m-3 (15-36 %) to PM2.5, although a fraction of secondary nitrate is also traffic-related but could not be estimated. Important contributions arise from secondary particles (nitrate, sulfate and organics) in PM2.5 (37-82 %) but also in PM10 (40-71 %), mostly at background sites, revealing the importance of abating gaseous precursors in designing air quality plans. Biomass burning (BB) contributions vary widely, from 14-24 % of PM10 in POR-TR, MLN-UB and FI-UB, 7 % in ATH-SUB, to < 2 % in BCN-UB. In PM2.5, BB is the second most important source in MLN-UB (21 %) and in POR-TR (18 %), the third one in FI-UB (21 %) and ATH-SUB (11 %), but is again negligible (< 2 %) in BCN-UB. This large variability among cities is mostly due to the degree of penetration of biomass for residential heating. In Barcelona natural gas is very well supplied across the city and is used as fuel in 96 % of homes, while in other cities, PM levels increase on an annual basis by 1-9 µg m-3 due to biomass burning influence. Other significant sources are the following. - Local dust, 7-12 % of PM10 at SUB and UB sites and 19 % at the TR site, revealing a contribution from road dust resuspension. In PM2.5 percentages decrease to 2-7 % at SUB-UB sites and 15 % at the TR site. - Industry, mainly metallurgy, contributing 4-11 % of PM10 (5-12 % in PM2.5), but only at BCN-UB, POR-TR and MLN-UB. No clear impact of industrial emissions was found in FI-UB and ATH-SUB. - Natural contributions from sea salt (13 % of PM10 in POR-TR, but only 2-7 % in the other cities) and Saharan dust (14 % in ATH-SUB, but less than 4 % in the other cities). During high pollution days, the largest sources (i.e. excluding secondary aerosol factors) of PM10 and PM2.5 are VEX + NEX in BCN-UB (27-22 %) and POR-TR (31-33 %), BB in FI-UB (30-33 %) and MLN-UB (35-26 %) and Saharan dust in ATH-SUB (52-45 %). During those days, there are also quite important industrial contributions in BCN-UB (17-18 %) and local dust in POR-TR (28-20 %).

A report on the introduction of ultrabrief pulse width ECT in a private psychiatric hospital.

PubMed

Galletly, Cherrie; Paterson, Tom; Burton, Cassandra

2012-03-01

We report on 6 months of data since the introduction of ultrabrief pulse width electroconvulsive therapy (UB ECT) at a private psychiatric hospital in Adelaide. Results suggest that psychiatrists welcomed the availability of UB ECT, with an increase in prescription of ECT. About a quarter of UB ECT patients changed to standard pulse width (SPW) ECT, but those who did respond to UB ECT had an equivalent response to those who had SPW ECT. Courses of treatment were longer with UB ECT, which was reflected in an increased length of stay.

Ubiquitin–Synaptobrevin Fusion Protein Causes Degeneration of Presynaptic Motor Terminals in Mice

PubMed Central

Liu, Yun; Li, Hongqiao; Sugiura, Yoshie; Han, Weiping; Gallardo, Gilbert; Khvotchev, Mikhail; Zhang, Yinan; Kavalali, Ege T.; Südhof, Thomas C.

2015-01-01

Protein aggregates containing ubiquitin (Ub) are commonly observed in neurodegenerative disorders, implicating the involvement of the ubiquitin proteasome system (UPS) in their pathogenesis. Here, we aimed to generate a mouse model for monitoring UPS function using a green fluorescent protein (GFP)-based substrate that carries a “noncleavable” N-terminal ubiquitin moiety (UbG76V). We engineered transgenic mice expressing a fusion protein, consisting of the following: (1) UbG76V, GFP, and a synaptic vesicle protein synaptobrevin-2 (UbG76V-GFP-Syb2); (2) GFP-Syb2; or (3) UbG76V-GFP-Syntaxin1, all under the control of a neuron-specific Thy-1 promoter. As expected, UbG76V-GFP-Syb2, GFP-Syb2, and UbG76V-GFP-Sytaxin1 were highly expressed in neurons, such as motoneurons and motor nerve terminals of the neuromuscular junction (NMJ). Surprisingly, UbG76V-GFP-Syb2 mice developed progressive adult-onset degeneration of motor nerve terminals, whereas GFP-Syb2 and UbG76V-GFP-Syntaxin1 mice were normal. The degeneration of nerve terminals in UbG76V-GFP-Syb2 mice was preceded by a progressive impairment of synaptic transmission at the NMJs. Biochemical analyses demonstrated that UbG76V-GFP-Syb2 interacted with SNAP-25 and Syntaxin1, the SNARE partners of synaptobrevin. Ultrastructural analyses revealed a marked reduction in synaptic vesicle density, accompanying an accumulation of tubulovesicular structures at presynaptic nerve terminals. These morphological defects were largely restricted to motor nerve terminals, as the ultrastructure of motoneuron somata appeared to be normal at the stages when synaptic nerve terminals degenerated. Furthermore, synaptic vesicle endocytosis and membrane trafficking were impaired in UbG76V-GFP-Syb2 mice. These findings indicate that UbG76V-GFP-Syb2 may compete with endogenous synaptobrevin, acting as a gain-of-function mutation that impedes SNARE function, resulting in the depletion of synaptic vesicles and degeneration of the nerve terminals. SIGNIFICANCE STATEMENT Degeneration of motor nerve terminals occurs in amyotrophic lateral sclerosis (ALS) patients as well as in mouse models of ALS, leading to progressive paralysis. What causes a motor nerve terminal to degenerate remains unknown. Here we report on transgenic mice expressing a ubiquitinated synaptic vesicle protein (UbG76V-GFP-Syb2) that develop progressive degeneration of motor nerve terminals. These mice may serve as a model for further elucidating the underlying cellular and molecular mechanisms of presynaptic nerve terminal degeneration. PMID:26290230

DOMINO: development of informative molecular markers for phylogenetic and genome-wide population genetic studies in non-model organisms.

PubMed

Frías-López, Cristina; Sánchez-Herrero, José F; Guirao-Rico, Sara; Mora, Elisa; Arnedo, Miquel A; Sánchez-Gracia, Alejandro; Rozas, Julio

2016-12-15

The development of molecular markers is one of the most important challenges in phylogenetic and genome wide population genetics studies, especially in studies with non-model organisms. A highly promising approach for obtaining suitable markers is the utilization of genomic partitioning strategies for the simultaneous discovery and genotyping of a large number of markers. Unfortunately, not all markers obtained from these strategies provide enough information for solving multiple evolutionary questions at a reasonable taxonomic resolution. We have developed Development Of Molecular markers In Non-model Organisms (DOMINO), a bioinformatics tool for informative marker development from both next generation sequencing (NGS) data and pre-computed sequence alignments. The application implements popular NGS tools with new utilities in a highly versatile pipeline specifically designed to discover or select personalized markers at different levels of taxonomic resolution. These markers can be directly used to study the taxa surveyed for their design, utilized for further downstream PCR amplification in a broader set taxonomic scope, or exploited as suitable templates to bait design for target DNA enrichment techniques. We conducted an exhaustive evaluation of the performance of DOMINO via computer simulations and illustrate its utility to find informative markers in an empirical dataset. DOMINO is freely available from www.ub.edu/softevol/domino CONTACT: elsanchez@ub.edu or jrozas@ub.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed Central

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

2012-01-01

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

Ubiquitin B in Cervical Cancer: Critical for the Maintenance of Cancer Stem-Like Cell Characters

PubMed Central

Wang, Yingying; Ji, Teng; Sun, Shujuan; Mo, Qingqing; Chen, Pingbo; Fang, Yong; Liu, Jia; Wang, Beibei; Zhou, Jianfeng; Ma, Ding; Wu, Peng

2013-01-01

Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells. PMID:24367661

Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.

PubMed Central

Bacci, B.; Cochran, E.; Nunzi, M. G.; Izeki, E.; Mizutani, T.; Patton, A.; Hite, S.; Sayre, L. M.; Autilio-Gambetti, L.; Gambetti, P.

1994-01-01

Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. We have now characterized the immunoreactivity of DA experimentally induced in rat by the administration of parabromophenylacetylurea (BPAU) and examined the subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched brain regions were consistent with an increase in the amount of Ub and BPP in DA. Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70. Antigenic characterization also indicated that the tubulovesicular membranes within DA derived largely from the smooth endoplasmic reticulum rather than from the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA intense Ub immunoreactivity was also detected in nonmembranous electron dense structures that were present only in these DA, probably because of the chronic course of INAD. Although BPP immunostaining may be related to accumulation of BPP-containing membranes in DA, Ub immunostaining is likely to result from activation of the Ub system by the neuron in the attempt to remove excessive and possibly abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer disease. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7512790

SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme

PubMed Central

Békés, Miklós; Rut, Wioletta; Kasperkiewicz, Paulina; Mulder, Monique P. C.; Ovaa, Huib; Drag, Marcin; Lima, Christopher D.; Huang, Tony T.

2015-01-01

Ubiquitin (Ub) and the ubiquitin-like modifier interferon stimulated gene 15 (ISG15) participate in the host defense of viral infections. Viruses, including the Severe Acute Respiratory Syndrome human coronavirus (SARS hCoV), have co-opted Ub/ISG15-conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub/ISG15-conjugated host proteins. Here, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle Eastern Respiratory Syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that similar to SARS PLpro, MERS PLpro is both a deubiquitinating and a deISGylating enzyme. Further analysis of the intrinsic deubiquitinating enzyme (DUB) activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, while SARS PLpro prefers to cleave Lys48-linked polyUb chains. Second, MERS PLpro cleaves polyUb chains in a “mono-distributive” manner (one Ub at a time), and SARS PLpro prefers to cleave K48-linked poly-Ub chains by sensing a di-Ub moiety as a minimal recognition element using a “di-distributive” cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses. PMID:25764917

Practical considerations in the use of ultrabrief ECT in clinical practice.

PubMed

Galletly, Cherrie; Clarke, Patrick; Paterson, Tom; Rigby, Ashlee; Gill, Shane

2014-03-01

Electroconvulsive therapy (ECT) is the most effective treatment for major depression. Brief pulse width (BPW; pulse width, 1.0 m/s) ECT is often associated with cognitive impairment. Ultrabrief (UB; pulse width, 0.3 m/s) ECT is better tolerated and causes less cognitive impairment so has been introduced as an alternative. Previous research has shown that more treatments are needed with UB ECT; however, there has not been any previous research into the impact of prescribing UB ECT on length of stay. This study reports naturalistic data collected from 258 inpatients in a private psychiatric hospital for 2 years since the introduction of UB ECT. Clinician and self-rated scales of depression severity and hospital service data were used to evaluate the number of ECT treatments, length of stay, and efficacy. Patients prescribed UB ECT had, on average, 10.9 treatments compared to 8.8 for BPW ECT. They also spent more time in hospital; 30.3 days from the first ECT treatment to discharge compared to 24.7 days for patients prescribed BPW ECT. Excluding patients who switched treatments, 54% of patients prescribed UB ECT responded compared to 66.7% of patients prescribed BPW ECT. More patients (n = 42) switched from UB to BPW than from BPW to UB (n = 3). In the 4 years since the introduction of UB ECT, the number of patients prescribed ECT has increased, and the mean number of treatments per patient (for all patients receiving ECT) has increased from 7.7 to 11.6. Ultrabrief ECT has significant advantages, reflected in the increased use of ECT since UB ECT became available. However, the greater number of treatments and the increased length of stay have important implications for service delivery, costs, and bed accessibility.

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

PubMed Central

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

2016-01-01

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

THE ROLE OF CYTOKINES IN UBD PROMOTER REGULATION AND MALLORY-DENK BODY-LIKE AGGRESOMES

PubMed Central

Oliva, Joan; Bardag-Gorce, Fawzia; Lin, Andrew; French, Barbara.A; French, Samuel W.

2010-01-01

Mallory-Denk bodies (MDBs) are found in chronic liver diseases. Previous studies showed that Diethyl-1, 4-dihydro-2,4,6,-trimethyl-3,5-pyridinedicarboxylate (DDC) induced formation of MDBs and the up regulation of UbD expression in mouse liver. UbD is a protein over expressed in hepatocellular carcinomas. It is a potential preneoplastic marker in the mouse. It is hypothesized that inflammatory cytokines play a critical role in UbD up regulation and MDB formation. TNFa and IFNg treatment of HCC cell line Hepa 1–6, induced the expression of UbD and the expression of genes coding for the immunoproteasome (LMP2, LMP7, and MECL-1 subunits). TNFa and IFNg induced the activity of the UbD promoter, using a luciferase assay. The co-treatment with TNFa and IFNg induced the activity of the UbD promoter through an Interferon Sequence Responsive Element (ISRE). In addition, long term treatment with TNFa and IFNg induced the formation of MDB-like aggresomes in Hepa 1–6 cells, which emphasizes the role of inflammation in the formation of MDBs leading to the formation of liver tumors, in the mouse. Identifying the mechanism that regulates gene expression of UbD supports the hypothesis that down regulation of UbD and the proinflammatory gene expression would prevent MDBs and HCC formation. Previous studies indicate that S-adenosylmethionine or betaine prevented IFNg induced UbD and MDB formation. PMID:20433827

Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.

PubMed

Békés, Miklós; van der Heden van Noort, Gerbrand J; Ekkebus, Reggy; Ovaa, Huib; Huang, Tony T; Lima, Christopher D

2016-05-19

Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

PubMed

Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Waite, Susan; Loo, Colleen K

2017-12-01

Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.

CYBERWAR-2012/13: Siegel 2011 Predicted Cyberwar Via ACHILLES-HEEL DIGITS BEQS BEC ZERO-DIGIT BEC of/in ACHILLES-HEEL DIGITS Log-Law Algebraic-Inversion to ONLY BEQS BEC Digit-Physics U Barabasi Network/Graph-Physics BEQS BEC JAMMING Denial-of-Access(DOA) Attacks 2012-Instantiations

NASA Astrophysics Data System (ADS)

Huffmann, Master; Siegel, Edward Carl-Ludwig

2013-03-01

Newcomb-Benford(NeWBe)-Siegel log-law BEC Digit-Physics Network/Graph-Physics Barabasi et.al. evolving-``complex''-networks/graphs BEC JAMMING DOA attacks: Amazon(weekends: Microsoft I.E.-7/8(vs. Firefox): Memorial-day, Labor-day,...), MANY U.S.-Banks:WF,BoA,UB,UBS,...instantiations AGAIN militate for MANDATORY CONVERSION to PARALLEL ANALOG FAULT-TOLERANT but slow(er) SECURITY-ASSURANCE networks/graphs in parallel with faster ``sexy'' DIGITAL-Networks/graphs:``Cloud'', telecomm: n-G,..., because of common ACHILLES-HEEL VULNERABILITY: DIGITS!!! ``In fast-hare versus slow-tortoise race, Slow-But-Steady ALWAYS WINS!!!'' (Zeno). {Euler [#s(1732)] ∑- ∏()-Riemann[Monats. Akad. Berlin (1859)] ∑- ∏()- Kummer-Bernoulli (#s)}-Newcomb [Am.J.Math.4(1),39 (81) discovery of the QUANTUM!!!]-{Planck (01)]}-{Einstein (05)]-Poincar e [Calcul Probabilités,313(12)]-Weyl[Goett. Nach.(14); Math.Ann.77,313(16)]-(Bose (24)-Einstein(25)]-VS. -Fermi (27)-Dirac(27))-Menger [Dimensiontheorie(29)]-Benford [J.Am. Phil.Soc.78,115(38)]-Kac[Maths Stats.-Reason. (55)]- Raimi [Sci.Am.221,109(69)]-Jech-Hill [Proc.AMS,123,3,887(95)] log-function

Antigen-specific CD8{sup +} T cells induced by the ubiquitin fusion degradation pathway

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

Imai, Takashi; Duan Xuefeng; Hisaeda, Hajime

We have developed a DNA vaccine encoding a fusion protein of ubiquitin (Ub) and target proteins at the N-terminus for effective induction of antigen-specific CD8{sup +} T cells. A series of expression plasmids encoding a model antigen, ovalbumin (OVA), fused with mutated Ub, was constructed. Western blotting analyses using COS7 cells transfected with these plasmids revealed that there were three types of amino acid causing different binding capacities between Ub and OVA. Natural Ub with a C-terminal glycine readily dissociated from OVA; on the other hand, artificially mutated Ub, the C-terminal amino acid of which had been exchanged to valinemore » or arginine, stably united with the polypeptide, while Ub with a C-terminal alanine partially dissociated. The ability of DNA vaccination to induce OVA-specific CD8{sup +} T cells closely correlated with the stability of Ub fusion to OVA. Our strategy could be used to optimize the effect of genetic vaccines on the induction of CD8{sup +} T cells.« less

A cascading activity-based probe sequentially targets E1–E2–E3 ubiquitin enzymes

PubMed Central

Mulder, Monique P.C.; Witting, Katharina; Berlin, Ilana; Pruneda, Jonathan N.; Wu, Kuen-Phon; Chang, Jer-Gung; Merkx, Remco; Bialas, Johanna; Groettrup, Marcus; Vertegaal, Alfred C.O.; Schulman, Brenda A.; Komander, David; Neefjes, Jacques; Oualid, Farid El; Ovaa, Huib

2016-01-01

Post-translational modifications of proteins with ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers, orchestrated by a cascade of specialized E1, E2 and E3 enzymes, control a staggering breadth of cellular processes. To monitor catalysis along these complex reaction pathways, we developed a cascading activity-based probe, UbDha. Akin to the native Ub, upon ATP-dependent activation by the E1, UbDha can travel downstream to the E2 (and subsequently E3) enzymes through sequential trans-thioesterifications. Unlike the native Ub, at each step along the cascade UbDha has the option to react irreversibly with active site cysteine residues of target enzymes, thus enabling their detection. We show that our cascading probe ‘hops’ and ‘traps’ catalytically active ubiquitin-modifying enzymes (but not their substrates) by a mechanism diversifiable to Ubls. Our founder methodology, amenable to structural studies, proteome-wide profiling and monitoring of enzymatic activities in living cells, presents novel and versatile tools to interrogate the Ub/Ubl cascades. PMID:27182664

$$|V_{ub}|$$ from $$B\\to\\pi\\ell\

DOE PAGES

Bailey, Jon A.; et al.

2015-07-23

We present a lattice-QCD calculation of the B → πℓν semileptonic form factors and a new determination of the CKM matrix element |V ub|. We use the MILC asqtad (2+1)-flavor lattice configurations at four lattice spacings and light-quark masses down to 1/20 of the physical strange-quark mass. We extrapolate the lattice form factors to the continuum using staggered chiral perturbation theory in the hard-pion and SU(2) limits. We employ a model-independent z parametrization to extrapolate our lattice form factors from large-recoil momentum to the full kinematic range. We introduce a new functional method to propagate information from the chiral-continuum extrapolationmore » to the z expansion. We present our results together with a complete systematic error budget, including a covariance matrix to enable the combination of our form factors with other lattice-QCD and experimental results. To obtain |V ub|, we simultaneously fit the experimental data for the B → πℓν differential decay rate obtained by the BABAR and Belle collaborations together with our lattice form-factor results. We find |V ub|=(3.72±0.16) × 10 –3, where the error is from the combined fit to lattice plus experiments and includes all sources of uncertainty. Our form-factor results bring the QCD error on |V ub| to the same level as the experimental error. We also provide results for the B → πℓν vector and scalar form factors obtained from the combined lattice and experiment fit, which are more precisely determined than from our lattice-QCD calculation alone. Lastly, these results can be used in other phenomenological applications and to test other approaches to QCD.« less

77 FR 40591 - Applications for New Awards; Veterans Upward Bound Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

...: Regular UB grants, UB Math and Science (UBMS) grants, and Veterans UB (VUB) grants. This notice announces... who in the first year of postsecondary education placed into college-level math and English without...

Quantifying Ubiquitin Signaling

PubMed Central

Ordureau, Alban; Münch, Christian; Harper, J. Wade

2015-01-01

Ubiquitin (UB)-driven signaling systems permeate biology, and are often integrated with other types of post-translational modifications (PTMs), most notably phosphorylation. Flux through such pathways is typically dictated by the fractional stoichiometry of distinct regulatory modifications and protein assemblies as well as the spatial organization of pathway components. Yet, we rarely understand the dynamics and stoichiometry of rate-limiting intermediates along a reaction trajectory. Here, we review how quantitative proteomic tools and enrichment strategies are being used to quantify UB-dependent signaling systems, and to integrate UB signaling with regulatory phosphorylation events. A key regulatory feature of ubiquitylation is that the identity of UB chain linkage types can control downstream processes. We also describe how proteomic and enzymological tools can be used to identify and quantify UB chain synthesis and linkage preferences. The emergence of sophisticated quantitative proteomic approaches will set a new standard for elucidating biochemical mechanisms of UB-driven signaling systems. PMID:26000850

USP7 is a SUMO deubiquitinase essential for DNA replication.

PubMed

Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia; Lopez-Contreras, Andres J; Ruppen, Isabel; Murga, Matilde; Muñoz, Javier; Mendez, Juan; Fernandez-Capetillo, Oscar

2016-04-01

Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7 inhibitors as anticancer agents.

The role of hybrid ubiquitin chains in the MyD88 and other innate immune signalling pathways.

PubMed

Cohen, Philip; Strickson, Sam

2017-07-01

The adaptor protein MyD88 is required for signal transmission by toll-like receptors and receptors of the interleukin-1 family of cytokines. MyD88 signalling triggers the formation of Lys63-linked and Met1-linked ubiquitin (K63-Ub, M1-Ub) chains within minutes. The K63-Ub chains, which are formed by the E3 ubiquitin ligases TRAF6, Pellino1 and Pellino2, activate TAK1, the master kinase that switches on mitogen-activated protein (MAP) kinase cascades and initiates activation of the canonical IκB kinase (IKK) complex. The M1-Ub chains, which are formed by the linear ubiquitin chain assembly complex (LUBAC), bind to the NEMO (NF-κB essential modulator) component of the IKK complex and are required for TAK1 to activate IKKs, but not MAP kinases. An essential E3 ligase-independent role of TRAF6 is to recruit LUBAC into the MyD88 signalling complex, where it recognises preformed K63-Ub chains attached to protein components of these complexes, such as IRAK1 (IL-1 receptor-associated kinase), producing ubiquitin chains containing both types of linkage, termed K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids, which is a feature of several innate immune signalling pathways, permits the co-recruitment of proteins that interact with either K63-Ub or M1-Ub chains. Two likely roles for K63/M1-Ub hybrids are to facilitate the TAK1-dependent activation of the IKK complex and to prevent the hyperactivation of these kinases by recruiting A20 and A20-binding inhibitor of NF-κB1 (ABIN1). These proteins restrict activation of the TAK1 and IKK complexes, probably by competing with them for binding to K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids may also regulate the rate at which the ubiquitin linkages in these chains are hydrolysed. The IKK-catalysed phosphorylation of some of its substrates permits their recognition by the E3 ligase SCF βTRCP , leading to their Lys48-linked ubiquitylation and proteasomal degradation. Innate immune signalling is therefore controlled by the formation and destruction of three different types of ubiquitin linkage.

The role of hybrid ubiquitin chains in the MyD88 and other innate immune signalling pathways

PubMed Central

Cohen, Philip; Strickson, Sam

2017-01-01

The adaptor protein MyD88 is required for signal transmission by toll-like receptors and receptors of the interleukin-1 family of cytokines. MyD88 signalling triggers the formation of Lys63-linked and Met1-linked ubiquitin (K63-Ub, M1-Ub) chains within minutes. The K63-Ub chains, which are formed by the E3 ubiquitin ligases TRAF6, Pellino1 and Pellino2, activate TAK1, the master kinase that switches on mitogen-activated protein (MAP) kinase cascades and initiates activation of the canonical IκB kinase (IKK) complex. The M1-Ub chains, which are formed by the linear ubiquitin chain assembly complex (LUBAC), bind to the NEMO (NF-κB essential modulator) component of the IKK complex and are required for TAK1 to activate IKKs, but not MAP kinases. An essential E3 ligase-independent role of TRAF6 is to recruit LUBAC into the MyD88 signalling complex, where it recognises preformed K63-Ub chains attached to protein components of these complexes, such as IRAK1 (IL-1 receptor-associated kinase), producing ubiquitin chains containing both types of linkage, termed K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids, which is a feature of several innate immune signalling pathways, permits the co-recruitment of proteins that interact with either K63-Ub or M1-Ub chains. Two likely roles for K63/M1-Ub hybrids are to facilitate the TAK1-dependent activation of the IKK complex and to prevent the hyperactivation of these kinases by recruiting A20 and A20-binding inhibitor of NF-κB1 (ABIN1). These proteins restrict activation of the TAK1 and IKK complexes, probably by competing with them for binding to K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids may also regulate the rate at which the ubiquitin linkages in these chains are hydrolysed. The IKK-catalysed phosphorylation of some of its substrates permits their recognition by the E3 ligase SCFβTRCP, leading to their Lys48-linked ubiquitylation and proteasomal degradation. Innate immune signalling is therefore controlled by the formation and destruction of three different types of ubiquitin linkage. PMID:28475177

The role of the ubiquitin proteasome pathway in keratin intermediate filament protein degradation.

PubMed

Rogel, Micah R; Jaitovich, Ariel; Ridge, Karen M

2010-02-01

Lung injury, whether caused by hypoxic or mechanical stresses, elicits a variety of responses at the cellular level. Alveolar epithelial cells respond and adapt to such injurious stimuli by reorganizing the cellular cytoskeleton, mainly accomplished through modification of the intermediate filament (IF) network. The structural and mechanical integrity in epithelial cells is maintained through this adaptive reorganization response. Keratin, the predominant IF expressed in epithelial cells, displays highly dynamic properties in response to injury, sometimes in the form of degradation of the keratin IF network. Post-translational modification, such as phosphorylation, targets keratin proteins for degradation in these circumstances. As with other structural and regulatory proteins, turnover of keratin is regulated by the ubiquitin (Ub)-proteasome pathway. The degradation process begins with activation of Ub by the Ub-activating enzyme (E1), followed by the exchange of Ub to the Ub-conjugating enzyme (E2). E2 shuttles the Ub molecule to the substrate-specific Ub ligase (E3), which then delivers the Ub to the substrate protein, thereby targeting it for degradation. In some cases of injury and IF-related disease, aggresomes form in epithelial cells. The mechanisms that regulate aggresome formation are currently unknown, although proteasome overload may play a role. Therefore, a more complete understanding of keratin degradation--causes, mechanisms, and consequences--will allow for a greater understanding of epithelial cell biology and lung pathology alike.

Overexpression of monoubiquitin improves photosynthesis in transgenic tobacco plants following high temperature stress.

PubMed

Tian, Fengxia; Gong, Jiangfeng; Zhang, Jin; Feng, Yanan; Wang, Guokun; Guo, Qifang; Wang, Wei

2014-09-01

The ubiquitin/26S proteasome system (Ub/26S) is implicated in abiotic stress responses in plants. In this paper, transgenic tobacco plants overexpressing Ta-Ub2 from wheat were used to study the functions of Ub in the improvement of photosynthesis under high temperature (45°C) stress. We observed higher levels of Ub conjugates in transgenic plants under high temperature stress conditions compared to wild type (WT) as a result of the constitutive overexpression of Ta-Ub2, suggesting increased protein degradation by the 26S proteasome system under high temperature stress. Overexpressing Ub increased the photosynthetic rate (Pn) of transgenic tobacco plants, consistent with the improved ATPase activity in the thylakoid membrane and enhanced efficiency of PSII photochemistry. The higher D1 protein levels following high temperature stress in transgenic plants than WT were also observed. These findings imply that Ub may be involved in tolerance of photosynthesis to high temperature stress in plants. Compared with WT, the transgenic plants showed lower protein carbonylation and malondialdehyde (MDA) levels, less reactive oxygen species (ROS) accumulation, but higher antioxidant enzyme activity under high temperature stress. These findings suggest that the improved antioxidant capacity of transgenic plants may be one of the most important mechanisms underlying Ub-regulated high temperature tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Role of Wnt5a-Ror2 Signaling in Morphogenesis of the Metanephric Mesenchyme during Ureteric Budding

PubMed Central

Qiao, Sen; Miyamoto, Mari; Okinaka, Yuka; Yamada, Makiko; Hashimoto, Ryuju; Iijima, Kazumoto; Otani, Hiroki; Hartmann, Christine; Nishinakamura, Ryuichi

2014-01-01

Development of the metanephric kidney begins with the induction of a single ureteric bud (UB) on the caudal Wolffian duct (WD) in response to GDNF (glial cell line-derived neurotrophic factor) produced by the adjacent metanephric mesenchyme (MM). Mutual interaction between the UB and MM maintains expression of GDNF in the MM, thereby supporting further outgrowth and branching morphogenesis of the UB, while the MM also grows and aggregates around the branched tips of the UB. Ror2, a member of the Ror family of receptor tyrosine kinases, has been shown to act as a receptor for Wnt5a to mediate noncanonical Wnt signaling. We show that Ror2 is predominantly expressed in the MM during UB induction and that Ror2- and Wnt5a-deficient mice exhibit duplicated ureters and kidneys due to ectopic UB induction. During initial UB formation, these mutant embryos show dysregulated positioning of the MM, resulting in spatiotemporally aberrant interaction between the MM and WD, which provides the WD with inappropriate GDNF signaling. Furthermore, the numbers of proliferating cells in the mutant MM are markedly reduced compared to the wild-type MM. These results indicate an important role of Wnt5a-Ror2 signaling in morphogenesis of the MM to ensure proper epithelial tubular formation of the UB required for kidney development. PMID:24891614

Progressive accumulation of ubiquitin and disappearance of alpha-synuclein epitope in multiple system atrophy-associated glial cytoplasmic inclusions: triple fluorescence study combined with Gallyas-Braak method.

PubMed

Sakamoto, Masaki; Uchihara, Toshiki; Nakamura, Ayako; Mizutani, Toshio; Mizusawa, Hidehiro

2005-10-01

Alpha-synuclein (alphaS) and ubiquitin (Ub) are shared constituents of glial cytoplasmic inclusions (GCIs) and Lewy bodies (LBs), both composed of fibrillary structures. Staining profiles of GCIs were investigated with triple immunofluorescence involving immunostaining for alphaS and Ub, both amplified with catalyzed reporter deposition, and a fluorochrome, thiazin red (TR) that has an affinity to fibrillary structures. After observation for the triple-fluorescent images, the sections were subsequently stained with the Gallyas-Braak method. Sections of putamen, cerebellar white matter and motor cortex from patients suffering from multiple system atrophy (MSA) with varying duration of the disease (4-15 years) were quantified for these staining profiles of Gallyas-positive GCIs. Although most of GCIs were positive for Ub and variably positive for alphaS, they were consistently negative for TR. The result was opposite in LBs in Lewy body disease with variable affinity to TR, suggesting that the construction of GCIs is different from that of LBs. These four staining features (alphaS, Ub, TR and Gallyas) alone failed to exhibit apparent correlation with disease duration, lesion site or severity of degeneration as reported previously. The fraction of alphaS-negative and Ub-positive GCIs, however, linearly increased along the disease progression, while that of alphaS-positive and Ub-negative GCIs decreased in contrast. This reciprocal change suggests that alphaS immunoreactivity in GCIs is being replaced by Ub immunoreactivity during the disease progression, which resulted in the ultimate predominance of alphaS-negative and Ub-positive GCIs in the most advanced case. Interestingly, this predominance of alphaS-negative and Ub-positive GCIs was a feature of motor cortex, where degeneration usually remains mild in spite of robust appearance of Gallyas-positive GCIs. Another fraction, alphaS-positive and Ub-positive GCIs were frequent in cerebellar white matter, suggesting that GCI evolution is heterogeneous and dependent also on area examined. Progressive accumulation of Ub with concomitant disappearance of alphaS epitope and their colocalization, partly shared with LBs, may represent a process of GCI formation, possibly linked to an aspect of degeneration in MSA.

Primary Health Care as a guide for assistance to infants at risk of neurodevelopmental disorders.

PubMed

Molini-Avejonas, Daniela Regina; Rondon-Melo, Silmara; Batista, Estela Ramos; Souza, Amanda Calsolari de; Dias, Daniela Cardilli; Samelli, Alessandra Gianella

2018-01-01

Purpose Characterize infants at risk of neurodevelopmental disorders according to sociodemographic and health profiles and describe their monitoring in Basic Health Units (UBS) under different management models. Methods Data were collected from medical records of infants at risk of neurodevelopmental disorders in the west region of the city of Sao Paulo from August 2013 to February 2014 (phase 1 - characterization; phase 2 - monitoring). Results Of the 225 individuals assessed in the first phase of the study, 51.1% were female and 7.11% were twins. Adolescent (45.2%), brown (50.56%), single (46.09%), complete primary education (47.60%) mothers were predominant. The mean number of prenatal visits was 7.12. Most mothers had vaginal delivery (62.22%) at mean gestational age of 37.05 weeks. Mean Apgar scores at the 1st and 5th minutes were 7.13 and 8.80, respectively. Mean weight at birth was 2597.21g., with 50.22% of newborns weighting ≤2500g. In its second phase, the study describes and compares the follow-up of 55 infants according to the UBS management model: 28 in UBS/"Estratégia Saúde da Família" (UBS/ESF) and 27 in traditional UBS (UBS/T). UBS/ESF presented higher mean of consultations (p=0.006). Longer interval between consultations was observed at UBS/T. No records of development milestones were found in 56% of the sample. Growth measures were better registered at UBS/ESF. In both management models, the number of consultations was smaller and the interval between them was shorter than those recommended by the Brazilian Ministry of Health. Conclusion According to the recommended guidelines of the "Rede Cegonha" public policy, gaps in the monitoring of infants at risk of neurodevelopmental disorders are still observed.

Ultrathin bronchoscopy for solitary pulmonary lesions in a region endemic for tuberculosis: a randomised pilot trial.

PubMed

Franzen, Daniel; Diacon, Andreas H; Freitag, Lutz; Schubert, Pawel T; Wright, Colleen A; Schuurmans, Macé M

2016-04-27

The evaluation of solitary pulmonary lesions (SPL) requires a balance between procedure-related morbidity and diagnostic yield, particularly in areas where tuberculosis (TB) is endemic. Data on ultrathin bronchoscopy (UB) for this purpose is limited. To evaluate feasibility and safety of UB compared to SB for diagnosis of SPL in a TB endemic region. In this prospective randomised trial we compared diagnostic yield and adverse events of UB with standard-size bronchoscopy (SB), both combined with fluoroscopy, in a cohort of patients with SPL located beyond the visible range of SB. We included 40 patients (mean age 55.2 years, 45 % male) with malignant SPL (n = 16; 40 %), tuberculous SPL (n = 11; 27.5 %) and other benign SPL (n = 13; 32.5 %). Mean procedure time in UB and SB was 30.6 and 26.0 min, respectively (p = 0.15). By trend, adverse events were recorded more often with UB than with SB (30.0 vs. 5.0 %, p = 0.091), including extensive coughing (n = 2), blocked working channel (n = 2), and arterial hypertension requiring therapeutic intervention (n = 1), all with UB. The overall diagnostic yield of UB compared to SB was 55.0 % vs. 80.0 %, respectively (p = 0.18). Sensitivity for the diagnosis of malignancy of UB and SB was 50.0 % and 62.5 %, respectively (p = 0.95). UB is not superior to SB for the evaluation of SPL in a region endemic with tuberculosis, when combined with fluoroscopic guidance only. ClinicalTrials.gov (Identifier: NCT02490059 ).

Urinary Bother as a Predictor of Postsurgical Changes in Urinary Function After Robotic Radical Prostatectomy.

PubMed

Murphy, Gregory; Haddock, Peter; Doak, Hoyt; Jackson, Max; Dorin, Ryan; Meraney, Anoop; Kesler, Stuart; Staff, Ilene; Wagner, Joseph R

2015-10-01

To characterize changes in indices of urinary function in prostatectomy patients with presurgical voiding symptoms. A retrospective analysis of our prostate cancer database identified robot-assisted radical prostatectomy patients between April 2007 and December 2011 who completed pre- and postsurgical (24 months) Expanded Prostate Cancer Index Composite-26 surveys. Gleason score, margins, D'Amico risk, prostate-specific antigen, radiotherapy, and nerve-sparing status were tabulated. Survey questions addressed urinary irritation/obstruction, incontinence, and overall bother. Responses were averaged to calculate a urinary sum (US) score. Patients were stratified according to the severity of their baseline urinary bother (UB), and changes in urinary indices determined at 24 months. A total of 737 patients were included. Postsurgical improvement in urinary obstruction, bother, and sum score was related to baseline UB (P <.001). Men with severe baseline bother had the greatest improvement in US (+9.3), whereas those with asymptomatic baseline UB experienced a decline in US (-2.8). All patients experienced a decline in urinary incontinence of 6.3-8.3 that was independent of baseline bother (P = .507). Patients with severe UB experienced positive outcomes, whereas those at asymptomatic baseline experienced negative US outcomes. Negative urinary incontinence outcomes were unrelated to baseline UB. Age, radiotherapy, and nerve-sparing status were not associated with improved UB (P = .029). However, baseline UB was significantly associated with improvement in postsurgical UB (P = .001). Baseline UB is a predictor of postsurgical improvement in urinary function. These data are helpful when counseling a subset of robot-assisted laparoscopic radical prostatectomy patients with severe preoperative urinary symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Urinary Biomarkers are Associated with Severity and Mechanism of Injury

PubMed Central

Janak, Jud C.; Stewart, Ian J.; Sosnov, Jonathan A.; Howard, Jeffrey T.; Siew, Edward D.; Chan, Mallory M.; Wickersham, Nancy; Ikizler, T. Alp; Chung, Kevin K.

2016-01-01

Combat-related blast trauma results in massive tissue injury and tends to involve multiple systems. Further, an acute measure of injury severity based on underlying biological mechanisms may be important for the triage and treatment of these types of patients. We hypothesized that urinary biomarkers (UBs) would reflect severity of injury and that they would be elevated for blast injuries compared to gunshot wounds (GSW) in a cohort of combat casualties. We also postulated that UBs would be higher in patients with burns compared to patients with non-burn trauma in a civilian cohort. Among 80 service members who sustained combat-related injuries, we performed generalized estimating equations to compare differences in log-transformed concentrations of the UBs by both (1) injury severity and (2) injury mechanism. Among 22 civilian patients, we performed Kruskal-Wallis tests to compare differences for the UBs stratified by burn and non-burn trauma. In the military cohort, with the exception of IL-18, all UBs were significantly (p<0.05) higher for patients with a severe combat-related injury (Injury Severity Score≥25). In addition, all crude UBs concentrations were significantly higher for blast vs. GSW patients (p<0.05). After adjusting for injury severity score and time of UB draw, KIM-1 (2.80 vs. 2.31; p=0.03) and LFABP (−1.11 vs. −1.92; p=0.02) were significantly higher for patients with a blast mechanism of injury. There were no significant differences in UBs between burn and non-burn civilian trauma patients. Future studies are needed to understand the physiologic response to trauma and the extent that UBs reflect these underlying processes. PMID:27798535

Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging and Lewy body disease.

PubMed

Hou, Xu; Fiesel, Fabienne C; Truban, Dominika; Castanedes Casey, Monica; Lin, Wen-Lang; Soto, Alexandra I; Tacik, Pawel; Rousseau, Linda G; Diehl, Nancy N; Heckman, Michael G; Lorenzo-Betancor, Oswaldo; Ferrer, Isidre; Arbelo, José M; Steele, John C; Farrer, Matthew J; Cornejo-Olivas, Mario; Torres, Luis; Mata, Ignacio F; Graff-Radford, Neill R; Wszolek, Zbigniew K; Ross, Owen A; Murray, Melissa E; Dickson, Dennis W; Springer, Wolfdieter

2018-06-27

Although exact causes of Parkinson disease (PD) remain enigmatic, mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuron susceptibility in both familial and sporadic PD. Two genes associated with recessive, early-onset PD encode the ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase PRKN/PARK2/Parkin, which together orchestrate a protective mitochondrial quality control (mitoQC) pathway. Upon stress, both enzymes cooperatively identify and decorate damaged mitochondria with phosphorylated poly-Ub (p-S65-Ub) chains. This specific label is subsequently recognized by autophagy receptors that further facilitate mitochondrial degradation in lysosomes (mitophagy). Here, we analyzed human post-mortem brain specimens and identified distinct pools of p-S65-Ub-positive structures that partially colocalized with markers of mitochondria, autophagy, lysosomes and/or granulovacuolar degeneration bodies. We further quantified levels and distribution of the 'mitophagy tag' in 2 large cohorts of brain samples from normal aging and Lewy body disease (LBD) cases using unbiased digital pathology. Somatic p-S65-Ub structures independently increased with age and disease in distinct brain regions and enhanced levels in LBD brain were age- and Braak tangle stage-dependent. Additionally, we observed significant correlations of p-S65-Ub with LBs and neurofibrillary tangle levels in disease. The degree of co-existing p-S65-Ub signals and pathological PD hallmarks increased in the pre-mature stage, but decreased in the late stage of LB or tangle aggregation. Altogether, our study provides further evidence for a potential pathogenic overlap among different forms of PD and suggests that p-S65-Ub can serve as a biomarker for mitochondrial damage in aging and disease.

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

PubMed Central

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-01-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages. PMID:24992446

PolyUbiquitin chain linkage topology selects the functions from the underlying binding landscape.

PubMed

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-07-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages.

Increase in ubiquitin-protein conjugates concomitant with the increase in proteolysis in rat skeletal muscle during starvation and atrophy denervation

NASA Technical Reports Server (NTRS)

Wing, S. S.; Haas, A. L.; Goldberg, A. L.

1995-01-01

The rapid loss of skeletal-muscle protein during starvation and after denervation occurs primarily through increased rates of protein breakdown and activation of a non-lysosomal ATP-dependent proteolytic process. To investigate whether protein flux through the ubiquitin (Ub)-proteasome pathway is enhanced, as was suggested by related studies, we measured, using specific polyclonal antibodies, the levels of Ub-conjugated proteins in normal and atrophying muscles. The content of these critical intermediates had increased 50-250% after food deprivation in the extensor digitorum longus and soleus muscles 2 days after denervation. Like rates of proteolysis, the amount of Ub-protein conjugates and the fraction of Ub conjugated to proteins increased progressively during food deprivation and returned to normal within 1 day of refeeding. During starvation, muscles of adrenalectomized rats failed to increase protein breakdown, and they showed 50% lower levels of Ub-protein conjugates than those of starved control animals. The changes in the pools of Ub-conjugated proteins (the substrates for the 26S proteasome) thus coincided with and can account for the alterations in overall proteolysis. In this pathway, large multiubiquitinated proteins are preferentially degraded, and the Ub-protein conjugates that accumulated in atrophying muscles were of high molecular mass (> 100 kDa). When innervated and denervated gastrocnemius muscles were fractionated, a significant increase in ubiquitinated proteins was found in the myofibrillar fraction, the proteins of which are preferentially degraded on denervation, but not in the soluble fraction. Thus activation of this proteolytic pathway in atrophying muscles probably occurs initially by increasing Ub conjugation to cell proteins. The resulting accumulation of Ub-protein conjugates suggests that their degradation by the 26S proteasome complex subsequently becomes rate-limiting in these catabolic states.

Quantifying ubiquitin signaling.

PubMed

Ordureau, Alban; Münch, Christian; Harper, J Wade

2015-05-21

Ubiquitin (UB)-driven signaling systems permeate biology, and are often integrated with other types of post-translational modifications (PTMs), including phosphorylation. Flux through such pathways is dictated by the fractional stoichiometry of distinct modifications and protein assemblies as well as the spatial organization of pathway components. Yet, we rarely understand the dynamics and stoichiometry of rate-limiting intermediates along a reaction trajectory. Here, we review how quantitative proteomic tools and enrichment strategies are being used to quantify UB-dependent signaling systems, and to integrate UB signaling with regulatory phosphorylation events, illustrated with the PINK1/PARKIN pathway. A key feature of ubiquitylation is that the identity of UB chain linkage types can control downstream processes. We also describe how proteomic and enzymological tools can be used to identify and quantify UB chain synthesis and linkage preferences. The emergence of sophisticated quantitative proteomic approaches will set a new standard for elucidating biochemical mechanisms of UB-driven signaling systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Prokaryotic Ubiquitin-Like Protein Modification

PubMed Central

Maupin-Furlow, Julie A.

2016-01-01

Prokaryotes form ubiquitin (Ub)-like isopeptide bonds on the lysine residues of proteins by at least two distinct pathways that are reversible and regulated. In mycobacteria, the C-terminal Gln of Pup (prokaryotic ubiquitin-like protein) is deamidated and isopeptide linked to proteins by a mechanism distinct from ubiquitylation in enzymology yet analogous to ubiquitylation in targeting proteins for destruction by proteasomes. Ub-fold proteins of archaea (SAMPs, small archaeal modifier proteins) and Thermus (TtuB, tRNA-two-thiouridine B) that differ from Ub in amino acid sequence, yet share a common β-grasp fold, also form isopeptide bonds by a mechanism that appears streamlined compared with ubiquitylation. SAMPs and TtuB are found to be members of a small group of Ub-fold proteins that function not only in protein modification but also in sulfur-transfer pathways associated with tRNA thiolation and molybdopterin biosynthesis. These multifunctional Ub-fold proteins are thought to be some of the most ancient of Ub-like protein modifiers. PMID:24995873

USP7 is a SUMO deubiquitinase essential for DNA replication

PubMed Central

Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia; Lopez-Contreras, Andres J; Ruppen, Isabel; Murga, Matilde; Muñoz, Javier; Mendez, Juan; Fernandez-Capetillo, Oscar

2016-01-01

Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates various aspects of DNA replication. We previously showed that the chromatin around replisomes is rich in SUMO and depleted in Ub, whereas an opposite pattern is observed in mature chromatin. How this SUMO-rich/Ub-low environment is maintained at sites of DNA replication is not known. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Chemical inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced to chromatin away from replisomes. Our findings provide a model to explain the differential accumulation of SUMO and Ub at replication forks, and identify an essential role of USP7 in DNA replication that should be taken into account for the use of USP7 inhibitors as anticancer agents. PMID:26950370

The developmental programme for genesis of the entire kidney is recapitulated in Wilms tumour.

PubMed

Fukuzawa, Ryuji; Anaka, Matthew R; Morison, Ian M; Reeve, Anthony E

2017-01-01

Wilms tumour (WT) is an embryonal tumour that recapitulates kidney development. The normal kidney is formed from two distinct embryological origins: the metanephric mesenchyme (MM) and the ureteric bud (UB). It is generally accepted that WT arises from precursor cells in the MM; however whether UB-equivalent structures participate in tumorigenesis is uncertain. To address the question of the involvement of UB, we assessed 55 Wilms tumours for the molecular features of MM and UB using gene expression profiling, immunohistochemsitry and immunofluorescence. Expression profiling primarily based on the Genitourinary Molecular Anatomy Project data identified molecular signatures of the UB and collecting duct as well as those of the proximal and distal tubules in the triphasic histology group. We performed immunolabeling for fetal kidneys and WTs. We focused on a central epithelial blastema pattern which is the characteristic of triphasic histology characterized by UB-like epithelial structures surrounded by MM and MM-derived epithelial structures, evoking the induction/aggregation phase of the developing kidney. The UB-like epithelial structures and surrounding MM and epithelial structures resembling early glomerular epithelium, proximal and distal tubules showed similar expression patterns to those of the developing kidney. These observations indicate WTs can arise from a precursor cell capable of generating the entire kidney, such as the cells of the intermediate mesoderm from which both the MM and UB are derived. Moreover, this provides an explanation for the variable histological features of mesenchymal to epithelial differentiation seen in WT.

Mechanism for recognition of polyubiquitin chains: balancing affinity through interplay between multivalent binding and dynamics.

PubMed

Markin, Craig J; Xiao, Wei; Spyracopoulos, Leo

2010-08-18

RAP80 plays a key role in signal transduction in the DNA damage response by recruiting proteins to DNA damage foci by binding K63-polyubiquitin chains with two tandem ubiquitin-interacting motifs (tUIM). It is generally recognized that the typically weak interaction between ubiquitin (Ub) and various recognition motifs is intensified by themes such as tandem recognition motifs and Ub polymerization to achieve biological relevance. However, it remains an intricate problem to develop a detailed molecular mechanism to describe the process that leads to amplification of the Ub signal. A battery of solution-state NMR methods and molecular dynamics simulations were used to demonstrate that RAP80-tUIM employs mono- and multivalent interactions with polyUb chains to achieve enhanced affinity in comparison to monoUb interactions for signal amplification. The enhanced affinity is balanced by unfavorable entropic effects that include partial quenching of rapid reorientation between individual UIM domains and individual Ub domains in the bound state. For the RAP80-tUIM-polyUb interaction, increases in affinity with increasing chain length are a result of increased numbers of mono- and multivalent binding sites in the longer polyUb chains. The mono- and multivalent interactions are characterized by intrinsically weak binding and fast off-rates; these weak interactions with fast kinetics may be an important factor underlying the transient nature of protein-protein interactions that comprise DNA damage foci.

The developmental programme for genesis of the entire kidney is recapitulated in Wilms tumour

PubMed Central

Anaka, Matthew R.; Morison, Ian M.; Reeve, Anthony E.

2017-01-01

Wilms tumour (WT) is an embryonal tumour that recapitulates kidney development. The normal kidney is formed from two distinct embryological origins: the metanephric mesenchyme (MM) and the ureteric bud (UB). It is generally accepted that WT arises from precursor cells in the MM; however whether UB-equivalent structures participate in tumorigenesis is uncertain. To address the question of the involvement of UB, we assessed 55 Wilms tumours for the molecular features of MM and UB using gene expression profiling, immunohistochemsitry and immunofluorescence. Expression profiling primarily based on the Genitourinary Molecular Anatomy Project data identified molecular signatures of the UB and collecting duct as well as those of the proximal and distal tubules in the triphasic histology group. We performed immunolabeling for fetal kidneys and WTs. We focused on a central epithelial blastema pattern which is the characteristic of triphasic histology characterized by UB-like epithelial structures surrounded by MM and MM-derived epithelial structures, evoking the induction/aggregation phase of the developing kidney. The UB-like epithelial structures and surrounding MM and epithelial structures resembling early glomerular epithelium, proximal and distal tubules showed similar expression patterns to those of the developing kidney. These observations indicate WTs can arise from a precursor cell capable of generating the entire kidney, such as the cells of the intermediate mesoderm from which both the MM and UB are derived. Moreover, this provides an explanation for the variable histological features of mesenchymal to epithelial differentiation seen in WT. PMID:29040332

Ubiquitinated proteins enriched from tumor cells by a ubiquitin binding protein Vx3(A7) as a potent cancer vaccine.

PubMed

Aldarouish, Mohanad; Wang, Huzhan; Zhou, Meng; Hu, Hong-Ming; Wang, Li-Xin

2015-04-16

Our previous studies have demonstrated that autophagosome-enriched vaccine (named DRibbles: DRiPs-containing blebs) induce a potent anti-tumor efficacy in different murine tumor models, in which DRibble-containing ubiquitinated proteins are efficient tumor-specific antigen source for the cross-presentation after being loaded onto dendritic cells. In this study, we sought to detect whether ubiquitinated proteins enriched from tumor cells could be used directly as a novel cancer vaccine. The ubiquitin binding protein Vx3(A7) was used to isolate ubiquitinated proteins from EL4 and B16-F10 tumor cells after blocking their proteasomal degradation pathway. C57BL/6 mice were vaccinated with different doses of Ub-enriched proteins via inguinal lymph nodes or subcutaneous injection and with DRibbles, Ub-depleted proteins and whole cell lysate as comparison groups, respectively. The lymphocytes from the vaccinated mice were re-stimulated with inactivated tumor cells and the levels of IFN-γ in the supernatant were detected by ELISA. Anti-tumor efficacy of Ub-enriched proteins vaccine was evaluated by monitoring tumor growth in established tumor mice models. Graphpad Prism 5.0 was used for all statistical analysis. We found that after stimulation with inactivated tumor cells, the lymphocytes from the Ub-enriched proteins-vaccinated mice secreted high level of IFN-γ in dose dependent manner, in which the priming vaccination via inguinal lymph nodes injection induced higher IFN-γ level than that via subcutaneous injection. Moreover, the level of secreted IFN-γ in the Ub-enriched proteins group was markedly higher than that in the whole cell lysate and Ub-depleted proteins. Interestingly, the lymphocytes from mice vaccinated with Ub-enriched proteins, but not Ub-depleted proteins and whole cell lysates, isolated from EL4 or B16-F10 tumor cells also produced an obvious level of IFN-γ when stimulated alternately with inactivated B16-F10 or EL4 tumor cells. Furthermore, Ub-enriched proteins vaccine showed a significant inhibitory effect on in vivo growth of homologous tumor, as well as allogeneic tumor, compared with Ub-depleted proteins and tumor cell lysate. Tumor growth was regressed after three times of vaccination with Ub-enriched proteins in contrast to other groups. These results indicated that Ub-enriched proteins isolated from tumor cells may have a potential as a potent vaccine for immunotherapy against cancer.

78 FR 12358 - UBS Financial Services, Inc., Wealth Management Americas Operations, Including On-Site Leased...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

..., Inc., Wealth Management Americas Operations, Including On-Site Leased Workers From Leafstone... Services, Inc., Wealth Management Americas Operations (UBS), Weehawken, New Jersey. The workers are engaged... to include all leased workers on-site at UBS Financial Services, Inc., Wealth Management Americas...

Immunohistochemical detection of ubiquitin-positive intracytoplasmic eosinophilic inclusion bodies in diffuse alveolar damage.

PubMed

Yamada, T; Uehara, K; Kawanishi, R; Mizutani, T; Sunagawa, K; Araya, J; Kawabata, Y

2006-06-01

To clarify the relationship between ubiquitin-positive pneumocytes and intracytoplasmic eosinophilic inclusion bodies (IB) in patients who died of diffuse alveolar damage (DAD). Eighteen patients with DAD were studied, in whom hyaline membranes were present in one or more out of five sections from each lobe of the lungs and 15 patients with no DAD. Light microscopy revealed hyaline membrane in over 25% of lobes from 18 patients with DAD. The cytoplasm of pneumocytes from six of 18 cases of DAD contained IB. Immunohistochemically, all IBs were characteristically positive for both ubiquitin (Ub) and cytokeratin KL-1. Cytoplasmic granules were also Ub+ in four cases of DAD without IB. IB+ or Ub+ pneumocytes were undetectable in non-DAD patients. We evaluated DAD severity based on hyaline membrane formation; the mean score in DAD with IB (3.60; n = 6) was significantly higher than that in Ub- (2.92; n = 8). Ub+ pneumocytes were found with or without IB among those cases with high DAD scores. These findings suggest that disordered proteolysis in the Ub-mediated proteasome system leads to the accumulation of abnormal ubiquitinated protein, which includes cytokeratin, in pneumocytes. This is the first report to suggest that Ub+ pneumocytes are associated with disease severity in patients with DAD.

Ubiquitin Regulates Caspase Recruitment Domain-mediated Signaling by Nucleotide-binding Oligomerization Domain-containing Proteins NOD1 and NOD2*

PubMed Central

Ver Heul, Aaron M.; Fowler, C. Andrew; Ramaswamy, S.; Piper, Robert C.

2013-01-01

NOD1 and NOD2 (nucleotide-binding oligomerization domain-containing proteins) are intracellular pattern recognition receptors that activate inflammation and autophagy. These pathways rely on the caspase recruitment domains (CARDs) within the receptors, which serve as protein interaction platforms that coordinately regulate immune signaling. We show that NOD1 CARD binds ubiquitin (Ub), in addition to directly binding its downstream targets receptor-interacting protein kinase 2 (RIP2) and autophagy-related protein 16-1 (ATG16L1). NMR spectroscopy and structure-guided mutagenesis identified a small hydrophobic surface of NOD1 CARD that binds Ub. In vitro, Ub competes with RIP2 for association with NOD1 CARD. In vivo, we found that the ligand-stimulated activity of NOD1 with a mutant CARD lacking Ub binding but retaining ATG16L1 and RIP2 binding is increased relative to wild-type NOD1. Likewise, point mutations in the tandem NOD2 CARDs at positions analogous to the surface residues defining the Ub interface on NOD1 resulted in loss of Ub binding and increased ligand-stimulated NOD2 signaling. These data suggest that Ub binding provides a negative feedback loop upon NOD-dependent activation of RIP2. PMID:23300079

Computing for Finance

ScienceCinema

None

2018-01-24

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followed by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Seti@Home. Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance. 4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.

Computing for Finance

ScienceCinema

None

2018-06-20

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followed by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry. Michael Yoo, Managing Director, Head of the Technical Council, UBS. Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse. Grid computing gets mentions in the press for community programs starting last decade with "Seti@Home". Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.

Computing for Finance

ScienceCinema

None

2018-01-25

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followed by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industries Adam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.

Computing for Finance

ScienceCinema

None

2018-02-02

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followed by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance. 4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.

Computing for Finance

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

None

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followedmore » by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Seti@Home. Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance. 4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.« less

Computing for Finance

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

None

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followedmore » by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry. Michael Yoo, Managing Director, Head of the Technical Council, UBS. Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse. Grid computing gets mentions in the press for community programs starting last decade with "Seti@Home". Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.« less

Computing for Finance

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

None

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followedmore » by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance. 4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.« less

Computing for Finance

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

None

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followedmore » by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.« less

Computing for Finance

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

None

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followedmore » by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industries Adam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.« less

Computing for Finance

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

None

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followedmore » by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Seti@Home. Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN. 3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.« less

Computing for Finance

ScienceCinema

None

2018-02-01

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followed by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN.3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.

Computing for Finance

ScienceCinema

None

2018-01-24

The finance sector is one of the driving forces for the use of distributed or Grid computing for business purposes. The speakers will review the state-of-the-art of high performance computing in the financial sector, and provide insight into how different types of Grid computing – from local clusters to global networks - are being applied to financial applications. They will also describe the use of software and techniques from physics, such as Monte Carlo simulations, in the financial world. There will be four talks of 20min each. The talk abstracts and speaker bios are listed below. This will be followed by a Q&A; panel session with the speakers. From 19:00 onwards there will be a networking cocktail for audience and speakers. This is an EGEE / CERN openlab event organized in collaboration with the regional business network rezonance.ch. A webcast of the event will be made available for subsequent viewing, along with powerpoint material presented by the speakers. Attendance is free and open to all. Registration is mandatory via www.rezonance.ch, including for CERN staff. 1. Overview of High Performance Computing in the Financial Industry Michael Yoo, Managing Director, Head of the Technical Council, UBS Presentation will describe the key business challenges driving the need for HPC solutions, describe the means in which those challenges are being addressed within UBS (such as GRID) as well as the limitations of some of these solutions, and assess some of the newer HPC technologies which may also play a role in the Financial Industry in the future. Speaker Bio: Michael originally joined the former Swiss Bank Corporation in 1994 in New York as a developer on a large data warehouse project. In 1996 he left SBC and took a role with Fidelity Investments in Boston. Unable to stay away for long, he returned to SBC in 1997 while working for Perot Systems in Singapore. Finally, in 1998 he formally returned to UBS in Stamford following the merger with SBC and has remained with UBS for the past 9 years. During his tenure at UBS, he has had a number of leadership roles within IT in development, support and architecture. In 2006 Michael relocated to Switzerland to take up his current role as head of the UBS IB Technical Council, responsible for the overall technology strategy and vision of the Investment Bank. One of Michael's key responsibilities is to manage the UBS High Performance Computing Research Lab and he has been involved in a number of initiatives in the HPC space. 2. Grid in the Commercial WorldFred Gedling, Chief Technology Officer EMEA and Senior Vice President Global Services, DataSynapse Grid computing gets mentions in the press for community programs starting last decade with Seti@Home. Government, national and supranational initiatives in grid receive some press. One of the IT-industries' best-kept secrets is the use of grid computing by commercial organizations with spectacular results. Grid Computing and its evolution into Application Virtualization is discussed and how this is key to the next generation data center. Speaker Bio: Fred Gedling holds the joint roles of Chief Technology Officer for EMEA and Senior Vice President of Global Services at DataSynapse, a global provider of application virtualisation software. Based in London and working closely with organisations seeking to optimise their IT infrastructures, Fred offers unique insights into the technology of virtualisation as well as the methodology of establishing ROI and rapid deployment to the immediate advantage of the business. Fred has more than fifteen years experience of enterprise middleware and high-performance infrastructures. Prior to DataSynapse he worked in high performance CRM middleware and was the CTO EMEA for New Era of Networks (NEON) during the rapid growth of Enterprise Application Integration. His 25-year career in technology also includes management positions at Goldman Sachs and Stratus Computer. Fred holds a First Class Bsc (Hons) degree in Physics with Astrophysics from the University of Leeds and had the privilege of being a summer student at CERN. 3. Opportunities for gLite in finance and related industriesAdam Vile, Head of Grid, HPC and Technical Computing, Excelian Ltd.gLite, the Grid software developed by the EGEE project, has been exceedingly successful as an enabling infrastructure, and has been a massive success in bringing together scientific and technical communities to provide the compute power to address previously incomputable problems. Not so in the finance industry. In its current form gLite would be a business disabler. There are other middleware tools that solve the finance communities compute problems much better. Things are moving on, however. There are moves afoot in the open source community to evolve the technology to address other, more sophisticated needs such as utility and interactive computing. In this talk, I will describe how Excelian is providing Grid consultancy services for the finance community and how, through its relationship to the EGEE project, Excelian is helping to identify and exploit opportunities as the research and business worlds converge. Because of the strong third party presence in the finance industry, such opportunities are few and far between, but they are there, especially as we expand sideways into related verticals such as the smaller hedge funds and energy companies. This talk will give an overview of the barriers to adoption of gLite in the finance industry and highlight some of the opportunities offered in this and related industries as the ideas around Grid mature. Speaker Bio: Dr Adam Vile is a senior consultant and head of the Grid and HPC practice at Excelian, a consultancy that focuses on financial markets professional services. He has spent many years in investment banking, as a developer, project manager and architect in both front and back office. Before joining Excelian he was senior Grid and HPC architect at Barclays Capital. Prior to joining investment banking, Adam spent a number of years lecturing in IT and mathematics at a UK University and maintains links with academia through lectures, research and through validation and steering of postgraduate courses. He is a chartered mathematician and was the conference chair of the Institute of Mathematics and its Applications first conference in computational Finance.4. From Monte Carlo to Wall Street Daniel Egloff, Head of Financial Engineering Computing Unit, Zürich Cantonal Bank High performance computing techniques provide new means to solve computationally hard problems in the financial service industry. First I consider Monte Carlo simulation and illustrate how it can be used to implement a sophisticated credit risk management and economic capital framework. From a HPC perspective, basic Monte Carlo simulation is embarrassingly parallel and can be implemented efficiently on distributed memory clusters. Additional difficulties arise for adaptive variance reduction schemes, if the information content in a sample is very small, and if the amount of simulated date becomes huge such that incremental processing algorithms are indispensable. We discuss the business value of an advanced credit risk quantification which is particularly compelling in these days. While Monte Carlo simulation is a very versatile tool it is not always the preferred solution for the pricing of complex products like multi asset options, structured products, or credit derivatives. As a second application I show how operator methods can be used to develop a pricing framework. The scalability of operator methods relies heavily on optimized dense matrix-matrix multiplications and requires specialized BLAS level-3 implementations provided by specialized FPGA or GPU boards. Speaker Bio: Daniel Egloff studied mathematics, theoretical physics, and computer science at the University of Zurich and the ETH Zurich. He holds a PhD in Mathematics from University of Fribourg, Switzerland. After his PhD he started to work for a large Swiss insurance company in the area of asset and liability management. He continued his professional career in the consulting industry. At KPMG and Arthur Andersen he consulted international clients and implemented quantitative risk management solutions for financial institutions and insurance companies. In 2002 he joined Zurich Cantonal Bank. He was assigned to develop and implement credit portfolio risk and economic capital methodologies. He built up a competence center for high performance and cluster computing. Currently, Daniel Egloff is heading the Financial Computing unit in the ZKB Financial Engineering division. He and his team is engineering and operating high performance cluster applications for computationally intensive problems in financial risk management.

Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis

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

Ji, Jiayao; Medical College of NanKai University, Tianjin; Li, Qinggang

2012-05-11

Highlights: Black-Right-Pointing-Pointer Overexpression of Robo2 caused reduced UB branching and glomerular number. Black-Right-Pointing-Pointer Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. Black-Right-Pointing-Pointer No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. Black-Right-Pointing-Pointer Overexpression of Robo2 affected MM cells migration and caused UB deficit. Black-Right-Pointing-Pointer The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2-Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2-Robo2 signaling is also importantmore » for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that overexpression of Robo2 by microinjection in embryonic kidneys is an effective approach to study the function of Robo2.« less

Materials Data on UB2Ru3 (SG:191) by Materials Project

DOE Data Explorer

Kristin Persson

2015-02-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on UB2Os3 (SG:191) by Materials Project

DOE Data Explorer

Kristin Persson

2015-02-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on UB2Ir3 (SG:191) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants.

PubMed

Amin, Sanjiv B; Wang, Hongyue

2018-01-01

To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day. For the 166 infants studied, peak UB significantly correlated with concomitant Ka (r = -0.44, P = .001) but not with concomitant TSB or BAMR after adjusting for GA. On multiple regression analyses, there was a significant association of concomitant Ka (-0.06, 95% CI -0.08 to -0.04, P = .0001), but not concomitant TSB or BAMR with peak UB after controlling for GA, birth weight, race, and sex. GA group was a significant effect modifier for the association between Ka and peak UB (0.03, 95% CI 0.02-0.04, P < .001). Interaction analyses showed the association between concomitant Ka and peak UB was significant for the 24-30 weeks GA group infants, but not for the 30 1/7 -33 weeks GA group infants. Peak UB was primarily associated with a decrease in binding affinity in infants ≤30 weeks GA. Interventions aimed at improving binding affinity may be important in decreasing the risk of bilirubin-induced neurotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

On the origin of the highest ozone episodes in Spain.

PubMed

Querol, X; Alastuey, A; Reche, C; Orio, A; Pallares, M; Reina, F; Dieguez, J J; Mantilla, E; Escudero, M; Alonso, L; Gangoiti, G; Millán, M

2016-12-01

The 2000-2015 occurrences of the highest ozone (O 3 ) pollution episodes in Spain were evaluated to investigate their origin. To this end, data series available for urban and regional background (UB and RB), traffic (TR) and industrial (IN) sites were analysed separately and intercompared. Results evidenced that during these 16years mean O 3 levels in the RB sites did not change significantly, and remained constantly high. However, there is a clear increase at the TR and UB sites. Although sensitivity analysis is needed to interpret the cause of this increasing trend, this might be caused probably by the lower O 3 titration intensity due to the preferential abatement of NO vs NO 2 , as supported from the neutral trend of O X (NO 2 +O 3 ) at these sites. We found that the exceedances of the hourly information threshold for O 3 (>180μg/m 3 ) are recorded mostly at UB and IN sites located in seven areas of Spain (specific hotspots or at the tail end of large urban plumes), and that these increased during summer heatwaves (i.e. 2003 and 2015). Although the external contribution of regional-to-subcontinental transported O 3 might be relevant during the highest O 3 episodes in the Western Mediterranean, our results evidenced that in the above specific areas, regional-local O 3 production decisively contributes to the exceedances of the information threshold. Also that the human protection threshold and the AOT40 are more frequently exceeded in the Central, Southern and Mediterranean sides of the Iberian Peninsula. The design of effective episode abatement measures is quite complex in those conditions, due to both the nonlinearity of the chemical processes of O 3 formation and destruction, and to the interplay with the complex meteorological setting, causing frequent recirculation and in situ aging of air masses. However, the combination of meteorological forecasting of the main recirculation processes and sensitivity analysis of NO X /VOC emission abatement measures might be powerful tools to evaluate the effectiveness of potential O 3 mitigation strategies. Finally we would like to highlight that the current UB, RB, IN and TR classification (somewhat subjective) is not adequate to interpret the origin of O 3 exceedances in complex areas of Southern Europe. Thus, a UB station recording exceedances, and located in a small city in the tail end of an urban plume of a large city, receives not only the contribution from its own UB, but mainly from the specific high O 3 RB caused by the urban plume transport. Copyright © 2016 Elsevier B.V. All rights reserved.

76 FR 78621 - Applications for New Awards; Upward Bound Program (Regular Upward Bound (UB))

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

... high school who in the first year of postsecondary education placed into college-level math and English... education placed into college-level math and English or needed remediation in those subjects. The Department... grants; Veterans UB grants; and UB Math and Science grants. This notice only announces deadlines and...

Polyubiquitin-sensor proteins reveal localization and linkage-type dependence of cellular ubiquitin signaling

PubMed Central

Sims, Joshua J.; Scavone, Francesco; Cooper, Eric M.; Kane, Lesley A.; Youle, Richard J.; Boeke, Jef D.; Cohen, Robert E.

2012-01-01

Polyubiquitin (polyUb) chain topology is thought to direct modified substrates to specific fates, but this function-topology relationship is poorly understood, as are the dynamics and subcellular locations of specific polyUb signals. Experimental access to these questions has been limited because linkage-specific inhibitors and in vivo sensors have been unavailable. Here we present a general strategy to track linkage-specific polyUb signals in yeast and mammalian cells, and to probe their functions. We designed several high-affinity lysine-63-polyUb-binding proteins and demonstrate their specificity both in vitro and in cells. We apply these tools as competitive inhibitors to dissect the polyUb-linkage dependence of NF-κB activation in several cell types, inferring the essential role of lysine-63-polyUb for signaling via the IL-1β and TNF-related weak inducer of apoptosis (TWEAK) but not TNF-α receptors. We anticipate live-cell imaging, proteomic, and biochemical applications for these tools, and extension of the design strategy to other polymeric ubiquitin-like protein modifications. PMID:22306808

A conserved catalytic residue in the ubiquitin-conjugating enzyme family

PubMed Central

Wu, Pei-Ying; Hanlon, Mary; Eddins, Michael; Tsui, Colleen; Rogers, Richard S.; Jensen, Jane P.; Matunis, Michael J.; Weissman, Allan M.; Wolberger, Cynthia P.; Pickart, Cecile M.

2003-01-01

Ubiquitin (Ub) regulates diverse functions in eukaryotes through its attachment to other proteins. The defining step in this protein modification pathway is the attack of a substrate lysine residue on Ub bound through its C-terminus to the active site cysteine residue of a Ub-conjugating enzyme (E2) or certain Ub ligases (E3s). So far, these E2 and E3 cysteine residues are the only enzyme groups known to participate in the catalysis of conjugation. Here we show that a strictly conserved E2 asparagine residue is critical for catalysis of E2- and E2/RING E3-dependent isopeptide bond formation, but dispensable for upstream and downstream reactions of Ub thiol ester formation. In constrast, the strictly conserved histidine and proline residues immediately upstream of the asparagine are dispensable for catalysis of isopeptide bond formation. We propose that the conserved asparagine side chain stabilizes the oxyanion intermediate formed during lysine attack. The E2 asparagine is the first non-covalent catalytic group to be proposed in any Ub conjugation factor. PMID:14517261

Personal Values, Social Capital, and Higher Education Student Career Decidedness: A New "Protean"-Informed Model

ERIC Educational Resources Information Center

Fearon, Colm; Nachmias, Stefanos; McLaughlin, Heather; Jackson, Stephen

2018-01-01

This study investigates the role of personal values as motivational antecedents for understanding higher education (HE) student career decidedness among university business school (UBS) students. We propose a new "protean"-informed HE student career decidedness model for theorizing how both personal values and social capital mediators…

Newborn Mouse Lens Proteome and Its Alteration by Lysine 6 Mutant Ubiquitin

PubMed Central

2015-01-01

Ubiquitin is a tag that often initiates degradation of proteins by the proteasome in the ubiquitin proteasome system. Targeted expression of K6W mutant ubiquitin (K6W-Ub) in the lens results in defects in lens development and cataract formation, suggesting critical functions for ubiquitin in lens. To study the developmental processes that require intact ubiquitin, we executed the most extensive characterization of the lens proteome to date. We quantified lens protein expression changes in multiple replicate pools of P1 wild-type and K6W-Ub-expressing mouse lenses. Lens proteins were digested with trypsin, peptides were separated using strong cation exchange and reversed-phase liquid chromatography, and tandem mass (MS/MS) spectra were collected with a linear ion trap. Transgenic mice that expressed low levels of K6W-Ub (low expressers) had normal, clear lenses at birth, whereas the lenses that expressed high levels of K6W-Ub (higher expressers) had abnormal lenses and cataracts at birth. A total of 2052 proteins were identified, of which 996 were reliably quantified and compared between wild-type and K6W-Ub transgenic mice. Consistent with a delayed developmental program, fiber-cell-specific proteins, such as γ-crystallins (γA, γB, γC, and γE), were down-regulated in K6W-Ub higher expressers. Up-regulated proteins were involved in energy metabolism, signal transduction, and proteolysis. The K6W-Ub low expressers exhibited delayed onset and milder cataract consistent with smaller changes in protein expression. Because lens protein expression changes occurred prior to lens morphological abnormalities and cataract formation in K6W-Ub low expressers, it appears that expression of K6W-Ub sets in motion a process of altered protein expression that results in developmental defects and cataract. PMID:24450463

Effect of cellular ubiquitin levels on the regulation of oxidative stress response and proteasome function via Nrf1

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

Lee, Donghee; Ryu, Kwon-Yul

The polyubiquitin genes Ubb and Ubc are upregulated under oxidative stress induced by arsenite [As(III)]. However, the role of ubiquitin (Ub) under As(III) exposure is not known in detail. In a previous study, we showed that the reduced viability observed in Ubc{sup −/−} mouse embryonic fibroblasts under As(III) exposure was not due to dysregulation of the Nrf2–Keap1 pathway, which prompted us to investigate another NFE2 family protein, nuclear factor erythroid 2-related factor 1 (Nrf1). In this study, we found that Ub deficiency due to Ubc knockdown in N2a cells reduced cell viability and proteasome activity under As(III) exposure. Furthermore, mRNAmore » levels of the proteasome subunit Psma1 were also reduced. In addition, Ub deficiency led to the nuclear accumulation of the p65 isoform of Nrf1 under As(III) exposure. Interestingly, the overexpression of p65-Nrf1 recapitulated the phenotypes of Ub-deficient N2a cells under As(III) exposure. On the other hand, Nrf1 knockdown suppressed the death of Ub-deficient N2a cells upon exposure to As(III). Therefore, the levels of p65-Nrf1 may play an important role in the maintenance of cell viability under oxidative stress induced by As(III). - Highlights: • N2a cells exhibit reduced viability upon exposure to As(III) via Ubc knockdown. • As(III)-induced proteasomal regulation is impaired in Ub-deficient N2a cells. • Ub deficiency leads to the nuclear accumulation of p65-Nrf1 under As(III) exposure. • p65 expression recapitulates As(III)-induced phenotypes of Ub-deficient N2a cells. • Nrf1 knockdown suppressed As(III)-induced death of Ub-deficient N2a cells.« less

Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog

PubMed Central

Spring-Connell, Alexander M.; Evich, Marina G.; Debelak, Harald; Seela, Frank; Germann, Markus W.

2016-01-01

A truly universal nucleobase enables a host of novel applications such as simplified templates for PCR primers, randomized sequencing and DNA based devices. A universal base must pair indiscriminately to each of the canonical bases with little or preferably no destabilization of the overall duplex. In reality, many candidates either destabilize the duplex or do not base pair indiscriminatingly. The novel base 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin- 4-amine) N8-(2′deoxyribonucleoside), a deoxyadenosine analog (UB), pairs with each of the natural DNA bases with little sequence preference. We have utilized NMR complemented with molecular dynamic calculations to characterize the structure and dynamics of a UB incorporated into a DNA duplex. The UB participates in base stacking with little to no perturbation of the local structure yet forms an unusual base pair that samples multiple conformations. These local dynamics result in the complete disappearance of a single UB proton resonance under native conditions. Accommodation of the UB is additionally stabilized via heightened backbone conformational sampling. NMR combined with various computational techniques has allowed for a comprehensive characterization of both structural and dynamic effects of the UB in a DNA duplex and underlines that the UB as a strong candidate for universal base applications. PMID:27566150

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

PubMed Central

Nakagawa, Takeya; Kajitani, Takuya; Togo, Shinji; Masuko, Norio; Ohdan, Hideki; Hishikawa, Yoshitaka; Koji, Takehiko; Matsuyama, Toshifumi; Ikura, Tsuyoshi; Muramatsu, Masami; Ito, Takashi

2008-01-01

Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di- and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di- and trimethylation of H3K4, resulting in regulation of transcriptional initiation. PMID:18172164

Silver and gold nanoparticles produced by pulsed laser ablation in liquid to investigate their interaction with Ubiquitin

NASA Astrophysics Data System (ADS)

Dell'Aglio, M.; Mangini, V.; Valenza, G.; De Pascale, O.; De Stradis, A.; Natile, G.; Arnesano, F.; De Giacomo, A.

2016-06-01

The interaction of nanoparticles (NPs) with proteins is widely investigated since it can be a key issue in addressing the problem of nanotoxicity, particularly in the case of biological and medical applications. In this work, silver and gold nanoparticles (AgNPs and AuNPs) were produced in water by Pulsed Laser Ablation in Liquid (PLAL) and allowed to react with Ubiquitin (Ub) (a small human protein essential for degradative processes in cells). NPs produced by PLAL are completely free of undesired contaminants and do not require the use of stabilizers. We found that the NPs + Ub system behaves differently if the NPs are or are not treated with a stabilizer before performing the interaction with Ub, since the presence of capping agents modifies the surface reactivity of the metal-NPs. The surface plasmon resonance (SPR) absorption spectroscopy was employed to monitor the fast changes occurring in the NP colloidal solutions upon interaction with Ub. The results obtained by SPR were confirmed by TEM analysis. Therefore, when Ub interacts with bare NPs a rapid aggregation occurs and, at the same time, Ub undergoes an amyloid transition. Notably, the aggregation of AuNPs occurs at a much greater rate than that of analogous AgNPs and the Ub fibrils that are formed can be imaged by thioflavin T fluorescence.

Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability.

PubMed

Ingle, Brandall L; Veber, Brandon C; Nichols, John W; Tornero-Velez, Rogelio

2016-11-28

The free fraction of a xenobiotic in plasma (F ub ) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data are scarce for environmentally relevant chemicals. The presented work explores the merit of utilizing available pharmaceutical data to predict F ub for environmentally relevant chemicals via machine learning techniques. Quantitative structure-activity relationship (QSAR) models were constructed with k nearest neighbors (kNN), support vector machines (SVM), and random forest (RF) machine learning algorithms from a training set of 1045 pharmaceuticals. The models were then evaluated with independent test sets of pharmaceuticals (200 compounds) and environmentally relevant ToxCast chemicals (406 total, in two groups of 238 and 168 compounds). The selection of a minimal feature set of 10-15 2D molecular descriptors allowed for both informative feature interpretation and practical applicability domain assessment via a bounded box of descriptor ranges and principal component analysis. The diverse pharmaceutical and environmental chemical sets exhibit similarities in terms of chemical space (99-82% overlap), as well as comparable bias and variance in constructed learning curves. All the models exhibit significant predictability with mean absolute errors (MAE) in the range of 0.10-0.18F ub . The models performed best for highly bound chemicals (MAE 0.07-0.12), neutrals (MAE 0.11-0.14), and acids (MAE 0.14-0.17). A consensus model had the highest accuracy across both pharmaceuticals (MAE 0.151-0.155) and environmentally relevant chemicals (MAE 0.110-0.131). The inclusion of the majority of the ToxCast test sets within the AD of the consensus model, coupled with high prediction accuracy for these chemicals, indicates the model provides a QSAR for F ub that is broadly applicable to both pharmaceuticals and environmentally relevant chemicals.

Crystal Chemistry and Magnetism of Ternary Actinoid Boron Carbides UB 1- xC 1+ x and U 1- xMxB 2C with M = Sc, Lu, and Th

NASA Astrophysics Data System (ADS)

Rogl, P.; Rupp, B.; Felner, I.; Fischer, P.

1993-06-01

Within the homogeneous range of uranium monocarbide UB 1- xC 1+ x, the crystal structures of stoichiometric UBC and of the carbon-rich solid solution UB 0.78C 1.22, have been refined from single-crystal X-ray counter data. From X-ray analysis crystal symmetry in both cases is consistent with the centro-symmetric space group Cmcm and there are no indications of superstructure formation. In contrast to the fully ordered atom arrangement revealed for stoichiometric UBC ( a = 0.35899(4), b = 1.19781(12), c = 0.33474(3) nm), random occupation by boron and carbon atoms is observed for the boron site in UB 0.78C 1.22 ( a = 0.35752(4), b = 1.18584(3), c = 0.33881(4) nm). For 279(278) reflections (|F 0| > 3σ) the obtained reliability factors R x = ∑|ΔF|/∑| F0| were R x = 0.069 for UBC and R x = 0.050 for UB 0.78C 1.22. Neutron powder diffraction experiments at 9 and 295 K unambiguously revealed full occupancy by the nonmetal atoms in UB 0.78C 1.22 and prove the statistical occupation of B and C atoms in the B-sites. For the orthorhombic symmetry Cmcm, refinement was not better than R1 = 0.044. A model calculation in monoclinic symmetry C12/ m1, however, resulted in a significant reduction of the residual value to R1 = 0.030, releasing spatial constraints on the boron atoms. Thus the boron-boron chain in Cmcm (B-B = 0.1874 nm) is dissolved into boron pairs (B-B = 0.1706 nm) which are loosely bound at a distance of 0.2043 nm. The formation of C-B-B-C groups corresponds to the structure types of ThBC and Th 3B 2C 3. The magnetic behavior has been investigated in the temperature range from 4.2 K to 1000 K for UB 1- xC 1+ x (UBC-type) and U 1- xMxB 2C (ThB 2C-type for the high temperature modification and 1-UB 2C-type for the low temperature modification) with U partially substituted by Th or Sc, Lu. From magnetic susceptibilities, the alloys UB 1- xC 1+ x reveal temperature independent paramagnetism with typical intermediate valence fluctuation behavior ( TSF ˜ 350 K). ThB 2C and 1-UB 2C both are temperature independent paramagnets, whereas h-UB 2C is a ferromagnet with the rather high Curie temperature TM = 80(2) K. TM and the saturation magnetiziation per U atom both successively decrease on substitution of U by Th, Sc, or Lu in UB 2C, whereas the U-moments remain practically unchanged at μ eff(U) ˜ 1.9 μ B. Uranium L 3-XANES (X-ray Absorption Near Edge Structure) spectroscopy revealed increased d-band localization, comparable to uranium-transition metal alloys, in nonmagnetic UB 1- xC 1+ x ( x = 0, 0.22). No superconductivity was observed down to 1.5 K; no hydrogen uptake was observed for UB 2C and ThB 2C even under hydrogen pressures as high as 7 × 10 7 Pa at 670 K.

Novel curcumin analogue UBS109 potently stimulates osteoblastogenesis and suppresses osteoclastogenesis: involvement in Smad activation and NF-κB inhibition.

PubMed

Yamaguchi, Masayoshi; Moore, Terry W; Sun, Aiming; Snyder, James P; Shoji, Mamoru

2012-08-01

Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss is induced due to decreased osteoblastic bone formation and increased osteoclastic bone resorption with various pathologic states. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Pharmacologic and functional food factors may play a role in the prevention of bone loss with aging. This study was undertaken to determine the effect of curcumin analogues (curcumin, EF31, ECMN909, and UBS109), which were newly synthesized, on osteoblastogenesis and osteoclastogenesis in vitro. Among these compounds, UBS109 had a unique stimulatory effect on osteoblastic differentiation and mineralization. UBS109 stimulated both basal and bone morphogenic protein-2 (BMP2)-increased Smad-luciferase activity, the Smad signaling of which is related to osteoblastogenesis. Such an effect was not seen with other compounds. Moreover, UBS109 potently suppressed tumor necrosis factor-α (TNF-α)-increased osteoblastic nuclear factor kappa B (NF-κB)-luciferase activity. In addition, EF31, ECMN909, and UBS109 had a suppressive effect on osteoclastogenesis as compared with that of curcumin. ECMN909 and UBS109 potently inhibited the receptor activator of NF-κB (RANK) ligand (RANKL)-increased preosteoclastic NF-κB-luciferase activity, in which NF-κB signaling plays a pivotal role in osteoclastogenesis. In the present study, curcumin analogue UBS109 was found to have a stimulating effect on osteoblastogenesis and a suppressive effect on osteoclastogenesis in vitro, suggesting an anabolic effect of the compound on bone mass.

Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats

PubMed Central

Lecker, Stewart H.; Solomon, Vered; Price, S. Russ; Kwon, Yong Tae; Mitch, William E.; Goldberg, Alfred L.

1999-01-01

Insulin deficiency (e.g., in acute diabetes or fasting) is associated with enhanced protein breakdown in skeletal muscle leading to muscle wasting. Because recent studies have suggested that this increased proteolysis is due to activation of the ubiquitin-proteasome (Ub-proteasome) pathway, we investigated whether diabetes is associated with an increased rate of Ub conjugation to muscle protein. Muscle extracts from streptozotocin-induced insulin-deficient rats contained greater amounts of Ub-conjugated proteins than extracts from control animals and also 40–50% greater rates of conjugation of 125I-Ub to endogenous muscle proteins. This enhanced Ub-conjugation occurred mainly through the N-end rule pathway that involves E214k and E3α. A specific substrate of this pathway, α-lactalbumin, was ubiquitinated faster in the diabetic extracts, and a dominant negative form of E214k inhibited this increase in ubiquitination rates. Both E214k and E3α were shown to be rate-limiting for Ub conjugation because adding small amounts of either to extracts stimulated Ub conjugation. Furthermore, mRNA for E214k and E3α (but not E1) were elevated 2-fold in muscles from diabetic rats, although no significant increase in E214k and E3α content could be detected by immunoblot or activity assays. The simplest interpretation of these results is that small increases in both E214k and E3α in muscles of insulin-deficient animals together accelerate Ub conjugation and protein degradation by the N-end rule pathway, the same pathway activated in cancer cachexia, sepsis, and hyperthyroidism. J. Clin. Invest. 104:1411–1420 (1999). PMID:10562303

Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats.

PubMed

Lecker, S H; Solomon, V; Price, S R; Kwon, Y T; Mitch, W E; Goldberg, A L

1999-11-01

Insulin deficiency (e.g., in acute diabetes or fasting) is associated with enhanced protein breakdown in skeletal muscle leading to muscle wasting. Because recent studies have suggested that this increased proteolysis is due to activation of the ubiquitin-proteasome (Ub-proteasome) pathway, we investigated whether diabetes is associated with an increased rate of Ub conjugation to muscle protein. Muscle extracts from streptozotocin-induced insulin-deficient rats contained greater amounts of Ub-conjugated proteins than extracts from control animals and also 40-50% greater rates of conjugation of (125)I-Ub to endogenous muscle proteins. This enhanced Ub-conjugation occurred mainly through the N-end rule pathway that involves E2(14k) and E3alpha. A specific substrate of this pathway, alpha-lactalbumin, was ubiquitinated faster in the diabetic extracts, and a dominant negative form of E2(14k) inhibited this increase in ubiquitination rates. Both E2(14k) and E3alpha were shown to be rate-limiting for Ub conjugation because adding small amounts of either to extracts stimulated Ub conjugation. Furthermore, mRNA for E2(14k) and E3alpha (but not E1) were elevated 2-fold in muscles from diabetic rats, although no significant increase in E2(14k) and E3alpha content could be detected by immunoblot or activity assays. The simplest interpretation of these results is that small increases in both E2(14k) and E3alpha in muscles of insulin-deficient animals together accelerate Ub conjugation and protein degradation by the N-end rule pathway, the same pathway activated in cancer cachexia, sepsis, and hyperthyroidism.

Efficacy of right unilateral ultrabrief pulse width ECT: a preliminary report.

PubMed

Magid, Michelle; Truong, Liz; Trevino, Kenneth; Husain, Mustafa

2013-12-01

Ultrabrief (right unilateral) electroconvulsive therapy (UB-RU ECT) is a newer form of ECT, which uses a shorter pulse width than the standard ECT (0.3 vs 1.0 millisecond, respectively). As a result, the use of UB ECT may provide a means of further decreasing ECT-related cognitive adverse effects. In 2011, the University of Texas Southwestern Department of ECT in Austin adopted a UB ECT protocol. The purpose of this study was to perform a preliminary evaluation of the effectiveness and efficiency of UB-RU ECT. This study also examined whether sex, age, or diagnosis affected response rates. This retrospective chart review identified 62 patients treated with the UB ECT protocol. An analysis of ECT response rates and demographic characteristics was conducted based on the data from clinical evaluations and Patient Health Questionnaire 9. Sixty-eight percent of patients in the study responded to ECT; 55% responded to UB pulse width RU ECT with another 13% responding when switched to standard pulse width bilateral ECT. The mean number of treatments in an index ECT series was 12.5. There was no statistically significant difference in response rates between bipolar and unipolar depressed patients. Men required progression to bilateral treatment more than women. This UB ECT protocol demonstrated a similar response rate when compared to standard ECT protocols; however, an increase in the number of treatments was required. Ultrabrief protocols are a viable option for both bipolar and unipolar depression. In men, UB ECT protocols may be less advantageous due to a need to overcome a potentially higher seizure threshold in men; however, additional research is needed to confirm this finding.

A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection.

PubMed

Troupin, Andrea; Londono-Renteria, Berlin; Conway, Michael J; Cloherty, Erin; Jameson, Samuel; Higgs, Stephen; Vanlandingham, Dana L; Fikrig, Erol; Colpitts, Tonya M

2016-09-01

Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats

NASA Technical Reports Server (NTRS)

Lecker, S. H.; Solomon, V.; Price, S. R.; Kwon, Y. T.; Mitch, W. E.; Goldberg, A. L.

1999-01-01

Insulin deficiency (e.g., in acute diabetes or fasting) is associated with enhanced protein breakdown in skeletal muscle leading to muscle wasting. Because recent studies have suggested that this increased proteolysis is due to activation of the ubiquitin-proteasome (Ub-proteasome) pathway, we investigated whether diabetes is associated with an increased rate of Ub conjugation to muscle protein. Muscle extracts from streptozotocin-induced insulin-deficient rats contained greater amounts of Ub-conjugated proteins than extracts from control animals and also 40-50% greater rates of conjugation of (125)I-Ub to endogenous muscle proteins. This enhanced Ub-conjugation occurred mainly through the N-end rule pathway that involves E2(14k) and E3alpha. A specific substrate of this pathway, alpha-lactalbumin, was ubiquitinated faster in the diabetic extracts, and a dominant negative form of E2(14k) inhibited this increase in ubiquitination rates. Both E2(14k) and E3alpha were shown to be rate-limiting for Ub conjugation because adding small amounts of either to extracts stimulated Ub conjugation. Furthermore, mRNA for E2(14k) and E3alpha (but not E1) were elevated 2-fold in muscles from diabetic rats, although no significant increase in E2(14k) and E3alpha content could be detected by immunoblot or activity assays. The simplest interpretation of these results is that small increases in both E2(14k) and E3alpha in muscles of insulin-deficient animals together accelerate Ub conjugation and protein degradation by the N-end rule pathway, the same pathway activated in cancer cachexia, sepsis, and hyperthyroidism.

Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C.

PubMed

Brown, Nicholas G; VanderLinden, Ryan; Watson, Edmond R; Weissmann, Florian; Ordureau, Alban; Wu, Kuen-Phon; Zhang, Wei; Yu, Shanshan; Mercredi, Peter Y; Harrison, Joseph S; Davidson, Iain F; Qiao, Renping; Lu, Ying; Dube, Prakash; Brunner, Michael R; Grace, Christy R R; Miller, Darcie J; Haselbach, David; Jarvis, Marc A; Yamaguchi, Masaya; Yanishevski, David; Petzold, Georg; Sidhu, Sachdev S; Kuhlman, Brian; Kirschner, Marc W; Harper, J Wade; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A

2016-06-02

Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination. Copyright © 2016 Elsevier Inc. All rights reserved.

The mechanism of OTUB1-mediated inhibition of ubiquitination

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

Wiener, Reuven; Zhang, Xiangbin; Wang, Tao

2013-04-08

Histones are ubiquitinated in response to DNA double-strand breaks (DSB), promoting recruitment of repair proteins to chromatin. UBC13 (also known as UBE2N) is a ubiquitin-conjugating enzyme (E2) that heterodimerizes with UEV1A (also known as UBE2V1) and synthesizes K63-linked polyubiquitin (K63Ub) chains at DSB sites in concert with the ubiquitin ligase (E3), RNF168 (ref. 3). K63Ub synthesis is regulated in a non-canonical manner by the deubiquitinating enzyme, OTUB1 (OTU domain-containing ubiquitin aldehyde-binding protein 1), which binds preferentially to the UBC13-Ub thiolester. Residues amino-terminal to the OTU domain, which had been implicated in ubiquitin binding, are required for binding to UBC13-Ub andmore » inhibition of K63Ub synthesis. Here we describe structural and biochemical studies elucidating how OTUB1 inhibits UBC13 and other E2 enzymes. We unexpectedly find that OTUB1 binding to UBC13-Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13-Ub, while at the same time disrupting interactions with UEV1A in a manner that depends on the OTUB1 N terminus. Crystal structures of an OTUB1-UBC13 complex and of OTUB1 bound to ubiquitin aldehyde and a chemical UBC13-Ub conjugate show that binding of free ubiquitin to OTUB1 triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N terminus, thus promoting binding of the conjugated donor ubiquitin in UBC13-Ub to OTUB1. The donor ubiquitin thus cannot interact with the E2 enzyme, which has been shown to be important for ubiquitin transfer. The N-terminal helix of OTUB1 is positioned to interfere with UEV1A binding to UBC13, as well as with attack on the thiolester by an acceptor ubiquitin, thereby inhibiting K63Ub synthesis. OTUB1 binding also occludes the RING E3 binding site on UBC13, thus providing a further component of inhibition. The general features of the inhibition mechanism explain how OTUB1 inhibits other E2 enzymes in a non-catalytic manner.« less

Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis.

PubMed

Zhang, Shao-Ling; Chen, Yun-Wen; Tran, Stella; Chenier, Isabelle; Hébert, Marie-Josée; Ingelfinger, Julie R

2007-07-01

Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high d-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.

Increased gibberellin contents contribute to accelerated growth and development of transgenic tobacco overexpressing a wheat ubiquitin gene.

PubMed

Wang, Guo-Kun; Zhang, Meng; Gong, Jiang-Feng; Guo, Qi-Fang; Feng, Ya-Nan; Wang, Wei

2012-12-01

Overexpressing TaUb2 promoted stem growth and resulted in early flowering in transgenic tobacco plants. Ubiquitin are involved in the production, metabolism and proper function of gibberellin. The ubiquitin-26S proteasome system (UPS), in which ubiquitin (Ub) functions as a marker, is a post-translational regulatory system that plays a prominent role in various biological processes. To investigate the impact of different Ub levels on plant growth and development, transgenic tobacco (Nicotiana tabacum L.) plants were engineered to express an Ub gene (TaUb2) from wheat (Triticum aestivum L.) under the control of cauliflower mosaic virus 35S promoter. Transgenic tobacco plants overexpressing TaUb2 demonstrated an accelerated growth rate at early stage and an early flowering phenotype in development. The preceding expression of MADS-box genes also corresponded to the accelerated developmental phenotypes of the transgenic tobacco plants compared to that of wild-type (WT). Total gibberellin (GA) and active GA contents in transgenic tobacco plants were higher than those in WT at the corresponding developmental stages, and some GA metabolism genes were upregulated. Treatment with GA(3) conferred a similarly accelerated grown rate in WT plants to that of transgenic tobacco plants, while growth was inhibited when transgenic tobacco plants were treated with a GA biosynthesis inhibitor. Thus, the results suggest that Ub are involved in the production, metabolism and proper function of GA, which is important in the regulation of plant growth and development.

Mechanism of phospho-ubiquitin induced PARKIN activation

PubMed Central

Wauer, Tobias; Simicek, Michal; Schubert, Alexander; Komander, David

2016-01-01

Summary The E3 ubiquitin ligase PARKIN (encoded by PARK2) and the protein kinase PINK1 (encoded by PARK6) are mutated in autosomal recessive juvenile Parkinsonism (AR-JP) and work together in the disposal of damaged mitochondria by mitophagy1–3. PINK1 is stabilised on the outside of depolarised mitochondria, and phosphorylates poly-ubiquitin (polyUb)4–8 as well as the PARKIN Ub-like (Ubl) domain9,10. These phosphorylation events lead to PARKIN recruitment to mitochondria, and activation by an unknown allosteric mechanism4–12. Here we present the crystal structure of Pediculus humanus PARKIN in complex with Ser65-phosphorylated ubiquitin (phosphoUb), revealing the molecular basis for PARKIN recruitment and activation. The phosphoUb binding site on PARKIN comprises a conserved phosphate pocket and harbours residues mutated in AR-JP patients. PhosphoUb binding leads to straightening of a helix in the RING1 domain, and the resulting conformational changes release the Ubl domain from the PARKIN core; this activates PARKIN. Moreover, phosphoUb-mediated Ubl release enhances Ubl phosphorylation by PINK1, leading to conformational changes within the Ubl domain and stabilisation of an open, active conformation of PARKIN. We redefine the role of the Ubl domain not only as an inhibitory13 but also as an activating element that is restrained in inactive PARKIN and released by phosphoUb. Our work opens new avenues to identify small molecule PARKIN activators. PMID:26161729

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

PubMed Central

Arruda, Jose A. L.; Nascimento, Luiz; Mehta, Pradeep K.; Rademacher, Donald R.; Sehy, John T.; Westenfelder, Christof; Kurtzman, Neil A.

1977-01-01

Measurement of urine to blood (U-B) carbon dioxide tension (PCO2) gradient during alkalinization of the urine has been suggested to assess distal H+ secretion. A fact that has not been considered in previous studies dealing with urinary PCO2 is that dissolution of HCO3 in water results in elevation of PCO2 which is directly proportional to the HCO3 concentration. To investigate the interrelationship of urinary HCO3 and urinary acidification, we measured U-B PCO2 in (a) the presence of enhanced H+ secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H+ secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H+ secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO3 levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO3 concentration and U-B PCO2. At similar plasma HCO3 levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally. At a very high plasma HCO3 (>50 meq/liter), BB rats raised urine pH, urine HCO3 concentration, and U-B PCO2 to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO3, and U-B PCO2 normally at moderately elevated plasma HCO3 levels; at very high plasma HCO3 levels, CRF rats achieved a highly alkaline urine but failed to raise U-B PCO2. Dogs and patients with CRF were also unable to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally at moderately elevated plasma HCO3 levels. In rats, dogs, and man, U-B PCO2 was directly related to urine HCO3 concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO3 levels, animals with a distal acidification defect failed to raise U-B PCO2; increasing the plasma HCO3 to very high levels resulted in a significant increase in urine HCO3 concentration and U-B PCO2. The observed urinary PCO2 was very close to the PCO2 which would be expected by simple dissolution of a comparable amount of HCO3 in water. These data demonstrate that, in highly alkaline urine, urinary PCO2 is largely determined by concentration of urinary HCO3 and cannot be used as solely indicating distal H+ secretion. PMID:893680

Ub-ISAP: a streamlined UNIX pipeline for mining unique viral vector integration sites from next generation sequencing data.

PubMed

Kamboj, Atul; Hallwirth, Claus V; Alexander, Ian E; McCowage, Geoffrey B; Kramer, Belinda

2017-06-17

The analysis of viral vector genomic integration sites is an important component in assessing the safety and efficiency of patient treatment using gene therapy. Alongside this clinical application, integration site identification is a key step in the genetic mapping of viral elements in mutagenesis screens that aim to elucidate gene function. We have developed a UNIX-based vector integration site analysis pipeline (Ub-ISAP) that utilises a UNIX-based workflow for automated integration site identification and annotation of both single and paired-end sequencing reads. Reads that contain viral sequences of interest are selected and aligned to the host genome, and unique integration sites are then classified as transcription start site-proximal, intragenic or intergenic. Ub-ISAP provides a reliable and efficient pipeline to generate large datasets for assessing the safety and efficiency of integrating vectors in clinical settings, with broader applications in cancer research. Ub-ISAP is available as an open source software package at https://sourceforge.net/projects/ub-isap/ .

Novel polyubiquitin imaging system, PolyUb-FC, reveals that K33-linked polyubiquitin is recruited by SQSTM1/p62.

PubMed

Nibe, Yoichi; Oshima, Shigeru; Kobayashi, Masanori; Maeyashiki, Chiaki; Matsuzawa, Yu; Otsubo, Kana; Matsuda, Hiroki; Aonuma, Emi; Nemoto, Yasuhiro; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Nakada, Shinichiro; Watanabe, Mamoru

2018-01-01

Ubiquitin chains are formed with 8 structurally and functionally distinct polymers. However, the functions of each polyubiquitin remain poorly understood. We developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay using Kusabira Green (KG) as a split fluorescent protein. The PolyUb-FC assay has the advantage that monoubiquitination is nonfluorescent and chain-specific polyubiquitination can be directly visualized in living cells without using antibodies. We applied the PolyUb-FC assay to examine K33-linked polyubiquitin. We demonstrated that SQSTM1/p62 puncta colocalized with K33-linked polyubiquitin and this interaction was modulated by the ZRANB1/TRABID-K29 and -K33 linkage-specific deubiquitinase (DUB). We further showed that the colocalization of K33-linked polyubiquitin and MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) puncta was impaired by SQSTM1/p62 deficiency. Taken together, these findings provide novel insights into how atypical polyubiquitin is recruited by SQSTM1/p62. Finally, we developed an inducible-PolyUb-FC system for visualizing chain-specific polyubiquitin. The PolyUb-FC will be a useful tool for analyzing the dynamics of atypical polyubiquitin chain generation.

Unified Research on Network-Based Hard/Soft Information Fusion

DTIC Science & Technology

2016-02-02

types). There are a number of search tree run parameters which must be set depending on the experimental setting. A pilot study was run to identify...Unlimited Final Report: Unified Research on Network-Based Hard/Soft Information Fusion The views, opinions and/or findings contained in this report...Final Report: Unified Research on Network-Based Hard/Soft Information Fusion Report Title The University at Buffalo (UB) Center for Multisource

Ubiquitin C-terminal electrophiles are activity-based probes for identification and mechanistic study of ubiquitin conjugating machinery.

PubMed

Love, Kerry Routenberg; Pandya, Renuka K; Spooner, Eric; Ploegh, Hidde L

2009-04-17

Protein modification by ubiquitin (Ub) and ubiquitin-like modifiers (Ubl) requires the action of activating (E1), conjugating (E2), and ligating (E3) enzymes and is a key step in the specific destruction of proteins. Deubiquitinating enzymes (DUBs) deconjugate substrates modified with Ub/Ubl's and recycle Ub inside the cell. Genome mining based on sequence homology to proteins with known function has assigned many enzymes to this pathway without confirmation of either conjugating or DUB activity. Function-dependent methodologies are still the most useful for rapid identification or assessment of biological activity of expressed proteins from cells. Activity-based protein profiling uses chemical probes that are active-site-directed for the classification of protein activities in complex mixtures. Here we show that the design and use of an expanded set of Ub-based electrophilic probes allowed us to recover and identify members of each enzyme class in the ubiquitin-proteasome system, including E3 ligases and DUBs with previously unverified activity. We show that epitope-tagged Ub-electrophilic probes can be used as activity-based probes for E3 ligase identification by in vitro labeling and activity studies of purified enzymes identified from complex mixtures in cell lysate. Furthermore, the reactivity of our probe with the HECT domain of the E3 Ub ligase ARF-BP1 suggests that multiple cysteines may be in the vicinity of the E2-binding site and are capable of the transfer of Ub to self or to a substrate protein.

Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer.

PubMed

Bhuripanyo, Karan; Wang, Yiyang; Liu, Xianpeng; Zhou, Li; Liu, Ruochuan; Duong, Duc; Zhao, Bo; Bi, Yingtao; Zhou, Han; Chen, Geng; Seyfried, Nicholas T; Chazin, Walter J; Kiyokawa, Hiroaki; Yin, Jun

2018-01-01

E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct "orthogonal UB transfer (OUT)" cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins. Purification of xUB-conjugated proteins followed by proteomics analysis enabled the identification of hundreds of potential substrates of E4B and CHIP in human embryonic kidney 293 cells. Kinase MAPK3 (mitogen-activated protein kinase 3), methyltransferase PRMT1 (protein arginine N -methyltransferase 1), and phosphatase PPP3CA (protein phosphatase 3 catalytic subunit alpha) were identified as the shared substrates of the two E3s. Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were confirmed as E4B substrates, and β-catenin and CDK4 (cyclin-dependent kinase 4) were confirmed as CHIP substrates. On the basis of the CHIP-CDK4 circuit identified by OUT, we revealed that CHIP signals CDK4 degradation in response to endoplasmic reticulum stress.

Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer

PubMed Central

Bhuripanyo, Karan; Wang, Yiyang; Liu, Xianpeng; Zhou, Li; Liu, Ruochuan; Duong, Duc; Zhao, Bo; Bi, Yingtao; Zhou, Han; Chen, Geng; Seyfried, Nicholas T.; Chazin, Walter J.; Kiyokawa, Hiroaki; Yin, Jun

2018-01-01

E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct “orthogonal UB transfer (OUT)” cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins. Purification of xUB-conjugated proteins followed by proteomics analysis enabled the identification of hundreds of potential substrates of E4B and CHIP in human embryonic kidney 293 cells. Kinase MAPK3 (mitogen-activated protein kinase 3), methyltransferase PRMT1 (protein arginine N-methyltransferase 1), and phosphatase PPP3CA (protein phosphatase 3 catalytic subunit alpha) were identified as the shared substrates of the two E3s. Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were confirmed as E4B substrates, and β-catenin and CDK4 (cyclin-dependent kinase 4) were confirmed as CHIP substrates. On the basis of the CHIP-CDK4 circuit identified by OUT, we revealed that CHIP signals CDK4 degradation in response to endoplasmic reticulum stress. PMID:29326975

Inhibition of Protein Ubiquitination by Paraquat and 1-Methyl-4-Phenylpyridinium Impairs Ubiquitin-Dependent Protein Degradation Pathways.

PubMed

Navarro-Yepes, Juliana; Anandhan, Annadurai; Bradley, Erin; Bohovych, Iryna; Yarabe, Bo; de Jong, Annemieke; Ovaa, Huib; Zhou, You; Khalimonchuk, Oleh; Quintanilla-Vega, Betzabet; Franco, Rodrigo

2016-10-01

Intracytoplasmic inclusions of protein aggregates in dopaminergic cells (Lewy bodies) are the pathological hallmark of Parkinson's disease (PD). Ubiquitin (Ub), alpha (α)-synuclein, p62/sequestosome 1, and oxidized proteins are the major components of Lewy bodies. However, the mechanisms involved in the impairment of misfolded/oxidized protein degradation pathways in PD are still unclear. PD is linked to mitochondrial dysfunction and environmental pesticide exposure. In this work, we evaluated the effects of the pesticide paraquat (PQ) and the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP(+)) on Ub-dependent protein degradation pathways. No increase in the accumulation of Ub-bound proteins or aggregates was observed in dopaminergic cells (SK-N-SH) treated with PQ or MPP(+), or in mice chronically exposed to PQ. PQ decreased Ub protein content, but not its mRNA transcription. Protein synthesis inhibition with cycloheximide depleted Ub levels and potentiated PQ-induced cell death. The inhibition of proteasomal activity by PQ was found to be a late event in cell death progression and had neither effect on the toxicity of either MPP(+) or PQ, nor on the accumulation of oxidized sulfenylated, sulfonylated (DJ-1/PARK7 and peroxiredoxins), and carbonylated proteins induced by PQ. PQ- and MPP(+)-induced Ub protein depletion prompted the dimerization/inactivation of the Ub-binding protein p62 that regulates the clearance of ubiquitinated proteins by autophagy. We confirmed that PQ and MPP(+) impaired autophagy flux and that the blockage of autophagy by the overexpression of a dominant-negative form of the autophagy protein 5 (dnAtg5) stimulated their toxicity, but there was no additional effect upon inhibition of the proteasome. PQ induced an increase in the accumulation of α-synuclein in dopaminergic cells and membrane-associated foci in yeast cells. Our results demonstrate that the inhibition of protein ubiquitination by PQ and MPP(+) is involved in the dysfunction of Ub-dependent protein degradation pathways.

Inhibition of protein ubiquitination by paraquat and 1-methyl-4-phenylpyridinium impairs ubiquitin-dependent protein degradation pathways

PubMed Central

Navarro-Yepes, Juliana; Anandhan, Annadurai; Bradley, Erin; Bohovych, Iryna; Yarabe, Bo; de Jong, Annemieke; Ovaa, Huib; Zhou, You; Khalimonchuk, Oleh; Quintanilla-Vega, Betzabet; Franco, Rodrigo

2016-01-01

Intracytoplasmic inclusions of protein aggregates in dopaminergic cells (Lewy bodies) are the pathological hallmark of Parkinson’s disease (PD). Ubiquitin (Ub), alpha [α]-synuclein, p62/sequestosome 1 and oxidized proteins are major components of Lewy bodies. However, the mechanisms involved in the impairment of misfolded/oxidized protein degradation pathways in PD are still unclear. PD is linked to mitochondrial dysfunction and environmental pesticide exposure. In this work, we evaluated the effect of the pesticide paraquat (PQ) and the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) on Ub-dependent protein degradation pathways. No increase in the accumulation of Ub-bound proteins or aggregates was observed in dopaminergic cells (SK-N-SH) treated with PQ or MPP+, or in mice chronically exposed to PQ. PQ decreased Ub protein content, but not its mRNA transcription. Protein synthesis inhibition with cycloheximide depleted Ub levels and potentiated PQ–induced cell death. Inhibition of proteasomal activity by PQ was found to be a late event in cell death progression, and had no effect on either the toxicity of MPP+ or PQ, or the accumulation of oxidized sulfenylated, sulfonylated (DJ-1/PARK7 and peroxiredoxins) and carbonylated proteins induced by PQ. PQ- and MPP+-induced Ub protein depletion prompted the dimerization/inactivation of the Ub-binding protein p62 that regulates the clearance of ubiquitinated proteins by autophagic. We confirmed that PQ and MPP+ impaired autophagy flux, and that the blockage of autophagy by the overexpression of a dominant-negative form of the autophagy protein 5 (dnAtg5) stimulated their toxicity, but there was no additional effect upon inhibition of the proteasome. PQ induced an increase in the accumulation of α-synuclein in dopaminergic cells and membrane associated foci in yeast cells. Our results demonstrate that inhibition of protein ubiquitination by PQ and MPP+ is involved in the dysfunction of Ub-dependent protein degradation pathways. PMID:26409479

UB Matrix Implementation for Inelastic Neutron Scattering Experiments

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

Lumsden, Mark D; Robertson, Lee; Yethiraj, Mohana

The UB matrix approach has been extended to handle inelastic neutron scattering experiments with differing k{sub i} and k{sub f}. We have considered the typical goniometer employed on triple-axis and time-of-flight spectrometers. Expressions are derived to allow for calculation of the UB matrix and for converting from observables to Q-energy space. In addition, we have developed appropriate modes for calculation of angles for a specified Q-energy position.

The ubiquitin conjugating enzyme UbcH10 competes with UbcH3 for binding to the SCF complex, a ubiquitin ligase involved in cell cycle progression

USDA-ARS?s Scientific Manuscript database

Ubiquitylation, which regulates most biological pathways, occurs through an enzymatic cascade involving a ubiquitin (ub) activating enzyme (E1), a ub conjugating enzyme (E2) and a ub ligase (E3). UbcH3 is the E2 that interacts with SCF (Skp1/Cul1/F-box protein) complex and ubiquitylates many protein...

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

Bailey, Jon A.; et al.

We present a lattice-QCD calculation of the B → πℓν semileptonic form factors and a new determination of the CKM matrix element |V ub|. We use the MILC asqtad (2+1)-flavor lattice configurations at four lattice spacings and light-quark masses down to 1/20 of the physical strange-quark mass. We extrapolate the lattice form factors to the continuum using staggered chiral perturbation theory in the hard-pion and SU(2) limits. We employ a model-independent z parametrization to extrapolate our lattice form factors from large-recoil momentum to the full kinematic range. We introduce a new functional method to propagate information from the chiral-continuum extrapolationmore » to the z expansion. We present our results together with a complete systematic error budget, including a covariance matrix to enable the combination of our form factors with other lattice-QCD and experimental results. To obtain |V ub|, we simultaneously fit the experimental data for the B → πℓν differential decay rate obtained by the BABAR and Belle collaborations together with our lattice form-factor results. We find |V ub|=(3.72±0.16) × 10 –3, where the error is from the combined fit to lattice plus experiments and includes all sources of uncertainty. Our form-factor results bring the QCD error on |V ub| to the same level as the experimental error. We also provide results for the B → πℓν vector and scalar form factors obtained from the combined lattice and experiment fit, which are more precisely determined than from our lattice-QCD calculation alone. Lastly, these results can be used in other phenomenological applications and to test other approaches to QCD.« less

Tight regulation of p53 activity by Mdm2 is required for ureteric bud growth and branching

PubMed Central

Hilliard, Sylvia; Aboudehen, Karam; Yao, Xiao; El-Dahr, Samir S.

2011-01-01

Mdm2 (Murine Double Minute-2) is required to control cellular p53 activity and protein levels. Mdm2 null embryos die of p53-mediated growth arrest and apoptosis at the peri-implantation stage. Thus, the absolute requirement for Mdm2 in organogenesis is unknown. This study examined the role of Mdm2 in kidney development, an organ which develops via epithelial-mesenchymal interactions and branching morphogenesis. Mdm2 mRNA and protein are expressed in the ureteric bud (UB) epithelium and metanephric mesenchyme (MM) lineages. We report here the results of conditional deletion of Mdm2 from the UB epithelium. UBmdm2−/− mice die soon after birth and uniformly display severe renal hypodysplasia due to defective UB branching and underdeveloped nephrogenic zone. Ex vivo cultured UBmdm2−/− explants exhibit arrested development of the UB and its branches and consequently develop few nephron progenitors. UBmdm2−/− cells have reduced proliferation rate and enhanced apoptosis. Although markedly reduced in number, the UB tips of UBmdm2−/− metanephroi continue to express c-ret and Wnt11; however, there was a notable reduction in Wnt9b, Lhx-1 and Pax-2 expression levels. We further show that the UBmdm2−/− mutant phenotype is mediated by aberrant p53 activity because it is rescued by UB-specific deletion of the p53 gene. These results demonstrate a critical and cell autonomous role for Mdm2 in the UB lineage. Mdm2-mediated inhibition of p53 activity is a prerequisite for renal organogenesis. PMID:21420949

The Long-Lasting Enhancing Effect of Distigmine on Acetylcholine-Induced Contraction of Guinea Pig Detrusor Smooth Muscle Correlates with Its Anticholinesterase Activity.

PubMed

Obara, Keisuke; Ogawa, Tsukasa; Chino, Daisuke; Tanaka, Yoshio

2017-01-01

Distigmine bromide (distigmine), a reversible, long-lasting cholinesterase (ChE) inhibitor, is used for the treatment of underactive bladder in Japan and has been shown to potentiate urinary bladder (UB) contractility. We studied the duration of distigmine's potentiating effects on acetylcholine (ACh)-induced UB contraction and its inhibitory effects on ChE activity, and compared that with those of other ChE inhibitors (neostigmine, pyridostigmine, and ambenonium). The duration of potentiating/inhibitory effects of ChE inhibitors, including distigmine, on ACh-induced guinea pig UB contraction/ChE activity was evaluated for 12 h following washout. Dissociation rate constants (k) of the inhibitors were also tentatively calculated based on the time courses of their ChE inhibitory effects. The potentiating effect of distigmine (10 -6  M) on ACh-induced UB contraction and its inhibitory effect on ChE activity were significantly sustained 12 h after washout. The potentiating effect of other ChE inhibitors on ACh-induced UB contraction, however, was sustained only until 3 h after washout. The ChE inhibitory effects of these inhibitors dissipated in a time-dependent manner after washout, with more than 75% of ChE activity restored by 4 h after washout. The k values of ChE inhibitors approached 0.50 h -1 , except for distigmine, where k could not be determined. Compared with that of other ChE inhibitors, the potentiating effect of distigmine on UB contractile function was significantly more sustainable following washout, which was likely associated with its corresponding long-lasting ChE inhibitory effect. Distigmine may associate more strongly with UB ChE than other ChE inhibitors, which would partly explain its sustained effects.

Source identification of PM2.5 at a port and an adjacent urban site in a coastal city of China: Impact of ship emissions and port activities.

PubMed

Xu, Lingling; Jiao, Ling; Hong, Zhenyu; Zhang, Yanru; Du, Wenjiao; Wu, Xin; Chen, Yanting; Deng, Junjun; Hong, Youwei; Chen, Jinsheng

2018-09-01

Daily PM 2.5 samples were collected simultaneously at an urban site (UB) and a nearby port-industrial site (PI) on the coast of southeastern China from April 2015 to January 2016. The PM 2.5 mass concentration at the PI (51.9μgm -3 ) was significantly higher than that at the UB. The V concentration at the PI was also significantly higher and well-correlated to the urban value, which suggests that shipping emissions had a significant impact on the PI and, to a lesser extent, on the urban area. A positive matrix factorization (PMF) analysis showed that secondary aerosols were the dominant contribution of PM 2.5 at both sites (36.4% at the PI and 27.2% at the UB), while the contribution of industry and ship emissions identified by V, Mn, and Ba at the PI (26.1%) were double those at the UB. The difference in each source contribution among the trajectory clusters that included significant differences and insignificant differences from the UB to the PI provided insight into the role of local impacts. With regards to the UB, local potential sources play important roles in industry and ship emissions, traffic emissions, fugitive dust, and in their contributions to secondary aerosols. A conditional probability function further revealed that the ship emissions and port activities distributed in the NE, E, and SSE wind sectors were responsible for the source contributions of industry and ship emissions and secondary aerosols at the UB. This study provides an example of investigating the impact of ship emissions and port activities on the surrounding air environment using land-based measurements. Copyright © 2018 Elsevier B.V. All rights reserved.

A first principles study of the electronic structure, elastic and thermal properties of UB2

NASA Astrophysics Data System (ADS)

Jossou, Ericmoore; Malakkal, Linu; Szpunar, Barbara; Oladimeji, Dotun; Szpunar, Jerzy A.

2017-07-01

Uranium diboride (UB2) has been widely deployed for refractory use and is a proposed material for Accident Tolerant Fuel (ATF) due to its high thermal conductivity. However, the applicability of UB2 towards high temperature usage in a nuclear reactor requires the need to investigate the thermomechanical properties, and recent studies have failed in highlighting applicable properties. In this work, we present an in-depth theoretical outlook of the structural and thermophysical properties of UB2, including but not limited to elastic, electronic and thermal transport properties. These calculations were performed within the framework of Density Functional Theory (DFT) + U approach, using Quantum ESPRESSO (QE) code considering the addition of Coulomb correlations on the uranium atom. The phonon spectra and elastic constant analysis show the dynamic and mechanical stability of UB2 structure respectively. The electronic structure of UB2 was investigated using full potential linear augmented plane waves plus local orbitals method (FP-LAPW+lo) as implemented in WIEN2k code. The absence of a band gap in the total and partial density of states confirms the metallic nature while the valence electron density plot reveals the presence of covalent bond between adjacent B-B atoms. We predicted the lattice thermal conductivity (kL) by solving Boltzmann Transport Equation (BTE) using ShengBTE. The second order harmonic and third-order anharmonic interatomic force constants required as input to ShengBTE was calculated using the Density-functional perturbation theory (DFPT). However, we predicted the electronic thermal conductivity (kel) using Wiedemann-Franz law as implemented in Boltztrap code. We also show that the sound velocity along 'a' and 'c' axes exhibit high anisotropy, which accounts for the anisotropic thermal conductivity of UB2.

Molecular dynamics of zinc-finger ubiquitin binding domains: a comparative study of histone deacetylase 6 and ubiquitin-specific protease 5.

PubMed

Dos Santos Passos, Carolina; Simões-Pires, Claudia A; Carrupt, Pierre-Alain; Nurisso, Alessandra

2016-12-01

HDAC6 is a unique cytoplasmic histone deacetylase characterized by two deacetylase domains, and by a zinc-finger ubiquitin binding domain (ZnF-UBP) able to recognize ubiquitin (Ub). The latter has recently been demonstrated to be involved in the progression of neurodegenerative diseases and in mediating infection by the influenza A virus. Nowadays, understanding the dynamic and energetic features of HDAC6 ZnF-UBP-Ub recognition is considered as a crucial step for the conception of HDAC6 potential modulators. In this study, the atomic, solvent-related, and thermodynamic features behind HDAC6 ZnF-UBP-Ub recognition have been analyzed through molecular dynamics simulations. The behavior was then compared to the prototypical ZnF-UBP from ubiquitin-specific protease 5 (USP5) in order to spot relevant differences useful for selective drug design. Principal component analysis highlighted flapping motions of the L2A loop which were lowered down upon Ub binding in both systems. While polar and nonpolar interactions involving Ub G75 and G76 residues were also common features stabilizing both complexes, salt bridges showed a different pattern, more significant in HDAC6 ZnF-UBP-Ub, whose energetic contribution in USP5 ZnF-UBP-Ub was compensated by the presence of a more stable bridging water molecule. Whereas molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) free energies of binding were comparable for both systems, in agreement with experiments, computational alanine scanning and free energy decomposition data revealed that HDAC6 E1141 and D1178 are potential hotspots for the design of selective HDAC6 modulators.

A Multi-Disciplinary University Research Initiative in Hard and Soft Information Fusion: Overview, Research Strategies and Initial Results

DTIC Science & Technology

2010-07-01

Multisource Information Fusion ( CMIF ) along with a team including the Pennsylvania State University (PSU), Iona College (Iona), and Tennessee State...License. 14. ABSTRACT The University at Buffalo (UB) Center for Multisource Information Fusion ( CMIF ) along with a team including the Pennsylvania...of CMIF current research on methods for Test and Evaluation ([7], [8]) involving for example large- factor-space experimental design techniques ([9

Removing cosmic spikes using a hyperspectral upper-bound spectrum method

DOE PAGES

Anthony, Stephen Michael; Timlin, Jerilyn A.

2016-11-04

Cosmic ray spikes are especially problematic for hyperspectral imaging because of the large number of spikes often present and their negative effects upon subsequent chemometric analysis. Fortunately, while the large number of spectra acquired in a hyperspectral imaging data set increases the probability and number of cosmic spikes observed, the multitude of spectra can also aid in the effective recognition and removal of the cosmic spikes. Zhang and Ben-Amotz were perhaps the first to leverage the additional spatial dimension of hyperspectral data matrices (DM). They integrated principal component analysis (PCA) into the upper bound spectrum method (UBS), resulting in amore » hybrid method (UBS-DM) for hyperspectral images. Here, we expand upon their use of PCA, recognizing that principal components primarily present in only a few pixels most likely correspond to cosmic spikes. Eliminating the contribution of those principal components in those pixels improves the cosmic spike removal. Both simulated and experimental hyperspectral Raman image data sets are used to test the newly developed UBS-DM-hyperspectral (UBS-DM-HS) method which extends the UBS-DM method by leveraging characteristics of hyperspectral data sets. As a result, a comparison is provided between the performance of the UBS-DM-HS method and other methods suitable for despiking hyperspectral images, evaluating both their ability to remove cosmic ray spikes and the extent to which they introduce spectral bias.« less

[Differences in momentum development when standing up from a chair between elderly with and without frequent falls history].

PubMed

Guzmán, Rodrigo Antonio; Prado, Hugo Enrique; Porcel Melián, Helvio; Cordier, Benoit

2009-01-01

The momentum of the upper body (UB) during transfer sit-to-stand (STS) could be sensitive to the deterioration of dynamic postural control, and also the risk of falls. The aim of this study is to quantify the differences in the momentum development on UB during the STS in a sample of fall and no-fall elderly subjects. MATERIAL AND MEHODS: The sample consisted of twenty three voluntary elderly subjects (n=23), six elderly adults with antecedents of frequent falls (more than two within a year period) and seventeen without histories of frequent falls. Through a motion analysis system we registered the kinematics of UB during STS, from which we calculated the momentum of UB. The determined analysis variables were: the maximum values of the vertical (P(V)M) and horizontal (P(H)M) lineal momenta, the minimum (L(Max)) and maximum (L(Min)) values of the angular momentum and maximum trunk flexion (thetaM(UB)). No difference was observed in P(H)M, L(Max) and L(Min) (P>0.05) between both groups. However, a significant difference was found for the variable P(V)M (P=0.03) and thetaM(UB) (P=0.03) between both groups. We can conclude that, for the sample studied, the frequent fall condition relates to a smaller capacity to develop vertical momentum and increase flexion of the upper body.

Removing cosmic spikes using a hyperspectral upper-bound spectrum method

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

Anthony, Stephen Michael; Timlin, Jerilyn A.

Cosmic ray spikes are especially problematic for hyperspectral imaging because of the large number of spikes often present and their negative effects upon subsequent chemometric analysis. Fortunately, while the large number of spectra acquired in a hyperspectral imaging data set increases the probability and number of cosmic spikes observed, the multitude of spectra can also aid in the effective recognition and removal of the cosmic spikes. Zhang and Ben-Amotz were perhaps the first to leverage the additional spatial dimension of hyperspectral data matrices (DM). They integrated principal component analysis (PCA) into the upper bound spectrum method (UBS), resulting in amore » hybrid method (UBS-DM) for hyperspectral images. Here, we expand upon their use of PCA, recognizing that principal components primarily present in only a few pixels most likely correspond to cosmic spikes. Eliminating the contribution of those principal components in those pixels improves the cosmic spike removal. Both simulated and experimental hyperspectral Raman image data sets are used to test the newly developed UBS-DM-hyperspectral (UBS-DM-HS) method which extends the UBS-DM method by leveraging characteristics of hyperspectral data sets. As a result, a comparison is provided between the performance of the UBS-DM-HS method and other methods suitable for despiking hyperspectral images, evaluating both their ability to remove cosmic ray spikes and the extent to which they introduce spectral bias.« less

Removing Cosmic Spikes Using a Hyperspectral Upper-Bound Spectrum Method.

PubMed

Anthony, Stephen M; Timlin, Jerilyn A

2017-03-01

Cosmic ray spikes are especially problematic for hyperspectral imaging because of the large number of spikes often present and their negative effects upon subsequent chemometric analysis. Fortunately, while the large number of spectra acquired in a hyperspectral imaging data set increases the probability and number of cosmic spikes observed, the multitude of spectra can also aid in the effective recognition and removal of the cosmic spikes. Zhang and Ben-Amotz were perhaps the first to leverage the additional spatial dimension of hyperspectral data matrices (DM). They integrated principal component analysis (PCA) into the upper bound spectrum method (UBS), resulting in a hybrid method (UBS-DM) for hyperspectral images. Here, we expand upon their use of PCA, recognizing that principal components primarily present in only a few pixels most likely correspond to cosmic spikes. Eliminating the contribution of those principal components in those pixels improves the cosmic spike removal. Both simulated and experimental hyperspectral Raman image data sets are used to test the newly developed UBS-DM-hyperspectral (UBS-DM-HS) method which extends the UBS-DM method by leveraging characteristics of hyperspectral data sets. A comparison is provided between the performance of the UBS-DM-HS method and other methods suitable for despiking hyperspectral images, evaluating both their ability to remove cosmic ray spikes and the extent to which they introduce spectral bias.

Biocalcification using Ureolytic Bacteria (UB) for strengthening Interlocking Compressed Earth Blocks (ICEB)

NASA Astrophysics Data System (ADS)

Zamer, M. M.; Irwan, J. M.; Othman, N.; Faisal, S. K.; Anneza, L. H.; Alshalif, A. F.; Teddy, T.

2018-02-01

Interlocking compressed earth blocks (ICEB) are soil based blocks that allows for mortarless construction. This characteristic resulted to faster the process of building walls and required less skilled labor as the blocks are laid dry and lock into place. Recently, implementation in using bacteria as construction material improvement is vigorously used in research in order pursuit the sustainable construction works. This paper provide the results of ureolytic bacteria (UB) throughout enrichment process in soil condition to acclimatize the ICEB environment, compressive strength of 1%, 3% and 5% UB and SEM analysis of ICEB. The bacteria were added as partial replacement of limestone water in ICEB. The results showed the optimal growth achieved based on the days and absorbance from optical density (OD) test which are in 12th days with absorbance of 0.55 whereas the results for strength shows the increment of 15.25% with 5% UB on 28th days of testing compared to control specimen. Therefore this study hopes that positive results from the UB as improving in strength of ICEB which will lead to improve others ICEB properties and others construction materials.

Proteomic snapshot of the EGF-induced ubiquitin network

PubMed Central

Argenzio, Elisabetta; Bange, Tanja; Oldrini, Barbara; Bianchi, Fabrizio; Peesari, Raghunath; Mari, Sara; Di Fiore, Pier Paolo; Mann, Matthias; Polo, Simona

2011-01-01

The activity, localization and fate of many cellular proteins are regulated through ubiquitination, a process whereby one or more ubiquitin (Ub) monomers or chains are covalently attached to target proteins. While Ub-conjugated and Ub-associated proteomes have been described, we lack a high-resolution picture of the dynamics of ubiquitination in response to signaling. In this study, we describe the epidermal growth factor (EGF)-regulated Ubiproteome, as obtained by two complementary purification strategies coupled to quantitative proteomics. Our results unveil the complex impact of growth factor signaling on Ub-based intracellular networks to levels that extend well beyond what might have been expected. In addition to endocytic proteins, the EGF-regulated Ubiproteome includes a large number of signaling proteins, ubiquitinating and deubiquitinating enzymes, transporters and proteins involved in translation and transcription. The Ub-based signaling network appears to intersect both housekeeping and regulatory circuitries of cellular physiology. Finally, as proof of principle of the biological relevance of the EGF-Ubiproteome, we demonstrated that EphA2 is a novel, downstream ubiquitinated target of epidermal growth factor receptor (EGFR), critically involved in EGFR biological responses. PMID:21245847

Tubulin chaperone E binds microtubules and proteasomes and protects against misfolded protein stress.

PubMed

Voloshin, Olga; Gocheva, Yana; Gutnick, Marina; Movshovich, Natalia; Bakhrat, Anya; Baranes-Bachar, Keren; Bar-Zvi, Dudy; Parvari, Ruti; Gheber, Larisa; Raveh, Dina

2010-06-01

Mutation of tubulin chaperone E (TBCE) underlies hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome with defective microtubule (MT) cytoskeleton. TBCE/yeast Pac2 comprises CAP-Gly, LRR (leucine-rich region), and UbL (ubiquitin-like) domains. TBCE folds alpha-tubulin and promotes alpha/beta dimerization. We show that Pac2 functions in MT dynamics: the CAP-Gly domain binds alpha-tubulin and MTs, and functions in suppression of benomyl sensitivity of pac2Delta mutants. Pac2 binds proteasomes: the LRR binds Rpn1, and the UbL binds Rpn10; the latter interaction mediates Pac2 turnover. The UbL also binds the Skp1-Cdc53-F-box (SCF) ubiquitin ligase complex; these competing interactions for the UbL may impact on MT dynamics. pac2Delta mutants are sensitive to misfolded protein stress. This is suppressed by ectopic PAC2 with both the CAP-Gly and UbL domains being essential. We propose a novel role for Pac2 in the misfolded protein stress response based on its ability to interact with both the MT cytoskeleton and the proteasomes.

A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes

NASA Astrophysics Data System (ADS)

Lu, Xiaolong; Malley, Konstantin R.; Brenner, Caitlin C.; Koroleva, Olga; Korolev, Sergey; Downes, Brian P.

2016-08-01

Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2~Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s.

A single ubiquitin is sufficient for cargo protein entry into MVBs in the absence of ESCRT ubiquitination

PubMed Central

Stringer, Daniel K.

2011-01-01

ESCRTs (endosomal sorting complexes required for transport) bind and sequester ubiquitinated membrane proteins and usher them into multivesicular bodies (MVBs). As Ubiquitin (Ub)-binding proteins, ESCRTs themselves become ubiquitinated. However, it is unclear whether this regulates a critical aspect of their function or is a nonspecific consequence of their association with the Ub system. We investigated whether ubiquitination of the ESCRTs was required for their ability to sort cargo into the MVB lumen. Although we found that Rsp5 was the main Ub ligase responsible for ubiquitination of ESCRT-0, elimination of Rsp5 or elimination of the ubiquitinatable lysines within ESCRT-0 did not affect MVB sorting. Moreover, by fusing the catalytic domain of deubiquitinating peptidases onto ESCRTs, we could block ESCRT ubiquitination and the sorting of proteins that undergo Rsp5-dependent ubiquitination. Yet, proteins fused to a single Ub moiety were efficiently delivered to the MVB lumen, which strongly indicates that a single Ub is sufficient in sorting MVBs in the absence of ESCRT ubiquitination. PMID:21242292

VizieR Online Data Catalog: Reference Catalogue of Bright Galaxies (RC1; de Vaucouleurs+ 1964)

NASA Astrophysics Data System (ADS)

de Vaucouleurs, G.; de Vaucouleurs, A.

1995-11-01

The Reference Catalogue of Bright Galaxies lists for each entry the following information: NGC number, IC number, or A number; A, B, or C designation; B1950.0 positions, position at 100 year precession; galactic and supergalactic positions; revised morphological type and source; type and color class in Yerkes list 1 and 2; Hubble-Sandage type; revised Hubble type according to Holmberg; logarithm of mean major diameter (log D) and ratio of major to minor diameter (log R) and their weights; logarithm of major diameter; sources of the diameters; David Dunlap Observatory type and luminosity class; Harvard photographic apparent magnitude; weight of V, B-V(0), U-B(0); integrated magnitude B(0) and its weight in the B system; mean surface brightness in magnitude per square minute of arc and sources for the B magnitude; mean B surface brightness derived from corrected Harvard magnitude; the integrated color index in the standard B-V system; "intrinsic" color index; sources of B-V and/or U-B; integrated color in the standard U-B system; observed radial velocity in km/sec; radial velocity corrected for solar motion in km/sec; sources of radial velocities; solar motion correction; and direct photographic source. The catalog was created by concatenating four files side by side. (1 data file).

Mapping the interactome of HPV E6 and E7 oncoproteins with the ubiquitin-proteasome system.

PubMed

Poirson, Juline; Biquand, Elise; Straub, Marie-Laure; Cassonnet, Patricia; Nominé, Yves; Jones, Louis; van der Werf, Sylvie; Travé, Gilles; Zanier, Katia; Jacob, Yves; Demeret, Caroline; Masson, Murielle

2017-10-01

Protein ubiquitination and its reverse reaction, deubiquitination, regulate protein stability, protein binding activity, and their subcellular localization. These reactions are catalyzed by the enzymes E1, E2, and E3 ubiquitin (Ub) ligases and deubiquitinases (DUBs). The Ub-proteasome system (UPS) is targeted by viruses for the sake of their replication and to escape host immune response. To identify novel partners of human papillomavirus 16 (HPV16) E6 and E7 proteins, we assembled and screened a library of 590 cDNAs related to the UPS by using the Gaussia princeps luciferase protein complementation assay. HPV16 E6 was found to bind to the homology to E6AP C terminus-type Ub ligase (E6AP), three really interesting new gene (RING)-type Ub ligases (MGRN1, LNX3, LNX4), and the DUB Ub-specific protease 15 (USP15). Except for E6AP, the binding of UPS factors did not require the LxxLL-binding pocket of HPV16 E6. LNX3 bound preferentially to all high-risk mucosal HPV E6 tested, whereas LNX4 bound specifically to HPV16 E6. HPV16 E7 was found to bind to several broad-complex tramtrack and bric-a-brac domain-containing proteins (such as TNFAIP1/KCTD13) that are potential substrate adaptors of Cullin 3-RING Ub ligases, to RING-type Ub ligases implicated in innate immunity (RNF135, TRIM32, TRAF2, TRAF5), to the substrate adaptor DCAF15 of Cullin 4-RING Ub ligase and to some DUBs (USP29, USP33). The binding to UPS factors did not require the LxCxE motif but rather the C-terminal region of HPV16 E7 protein. The identified UPS factors interacted with most of E7 proteins across different HPV types. This study establishes a strategy for the rapid identification of interactions between host or pathogen proteins and the human ubiquitination system. © 2017 Federation of European Biochemical Societies.

Executive and social-cognitive determinants of environmental dependency syndrome in behavioral frontotemporal dementia.

PubMed

Flanagan, Emma C; Lagarde, Julien; Hahn, Valérie; Guichart-Gomez, Elodie; Sarazin, Marie; Hornberger, Michael; Bertoux, Maxime

2018-05-01

Environmental dependency syndrome (EDS), including utilization (UB) and imitation (IB) behaviors, is often reported in behavioral variant frontotemporal dementia (bvFTD). These behaviors are commonly attributed to executive dysfunction. However, inconsistent associations between EDS and poor executive performance has led to an alternative "social hypothesis," instead implicating patients' misinterpretation of the examiner's intention. We investigated the possible explanatory cognitive mechanisms of EDS in bvFTD by relating UB and IB to performance on tests of executive functioning and theory of mind (ToM). This study analyzed retrospective data of 32 bvFTD patients. Data included scores of UB and IB, various executive measures, and ToM assessment using the faux pas test, from which we extracted a mental attribution score. Of the patients, 15.6% and 40.6% exhibited UB and IB, respectively. We conducted an automatic linear modeling analysis with executive and mental attribution measures as predictor variables, and UB and IB sequentially considered as target variables. ToM mental attribution score, visual abstraction and flexibility measures from the Wisconsin Card Sorting Test, and motor sequence performance significantly (corrected ps < .05) predicted IB. No executive or ToM measures significantly predicted UB. These findings reveal a complex interaction between executive dysfunction and mental attribution deficits influencing the prevalence of EDS in bvFTD. Further investigation is required to improve our understanding of the mechanisms underlying these behaviors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Resistance in mango against infection by Ceratocystis fimbriata.

PubMed

Araujo, Leonardo; Bispo, Wilka Messner Silva; Cacique, Isaías Severino; Moreira, Wiler Ribas; Rodrigues, Fabrício Ávila

2014-08-01

This study was designed to characterize and describe host cell responses of stem tissue to mango wilt disease caused by the fungus Ceratocystis fimbriata in Brazil. Disease progress was followed, through time, in inoculated stems for two cultivars, 'Ubá' (field resistant) and 'Haden' (field susceptible). Stem sections from inoculated areas were examined using fluorescence light microscopy and transmission and scanning electron microscopy, coupled with energy-dispersive X-ray microanalysis. Tissues from Ubá colonized by C. fimbriata had stronger autofluorescence than those from Haden. The X-ray microanalysis revealed that the tissues of Ubá had higher levels of insoluble sulfur and calcium than those of Haden. Scanning electron microscopy revealed that fungal hyphae, chlamydospores (aleurioconidia), and perithecia-like structures of C. fimbriata were more abundant in Haden relative to Ubá. At the ultrastructural level, pathogen hyphae had grown into the degraded walls of parenchyma, fiber cells, and xylem vessels in the tissue of Haden. However, in Ubá, plant cell walls were rarely degraded and hyphae were often surrounded by dense, amorphous granular materials and hyphae appeared to have died. Taken together, the results of this study characterize the susceptible and resistant basal cell responses of mango stem tissue to infection by C. fimbriata.

The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy.

PubMed

Liu, Xuezhao; Li, Yang; Wang, Xin; Xing, Ruxiao; Liu, Kai; Gan, Qiwen; Tang, Changyong; Gao, Zhiyang; Jian, Youli; Luo, Shouqing; Guo, Weixiang; Yang, Chonglin

2017-05-01

Autophagy-dependent clearance of ubiquitinated and aggregated proteins is critical to protein quality control, but the underlying mechanisms are not well understood. Here, we report the essential role of the BEACH (beige and Chediak-Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein foci, and its loss causes accumulation of Ub proteins and the autophagy cargo receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins by p62. Furthermore, WDR81 interacts with LC3C through canonical LC3-interacting regions in the BEACH domain, promoting LC3C recruitment to ubiquitinated proteins. Inactivation of LC3C or defective autophagy results in accumulation of Ub protein aggregates enriched for WDR81. In mice, WDR81 inactivation causes accumulation of p62 bodies in cortical and striatal neurons in the brain. These data suggest that WDR81 coordinates p62 and LC3C to facilitate autophagic removal of Ub proteins, and provide important insights into CAMRQ2 syndrome, a WDR81-related developmental disorder. © 2017 Liu et al.

The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy

PubMed Central

Xing, Ruxiao; Tang, Changyong; Gao, Zhiyang

2017-01-01

Autophagy-dependent clearance of ubiquitinated and aggregated proteins is critical to protein quality control, but the underlying mechanisms are not well understood. Here, we report the essential role of the BEACH (beige and Chediak–Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein foci, and its loss causes accumulation of Ub proteins and the autophagy cargo receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins by p62. Furthermore, WDR81 interacts with LC3C through canonical LC3-interacting regions in the BEACH domain, promoting LC3C recruitment to ubiquitinated proteins. Inactivation of LC3C or defective autophagy results in accumulation of Ub protein aggregates enriched for WDR81. In mice, WDR81 inactivation causes accumulation of p62 bodies in cortical and striatal neurons in the brain. These data suggest that WDR81 coordinates p62 and LC3C to facilitate autophagic removal of Ub proteins, and provide important insights into CAMRQ2 syndrome, a WDR81-related developmental disorder. PMID:28404643

Structural and functional characterization of a ubiquitin variant engineered for tight and specific binding to an alpha-helical ubiquitin interacting motif.

PubMed

Manczyk, Noah; Yates, Bradley P; Veggiani, Gianluca; Ernst, Andreas; Sicheri, Frank; Sidhu, Sachdev S

2017-05-01

Ubiquitin interacting motifs (UIMs) are short α-helices found in a number of eukaryotic proteins. UIMs interact weakly but specifically with ubiquitin conjugated to other proteins, and in so doing, mediate specific cellular signals. Here we used phage display to generate ubiquitin variants (UbVs) targeting the N-terminal UIM of the yeast Vps27 protein. Selections yielded UbV.v27.1, which recognized the cognate UIM with high specificity relative to other yeast UIMs and bound with an affinity more than two orders of magnitude higher than that of ubiquitin. Structural and mutational studies of the UbV.v27.1-UIM complex revealed the molecular details for the enhanced affinity and specificity of UbV.v27.1, and underscored the importance of changes at the binding interface as well as at positions that do not contact the UIM. Our study highlights the power of the phage display approach for selecting UbVs with unprecedented affinity and high selectivity for particular α-helical UIM domains within proteomes, and it establishes a general approach for the development of inhibitors targeting interactions of this type. © 2017 The Protein Society.

Aggregation Pathways of Native-Like Ubiquitin Promoted by Single-Point Mutation, Metal Ion Concentration, and Dielectric Constant of the Medium.

PubMed

Fermani, Simona; Calvaresi, Matteo; Mangini, Vincenzo; Falini, Giuseppe; Bottoni, Andrea; Natile, Giovanni; Arnesano, Fabio

2018-03-15

Ubiquitin-positive protein aggregates are biomarkers of neurodegeneration, but the molecular mechanism responsible for their formation and accumulation is still unclear. Possible aggregation pathways of human ubiquitin (hUb) promoted by both intrinsic and extrinsic factors, are here investigated. By a computational analysis, two different hUb dimers are indicated as possible precursors of amyloid-like structures, but their formation is disfavored by an electrostatic repulsion involving Glu16 and other carboxylate residues present at the dimer interface. Experimental data on the E16V mutant of hUb shows that this single-point mutation, although not affecting the overall protein conformation, promotes protein aggregation. It is sufficient to shift the same mutation by only two residues (E18V) to regain the behavior of wild-type hUb. The neutralization of Glu16 negative charge by a metal ion and a decrease of the dielectric constant of the medium by addition of trifluoroethanol (TFE), also promote hUb aggregation. The outcomes of this research have important implications for the prediction of physiological parameters that favor aggregate formation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Artificial Recruitment of UAF1-USP Complexes by a PHLPP1-E1 Chimeric Helicase Enhances Human Papillomavirus DNA Replication

PubMed Central

Gagnon, David; Lehoux, Michaël

2015-01-01

ABSTRACT The E1 helicase from anogenital human papillomavirus (HPV) types interacts with the cellular WD repeat-containing protein UAF1 in complex with the deubiquitinating enzyme USP1, USP12, or USP46. This interaction stimulates viral DNA replication and is required for maintenance of the viral episome in keratinocytes. E1 associates with UAF1 through a short UAF1-binding site (UBS) located within the N-terminal 40 residues of the protein. Here, we investigated if the E1 UBS could be replaced by the analogous domain from an unrelated protein, the pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1). We found that PHLPP1 and E1 interact with UAF1 in a mutually exclusive manner and mapped the minimal PHLPP1 UBS (PUBS) to a 100-amino-acid region sufficient for assembly into UAF1-USP complexes. Similarly to the E1 UBS, overexpression of PUBS in trans inhibited HPV DNA replication, albeit less efficiently. Characterization of a PHLPP1-E1 chimeric helicase revealed that PUBS could partially substitute for the E1 UBS in enhancing viral DNA replication and that the stimulatory effect of PUBS likely involves recruitment of UAF1-USP complexes, as it was abolished by mutations that weaken UAF1-binding and by overexpression of catalytically inactive USPs. Although functionally similar to the E1 UBS, PUBS is larger in size and requires both the WD repeat region and C-terminal ubiquitin-like domain of UAF1 for interaction, in contrast to E1, which does not contact the latter. Overall, this comparison of two heterologous UBSs indicates that these domains function as transferable protein interaction modules and provide further evidence that the association of E1 with UAF1-containing deubiquitinating complexes stimulates HPV DNA replication. IMPORTANCE The E1 protein from anogenital HPV types interacts with the UAF1-associated deubiquitinating enzymes USP1, USP12, and USP46 to stimulate replication of the viral genome. Little is known about the molecular nature of the E1-UAF1 interaction and, more generally, how UAF1-USP complexes recognize their substrate proteins. To address this question, we characterized the UAF1-binding site (UBS) of PHLPP1, a protein unrelated to E1. Using a PHLPP1-E1 chimeric helicase, we show that the PHLPP1 UBS (PUBS) can partially substitute for the E1 UBS in stimulating HPV DNA replication. This stimulation required conserved sequences in PUBS that meditate its interaction with UAF1, including a motif common to the E1 UBS. These results indicate that UAF1-binding sequences function as transferable protein interaction modules and provide further evidence that UAF1-USP complexes stimulate HPV DNA replication. PMID:25833051

Artificial Recruitment of UAF1-USP Complexes by a PHLPP1-E1 Chimeric Helicase Enhances Human Papillomavirus DNA Replication.

PubMed

Gagnon, David; Lehoux, Michaël; Archambault, Jacques

2015-06-01

The E1 helicase from anogenital human papillomavirus (HPV) types interacts with the cellular WD repeat-containing protein UAF1 in complex with the deubiquitinating enzyme USP1, USP12, or USP46. This interaction stimulates viral DNA replication and is required for maintenance of the viral episome in keratinocytes. E1 associates with UAF1 through a short UAF1-binding site (UBS) located within the N-terminal 40 residues of the protein. Here, we investigated if the E1 UBS could be replaced by the analogous domain from an unrelated protein, the pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1). We found that PHLPP1 and E1 interact with UAF1 in a mutually exclusive manner and mapped the minimal PHLPP1 UBS (PUBS) to a 100-amino-acid region sufficient for assembly into UAF1-USP complexes. Similarly to the E1 UBS, overexpression of PUBS in trans inhibited HPV DNA replication, albeit less efficiently. Characterization of a PHLPP1-E1 chimeric helicase revealed that PUBS could partially substitute for the E1 UBS in enhancing viral DNA replication and that the stimulatory effect of PUBS likely involves recruitment of UAF1-USP complexes, as it was abolished by mutations that weaken UAF1-binding and by overexpression of catalytically inactive USPs. Although functionally similar to the E1 UBS, PUBS is larger in size and requires both the WD repeat region and C-terminal ubiquitin-like domain of UAF1 for interaction, in contrast to E1, which does not contact the latter. Overall, this comparison of two heterologous UBSs indicates that these domains function as transferable protein interaction modules and provide further evidence that the association of E1 with UAF1-containing deubiquitinating complexes stimulates HPV DNA replication. The E1 protein from anogenital HPV types interacts with the UAF1-associated deubiquitinating enzymes USP1, USP12, and USP46 to stimulate replication of the viral genome. Little is known about the molecular nature of the E1-UAF1 interaction and, more generally, how UAF1-USP complexes recognize their substrate proteins. To address this question, we characterized the UAF1-binding site (UBS) of PHLPP1, a protein unrelated to E1. Using a PHLPP1-E1 chimeric helicase, we show that the PHLPP1 UBS (PUBS) can partially substitute for the E1 UBS in stimulating HPV DNA replication. This stimulation required conserved sequences in PUBS that meditate its interaction with UAF1, including a motif common to the E1 UBS. These results indicate that UAF1-binding sequences function as transferable protein interaction modules and provide further evidence that UAF1-USP complexes stimulate HPV DNA replication. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

77 FR 3751 - Extension of Deadlines; Upward Bound Program (Regular Upward Bound (UB))

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

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Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-04

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

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Novel synthetic curcumin analogs as potent antiangiogenic agents in colorectal cancer.

PubMed

Rajitha, Balney; Nagaraju, Ganji Purnachandra; Shaib, Walid L; Alese, Olatunji B; Snyder, James P; Shoji, Mamoru; Pattnaik, Subasini; Alam, Afroz; El-Rayes, Bassel F

2017-01-01

The transcription factor NF-κB plays a central role in angiogenesis in colorectal cancer (CRC). Curcumin is a natural dietary product that inhibits NF-κB. The objective of this study is to evaluate the antiangiogenic effects of curcumin and two potent synthetic analogues (EF31 and UBS109) in CRC. IC 50 values for curcumin, EF31, and UBS109 were determined in the HCT116 and HT-29 cell lines. HUVEC tube formation, egg CAM assay, and matrigel plug assays revealed decreased angiogenesis in cell lines treated with curcumin, EF31, or UBS109. Curcumin and its analogues significantly inhibited VEGF-A synthesis and secretion in both cell lines in association with loss of HIF-1α, COX-2, and p-STAT-3 expression. Nuclear NF-κB expression was inhibited by curcumin, EF31, and UBS109. Transfection of p65-NF-κB in HCT116 and HT-29 cells resulted in increased expression of HIF-1α, COX-2, STAT-3, and VEGF-A. Treatment with curcumin, EF31, or UBS109 inhibited these effects in transfected cell lines. In mice carrying HCT116 and HT-29 cell xenografts, EF31 and UBS109 inhibited subcutaneous tumor growth and potentiated the effects of oxaliplatin and 5-FU. Tumors from treated animals revealed inhibition of HIF-1α, COX-2, p-STAT-3, and VEGF expression. Our findings suggest that inhibition of NF-κB leading to decreased transcription and expression of HIF-1α, COX-2, STAT-3, and VEGF is a rational approach for antiangiogenic therapy in CRC. The distinctive properties of EF31 and UBS109 make them promising therapeutic agents for development in CRC as single agents or as part of combination chemotherapy regimens. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A DNA vaccine co-expressing Trichinella spiralis MIF and MCD-1 with murine ubiquitin induces partial protective immunity in mice.

PubMed

Tang, F; Xu, L; Yan, R; Song, X; Li, X

2013-03-01

Co-expression of Trichinella spiralis macrophage migration inhibitory factor (TsMIF) with T. spiralis cystatin-like domain protein (TsMCD-1) in a DNA vaccine induces a Th1 immune response and partial protection against T. spiralis infection. The present study evaluated whether co-expression of mouse ubiquitin (Ub) with TsMIF and TsMCD-1 might improve the immune response against T. spiralis infection. Groups of BALB/c mice were immunized twice at 2-week intervals with 100 μg of plasmid DNA encoding either a TsMIF-TsMCD-1 fusion protein (pVAX1-Tsmif-Tsmcd-1) or an Ub-co-expressing triple fusion protein Ub-TsMIF-TsMCD-1 (pVAX1-Ub-Tsmif-Tsmcd-1). Control animals were immunized with pVAX1-Ub or blank vector plasmid. Specific antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, IgA, IgE) against the recombinant protein TsMIF-TsMCD-1, serum cytokines (interferon (IFN)-γ, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-β1 and IL-17), CD4+/CD8+ T cells and cytotoxic T lymphocyte (CTL) responses were monitored. Challenge infection was performed 2 weeks after the second immunization and worm burden was assayed at 35 days post-challenge. Antibody responses induced by pVAX1-Ub-Tsmif-Tsmcd-1 were significantly lower than for TsMIF-TsMCD-1, but the vaccine induced increased levels of Th1 cytokine (IFN-γ) and increased T-cell cytotoxicity. The reduction of worm burden (37.95%) following immunization with pVAX1-Ub-Tsmif-Tsmcd-1 was significantly greater than that induced by the pVAX1-Tsmif-Tsmcd-1 vaccine (23.17%; P< 0.05).

Bone breaking strength and apparent metabolisability of calcium and phosphorus in selected and unselected broiler chicken genotypes.

PubMed

McDevitt, R M; McEntee, G M; Rance, K A

2006-10-01

1. The present study examined the bone strength and apparent mineral metabolisability of a selected broiler chicken compared with those of a relatively unselected genotype. 2. Selected (SB) and unselected genotypes (UB) were reared under standard conditions and were fed on either a high quality (HQ) or a low quality (LQ) diet. Tibiotarsi samples were collected at 42 d from SB and compared to tibiotarsi from UB of the same age and the same body mass (BM). 3. Bones were assessed for: bone breaking strength (BBS), morphology (weight and length), and both organic (OM) and inorganic content (ASH). Apparent dry matter digestibility and the coefficient of apparent metabolisability of calcium and phosphorus were determined at the same BM. 4. The BBS of SB (214 +/- 9 N) was greater than that of same-age UB (119 +/- 8 N) but the same as that of same-BM UB (218 +/- 10 N). At the same age, the SB had stronger, heavier bones with more ash and organic matter per unit length of tibiotarsus than UB. At the same BM, the tibiotarsi of the SB were shorter and lighter, with a higher ash and a similar organic content than the bones of the UB. At the same BM, BBS was about 15% lower in both genotypes fed on the LQ compared to the HQ diet. 5. The coefficients of apparent metabolisability of calcium and phosphorus were the same in both genotypes when fed on the HQ diet, but were lower in the SB than in the UB genotype when the birds were given the LQ diet. 6. The tibiotarsi of the selected broilers were stronger, or at least as strong, as those of the unselected broiler genotype, which may be due to similar levels of apparent calcium metabolisability of the selected chickens.

Ubiquitinated Proteome: Ready for Global?*

PubMed Central

Shi, Yi; Xu, Ping; Qin, Jun

2011-01-01

Ubiquitin (Ub) is a small and highly conserved protein that can covalently modify protein substrates. Ubiquitination is one of the major post-translational modifications that regulate a broad spectrum of cellular functions. The advancement of mass spectrometers as well as the development of new affinity purification tools has greatly expedited proteome-wide analysis of several post-translational modifications (e.g. phosphorylation, glycosylation, and acetylation). In contrast, large-scale profiling of lysine ubiquitination remains a challenge. Most recently, new Ub affinity reagents such as Ub remnant antibody and tandem Ub binding domains have been developed, allowing for relatively large-scale detection of several hundreds of lysine ubiquitination events in human cells. Here we review different strategies for the identification of ubiquitination site and discuss several issues associated with data analysis. We suggest that careful interpretation and orthogonal confirmation of MS spectra is necessary to minimize false positive assignments by automatic searching algorithms. PMID:21339389

Crystallization and preliminary X-ray diffraction studies of the ubiquitin-like (UbL) domain of the human homologue A of Rad23 (hHR23A) protein.

PubMed

Chen, Yu Wai; Tajima, Toshitaka; Rees, Martin; Garcia-Maya, Mitla

2009-09-01

Human homologue A of Rad23 (hHR23A) plays dual roles in DNA repair as well as serving as a shuttle vehicle targeting polyubiquitinated proteins for degradation. Its N-terminal ubiquitin-like (UbL) domain interacts with the 19S proteasomal cap and provides the docking mechanism for protein delivery. Pyramidal crystals of the UbL domain of hHR23A were obtained by the hanging-drop vapour-diffusion method with ammonium sulfate as the crystallizing agent. The crystals diffracted to beyond 2 A resolution and belonged to the hexagonal space group P6(5)22, with unit-cell parameters a = b = 78.48, c = 63.57 A. The structure was solved by molecular replacement using the UbL domain of yeast Dsk2 as the search model.

Variability of Phytoplankton Size Structure in Response to Changes in Coastal Upwelling Intensity in the Southwestern East Sea

NASA Astrophysics Data System (ADS)

Shin, Jung-Wook; Park, Jinku; Choi, Jang-Geun; Jo, Young-Heon; Kang, Jae Joong; Joo, HuiTae; Lee, Sang Heon

2017-12-01

The aim of this study was to examine the size structure of phytoplankton under varying coastal upwelling intensities and to determine the resulting primary productivity in the southwestern East Sea. Samples of phytoplankton assemblages were collected on five occasions from the Hupo Bank, off the east coast of Korea, during 2012-2013. Because two major surface currents have a large effect on water mass transport in this region, we first performed a Backward Particle Tracking Experiment (BPTE) to determine the coastal sea from which the collected samples originated according to advection time of BPTE particles, following which we used upwelling age (UA) to determine the intensity of coastal upwelling in the region of origin for each sample. Only samples that were affected by coastal upwelling in the region of origin were included in subsequent analyses. We found that as UA increased, there was a decreasing trend in the concentration of picophytoplankton, and increasing trends in the concentration of nanophytoplankton and microphytoplankton. We also examined the relationship between the size structure of phytoplankton and primary productivity in the Ulleung Basin (UB), which has experienced significant variation over the past decade. We found that primary productivity in UB was closely related to the strength of the southerly wind, which is the most important mechanism for coastal upwelling in the southwestern East Sea. Thus, the size structure of phytoplankton is determined by the intensity of coastal upwelling, which is regulated by the southerly wind, and makes an important contribution to primary productivity.

ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response.

PubMed

Malakhova, Oxana A; Zhang, Dong-Er

2008-04-04

Interferons regulate diverse immune functions through the transcriptional activation of hundreds of genes involved in anti-viral responses. The interferon-inducible ubiquitin-like protein ISG15 is expressed in cells in response to a variety of stress conditions like viral or bacterial infection and is present in its free form or is conjugated to cellular proteins. In addition, protein ubiquitination plays a regulatory role in the immune system. Many viruses modulate the ubiquitin (Ub) pathway to alter cellular signaling and the antiviral response. Ubiquitination of retroviral group-specific antigen precursors and matrix proteins of the Ebola, vesicular stomatitis, and rabies viruses by Nedd4 family HECT domain E3 ligases is an important step in facilitating viral release. We found that Nedd4 is negatively regulated by ISG15. Free ISG15 specifically bound to Nedd4 and blocked its interaction with Ub-E2 molecules, thus preventing further Ub transfer from E2 to E3. Furthermore, overexpression of ISG15 diminished the ability of Nedd4 to ubiquitinate viral matrix proteins and led to a decrease in the release of Ebola VP40 virus-like particles from the cells. These results point to a mechanistically novel function of ISG15 in the enhancement of the innate anti-viral response through specific inhibition of Nedd4 Ub-E3 activity. To our knowledge, this is the first example of a Ub-like protein with the ability to interfere with Ub-E2 and E3 interaction to inhibit protein ubiquitination.

Health professionals in the process of vaccination against hepatitis B in two basic units of Belo Horizonte: a qualitative evaluation.

PubMed

Lages, Annelisa Santos; França, Elisabeth Barboza; Freitas, Maria Imaculada de Fátima

2013-06-01

According to the Vaccine Coverage Survey, performed in 2007, the immunization coverage against hepatitis B in Belo Horizonte, for infants under one year old, was below the level proposed by the Brazilian National Program of Immunization. This vaccine was used as basis for evaluating the involvement of health professionals in the process of vaccination in two Basic Health Units (UBS, acronym in Portuguese) in the city. This study is qualitative and uses the notions of Social Representations Theory and the method of Structural Analysis of Narrative to carry out the interviews and data analysis. The results show flaws related to controlling and use of the mirror card and the parent orientation, and also the monitoring of vaccination coverage (VC) and use of VC data as input for planning health actions. It was observed that the working process in the UBS is focused on routine tasks, with low creativity of the professionals, which includes representations that maintain strong tendency to value activities focused on the health of individuals to the detriment of public health actions. In conclusion, the vaccination process fault can be overcome with a greater appreciation of everyday actions and with a much better use of local information about vaccination, and some necessary adjustments within the UBS to improve public health actions.

[Photodynamic therapy of urinary bladder cancer using a chlorin based photosensitizer].

PubMed

Iagudaev, D M; Martov, A G; Sorokatyĭ, A E; Geĭnits, A V

2006-01-01

Photodynamic therapy (PDT) is a modem, low-invasive method of urinary bladder (UB) cancer treatment. PDT can induce complete or partial destruction of the tumor, reduce recurrence rate, provide assistance to elderly patients with compromised somatic status who are not radically operable. A combined technique improves the results of photodynamic therapy in patients with surface and invasive UB cancer of stage T2 because photodynamic impact affects not only the tumor but also all UB mucosa by light fiber with cylindric diffusor introduced in a silicon balloon with water. This leads to tumor destruction and a recurrence rate decrease.

How Chemical Synthesis of Ubiquitin Conjugates Helps To Understand Ubiquitin Signal Transduction.

PubMed

Hameed, Dharjath S; Sapmaz, Aysegul; Ovaa, Huib

2017-03-15

Ubiquitin (Ub) is a small post-translational modifier protein involved in a myriad of biochemical processes including DNA damage repair, proteasomal proteolysis, and cell cycle control. Ubiquitin signaling pathways have not been completely deciphered due to the complex nature of the enzymes involved in ubiquitin conjugation and deconjugation. Hence, probes and assay reagents are important to get a better understanding of this pathway. Recently, improvements have been made in synthesis procedures of Ub derivatives. In this perspective, we explain various research reagents available and how chemical synthesis has made an important contribution to Ub research.

A multivariate relationship for the impact sensitivities of energetic N-nitrocompounds based on bond dissociation energy.

PubMed

Li, Jinshan

2010-02-15

The ZPE-corrected N-NO(2) bond dissociation energies (BDEs(ZPE)) of a series of model N-nitrocompounds and typical energetic N-nitrocompounds have been calculated using density functional theory methods. Computed results show that using the 6-31G** basis set the UB3LYP calculated BDE(ZPE) is similar to the B3PW91 but is less than the UB3P86 and that for both UB3P86 and UB3PW91 methods the 6-31G(**) calculated BDE(ZPE) is close to the 6-31++G(**). For the series of model N-nitrocompounds it is drawn from the NBO analysis that at the UB3LYP/6-31G(**) level the order of BDE(ZPE) is not only in line with that of bond order but also with that of the energy gap between N-NO(2) bond and antibond orbitals. For the typical energetic N-nitrocompounds the impact sensitivity is strongly related to the BDE(ZPE) indeed, and based on the BDEs(ZPE) calculated at different density functional theory levels this work has established a good multivariate correlation of impact sensitivity with molecular parameters, which provides a method to address the sensitivity problem.

Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice

PubMed Central

Chala, Bayissa; Choi, Min-Ho; Moon, Kyung Chul; Kim, Hyung Suk; Kwak, Cheol; Hong, Sung-Tae

2017-01-01

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs. PMID:28285503

Bacterial carbonate precipitation improves water absorption of interlocking compressed earth block (ICEB)

NASA Astrophysics Data System (ADS)

Zamer, M. M.; Irwan, J. M.; Othman, N.; Faisal, S. K.; Anneza, L. H.; Alshalif, A. F.; Teddy, T.

2017-11-01

Interlocking compressed earth blocks (ICEB) are soil based blocks that allows for mortarless construction. The addition of many alternative materials into interlocking block in order to improve the durability has been reported. However there are currently lack of report and evidence on the application of biocalcification or microbiologically induced calcite precipitation (MICP) in improving the engineering properties of ICEB. This paper evaluate the effect of UB in improving the water absorption properties of ICEB. This paper also provide the results on SEM analysis of addition of 1%, 3% and 5% UB in ICEB. The bacteria were added as partial replacement of limestone water in ICEB. The results showed the reduction of 14.72% with 5% UB on initial water absorption followed by the results for water absorption by 24-hour soaking which also indicates reduction of 14.68% with 5% UB on 28th days of testing compared to control specimen. It was expected that the reduction of water absorption was due to the plugging of pores by the bacterial calcite which prevent ingression of water in ICEB samples. Therefore this study hopes that the positive results from the UB as improving in water absorption of ICEB will lead to improve others ICEB properties and others construction materials.

Winter Eurasian cooling linked with the Atlantic Multidecadal Oscillation

NASA Astrophysics Data System (ADS)

Luo, Dehai; Chen, Yanan; Dai, Aiguo; Mu, Mu; Zhang, Renhe; Ian, Simmonds

2017-12-01

In this paper, we analyze observational and reanalysis data to demonstrate that the Atlantic Multidecadal Oscillation (AMO) significantly modulates winter Eurasian surface air temperature through its impact on the shape, frequency and persistence of Ural blocking (UB) events that last for 10-20 d. This impact results from changes in mid-high latitude westerly winds over Eurasia associated with the warming in the Barents-Kara Seas (BKS) through the AMO-driven high sea surface temperature and sea-ice decline and resultant weakening in meridional temperature gradients. The BKS warming has a strongest positive correlation with the AMO at a time lag of about 14 years. During the recent positive AMO phase, more persistent northwest-southeast (NW-SE) oriented UB events are favored by weakened westerly winds in Eurasian mid-high latitudes. Through cold atmospheric advection and radiative cooling, such UB events produce a strong, persistent and widespread cooling over Eurasia and enhance BKS warming during 1999-2015. However, the positive AMO phase cannot directly produce the Eurasian cooling if the UB is absent. Thus, we conclude that the recent AMO phase change is a major cause of the recent winter cooling over Eurasia through its impact on BKS temperature and sea ice, which in turn affect the meridional temperature gradient, the westerly winds and the UB events.

78 FR 25259 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... all regular UB projects. To do so, project directors will be asked to complete a 40 minute survey. This survey will serve two main purposes: 1. To describe the services and strategies that Upward Bound... to provide other services as well. The survey will attempt to capture program offerings, requirements...

Diagnostic accuracy of urinary biomarkers in infants younger than 3 months with urinary tract infection

PubMed Central

Jung, Nani; Byun, Hye Jin; Park, Jae Hyun; Kim, Joon Sik; Kim, Hae Won

2018-01-01

Purpose The aim of this study was to evaluate the diagnostic accuracy of urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (uNGAL) and β-2 microglobulin (uB2MG), in early detection of urinary tract infection (UTI) in infants aged <3 months with fever. Methods A total of 422 infants aged <3 months (male:female=267:155; mean age, 56.4 days), who were admitted for fever, were retrospectively included in this study. We compared uNGAL and uB2MG between the UTI and non-UTI groups at the time of admission. The sensitivity, specificity, accuracy, and area under the curve (AUC) of uNGAL and uB2MG for use in diagnosing UTI were assessed. Results Among 422 patients, 102 (24.2%) were diagnosed with UTI. Levels of uNGAL were higher in the UTI group than in the non-UTI group (366.6 ng/mL vs. 26.9 ng/mL, P<0.001). Levels of uB2MG were not different between the 2 groups. Multivariate analysis revealed that uNGAL was an independent predictive factor for UTI (P=0.033). The sensitivity, specificity, and accuracy were 90.2%, 92.5%, and 91.9% for uNGAL, and 48.0%, 43.8%, and 44.8% for uB2MG, respectively. AUC of uNGAL was 0.942 and that of uB2MG was 0.407. Conclusion Accuracy of uNGAL in the diagnosis of UTI is high in febrile infants aged <3 months. uNGAL can help in the early diagnosis and treatment of UTI in infants. PMID:29441109

Pulmonary inflammation-induced loss and subsequent recovery of skeletal muscle mass require functional poly-ubiquitin conjugation.

PubMed

Ceelen, Judith J M; Schols, Annemie M W J; Thielen, Nathalie G M; Haegens, Astrid; Gray, Douglas A; Kelders, Marco C J M; de Theije, Chiel C; Langen, Ramon C J

2018-05-02

Pulmonary inflammation in response to respiratory infections can evoke muscle wasting. Increased activity of the ubiquitin (Ub)-proteasome system (UPS) and the autophagy lysosome pathway (ALP) have been implicated in inflammation-induced muscle atrophy. Since poly-Ub conjugation is required for UPS-mediated proteolysis and has been implicated in the ALP, we assessed the effect of impaired ubiquitin conjugation on muscle atrophy and recovery following pulmonary inflammation, and compared activation and suppression of these proteolytic systems to protein synthesis regulation. Pulmonary inflammation was induced in mice by an intratracheal instillation of LPS. Proteolysis (UPS and ALP) and synthesis signaling were examined in gastrocnemius muscle homogenates. Ub-conjugation-dependency of muscle atrophy and recovery was addressed using Ub-K48R (K48R) mice with attenuated poly-ubiquitin conjugation, and compared to UBWT control mice. Pulmonary inflammation caused a decrease in skeletal muscle mass which was accompanied by a rapid increase in expression of UPS and ALP constituents and reduction in protein synthesis signaling acutely after LPS. Muscle atrophy was attenuated in K48R mice, while ALP and protein synthesis signaling were not affected. Muscle mass recovery starting 72 h post LPS, correlated with reduced expression of UPS and ALP constituents and restoration of protein synthesis signaling. K48R mice however displayed impaired recovery of muscle mass. Pulmonary inflammation-induced muscle atrophy is in part attributable to UPS-mediated proteolysis, as activation of ALP- and suppression of protein synthesis signaling occur independently of poly-Ub conjugation during muscle atrophy. Recovery of muscle mass following pulmonary inflammation involves inverse regulation of proteolysis and protein synthesis signaling, and requires a functional poly-Ub conjugation.

Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I.

PubMed

Lang, Charles H; Huber, Danuta; Frost, Robert A

2007-01-01

The present study determined whether thermal injury increases the expression of the ubiquitin (Ub) E3 ligases referred to as muscle ring finger (MuRF)-1 and muscle atrophy F-box (MAFbx; aka atrogin-1), which are muscle specific and responsible for the increased protein breakdown observed in other catabolic conditions. After 48 h of burn injury (40% total body surface area full-thickness scald burn) gastrocnemius weight was reduced, and this change was associated with an increased mRNA abundance for atrogin-1 and MuRF-1 (3.1- to 8-fold, respectively). Similarly, burn increased polyUb mRNA content in the gastrocnemius twofold. In contrast, there was no burn-induced atrophy of the soleus and no significant change in atrogin-1, MuRF-1, or polyUb mRNA. Burns also did not alter E3 ligase expression in heart. Four hours after administration of the anabolic agent insulin-like growth factor (IGF)-I to burned rats, the mRNA content of atrogin-1 and polyUb in gastrocnemius had returned to control values and the elevation in MuRF-1 was reduced 50%. In contrast, leucine did not alter E3 ligase expression. In a separate study, in vivo administration of the proteasome inhibitor Velcade prevented burn-induced loss of muscle mass determined at 48 h. Finally, administration of the glucocorticoid receptor antagonist RU-486 did not prevent burn-induced atrophy of the gastrocnemius or the associated elevation in atrogin-1, MuRF-1, or polyUb. In summary, the acute muscle wasting accompanying thermal injury is associated with a glucocorticoid-independent increase in the expression of several Ub E3 ligases that can be downregulated by IGF-I.

Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity

PubMed Central

Ma, Qi; Ruan, Hongyu; Peng, Lisheng; Zhang, Mingjie; Gack, Michaela U.

2017-01-01

Ubiquitination-directed proteasomal degradation of synaptic proteins, presumably mediated by lysine 48 (K48) of ubiquitin, is a key mechanism in synapse and neural circuit remodeling. However, more than half of polyubiquitin (polyUb) species in the mammalian brain are estimated to be non-K48; among them, the most abundant is Lys 63 (K63)-linked polyUb chains that do not tag substrates for degradation but rather modify their properties and activity. Virtually nothing is known about the role of these nonproteolytic polyUb chains at the synapse. Here we report that K63-polyUb chains play a significant role in postsynaptic protein scaffolding and synaptic strength and plasticity. We found that the postsynaptic scaffold PSD-95 (postsynaptic density protein 95) undergoes K63 polyubiquitination, which markedly modifies PSD-95’s scaffolding potentials, enables its synaptic targeting, and promotes synapse maturation and efficacy. TNF receptor-associated factor 6 (TRAF6) is identified as a direct E3 ligase for PSD-95, which, together with the E2 complex Ubc13/Uev1a, assembles K63-chains on PSD-95. In contrast, CYLD (cylindromatosis tumor-suppressor protein), a K63-specific deubiquitinase enriched in postsynaptic densities, cleaves K63-chains from PSD-95. We found that neuronal activity exerts potent control of global and synaptic K63-polyUb levels and, through NMDA receptors, drives rapid, CYLD-mediated PSD-95 deubiquitination, mobilizing and depleting PSD-95 from synapses. Silencing CYLD in hippocampal neurons abolishes NMDA-induced chemical long-term depression. Our results unveil a previously unsuspected role for nonproteolytic polyUb chains in the synapse and illustrate a mechanism by which a PSD-associated K63-linkage–specific ubiquitin machinery acts on a major postsynaptic scaffold to regulate synapse organization, function, and plasticity. PMID:28973854

Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

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

Vuong, Tram Thu; Berger, Christian; Bertelsen, Vibeke

The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub{sub 4}) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub{sub 4} chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub{sub 4} was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub{sub 4} was constitutively internalizedmore » and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub{sub 4} was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.« less

Two-sided Ubiquitin Binding of NF-κB Essential Modulator (NEMO) Zinc Finger Unveiled by a Mutation Associated with Anhidrotic Ectodermal Dysplasia with Immunodeficiency Syndrome*

PubMed Central

Ngadjeua, Flora; Chiaravalli, Jeanne; Traincard, François; Raynal, Bertrand; Fontan, Elisabeth; Agou, Fabrice

2013-01-01

Hypomorphic mutations in the X-linked human NEMO gene result in various forms of anhidrotic ectodermal dysplasia with immunodeficiency. NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain. Here, we investigated the effect of the D406V mutation found in the NEMO ZF of an ectodermal dysplasia with immunodeficiency patients. This point mutation does not impair the folding of NEMO ZF or mono-ubiquitin binding but is sufficient to alter NEMO function, as NEMO-deficient fibroblasts and Jurkat T lymphocytes reconstituted with full-length D406V NEMO lead to partial and strong defects in NF-κB activation, respectively. To further characterize the ubiquitin binding properties of NEMO ZF, we employed di-ubiquitin (di-Ub) chains composed of several different linkages (Lys-48, Lys-63, and linear (Met-1-linked)). We showed that the pathogenic mutation preferentially impairs the interaction with Lys-63 and Met-1-linked di-Ub, which correlates with its ubiquitin binding defect in vivo. Furthermore, sedimentation velocity and gel filtration showed that NEMO ZF, like other NEMO related-ZFs, binds mono-Ub and di-Ub with distinct stoichiometries, indicating the presence of a new Ub site within the NEMO ZF. Extensive mutagenesis was then performed on NEMO ZF and characterization of mutants allowed the proposal of a structural model of NEMO ZF in interaction with a Lys-63 di-Ub chain. PMID:24100029

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

PubMed

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

2017-07-21

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

UbSRD: The Ubiquitin Structural Relational Database.

PubMed

Harrison, Joseph S; Jacobs, Tim M; Houlihan, Kevin; Van Doorslaer, Koenraad; Kuhlman, Brian

2016-02-22

The structurally defined ubiquitin-like homology fold (UBL) can engage in several unique protein-protein interactions and many of these complexes have been characterized with high-resolution techniques. Using Rosetta's structural classification tools, we have created the Ubiquitin Structural Relational Database (UbSRD), an SQL database of features for all 509 UBL-containing structures in the PDB, allowing users to browse these structures by protein-protein interaction and providing a platform for quantitative analysis of structural features. We used UbSRD to define the recognition features of ubiquitin (UBQ) and SUMO observed in the PDB and the orientation of the UBQ tail while interacting with certain types of proteins. While some of the interaction surfaces on UBQ and SUMO overlap, each molecule has distinct features that aid in molecular discrimination. Additionally, we find that the UBQ tail is malleable and can adopt a variety of conformations upon binding. UbSRD is accessible as an online resource at rosettadesign.med.unc.edu/ubsrd. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses

PubMed Central

Frias-Staheli, Natalia; Giannakopoulos, Nadia V.; Kikkert, Marjolein; Taylor, Shannon L.; Bridgen, Anne; Paragas, Jason J.; Richt, Juergen A.; Rowland, Raymond R.; Schmaljohn, Connie S.; Lenschow, Deborah J.; Snijder, Eric J.; García-Sastre, Adolfo; Virgin, Herbert Whiting

2007-01-01

Summary Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways. PMID:18078692

Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription

PubMed Central

Wozniak, Glenn G.

2014-01-01

Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression. PMID:25085417

Effect of oral supplementation of the probiotic capsule UB-01BV in the treatment of patients with bacterial vaginosis.

PubMed

Sudha, M Ratna; Maurya, A K

2012-06-01

Bacterial vaginosis (BV) is a common condition affecting millions of women annually and is characterised by a reduction in native lactobacilli. Antimicrobial therapy used to cure the disease is often found to be ineffective. We postulate that the potential probiotic capsule UB-01BV might be efficient in the treatment of BV. In the present study, 30 Indian women diagnosed with BV presenting symptoms such as white discharge, pH greater than 4.7, increased discharge, odour, colour of discharge and pruritus were included. All subjects were assigned to receive two potential probiotic capsules UB-01BV a day for 7 days. At the end of the treatment all subjects showed significant (P<0.001) positive response as revealed by a reduction in vaginosis symptoms. Therefore, the results of the present study provide the first preliminary evidence that the potential probiotic capsule UB-01BV can exert a significant reduction in vaginal infection.

Trends in Respiratory Syncytial Virus and Bronchiolitis Hospitalization Rates in High-Risk Infants in a United States Nationally Representative Database, 1997–2012

PubMed Central

Doucette, Abigail; Jiang, Xiaohui; Fryzek, Jon; Coalson, Jenna; McLaurin, Kimmie; Ambrose, Christopher S.

2016-01-01

Background Respiratory syncytial virus (RSV) causes significant pediatric morbidity and is the most common cause of bronchiolitis. Bronchiolitis hospitalizations declined among US infants from 2000‒2009; however, rates in infants at high risk for RSV have not been described. This study examined RSV and unspecified bronchiolitis (UB) hospitalization rates from 1997‒2012 among US high-risk infants. Methods The Kids’ Inpatient Database (KID) infant annual RSV (ICD-9 079.6, 466.11, 480.1) and UB (ICD-9 466.19, 466.1) hospitalization rates were estimated using weighted counts. Denominators were based on birth hospitalizations with conditions associated with high-risk for RSV: chronic perinatal respiratory disease (chronic lung disease [CLD]); congenital airway anomalies (CAA); congenital heart disease (CHD); Down syndrome (DS); and other genetic, metabolic, musculoskeletal, and immunodeficiency conditions. Preterm infants could not be identified. Hospitalizations were characterized by mechanical ventilation, inpatient mortality, length of stay, and total cost (2015$). Poisson and linear regression were used to test statistical significance of trends. Results RSV and UB hospitalization rates were substantially elevated for infants with higher-risk CHD, CLD, CAA and DS without CHD compared with all infants. RSV rates declined by 47.0% in CLD and 49.7% in higher-risk CHD infants; no other declines in high-risk groups were observed. UB rates increased in all high-risk groups except for a 22.5% decrease among higher-risk CHD. Among high-risk infants, mechanical ventilation increased through 2012 to 20.4% and 13.5% of RSV and UB hospitalizations; geometric mean cost increased to $31,742 and $25,962, respectively, and RSV mortality declined to 0.9%. Conclusions Among high-risk infants between 1997 and 2012, RSV hospitalization rates declined among CLD and higher-risk CHD infants, coincident with widespread RSV immunoprophylaxis use in these populations. UB hospitalization rates increased in all high-risk groups except higher-risk CHD, suggesting improvement in the health status of higher-risk CHD infants, potentially due to enhanced surgical interventions. Mechanical ventilation use and RSV and UB hospitalization costs increased while RSV mortality declined. PMID:27050095

Comparison of the measurements of a novel optical biometry: Nidek AL-Scan with Sirius and a ultrasound biometry.

PubMed

Çağlar, Çağatay; Kocamış, Sücattin İlker; Demir, Emre; Durmuş, Mustafa

2017-06-01

To investigate the accuracy of the measurements of Nidek AL-Scan by comparing with Sirius (CSO, Florence, Italy), a corneal tomography which also employs the Scheimpflug principle, and a commonly used device, ultrasound biometry (UB) (Aviso A/B, Quantel Medical, MT, USA). Right eyes of 85 healthy volunteers (58 women 27 men) with a mean age of 39.24 ± 14.37 years (range 15-68) were enrolled into this comparative prospective study. Average K 2.4, average K 3.3, CCT (central corneal thickness), WTW (white to white distance), ACD (anterior chamber depth) and AL (axial length) were obtained from the AL-Scan and compared with average SimK, CCT, WTW (horizontal anterior chamber diameter) and ACD obtained from Sirius and also compared with ACD and AL obtained from UB. The statistically significant difference was found between all of the measurements (p < 0.001) except the average keratometry values (K2.4, K3.3, SimK) (p = 0.083). There was a perfect correlation between keratometry, CCT and AL measurements of the devices (ICC = 0.977, 0.954, 0.923, respectively) and there was a strong correlation between the WTW measurements of AL-Scan and Sirius (ICC = 0.865). While ACD parameter of AL-Scan and UB showed a perfect correlation (ICC = 0.977), there was a moderate correlation between AL-Scan and Sirius and also between UB and Sirius (ICC = 0.608 and 0.664, respectively). There was a high correlation between the all measurements, besides ACD, of AL-Scan and Sirius and they can be used interchangeably for average keratometry and WTW confidently. However, ACD and CCT have a broader 95 % LoA (-0.039 to 0.744 and -24.985 to 3.691, respectively). In addition, AL-Scan and UB were in good agreement regarding ACD, while differences in AL measurements of UB and AL-Scan were clinically important (95 % LoA = -0.091 to 0.703). Furthermore, UB and Sirius have a moderate agreement regarding ACD (95 % LoA = -0.047 to 0.680).

Low-temperature synthesis of actinide tetraborides by solid-state metathesis reactions

DOEpatents

Lupinetti, Anthony J [Los Alamos, NM; Garcia, Eduardo [Los Alamos, NM; Abney, Kent D [Los Alamos, NM

2004-12-14

The synthesis of actinide tetraborides including uranium tetraboride (UB.sub.4), plutonium tetraboride (PuB.sub.4) and thorium tetraboride (ThB.sub.4) by a solid-state metathesis reaction are demonstrated. The present method significantly lowers the temperature required to .ltoreq.850.degree. C. As an example, when UCl.sub.4 is reacted with an excess of MgB.sub.2, at 850.degree. C., crystalline UB.sub.4 is formed. Powder X-ray diffraction and ICP-AES data support the reduction of UCl.sub.3 as the initial step in the reaction. The UB.sub.4 product is purified by washing water and drying.

Pharmacological Inhibitors of the Proteosome in Atrophying Muscles

NASA Technical Reports Server (NTRS)

Goldberg, Alfred

1999-01-01

It is now clear that the marked loss of muscle mass that occurs with disuse, denervation or in many systemic diseases (cancer cachexia, sepsis, acidosis, various endocrine disorders) is due primarily to accelerated degradation of muscle proteins, especially myofibrillar components. Recent work primarily in Dr. Goldberg's laboratory had suggested that in these diverse conditions, the enhancement of muscle proteolysis results mainly from activation of the Ub-proteasome degradative pathway. In various experimental models of atrophy, rat muscles show a common series of changes indicative of activation of this pathway, including increases in MRNA for Ub and proteasome subunits, content of ubiquitinated proteins, and sensitivity to inhibitors of the proteasome. In order to understand the muscle atrophy seen in weightlessness, Dr. Goldberg's laboratory is collaborating with Dr. Baldwin in studies to define the changes in these parameters upon hind-limb suspension. Related experiments will explore the effects on this degradative system of exercise regimens and also of glucocorticoids, which are known to rise in space personnel and to promote muscle, especially in inactive muscles. The main goals will be: (A) to define the enzymatic changes leading to enhanced activity of the Ub-proteasome pathway in inactive muscles upon hind-limb suspension, and the effects on this system of exposure to glucocorticoids or exercise; and (B) to learn whether inhibitors of the Ub-proteasome pathway may be useful in retarding the excessive proteolysis in atrophying muscles. Using muscle extracts, Dr. Goldberg's group hopes to define the rate-limiting, enzymatic changes that lead to the accelerated Ub-conjugation and protein degradation. They have recently developed cell-free preparations from atrophying rat muscles, in which Ub-conjugation to muscle proteins is increased above control levels. Because these new preparations seem to reproduce the changes occurring in vivo, they will analyze in depth extracts from normal and atrophying muscles to compare the activities of the Ub-activating enzyme (El), the various LTh-carrier proteins (E2s), and Ub-protein ligases (E3s). Recent studies of other types of muscle wasting -suggest a very important role in muscle proteolysis of certain ubiquitination enzymes, E214k and E3-alpha(i.e. components of the "N-end pathway"). Future studies will focus in understanding their role and test whether they are in fact critical for muscle atrophy in vivo. Since weightlessness leads to a specific loss of contractile proteins and to a switching of myosin isotypes, Dr. Goldberg's group will attempt to identify the ubiquitination enzymes specifically involved in myosin degradation both in normal muscle and after hind-limb suspension.

Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

NASA Astrophysics Data System (ADS)

Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.

2014-09-01

The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric β2-adrenoreceptors and the activity of two factors which are involved in β2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric β2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

The trans-neptunian object UB313 is larger than Pluto.

PubMed

Bertoldi, F; Altenhoff, W; Weiss, A; Menten, K M; Thum, C

2006-02-02

The most distant known object in the Solar System, 2003 UB313 (97 au from the Sun), was recently discovered near its aphelion. Its high eccentricity and inclination to the ecliptic plane, along with its perihelion near the orbit of Neptune, identify it as a member of the 'scattered disk'. This disk of bodies probably originates in the Kuiper belt objects, which orbit near the ecliptic plane in circular orbits between 30 and 50 au, and may include Pluto as a member. The optical brightness of 2003 UB313, if adjusted to Pluto's distance, is greater than that of Pluto, which suggested that it might be larger than Pluto. The actual size, however, could not be determined from the optical measurements because the surface reflectivity (albedo) was unknown. Here we report observations of the thermal emission of 2003 UB313 at a wavelength of 1.2 mm, which in combination with the measured optical brightness leads to a diameter of 3,000 +/- 300 +/- 100 km. Here the first error reflects measurement uncertainties, while the second derives from the unknown object orientation. This makes 2003 UB313 the largest known trans-neptunian object, even larger than Pluto (2,300 km). The albedo is 0.60 +/- 0.10 +/- 0.05, which is strikingly similar to that of Pluto, suggesting that the methane seen in the optical spectrum causes a highly reflective icy surface.

Effect of cellular ubiquitin levels on the regulation of oxidative stress response and proteasome function via Nrf1.

PubMed

Lee, Donghee; Ryu, Kwon-Yul

2017-04-01

The polyubiquitin genes Ubb and Ubc are upregulated under oxidative stress induced by arsenite [As(III)]. However, the role of ubiquitin (Ub) under As(III) exposure is not known in detail. In a previous study, we showed that the reduced viability observed in Ubc -/- mouse embryonic fibroblasts under As(III) exposure was not due to dysregulation of the Nrf2-Keap1 pathway, which prompted us to investigate another NFE2 family protein, nuclear factor erythroid 2-related factor 1 (Nrf1). In this study, we found that Ub deficiency due to Ubc knockdown in N2a cells reduced cell viability and proteasome activity under As(III) exposure. Furthermore, mRNA levels of the proteasome subunit Psma1 were also reduced. In addition, Ub deficiency led to the nuclear accumulation of the p65 isoform of Nrf1 under As(III) exposure. Interestingly, the overexpression of p65-Nrf1 recapitulated the phenotypes of Ub-deficient N2a cells under As(III) exposure. On the other hand, Nrf1 knockdown suppressed the death of Ub-deficient N2a cells upon exposure to As(III). Therefore, the levels of p65-Nrf1 may play an important role in the maintenance of cell viability under oxidative stress induced by As(III). Copyright © 2017 Elsevier Inc. All rights reserved.

A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT.

PubMed

Loo, Colleen; Sheehan, Patrick; Pigot, Melissa; Lyndon, William

2007-11-01

Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.

Upward Bound: An Untapped Fountain Of Youth Wanting To Learn About Math And Science

NASA Astrophysics Data System (ADS)

Gillis-Davis, J. J.; Sherman, S. B.; Gillis-Davis, L. C.; Svelling, K. L.

2009-12-01

We developed a two-phased curricula aimed at high school students in Hawaii’s Upward Bound (UB) programs. The course, called “Tour Through the Solar System”, was tested in the summer 2008-2009 programs of two of the four Hawaii UB programs. Authorized by Congress in 1965, UB is a federal program funded by the U.S. Department of Education to serve students underrepresented in higher education. Students enrolled in UB are predominantly low income, or from families in which neither parent holds a bachelor’s degree. UB programs make a measurable improvement in retaining high school students in the education pipeline in part by using innovative educational and outreach programs to spark students’ interest in learning while building academic self-confidence. Curricula developed for UB are sustainable because there are 964 programs in the United States, and U territories. Education and outreach products can be presented at regional and national meetings, which directors of the UB programs attend. Broad regulations and varied instruction formats allow curriculum developers a flexible and creative framework for developing classes. For instance, regulations stipulate that programs must provide participants with academic instruction in mathematics, laboratory sciences, composition, literature, and foreign languages in preparation for college entrance. UB meets these guidelines through school-year academic activities and a six-week summer school program. In designing our curricula the primary goals were to help students learn how to learn and encourage them to develop an interest in the fields of science, technology, engineering and math using NASA planetary data sets in a Problem-Based Learning (PBL) environment. Our focus on planetary science stems from our familiarity with the data sets, our view that NASA data sets are a naturally inspirational tool to engage high school students, and its cross-disciplinary character: encompassing geology, chemistry, astronomy, physics, math, and engineering. In addition, learning science through inquiry and experimentation lends tangible examples to abstract principles. Our curricula (available on-line for sharing) are comprised of (1) modular classroom lesson plans, (2) teacher tutorials, and (3) hands-on laboratory experiments. Each set of summer classes has a theme; the first set of summer classes centered on factors that affect climate on any planet. For example, students measured solar activity by counting sunspots and learned about the greenhouse effect by conducting experiments with colored bottles. The second summer focused on how the electromagnetic spectrum is fundamental to remote sensing. During our summer 2009 program the Lunar Reconnaissance Orbiter launched, and with its many instruments served as a shining example of how the electromagnetic spectrum is used to study planetary bodies. Thus, NASA archived and student-collected data sets used in a PBL setting provide the basic foundation for helping students learn science and math concepts, while the UB programs ensure sustainability by providing a fountain of youth who want to learn.

Effective Utilization of ICT in English Language Learning--The Case of University of Botswana Undergraduates

ERIC Educational Resources Information Center

Umunnakwe, Ngozi; Sello, Queen

2016-01-01

The study investigates the effective utilization of Information and Communication Technology (ICT) by first year undergraduates of the University of Botswana (UB) in their reading and writing skills. The first year students are not first language (L1) learners of English. They have not utilized computers for learning reading and writing in their…

Educating Normal Breast Mucosa to Prevent Breast Cancer

DTIC Science & Technology

2013-05-01

REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average...cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U...b. ABSTRACT U c. THIS PAGE U UU 19b. TELEPHONE NUMBER (include area code) Table of Contents Page

Medical education and faculty development: a new role for the health sciences librarian.

PubMed Central

Schwartz, D G

1995-01-01

This paper describes the roles and responsibilities of the associate director for medical education at the Primary Care Resource Center (PCRC), School of Medicine and Biomedical Sciences, State University of New York at Buffalo (UB). The PCRC was established to increase the number of UB medical school graduates who selected graduate medical education in the generalist disciplines. The associate director, who is a health sciences librarian, has established collaborative working relationships with primary care physicians in the clinical departments of family medicine, pediatrics, and internal medicine with the goal of improving the teaching effectiveness of faculty and residents. Another goal is to incorporate the use of computerized information technologies into clinical practice by training physicians and residents, at specially equipped ambulatory training sites, in how to access and manage information for the purpose of providing quality medical care. This has been accomplished in part through the provision of highly personalized instruction to participants. In addition to describing these activities, this paper examines how the duties of the associate director reflect the potential for long-term change in the roles and responsibilities of health sciences librarians, whether they work in a traditional or nontraditional setting. PMID:8547911

Ground state sign-changing solutions for fractional Kirchhoff equations in bounded domains

NASA Astrophysics Data System (ADS)

Luo, Huxiao; Tang, Xianhua; Gao, Zu

2018-03-01

We study the existence of ground state sign-changing solutions for the fractional Kirchhoff problem. Under mild assumptions on the nonlinearity, by using some new analytical skills and the non-Nehari manifold method, we prove that the fractional Kirchhoff problem possesses a ground state sign-changing solution ub. Moreover, we show that the energy of ub is strictly larger than twice that of the ground state solutions of Nehari-type. Finally, we establish the convergence property of ub as the parameter b ↘ 0. Our results generalize some results obtained by Shuai [J. Differ. Equations 259, 1256 (2015)] and Tang and Cheng [J. Differ. Equations 261, 2384 (2016)].

78 FR 56740 - Grant of Individual Exemption Involving UBS AG (UBS or the Applicant); Located in Zurich...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... requirements: (1) An independent auditor, who has appropriate technical training and proficiency with Title I of ERISA, shall conduct an annual written audit; (2) The audit shall specifically require the auditor... and written policies and procedures requirements described in paragraph (f); (4) The auditor shall...

78 FR 66955 - Exemptions From Certain Prohibited Transaction Restrictions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... Auction Rate Securities by UBS AG (ARS Rights) in connection with a Settlement Agreement, (b) the sale of an Auction Rate Security to UBS pursuant to such ARS Rights, where such sale (a Settlement Sale) is... the offer of ARS Rights (the ARS Rights Offer) are consistent with the requirements set forth in the...

The Effectiveness of Upward Bound in Preparing Disadvantaged Youth for Postsecondary Education.

ERIC Educational Resources Information Center

Steel, Lauri; Schubert, Jane G.

The effectiveness of Upward Bound (UB), a federally funded program to assist high-ability disadvantaged youth in completing programs in higher education, is addressed in this study. The study sought to determine if participation in UB enhances high school performance and participation in postsecondary education, especially in comparison to non-UB…

Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation.

PubMed

Scott, Daniel C; Rhee, David Y; Duda, David M; Kelsall, Ian R; Olszewski, Jennifer L; Paulo, Joao A; de Jong, Annemieke; Ovaa, Huib; Alpi, Arno F; Harper, J Wade; Schulman, Brenda A

2016-08-25

Hundreds of human cullin-RING E3 ligases (CRLs) modify thousands of proteins with ubiquitin (UB) to achieve vast regulation. Current dogma posits that CRLs first catalyze UB transfer from an E2 to their client substrates and subsequent polyubiquitylation from various linkage-specific E2s. We report an alternative E3-E3 tagging cascade: many cellular NEDD8-modified CRLs associate with a mechanistically distinct thioester-forming RBR-type E3, ARIH1, and rely on ARIH1 to directly add the first UB and, in some cases, multiple additional individual monoubiquitin modifications onto CRL client substrates. Our data define ARIH1 as a component of the human CRL system, demonstrate that ARIH1 can efficiently and specifically mediate monoubiquitylation of several CRL substrates, and establish principles for how two distinctive E3s can reciprocally control each other for simultaneous and joint regulation of substrate ubiquitylation. These studies have broad implications for CRL-dependent proteostasis and mechanisms of E3-mediated UB ligation. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of backpack carrying on forced vital capacity in cystic fibrosis: A randomized crossover-controlled trial.

PubMed

Combret, Yann; Medrinal, Clement; Prieur, Guillaume; Robledo Quesada, Aurora; Le Roux, Pascal; Reychler, Grégory

2018-01-01

Backpack carrying impacts lung function in healthy children but the effect in children with cystic fibrosis (CF) is unknown. Three backpack positions were tested: no backpack (NB), a 12.5% body-weight backpack carried bilaterally (BB) or unilaterally (UB), at rest and during a 10 minute walk. Primary outcome was forced vital capacity (FVC). Secondary outcomes included comparison of cardio-respiratory variables within and between groups. Nine children with CF (13.3±2.6 years; FEV1 66±22%) and 18 healthy children (13.8±1.8 years; FEV1 107±30%) were included. FVC was reduced with UB compared to NB (68.5±23.3% vs 72.1±24.3%, p = 0.024) in children with CF. FEV1, MIP and MEP decreased more with UB in children with CF than in healthy peers. Increases in VO2, VCO2 and minute ventilation with UB were greater in the CF group during walking. Unilateral backpack wearing affects FVC in children with CF and requires greater cardio-respiratory adjustments compared to healthy peers.

Vortex ring formation at the open end of a shock tube: A particle image velocimetry study

NASA Astrophysics Data System (ADS)

Arakeri, J. H.; Das, D.; Krothapalli, A.; Lourenco, L.

2004-04-01

The vortex ring generated subsequent to the diffraction of a shock wave from the open end of a shock tube is studied using particle image velocimetry. We examine the early evolution of the compressible vortex ring for three-exit shock Mach numbers, 1.1, 1.2, and 1.3. For the three cases studied, the ring formation is complete at about tUb/D=2, where t is time, Ub is fluid velocity behind shock as it exits the tube and D is tube diameter. Unlike in the case of piston generated incompressible vortex rings where the piston velocity variation with time is usually trapezoidal, in the shock-generated vortex ring case the exit fluid velocity doubles from its initial value Ub before it slowly decays to zero. At the end of the ring formation, its translation speed is observed to be about 0.7 Ub. During initial formation and propagation, a jet-like flow exists behind the vortex ring. The vortex ring detachment from the tailing jet, commonly referred to as pinch-off, is briefly discussed.

Replication Protein A (RPA) deficiency activates the Fanconi anemia DNA repair pathway.

PubMed

Jang, Seok-Won; Jung, Jin Ki; Kim, Jung Min

2016-09-01

The Fanconi anemia (FA) pathway regulates DNA inter-strand crosslink (ICL) repair. Despite our greater understanding of the role of FA in ICL repair, its function in the preventing spontaneous genome instability is not well understood. Here, we show that depletion of replication protein A (RPA) activates the FA pathway. RPA1 deficiency increases chromatin recruitment of FA core complex, leading to FANCD2 monoubiquitination (FANCD2-Ub) and foci formation in the absence of DNA damaging agents. Importantly, ATR depletion, but not ATM, abolished RPA1 depletion-induced FANCD2-Ub, suggesting that ATR activation mediated FANCD2-Ub. Interestingly, we found that depletion of hSSB1/2-INTS3, a single-stranded DNA-binding protein complex, induces FANCD2-Ub, like RPA1 depletion. More interestingly, depletion of either RPA1 or INTS3 caused increased accumulation of DNA damage in FA pathway deficient cell lines. Taken together, these results indicate that RPA deficiency induces activation of the FA pathway in an ATR-dependent manner, which may play a role in the genome maintenance.

Wavelet-analysis of gastric microcirculation in rats with ulcer bleedings

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Semyachkina-Glushkovskaya, O. V.; Pavlova, O. N.; Bibikova, O. A.; Kurths, J.

2013-10-01

Nitric oxide (NO) plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhagic stress. Because the impaired gastric mucosal blood flow is the major cause of gastroduodenal lesions including ulcer bleeding (UB), we study in this work the NO-ergic mechanism responsible for regulation of this blood flow. Our study is performed in rats with a model of stress-induced UB using laser Doppler flowmetry (LDF) that characterizes the rate of blood flow by measuring a Doppler shift of the laser beam scattered by the moving red blood cells. Numerical analysis of LDF-data is based on the discrete wavelet-transform (DWT) using Daubechies wavelets aiming to quantify influences of NO on the gastric microcirculation. We show that the stress-induced UB is associated with an increased level of NO in the gastric tissue and a stronger vascular sensitivity to pharmacological modulation of NO-production by L-NAME. We demonstrate that wavelet-based analyses of NO-dependent regulation of gastric microcirculation can provide an effective endoscopic diagnostics of a risk of UB.

Positive association between hypertension and urinary bladder cancer: epidemiologic evidence involving 79,236 propensity score-matched individuals.

PubMed

Kok, Victor C; Zhang, Han-Wei; Lin, Chin-Teng; Huang, Shih-Chung; Wu, Ming-Feng

2018-06-18

We hypothesized that hypertensive patients harbor a higher risk of urinary bladder (UB) cancer. We performed a population-based cohort study on adults using a National Health Insurance Research Database (NHIRD) dataset. Hypertension and comparison non-hypertensive (COMP) groups comprising 39,618 patients each were propensity score-matched by age, sex, index date, and medical comorbidities. The outcome was incident UB cancer validated using procedure codes. We constructed multivariable Cox models to derive adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Cumulative incidence was compared using a log-rank test. During a total follow-up duration of 380,525 and 372,020 person-years in the hypertension and COMP groups, 248 and 186 patients developed UB cancer, respectively, representing a 32% increase in the risk (aHR, 1.32; 95% CI, 1.09-1.60). Hypertensive women harbored a significantly increased risk of UB cancer (aHR, 1.55; 95% CI, 1.12-2.13) compared with non-hypertensive women, whereas men with hypertension had a statistically non-significant increased risk (aHR, 1.22; 95% CI, 0.96-1.55). The sensitivity analysis demonstrated that the increased risk was sustained throughout different follow-up durations for the entire cohort; a statistical increase in the risk was also noted among hypertensive men. This nationwide population-based propensity score-matched cohort study supports a positive association between hypertension and subsequent UB cancer development.

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2017-01-02

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

Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin

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

Capodagli, Glenn C.; McKercher, Marissa A.; Baker, Erica A.

Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage ofmore » posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 {angstrom}, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.« less

Complementation of a Fanconi anemia group A cell line by UbA{sup 52}

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

Moses, R.E.; Heina, J.A.; Jakobs, P.M.

1994-09-01

Cells from patients with Fanconi anemia (FA) display chromosomal instability and increased sensitivity to mitomycin C (MMC) and diepoxybutane (DEB) relative to normal cells. Several genes act in this pathway of DNA damage processing based upon four known complementation groups in FA. We have made a cDNA expression library in a vector with a G418 selectable marker to identify FA genes other than the FA-C group. Approximately 1 x 10{sup 6} independent cDNA clones were isolated with an average cDNA size of 1.5 kb. Five cell lines resistant to MMC and DEB were isolated from 6 x 10{sup 6} G418-resistantmore » transfectants from 65 individual transfections of the FA-A fibroblast line GM6914. The isolated cell lines also showed normal chromosome stability. The same cDNA (600 bp) was recovered from three independent cell lines by PCR using flanking sequence primers. The gene has sequence identity with a known gene, the ubiquitin fusion gene, UbA{sub 52}. Interestingly, each of the cDNAs were inserted in antisense orientation relative to the cytomegalovirus (CMV) promoter as determined by sequencing and PCR using UbA{sub 52}-specific internal primers. Southern blot analysis indicated the cell lines had distinct chromosomal insertion sites. Mutation analysis by chemical cleavage showed no reading frame mutations, indicating that UbA{sub 52} is not the FA-A gene. Re-transfection with the UbA{sub 52} gene in antisense gave complementation for MMC, DEB and chromosome stability to varying degrees. Re-transfection of the antisense construct with the CMV promotor removed or with a sense construct did not alter the MMC sensitivity. We conclude that the antisense UbA{sub 52} gene has a non-specific effect, perhaps acting by altering the cell cycle or susceptibility to apoptosis.« less

Feasibility of Ultrasound-Based Computational Fluid Dynamics as a Mitral Valve Regurgitation Quantification Technique: Comparison with 2-D and 3-D Proximal Isovelocity Surface Area-Based Methods.

PubMed

Jamil, Muhammad; Ahmad, Omar; Poh, Kian Keong; Yap, Choon Hwai

2017-07-01

Current Doppler echocardiography quantification of mitral regurgitation (MR) severity has shortcomings. Proximal isovelocity surface area (PISA)-based methods, for example, are unable to account for the fact that ultrasound Doppler can measure only one velocity component: toward or away from the transducer. In the present study, we used ultrasound-based computational fluid dynamics (Ub-CFD) to quantify mitral regurgitation and study its advantages and disadvantages compared with 2-D and 3-D PISA methods. For Ub-CFD, patient-specific mitral valve geometry and velocity data were obtained from clinical ultrasound followed by 3-D CFD simulations at an assumed flow rate. We then obtained the average ratio of the ultrasound Doppler velocities to CFD velocities in the flow convergence region, and scaled CFD flow rate with this ratio as the final measured flow rate. We evaluated Ub-CFD, 2-D PISA and 3-D PISA with an in vitro flow loop, which featured regurgitation flow through (i) a simplified flat plate with round orifice and (ii) a 3-D printed realistic mitral valve and regurgitation orifice. The Ub-CFD and 3-D PISA methods had higher precision than the 2-D PISA method. Ub-CFD had consistent accuracy under all conditions tested, whereas 2-D PISA had the lowest overall accuracy. In vitro investigations indicated that the accuracy of 2-D and 3-D PISA depended significantly on the choice of aliasing velocity. Evaluation of these techniques was also performed for two clinical cases, and the dependency of PISA on aliasing velocity was similarly observed. Ub-CFD was robustly accurate and precise and has promise for future translation to clinical practice. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Hungatella effluvii gen. nov., sp. nov., an obligately anaerobic bacterium isolated from an effluent treatment plant, and reclassification of Clostridium hathewayi as Hungatella hathewayi gen. nov., comb. nov.

PubMed

Kaur, Sukhpreet; Yawar, Mir; Kumar, P Anil; Suresh, K

2014-03-01

A Gram-stain-positive, rod-shaped, spore-forming and strictly anaerobic bacterium, designated UB-B.2(T), was isolated from an industrial effluent anaerobic digester sample. It grew optimally at 30 °C and pH 7.0. Comparative analysis of the 16S rRNA gene sequence confirmed that strain UB-B.2(T) was closely related to Clostridium hathewayi DSM 13479(T) (97.84% similarity), a member of rRNA gene cluster XIVa of the genus Clostridium, and formed a coherent cluster with other related members of the Blautia (Clostridium) coccoides rRNA group in phylogenetic analyses. The end products of glucose fermentation by strain UB-B.2(T) were acetate and propionate. The G+C content of the DNA was 51.4 mol%. Although strain UB-B.2(T) showed 97.8% 16S rRNA gene sequence identity to the type strain of C. hathewayi, it exhibited only 38.4% relatedness at the whole-genome level. It also showed differences from its closest phylogenetic relative, C. hathewayi DSM 13479(T), in phenotypic characteristics such as hydrolysis of aesculin, starch and urea and fermentation end products. Both strains showed phenotypic differences from the members of rRNA gene cluster XIVa of the genus Clostridium. Based on these differences, C. hathewayi DSM 13479(T) and strain UB-B.2(T) were identified as representatives of a new genus of the family Clostridiaceae. Thus, we propose the reclassification of Clostridium hathewayi as Hungatella hathewayi gen. nov., comb. nov., the type species of the new genus (type strain DSM 13479(T) = CCUG 43506(T) = MTCC 10951(T)). Strain UB-B.2(T) ( = MTCC 11101(T) = DSM 24995(T)) is assigned to the novel species Hungatella effluvii gen. nov., sp. nov as the type strain.

Inactivation of USP14 Perturbs Ubiquitin Homeostasis and Delays the Cell Cycle in Mouse Embryonic Fibroblasts and in Fruit Fly Drosophila.

PubMed

Lee, Jung Hoon; Park, Seoyoung; Yun, Yejin; Choi, Won Hoon; Kang, Min-Ji; Lee, Min Jae

2018-01-01

The 26S proteasome is the key proteolytic complex for recognition and degradation of polyubiquitinated target substrates in eukaryotes. Among numerous proteasome-associated proteins, a deubiquitinating enzyme (DUB) USP14 has been identified as an endogenous inhibitor of the proteasome. Here, we explored the complex regulatory functions of USP14 that involve ubiquitin (Ub) homeostasis and substrate degradation in flies and mammals. USP14-null primary and immortalized mouse embryonic fibroblasts (MEFs) and USP14 knocked-down Drosophila were analyzed in this study. We measured proteasome and DUB activities using fluorogenic reporter substrates and adduct-forming probes. To examine the levels of ubiquitin, we performed immunoblotting and immunohistochemistry. Mass spectrometry (MS) was used to examine polyUb chain linkages and USP14-interacing proteins. Cell cycle was analyzed by flow cytometry, BrdU labeling, and phospho-histone H3 staining. The homeostasis of Ub in USP14-/-MEFs was markedly perturbed because of facilitated clearance of Ub. This phenomenon was recapitulated in muscles of USP14-deficient Drosophila with old ages. Absolute quantitation using MS also revealed that USP14-/- MEFs contained significantly increased amounts of Ub, compared with wild-type. The key phenotype of USP14-/- MEFs was their delayed proliferation originated from prolonged interphase possibly through aberrant degradation of cyclins A and B1. We found that knocking down USP14 in Drosophila resulted in delayed eye development associated with reduced mitotic activity. Our study identifies novel cellular functions of USP14 not only in cellular Ub hometostasis but also in cell cycle progression. USP14 was also essential for proper Drosophila eye development. These results strongly suggest that the USP14-mediated proteasome activity regulation may be directly related to various human diseases including cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

Teaching Project-Based Assessment in 12 Days in a Developing Country

ERIC Educational Resources Information Center

Hargis, Jace

2007-01-01

Through a partnership between the University of North Florida (UNF) and the University of Belize (UB), faculty members from UNF taught a graduate course on Assessment and Measurement at UB to train in-service teachers and principals in the area of educational leadership. Two classes totalling 71 graduate students were taught during a three-week…

Working Connections: Suzan Lee--UBS Securities LLC, New York

ERIC Educational Resources Information Center

Library Journal, 2004

2004-01-01

This article is about Suzan Lee of UBS Securities LLC in New York, a person who is dedicated to connecting aspiring professionals to opportunities in the world of special libraries. In 1999, Lee realized that most library students had only one resource for internships--their library schools--and that these offerings focused largely on public and…

Strategic Intelligence and National Security. A Selected Bibliography

DTIC Science & Technology

1991-09-01

McCann & Geoghegan, 1981. (MHI D810 S7R39 1981) Rendel , Alexander M. APPOIINTMENT IN CRETE: THE STORY OF A BRITISH AGENT. London: Wlngate, 1953. (MHI...UB250 I 57) Mathams, R.H. SUB ROSA: MEMOIRS OF AN AUSTRALIAN INTELLIGENCE ANALYST. Boston: Allen & Unwin, 1902. (UB251 A8M37) Phelps, Ruth H.; Englert

78 FR 43930 - Proposed Exemptions From Certain Prohibited Transaction Restrictions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-22

...), of certain rights issued to owners of Auction Rate Securities by UBS AG (ARS Rights) in connection with a Settlement Agreement, (b) the sale of an Auction Rate Security to UBS pursuant to such ARS... in Section III (a) The terms and delivery of the offer of ARS Rights (the ARS Rights Offer) are...

77 FR 22792 - Non-Competitive Program Expansion Supplement To Revise, Update, and Disseminate Educational...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... Medical Center UB4HP19192 Kansas 429,472.00 42,222 Research Institute. University of Kentucky Research....00 42,222 West Virginia University Research UB4HP19050 West Virginia 428,800.00 42,222 Corp... benefits for program evaluative purposes since the GEC grantees already have evaluation requirements with...

Is the U-B color sufficient for identifying water of hydration on solar system bodies?

NASA Technical Reports Server (NTRS)

Vilas, Faith

1995-01-01

The U-B color has been suggested as a predictor of the presence of water of hydration on asteroids. Photometry from the Eight-Color Asteroid Survey (ECAS) was used to test this concept. An overlap in U-B color prevents this magnitude difference from distinguishing between surface material that was thermally processed at higher temperatures and surface material that was aqueously altered. Two tests of the presence of water of hydration using visible spectral region photometry failed to flag those few higher albedo M- and E-class asteroids having photometry that shows a 3.0-micrometers water of hydration absorption. These asteroids probably contain little or no oxidized iron in their surface material.

Symptomatic complex partial status epilepticus manifesting as utilization behavior of a mobile phone.

PubMed

Carota, Antonio; Novy, Jan; Rossetti, Andrea O

2009-03-01

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Optical properties of graphene superlattices.

PubMed

Le, H Anh; Ho, S Ta; Nguyen, D Chien; Do, V Nam

2014-10-08

In this work, the optical responses of graphene superlattices, i.e. graphene subjected to a periodic scalar potential, are theoretically reported. The optical properties were studied by investigating the optical conductivity, which was calculated using the Kubo formalism. It was found that the optical conductivity becomes dependent on the photon polarization and is suppressed in the photon energy range of (0, Ub), where Ub is the potential barrier height. In the higher photon energy range, i.e. Ω > Ub, the optical conductivity is, however, almost identical to that of pristine graphene. Such behaviors of the optical conductivity are explained microscopically through the analysis of the elements of optical matrices and effectively through a simple model, which is based on the Pauli blocking mechanism.

Ubiquitinated Proteins Isolated From Tumor Cells Are Efficient Substrates for Antigen Cross-Presentation.

PubMed

Yu, Guangjie; Moudgil, Tarsem; Cui, Zhihua; Mou, Yongbin; Wang, Lixin; Fox, Bernard A; Hu, Hong-Ming

2017-06-01

We have previously shown that inhibition of the proteasome causes defective ribosomal products to be shunted into autophagosomes and subsequently released from tumor cells as defective ribosomal products in Blebs (DRibbles). These DRibbles serve as an excellent source of antigens for cross-priming of tumor-specific T cells. Here, we examine the role of ubiquitinated proteins (Ub-proteins) in this pathway. Using purified Ub-proteins from tumor cells that express endogenous tumor-associated antigen or exogenous viral antigen, we tested the ability of these proteins to stimulate antigen-specific T-cell responses, by activation of monocyte-derived dendritic cells generated from human peripheral blood mononuclear cells. Compared with total cell lysates, we found that purified Ub-proteins from both a gp100-specific melanoma cell line and from a lung cancer cell line expressing cytomegalovirus pp65 antigen produced a significantly higher level of IFN-γ in gp100- or pp65-specific T cells, respectively. In addition, Ub-proteins from an allogeneic tumor cell line could be used to stimulate tumor-infiltrating lymphocytes isolated and expanded from non-small cell lung cancer patients. These results establish that Ub-proteins provide a relevant source of antigens for cross-priming of antitumor immune responses in a variety of settings, including endogenous melanoma and exogenous viral antigen presentation, as well as antigen-specific tumor-infiltrating lymphocytes. Thus, ubiquitin can be used as an affinity tag to enrich for unknown tumor-specific antigens from tumor cell lysates to stimulate tumor-specific T cells ex vivo or to be used as vaccines to target short-lived proteins.

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

PubMed Central

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

2017-01-01

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

Understanding by Design (UbD) in EFL Teaching: Teachers' Professional Development and Students' Achievement

ERIC Educational Resources Information Center

Yurtseven, Nihal; Altun, Sertel

2017-01-01

Concepts such as teachers' professional development and students' achievement act as the driving force for the development of each in a causal relationship in EFL teaching, as in many other disciplines. The purpose of this study is to investigate the change Understanding by Design (UbD) made on teachers' professional development and students'…

Functional crosstalk between histone H2B ubiquitylation and H2A modifications and variants.

PubMed

Wojcik, Felix; Dann, Geoffrey P; Beh, Leslie Y; Debelouchina, Galia T; Hofmann, Raphael; Muir, Tom W

2018-04-11

Ubiquitylation of histone H2B at lysine residue 120 (H2BK120ub) is a prominent histone posttranslational modification (PTM) associated with the actively transcribed genome. Although H2BK120ub triggers several critical downstream histone modification pathways and changes in chromatin structure, less is known about the regulation of the ubiquitylation reaction itself, in particular with respect to the modification status of the chromatin substrate. Here we employ an unbiased library screening approach to profile the impact of pre-existing chromatin modifications on de novo ubiquitylation of H2BK120 by the cognate human E2:E3 ligase pair, UBE2A:RNF20/40. Deposition of H2BK120ub is found to be highly sensitive to PTMs on the N-terminal tail of histone H2A, a crosstalk that extends to the common histone variant H2A.Z. Based on a series of biochemical and cell-based studies, we propose that this crosstalk contributes to the spatial organization of H2BK120ub on gene bodies, and is thus important for transcriptional regulation.

Activation of the Slx5–Slx8 Ubiquitin Ligase by Poly-small Ubiquitin-like Modifier Conjugates*S⃞

PubMed Central

Mullen, Janet R.; Brill, Steven J.

2008-01-01

Protein sumoylation is a regulated process that is important for the health of human and yeast cells. In budding yeast, a subset of sumoylated proteins is targeted for ubiquitination by a conserved heterodimeric ubiquitin (Ub) ligase, Slx5–Slx8, which is needed to suppress the accumulation of high molecular weight small ubiquitin-like modifier (SUMO) conjugates. Structure-function analysis indicates that the Slx5–Slx8 complex contains multiple SUMO-binding domains that are collectively required for in vivo function. To determine the specificity of Slx5–Slx8, we assayed its Ub ligase activity using sumoylated Siz2 as an in vitro substrate. In contrast to unsumoylated or multisumoylated Siz2, substrates containing poly-SUMO conjugates were efficiently ubiquitinated by Slx5–Slx8. Although Siz2 itself was ubiquitinated, the bulk of the Ub was conjugated to SUMO residues. Slx5–Slx8 primarily mono-ubiquitinated the N-terminal SUMO moiety of the chain. These data indicate that the Slx5–Slx8 Ub ligase is stimulated by poly-SUMO conjugates and that it can ubiquitinate a poly-SUMO chain. PMID:18499666

Inherent dynamics within the Crimean-Congo Hemorrhagic fever virus protease are localized to the same region as substrate interactions

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

Eisenmesser, Elan Z.; Capodagli, Glenn; Armstrong, Geoffrey S.

Crimean-Congo Hemorrhagic fever virus (CCHFV) is one of several lethal viruses that encodes for a viral ovarian tumor domain (vOTU), which serves to cleave and remove multiple proteins involved in cellular signaling such as ubiquitin (Ub) and interferon stimulated gene produce 15 (ISG15). Such manipulation of the host cell machinery serves to downregulate the host response and, therefore, complete characterization of these proteases is important. While several structures of the CCHFV vOTU protease have been solved, both free and bound to Ub and ISG15, few structural differences have been found and little insight has been gained as to the dynamicmore » plasticity of this protease. Therefore, we have used NMR relaxation experiments to probe the dynamics of CCHV vOTU, both alone and in complex with Ub, thereby discovering a highly dynamic protease that exhibits conformational exchange within the same regions found to engage its Ub substrate. These experiments reveal a structural plasticity around the N-terminal regions of CCHV vOTU, which are unique to vOTUs, and provide a rationale for engaging multiple substrates with the same binding site.« less

Superhump and outburst activity of the cataclysmic variable RZ LMi in the U- and optical passbands

NASA Astrophysics Data System (ADS)

Shugarov, S. Y.; Katysheva, N. A.; Chochol, D.; Krushevska, V. N.; Vozyakova, O. V.

2018-05-01

An analysis of the new U,B,V,RC,IC-photometry of the cataclysmic variable RZ LMi obtained in 2016-17 showed the largest (U-B) colour excess in quiescence as well as during the decline of brightness, associated with the outbursts activity. The smallest (U-B) colour excess was found during the brightness increase from the quiescence. In contrast to the (U-B) colour index, the (B-V),(V-RC),(RC-IC) colour indices exhibits the largest colour excesses near the maximum of the outburst and the smallest during the quiescence. The (B-V) colour index showed also a large excess 1-2 days before a minimum. The detailed study of superhumps during the maximum of activity reveals the largest (U-B) colour excess at the time of the minimum brightness of superhumps. The (B-RC) colour index exhibits a similar behaviour, but with a phase shift of +0.1-{+}0.2 period of superhumps. The tracks in two-colour and colour-magnitude diagrams during superoutbursts are compared with the data for other cataclysmic variables during their outbursts as well as with published theoretical calculations.

[Symbolical violence in the access of disabled persons to basic health units].

PubMed

de França, Inacia Sátiro Xavier; Pagliuca, Lorita Marlena Freitag; Baptista, Rosilene Santos; de França, Eurípedes Gil; Coura, Alexsandro Silva; de Souza, Jeová Alves

2010-01-01

A descriptive study which aimed to characterize the conditions of people with disabilities (PD) in the Basic Health Units-UBS. Data were collected in January 2009 in 20 UBSF. It was used digital camera and check list based on the 9050-NBR ABNT. The results showed: Access town - no traffic lights (100%) of lanes for pedestrians (100%), bumpy sidewalks (90%); Access in UBS: non-standard ports (30%) staircases without banisters (20%); floor outside the standard (75%), in disagreement with standard mobile (20%), drinking at odds with standard (55%), making it difficult to people with disabilities to use a filter (30%), has no drinking or filters (15%); telephones installed inadequately (55%); inaccessible restrooms (96%). Access to UBS of PD is permeated by the symbolic violence.

Understanding high wintertime ozone pollution events in an oil and natural gas producing region of the western US

NASA Astrophysics Data System (ADS)

Ahmadov, R.; McKeen, S.; Trainer, M.; Banta, R.; Brewer, A.; Brown, S.; Edwards, P. M.; de Gouw, J. A.; Frost, G. J.; Gilman, J.; Helmig, D.; Johnson, B.; Karion, A.; Koss, A.; Langford, A.; Lerner, B.; Olson, J.; Oltmans, S.; Peischl, J.; Pétron, G.; Pichugina, Y.; Roberts, J. M.; Ryerson, T.; Schnell, R.; Senff, C.; Sweeney, C.; Thompson, C.; Veres, P.; Warneke, C.; Wild, R.; Williams, E. J.; Yuan, B.; Zamora, R.

2014-08-01

Recent increases in oil and natural gas (NG) production throughout the western US have come with scientific and public interest in emission rates, air quality and climate impacts related to this industry. This study uses a regional scale air quality model WRF-Chem to simulate high ozone (O3) episodes during the winter of 2013 over the Uinta Basin (UB) in northeastern Utah, which is densely populated by thousands of oil and NG wells. The high resolution meteorological simulations are able to qualitatively reproduce the wintertime cold pool conditions that occurred in 2013, allowing the model to reproduce the observed multi-day buildup of atmospheric pollutants and accompanying rapid photochemical ozone formation in the UB. Two different emission scenarios for the oil and NG sector were employed in this study. The first emission scenario (bottom-up) was based on the US EPA National Emission Inventory (NEI) (2011, version 1) for the oil and NG sector for the UB. The second emission scenario (top-down) was based on the previously derived estimates of methane (CH4) emissions and a regression analysis for multiple species relative to CH4 concentration measurements in the UB. WRF-Chem simulations using the two emission data sets resulted in significant differences for concentrations of most gas-phase species. Evaluation of the model results shows greater underestimates of CH4 and other volatile organic compounds (VOCs) in the simulation with the NEI-2011 inventory than the case when the top-down emission scenario was used. Unlike VOCs, the NEI-2011 inventory significantly overestimates the emissions of nitrogen oxides (NOx), while the top-down emission scenario results in a moderate negative bias. Comparison of simulations using the two emission data sets reveals that the top-down case captures the high O3 episodes. In contrast, the simulation case using the bottom-up inventory is not able to reproduce any of the observed high O3 concentrations in the UB. A sensitivity analysis reveals that the major factors driving high wintertime O3 in the UB are shallow boundary layers with light winds, high emissions of VOCs from oil and NG operations compared to NOx emissions, enhancement of photolysis fluxes and reduction of O3 loss from deposition due to snow cover. Simple emission reduction scenarios show that the UB O3 production is VOC sensitive and NOx insensitive. The model results show a disproportionate contribution of aromatic VOCs to O3 formation relative to all other VOC emissions. We also present modeling results for winter of 2012, when high O3 levels were not observed in the UB. The air quality model together with the top-down emission framework presented here may help to address the emerging science and policy related questions surrounding the environmental impact of oil and NG drilling in western US.

45 CFR 60.20 - Confidentiality of National Practitioner Data Bank information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.20 Confidentiality of National Practitioner Data Bank information. (a) Limitations on disclosure. Information... 45 Public Welfare 1 2013-10-01 2013-10-01 false Confidentiality of National Practitioner Data Bank...

45 CFR 60.20 - Confidentiality of National Practitioner Data Bank information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.20 Confidentiality of National Practitioner Data Bank information. (a) Limitations on disclosure. Information... 45 Public Welfare 1 2014-10-01 2014-10-01 false Confidentiality of National Practitioner Data Bank...

Understanding high wintertime ozone pollution events in an oil- and natural gas-producing region of the western US

NASA Astrophysics Data System (ADS)

Ahmadov, R.; McKeen, S.; Trainer, M.; Banta, R.; Brewer, A.; Brown, S.; Edwards, P. M.; de Gouw, J. A.; Frost, G. J.; Gilman, J.; Helmig, D.; Johnson, B.; Karion, A.; Koss, A.; Langford, A.; Lerner, B.; Olson, J.; Oltmans, S.; Peischl, J.; Pétron, G.; Pichugina, Y.; Roberts, J. M.; Ryerson, T.; Schnell, R.; Senff, C.; Sweeney, C.; Thompson, C.; Veres, P. R.; Warneke, C.; Wild, R.; Williams, E. J.; Yuan, B.; Zamora, R.

2015-01-01

Recent increases in oil and natural gas (NG) production throughout the western US have come with scientific and public interest in emission rates, air quality and climate impacts related to this industry. This study uses a regional-scale air quality model (WRF-Chem) to simulate high ozone (O3) episodes during the winter of 2013 over the Uinta Basin (UB) in northeastern Utah, which is densely populated by thousands of oil and NG wells. The high-resolution meteorological simulations are able qualitatively to reproduce the wintertime cold pool conditions that occurred in 2013, allowing the model to reproduce the observed multi-day buildup of atmospheric pollutants and the accompanying rapid photochemical ozone formation in the UB. Two different emission scenarios for the oil and NG sector were employed in this study. The first emission scenario (bottom-up) was based on the US Environmental Protection Agency (EPA) National Emission Inventory (NEI) (2011, version 1) for the oil and NG sector for the UB. The second emission scenario (top-down) was based on estimates of methane (CH4) emissions derived from in situ aircraft measurements and a regression analysis for multiple species relative to CH4 concentration measurements in the UB. Evaluation of the model results shows greater underestimates of CH4 and other volatile organic compounds (VOCs) in the simulation with the NEI-2011 inventory than in the case when the top-down emission scenario was used. Unlike VOCs, the NEI-2011 inventory significantly overestimates the emissions of nitrogen oxides (NOx), while the top-down emission scenario results in a moderate negative bias. The model simulation using the top-down emission case captures the buildup and afternoon peaks observed during high O3 episodes. In contrast, the simulation using the bottom-up inventory is not able to reproduce any of the observed high O3 concentrations in the UB. Simple emission reduction scenarios show that O3 production is VOC sensitive and NOx insensitive within the UB. The model results show a disproportionate contribution of aromatic VOCs to O3 formation relative to all other VOC emissions. The model analysis reveals that the major factors driving high wintertime O3 in the UB are shallow boundary layers with light winds, high emissions of VOCs from oil and NG operations compared to NOx emissions, enhancement of photolysis fluxes and reduction of O3 loss from deposition due to snow cover.

The Understanding by Design Guide to Advanced Concepts in Creating and Reviewing Units

ERIC Educational Resources Information Center

McTighe, Jay; Wiggins, Grant

2012-01-01

Regardless of your stage at implementing the design tools and using the improved template for Understanding by Design[R] (UbD), this companion to "The UbD Guide to Creating High-Quality Units" is essential for taking your work to a higher plane. This volume features a set of hands-on modules containing worksheets, models, and self-assessments that…

Liver Cytochrome P450 3A Ubiquitination in Vivo by gp78/Autocrine Motility Factor Receptor and C Terminus of Hsp70-interacting Protein (CHIP) E3 Ubiquitin Ligases

PubMed Central

Kim, Sung-Mi; Acharya, Poulomi; Engel, Juan C.; Correia, Maria Almira

2010-01-01

CYP3A4 is a dominant human liver cytochrome P450 enzyme engaged in the metabolism and disposition of >50% of clinically relevant drugs and held responsible for many adverse drug-drug interactions. CYP3A4 and its mammalian liver CYP3A orthologs are endoplasmic reticulum (ER)-anchored monotopic proteins that undergo ubiquitin (Ub)-dependent proteasomal degradation (UPD) in an ER-associated degradation (ERAD) process. These integral ER proteins are ubiquitinated in vivo, and in vitro studies have identified the ER-integral gp78 and the cytosolic co-chaperone, CHIP (C terminus of Hsp70-interacting protein), as the relevant E3 Ub-ligases, along with their cognate E2 Ub-conjugating enzymes UBC7 and UbcH5a, respectively. Using lentiviral shRNA templates targeted against each of these Ub-ligases, we now document that both E3s are indeed physiologically involved in CYP3A ERAD/UPD in cultured rat hepatocytes. Accordingly, specific RNAi resulted in ≈80% knockdown of each hepatic Ub-ligase, with a corresponding ≈2.5-fold CYP3A stabilization. Surprisingly, however, such stabilization resulted in increased levels of functionally active CYP3A, thereby challenging the previous notion that E3 recognition and subsequent ERAD of CYP3A proteins required ab initio their structural and/or functional inactivation. Furthermore, coexpression in HepG2 cells of both CYP3A4 and gp78, but not its functionally inactive RING-finger mutant, resulted in enhanced CYP3A4 loss greater than that in corresponding cells expressing only CYP3A4. Stabilization of a functionally active CYP3A after RNAi knockdown of either of the E3s, coupled with the increased CYP3A4 loss on gp78 or CHIP coexpression, suggests that ERAD-associated E3 Ub-ligases can influence clinically relevant drug metabolism by effectively regulating the physiological CYP3A content and consequently its function. PMID:20819951

45 CFR 60.21 - How to dispute the accuracy of National Practitioner Data Bank information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Practitioner Data Bank information. 60.21 Section 60.21 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.21 How to dispute the accuracy of National Practitioner Data Bank information. (a...

45 CFR 60.21 - How to dispute the accuracy of National Practitioner Data Bank information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Practitioner Data Bank information. 60.21 Section 60.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.21 How to dispute the accuracy of National Practitioner Data Bank information. (a...

12 CFR 407.7 - Relationship to Freedom of Information Act.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Relationship to Freedom of Information Act. 407.7 Section 407.7 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES REGULATIONS GOVERNING PUBLIC OBSERVATION OF EX-IM BANK MEETINGS § 407.7 Relationship to Freedom of Information Act. Nothing in...

Recent Rapid Decline of the Arctic Winter Sea Ice in the Barents-Kara Seas Owing to Combined Effects of the Ural Blocking and SST

NASA Astrophysics Data System (ADS)

Luo, Binhe; Yao, Yao

2018-04-01

This study investigates why the Arctic winter sea ice loss over the Barents-Kara Seas (BKS) is accelerated in the recent decade. We first divide 1979-2013 into two time periods: 1979-2000 (P1) and 2001-13 (P2), with a focus on P2 and the difference between P1 and P2. The results show that during P2, the rapid decline of the sea ice over the BKS is related not only to the high sea surface temperature (SST) over the BKS, but also to the increased frequency, duration, and quasi-stationarity of the Ural blocking (UB) events. Observational analysis reveals that during P2, the UB tends to become quasi stationary and its frequency tends to increase due to the weakening (strengthening) of zonal winds over the Eurasia (North Atlantic) when the surface air temperature (SAT) anomaly over the BKS is positive probably because of the high SST. Strong downward infrared (IR) radiation is seen to occur together with the quasi-stationary and persistent UB because of the accumulation of more water vapor over the BKS. Such downward IR favors the sea ice decline over the BKS, although the high SST over the BKS plays a major role. But for P1, the UB becomes westward traveling due to the opposite distribution of zonal winds relative to P2, resulting in weak downward IR over the BKS. This may lead to a weak decline of the sea ice over the BKS. Thus, it is likely that the rapid decline of the sea ice over the BKS during P2 is attributed to the joint effects of the high SST over the BKS and the quasi-stationary and long-lived UB events.

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

Jester, Sebastian; Schneider, Donald P.; Richards, Gordon T.

The author investigates the extent to which the Palomar-Green (PG) Bright Quasar Survey (BQS) is complete and representative of the general quasar population by comparing with imaging and spectroscopy from the Sloan Digital Sky Survey. A comparison of SDSS and PG photometry of both stars and quasars reveals the need to apply a color and magnitude recalibration to the PG data. Using the SDSS photometric catalog, they define the PG's parent sample of objects that are not main-sequence stars and simulate the selection of objects from this parent sample using the PG photometric criteria and errors. This simulation shows thatmore » the effective U-B cut in the PG survey is U-B < -0.71, implying a color-related incompleteness. As the color distribution of bright quasars peaks near U-B = -0.7 and the 2-{sigma} error in U-B is comparable to the full width of the color distribution of quasars, the color incompleteness of the BQS is approximately 50% and essentially random with respect to U-B color for z < 0.5. There is however, a bias against bright quasars at 0.5 < z < 1, which is induced by the color-redshift relation of quasars (although quasars at z > 0.5 are inherently rare in bright surveys in any case). They find no evidence for any other systematic incompleteness when comparing the distributions in color, redshift, and FIRST radio properties of the BQS and a BQS-like subsample of the SDSS quasar sample. However, the application of a bright magnitude limit biases the BQS toward the inclusion of objects which are blue in g-i, in particular compared to the full range of g-i colors found among the i-band limited SDSS quasars, and even at i-band magnitudes comparable to those of the BQS objects.« less

CSN-associated USP48 confers stability to nuclear NF-κB/RelA by trimming K48-linked Ub-chains.

PubMed

Schweitzer, Katrin; Naumann, Michael

2015-02-01

Diligent balance of nuclear factor kappa B (NF-κB) activity is essential owing to NF-κB's decisive role in cellular processes including inflammation, immunity and cell survival. Ubiquitin/proteasome-system (UPS)-dependent degradation of activated NF-κB/RelA involves the cullin-RING-ubiquitin-ligase (CRL) ECS(SOCS1). The COP9 signalosome (CSN) controls ubiquitin (Ub) ligation by CRLs through the removal of the CRL-activating Ub-like modifier NEDD8 from their cullin subunits and through deubiquitinase (DUB) activity of associated DUBs. However, knowledge about DUBs involved in the regulation of NF-κB activity within the nucleus is scarce. In this study we observed that USP48, a DUB of hitherto ill-defined function identified through a siRNA screen, associates with the CSN and RelA in the nucleus. We show that USP48 trims rather than completely disassembles long K48-linked free and substrate-anchored Ub-chains, a catalytic property only shared with ataxin-3 (Atx3) and otubain-1 (OTU1), and that USP48 Ub-chain-trimming activity is regulated by casein-kinase-2 (CK2)-mediated phosphorylation in response to cytokine-stimulation. Functionally, we demonstrate for the first time the CSN and USP48 to cooperatively stabilize the nuclear pool of RelA, thereby facilitating timely induction and shutoff of NF-κB target genes. In summary, this study demonstrates that USP48, a nuclear DUB regulated by CK2, controls the UPS-dependent turnover of activated NF-κB/RelA in the nucleus together with the CSN. Thereby USP48 contributes to a timely control of immune responses. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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

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

2015-03-23

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

Conformational Dynamics Modulate Activation of the Ubiquitin Conjugating Enzyme Ube2g2

PubMed Central

2017-01-01

The ubiquitin conjugating enzyme Ube2g2 together with its cognate E3 ligase gp78 catalyzes the synthesis of lysine-48 polyubiquitin chains constituting signals for the proteasomal degradation of misfolded proteins in the endoplasmic reticulum. Here, we employ NMR spectroscopy in combination with single-turnover diubiquitin formation assays to examine the role of the RING domain from gp78 in the catalytic activation of Ube2g2∼Ub conjugates. We find that approximately 60% of the Ube2g2∼Ub conjugates occupy a closed conformation in the absence of gp78-RING, with the population increasing to 82% upon gp78-RING binding. As expected, strong mutations in the hydrophobic patch residues of the ∼Ub moiety result in Ube2g2∼Ub populating only open states with corresponding loss of the ubiquitin conjugation activity. Less disruptive mutations introduced into the hydrophobic patch of the ∼Ub moiety also destabilize the closed conformational state, yet the corresponding effect on the ubiquitin conjugation activity ranges from complete loss to an enhancement of the catalytic activity. These results present a picture in which Ube2g2’s active site is in a state of continual dynamic flux with the organization of the active site into a catalytically viable conformation constituting the rate-limiting step for a single ubiquitin ligation event. Ube2g2’s function as a highly specific K48-polyubiquitin chain elongator leads us to speculate that this may be a strategy by which Ube2g2 reduces the probability of nonproductive catalytic outcomes in the absence of available substrate. PMID:28884161

12 CFR 404.6 - Release of records under the Freedom of Information Act.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Release of records under the Freedom of Information Act. 404.6 Section 404.6 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.6 Release of...

12 CFR 40.11 - Limits on redisclosure and reuse of information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... own marketing purposes. (b)(1) Information a bank receives outside of an exception. If a bank receives... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Limits on redisclosure and reuse of information. 40.11 Section 40.11 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY PRIVACY...

Measurement of |V{sub ub}| from Inclusive Charmless Semileptonic B Decays

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

Urquijo, P.; Barberio, E.; Limosani, A.

2010-01-15

We present the partial branching fraction for inclusive charmless semileptonic B decays and the corresponding value of the Cabibbo-Kobayashi-Maskawa matrix element |V{sub ub}|, using a multivariate analysis method to access {approx}90% of the B->X{sub u}lnu phase space. This approach dramatically reduces the theoretical uncertainties from the b-quark mass and nonperturbative QCD compared to all previous inclusive measurements. The results are based on a sample of 657x10{sup 6} BB pairs collected with the Belle detector. We find that {Delta}B(B->X{sub u}l{nu};p{sub l}{sup *B}>1.0 GeV/c)=1.963x(1+-0.088{sub stat}+-0.081{sub syst})x10{sup -3}. Corresponding values of |V{sub ub}| are extracted using several theoretical calculations.

12 CFR 978.5 - Storage of confidential information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Storage of confidential information. 978.5... OPERATIONS AND AUTHORITIES BANK REQUESTS FOR INFORMATION § 978.5 Storage of confidential information. Each Bank shall: (a) Store all identified confidential information in secure storage areas or filing...

Sensory Information Processing

DTIC Science & Technology

1977-04-01

deblurred image is shown in Figure lUb. This result, with no sensor noise , shows a good representation of the original double star. The orientation of the...which we Page 21 performed to test the theory and to provide an indication of the effects of sensor noise on the performances of these procedures...34^-^^^^-^-^ Page 37 2 Labeyrie has shown experimentally that<|S(u)| > has useful signal-to- noise ratio out to the diffraction limit of the telescope. Korff

The Military Profession. A Selected Bibliography

DTIC Science & Technology

2006-09-19

CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 23 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b . ABSTRACT...rev. and expanded. Boston: McGraw-Hill, 2005. 762pp. (UB147 .F87 2005) Forsythe, George B ., et al. "Professional Identity Development for...Ohio State University, 1977. 29pp. (UB147 .M55) Moore, Wilbert E. The Professions: Roles and Rules. New York: Russell Sage Foundation, 1970

[Effect of cryopreservation on umbilical blood cells and its mechanism].

PubMed

Li, Xin; Chen, Fangping; Jiang, Tiebin; Wang, Erhua; Liu, Jing

2013-07-01

To evaluate the effect of cryopreservation on clonogenic ability and apoptosis rate of mono-nuclear cells and CD34+ cells in umbilical blood (UB), and to choose the index to present the freezing injury and optimize the cryopreservation of UB. The mono-nuclear cells (MNC) and CD34+ cells were separated from UB and frozen.After 30 days, they were thawed in warm water. Clonogenic capacity and clonogenic recovery before and after the cryopreservation was compared. We also used Annexin V-FITC-PI to investigate the apoptosis rate of the cells before and after the cryopreservation of these 2 types of cells. The number of colony forming unit-granulocyte/monocyte (CFU-GMs) was not changed after freezing and thawing in both MNCs and CD34+ cells, while the number of colony forming unit-granulocyte, erythrocyte, monocyte and megakaryocyte (CFU-GEMM) was obviously reduced after freezing in CD34+ cells. The 2 types of cryopreserved cells had certain degree of apoptosis before the cryopreservation. MNC-type cryopreservation increased the cells apoptosis a little, while CD34+-type cryopreservation increased more. The cells have certain degree of apoptosis before the cryopreservation. The freezing and thawing procedure does affect the early stage progenitor cells-CFU-GEMM in the CD34+- type cryopreserved cells in UB. The damage may be induced by the cell apoptosis.

Genetic immunization based on the ubiquitin-fusion degradation pathway against Trypanosoma cruzi

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

Chou, Bin; Department of Parasitology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582; Hiromatsu, Kenji, E-mail: khiromatsu@fukuoka-u.ac.jp

2010-02-12

Cytotoxic CD8{sup +} T cells are particularly important to the development of protective immunity against the intracellular protozoan parasite, Trypanosoma cruzi, the etiological agent of Chagas disease. We have developed a new effective strategy of genetic immunization by activating CD8{sup +} T cells through the ubiquitin-fusion degradation (UFD) pathway. We constructed expression plasmids encoding the amastigote surface protein-2 (ASP-2) of T. cruzi. To induce the UFD pathway, a chimeric gene encoding ubiquitin fused to ASP-2 (pUB-ASP-2) was constructed. Mice immunized with pUB-ASP-2 presented lower parasitemia and longer survival period, compared with mice immunized with pASP-2 alone. Depletion of CD8{sup +}more » T cells abolished protection against T. cruzi in mice immunized with pUB-ASP-2 while depletion of CD4{sup +} T cells did not influence the effective immunity. Mice deficient in LMP2 or LMP7, subunits of immunoproteasomes, were not able to develop protective immunity induced. These results suggest that ubiquitin-fused antigens expressed in antigen-presenting cells were effectively degraded via the UFD pathway, and subsequently activated CD8{sup +} T cells. Consequently, immunization with pUB-ASP-2 was able to induce potent protective immunity against infection of T. cruzi.« less

[Prevalence and factors associated with metabolic syndrome in users of primary healthcare units in São Paulo--SP, Brazil].

PubMed

Leitão, Maria Paula Carvalho; Martins, Ignez Salas

2012-01-01

To determine the relationship between metabolic syndrome (MS) and socioeconomic level, life style, health status, family history of morbidity, and residence areas. This is a cross-sectional cohort study. The random sample consisted of users of two primary health care units (Unidades Básicas de Saúde--UBSs) in the city of São Paulo--Jardim Comercial (UBS1), and Jardim Germânia (UBS2), a total of 452 subjects. The NCEP ATP IIIcriterion was used to diagnose MS. Weight, height, abdominal and hip circumferences were measured for the anthropometric evaluation. A general questionnaire was used to obtain sociodemographic and socioeconomic data; family history; medical history; behavioral habits such as smoking, drinking, and physical activity. Multivariate logistic regression was used to establish the association between explanatory variables of interest and MS. At UBS1, MS percentage was 56.1%; at UBS2, 34.0%. There was a direct and significant association between MS and age, female gender, race, smoking, drinking, physical activity level, stress, and family history of heart disease and diabetes mellitus. Education level showed an inverse association. Subjects living in a lower socioeconomic level neighborhood had a higher MS risk. The results suggest that the morbidities that compose MS are a serious publichealth problem in that population.

Role of fibroblast growth factor receptor signaling in kidney development.

PubMed

Bates, Carlton M

2011-09-01

Fibroblast growth factor receptors (Fgfrs) are expressed throughout the developing kidney. Several early studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB). Transgenic mice that over-express a dominant negative receptor isoform develop renal aplasia/severe dysplasia, confirming the importance of Fgfrs in renal development. Furthermore, global deletion of Fgf7, Fgf10, and Fgfr2IIIb (isoform that binds Fgf7 and Fgf10) in mice leads to small kidneys with fewer collecting ducts and nephrons. Deletion of Fgfrl1, a receptor lacking intracellular signaling domains, causes severe renal dysgenesis. Conditional targeting of Fgf8 from the MM interrupts nephron formation. Deletion of Fgfr2 from the UB results in severe ureteric branching and stromal mesenchymal defects, although loss of Frs2α (major signaling adapter for Fgfrs) in the UB causes only mild renal hypoplasia. Deletion of both Fgfr1 and Fgfr2 in the MM results in renal aplasia with defects in MM formation and initial UB elongation and branching. Loss of Fgfr2 in the MM leads to many renal and urinary tract anomalies as well as vesicoureteral reflux. Thus, Fgfr signaling is critical for patterning of virtually all renal lineages at early and later stages of development.

Treatment of toluene and its by-products using an electron beam/ultra-fine bubble hybrid system

NASA Astrophysics Data System (ADS)

Son, Youn-Suk; Kim, Tae-Hun; Choi, Chang Yong; Park, Jun-Hyeong; Ahn, Ji-Won; Dinh, Trieu-Vuong

2018-03-01

Although, until quite recently, many technologies (electron beam (EB), plasma, and ultraviolet) have been studied to overcome disadvantages of conventional methods (such as absorption, adsorption, biofiltration and incineration) for treatment of volatile organic compounds (VOCs), their techniques still have some problems such as formation of a by-product. Generally, it is reported that various by-products are generated from the EB irradiation process to remove VOCs. Therefore, we developed an electron beam/ultra-fine bubble (EB/UB) hybrid system to enhance removal efficiency of a VOC (toluene) and to reduce its by-products formed by electron beam irradiation. As a result, the removal efficiency of toluene (30 ppm) by only EB (10 kGy) was 80.1%. However, the removal efficiency of toluene using the hybrid system (water temperature: 5 ℃) was increased up to 17% when compared to only EB (10 kGy). Additionally, the 65.2% of ozone formed from the EB process was removed in UB reactor. In case of other trace by-products such as undesired VOCs and aldehydes, the levels were lowered down to the below detection limit by the subsequent UB reactor. We also found that the amount of toluene collected and solubilized into water is affected by the water temperature in the UB reactor.

12 CFR 408.7 - Environmental information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Environmental information. 408.7 Section 408.7 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES PROCEDURES FOR COMPLIANCE WITH THE NATIONAL ENVIRONMENTAL POLICY ACT Eximbank Implementing Procedures § 408.7 Environmental information. Interested persons...

12 CFR 408.7 - Environmental information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Environmental information. 408.7 Section 408.7 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES PROCEDURES FOR COMPLIANCE WITH THE NATIONAL ENVIRONMENTAL POLICY ACT Eximbank Implementing Procedures § 408.7 Environmental information. Interested persons...

45 CFR 60.18 - Requesting information from the National Practitioner Data Bank.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Practitioner Data Bank. 60.18 Section 60.18 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.18 Requesting information from the National Practitioner Data Bank. (a) Who may request...

45 CFR 60.18 - Requesting information from the National Practitioner Data Bank.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Practitioner Data Bank. 60.18 Section 60.18 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.18 Requesting information from the National Practitioner Data Bank. (a) Who may request...

12 CFR 1.5 - Safe and sound banking practices; credit information required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Safe and sound banking practices; credit... TREASURY INVESTMENT SECURITIES § 1.5 Safe and sound banking practices; credit information required. (a) A national bank shall adhere to safe and sound banking practices and the specific requirements of this part...

12 CFR 1.5 - Safe and sound banking practices; credit information required.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Safe and sound banking practices; credit... TREASURY INVESTMENT SECURITIES § 1.5 Safe and sound banking practices; credit information required. (a) A national bank shall adhere to safe and sound banking practices and the specific requirements of this part...

12 CFR 1.5 - Safe and sound banking practices; credit information required.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Safe and sound banking practices; credit... TREASURY INVESTMENT SECURITIES § 1.5 Safe and sound banking practices; credit information required. (a) A national bank shall adhere to safe and sound banking practices and the specific requirements of this part...

12 CFR 1.5 - Safe and sound banking practices; credit information required.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Safe and sound banking practices; credit... TREASURY INVESTMENT SECURITIES § 1.5 Safe and sound banking practices; credit information required. (a) A national bank shall adhere to safe and sound banking practices and the specific requirements of this part...

12 CFR 1.5 - Safe and sound banking practices; credit information required.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Safe and sound banking practices; credit... TREASURY INVESTMENT SECURITIES § 1.5 Safe and sound banking practices; credit information required. (a) A national bank shall adhere to safe and sound banking practices and the specific requirements of this part...

Generation of branching ureteric bud tissues from human pluripotent stem cells.

PubMed

Mae, Shin-Ichi; Ryosaka, Makoto; Toyoda, Taro; Matsuse, Kyoko; Oshima, Yoichi; Tsujimoto, Hiraku; Okumura, Shiori; Shibasaki, Aya; Osafune, Kenji

2018-01-01

Recent progress in kidney regeneration research is noteworthy. However, the selective and robust differentiation of the ureteric bud (UB), an embryonic renal progenitor, from human pluripotent stem cells (hPSCs) remains to be established. The present study aimed to establish a robust induction method for branching UB tissue from hPSCs towards the creation of renal disease models. Here, we found that anterior intermediate mesoderm (IM) differentiates from anterior primitive streak, which allowed us to successfully develop an efficient two-dimensional differentiation method of hPSCs into Wolffian duct (WD) cells. We also established a simplified procedure to generate three-dimensional WD epithelial structures that can form branching UB tissues. This system may contribute to hPSC-based regenerative therapies and disease models for intractable disorders arising in the kidney and lower urinary tract. Copyright © 2017 Elsevier Inc. All rights reserved.

Constructing kidney-like tissues from cells based on programs for organ development: toward a method of in vitro tissue engineering of the kidney.

PubMed

Rosines, Eran; Johkura, Kohei; Zhang, Xing; Schmidt, Heidi J; Decambre, Marvalyn; Bush, Kevin T; Nigam, Sanjay K

2010-08-01

The plausibility of constructing vascularized three-dimensional (3D) kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct (WD), and the metanephric mesenchyme (MM). We found that isolated MMs were capable of inducing branching morphogenesis of the WD (an epithelial tube) in recombination cultures; suggesting that the isolated MM retains inductive capacity for WD-derived epithelial tubule cells other than those from the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells from UB and mouse inner medullary collecting duct cell (IMCD) lines, which are ultimately of WD origin, were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (IMCD). This supports the view that the collecting system can be constructed from certain epithelial cells (those ultimately of WD origin) when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced factors that stimulate UB branching morphogenesis, whereas another, rat inducible metanephric mesenchyme (RIMM-18), supported WD budding as a feeder layer. This indicates that some MM functions can be recapitulated by cells. Although engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, we addressed the issue of optimal macro- and micro-patterning of kidney-like tissue, which might be necessary for function of an organ assembled using a tissue engineering approach. To identify suitable conditions, 3D reconstructions of HoxB7-green fluorescent protein mouse rudiments (E12) cultured on a filter or suspended in a collagen gel (type I or type IV) revealed that type IV collagen 3D culture supports the deepest tissue growth (600 +/- 8 microm) and the largest kidney volume (0.22 +/- 0.02 mm(3)), and enabled the development of an umbrella-shaped collecting system such as occurs in vivo. Taken together with prior work (Rosines et al., 2007; Steer et al., 2002), these results support the plausibility of a developmental strategy for constructing and propagating vascularized 3D kidney-like tissues from recombinations of cultured renal progenitor cells and/or primordial tissue.

12 CFR 229.58 - Mode of delivery of information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... receive account information. If a bank is required to provide an original check or a sufficient copy, the... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Mode of delivery of information. 229.58 Section... delivery of information. A bank may deliver any notice or other information that it is required to provide...

45 CFR 60.15 - Confidentiality of National Practitioner Data Bank information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Disclosure of Information by the National Practitioner Data Bank § 60.15 Confidentiality of National Practitioner Data Bank information. (a) Limitations on disclosure. Information reported to the NPDB is... 45 Public Welfare 1 2012-10-01 2012-10-01 false Confidentiality of National Practitioner Data Bank...

12 CFR Appendix A to Part 630 - Supplemental Information Disclosure Guidelines

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Supplemental Information Disclosure Guidelines A Appendix A to Part 630 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DISCLOSURE..., App. A Appendix A to Part 630—Supplemental Information Disclosure Guidelines Supplemental information...

12 CFR Appendix A to Part 630 - Supplemental Information Disclosure Guidelines

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Supplemental Information Disclosure Guidelines A Appendix A to Part 630 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DISCLOSURE..., App. A Appendix A to Part 630—Supplemental Information Disclosure Guidelines Supplemental information...

45 CFR 60.15 - Confidentiality of National Practitioner Data Bank information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Disclosure of Information by the National Practitioner Data Bank § 60.15 Confidentiality of National Practitioner Data Bank information. (a) Limitations on disclosure. Information reported to the NPDB is... 45 Public Welfare 1 2011-10-01 2011-10-01 false Confidentiality of National Practitioner Data Bank...

12 CFR Appendix A to Part 630 - Supplemental Information Disclosure Guidelines

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Supplemental Information Disclosure Guidelines A Appendix A to Part 630 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DISCLOSURE..., App. A Appendix A to Part 630—Supplemental Information Disclosure Guidelines Supplemental information...

12 CFR Appendix A to Part 630 - Supplemental Information Disclosure Guidelines

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Supplemental Information Disclosure Guidelines A Appendix A to Part 630 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DISCLOSURE..., App. A Appendix A to Part 630—Supplemental Information Disclosure Guidelines Supplemental information...

77 FR 70544 - Agency Information Collection Activities; Proposed Information Collection; Comment Request; Bank...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... Activities; Proposed Information Collection; Comment Request; Bank Secrecy Act/Money Laundering Risk... entitled, ``Bank Secrecy Act/Money Laundering Risk Assessment,'' also known as the Money Laundering Risk... collection of information set forth in this document. Bank Secrecy Act/Money Laundering Risk Assessment (OMB...

12 CFR 1202.3 - What information can I obtain through FOIA?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false What information can I obtain through FOIA? 1202.3 Section 1202.3 Banks and Banking FEDERAL HOUSING FINANCE AGENCY ORGANIZATION AND OPERATIONS FREEDOM OF INFORMATION ACT § 1202.3 What information can I obtain through FOIA? (a) General. FHFA...

12 CFR 1016.6 - Information to be included in privacy notices.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Information to be included in privacy notices. 1016.6 Section 1016.6 Banks and Banking BUREAU OF CONSUMER FINANCIAL PROTECTION PRIVACY OF CONSUMER FINANCIAL INFORMATION (REGULATION P) Privacy and Opt Out Notices § 1016.6 Information to be included in...

The influence of demeanor on scores from two validated feline pain assessment scales during the perioperative period.

PubMed

Buisman, Mandy; Hasiuk, Michelle M M; Gunn, Marta; Pang, Daniel S J

2017-05-01

To evaluate the effects of demeanor on validated pain assessment scales. Prospective, blind, clinical trial. Thirty three adult domestic cats scheduled for orchiectomy. Cats were assessed for pain pre (baseline) and 1, 2, 4 hours postoperatively using two validated pain scales [Composite Measures Pain Scale-Feline (rCMPS-F) and UNESP-Botucatu multidimensional composite pain scale (psychomotor and pain expression subscales; U-B MCPS-psych and -painex)], and a demeanor scale. Return of sternal recumbency and postoperative feeding were recorded. Anesthesia consisted of a single intramuscular injection of dexmedetomidine-ketamine-hydromorphone with intratesticular lidocaine and atipamezole and meloxicam postoperatively. Following data collection, cats were assigned to two groups based on baseline demeanor scores (LO ≤ 5/21, 18 cats; HI ≥ 6/21, 15 cats) and data from each group compared. Baseline demeanor predicted pain scores with the U-B MCPS-psych scale: baseline [LO 0 (0-0), HI 2 (0-6), p = 0.0005], 1 hour [LO 1 (0-5), HI 3 (1-5), p = 0.02], and 4 hours [LO 0 (0-2), HI 1 (0-6), p = 0.01]. A similar pattern was observed with the rCMPS-F. This resulted in more crossings of the analgesic intervention threshold in the HI group: U-B UNESP-psych (9 versus 1, p = 0.005) and rCMPS-F (23 versus 3, p < 0.0001). In contrast, U-B MCPS-painex scores did not differ between LO/HI groups: baseline (p > 0.99), 1 hour (p = 0.34), 2 hours (p > 0.99) and 4 hours (p = 0.31). LO cats ate sooner (61% versus 33% by 1 hour, p < 0.0001) despite similar times to sternal recumbency (p = 0.48). Demeanor affected pain assessment with U-B UNESP-psych and rCMPS-F scales, but not U-B UNESP-painex scale. Demeanor had a significant effect on postoperative feeding. These data highlight the potential for demeanor to confound pain assessment. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation.

PubMed

Ho, Yik-Khuan; Zhi, Huijun; Bowlin, Tara; Dorjbal, Batsukh; Philip, Subha; Zahoor, Muhammad Atif; Shih, Hsiu-Ming; Semmes, Oliver John; Schaefer, Brian; Glover, J N Mark; Giam, Chou-Zen

2015-08-01

Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells.

HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation

PubMed Central

Ho, Yik-Khuan; Zhi, Huijun; Bowlin, Tara; Dorjbal, Batsukh; Philip, Subha; Zahoor, Muhammad Atif; Shih, Hsiu-Ming; Semmes, Oliver John; Schaefer, Brian; Glover, J. N. Mark; Giam, Chou-Zen

2015-01-01

Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells. PMID:26285145

The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity.

PubMed

Ando, Maya; Fiesel, Fabienne C; Hudec, Roman; Caulfield, Thomas R; Ogaki, Kotaro; Górka-Skoczylas, Paulina; Koziorowski, Dariusz; Friedman, Andrzej; Chen, Li; Dawson, Valina L; Dawson, Ted M; Bu, Guojun; Ross, Owen A; Wszolek, Zbigniew K; Springer, Wolfdieter

2017-04-24

Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson's disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degradation in order to prevent their accumulation and eventually cell death. Homozygous or compound heterozygous loss of either gene function disrupts this protective pathway, though at different steps and by distinct mechanisms. While structure and function of PARKIN variants have been well studied, PINK1 mutations remain poorly characterized, in particular under endogenous conditions. A better understanding of the exact molecular pathogenic mechanisms underlying the pathogenicity is crucial for rational drug design in the future. Here, we characterized the pathogenicity of the PINK1 p.I368N mutation on the clinical and genetic as well as on the structural and functional level in patients' fibroblasts and in cell-based, biochemical assays. Under endogenous conditions, PINK1 p.I368N is expressed, imported, and N-terminally processed in healthy mitochondria similar to PINK1 wild type (WT). Upon mitochondrial damage, however, full-length PINK1 p.I368N is not sufficiently stabilized on the outer mitochondrial membrane (OMM) resulting in loss of mitochondrial quality control. We found that binding of PINK1 p.I368N to the co-chaperone complex HSP90/CDC37 is reduced and stress-induced interaction with TOM40 of the mitochondrial protein import machinery is abolished. Analysis of a structural PINK1 p.I368N model additionally suggested impairments of Ub kinase activity as the ATP-binding pocket was found deformed and the substrate Ub was slightly misaligned within the active site of the kinase. Functional assays confirmed the lack of Ub kinase activity. Here we demonstrated that mutant PINK1 p.I368N can not be stabilized on the OMM upon mitochondrial stress and due to conformational changes in the active site does not exert kinase activity towards Ub. In patients' fibroblasts, biochemical assays and by structural analyses, we unraveled two pathomechanisms that lead to loss of function upon mutation of p.I368N and highlight potential strategies for future drug development.

12 CFR 404.25 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Applicability. 404.25 Section 404.25 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Demands for Testimony of Current... personnel, in connection with legal proceedings to which Ex-Im Bank is not a party, regarding information...

12 CFR 404.3 - Public reference facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Public reference facilities. 404.3 Section 404.3 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.3 Public reference facilities. Ex-Im Bank...

78 FR 73407 - Information Sharing Among Federal Home Loan Banks

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-06

... Home Loan Banks AGENCY: Federal Housing Finance Agency. ACTION: Final rule. SUMMARY: Section 1207 of the Housing and Economic Recovery Act of 2008 (HERA) amended the Federal Home Loan Bank Act (Bank Act... to each Federal Home Loan Bank (Bank) information relating to the financial condition of all other...

12 CFR 1805.805 - Information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 9 2012-01-01 2012-01-01 false Information. 1805.805 Section 1805.805 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS PROGRAM Terms and Conditions of Assistance § 1805.805 Information. The Fund...

12 CFR 1805.805 - Information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Information. 1805.805 Section 1805.805 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS PROGRAM Terms and Conditions of Assistance § 1805.805 Information. The Fund...

12 CFR 1805.805 - Information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 9 2013-01-01 2013-01-01 false Information. 1805.805 Section 1805.805 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS PROGRAM Terms and Conditions of Assistance § 1805.805 Information. The Fund...

12 CFR 1805.805 - Information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Information. 1805.805 Section 1805.805 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS PROGRAM Terms and Conditions of Assistance § 1805.805 Information. The Fund...

12 CFR 1805.805 - Information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Information. 1805.805 Section 1805.805 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS PROGRAM Terms and Conditions of Assistance § 1805.805 Information. The Fund...

78 FR 73415 - Information To Be Distributed to the Federal Home Loan Banks and the Office of Finance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-06

...Section 20A of the Federal Home Loan Bank Act (Bank Act), requires the Director of the Federal Housing Finance Agency (FHFA) to make available to the Federal Home Loan Banks (Banks) such reports, records, or other information as may be available, relating to the condition of any Bank in order to enable each Bank to evaluate the financial condition of one or more of the other Banks individually and the Bank System as a whole. FHFA has adopted, and published in this issue of the Federal Register, a regulation to implement the statutory information sharing provisions, which will be located at 12 CFR part 1260. As required by Sec. 1260.2(b) of that regulation, FHFA is providing this notification to the Banks and the Bank System's Office of Finance of the categories of information that it will distribute under part 1260 beginning on the effective date noted below.

The impact of traditional fire management on soil carbon and nitrogen pools in a montane forest, southern Ethiopia

Treesearch

Dong-Gill Kim; Habitamu Taddese; Abrham Belay; Randy Kolka

2016-01-01

We conducted studies to assess the impact of traditional fire management on soil organic carbon and total nitrogen pools. We compared organic carbon and total nitrogen pools in forest floor and mineral soil (0–100-cm depth) in three areas burned by local communities (B) with adjacent unburned areas (UB) (three paired sites; 1, 5 and 9 years since fire; hereafter B1-UB...

Molecular Basis for Phosphorylation-dependent SUMO Recognition by the DNA Repair Protein RAP80.

PubMed

Anamika; Spyracopoulos, Leo

2016-02-26

Recognition and repair of double-stranded DNA breaks (DSB) involves the targeted recruitment of BRCA tumor suppressors to damage foci through binding of both ubiquitin (Ub) and the Ub-like modifier SUMO. RAP80 is a component of the BRCA1 A complex, and plays a key role in the recruitment process through the binding of Lys(63)-linked poly-Ub chains by tandem Ub interacting motifs (UIM). RAP80 also contains a SUMO interacting motif (SIM) just upstream of the tandem UIMs that has been shown to specifically bind the SUMO-2 isoform. The RAP80 tandem UIMs and SIM function collectively for optimal recruitment of BRCA1 to DSBs, although the molecular basis of this process is not well understood. Using NMR spectroscopy, we demonstrate that the RAP80 SIM binds SUMO-2, and that both specificity and affinity are enhanced through phosphorylation of the canonical CK2 site within the SIM. The affinity increase results from an enhancement of electrostatic interactions between the phosphoserines of RAP80 and the SIM recognition module within SUMO-2. The NMR structure of the SUMO-2·phospho-RAP80 complex reveals that the molecular basis for SUMO-2 specificity is due to isoform-specific sequence differences in electrostatic SIM recognition modules. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

NASA Technical Reports Server (NTRS)

Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

1993-01-01

Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

In vitro colonic fermentation and glycemic response of different kinds of unripe banana flour.

PubMed

Menezes, Elizabete Wenzel; Dan, Milana C T; Cardenette, Giselli H L; Goñi, Isabel; Bello-Pérez, Luis Arturo; Lajolo, Franco M

2010-12-01

This work aimed to study the in vitro colonic fermentation profile of unavailable carbohydrates of two different kinds of unripe banana flour and to evaluate their postprandial glycemic responses. The unripe banana mass (UBM), obtained from the cooked pulp of unripe bananas (Musa acuminata, Nanicão variety), and the unripe banana starch (UBS), obtained from isolated starch of unripe banana, plantain type (Musa paradisiaca) in natura, were studied. The fermentability of the flours was evaluated by different parameters, using rat inoculum, as well as the glycemic response produced after the ingestion by healthy volunteers. The flours presented high concentration of unavailable carbohydrates, which varied in the content of resistant starch, dietary fiber and indigestible fraction (IF). The in vitro colonic fermentation of the flours was high, 98% for the UBS and 75% for the UBM when expressed by the total amount of SCFA such as acetate, butyrate and propionate in relation to lactulose. The increase in the area under the glycemic curve after ingestion of the flours was 90% lower for the UBS and 40% lower for the UBM than the increase produced after bread intake. These characteristics highlight the potential of UBM and UBS as functional ingredients. However, in vivo studies are necessary in order to evaluate the possible benefit effects of the fermentation on intestinal health.

Peroxisomal monoubiquitinated PEX5 interacts with the AAA ATPases PEX1 and PEX6 and is unfolded during its dislocation into the cytosol.

PubMed

Pedrosa, Ana G; Francisco, Tânia; Bicho, Diana; Dias, Ana F; Barros-Barbosa, Aurora; Hagmann, Vera; Dodt, Gabriele; Rodrigues, Tony A; Azevedo, Jorge E

2018-06-08

PEX1 and PEX6 are two members of the ATPases Associated with diverse cellular Activities (AAA) family and the core components of the receptor export module (REM) of the peroxisomal matrix protein import machinery. Their role is to extract monoubiquitinated PEX5, the peroxisomal protein shuttling receptor, from the peroxisomal membrane docking/translocation module (DTM), so that a new cycle of protein transportation can start. Recent data have shown that PEX1 and PEX6 form a heterohexameric complex which unfolds substrates by processive threading. However, whether the natural substrate of the PEX1.PEX6 complex is monoubiquitinated PEX5 (Ub-PEX5) itself or some Ub-PEX5-interacting component(s) of the DTM remains unknown. In this work, we used an established cell-free in vitro system coupled with photoaffinity crosslinking and protein PEGylation assays to address this problem. We provide evidence suggesting that DTM-embedded Ub-PEX5 interacts directly with both PEX1 and PEX6 through its ubiquitin moiety and that the PEX5 polypeptide chain is globally unfolded during the ATP-dependent extraction event. These findings strongly suggest that DTM-embedded Ub-PEX5 is a bona fide substrate of the PEX1.PEX6 complex. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

12 CFR 13.5 - Customer information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Customer information. 13.5 Section 13.5 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY GOVERNMENT SECURITIES SALES...) The customer's investment objectives; and (d) Such other information used or considered to be...

12 CFR 40.6 - Information to be included in privacy notices.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Information to be included in privacy notices. 40.6 Section 40.6 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY PRIVACY OF CONSUMER FINANCIAL INFORMATION Privacy and Opt Out Notices § 40.6 Information to be included in...

12 CFR 40.6 - Information to be included in privacy notices.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Information to be included in privacy notices. 40.6 Section 40.6 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY PRIVACY OF CONSUMER FINANCIAL INFORMATION Privacy and Opt Out Notices § 40.6 Information to be included in...

12 CFR 573.6 - Information to be included in privacy notices.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Information to be included in privacy notices. 573.6 Section 573.6 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PRIVACY OF CONSUMER FINANCIAL INFORMATION Privacy and Opt Out Notices § 573.6 Information to be included in...

12 CFR 404.5 - Time for processing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Time for processing. 404.5 Section 404.5 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.5 Time for processing. (a) General. Ex-Im Bank...

12 CFR 404.9 - Schedule of fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Schedule of fees. 404.9 Section 404.9 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.9 Schedule of fees. (a) General. Ex-Im Bank shall...

Nanoscale multilayer Me-graphite coatings grown by combined steered cathodic arc/unbalanced magnetron sputtering

NASA Astrophysics Data System (ADS)

Kok, Yin Nan

Low friction, nanoscale multilayer carbon/chromium (C/Cr) coatings were successfully deposited by the combined steered cathodic arc/unbalanced magnetron sputtering technique (also known as Arc Bond Sputtering or ABS) using a Hauzer HTC 1000-4 PVD coater. The work described in this thesis has been directed towards understanding the effect of ion irradiation on the composition, microstructure, and functional properties of C/Cr coatings. This has been achieved by varying the bias voltage, U[B], over a wide range between -65 V and -550 V. C/Cr coatings were deposited in three major steps: (i) Cr+ ion etching using a steered cathodic arc discharge at a substrate bias voltage of -1200 V, (ii) deposition of a 0.25 mum thick CrN base layer by reactive unbalanced magnetron sputtering to enhance the adhesion, and (iii) deposition of C/Cr coatings by unbalanced magnetron sputtering from three graphite targets and one chromium target at 260°C. The coatings were deposited at different bias voltages (U[B]) from -65 V to -550 V in a non-reactive Ar atmosphere.C/Cr coatings exhibit excellent adhesion (critical load, L[C] > 70 N), with hardness ranging from 6.8 to 25.1 GPa depending on the bias voltage. The friction coefficient of C/Cr coatings was found to reduce from 0.22 to 0.16 when the bias voltage was increased from U[B] = -65 to -95 V. The relevance of C/Cr coatings for actual practical applications was demonstrated using dry high-speed milling trials on automotive aluminium alloy (Al-Si8Cu3Fe). The results showed that C/Cr coated cemented carbide ball-nose end mills prepared at U[B] = -95 V (70 at.% C, 30 at.% Cr) enhance the tool performance and the tool life compared to the uncoated tools by a factor of two, suggesting the potential for use in dry high-speed machining of "sticky" alloys such as aluminum. Different film morphologies were observed in the investigated bias voltage range between U[B] = -65 and -550 V using XTEM. With increasing bias voltage from U[B] = -65 to -95 V, the structure changed from columnar, with carbon accumulated at the column boundaries, to a dense structure which comprised randomly distributed onionlike carbon clusters. A novel nanostructure was observed within this bias voltage range, in which the basic nano-lamellae obtained as a result of substrate rotation in front of the C and Cr targets were modified by an ion-irradiation induced nanocolumnar structure. Further increases in the bias voltage to U[B] = -350 V and U[B] = -450 V led to segregation and self-organisation of the carbon atoms induced by the high energy ion bombardment and, finally, to the formation of a new type of self-organised multilayer structure. A coating growth model accounting for the influence of ion bombardment on the growing C/Cr film was introduced to explain the phase separation and formation of the selforganised layered nanostructure.A novel experimental set-up for the investigation of tribocorrosion was built based on a modification of the conventional Scanning Reference Electrode Technique (SRET). The device comprises a ball on rotating cylinder contact configuration combined with a SRET electrochemical device. This combination may contribute significantly to the understanding of wear-corrosion synergism.

12 CFR 568.5 - Protection of customer information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Protection of customer information. 568.5 Section 568.5 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITY PROCEDURES § 568.5 Protection of customer information. Savings associations and their subsidiaries (except...

12 CFR 1253.5 - Confidential information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requesting comment on an Enterprise new product, as public information, except as provided in paragraphs (b... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Confidential information. 1253.5 Section 1253.5 Banks and Banking FEDERAL HOUSING FINANCE AGENCY ENTERPRISES PRIOR APPROVAL FOR ENTERPRISE PRODUCTS...

Personalized query suggestion based on user behavior

NASA Astrophysics Data System (ADS)

Chen, Wanyu; Hao, Zepeng; Shao, Taihua; Chen, Honghui

Query suggestions help users refine their queries after they input an initial query. Previous work mainly concentrated on similarity-based and context-based query suggestion approaches. However, models that focus on adapting to a specific user (personalization) can help to improve the probability of the user being satisfied. In this paper, we propose a personalized query suggestion model based on users’ search behavior (UB model), where we inject relevance between queries and users’ search behavior into a basic probabilistic model. For the relevance between queries, we consider their semantical similarity and co-occurrence which indicates the behavior information from other users in web search. Regarding the current user’s preference to a query, we combine the user’s short-term and long-term search behavior in a linear fashion and deal with the data sparse problem with Bayesian probabilistic matrix factorization (BPMF). In particular, we also investigate the impact of different personalization strategies (the combination of the user’s short-term and long-term search behavior) on the performance of query suggestion reranking. We quantify the improvement of our proposed UB model against a state-of-the-art baseline using the public AOL query logs and show that it beats the baseline in terms of metrics used in query suggestion reranking. The experimental results show that: (i) for personalized ranking, users’ behavioral information helps to improve query suggestion effectiveness; and (ii) given a query, merging information inferred from the short-term and long-term search behavior of a particular user can result in a better performance than both plain approaches.

Comparison Between a New, Two-component Compression System With Zinc Paste Bandages for Leg Ulcer Healing: A Prospective, Multicenter, Randomized, Controlled Trial Monitoring Sub-bandage Pressures.

PubMed

Mosti, Giovanni; Crespi, Aldo; Mattaliano, Vincenzo

2011-05-01

Compression therapy is standard treatment for venous leg ulcers. The authors prefer multi-layer, multi-component, stiff, high-pressure bandages to treat venous leg ulcers. The Unna boot (UB) is an example of this type of bandage. The aim of this study was to compare the effectiveness and tolerability of UB to a new, two-component bandage. One hundred (100) patients with venous ulcers were randomized into two groups: group A (n = 50) received UB and group B (n = 50) 3M™ Coban™ 2 Layer Compression System (C2L). All patients were followed weekly for 3 months and then monthly until complete healing was achieved. The primary outcomes were: ulcer healing or surface reduction; pain; and exudate control. The secondary outcomes were: ease of application and removal of the bandage, pressure exerted in the supine and standing position after application and before removal, and bandage comfort. C2L was associated with 100% ulcer healing; 47 out of 50 cases healed within the first 3 months after application of the bandage. Compared with the UB, there was no statistically significant difference. In both groups the effect of compression on pain and overall well being was excellent; pain decreased by 50% within 1-2 weeks and remained low throughout the duration of treatment and overall well being improved significantly. There was no significant difference between the two systems concerning level of comfort. C2L proved to be effective in treating venous ulcers due to its stiffness and pressure. Its effectiveness was similar to UB, which is often considered the gold-standard compression device for venous ulcers. This fact, in combination with high tolerability and ease of application and removal, make this new bandage particularly suitable for the treatment of venous leg ulcers. .

RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex

DOE PAGES

Brown, Nicholas G.; VanderLinden, Ryan; Watson, Edmond R.; ...

2015-03-30

For many E3 ligases, a mobile RING (Really Interesting New Gene) domain stimulates ubiquitin (Ub) transfer from a thioester-linked E2~Ub intermediate to a lysine on a remotely bound disordered substrate. One such E3 is the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), which controls cell division by ubiquitinating cell cycle regulators to drive their timely degradation. Intrinsically disordered substrates are typically recruited via their KEN-box, D-box, and/or other motifs binding to APC and a coactivator such as CDH1. On the opposite side of the APC, the dynamic catalytic core contains the cullin-like subunit APC2 and its RING partner APC11, which collaboratesmore » with the E2 UBCH10 (UBE2C) to ubiquitinate substrates. However, how dynamic RING–E2~Ub catalytic modules such as APC11–UBCH10~Ub collide with distally tethered disordered substrates remains poorly understood. In this paper, we report structural mechanisms of UBCH10 recruitment to APC CDH1 and substrate ubiquitination. Unexpectedly, in addition to binding APC11’s RING, UBCH10 is corecruited via interactions with APC2, which we visualized in a trapped complex representing an APC CDH1–UBCH10~Ub–substrate intermediate by cryo-electron microscopy, and in isolation by X-ray crystallography. To our knowledge, this is the first structural view of APC, or any cullin–RING E3, with E2 and substrate juxtaposed, and it reveals how tripartite cullin–RING–E2 interactions establish APC’s specificity for UBCH10 and harness a flexible catalytic module to drive ubiquitination of lysines within an accessible zone. Finally, we propose that multisite interactions reduce the degrees of freedom available to dynamic RING E3–E2~Ub catalytic modules, condense the search radius for target lysines, increase the chance of active-site collision with conformationally fluctuating substrates, and enable regulation.« less

12 CFR 4.36 - Disclosure of non-public OCC information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Disclosure of non-public OCC information. 4.36 Section 4.36 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ORGANIZATION AND FUNCTIONS, AVAILABILITY AND RELEASE OF INFORMATION, CONTRACTING OUTREACH PROGRAM, POST-EMPLOYMENT...

12 CFR 4.36 - Disclosure of non-public OCC information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Disclosure of non-public OCC information. 4.36 Section 4.36 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ORGANIZATION AND FUNCTIONS, AVAILABILITY AND RELEASE OF INFORMATION, CONTRACTING OUTREACH PROGRAM, POST-EMPLOYMENT...

12 CFR 4.36 - Disclosure of non-public OCC information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Disclosure of non-public OCC information. 4.36 Section 4.36 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ORGANIZATION AND FUNCTIONS, AVAILABILITY AND RELEASE OF INFORMATION, CONTRACTING OUTREACH PROGRAM, POST-EMPLOYMENT...

12 CFR 4.36 - Disclosure of non-public OCC information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Disclosure of non-public OCC information. 4.36 Section 4.36 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ORGANIZATION AND FUNCTIONS, AVAILABILITY AND RELEASE OF INFORMATION, CONTRACTING OUTREACH PROGRAM, POST-EMPLOYMENT...

12 CFR 911.7 - Availability of unpublished information by testimony.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Availability of unpublished information by testimony. 911.7 Section 911.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.7 Availability of unpublished...

12 CFR 911.8 - Availability of unpublished information by document.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Availability of unpublished information by document. 911.8 Section 911.8 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.8 Availability of unpublished...

12 CFR 911.7 - Availability of unpublished information by testimony.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Availability of unpublished information by testimony. 911.7 Section 911.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.7 Availability of unpublished...

12 CFR 911.8 - Availability of unpublished information by document.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Availability of unpublished information by document. 911.8 Section 911.8 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.8 Availability of unpublished...

12 CFR 911.8 - Availability of unpublished information by document.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Availability of unpublished information by document. 911.8 Section 911.8 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.8 Availability of unpublished...

12 CFR 911.8 - Availability of unpublished information by document.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Availability of unpublished information by document. 911.8 Section 911.8 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.8 Availability of unpublished...

12 CFR 911.7 - Availability of unpublished information by testimony.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Availability of unpublished information by testimony. 911.7 Section 911.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.7 Availability of unpublished...

12 CFR 741.220 - Privacy of consumer financial information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Privacy of consumer financial information. 741.220 Section 741.220 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING... Privacy of consumer financial information. Any credit union which is insured pursuant to Title II of the...

12 CFR 741.220 - Privacy of consumer financial information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Privacy of consumer financial information. 741.220 Section 741.220 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING... Privacy of consumer financial information. Any credit union which is insured pursuant to Title II of the...

12 CFR 741.220 - Privacy of consumer financial information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Privacy of consumer financial information. 741.220 Section 741.220 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING... Privacy of consumer financial information. Any credit union which is insured pursuant to title II of the...

12 CFR 741.220 - Privacy of consumer financial information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Privacy of consumer financial information. 741.220 Section 741.220 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING... Privacy of consumer financial information. Any credit union which is insured pursuant to Title II of the...

12 CFR 741.220 - Privacy of consumer financial information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Privacy of consumer financial information. 741.220 Section 741.220 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING... Privacy of consumer financial information. Any credit union which is insured pursuant to Title II of the...

12 CFR 41.83 - Disposal of consumer information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Duties of Users of Consumer Reports Regarding Address Discrepancies and Records Disposal § 41.83 Disposal of consumer information. (a) Definitions as used in this section. (1) Bank means national banks... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Disposal of consumer information. 41.83 Section...

12 CFR 516.120 - What information should a comment include?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What information should a comment include? 516.120 Section 516.120 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY APPLICATION PROCESSING PROCEDURES Comment Procedures § 516.120 What information should a comment include? (a...

12 CFR 41.83 - Disposal of consumer information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Disposal of consumer information. 41.83 Section... Duties of Users of Consumer Reports Regarding Address Discrepancies and Records Disposal § 41.83 Disposal of consumer information. (a) Definitions as used in this section. (1) Bank means national banks...

12 CFR Appendix E to Part 208 - Capital Adequacy Guidelines for State Member Banks; Market Risk Measure

Code of Federal Regulations, 2010 CFR

2010-01-01

... provide information about the impact of adverse market events on a bank's covered positions. Backtests provide information about the accuracy of an internal model by comparing a bank's daily VAR measures to... Banks; Market Risk Measure E Appendix E to Part 208 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF...

Stochastic Network Interdiction

DTIC Science & Technology

1998-04-01

UB(6, g) are monotonic in the sense that if 69 is a refinement of 6: wI~6! < wI~69! and w# ~6, g! > w# ~69, g!. See Hausch and Ziemba (1983) for...of Vulnerability—The Integrity Family. Networks 24, 207–213. HAUSCH, D. B., AND W. T. ZIEMBA . 1983. Bounds on the Value of Information in Uncertain...Decision Problems II. Stochastics 10, 181–217. HUANG, C. C., W. T. ZIEMBA , AND A. BEN-TAL. 1977. Bounds on the Expectation of a Convex Function of a

"Cocoa and Chocolate: Science and  Gastronomy"-The Second Annual Workshop of the  Research Institute on Nutrition and Food Security  (INSA): 9 November 2016.

PubMed

Massot-Cladera, Malen; Pérez-Cano, Francisco; Llorach, Rafael; Urpi-Sarda, Mireia

2017-02-17

The Research Institute on Nutrition and Food Security at the University of Barcelona (INSA-UB) was founded in 2005 by twenty-two research groups from the Faculties of Pharmacy and Food Science; Biology; Chemistry; and Geography and History, as well as other UB-affiliated centers and hospitals [...].

A New Cell-Free System to Study BRCA1 Function

DTIC Science & Technology

2015-05-01

analyzed by denaturing polyacrylamide gel electrophoresis. UbVS treatment had no effect on the arrival of leading strands at the ICL (Figure 2G in [3...of leading strands to the -1 position, as well as formation of all downstream nascent strand products (Figure 2G in [3], compare lanes 7-11 with 13...17). Addition of free ubiquitin with UbVS restored Approach, Insertion, and Extension, albeit with delayed kinetics (Figure 2G in [3], lanes 19-23

A molecular model for illegitimate recombination in Bacillus subtilis.

PubMed

Temeyer, K B; Hopkins, K M; Chapman, L F

1991-01-01

The recombinant DNA junctions at which pUB110 and Bacillus subtilis chromosomal DNA were joined to form the plasmid pKBT1 were cloned and sequenced. From the sequencing data we conclude that the pUB110 sequence is intact in the pair of cloned pKBT1 fragments and pTL12 sequences are not present. A molecular model for the formation of pKBT1 based on structural motifs characteristic of the joint sites is presented.

12 CFR 989.3 - Requirement to provide financial and other information to the Finance Board and the Office of...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Requirement to provide financial and other information to the Finance Board and the Office of Finance. 989.3 Section 989.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD OFFICE OF FINANCE FINANCIAL STATEMENTS OF THE BANKS § 989.3 Requirement to provide financial and other information to the...

12 CFR 404.11 - Administrative appeal.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Administrative appeal. 404.11 Section 404.11 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.11 Administrative appeal. (a) General...

12 CFR Appendix A to Part 630 - Supplemental Information Disclosure Guidelines

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Supplemental Information Disclosure Guidelines A Appendix A to Part 630 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DISCLOSURE TO INVESTORS IN SYSTEMWIDE AND CONSOLIDATED BANK DEBT OBLIGATIONS OF THE FARM CREDIT SYSTEM Pt. 630...

12 CFR 404.4 - Request requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Request requirements. 404.4 Section 404.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.4 Request requirements. (a) Form. Requests...

12 CFR 404.8 - Initial determination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Initial determination. 404.8 Section 404.8 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.8 Initial determination. (a) Authority to...

45 CFR 60.17 - Information which hospitals must request from the National Practitioner Data Bank.

Code of Federal Regulations, 2013 CFR

2013-10-01

... National Practitioner Data Bank. 60.17 Section 60.17 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.17 Information which hospitals must request from the National Practitioner Data...

45 CFR 60.17 - Information which hospitals must request from the National Practitioner Data Bank.

Code of Federal Regulations, 2014 CFR

2014-10-01

... National Practitioner Data Bank. 60.17 Section 60.17 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION NATIONAL PRACTITIONER DATA BANK Disclosure of Information by the National Practitioner Data Bank § 60.17 Information which hospitals must request from the National Practitioner Data...

12 CFR 510.5 - Release of unpublished OTS information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 6 2012-01-01 2012-01-01 false Release of unpublished OTS information. 510.5 Section 510.5 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY MISCELLANEOUS ORGANIZATIONAL REGULATIONS § 510.5 Release of unpublished OTS information. (a) Scope. (1) This section applies to...

12 CFR 133.8 - Release of information under FOIA.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Release of information under FOIA. 133.8 Section 133.8 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY DISCLOSURE AND REPORTING OF CRA-RELATED AGREEMENTS § 133.8 Release of information under FOIA. The OCC will make covered...

12 CFR 911.4 - Requests for unpublished information by document or testimony.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Requests for unpublished information by document or testimony. 911.4 Section 911.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.4 Requests for...

12 CFR 911.4 - Requests for unpublished information by document or testimony.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Requests for unpublished information by document or testimony. 911.4 Section 911.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.4 Requests for...

12 CFR 911.3 - Prohibition on unauthorized use and disclosure of unpublished information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Prohibition on unauthorized use and disclosure of unpublished information. 911.3 Section 911.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.3...

12 CFR 911.4 - Requests for unpublished information by document or testimony.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Requests for unpublished information by document or testimony. 911.4 Section 911.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.4 Requests for...

12 CFR 911.4 - Requests for unpublished information by document or testimony.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Requests for unpublished information by document or testimony. 911.4 Section 911.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.4 Requests for...

12 CFR 911.3 - Prohibition on unauthorized use and disclosure of unpublished information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Prohibition on unauthorized use and disclosure of unpublished information. 911.3 Section 911.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.3...

Network Performance Modeling, Design and Dimensioning Methodologies

DTIC Science & Technology

2000-01-01

Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the...failing to comply with a collection of information if it does not display a currently valid OMB control number. 1 . REPORT DATE 2000 2. REPORT TYPE 3...eveEeEeveEeveEeEeveEe,eveEeveEeúèOÍ ÏReéÏ 8i RSQR R�eEeEeve,eEeveEeveEeEeveEeveEe,eveEeEeveEeveEeEeveEe,eveEeveEeúèOæ Í 6H¼2 .),576& ;D8¢;= 1 1u$B+.$0#2

New Crop Selection

NASA Technical Reports Server (NTRS)

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

2018-01-01

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

[Access to primary healthcare services: still a way to go].

PubMed

Mendes, Antônio da Cruz Gouveia; Miranda, Gabriella Morais Duarte; Figueiredo, Karla Erika Gouveia; Duarte, Petra Oliveira; Furtado, Betise Mery Alencar Sousa Macau

2012-11-01

This study seeks to evaluate accessibility to the Basic Units of the Family Health Strategy (ESF-UB) and Traditional Basic Units (BU-T) in the city of Recife in 2009. Data were collected through three instruments: a roadmap for systematic observation of the units and questionnaires for users and professional units. This is a descriptive cross-sectional study using a quantitative approach, and 1180 users, 61 doctors and 56 nurses were interviewed. The results showed good ties and recognition of users whereby primary healthcare is seen as the access portal to the health system. In the comparison between ESF-UB and UB-T, evaluations are always more favorable to the family healthcare strategy, though with relatively insignificant differences. The overall result revealed widespread dissatisfaction with the difficulty of obtaining drugs and taking tests, and also with the waiting times and access to specialized care. This showed the existence of organizational problems that may constitute barriers limiting accessibility to basic healthcare services for users.

Structurally distinct ubiquitin- and sumo-modified PCNA: implications for their distinct roles in the DNA damage response.

PubMed

Tsutakawa, Susan E; Yan, Chunli; Xu, Xiaojun; Weinacht, Christopher P; Freudenthal, Bret D; Yang, Kun; Zhuang, Zhihao; Washington, M Todd; Tainer, John A; Ivanov, Ivaylo

2015-04-07

Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. We used hybrid methods to identify atomic models of PCNAK107-Ub and PCNAK164-SUMO consistent with small-angle X-ray scattering data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations. These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The electromyographic activity of the external and internal urethral sphincters and urinary bladder on vaginal distension and its role in preventing vaginal soiling with urine during sexual intercourse.

PubMed

Shafik, Ahmed; Shafik, Ali A; Shafik, Ismail A; El Sibai, Olfat

2008-03-01

We investigated the hypothesis that external (EUS) and internal (IUS) urethral sphincters and urinary bladder (UB) respond to penile thrusting (PT) of vagina in a way that prevents urinary leakage during coitus. Vaginal condom was inflated with air in increments of 50-300 ml and EMG of EUS and IUS and vaginal pressure were recorded; test was repeated after anesthetization of vagina, UB, EUS, and IUS. Vaginal distension effected reduction of vesical pressure but increase of IUS EMG until the 150 ml distension was reached, beyond which more vaginal distension caused no further effect; EUS EMG showed no response. Vaginal distension while vagina, UB, EUS, and IUS had been separately anesthetized, produced no change. Vaginal balloon distension appears to effect vesical relaxation and increased IUS tone. This seems to provide a mechanism to avoid urine leakage during coitus and to occur through a reflex we term 'vagino-urethrovesical reflex'.

The yeast Alix homolog, Bro1, functions as a ubiquitin receptor for protein sorting into multivesicular endosomes

PubMed Central

Pashkova, Natasha; Gakhar, Lokesh; Winistorfer, Stanley; Sunshine, Anna B.; Rich, Matthew; Dunham, Maitreya J.; Yu, Liping; Piper, Robert

2013-01-01

SUMMARY Sorting of ubiquitinated membrane proteins into lumenal vesicles of multivesicular bodies is mediated by the ESCRT apparatus and accessory proteins such as Bro1, which recruits the deubiquitinating enzyme Doa4 to remove ubiquitin from cargo. Here we propose that Bro1 works as a receptor for the selective sorting of ubiquitinated cargos. We found synthetic genetic interactions between BRO1 and ESCRT-0, suggesting Bro1 functions similarly to ESCRT-0. Multiple structural approaches demonstrated that Bro1 binds ubiquitin via the N-terminal trihelical arm of its middle V domain. Mutants of Bro1 that lack the ability to bind Ub were dramatically impaired in their ability to sort Ub-cargo membrane proteins, but only when combined with hypomorphic alleles of ESCRT-0. These data suggest that Bro1 and other Bro1 family members function in parallel with ESCRT-0 to recognize and sort Ub-cargos. PMID:23726974

Structurally Distinct Ubiquitin- and Sumo-Modified PCNA: Implications for Their Distinct Roles in the DNA Damage Response

DOE PAGES

Tsutakawa, Susan E.; Yan, Chunli; Xu, Xiaojun; ...

2015-03-12

Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. Here, we used hybrid methods to identify atomic models of PCNA K107-Ub and PCNA K164-SUMO consistent with small-angle X-ray scattering data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations.more » These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. In conclusion, the unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation.« less

Strategy to approach stable production of recombinant nattokinase in Bacillus subtilis.

PubMed

Chen, Po Ting; Chiang, Chung-Jen; Chao, Yun-Peng

2007-01-01

Bacillus subtilis (B. subtilis) is widely accepted as an excellent host cell for the secretory production of recombinant proteins. In this study, a shuttle vector was constructed by fusion of Staphylococcus aureus (S. aureus) plasmid pUB110 with Escherichia coli (E. coli) plasmid pUC18 and used for the expression of nattokinase in B. subtilis. The pUB110/pUC-based plasmid was found to exhibit high structural instability with the identification of a DNA deletion between two repeated regions. An initial attempt was made to eliminate the homologous site in the plasmid, whereas the stability of the resulting plasmid was not improved. In an alternative way, the pUC18-derived region in this hybrid vector was replaced by the suicidal R6K plasmid origin of E. coli. As a consequence, the pUB110/R6K-based plasmid displayed full structural stability, leading to a high-level production of recombinant nattokinase in the culture broth. This was mirrored by the detection of a very low level of high molecular weight DNAs generated by the plasmid. Moreover, 2-fold higher nattokinase production was obtained by B. subtilis strain carrying the pUB110/R6K-based plasmid as compared to the cell with the pAMbeta1-derived vector, a plasmid known to have high structural stability. Overall, it indicates the feasibility of the approach by fusing two compatible plasmid origins for stable and efficient production of recombinant nattokinase in B. subtilis.

Effects of psychosocial strain on back symptoms in Tehran general hospital nursing personnel.

PubMed

Golabadi, Majid; Attarchi, Mirsaeed; Raeisi, Saeed; Namvar, Mohamad

2013-12-01

Nursing is a stressful and highly demanding job. The aim of this study was to investigate the association between psychosocial job strain and the prevalence of back symptoms in nursing personnel using the demand-control model. In a cross-sectional study, 545 nursing professionals answered to a self-administered questionnaire on demography, job content, and lower and upper back symptoms (LBS and UBS, respectively). Based on their answers, the participants were grouped as follows: low strain, high strain, active job, and passive job. The groups were compared in regard to the prevalence of LBS and UBS (totalling 58.5% and 47.9%, respectively) over the past 12 months. We found no association between job control and back symptoms, but participants with high psychosocial job demands showed greater risk of LBS (OR=1.57 and p=0.014) and UBS (OR=1.73 and p=0.005) than those with low job demands. LBS in the low strain, high strain, and active job groups was more prevalent than in the passive group (OR=1.64, OR=2.49 and OR=1.90, respectively; p≤0.05). In addition, the high strain group showed greater prevalence of UBS than the passive group (OR=1.82 and p=0.019). Our study suggests that psychosocial job strain, high psychosocial demands in particular, may be associated with greater prevalence of back symptoms in nursing personnel. Our findings may help to design preventive measures that would lower the prevalence of musculoskeletal disorders in this profession.

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

Zhang, Wei; Sartori, Maria A.; Makhnevych, Taras

Post-translational modification of the p53 signaling pathway plays an important role in cell cycle progression and stress-induced apoptosis. Indeed, a large body of work has shown that dysregulation of p53 and its E3 ligase MDM2 by the ubiquitin-proteasome system (UPS) promotes carcinogenesis and malignant transformation. Thus, drug discovery efforts have focused on the restoration of wild-type p53 activity or inactivation of oncogenic mutant p53 by targeted inhibition of UPS components, particularly key deubiquitinases (DUBs) of the ubiquitin-specific protease (USP) class. However, development of selective small-molecule USP inhibitors has been challenging, partly due to the highly conserved structural features of themore » catalytic sites across the class. To tackle this problem, we devised a protein engineering strategy for rational design of inhibitors for DUBs and other UPS proteins. We employed a phage-displayed ubiquitin variant (UbV) library to develop inhibitors targeting the DUBs USP7 and USP10, which are involved in regulating levels of p53 and MDM2. We were able to identify UbVs that bound USP7 or USP10 with high affinity and inhibited deubiquitination activity. We solved the crystal structure of UbV.7.2 and rationalized the molecular basis for enhanced affinity and specificity for USP7. Finally, cell death was increased significantly by UbV.7.2 expression in a colon cancer cell line that was treated with the chemotherapy drug cisplatin, demonstrating the therapeutic potential of inhibiting USP7 by this approach« less

12 CFR 404.10 - Fee waivers or reductions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Fee waivers or reductions. 404.10 Section 404.10 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.10 Fee waivers or reductions. (a) General...

12 CFR 229.58 - Mode of delivery of information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Mode of delivery of information. 229.58 Section 229.58 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... bank instead may provide an electronic image of the original check or sufficient copy if the recipient...

12 CFR 620.21 - Contents of the information statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Contents of the information statement. 620.21... days, before the meeting. If the Farm Credit bank or association will use an online meeting space as... meeting space. This information does not need to be part of an AMIS issued by a Farm Credit bank if no...

12 CFR 620.21 - Contents of the information statement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Contents of the information statement. 620.21... days, before the meeting. If the Farm Credit bank or association will use an online meeting space as... meeting space. This information does not need to be part of an AMIS issued by a Farm Credit bank if no...

12 CFR 911.6 - Persons and entities with access to unpublished information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Persons and entities with access to unpublished information. 911.6 Section 911.6 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.6 Persons and entities with access to...

12 CFR 911.6 - Persons and entities with access to unpublished information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Persons and entities with access to unpublished information. 911.6 Section 911.6 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.6 Persons and entities with access to...

12 CFR 911.6 - Persons and entities with access to unpublished information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Persons and entities with access to unpublished information. 911.6 Section 911.6 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.6 Persons and entities with access to...

12 CFR 911.6 - Persons and entities with access to unpublished information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Persons and entities with access to unpublished information. 911.6 Section 911.6 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS AVAILABILITY OF UNPUBLISHED INFORMATION § 911.6 Persons and entities with access to...

12 CFR 550.90 - What information must I include in my application?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 5 2011-01-01 2011-01-01 false What information must I include in my application? 550.90 Section 550.90 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY FIDUCIARY POWERS OF SAVINGS ASSOCIATIONS Obtaining Fiduciary Powers § 550.90 What information must I include...

12 CFR 550.90 - What information must I include in my application?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What information must I include in my application? 550.90 Section 550.90 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY FIDUCIARY POWERS OF SAVINGS ASSOCIATIONS Obtaining Fiduciary Powers § 550.90 What information must I include...

12 CFR 513.6 - Duty to file information concerning adverse judicial or administrative action.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Duty to file information concerning adverse judicial or administrative action. 513.6 Section 513.6 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PRACTICE BEFORE THE OFFICE § 513.6 Duty to file information concerning adverse...

12 CFR 516.55 - What information must I include in my public notice?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What information must I include in my public notice? 516.55 Section 516.55 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY APPLICATION PROCESSING PROCEDURES Publication Requirements § 516.55 What information must I include in my...

12 CFR 1024.6 - Special information booklet at time of loan application.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Special information booklet at time of loan application. 1024.6 Section 1024.6 Banks and Banking BUREAU OF CONSUMER FINANCIAL PROTECTION REAL ESTATE SETTLEMENT PROCEDURES ACT (REGULATION X) § 1024.6 Special information booklet at time of loan application. (a...

12 CFR 155.300 - Must I inform the OCC before I use electronic means or facilities?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Must I inform the OCC before I use electronic means or facilities? 155.300 Section 155.300 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ELECTRONIC OPERATIONS § 155.300 Must I inform the OCC before I use electronic means...

12 CFR 252.135 - Data and information required to be submitted in support of the Board's analyses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Data and information required to be submitted in support of the Board's analyses. 252.135 Section 252.135 Banks and Banking FEDERAL RESERVE SYSTEM... (REGULATION YY) Supervisory Stress Test Requirements for Covered Companies § 252.135 Data and information...

12 CFR 252.135 - Data and information required to be submitted in support of the Board's analyses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Data and information required to be submitted in support of the Board's analyses. 252.135 Section 252.135 Banks and Banking FEDERAL RESERVE SYSTEM... (REGULATION YY) Supervisory Stress Test Requirements for Covered Companies § 252.135 Data and information...

12 CFR 516.20 - What information must I include in my draft business plan?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What information must I include in my draft business plan? 516.20 Section 516.20 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE... What information must I include in my draft business plan? If you must submit a draft business plan...

12 CFR 19.15 - Opportunity for informal settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Opportunity for informal settlement. 19.15 Section 19.15 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY RULES OF PRACTICE... resolution, is admissible as evidence in any proceeding. ...

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

PubMed Central

Lau, Alan F.

2009-01-01

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

Worldwide photometry and lightcurve observations of 1 Ceres during the 1975-1976 apparition

NASA Technical Reports Server (NTRS)

Tedesco, E. F.; Taylor, R. C.; Drummond, J.; Harwood, D.; Nickoloff, I.; Scaltriti, F.; Zappala, V.; Schober, H. J.

1983-01-01

Lightcurves and UBV photometry of Ceres from the 1975-1976 apparition are presented. The synodic period is 0.37812 + or 0.00004 day, the mean absolute V magnitude is 3.61 + or 0.03, and the phase coefficient is 0.040 + or - 0.001 mag/deg. The U-B and B-V phase coefficients are +0.0015 + or - 0.0007 and +0.0006 + or - 0.0003 mag/deg, respectively. The colors at zero phase are B-V = +0.70 + or - 0.01 and U-B = +0.41 + or 0.01.

Fort Sill Oklahoma/Post Field. Revised Uniform Summary of Surface Weather Observations

DTIC Science & Technology

1975-06-23

TEMPERATURE DEPRESSIO (F) TOTAL TOTAL (F) 0 t .2 3-4 5 6 7 - ,9 I 1 1 1 .1 516 17 -18119 -20 21 22 23 -2412S.26 27 -2 9 3, 1i ’’WB ~ ub e ub~ we.. 2/ 1...Temp WET BULB TEMPERATURE DEPRESSIO (F) TOTAL _ TOTAL F)/ 03 1 .2 3C 4, 0 1-1 I3- 5, 6 1 .1 9-20 2 2_3- 5-." 26 27 -28 D.B W .2 0 31b We B lle on 90

Accurate Methods for Large Molecular Systems (Postprint)

DTIC Science & Technology

2009-01-06

D S A FB , C A o n Se pt em be r 23 , 2 00 9 | h ttp :// pu bs .a cs .o rg P ub lic at io n D at e (W eb ): A pr il 15 , 2 00 9 | d oi...r 23 , 2 00 9 | h ttp :// pu bs .a cs .o rg P ub lic at io n D at e (W eb ): A pr il 15 , 2 00 9 | d oi : 1 0. 10 21 /jp 81 15 19 x As noted...basis set is 6-31++G( d ,

12 CFR 13.5 - Customer information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Customer information. 13.5 Section 13.5 Banks... PRACTICES § 13.5 Customer information. Prior to the execution of a transaction recommended to a non... obtain information concerning: (a) The customer's financial status; (b) The customer's tax status; (c...

12 CFR 368.5 - Customer information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Customer information. 368.5 Section 368.5 Banks... GOVERNMENT SECURITIES SALES PRACTICES § 368.5 Customer information. Prior to the execution of a transaction... make reasonable efforts to obtain information concerning: (a) The customer's financial status; (b) The...

Knowledge, beliefs, and decisions of pregnant Australian women concerning donation and storage of umbilical cord blood: a population-based survey.

PubMed

Jordens, Christopher F C; Kerridge, Ian H; Stewart, Cameron L; O'Brien, Tracey A; Samuel, Gabrielle; Porter, Maree; O'Connor, Michelle A C; Nassar, Natasha

2014-12-01

Many women giving birth in Australian hospitals can choose to donate their child's umbilical cord blood to a public cord blood bank or pay to store it privately. We conducted a survey to determine the proportion and characteristics of pregnant women who are aware of umbilical cord blood (UCB) banking and who have considered and decided about this option. The survey also sought to ascertain information sources, knowledge, and beliefs about UCB banking, and the effect of basic information about UCB on decisions. Researchers and hospital maternity staff distributed a survey with basic information about UCB banking to 1,873 women of at least 24 weeks' gestation who were attending antenatal classes and hospital clinics in 14 public and private maternity hospitals in New South Wales. Most respondents (70.7%) were aware of UCB banking. Their main information sources were leaflets from hospital clinics, print media, antenatal classes, TV, radio, friends, and relatives. Knowledge about UCB banking was patchy, and respondents overestimated the likelihood their child would need or benefit from UCB. Women who were undecided about UCB banking were younger, less educated, or from ethnic or rural backgrounds. After providing basic information about UCB banking, the proportion of respondents who indicated they had decided whether or not to donate or store UCB more than doubled from 30.0 to 67.7 percent. Basic information for parents about UCB banking can affect planned decisions about UCB banking. Information should be accurate and balanced, should counter misconceptions, and should target specific groups. © 2014 Wiley Periodicals, Inc.

The security concern on internet banking adoption among Malaysian banking customers.

PubMed

Sudha, Raju; Thiagarajan, A S; Seetharaman, A

2007-01-01

The existing literatures highlights that the security is the primary factor which determines the adoption of Internet banking technology. The secondary information on Internet banking development in Malaysia shows a very slow growth rate. Hence, this study aims to study the banking customers perception towards security concern and Internet banking adoption through the information collected from 150 sample respondents. The data analysis reveals that the customers have much concern about security and privacy issue in adoption of Internet banking, whether the customers are adopted Internet banking or not. Hence, it infers that to popularize Internet banking system there is a need for improvement in security and privacy issue among the banking customers.

Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species

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

Deaton, M. K.; Dzimianski, J. V.; Daczkowski, C. M.

ABSTRACT The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities ofmore » vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another. IMPORTANCEViral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.« less

Measurement of branching fraction ratios and CP asymmetries in B →D0 CPK decays with the BABAR detector

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

Marchiori, Giovanni

2005-06-23

The primary goals of the BABAR experiment are the detection of CP violation (CPV) in the B meson system, the precise measurement of some of the elements of the CKM matrix and the measurement of the rates of rare B meson decays. At present, BABAR has achieved major successes: (1) the discovery, in neutral B decays, of direct and mixing-induced CP violation; (2) accurate measurements of the magnitudes of the CKM matrix elements |V cb| and |V ub|; (3) a precise measurement of the CKM parameter β {triple_bond} arg[- V cdV* cb/V tdV* tb]; (4) a first measurement of themore » CKM parameters α (triple bond) arg[- V tdV* tb/V udV* ub], γ (triple bond) arg[- V udV* ub/V cdV* cb]; and (5) the observation of several rare B decays and the discovery of new particles (in the charmed and charmonium mesons spectroscopy). However, the physics program of BABAR is not yet complete. Two of the key elements of this program that still need to be achieved are: (1) the observation of direct CP violation in charged B decays, which would constitute the first evidence of direct CPV in a charged meson decay; and (2) the precise measurement of α and γ, which are necessary ingredients for a stringent test of the Standard Model predictions in the quark electroweak sector. A possibility for the discovery of direct CP violation in charged B decays would be the observation of a non-vanishing rate asymmetry in the Cabibbo-suppressed decay B - → D 0 K -, with the D 0 decaying to either a CP-even or a CP-odd eigenstate. This class of decays can also provide theoretically-clean information on γ.« less

78 FR 57853 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

... EXPORT-IMPORT BANK [Public Notice 2013-6007] Agency Information Collection Activities: Comment Request AGENCY: Export-Import Bank of the United States. ACTION: Submission for OMB review and comments... Export-Import Banks of the United States (Ex-Im Bank), as part of its continuing effort to reduce...

12 CFR 309.3 - Federal Register publication.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Federal Register publication. 309.3 Section 309.3 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE DISCLOSURE OF INFORMATION § 309.3 Federal Register publication. The FDIC publishes the following information in...

12 CFR 309.3 - Federal Register publication.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Federal Register publication. 309.3 Section 309.3 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE DISCLOSURE OF INFORMATION § 309.3 Federal Register publication. The FDIC publishes the following information in...

A Method for Evaluating Information Security Governance (ISG) Components in Banking Environment

NASA Astrophysics Data System (ADS)

Ula, M.; Ula, M.; Fuadi, W.

2017-02-01

As modern banking increasingly relies on the internet and computer technologies to operate their businesses and market interactions, the threats and security breaches have highly increased in recent years. Insider and outsider attacks have caused global businesses lost trillions of Dollars a year. Therefore, that is a need for a proper framework to govern the information security in the banking system. The aim of this research is to propose and design an enhanced method to evaluate information security governance (ISG) implementation in banking environment. This research examines and compares the elements from the commonly used information security governance frameworks, standards and best practices. Their strength and weakness are considered in its approaches. The initial framework for governing the information security in banking system was constructed from document review. The framework was categorized into three levels which are Governance level, Managerial level, and technical level. The study further conducts an online survey for banking security professionals to get their professional judgment about the ISG most critical components and the importance for each ISG component that should be implemented in banking environment. Data from the survey was used to construct a mathematical model for ISG evaluation, component importance data used as weighting coefficient for the related component in the mathematical model. The research further develops a method for evaluating ISG implementation in banking based on the mathematical model. The proposed method was tested through real bank case study in an Indonesian local bank. The study evidently proves that the proposed method has sufficient coverage of ISG in banking environment and effectively evaluates the ISG implementation in banking environment.

Summer primary productivity and phytoplankton community composition driven by different hydrographic structures in the East/Japan Sea and the Western Subarctic Pacific

NASA Astrophysics Data System (ADS)

Kwak, Jung Hyun; Lee, Sang Heon; Hwang, Jeomshik; Suh, Young-Sang; Je Park, Hyun; Chang, Kyung-Il; Kim, Kyung-Ryul; Kang, Chang-Keun

2014-07-01

The East/Japan Sea (EJS) is a highly productive marginal sea in the northwest Pacific, consisting of three basins (Ulleung Basin: UB, Yamato Basin: YB, and Japan Basin: JB). To find causes of the reportedly high primary productivity in summer in the EJS, especially in the UB, we measured primary productivity, phytoplankton composition, and other environmental variables. The water column was strongly stratified in the EJS compared with the Western Subarctic Pacific (WSP). Integrated primary productivity was two times higher in the EJS (612 mg C m-2 d-1) than in the WSP (291 mg C m-2 d-1). The vertical distributions of physicochemical and biological factors confirmed that production in the subsurface chlorophyll maximum layer in the study regions was an important factor regulating primary productivity within the water column. While picoplankton (<2.7 µm) dominated in the WSP, JB, and YB, micro/nanoplankton (≥2.7 µm) dominated in the UB. Contribution by picoplankton to total biomass and primary productivity in the UB was significantly lower than in the other regions. CHEMTAX analysis using marker pigments showed that diverse phytoplankton groups inhabited the study regions. Cluster and canonical correspondence analyses showed high correlation between the spatial variation in phytoplankton assemblages with the water mass properties mainly represented by water temperature and nitrate concentration. Overall, our results suggest that the hydrographic structure of water column in the study region is an important controlling factor of the biomass and productivity of phytoplankton as well as their diversity in size and taxonomic groups.

[The effects of different welding wires on the mechanical properties of laser welding joints].

PubMed

Huang, Qing-feng; Zhang, Jian-zhong; Jiang, Wei-dong; Li, Quan; Yu, Jin-xing

2006-08-01

To evaluate the mechanical properties and microstructure of laser-welded joints with different welding wires for clinical use of welding wire. The standard tensile test and three-point bending test rods were made from Co-Cr and Ni-Cr alloy, and were laser-welded with different welding wire (commercially welding wire and casting wire). Then the tensile rods were tested for the ultimate tensile strength (UTS), and the bending rods for the ultimate bending strength (UBS). The results was analyzed by one-way ANOVA. The tensile fracture surface were examined by scanning electron microscopy (SEM). Metallurgical analysis were also performed on polished longitudinal sectioned samples. For Co-Cr alloy, the UTS of casting wire group and commercially welding wire group was respectively (606.40+/-82.53)MPa and (693.61+/-47.68)MPa; the UBS was respectively (997.95+/-88.89)MPa and (1160.76+/-91.59)MPa. ANOVA showed a significant difference of UTS and UBS between the two groups at the 0.05 level (P<0.05). For Ni-Cr alloy, the UTS of casting wire group and commercially welding wire group was respectively (558.14+/-46.75)MPa and (582.32+/-35.43)MPa; the UBS was respectively (1084.75+/-46.02)MPa and (1078.29+/-36.25)MPa. There was no significant difference between the two groups (P>0.05). SEM and metallurgical examination showed the welded zone exhibiting more cracks in the casting wire group than in the commercially welding wire group. It would be advisable to work with commercially welding wire for the joints that need better strength.

[Assessment of epidemiological profile of patients and their difficulties for the first query in the screening ambulatory of Nephrology UNIFESP-EPM].

PubMed

Padovani, Cícera Sebastiana da Silva

2012-01-01

The aim of this study was to evaluate the epidemiologic profile of patients and difficulties of patients referred by basic health units (UBS) or other hospitals, outpatient screening of the Division of Nephrology, Hospital São Paulo (UNIFESP) for evaluation and treatment kidney disease. From February to September 2009, has been evaluated 341 patients referred from UBS in São Paulo and other parts of the Country. Of these patients, 26% (86/341) required for new tests to confirm the diagnosis doubtful for referrals, incomplete, or because of the waiting period for the care and exams, which ranged from one week to three years, and part of them did not bring any kind of examination for the evaluation, 12% (45/341) returned for follow-up at the unit location, 13% (46/341) were referred for treatment site closest to their residence, 47% (164/341) for our sub-specialty Clinics of Nephrology (HSP): 24% (82/341) uremia, 8% (27/341) with polycystic kidney disease, 7% (23/341) for hypertension, 4% (16/341) renal Lithiasis and 4% (16/341) nephritis. Our results suggest investments investment in infrastructure in the training of officials of UBS and HSP, reorganization of central references for better management and referral of patients, humanization of care and training of health professionals for outpatient care at UBS in preventive work and basic monitoring of patients, particularly those with diabetes mellitus and hypertension, which can lead to the development of chronic kidney disease (CKD).

Finding out about sperm banking: what information is available online for men diagnosed with cancer?

PubMed

Merrick, H; Wright, E; Pacey, A A; Eiser, C

2012-09-01

Sperm banking is routinely offered to men where there is a risk of infertility following cancer treatment but uptake is lower than expected. Since these men may turn to the internet for information, we used the search engine www.google.com to identify the material available about sperm banking and fertility preservation options. Sixty-six resources (NHS/Private Clinic, Charity, Press Releases, General and Forums/Blogs) fulfilled the criteria for inclusion and were examined for quality including readability, layout and content. The most frequently reported information related to: (1) effects of cancer treatment on fertility (77.3%); (2) reasons to bank sperm (69.7%); and (3) fertility recovery after treatment (57.6%). Information about maintaining contact with the sperm bank (18.2%) and disposal of banked samples (10.6%) was less often included. The quality of information available on the Internet about sperm banking was variable. The readability of all resources was assessed as 'fairly difficult', i.e. reading skills required were too complex for the average member of the public to understand. Furthermore, visual presentation of material (e.g. lay out) did not facilitate easy reading. More attention should be given to information about longer-term issues, such as fertility recovery and the use or disposal of banked sperm.

12 CFR 404.1 - General provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure... Freedom of Information Act (FOIA), 5 U.S.C. 552, at the Export-Import Bank of the United States (Ex-Im... address. The Export-Import Bank of the United States is located at 811 Vermont Avenue, NW, Washington, DC...

77 FR 59922 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... EXPORT-IMPORT BANK OF THE UNITED STATES [Public Notice 2012-0521] Agency Information Collection Activities: Comment Request AGENCY: Export-Import Bank of the United States. ACTION: Submission for OMB.... SUMMARY: The Export-Import Bank of the United States (Ex-Im Bank), as a part of its continuing effort to...

78 FR 1859 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... EXPORT-IMPORT BANK [Public Notice 2013-0101] Agency Information Collection Activities: Comment Request AGENCY: Export-Import Bank of the United States. ACTION: Submission for OMB Review and Comments... Insurance Policy SUMMARY: The Export-Import Bank of the United States (Ex-Im Bank), as a part of its...

78 FR 77125 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... EXPORT-IMPORT BANK OF THE UNITED STATES [Public Notice: 2013-3007] Agency Information Collection Activities: Comment Request AGENCY: Export-Import Bank of the United States. ACTION: Submission for OMB... Policy. SUMMARY: The Export-Import Banks of the United States (Ex-Im Bank), as part of its continuing...

12 CFR 1101.1 - Scope and purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Scope and purpose. 1101.1 Section 1101.1 Banks and Banking FEDERAL FINANCIAL INSTITUTIONS EXAMINATION COUNCIL DESCRIPTION OF OFFICE, PROCEDURES, PUBLIC INFORMATION § 1101.1 Scope and purpose. This part implements the Freedom of Information Act (FOIA...

78 FR 69085 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... EXPORT-IMPORT BANK [Public Notice: 2013-3005] Agency Information Collection Activities: Comment Request AGENCY: Export-Import Bank of the United States. ACTION: Submission for OMB review and comments.... SUMMARY: The Export-Import Banks of the United States (Ex-Im Bank), as part of its continuing effort to...

12 CFR 604.440 - Requests for information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Requests for information. 604.440 Section 604.440 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS FARM CREDIT ADMINISTRATION... electronic recording of a closed meeting, or closed portion of a meeting, to the extent not exempt from...

12 CFR 604.440 - Requests for information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Requests for information. 604.440 Section 604.440 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS FARM CREDIT ADMINISTRATION... electronic recording of a closed meeting, or closed portion of a meeting, to the extent not exempt from...

78 FR 59096 - Agency Information Collection Activities: Information Collection Renewal; Comment Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

... savings associations). The OCC requires independent credit card banks and independent credit card Federal... by the bank or Federal savings association. Independent credit card banks and independent credit card... credit card operations and are not affiliated with a full service national bank or Federal savings...

12 CFR 622.6 - Opportunity for informal settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Opportunity for informal settlement. 622.6 Section 622.6 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM RULES OF PRACTICE AND... of a proceeding, without prejudice to the rights of the parties. No offer or proposal shall be...

12 CFR 1102.35 - Opportunity for informal settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Opportunity for informal settlement. 1102.35 Section 1102.35 Banks and Banking FEDERAL FINANCIAL INSTITUTIONS EXAMINATION COUNCIL APPRAISER REGULATION... settlement of a proceeding, without prejudice to the rights of the parties. No offer or proposal shall be...

12 CFR 1402.12 - Identification of records requested.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Identification of records requested. 1402.12 Section 1402.12 Banks and Banking FARM CREDIT SYSTEM INSURANCE CORPORATION RELEASING INFORMATION... information as to dates, titles, and subject matter, so that such records may be located without undue search...

12 CFR 308.15 - Opportunity for informal settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Opportunity for informal settlement. 308.15 Section 308.15 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE... Counsel written offers or proposals for settlement of a proceeding, without prejudice to the rights of any...

12 CFR 747.15 - Opportunity for informal settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Opportunity for informal settlement. 747.15 Section 747.15 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS... settlement of a proceeding, without prejudice to the rights of any of the parties. No such offer or proposal...

78 FR 15121 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Bank...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... Activities; Submission for OMB Review; Comment Request; Bank Secrecy Act/Money Laundering Risk Assessment... information collection titled ``Bank Secrecy Act/Money Laundering Risk Assessment,'' also known as the Money... for review and clearance. Bank Secrecy Act/Money Laundering Risk Assessment (OMB Control Number 1557...

12 CFR 263.15 - Opportunity for informal settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Opportunity for informal settlement. 263.15 Section 263.15 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL... proposal, or any subsequent negotiation or resolution, is admissible as evidence in any proceeding. ...

12 CFR 1780.14 - Opportunity for informal settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Opportunity for informal settlement. 1780.14 Section 1780.14 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF HOUSING... part. No settlement offer or proposal, or any subsequent negotiation or resolution, is admissible as...

12 CFR 717.28 - Effective date, compliance date, and prospective application.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Effective date, compliance date, and prospective application. 717.28 Section 717.28 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION... eligibility information when such information is placed into a common database and is accessible by you. ...

12 CFR 717.28 - Effective date, compliance date, and prospective application.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Effective date, compliance date, and prospective application. 717.28 Section 717.28 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION... eligibility information when such information is placed into a common database and is accessible by you. ...

12 CFR 717.28 - Effective date, compliance date, and prospective application.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Effective date, compliance date, and prospective application. 717.28 Section 717.28 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION... eligibility information when such information is placed into a common database and is accessible by you. ...

12 CFR 717.28 - Effective date, compliance date, and prospective application.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Effective date, compliance date, and prospective application. 717.28 Section 717.28 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION... eligibility information when such information is placed into a common database and is accessible by you. ...

12 CFR 717.28 - Effective date, compliance date, and prospective application.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Effective date, compliance date, and prospective application. 717.28 Section 717.28 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION... eligibility information when such information is placed into a common database and is accessible by you. ...

Documentation for the machine-readable version of the Bright Star Catalogue

NASA Technical Reports Server (NTRS)

Warren, W. H., Jr.

1982-01-01

The machine-readable version of The Bright Star Catalogue, 4th edition, is described. In addition to the large number of newly determined fundamental data, such as photoelectric magnitudes, MK spectral types, parallaxes, and radial velocities, the new version contains data and information not included in the third edition such as the identification of IR sources, U-B and R-I colors, radial velocity comments (indication and identification of spectroscopic and occultation binaries), and projected rotational velocities. The equatorial coordinates for equinoxes 1900 and 2000 are recorded to greater precision details concerning variability, spectral characteristics, duplicity, and group membership are included. Data compiled through 1979, some information and variable-star designations found through 1981 are considered.

Electronic properties and optical absorption of a phosphorene quantum dot

NASA Astrophysics Data System (ADS)

Liang, F. X.; Ren, Y. H.; Zhang, X. D.; Jiang, Z. T.

2018-03-01

Using the tight-binding Hamiltonian approach, we theoretically study the electronic and optical properties of a triangular phosphorene quantum dot (PQD) including one normal zigzag edge and two skewed armchair edges (ZAA-PQD). It is shown that the energy spectrum can be classified into the filled band (FB), the zero-energy band (ZB), and the unfilled band (UB). Numerical calculations of the FB, ZB, and UB probability distributions show that the FB and the UB correspond to the bulk states, while the ZB corresponds to the edge states, which appear on all of the three edges of the ZAA-PQD sharply different from the other PQDs. We also find that the strains and the electric fields can affect the energy levels inhomogeneously. Then the optical properties of the ZAA-PQD are investigated. There appear some strong low-energy optical absorption peaks indicating its sensitive low-energy optical response that is absent in other PQDs. Moreover, the strains and the electric fields can make inhomogeneous influences on the optical spectrum of the ZAA-PQD. This work may provide a useful reference for designing the electrical, mechanical, and optical PQD devices.

Divergence in Ubiquitin Interaction and Catalysis among the Ubiquitin-Specific Protease Family Deubiquitinating Enzymes.

PubMed

Tencer, Adam H; Liang, Qin; Zhuang, Zhihao

2016-08-23

Deubiquitinating enzymes (DUBs) are responsible for reversing mono- and polyubiquitination of proteins and play essential roles in numerous cellular processes. Close to 100 human DUBs have been identified and are classified into five families, with the ubiquitin-specific protease (USP) family being the largest (>50 members). The binding of ubiquitin (Ub) to USP is strikingly different from that observed for the DUBs in the ubiquitin C-terminal hydrolase (UCH) and ovarian tumor domain protease (OTU) families. We generated a panel of mutant ubiquitins and used them to probe the ubiquitin's interaction with a number of USPs. Our results revealed a remarkable divergence of USP-Ub interactions among the USP catalytic domains. Our double-mutant cycle analysis targeting the ubiquitin residues located in the tip, the central body, and the tail of ubiquitin also demonstrated different crosstalk among the USP-Ub interactions. This work uncovered intriguing divergence in the ubiquitin-binding mode in the USP family DUBs and raised the possibility of targeting the ubiquitin-binding hot spots on USPs for selective inhibition of USPs by small molecule antagonists.

Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II.

PubMed

Dong, L-F; Low, P; Dyason, J C; Wang, X-F; Prochazka, L; Witting, P K; Freeman, R; Swettenham, E; Valis, K; Liu, J; Zobalova, R; Turanek, J; Spitz, D R; Domann, F E; Scheffler, I E; Ralph, S J; Neuzil, J

2008-07-17

Alpha-tocopheryl succinate (alpha-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of alpha-TOS has not been identified. Here, we show that alpha-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q(P) and Q(D), respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of alpha-TOS compared to that of UbQ for the Q(P) and Q(D) sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of alpha-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to alpha-TOS. We propose that alpha-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy.

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

PubMed Central

Dong, Lan-Feng; Low, Pauline; Dyason, Jeffrey C.; Wang, Xiu-Fang; Prochazka, Lubomir; Witting, Paul K.; Freeman, Ruth; Swettenham, Emma; Valis, Karel; Liu, Ji; Zobalova, Renata; Turanek, Jaroslav; Spitz, Doug R.; Domann, Frederick E.; Scheffler, Immo E.; Ralph, Stephen J.; Neuzil, Jiri

2009-01-01

α-Tocopheryl succinate (α-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of α-TOS has not been identified. Here we show that α-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ) binding site (QP and QD, respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of α-TOS compared to that of UbQ for the QP and QD sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and undergo apoptosis in the presence of α-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to α-TOS. We propose that α-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy. PMID:18372923

Role of fibroblast growth factor receptor signaling in kidney development

PubMed Central

2011-01-01

Fibroblast growth factor receptors (Fgfrs) consist of four signaling family members and one nonsignaling “decoy” receptor, Fgfr-like 1 (Fgfrl1), all of which are expressed in the developing kidney. Several studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB) in cultured tissues. Transgenic and conditional knockout approaches in whole animals have shown that Fgfr1 and Fgfr2 (predominantly the IIIc isoform) in kidney mesenchyme are critical for early MM and UB formation. Conditional deletion of the ligand, Fgf8, in nephron precursors or global deletion of Fgfrl1 interrupts nephron formation. Fgfr2 (likely the IIIb isoform signaling downstream of Fgf7 and Fgf10) is critical for ureteric morphogenesis. Moreover, Fgfr2 appears to act independently of Frs2α (the major signaling adapter for Fgfrs) in regulating UB branching. Loss of Fgfr2 in the MM leads to many kidney and urinary tract anomalies, including vesicoureteral reflux. Thus Fgfr signaling is critical for patterning of virtually all renal lineages at early and later stages of development. PMID:21613421

Role of fibroblast growth factor receptor signaling in kidney development.

PubMed

Bates, Carlton M

2011-08-01

Fibroblast growth factor receptors (Fgfrs) consist of four signaling family members and one nonsignaling "decoy" receptor, Fgfr-like 1 (Fgfrl1), all of which are expressed in the developing kidney. Several studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB) in cultured tissues. Transgenic and conditional knockout approaches in whole animals have shown that Fgfr1 and Fgfr2 (predominantly the IIIc isoform) in kidney mesenchyme are critical for early MM and UB formation. Conditional deletion of the ligand, Fgf8, in nephron precursors or global deletion of Fgfrl1 interrupts nephron formation. Fgfr2 (likely the IIIb isoform signaling downstream of Fgf7 and Fgf10) is critical for ureteric morphogenesis. Moreover, Fgfr2 appears to act independently of Frs2α (the major signaling adapter for Fgfrs) in regulating UB branching. Loss of Fgfr2 in the MM leads to many kidney and urinary tract anomalies, including vesicoureteral reflux. Thus Fgfr signaling is critical for patterning of virtually all renal lineages at early and later stages of development.

12 CFR 980.7 - Examinations; requests for additional information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... new business activity, nothing in this part shall limit the right of the Finance Board at any time to... business activity is consistent with the housing finance and community lending mission of the Banks and the... information. 980.7 Section 980.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD NEW FEDERAL HOME LOAN BANK...

12 CFR 980.7 - Examinations; requests for additional information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... new business activity, nothing in this part shall limit the right of the Finance Board at any time to... business activity is consistent with the housing finance and community lending mission of the Banks and the... information. 980.7 Section 980.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD NEW FEDERAL HOME LOAN BANK...

78 FR 32387 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-30

..., maintenance, and purchase of services to provide information. Proposal to approve under OMB delegated...: Bank Holding Companies (BHCs), foreign banking organizations (FBOs), state member banks (SMBs), and... 12 U.S.C. 1467a(c)(2)(H); section 8(a) of the International Banking Act, 12 U.S.C. 3106(a); sections...

12 CFR 792.68 - Use and collection of Social Security numbers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... INFORMATION ACT AND PRIVACY ACT, AND BY SUBPOENA; SECURITY PROCEDURES FOR CLASSIFIED INFORMATION The Privacy... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Use and collection of Social Security numbers. 792.68 Section 792.68 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING THE...

12 CFR 792.68 - Use and collection of Social Security numbers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... INFORMATION ACT AND PRIVACY ACT, AND BY SUBPOENA; SECURITY PROCEDURES FOR CLASSIFIED INFORMATION The Privacy... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Use and collection of Social Security numbers. 792.68 Section 792.68 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING THE...

12 CFR 792.68 - Use and collection of Social Security numbers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... INFORMATION ACT AND PRIVACY ACT, AND BY SUBPOENA; SECURITY PROCEDURES FOR CLASSIFIED INFORMATION The Privacy... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Use and collection of Social Security numbers. 792.68 Section 792.68 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING THE...

77 FR 37041 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... EXPORT-IMPORT BANK OF THE U.S. [Public Notice 2012-0111] Agency Information Collection Activities: Final Collection; Comment Request AGENCY: Export-Import Bank of the U.S. ACTION: Submission for OMB... Credit Insurance Policy. SUMMARY: The Export-Import Bank of the United States (Ex-Im Bank), as a part of...

77 FR 35679 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-14

... EXPORT-IMPORT BANK OF THE UNITED STATES [Public Notice 2012-0134] Agency Information Collection Activities: Final Collection; Comment Request AGENCY: Export-Import Bank of the U.S. ACTION: Submission for...: The Export-Import Bank of the United States (Ex-Im Bank), as a part of its continuing effort to reduce...

77 FR 76036 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... EXPORT-IMPORT BANK OF THE U.S. [Public Notice 2012-0555] Agency Information Collection Activities: Final Collection; Comment Request AGENCY: Export-Import Bank of the U.S. ACTION: Submission for OMB.... SUMMARY: The Export-Import Bank of the United States (Ex-Im Bank), as a part of its continuing effort to...

77 FR 16549 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-21

... EXPORT-IMPORT BANK OF THE U.S. [Public Notice 2012-0087] Agency Information Collection Activities: Final Collection; Comment Request AGENCY: Export-Import Bank of the U.S. ACTION: Submission for OMB... Credit Insurance Policy. SUMMARY: The Export-Import Bank of the United States (Ex-Im Bank), as a part of...

12 CFR Appendix C to Part 325 - Risk-Based Capital for State Non-Member Banks: Market Risk

Code of Federal Regulations, 2010 CFR

2010-01-01

... provide information about the impact of adverse market events on a bank's covered positions. Backtests provide information about the accuracy of an internal model by comparing a bank's daily VAR measures to... determines the bank meets such criteria as a consequence of accounting, operational, or similar...

76 FR 4110 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-24

... EXPORT-IMPORT BANK OF THE U.S. [Public Notice 2011-0002] Agency Information Collection Activities: Final Collection; Comment Request AGENCY: Export-Import Bank of the U.S. ACTION: Submission for OMB...-Import Bank of the United States (Ex-Im Bank), as a part of its continuing effort to reduce paperwork and...

76 FR 69270 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

... Performance of Bank Services. No comments were received. Therefore, the FDIC hereby gives notice of submission... Approved Collection of Information 1. Title: Notification of Performance of Bank Services. OMB Number: 3064... relationship with a bank service corporation. Form 6120/06 (Notification of Performance of Bank Services) may...

76 FR 64944 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... EXPORT-IMPORT BANK OF THE U.S. [Public Notice 2011-076] Agency Information Collection Activities: Final Collection; Comment Request AGENCY: Export-Import Bank of the U.S. ACTION: Submission for OMB... between a U.S. exporter, Ex-Im Bank, and a foreign export credit agency; the information collected...

77 FR 284 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-04

... EXPORT-IMPORT BANK OF THE U.S. [Public Notice 2011-0080] Agency Information Collection Activities: Final Collection; Comment Request AGENCY: Export-Import Bank of the U.S. ACTION: Submission for OMB... between a U.S. exporter, Ex-Im Bank, and a foreign export credit agency; the information collected...

12 CFR 1272.7 - Examinations; requests for additional information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... information. 1272.7 Section 1272.7 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS NEW BUSINESS ACTIVITIES § 1272.7 Examinations; requests for additional information. (a) General... business activity, nothing in this part shall limit the right of the FHFA at any time to: (1) Request...

12 CFR 1272.7 - Examinations; requests for additional information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... information. 1272.7 Section 1272.7 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS NEW BUSINESS ACTIVITIES § 1272.7 Examinations; requests for additional information. (a) General... business activity, nothing in this part shall limit the right of the FHFA at any time to: (1) Request...

12 CFR 1272.7 - Examinations; requests for additional information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... information. 1272.7 Section 1272.7 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS NEW BUSINESS ACTIVITIES § 1272.7 Examinations; requests for additional information. (a) General... business activity, nothing in this part shall limit the right of the FHFA at any time to: (1) Request...

45 CFR 60.15 - Confidentiality of National Practitioner Data Bank information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Confidentiality of National Practitioner Data Bank information. 60.15 Section 60.15 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NATIONAL PRACTITIONER DATA BANK FOR ADVERSE INFORMATION ON PHYSICIANS AND OTHER HEALTH CARE PRACTITIONERS...

12 CFR 352.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... activities, and Electronic and Information Technology set forth in § 352.2. (b) “Electronic and Information Technology” (“EIT”) has the same meaning as “information technology” except EIT also includes any equipment... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Definitions. 352.3 Section 352.3 Banks and...

Palmprint and face score level fusion: hardware implementation of a contactless small sample biometric system

NASA Astrophysics Data System (ADS)

Poinsot, Audrey; Yang, Fan; Brost, Vincent

2011-02-01

Including multiple sources of information in personal identity recognition and verification gives the opportunity to greatly improve performance. We propose a contactless biometric system that combines two modalities: palmprint and face. Hardware implementations are proposed on the Texas Instrument Digital Signal Processor and Xilinx Field-Programmable Gate Array (FPGA) platforms. The algorithmic chain consists of a preprocessing (which includes palm extraction from hand images), Gabor feature extraction, comparison by Hamming distance, and score fusion. Fusion possibilities are discussed and tested first using a bimodal database of 130 subjects that we designed (uB database), and then two common public biometric databases (AR for face and PolyU for palmprint). High performance has been obtained for recognition and verification purpose: a recognition rate of 97.49% with AR-PolyU database and an equal error rate of 1.10% on the uB database using only two training samples per subject have been obtained. Hardware results demonstrate that preprocessing can easily be performed during the acquisition phase, and multimodal biometric recognition can be treated almost instantly (0.4 ms on FPGA). We show the feasibility of a robust and efficient multimodal hardware biometric system that offers several advantages, such as user-friendliness and flexibility.

Finding faults with the data

NASA Astrophysics Data System (ADS)

Showstack, Randy

Rudolph Giuliani and Hillary Rodham Clinton are crisscrossing upstate New York looking for votes in the U.S. Senate race. Also cutting back and forth across upstate New York are hundreds of faults of a kind characterized by very sporadic seismic activity according to Robert Jacobi, professor of geology at the University of Buffalo (UB), who conducted research with fellow UB geology professor John Fountain."We have proof that upstate New York is crisscrossed by faults," Jacobi said. "In the past, the Appalachian Plateau—which stretches from Albany to Buffalo—was considered a pretty boring place structurally without many faults or folds of any significance."

Ubiquitin ligase activity of TFIIH and the transcriptional response to DNA damage.

PubMed

Takagi, Yuichiro; Masuda, Claudio A; Chang, Wei-Hau; Komori, Hirofumi; Wang, Dong; Hunter, Tony; Joazeiro, Claudio A P; Kornberg, Roger D

2005-04-15

Core transcription factor (TF) IIH purified from yeast possesses an E3 ubiquitin (Ub) ligase activity, which resides, at least in part, in a RING finger (RNF) domain of the Ssl1 subunit. Yeast strains mutated in the Ssl1 RNF domain are sensitive to ultraviolet (UV) light and to methyl methanesulfonate (MMS). This increased sensitivity to DNA-damaging agents does not reflect a deficiency in nucleotide excision repair. Rather, it correlates with reduced transcriptional induction of genes involved in DNA repair, suggesting that the E3 Ub ligase activity of TFIIH mediates the transcriptional response to DNA damage.

Marine realms information bank: A distributed geolibrary for the ocean

USGS Publications Warehouse

Marincioni, F.; Lightsom, F.; ,

2002-01-01

The Marine Realms Information Bank (MRIB) is a prototype web-based distributed geolibrary that organizes, indexes, and delivers online information about the oceanic and coastal environments. It implements the distributed geolibrary concept to organize, index, and deliver online information about the oceanic and coastal environments. The significance of MRIB lies both in the utility of the information bank and in the implementation of the distributed geolibraries concept.

75 FR 9226 - Agency Information Collection Activities; Proposed Collection; Comment Request; Human Tissue...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... establishments of which 145 are conventional tissue banks and 112 are eye tissue banks. Based on information...,115 donors of eye tissue each year. Accredited members of the American Association of Tissue Banks... system, 90 percent of the conventional tissue banks are members of AATB (145 x 90% = 130), and 77 percent...

12 CFR 555.300 - Must I inform OTS before I use electronic means or facilities?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Must I inform OTS before I use electronic means or facilities? 555.300 Section 555.300 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY ELECTRONIC OPERATIONS Requirements Applicable to All Savings Associations § 555.300 Must...

12 CFR Appendix E to Part 225 - Capital Adequacy Guidelines for Bank Holding Companies: Market Risk Measure

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM BANK HOLDING COMPANIES AND CHANGE IN BANK CONTROL... Stress tests provide information about the impact of adverse market events on a bank's covered positions. Backtests provide information about the accuracy of an internal model by comparing an organization's daily...

12 CFR 261a.4 - Fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Fees. 261a.4 Section 261a.4 Banks and Banking... TO PERSONAL INFORMATION UNDER THE PRIVACY ACT OF 1974 General Provisions § 261a.4 Fees. (a) Copies of... Availability of Information, § 261.10 of this part. (b) No fee. Documents may be furnished without charge where...

31 CFR 128.5 - Recordkeeping requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... General Information § 128.5 Recordkeeping requirements. Banks, other depository institutions, International Banking Facilities, bank holding companies, brokers and dealers, and nonbanking enterprises subject to the jurisdiction of the United States shall maintain all information necessary to make a...

31 CFR 128.5 - Recordkeeping requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... General Information § 128.5 Recordkeeping requirements. Banks, other depository institutions, International Banking Facilities, bank holding companies, brokers and dealers, and nonbanking enterprises subject to the jurisdiction of the United States shall maintain all information necessary to make a...

31 CFR 128.5 - Recordkeeping requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... General Information § 128.5 Recordkeeping requirements. Banks, other depository institutions, International Banking Facilities, bank holding companies, brokers and dealers, and nonbanking enterprises subject to the jurisdiction of the United States shall maintain all information necessary to make a...

31 CFR 128.5 - Recordkeeping requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... General Information § 128.5 Recordkeeping requirements. Banks, other depository institutions, International Banking Facilities, bank holding companies, brokers and dealers, and nonbanking enterprises subject to the jurisdiction of the United States shall maintain all information necessary to make a...

48 CFR 252.232-7011 - Payments in Support of Emergencies and Contingency Operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... Internal Revenue Code. (ix) Electronic funds transfer banking information. (A) The Contractor shall include electronic funds transfer banking information on the invoice only if required elsewhere in this contract. (B) If electronic funds transfer banking information is not required to be on the invoice, in order for...

38 CFR 1.460 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... with an Organ Procurement Organization, eye bank or tissue bank with written, detailed responsibilities...-being of the user. Eye bank and tissue bank. The term “eye bank and tissue bank” means an “establishment... bank, and/or tissue bank as defined in this section. Records. The term “records” means any information...

38 CFR 1.460 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... with an Organ Procurement Organization, eye bank or tissue bank with written, detailed responsibilities...-being of the user. Eye bank and tissue bank. The term “eye bank and tissue bank” means an “establishment... bank, and/or tissue bank as defined in this section. Records. The term “records” means any information...

38 CFR 1.460 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... with an Organ Procurement Organization, eye bank or tissue bank with written, detailed responsibilities...-being of the user. Eye bank and tissue bank. The term “eye bank and tissue bank” means an “establishment... bank, and/or tissue bank as defined in this section. Records. The term “records” means any information...

38 CFR 1.460 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... with an Organ Procurement Organization, eye bank or tissue bank with written, detailed responsibilities...-being of the user. Eye bank and tissue bank. The term “eye bank and tissue bank” means an “establishment... bank, and/or tissue bank as defined in this section. Records. The term “records” means any information...

12 CFR 404.25 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Applicability. 404.25 Section 404.25 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Demands for Testimony of Current and Former Ex-Im Bank Personnel and for Production of Ex-Im Bank Records § 404.25 Applicability. This...

Do aerosols influence the diurnal variation of H2O2 in the atmosphere?

NASA Astrophysics Data System (ADS)

Liang, H.; Chen, Z.; Wu, Q.; Huang, D.; Zhao, Y.

2013-12-01

Hydrogen peroxide (H2O2) and organic peroxides are crucial reactive species that are involved in the cycling of HOx (OH and HO2) radicals and the formation of secondary inorganic and organic aerosols in the atmosphere. Despite the importance of peroxides, their formation and removal mechanisms with the coexistence of aerosols are as yet less well known. From June 10 to July 15 2013, summertime surface measurements for atmospheric peroxides were simultaneously obtained in urban Beijing (UB) and Gucheng (GC). The UB site is located in the northern downtown of Beijing city, while the GC site is a rural site located in the North China Plain and ~100 km southwest of Beijing. In both sites, the major peroxides were determined to be H2O2, methyl hydroperoxide (MHP), peroxyformic acid (PFA) and peroxyacetic acid (PAA). By comparing the concentrations of PFA and PAA in the gas phase and rainwater, for the first time, we estimated the Henry's law constant for PFA as ~210 M atm-1 at 298 K, a quarter of that for PAA. Interestingly, we observed different H2O2 profiles in the two sites as follows: (i) the average concentration of H2O2 in UB was 50% higher than that in GC; (ii) H2O2 in GC reached its peak concentration at around 15:30, whereas the peak concentration in UB appeared at as late as 21:00; and (iii) the daily variation of H2O2 in GC generally kept consistent with that of O3 and organic peroxides while it was not always the case in UB. These differences indicate a hitherto unrecognized storage-release mechanism for H2O2 in UB, that is, an extra sink in the noontime and an extra source in the early evening. The extra source of H2O2 would enhance the aerosol phase OH radical in the early evening by the Fenton reaction. A box model analysis shows that the impacts of aerosols were majorly responsible to this unrecognized mechanism, although NOx, regional transport and planet boundary layer height also contributed a minor part. Aerosols participated in the storage-release mechanism in two potential ways. The first is the catalytic reaction of aerosol-phase soluble transition metal ions (ATMIs). ATMIs could convert HO2 to either H2O or H2O2, depending on their abundance and composition. In UB, the high ATMIs are presumed to convert most HO2 to H2O in the noontime and to H2O2 in the early evening, resulting in a different diurnal profile of H2O2. The second is the formation and hydrolysis of H2O2-related complex. In the noontime, H2O2 could be taken up onto the aerosols and then combine with organic matters to form complexes such as hydroxyalkyl hydroperoxides and secondary organic aerosols. In the early evening, however, these complexes could hydrolyze to generate H2O2 and release into the gas phase. The impacts of aerosols on H2O2, and probably on HO2 radicals over the polluted regions should be taken into consideration in the atmospheric model.

Identification, Characterization and Expression Profiling of Stress-Related Genes in Easter Lily (Lilium formolongi)

PubMed Central

Howlader, Jewel; Park, Jong-In; Robin, Arif Hasan Khan; Sumi, Kanij Rukshana; Nou, Ill-Sup

2017-01-01

Biotic and abiotic stresses are the major causes of crop loss in lily worldwide. In this study, we retrieved 12 defense-related expressed sequence tags (ESTs) from the NCBI database and cloned, characterized, and established seven of these genes as stress-induced genes in Lilium formolongi. Using rapid amplification of cDNA ends PCR (RACE-PCR), we successfully cloned seven full-length mRNA sequences from L. formolongi line Sinnapal lily. Based on the presence of highly conserved characteristic domains and phylogenetic analysis using reference protein sequences, we provided new nomenclature for the seven nucleotide and protein sequences and submitted them to GenBank. The real-time quantitative PCR (qPCR) relative expression analysis of these seven genes, including LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfUb, LfCyt-b5, and LfRab, demonstrated that they were differentially expressed in all organs examined, possibly indicating functional redundancy. We also investigated the qPCR relative expression levels under two biotic and four abiotic stress conditions. All seven genes were induced by Botrytis cinerea treatment, and all genes except LfHsp70-3 and LfHsp90 were induced by Botrytis elliptica treatment; these genes might be associated with disease tolerance mechanisms in L. formolongi. In addition, LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfUb, and LfCyt-b5 were induced by heat treatment, LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, and LfCyt-b5 were induced by cold treatment, and LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfCy-b5, and LfRab were induced by drought and salt stress, indicating their likely association with tolerance to these stress conditions. The stress-induced candidate genes identified in this study provide a basis for further functional analysis and the development of stress-resistant L. formolongi cultivars.

Changes in Anthropometry, Upper-Body Strength, and Nutrient Intake in Professional Australian Football Players During a Season.

PubMed

Bilsborough, Johann C; Greenway, Kate; Livingston, Steuart; Cordy, Justin; Coutts, Aaron J

2016-04-01

The purpose of this study was to examine the seasonal changes in body composition, nutrition, and upper-body (UB) strength in professional Australian Football (AF) players. The prospective longitudinal study examined changes in anthropometry (body mass, fat-free soft-tissue mass [FFSTM], and fat mass) via dual-energy X-ray absorptiometry 5 times during an AF season (start preseason, midpreseason, start season, midseason, end season) in 45 professional AF players. Dietary intakes and strength (bench press and bench pull) were also assessed at these time points. Players were categorized as experienced (>4 y experience, n = 23) or inexperienced (<4 y experience, n = 22). Fat mass decreased during the preseason but was stable through the in-season for both groups. %FFSTM was increased during the preseason and remained constant thereafter. UB strength increased during the preseason and was maintained during the in-season. Changes in UB FFSTM were related to changes in UB-strength performance (r = .37-.40). Total energy and carbohydrate intakes were similar between the experienced and inexperienced players during the season, but there was a greater ratio of dietary fat intake at the start-preseason point and an increased alcohol, reduced protein, and increased total energy intake at the end of the season. The inexperienced players consumed more fat at the start of season and less total protein during the season than the experienced players. Coaches should also be aware that it can take >1 y to develop the appropriate levels of FFSTM in young players and take a long-term view when developing the physical and performance abilities of inexperienced players.

Study of B̄→X ulν̄ decays in BB̄ events tagged by a fully reconstructed B-meson decay and determination of |V ub|

DOE PAGES

Lees, J. P.; Poireau, V.; Tisserand, V.; ...

2012-08-07

We report measurements of partial branching fractions for inclusive charmless semileptonic B decays B¯¯¯→X ulν¯ and the determination of the Cabibbo–Kobayashi–Maskawa (CKM) matrix element |V ub|. The analysis is based on a sample of 467×10⁶ Υ(4S)→BB¯¯¯ decays recorded with the BABAR detector at the PEP-II e⁺e⁻ storage rings. We select events in which the decay of one of the B mesons is fully reconstructed and an electron or a muon signals the semileptonic decay of the other B meson. We measure partial branching fractions ΔB in several restricted regions of phase space and determine the CKM element |V ub| basedmore » on different QCD predictions. For decays with a charged lepton momentum p * l>1.0 GeV in the B meson rest frame, we obtain ΔB=(1.80±0.13stat±0.15sys±0.02theo)×10⁻³ from a fit to the two-dimensional M X-q² distribution. Here, M X refers to the invariant mass of the final state hadron X and q² is the invariant mass squared of the charged lepton and neutrino. From this measurement we extract |V ub|=(4.33±0.24 exp±0.15 theo)×10⁻³ as the arithmetic average of four results obtained from four different QCD predictions of the partial rate. We separately determine partial branching fractions for B¯¯¯0 and B⁻ decays and derive a limit on the isospin breaking in B¯¯¯→X ulν¯ decays.« less

Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors.

PubMed

Landais, Igor; Hiddingh, Sanne; McCarroll, Matthew; Yang, Chao; Sun, Aiming; Turker, Mitchell S; Snyder, James P; Hoatlin, Maureen E

2009-12-31

The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity. Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells. These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds.

Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors

PubMed Central

2009-01-01

Background The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity. Results Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells. Conclusions These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds. PMID:20043851

FANC Pathway Promotes UV-Induced Stalled Replication Forks Recovery by Acting Both Upstream and Downstream Polη and Rev1

PubMed Central

Renaud, Emilie; Rosselli, Filippo

2013-01-01

To cope with ultraviolet C (UVC)-stalled replication forks and restart DNA synthesis, cells either undergo DNA translesion synthesis (TLS) by specialised DNA polymerases or tolerate the lesions using homologous recombination (HR)-based mechanisms. To gain insight into how cells manage UVC-induced stalled replication forks, we analysed the molecular crosstalk between the TLS DNA polymerases Polη and Rev1, the double-strand break repair (DSB)-associated protein MDC1 and the FANC pathway. We describe three novel functional interactions that occur in response to UVC-induced DNA lesions. First, Polη and Rev1, whose optimal expression and/or relocalisation depend on the FANC core complex, act upstream of FANCD2 and are required for the proper relocalisation of monoubiquitinylated FANCD2 (Ub-FANCD2) to subnuclear foci. Second, during S-phase, Ub-FANCD2 and MDC1 relocalise to UVC-damaged nuclear areas or foci simultaneously but independently of each other. Third, Ub-FANCD2 and MDC1 are independently required for optimal BRCA1 relocalisation. While RPA32 phosphorylation (p-RPA32) and RPA foci formation were reduced in parallel with increasing levels of H2AX phosphorylation and MDC1 foci in UVC-irradiated FANC pathway-depleted cells, MDC1 depletion was associated with increased UVC-induced Ub-FANCD2 and FANCD2 foci as well as p-RPA32 levels and p-RPA32 foci. On the basis of the previous observations, we propose that the FANC pathway participates in the rescue of UVC-stalled replication forks in association with TLS by maintaining the integrity of ssDNA regions and by preserving genome stability and preventing the formation of DSBs, the resolution of which would require the intervention of MDC1. PMID:23365640

12 CFR 1511.7 - Liability of the Funding Corporation and Federal Reserve Banks.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Liability of the Funding Corporation and Federal Reserve Banks. 1511.7 Section 1511.7 Banks and Banking DEPARTMENT OF THE TREASURY RESOLUTION... Banks. The Funding Corporation and the Federal Reserve Banks may rely on the information provided in a...

76 FR 71436 - Agency Information Collection Activities Proposed Information Collection; Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... before the customer completes the purchase of the contract. There are special rules for transactions by... customers who buy DCCs and DSAs from national banks and ensure that national banks provide these products in... appropriate: Anti-tying--A bank must inform the customer that purchase of the product is optional and neither...

Supporting Informal Learning by Traders in Investment Banks

ERIC Educational Resources Information Center

Chivers, Geoffrey

2011-01-01

Purpose: The main aims of this paper are to determine the extent to which experienced traders in investment banks based in London are learning by informal methods, which methods are to the fore, and whether HRD staff are providing support for informal learning. It also seeks to find evidence that such investment banks were attempting to become…

12 CFR 404.28 - Notification of General Counsel required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Notification of General Counsel required. 404.28 Section 404.28 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Demands for Testimony of Current and Former Ex-Im Bank Personnel and for Production of Ex-Im Bank Records...

Roles of F-box proteins in human digestive system tumors (Review).

PubMed

Gong, Jian; Lv, Liang; Huo, Jirong

2014-12-01

F-box proteins (FBPs), the substrate-recognition subunit of E3 ubiquitin (Ub) ligase, are the important components of Ub proteasome system (UPS). FBPs are involved in multiple cellular processes through ubiquitylation and subsequent degradation of their target proteins. Many studies have described the roles of FBPs in human cancers. Digestive system tumors account for a large proportion of all the tumors, and their mortality is very high. This review summarizes for the first time the roles of FBPs in digestive system tumorige-nesis and tumor progression, aiming at finding new routes for the rational design of targeted anticancer therapies in digestive system tumors.

JPRS Report. East Asia: Japan

DTIC Science & Technology

1987-07-09

factions becoming political parties could S^«ntaJ* a bi??! r l3SUe WaS thS introduction of the system of proportional lllttlT,\\T Wlth ’ restricted...eleCti°n iS h6ld ° r n0t- are ca’led "soap bubbL plrty members « but still yet the LDP’s organizational strength is overpowering when ::C Wlth the m...are cases of overlapping and inaccurate but In ihe 2dTX?eSedly/Ub80ribla8 Party memb6rS ° r b°°3t- "ub members station thf orL af cities of the

Surveying Medical Students to Gauge Library Use and Plan for a New Medical Library.

PubMed

Aronoff, Nell

2016-01-01

In spring 2015, a 45-question survey was e-mailed to 585 medical students at the University at Buffalo (UB) in order to gauge their use of library spaces, resources, equipment, and services at UB's Health Sciences Library and plan for a library space located within a new medical school building. Students' self-reported use of the library during the academic year is presented along with the features they would like to see in their ideal library space. The responses generated in the survey are a barometer of current use and will be used in the planning process.

SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy.

PubMed

Xu, Muyu; Moresco, James J; Chang, Max; Mukim, Amey; Smith, Davey; Diedrich, Jolene K; Yates, John R; Jones, Katherine A

2018-05-23

HIV-1 Tat is a key regulator of viral transcription, however little is known about the mechanisms that control its turnover in T cells. Here we use a novel proteomics technique, called DiffPOP, to identify the molecular target of JIB-04, a small molecule compound that potently and selectively blocks HIV-1 Tat expression, transactivation, and virus replication in T cell lines. Mass-spectrometry analysis of whole-cell extracts from 2D10 Jurkat T cells revealed that JIB-04 targets Serine Hydroxymethyltransferase 2 (SHMT2), a regulator of glycine biosynthesis and an adaptor for the BRCC36 K63Ub-specific deubiquitinase in the BRISC complex. Importantly, knockdown of SHMT1,2 or BRCC36, or exposure of cells to JIB-04, strongly increased Tat K63Ub-dependent destruction via autophagy. Moreover, point mutation of multiple lysines in Tat, or knockdown of BRCC36 or SHMT1,2, was sufficient to prevent destruction of Tat by JIB-04. We conclude that HIV-1 Tat levels are regulated through K63Ub-selective autophagy mediated through SHMT1,2 and the BRCC36 deubiquitinase.

Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy.

PubMed

Potting, Christoph; Crochemore, Christophe; Moretti, Francesca; Nigsch, Florian; Schmidt, Isabel; Manneville, Carole; Carbone, Walter; Knehr, Judith; DeJesus, Rowena; Lindeman, Alicia; Maher, Rob; Russ, Carsten; McAllister, Gregory; Reece-Hoyes, John S; Hoffman, Gregory R; Roma, Guglielmo; Müller, Matthias; Sailer, Andreas W; Helliwell, Stephen B

2018-01-09

PARKIN, an E3 ligase mutated in familial Parkinson's disease, promotes mitophagy by ubiquitinating mitochondrial proteins for efficient engagement of the autophagy machinery. Specifically, PARKIN-synthesized ubiquitin chains represent targets for the PINK1 kinase generating phosphoS65-ubiquitin (pUb), which constitutes the mitophagy signal. Physiological regulation of PARKIN abundance, however, and the impact on pUb accumulation are poorly understood. Using cells designed to discover physiological regulators of PARKIN abundance, we performed a pooled genome-wide CRISPR/Cas9 knockout screen. Testing identified genes individually resulted in a list of 53 positive and negative regulators. A transcriptional repressor network including THAP11 was identified and negatively regulates endogenous PARKIN abundance. RNAseq analysis revealed the PARKIN-encoding locus as a prime THAP11 target, and THAP11 CRISPR knockout in multiple cell types enhanced pUb accumulation. Thus, our work demonstrates the critical role of PARKIN abundance, identifies regulating genes, and reveals a link between transcriptional repression and mitophagy, which is also apparent in human induced pluripotent stem cell-derived neurons, a disease-relevant cell type. Copyright © 2018 the Author(s). Published by PNAS.

Studies of Inviscid Flux Schemes for Acoustics and Turbulence Problems

NASA Technical Reports Server (NTRS)

Morris, Chris

2013-01-01

Five different central difference schemes, based on a conservative differencing form of the Kennedy and Gruber skew-symmetric scheme, were compared with six different upwind schemes based on primitive variable reconstruction and the Roe flux. These eleven schemes were tested on a one-dimensional acoustic standing wave problem, the Taylor-Green vortex problem and a turbulent channel flow problem. The central schemes were generally very accurate and stable, provided the grid stretching rate was kept below 10%. As near-DNS grid resolutions, the results were comparable to reference DNS calculations. At coarser grid resolutions, the need for an LES SGS model became apparent. There was a noticeable improvement moving from CD-2 to CD-4, and higher-order schemes appear to yield clear benefits on coarser grids. The UB-7 and CU-5 upwind schemes also performed very well at near-DNS grid resolutions. The UB-5 upwind scheme does not do as well, but does appear to be suitable for well-resolved DNS. The UF-2 and UB-3 upwind schemes, which have significant dissipation over a wide spectral range, appear to be poorly suited for DNS or LES.

Effect of low current density and low frequency on oxidation resistant and coating activity of coated FeCrAl substrate by γ-Al2O3 powder

NASA Astrophysics Data System (ADS)

Leman, A. M.; Feriyanto, Dafit; Zakaria, Supaat; Sebayang, D.; Rahman, Fakhrurrazi; Jajuli, Afiqah

2017-09-01

High oxidation resistant is the needed material properties for material that operates in high temperature such as catalytic converter material. FeCrAl alloy acts as metallic material and is used as substrate material that is coated by ceramic material i.e. γ-Al2O3. The main purpose of this research is to increase oxidation resistant of metallic material as it will help improve the life time of metallic catalytic converter. Ultrasonic technique (UB) and Nickel electroplating technique (EL) were used to achieve the objective. UB was carried out using various time of 1, 1.5, 2, 2.5 and 3 h, in low frequency of 35 kHz and ethanol as the electrolyte. Meanwhile, EL was conducted using various times of 15, 30, 45, 60 and 75 minutes, DC power supply was 1.28A and sulphamate type as the solution. The characterization and analysis were carried out using Scanning Electron Microscopy (SEM) and box furnace at various temperature of 1000, 1100 and 1200 °C. SEM analysis shows the surface morphology of treated and untreated samples. Untreated samples shows finer surface structure as compared to UB and EL samples. It was caused by γ-Al2O3 which was embedded during UB and EL process on the surface of FeCrAl substrate to develop protective oxide layer. The layer was used to protect the substrate from extreme environment condition and temperature operation. Oxidation resistant analysis shows that treated samples had lower mass change as compared to untreated samples. Lowest mass change of treated samples were located at UB 1.5 h and EL at 30 minute with 0.00475 g and 0.00243 g for temperature of 1000 °C, 0.00495 g and 000284 g for temperature of 1100 °C and 0.00519 g and 0.00304 g for temperature 1200 °C, Based on the overall results, it can be concluded that EL 30 minute samples was the appropriate parameter to coat FeCrAl by γ-Al2O3 to develop metallic catalytic converter that is high oxidation resistant in high temperature operation.

12 CFR 611.1221 - Submission to FCA of plan of termination and disclosure information; other required submissions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Submission to FCA of plan of termination and disclosure information; other required submissions. 611.1221 Section 611.1221 Banks and Banking FARM CREDIT... mail the equity holder notice under § 611.1210(b). If you send us the plan of termination in electronic...

12 CFR 611.1221 - Submission to FCA of plan of termination and disclosure information; other required submissions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Submission to FCA of plan of termination and disclosure information; other required submissions. 611.1221 Section 611.1221 Banks and Banking FARM CREDIT... mail the equity holder notice under § 611.1210(b). If you send us the plan of termination in electronic...

12 CFR 404.12 - General provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Access to Records Under the..., at the Export-Import Bank of the United States (Ex-Im Bank). (b) Relationship to the Freedom of... designated alternate. (e) Ex-Im Bank address. The Export-Import Bank of the United States is located at 811...

12 CFR 1271.22 - Computer data.

Code of Federal Regulations, 2014 CFR

2014-01-01

... computer system. Any such arrangement shall ensure the security of the computerized data stored in a Bank's... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Computer data. 1271.22 Section 1271.22 Banks... BANK OPERATIONS AND AUTHORITIES Bank Requests for Information § 1271.22 Computer data. Nothing in this...

12 CFR 404.24 - General provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of expert or opinion testimony by Ex-Im Bank personnel regarding matters related to the performance... 12 Banks and Banking 4 2010-01-01 2010-01-01 false General provisions. 404.24 Section 404.24 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Demands for Testimony of...

78 FR 55254 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... EXPORT IMPORT BANK [Public Notice 2013-6005] Agency Information Collection Activities: Comment Request AGENCY: Export-Import Bank of the United States. ACTION: Submission for OMB review and comments... applicant and transaction for Ex-Im Bank assistance under its programs. Affected Public: This form affects...

12 CFR 1273.9 - Audit Committee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the accurate and meaningful combination of information submitted by the Banks in the Bank System's... prevention or detection of management override or compromise of the internal control system; and (ii... information submitted by the Banks to the OF to be combined to create accurate and meaningful combined...

US-Canada Great Lakes Regional Specimen Bank Feasibility Study.

PubMed

Kerry, A; Edmonds, C J; Landon, L; Yonker, T L

1993-11-01

A study to examine the feasibility of establishing a Regional Specimen Bank in the Great Lakes area of the United States and Canada has recently been initiated by the Michigan Audubon Society. There are several existing formal and informal specimen banking facilities active in the region but their combined adequacy has not been evaluated. This feasibility study will establish the need and use of a regional bank and the institution(s) necessary to satisfy this need will be recommended. The study will address the scope required to meet present and future needs including the types of specimens to be represented in the bank, geographic coverage and protocols for collection, shipping, processing, analysis and storage. A management policy of the bank will be developed encompassing business operation, costs, governing structure and personnel requirements. The legal requirements of the bank will be determined with regards to the acquisition of samples, transport across national boundaries, access to specimens and information, and liability during operation. An effective information dissemination network will be recommended that is compatible with national and international partners, will facilitate technology and information transfer and support the quality and status of the bank. Determination of secure, long-term funding sources will be one of the key elements to ensuring a safe repository. This feasibility study is funded by the Great Lakes Protection Fund.

Why banks say NO to great healthcare practitioners. Five reasons why banks reject loans to quality small-business owners and what you can do about it.

PubMed

Warrick, Cheree

2014-01-01

If you have a dream of opening or expanding a practice, then bank lending is probably an option you've considered. However, many practitioners are under the false assumption that banks are currently not lending. Untrue! Between 2008 and 2012, banks have loaned an average of $216 billion to small businesses throughout the United States each year. There are two aspects to a bank loan package: (1) your loan application with tax information, asset information, etc.; and (2) your business plan. This article delves into the five reasons banks say "no" to a great healthcare practitioner and what you should include in your business plan to not only have the bank say "yes" to financing your business but also to create a situation where multiple banks are offering to lend you money.