MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

PubMed Central

Das, Mitali; Singh, Sunita; Pradhan, Satyajit

2014-01-01

As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2–7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the “MCM paradox.” Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology. PMID:25386362

MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3.

PubMed

Mimura, Satoru; Kubota, Yumiko; Takisawa, Haruhiko

2018-01-01

The minichromosome maintenance (MCM) complex, consisting of six subunits, Mcm2-7, is loaded onto replication origins through loading factors (origin recognition complex [ORC], Cdc6, and Cdt1) and forms an MCM double hexamer that licenses the initiation of DNA replication. Previous studies with Xenopus egg extracts showed that loading factors, especially Cdc6, dissociate from chromatin on MCM loading, but the molecular mechanism and physiological significance remain largely unknown. Using a cell-free system for MCM loading onto plasmid DNA in Xenopus egg extracts, we found that MCM loaded onto DNA prevents DNA binding of the loading factors ORC, Cdc6, and Cdt1. We further report that a peptide of the C-terminal region of MCM3 (MCM3-C), previously implicated in the initial association with ORC/Cdc6 in budding yeast, prevents ORC/Cdc6/Cdt1 binding to DNA in the absence of MCM loading. ATP-γ-S suppresses inhibitory activities of both the MCM loaded onto DNA and the MCM3-C peptide. Other soluble factors in the extract, but neither MCM nor Cdt1, are required for the activity. Conservation of the amino acid sequences of MCM3-C and its activity in vertebrates implies a novel negative autoregulatory mechanism that interferes with MCM loading in the vicinity of licensed origins to ensure proper origin licensing.

Skin tightening with a combined unipolar and bipolar radiofrequency device.

PubMed

Mayoral, Flor A

2007-02-01

Monopolar radiofrequency (RF) devices are well established treatment modalities for tightening facial skin. A 60-year-old woman presented with a desire to tighten the lax skin and improve the appearance of both upper arms. A combination unipolar and bipolar RF device may provide volume reduction as well as skin tightening in the upper arm.

Croton megalobotrys Müll Arg. and Vitex doniana (Sweet): Traditional medicinal plants in a three-step treatment regimen that inhibit in vitro replication of HIV-1.

PubMed

Tietjen, Ian; Gatonye, Teresia; Ngwenya, Barbara N; Namushe, Amos; Simonambanga, Sundana; Muzila, Mbaki; Mwimanzi, Philip; Xiao, Jianbo; Fedida, David; Brumme, Zabrina L; Brockman, Mark A; Andrae-Marobela, Kerstin

2016-09-15

Human Immunodeficiency Virus (HIV) strains resistant to licensed anti-retroviral drugs (ARVs) continue to emerge. On the African continent, uneven access to ARVs combined with occurrence of side-effects after prolonged ARV therapy have led to searches for traditional medicines as alternative or complementary remedies to conventional HIV/AIDS management. Here we characterize a specific three-step traditional HIV/AIDS treatment regimen consisting of Cassia sieberiana root, Vitex doniana root, and Croton megalobotrys bark by combining qualitative interviews of traditional medical knowledge users in Botswana with in vitro HIV replication studies. Crude extracts from a total of seven medicinal plants were tested for in vitro cytotoxicity and inhibition of wild-type (NL4.3) and ARV-resistant HIV-1 replication in an immortalized GFP-reporter CD4+ T-cell line. C. sieberiana root, V. doniana root, and C. megalobotrys bark extracts inhibited HIV-1NL4.3 replication with dose-dependence and without concomitant cytotoxicity. C. sieberiana and V. doniana extracts inhibited HIV-1 replication by 50% at 84.8µg/mL and at 25µg/mL, respectively, while C. megalobotrys extracts inhibited HIV-1 replication by a maximum of 45% at concentrations as low as 0.05µg/mL. Extracts did not interfere with antiviral activities of licensed ARVs when applied in combination and exhibited comparable efficacies against viruses harboring major resistance mutations to licensed protease, reverse-transcriptase, or integrase inhibitors. We report for the first time a three-step traditional HIV/AIDS regimen, used alone or in combination with standard ARV regimens, where each step exhibited more potent ability to inhibit HIV replication in vitro. Our observations support the "reverse pharmacology" model where documented clinical experiences are used to identify natural products of therapeutic value. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Stress levels for well-fitting implant superstructures as a function of tightening force levels, tightening sequence, and different operators.

PubMed

Nissan, J; Gross, M; Shifman, A; Assif, D

2001-07-01

Unfavorable stress distribution and occlusal overload have been reported to result in failures ranging from screw loosening to loss of osseointegration. The purpose of this study was to assess the effect of different tightening forces and sequences, with different operators, on stresses generated on an accurately fitting implant superstructure on multiple working casts made with a splinted impression technique. The effects of different tightening forces (10 and 20 Ncm) were assessed with the use of 30 stone casts made from a metal master model with a splinted impression technique. Stresses generated were recorded by 4 strain gauges attached to the superior surface of the master framework. A multiple analysis of variance with repeated measures was performed to test for significant differences among the groups. Tightening force values at 10 Ncm ranged from 150.43 to 256 Ncm. At 20 Ncm, microstrain values ranged from 149.43 to 284.37 Ncm. Microstrain values related to the sequence of tightening ranged from 150.8 to 308.43 Ncm (left to right) and 154.63 to 274.80 Ncm (right to left). For the different operators, microstrain values ranged from 100.13 to 206.07 Ncm. No statistically significant differences among the variables of tightening force, tightening sequence, and operators were found ( P >.05). The interaction between groups and strain gauges was also found to be nonsignificant (P >.05). The potential of variable tightening force and tightening sequence to generate unfavorable preload stresses can be minimized through use of the splinted impression technique, which ensures an accurately fitting superstructure.

Replicating Project LINC in Two Midwestern States. Implications for Policy Development.

ERIC Educational Resources Information Center

Westmoreland, Donna; Grigbsy, Karen; Brown, Linda; Latessa, Philip; Huber, Debra

1998-01-01

Project LINC (Ladders in Nursing Careers), a New York project to provide career advancement opportunities to disadvantaged nurses' aides and licensed practical nurses, was replicated in Iowa and North Dakota. Success factors included clear mission, organizational learning, learning contracts, financial aid, and shared commitment. Implications were…

The Temporal Regulation of S Phase Proteins During G1

PubMed Central

Grant, Gavin D.; Cook, Jeanette G.

2018-01-01

Successful DNA replication requires intimate coordination with cell cycle progression. Prior to DNA replication initiation in S phase, a series of essential preparatory events in G1 phase ensures timely, complete, and precise genome duplication. Among the essential molecular processes are regulated transcriptional upregulation of genes that encode replication proteins, appropriate post-transcriptional control of replication factor abundance and activity, and the assembly of DNA-loaded protein complexes to license replication origins. In this chapter we describe these critical G1 events necessary for DNA replication and their regulation in the context of both cell cycle entry and cell cycle progression. PMID:29357066

The path from student to mentor and from chromosomes to replication to genomics.

PubMed

Gerbi, Susan A

2016-11-01

The American Society for Cell Biology Women in Cell Biology Sandra Masur Senior Award recognizes leadership in scientific accomplishments and in mentoring, which are intertwined. My development as a scientist reflects important mentors in my life, including my father and Joe Gall, who is my "Doktor Vater." In turn, as an established investigator, my scientific successes in researching 1) chromosomes, their replication and genomics, and 2) ribosomes, their structure, evolution, and biogenesis, reflects the hard work of my students and postdocs, for whom I act as a mentor, guiding them in their research and along their career paths. © 2016 Gerbi. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Motor-driven screwing and transporting tool for reactor pressure vessel head retaining fastenings

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

Scholz, M.

1977-09-13

The invention concerns a motor-driven screwing and transporting tool for tightening or loosening the threaded studs and associated tightening nuts of the head bolting of pressure vessels. After the tightening nuts are loosened or before they are tightened, the weight of the studs is taken over by rotating bearings that can be lifted, so that the studs with their tightening nuts can be screwed in or out, the screw threads of the studs being thus weight-relieved. The invention is intended primarily for nuclear reactor pressure vessels. 21 claims, 6 figures.

Replication licensing and the DNA damage checkpoint

PubMed Central

Cook, Jeanette Gowen

2011-01-01

Accurate and timely duplication of chromosomal DNA requires that replication be coordinated with processes that ensure genome integrity. Significant advances in determining how the earliest steps in DNA replication are affected by DNA damage have highlighted some of the mechanisms to establish that coordination. Recent insights have expanded the relationship between the ATM and ATR-dependent checkpoint pathways and the proteins that bind and function at replication origins. These findings suggest that checkpoints and replication are more intimately associated than previously appreciated, even in the absence of exogenous DNA damage. This review summarizes some of these developments. PMID:19482602

Preloads generated with repeated tightening in three types of screws used in dental implant assemblies.

PubMed

Byrne, Declan; Jacobs, Stuart; O'Connell, Brian; Houston, Frank; Claffey, Noel

2006-01-01

Abutment screw loosening, especially in the case of cemented single tooth restorations, is a cause of implant restoration failure. This study compared three screws (titanium alloy, gold alloy, and gold-coated) with similar geometry by recording the preload induced when torques of 10, 20, and 35 Ncm were used for fixation. Two abutment types were used-prefabricated preparable abutments and cast-on abutments. A custom-designed rig was used to measure preload in the abutment-screw-implant assembly with a strain gauge. Ten screws of each type were sequentially tightened to 10, 20, and 35 Ncm on ten of the two abutment types. The same screws were then loosened and re-tightened. This procedure was repeated. Thus, each screw was tightened on three occasions to the three insertion torques. A linear regression model was used to analyze the effects on preload values of screw type and abutment type for each of the three insertion torques. The results indicated that the gold-coated screw generated the highest preloads for all insertion torques and for each tightening episode. Further analysis focused on the effects of screw type and abutment type for each episode of tightening and for each fixation torque. The gold-coated screw, fixed to the prefabricated abutment, displayed higher preloads for the first tightening at 10, 20, and 35 Ncm. Conversely, the same screw fixed to the cast-on abutment showed higher values for the second and third tightening for all fixation torques. All screws showed decay in preload with the number of times tightened. Given the higher preloads generated using the gold-coated screw with both abutment types, it is more likely that this type of screw will maintain a secure joint when tightened for the second and third time. All screw types displayed some decay in preload with repeated tightening, irrespective of abutment type and insertion torque. The gold-coated screw showed markedly higher preloads for all insertion torques and for all instances of tightening when compared with the uncoated screws.

Displacement of screw-retained single crowns into implants with conical internal connections.

PubMed

Yilmaz, Burak; Seidt, Jeremy D; McGlumphy, Edwin A; Clelland, Nancy L

2013-01-01

Internal conical implant-abutment connections without platforms may lead to axial displacement of crowns during screw tightening. This displacement may affect proximal contacts, incisal edge position, or occlusion. This study aimed to measure the displacement of screw-retained single crowns into an implant in three dimensions during screw tightening by hand or via torque driver. A stereolithic acrylic resin cast was created using computed tomography data from a patient missing the maxillary right central incisor. A 4.0- × 11-mm implant was placed in the edentulous site. Five porcelain-fused-to-metal single crowns were made using "cast-to" abutments. Crowns were tried on the stereolithic model, representing the patient, and hand tightened. The spatial relationship of crowns to the model after hand tightening was determined using three-dimensional digital image correlation (3D DIC), an optical measurement technique. The crowns were then tightened using a torque driver to 20 Ncm and the relative crown positions were again recorded. Testing was repeated three times for each crown, and displacement of the crowns was compared between the hand-tightened and torqued states. Commercial image correlation software was used to analyze the data. Mean vertical and horizontal crown displacement values were calculated after torqueing. The interproximal contacts were evaluated before and after torquing using an 8-μm aluminum foil shim. There were vertical and horizontal differences in crown positions between hand tightening and torqueing. Although these were small in magnitude, detectable displacements occurred in both apical and facial directions. After hand tightening, the 8-μm shim could be dragged without tearing. However, after torque tightening, the interproximal contacts were too tight and the 8-μm shim could not be dragged without tearing. Differences between hand tightening and torque tightening should be taken into consideration during laboratory and clinical adjustments to prevent esthetic and functional complications.

Dormant origins as a built-in safeguard in eukaryotic DNA replication against genome instability and disease development.

PubMed

Shima, Naoko; Pederson, Kayla D

2017-08-01

DNA replication is a prerequisite for cell proliferation, yet it can be increasingly challenging for a eukaryotic cell to faithfully duplicate its genome as its size and complexity expands. Dormant origins now emerge as a key component for cells to successfully accomplish such a demanding but essential task. In this perspective, we will first provide an overview of the fundamental processes eukaryotic cells have developed to regulate origin licensing and firing. With a special focus on mammalian systems, we will then highlight the role of dormant origins in preventing replication-associated genome instability and their functional interplay with proteins involved in the DNA damage repair response for tumor suppression. Lastly, deficiencies in the origin licensing machinery will be discussed in relation to their influence on stem cell maintenance and human diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of the Optimum Torque to Tighten the Smartpegs of Magnetic Resonance Frequency Analyses Devices: An Ex Vivo Study.

PubMed

Geckili, Onur; Cilingir, Altug; Bural, Canan; Bilmenoglu, Caglar; Bilhan, Hakan

2015-12-01

The aim of this study was to find an optimal value for tightening the Smartpegs for magnetic radiofrequency analysis devices (RFAs) devices. Thirty implants were placed in 3 cow ribs. The RFA value of each implant was measured in buccal and mesial directions after tightening the Smartpegs with 1, 3, 4, 8, 9, 10, and 11 Ncm. Additionally, 4 different examiners measured the RFA after hand tightening the Smartpegs, and the results were compared. The buccal implant stability quotient (ISQ) values when the Smartpegs were tightened to 1Ncm were significantly lower than the ISQ values when the Smartpegs were tightened to 3, 4, 8, 9, 10, and 11 Ncm (P < .05). The mesial ISQ values when the Smartpegs were tightened to 1, 3, and 4 Ncm were significantly lower than the ISQ values when the Smartpegs were tightened with higher torque values (P < .05). The buccal measurements made by 1 examiner was significantly lower than 3 Ncm (P < .05), and the buccal measurements made by 1 examiner was significantly lower than 4 Ncm (P < .05). The mesial ISQ values measured by 2 examiners were significantly lower than 3 Ncm (P < .05), and the mesial ISQ values measured by the other 2 examiners were significantly lower than 8 Ncm (P < .05). The tightening of the Smartpegs should be standardized by the manufacturer to a range of 5-8 Ncm in order to gain reliable objective RFA values, instead of leaving it to subjective finger pressure.

Microleakage of the prosthetic abutment/implant interface with internal and external connection: in vitro study.

PubMed

Larrucea Verdugo, Carlos; Jaramillo Núñez, Guido; Acevedo Avila, Ariel; Larrucea San Martín, Carlo

2014-09-01

This study determined the degree of marginal microleakage of the abutment-implant interface on platforms with Morse taper connection and external connection. For this in vitro study, 42 implants, 21 with external connection and 21 with Morse taper connection, were used, immersed in acrylic resin cylinders. Each implant was joined by a prosthetic abutment screw tightened at different degrees, forming the six study groups: (1) External connection, manual tightening (2) External connection, 20 Newton (N) tightening (3) External connection, 30 N tightening (4) Morse taper connection, manual tightening (5) Morse taper connection, 20 N tightening (6) orse taper connection, 30 N tightening. All samples were subjected to load cycling and thermocycling. Then, they were submerged in a solution of 0.2% methylene blue for 24 h. Finally, the microleakage was measured via 20× optical microscopy in each study group, average was obtained, and Mann-Whitney test was applied. Statistically significant differences (P < 0.001) were found between the levels of microleakage presented in the Morse taper connection implants (1.48) and external connection implants (2.8) in all three types of tightening. Microleakage levels decreases when increasing torque is applied to the screws. Morse taper connection implants showed lower levels of microleakage than external connection implants; also, it was observed that microleakage decreases in the way torque increases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effect of different screw-tightening techniques on the stress generated on an internal-connection implant superstructure.

PubMed

Choi, Jung-Han; Lim, Young-Jun; Kim, Chang-Whe; Kim, Myung-Joo

2009-01-01

This study evaluated the effect of different screw-tightening sequences, forces, and methods on the stresses generated on a well-fitting internal-connection implant (Astra Tech) superstructure. A metal framework directly connected to four parallel implants was fabricated on a fully edentulous mandibular resin model. Six stone casts with four implant replicas were made from a pickup impression of the superstructure to represent a "well-fitting" situation. Stresses generated by four screw-tightening sequences (1-2-3-4, 4-3-2-1, 2-4-3-1, and 2-3-1-4), two forces (10 and 20 Ncm), and two methods (one-step and two-step) were evaluated. In the two-step method, screws were tightened to the initial torque (10 Ncm) in a predetermined screw-tightening sequence and then to the final torque (20 Ncm) in the same sequence. Stresses were recorded twice by three strain gauges attached to the framework (superior face midway between abutments). Deformation data were analyzed using multiple analysis of variance at a .05 level of statistical significance. In all stone casts, stresses were produced by the superstructure connection, regardless of screw-tightening sequence, force, and method. No statistically significant differences for superstructure preload stresses were found based on screw-tightening sequences (-180.0 to -181.6 microm/m) or forces (-163.4 and -169.2 microm/m) (P > .05). However, different screw-tightening methods induced different stresses on the superstructure. The two-step screw-tightening method (-180.1 microm/m) produced significantly higher stress than the one-step method (-169.2 microm/m) (P = .0457). Within the limitations of this in vitro study, screw-tightening sequence and force were not critical factors in the stress generated on a well-fitting internal-connection implant superstructure. The stress caused by the two-step method was greater than that produced using the one-step method. Further studies are needed to evaluate the effect of screw-tightening techniques on preload stress in various different clinical situations.

A Role of hIPI3 in DNA Replication Licensing in Human Cells.

PubMed

Huang, Yining; Amin, Aftab; Qin, Yan; Wang, Ziyi; Jiang, Huadong; Liang, Lu; Shi, Linjing; Liang, Chun

2016-01-01

The yeast Ipi3p is required for DNA replication and cell viability in Sacharomyces cerevisiae. It is an essential component of the Rix1 complex (Rix1p/Ipi2p-Ipi1p-Ipi3p) that is required for the processing of 35S pre-rRNA in pre-60S ribosomal particles and for the initiation of DNA replication. The human IPI3 homolog is WDR18 (WD repeat domain 18), which shares significant homology with yIpi3p. Here we report that knockdown of hIPI3 resulted in substantial defects in the chromatin association of the MCM complex, DNA replication, cell cycle progression and cell proliferation. Importantly, hIPI3 silencing did not result in a reduction of the protein level of hCDC6, hMCM7, or the ectopically expressed GFP protein, indicating that protein synthesis was not defective in the same time frame of the DNA replication and cell cycle defects. Furthermore, the mRNA and protein levels of hIPI3 fluctuate in the cell cycle, with the highest levels from M phase to early G1 phase, similar to other pre-replicative (pre-RC) proteins. Moreover, hIPI3 interacts with other replication-initiation proteins, co-localizes with hMCM7 in the nucleus, and is important for the nuclear localization of hMCM7. We also found that hIPI3 preferentially binds to the origins of DNA replication including those at the c-Myc, Lamin-B2 and β-Globin loci. These results indicate that hIPI3 is involved in human DNA replication licensing independent of its role in ribosome biogenesis.

Effect of the coefficient of friction and tightening speed on the preload induced at the dental implant complex with the finite element method.

PubMed

Bulaqi, Haddad Arabi; Mousavi Mashhadi, Mahmoud; Geramipanah, Farideh; Safari, Hamed; Paknejad, Mojgan

2015-05-01

To prevent screw loosening, a clear understanding of the factors influencing secure preload is necessary. The purpose of this study was to investigate the effect of coefficient of friction and tightening speed on screw tightening based on energy distribution method with exact geometric modeling and finite element analysis. To simulate the proper boundary conditions of the screw tightening process, the supporting bone of an implant was considered. The exact geometry of the implant complex, including the Straumann dental implant, direct crown attachment, and abutment screw were modeled with Solidworks software. Abutment screw/implant and implant/bone interfaces were designed as spiral thread helixes. The screw-tightening process was simulated with Abaqus software, and to achieve the target torque, an angular displacement was applied to the abutment screw head at different coefficients of friction and tightening speeds. The values of torque, preload, energy distribution, elastic energy, and efficiency were obtained at the target torque of 35 Ncm. Additionally, the torque distribution ratio and preload simulated values were compared to theoretically predicted values. Upon reducing the coefficient of friction and enhancing the tightening speed, the angle of turn increased at the target torque. As the angle of turn increased, the elastic energy and preload also increased. Additionally, by increasing the coefficient of friction, the frictional dissipation energy increased but the efficiency decreased, whereas the increase in tightening speed insignificantly affected efficiency. The results of this study indicate that the coefficient of friction is the most influential factor on efficiency. Increasing the tightening speed lowered the response rate to the frictional resistance, thus diminishing the coefficient of friction and slightly increasing the preload. Increasing the tightening speed has the same result as reducing the coefficient of friction. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

The effect of the use of a counter-torque device on the abutment-implant complex.

PubMed

Lang, L A; May, K B; Wang, R F

1999-04-01

Little is known about the condition of the abutment-screw joint before loading, after the development of the preload. This study examined the tightening force transmitted to the implant with and without the use of a counter-torque device during the tightening of the abutment screw. Forty Brânemark implants and 10 CeraOne, Estheticone, Procera, and AurAdapt abutments formed the experimental populations. Samples in each group were further divided into 2 groups, 1 group was tightened with a torque controller without the use of a counter-torque device, whereas the other used the counter-torque device. Samples were positioned in a special holder within the grips of a Tohnichi BTG-6 torque gauge for measuring transmitted forces. There were significant differences (P =. 0001) in the tightening forces transmitted to the implant with and without the use of a counter-torque device when tightening the abutment screws. An average of 91% of the recommended preload tightening torque was transmitted to the implant-bone interface in the absence of a counter-torque device. In all abutment systems, less than 10% of the recommended preload tightening torque was transmitted to the implant when the counter-torque device was used.

Fixtures Hold Nuts During Tightening Of Bolts

NASA Technical Reports Server (NTRS)

Gyekenyesi, John Z.

1993-01-01

Two fixtures designed for use on cross-head of tensile testing machine simplify adjustments of crosshead to accommodate specimens of various lengths. Two cagelike fixtures hold pairs of nuts, preventing nuts from turning while bolts are tightened. Enable one person acting alone to tighten bolts.

Tightening force and torque of nonlocking screws in a reverse shoulder prosthesis.

PubMed

Terrier, A; Kochbeck, S H; Merlini, F; Gortchacow, M; Pioletti, D P; Farron, A

2010-07-01

Reversed shoulder arthroplasty is an accepted treatment for glenohumeral arthritis associated to rotator cuff deficiency. For most reversed shoulder prostheses, the baseplate of the glenoid component is uncemented and its primary stability is provided by a central peg and peripheral screws. Because of the importance of the primary stability for a good osteo-integration of the baseplate, the optimal fixation of the screws is crucial. In particular, the amplitude of the tightening force of the nonlocking screws is clearly associated to this stability. Since this force is unknown, it is currently not accounted for in experimental or numerical analyses. Thus, the primary goal of this work is to measure this tightening force experimentally. In addition, the tightening torque was also measured, to estimate an optimal surgical value. An experimental setup with an instrumented baseplate was developed to measure simultaneously the tightening force, tightening torque and screwing angle, of the nonlocking screws of the Aquealis reversed prosthesis. In addition, the amount of bone volume around each screw was measured with a micro-CT. Measurements were performed on 6 human cadaveric scapulae. A statistically correlated relationship (p<0.05, R=0.83) was obtained between the maximal tightening force and the bone volume. The relationship between the tightening torque and the bone volume was not statistically significant. The experimental relationship presented in this paper can be used in numerical analyses to improve the baseplate fixation in the glenoid bone. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Chassis unit insert tightening-extract device

NASA Technical Reports Server (NTRS)

Haerther, L. W.; Zimmerman, P. A. (Inventor)

1964-01-01

The invention relates to the insertion and extraction of rack mounted electronic units and in particular to a screw thread insert tightening and extract device, for chassis units having a collar which may be rotatably positioned manually for the insert tightening or extraction of various associated chassis units, as desired.

78 FR 23686 - Airworthiness Directives; Eurocopter France Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

.... Interference from this missing blind hole does not permit correct axial tightening of the TGB casing, even if the correct torque load is applied to the attachment bolt. Insufficient tightening of the bolt can..., could result in insufficient tightening of the TGB casing, damage to the TGB attachment, cracking under...

DNA Replication Origins and Fork Progression at Mammalian Telomeres

PubMed Central

Higa, Mitsunori; Fujita, Masatoshi; Yoshida, Kazumasa

2017-01-01

Telomeres are essential chromosomal regions that prevent critical shortening of linear chromosomes and genomic instability in eukaryotic cells. The bulk of telomeric DNA is replicated by semi-conservative DNA replication in the same way as the rest of the genome. However, recent findings revealed that replication of telomeric repeats is a potential cause of chromosomal instability, because DNA replication through telomeres is challenged by the repetitive telomeric sequences and specific structures that hamper the replication fork. In this review, we summarize current understanding of the mechanisms by which telomeres are faithfully and safely replicated in mammalian cells. Various telomere-associated proteins ensure efficient telomere replication at different steps, such as licensing of replication origins, passage of replication forks, proper fork restart after replication stress, and dissolution of post-replicative structures. In particular, shelterin proteins have central roles in the control of telomere replication. Through physical interactions, accessory proteins are recruited to maintain telomere integrity during DNA replication. Dormant replication origins and/or homology-directed repair may rescue inappropriate fork stalling or collapse that can cause defects in telomere structure and functions. PMID:28350373

DUB3 and USP7 de-ubiquitinating enzymes control replication inhibitor Geminin: molecular characterization and associations with breast cancer.

PubMed

Hernández-Pérez, S; Cabrera, E; Salido, E; Lim, M; Reid, L; Lakhani, S R; Khanna, K K; Saunus, J M; Freire, R

2017-08-17

Correct control of DNA replication is crucial to maintain genomic stability in dividing cells. Inappropriate re-licensing of replicated origins is associated with chromosomal instability (CIN), a hallmark of cancer progression that at the same time provides potential opportunities for therapeutic intervention. Geminin is a critical inhibitor of the DNA replication licensing factor Cdt1. To properly achieve its functions, Geminin levels are tightly regulated through the cell cycle by ubiquitin-dependent proteasomal degradation, but the de-ubiquitinating enzymes (DUBs) involved had not been identified. Here we report that DUB3 and USP7 control human Geminin. Overexpression of either DUB3 or USP7 increases Geminin levels through reduced ubiquitination. Conversely, depletion of DUB3 or USP7 reduces Geminin levels, and DUB3 knockdown increases re-replication events, analogous to the effect of Geminin depletion. In exploring potential clinical implications, we found that USP7 and Geminin are strongly correlated in a cohort of invasive breast cancers (P<1.01E-08). As expected, Geminin expression is highly prognostic. Interestingly, we found a non-monotonic relationship between USP7 and breast cancer-specific survival, with both very low or high levels of USP7 associated with poor outcome, independent of estrogen receptor status. Altogether, our data identify DUB3 and USP7 as factors that regulate DNA replication by controlling Geminin protein stability, and suggest that USP7 may be involved in Geminin dysregulation during breast cancer progression.

78 FR 70205 - Airworthiness Directives; Eurocopter France Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

... 332 L2 and Model EC 225 LP helicopters. According to EASA, analysis of tightening torques revealed some cases of tightening torque loss, which can lead to the formation of a crack at the MGB bar... rear of the MGB bar attaching fittings for tightening torque loss and, if the loss is equal to or...

Skin tightening.

PubMed

Woolery-Lloyd, Heather; Kammer, Jenna N

2011-01-01

Skin tightening describes the treatment of skin laxity via radiofrequency (RF), ultrasound, or light-based devices. Skin laxity on the face is manifested by progressive loss of skin elasticity, loosening of the connective tissue framework, and deepening of skin folds. This results in prominence of submandibular and submental tissues. Genetic factors (chronological aging) and extrinsic factors (ultraviolet radiation) both contribute to skin laxity. There are many RF, ultrasound, and light-based devices directed at treating skin laxity. All of these devices target and heat the dermis to induce collagen contraction. Heating of the dermis causes collagen denaturation and immediate collagen contraction in addition to long-term collagen remodeling. Via RF, light, or ultrasound, these skin tightening devices deliver heat to the dermis to create new collagen and induce skin tightening. This chapter will provide an overview of the various skin tightening devices. Copyright © 2011 S. Karger AG, Basel.

The effect of different screw-tightening techniques on the strain generated on an internal-connection implant superstructure. Part 2: Models created with a splinted impression technique.

PubMed

Choi, Jung-Han

2011-01-01

This study aimed to evaluate the effect of different screw-tightening sequences, torques, and methods on the strains generated on an internal-connection implant (Astra Tech) superstructure with good fit. An edentulous mandibular master model and a metal framework directly connected to four parallel implants with a passive fit to each other were fabricated. Six stone casts were made from a dental stone master model by a splinted impression technique to represent a well-fitting situation with the metal framework. Strains generated by four screw-tightening sequences (1-2-3-4, 4-3-2-1, 2-4-3-1, and 2-3-1-4), two torques (10 and 20 Ncm), and two methods (one-step and two-step) were evaluated. In the two-step method, screws were tightened to the initial torque (10 Ncm) in a predetermined screw-tightening sequence and then to the final torque (20 Ncm) in the same sequence. Strains were recorded twice by three strain gauges attached to the framework (superior face midway between abutments). Deformation data were analyzed using multiple analysis of variance at a .05 level of statistical significance. In all stone casts, strains were produced by connection of the superstructure, regardless of screw-tightening sequence, torque, and method. No statistically significant differences in superstructure strains were found based on screw-tightening sequences (range, -409.8 to -413.8 μm/m), torques (-409.7 and -399.1 μm/m), or methods (-399.1 and -410.3 μm/m). Within the limitations of this in vitro study, screw-tightening sequence, torque, and method were not critical factors for the strain generated on a well-fitting internal-connection implant superstructure by the splinted impression technique. Further studies are needed to evaluate the effect of screw-tightening techniques on the preload stress in various different clinical situations.

Measurements of Repeated Tightening and Loosening Torque of Seven Different Implant/Abutment Connection Designs and Their Modifications: An In Vitro Study.

PubMed

Butkevica, Alena; Nathanson, Dan; Pober, Richard; Strating, Herman

2018-02-01

Repeated tightening and loosening of the abutment screw may alter its mechanical and physical properties affecting the optimal torque and ultimate reliability of an implant/abutment connection. The purpose of this study was to evaluate the effect of repeated tightening and loosening of implant/abutment screws on the loosening torque of implant/abutment connections of commercially available implant systems. Seven different implant/abutment connections and their modifications were tested. The screws of each system were tightened according to the manufacturer's specifications. After 20 minutes the screws were loosened. This procedure was repeated ten times, and the differences between the 1st and 10th cycle were expressed as a percentage change RTq(%) and correlated with initial torque, the number of threads, the length of shank, and thread surface area employing Spearman's analysis. All systems showed significant differences in residual torque (RTq) value (p < 0.05) between the 1st and 10th cycle except groups 6 and 11 (p > 0.05). All connections but group 3 (p = 1.000) showed a significant change from the initial torque (ITq) to the RTq values. The first successive RTq values increased in two connection groups 1 and 2. The remaining connections showed reduced RTq values ranging from -1.2 % (group 5) to -23.5% (group 6). The RTq values declined gradually with every repeated tightening in groups 1, 2, 3, 8, 9, 11, 12. In group 2, after the tenth tightening the RTq was still above the ITq value. Only length of shank demonstrated a correlation with the RTq(%) change over the successive tightening loosening cycles (p < 0.05). Repeated tightening and loosening of implant/abutment screws caused varying torque level changes among the different systems. These observations can probably be attributed to connection design. Limiting the number of tightening/loosening cycles in clinical and laboratory procedures is advisable for most of the implant systems tested. © 2016 by the American College of Prosthodontists.

Long-term Nasal and Peri-oral Tightening by a Single Fractional Noninsulated Microneedle Radiofrequency Treatment

PubMed Central

2017-01-01

Background: The skin tightening effects induced by non-insulated microneedle radiofrequency have proved long-lasting. Our previous three-dimensional volumetric assessment showed significant facial tightening for up to six months. However, nasal and peri-oral tightening effects lasted longer. The objective of this study was to investigate the distribution of the long-term volumetric reduction in facial area induced by a single fractional non-insulated microneedle radiofrequency treatment. Methods: Fifteen Asian patients underwent full facial skin tightening using a sharply tapered non-insulated microneedle radiofrequency applicator with a novel fractionated pulse mode. Three-dimensional volumetric assessments were performed at six and 12 months post-treatment. Patients rated their satisfaction using a 5-point scale at each follow up. Results: Objective assessments with superimposed three-dimensional color images showed significant volumetric reduction in the nasal and peri-oral areas at 12 months post-treatment in all patients. Median volumetric reductions at six and 12 months post-treatment were 13.1 and 12.3ml, respectively. All of the patients were satisfied with their results 12 months post-treatment. Side effects were not observed. Conclusions: This single fractional NIMNRF treatment provided long-lasting nasal and peri-oral tightening as shown via 3D volumetric assessment. Moreover, NIMNRF produced minimal complications, downtime, and few side effects. This approach provides safe and effective treatment of skin tightening. PMID:28367261

Automated Bone Screw Tightening to Adaptive Levels of Stripping Torque.

PubMed

Reynolds, Karen J; Mohtar, Aaron A; Cleek, Tammy M; Ryan, Melissa K; Hearn, Trevor C

2017-06-01

To use relationships between tightening parameters, related to bone quality, to develop an automated system that determines and controls the level of screw tightening. An algorithm relating current at head contact (IHC) to current at construct failure (Imax) was developed. The algorithm was used to trigger cessation of screw insertion at a predefined tightening level, in real time, between head contact and maximum current. The ability of the device to stop at the predefined level was assessed. The mean (±SD) current at which screw insertion ceased was calculated to be [51.47 ± 9.75% × (Imax - IHC)] + IHC, with no premature bone failures. A smart screwdriver was developed that uses the current from the motor driving the screw to predict the current at which the screw will strip the bone threads. The device was implemented and was able to achieve motor shut-off and cease tightening at a predefined threshold, with no premature bone failures.

76 FR 53312 - Airworthiness Directives; Agusta S.p.A. Model A109A and A109AII Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... disassembling the tail rotor hub and blades assembly and inspecting for damage. If the tightening torque value..., and no further action is required. If the tightening torque value is greater than 700 kgcm, the hub plug must be replaced with an airworthy part. Torque the new hub plug to the specified tightening...

Commercial motorcycle drivers' perceptions of risk and road safety in urban Nigeria: an explorative study.

PubMed

Sanusi, Adebayo Adesola; Emmelin, Maria

2015-01-01

Road traffic injury is a great public health challenge with an emerging trend of increasing rates and high mortality involving commercial motorcycles in Nigeria. A qualitative approach was used with 10 in-depth interviews conducted to explore the risk perceptions of commercial motorcyclists in Ibadan, Nigeria. The data analysis using manifest and latent content analysis resulted in an overarching theme: inadequate structures and internalised norms prevent change. The three themes leading to the overarching theme are: risk-taking as generally acceptable; risk-taking as an intrinsic part of occupation; and risk-taking as a way to make ends meet. The study suggests that there is a great need for adequate regulation as regards training and licensing of riders. Also the need to tighten enforcement of traffic rules is paramount to road safety in Nigeria.

Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae.

PubMed

Oling, David; Masoom, Rehan; Kvint, Kristian

2014-06-15

Ubp3 is a conserved ubiquitin protease that acts as an antisilencing factor in MAT and telomeric regions. Here we show that ubp3∆ mutants also display increased silencing in ribosomal DNA (rDNA). Consistent with this, RNA polymerase II occupancy is lower in cells lacking Ubp3 than in wild-type cells in all heterochromatic regions. Moreover, in a ubp3∆ mutant, unequal recombination in rDNA is highly suppressed. We present genetic evidence that this effect on rDNA recombination, but not silencing, is entirely dependent on the silencing factor Sir2. Further, ubp3∆ sir2∆ mutants age prematurely at the same rate as sir2∆ mutants. Thus our data suggest that recombination negatively influences replicative life span more so than silencing. However, in ubp3∆ mutants, recombination is not a prerequisite for aging, since cells lacking Ubp3 have a shorter life span than isogenic wild-type cells. We discuss the data in view of different models on how silencing and unequal recombination affect replicative life span and the role of Ubp3 in these processes. © 2014 Öling et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A novel non-invasive radiofrequency dermal heating device for skin tightening of the face and neck.

PubMed

Nelson, Andrew A; Beynet, David; Lask, Gary P

2015-01-01

Loose, lax skin is a common cosmetic complaint. Previous non-invasive skin tightening devices had modest efficacy and were associated with pain or downtime. New technologies may allow for effective skin tightening with a series of radiofrequency (RF) treatments with no downtime. To evaluate the efficacy and safety of a novel bipolar RF device for skin tightening. Fifteen consecutive female patients were enrolled in the case series; 14 completed the study and were included in the analysis. The device under investigation is a novel, bipolar RF device allowing for achievement and maintenance of optimal dermal temperatures to stimulate collagen remodeling and skin tightening. Patients underwent a series of 4-6 weekly treatments. Three blinded, experienced cosmetic physicians evaluated paired pre-treatment and post-treatment photographs and determined the associated improvement, if any. All patients (14/14) were determined to have a clinical improvement, as the pre-treatment and post-treatment photographs were correctly identified by the evaluators. It was observed that 21% (3/14) of patients had significant improvement, 50% (7/14) had moderate improvement, and 29% (4/14) had mild improvement. No pain, side effects, or adverse events were observed. This novel bipolar RF device represents a safe, effective treatment option for non-invasive skin tightening.

Dynamic fatigue performance of implant-abutment assemblies with different tightening torque values.

PubMed

Xia, Dandan; Lin, Hong; Yuan, Shenpo; Bai, Wei; Zheng, Gang

2014-01-01

Implant-abutment assemblies are usually subject to long-term cyclic loading. To evaluate the dynamic fatigue performance of implant-abutment assemblies with different tightening torque values, thirty implant-abutment assemblies (Zimmer Dental, Carlsbad, CA, USA) were randomly assigned to three tightening groups (24 Ncm; 30 Ncm; 36 Ncm), each consisted of 10 implants. Five specimens from each group were unscrewed, and their reverse torque values recorded. The remaining specimens were subjected to a load between 30 N~300 N at a loading frequency of 15 Hz for 5 × 10(6) cycles. After fatigue tests, residual reverse torque values were recorded if available. In the 24 Ncm tightening group, all the implants fractured at the first outer thread of the implant after fatigue loading, with fatigue crack propagation at the fractured surface showed by SEM observation. For the 30 Ncm and 36 Ncm tightening groups, a statistical significant difference (p<0.05) between the unloaded and loaded groups was revealed. Compared with the unloaded specimens, the specimens went through fatigue loading had decreased reverse torque values. It was demonstrated that insufficient torque will lead to poor fatigue performance of dental implant-abutment assemblies and abutment screws should be tightened to the torque recommended by the manufacturer. It was also concluded that fatigue loading would lead to preload loss.

Dynamic interaction of Y RNAs with chromatin and initiation proteins during human DNA replication

PubMed Central

Zhang, Alice Tianbu; Langley, Alexander R.; Christov, Christo P.; Kheir, Eyemen; Shafee, Thomas; Gardiner, Timothy J.; Krude, Torsten

2011-01-01

Non-coding Y RNAs are required for the initiation of chromosomal DNA replication in mammalian cells. It is unknown how they perform this function or if they associate with a nuclear structure during DNA replication. Here, we investigate the association of Y RNAs with chromatin and their interaction with replication proteins during DNA replication in a human cell-free system. Our results show that fluorescently labelled Y RNAs associate with unreplicated euchromatin in late G1 phase cell nuclei before the initiation of DNA replication. Following initiation, Y RNAs are displaced locally from nascent and replicated DNA present in replication foci. In intact human cells, a substantial fraction of endogenous Y RNAs are associated with G1 phase nuclei, but not with G2 phase nuclei. Y RNAs interact and colocalise with the origin recognition complex (ORC), the pre-replication complex (pre-RC) protein Cdt1, and other proteins implicated in the initiation of DNA replication. These data support a molecular ‘catch and release’ mechanism for Y RNA function during the initiation of chromosomal DNA replication, which is consistent with Y RNAs acting as replication licensing factors. PMID:21610089

Role of the Windlass in Improvised Tourniquet Use on a Manikin Hemorrhage Model

DTIC Science & Technology

2015-01-01

windlass to better understand the role of the windlass in tightening the tourniquet strap. Methods: An experiment was designed to test the...longer bystanders, these responders gave first aid by wrapping and tightening a shirt around a limb, and these makeshift tourniquets reportedly helped...improvising tourniquets is to twist a strap with a windlass to gain mechanical advantage in tightening . However, to our knowledge, no one in Boston

Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

PubMed

Fenwick, Aimee L; Kliszczak, Maciej; Cooper, Fay; Murray, Jennie; Sanchez-Pulido, Luis; Twigg, Stephen R F; Goriely, Anne; McGowan, Simon J; Miller, Kerry A; Taylor, Indira B; Logan, Clare; Bozdogan, Sevcan; Danda, Sumita; Dixon, Joanne; Elsayed, Solaf M; Elsobky, Ezzat; Gardham, Alice; Hoffer, Mariette J V; Koopmans, Marije; McDonald-McGinn, Donna M; Santen, Gijs W E; Savarirayan, Ravi; de Silva, Deepthi; Vanakker, Olivier; Wall, Steven A; Wilson, Louise C; Yuregir, Ozge Ozalp; Zackai, Elaine H; Ponting, Chris P; Jackson, Andrew P; Wilkie, Andrew O M; Niedzwiedz, Wojciech; Bicknell, Louise S

2016-07-07

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

DNA replication machinery is required for development in Drosophila.

PubMed

Kohzaki, Hidetsugu; Asano, Maki; Murakami, Yota

2018-01-01

 In Drosophila , some factors involved in chromosome replication seem to be involved in gene amplification and endoreplication, which are actively utilized in particular tissue development, but direct evidence has not been shown. Therefore, we examined the effect of depletion of replication factors on these processes. First, we confirmed RNAi knockdown can be used for the depletion of replication factors by comparing the phenotypes of RNAi knockdown and deletion or point mutants of the components of DNA licensing factor, MCM2, MCM4 and Cdt1. Next, we found that tissue-specific RNAi knockdown of replication factors caused tissue-specific defects, probably due to defects in DNA replication. In particular, we found that depletion inhibited gene amplification of the chorion gene in follicle cells and endoreplication in salivary glands, showing that chromosomal DNA replication factors are required for these processes. Finally, using RNAi, we screened the genes for chromosomal DNA replication that affected tissue development. Interestingly, wing specific knockdown of Mcm10 induced wing formation defects. These results suggest that some components of chromosomal replication machinery are directly involved in tissue development.

Alcohol environments and disparities in exposure associated with adolescent drinking in California.

PubMed

Truong, Khoa Dang; Sturm, Roland

2009-02-01

We investigated sociodemographic disparities in alcohol environments and their relationship with adolescent drinking. We geocoded and mapped alcohol license data with ArcMap to construct circular buffers centered at 14 595 households with children that participated in the California Health Interview Survey. We calculated commercial sources of alcohol in each buffer. Multivariate logistic regression differentiated the effects of alcohol sales on adolescents' drinking from their individual, family, and neighborhood characteristics. Alcohol availability, measured by mean and median number of licenses, was significantly higher around residences of minority and lower-income families. Binge drinking and driving after drinking among adolescents aged 12 to 17 years were significantly associated with the presence of alcohol retailers within 0.5 miles of home. Simulation of changes in the alcohol environment showed that if alcohol sales were reduced from the mean number of alcohol outlets around the lowest-income quartile of households to that of the highest quartile, prevalence of binge drinking would fall from 6.4% to 5.6% and driving after drinking from 7.9% to 5.9%. Alcohol outlets are concentrated in disadvantaged neighborhoods and can contribute to adolescent drinking. To reduce underage drinking, environmental interventions need to curb opportunities for youth to obtain alcohol from commercial sources by tightening licensure, enforcing minimum-age drinking laws, or other measures.

Screw joint stability after the application of retorque in implant-supported dentures under simulated masticatory conditions.

PubMed

Farina, Ana Paula; Spazzin, Aloísio Oro; Consani, Rafael Leonardo Xediek; Mesquita, Marcelo Ferraz

2014-06-01

Screws can loosen through mechanisms that have not been clearly established. The purpose of this study was to evaluate the influence of the tightening technique (the application of torque and retorque on the joint stability of titanium and gold prosthetic screws) in implant-supported dentures under different fit levels after 1 year of simulated masticatory function by means of mechanical cycling. Ten mandibular implant-supported dentures were fabricated, and 20 cast models were prepared by using the dentures to create 2 fit levels: passive fit and created misfit. The tightening protocol was evaluated according to 4 distinct profiles: without retorque plus titanium screws, without retorque plus gold screws, retorque plus titanium screws, and retorque plus gold screws. In the retorque application, the screws were tightened to 10 Ncm and retightened to 10 Ncm after 10 minutes. The screw joint stability after 1 year of simulated clinical function was measured with a digital torque meter. Data were analyzed statistically by 2-way ANOVA and Tukey honestly significant difference (HSD) post hoc tests (α=.05). The factors of fit level and tightening technique as well as the interaction between the factors, were statistically significant. The misfit decreases the loosening torque. The retorque application increased joint stability independent of fit level or screw material, which suggests that this procedure should be performed routinely during the tightening of these devices. All tightening techniques revealed reduced loosening torque values that were significantly lower in misfit dentures than in passive fit dentures. However, the retorque application significantly increased the loosening torque when titanium and gold screws were used. Therefore, this procedure should be performed routinely during screw tightening. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Comparison of the passivity between cast alloy and laser-welded titanium overdenture bars.

PubMed

Paiva, Jose; Givan, Daniel A; Broome, James C; Lemons, Jack E; McCracken, Michael S

2009-12-01

The purpose of this study was to investigate the fit of cast alloy overdenture and laser-welded titanium-alloy bars by measuring induced strain upon tightening of the bars on a master cast as well as a function of screw tightening sequence. Four implant analogs were secured into Type IV dental stone to simulate a mandibular edentulous patient cast, and two groups of four overdenture bars were fabricated. Group I was four cast alloy bars and Group II was four laser-welded titanium bars. The cast alloy bars included Au-Ag-Pd, Pd-Ag-Au, Au-Ag-Cu-Pd, and Ag-Pd-Cu-Au, while the laser-welded bars were all Ti-Al-V alloy. Bars were made from the same master cast, were torqued into place, and the total strain in the bars was measured through five strain gauges bonded to the bar between the implants. Each bar was placed and torqued 27 times to 30 Ncm per screw using three tightening sequences. Data were processed through a strain amplifier and analyzed by computer using StrainSmart software. Data were analyzed by ANOVA and Tukey's post hoc test. Significant differences were found between alloy types. Laser-welded titanium bars tended to have lower strains than corresponding cast bars, although the Au-Ag-Pd bar was not significantly different. The magnitudes of total strain were the least when first tightening the ends of the bar. The passivity of implant overdenture bars was evaluated using total strain of the bar when tightening. Selecting a high modulus of elasticity cast alloy or use of laser-welded bar design resulted in the lowest average strain magnitudes. While the effect of screw tightening sequence was minimal, tightening the distal ends first demonstrated the lowest strain, and hence the best passivity.

Displacement of screw-retained splinted and nonsplinted restorations into implants with conical internal connections.

PubMed

Yilmaz, Burak; Seidt, Jeremy D; Clelland, Nancy L

2014-01-01

Variable abutment displacement could potentially affect proximal contacts, incisal edge position, or occlusion of implant-supported prostheses. This study aimed to measure and compare displacements of splinted and nonsplinted restorations into implants featuring internal conical connections as screws were tightened by hand or by torque driver. A stereolithic resin model was printed using computed tomography data from a patient missing mandibular left first and second molars. Two 5.0 × 11-mm implants were placed in the edentulous site using a surgical guide. Two sets (splinted and nonsplinted) of gold screw-retained prostheses were made indirectly to fit the implants in the stereolithic model representing the patient. The axial position of the crowns relative to a fixed location on the model was recorded following hand tightening using the three-dimensional image correlation technique and image correlation software. A pair of high-resolution digital cameras provided a synchronized view of the model during the experiment. Relative crown positions were again recorded after tightening with a torque driver to 25 Ncm. Testing was repeated randomly three times for each set of crowns. Displacement data after torque tightening were compared using a factorial analysis of variance with JMP 9.0 software (SAS) followed by a Tukey-Kramer post hoc test (α = .05). Interproximal contacts were evaluated using an 8-μm tin foil shim after tightening by hand and torque driver. Displacements for splinted and nonsplinted restorations differed only in a buccal direction. The nonsplinted crowns displaced significantly more than splinted crowns. Discernible differences were observed for the tin foil shim when dragged through proximal contacts following hand versus torque tightening. Differences between screw tightening by hand or torque driver should be taken into consideration during laboratory and clinical adjustments to prevent esthetic and functional complications.

Variation in the total lengths of abutment/implant assemblies generated with a function of applied tightening torque in external and internal implant-abutment connection.

PubMed

Kim, Ki-Seong; Lim, Young-Jun; Kim, Myung-Joo; Kwon, Ho-Beom; Yang, Jae-Ho; Lee, Jai-Bong; Yim, Soon-Ho

2011-08-01

Settling (embedment relaxation), which is the main cause for screw loosening, is developed by microroughness between implant and abutment metal surface. The objective of this study was to evaluate and compare the relationship between the level of applied torque and the settling of abutments into implants in external and internal implant-abutment connection. Five different implant-abutment connections were used (Ext, External butt joint + two-piece abutment; Int-H2, Internal hexagon + two-piece abutment; Int-H1, Internal hexagon + one-piece abutment; Int-O2, Internal octagon + two-piece abutment; Int-O1, Internal octagon + one-piece abutment). All abutments of each group were assembled and tightened with corresponding implants by a digital torque gauge. The total lengths of implant-abutment samples were measured at each torque (5, 10, 30 N cm and repeated 30 N cm with 10-min interval) by an electronic digital micrometer. The settling values were calculated by changes between the total lengths of implant-abutment samples. All groups developed settling with repeated tightening. The Int-H2 group showed markedly higher settling for all instances of tightening torque and the Ext group was the lowest. Statistically significant differences were found in settling values between the groups and statistically significant increases were observed within each group at different tightening torques (P<0.05). After the second tightening of 30 N cm, repeated tightening showed almost constant settling values. Results from the present study suggested that to minimize the settling effect, abutment screws should be retightened at least twice at 30 N cm torque at a 10-min interval in all laboratory and clinical procedures. © 2010 John Wiley & Sons A/S.

Design of a Combined Ballistic Simulator and Primer Force Experimental Fixture

DTIC Science & Technology

2015-08-01

preload bolt and breech, and between the breech and chamber, were found to be too loose. When heavy grease or Teflon tape was used to tighten the...increase the difficulty of removing and tightening the breech. The preload bolt does not have to be removed between firing and in future designs could use... tightened it could loosen the primer plate, so left-handed threads were machined on the primer plate. The ballistic simulator fixture was occasionally

Development of Anti-Loosening Performance of Hyper Lock Nut

NASA Astrophysics Data System (ADS)

Nishiyama, Shuji; Migita, Hiroaki; Kataoka, Mitumasa; Nakasaki, Nobuyuki; Murano, Kohshi

Bolted joints are widely used in mechanical structures as they allow easy disassembly for maintenance without high cost. However, vibration-induced loosening due to dynamic loading remains a long-unresolved issue. We have developed a new type of nut named the hyper lock nut (HLN) that offers anti-loosening performance without a complicated tightening process and tools. In this study, we investigated the mechanisms of joints bolted with the HLN, and tightening behavior was analyzed using the three-dimensional finite element method. The analytical results were compared with the experimental results for the HLN, and close qualitative agreement was observed between the two with respect to displacement, tightening force and tightening torque. We found a number of new aspects and plus points for joints bolted with the HLN in comparison to those fastened with JIS standard nuts. It was found that the tightening torque of the HLN is higher than that of JIS standard nuts, and that satisfactory anti-loosening performance can be realized through the thread contact force at the slit region and the angular face of the bearing surface.

Loss of preload in screwed implant joints as a function of time and tightening/untightening sequences.

PubMed

Bernardes, Sérgio Rocha; da Gloria Chiarello de Mattos, Maria; Hobkirk, John; Ribeiro, Ricardo Faria

2014-01-01

The purpose of this study was to determine whether abutment screw tightening and untightening influenced loss of preload in three different implant/abutment interfaces, or on the implant body. Five custom-fabricated machined titanium implants were used, each with its respective abutment, with different connection types, retention screws, and torque values (external hexagon with titanium screw/32 Ncm, external hexagon with coated screw/32 Ncm, internal hexagon/20 Ncm and internal conical/20 and 32 Ncm). Each implant tested had two strain gauges attached and was submitted to five tightening/untightening sequences. External hexagons resulted in the lowest preload values generated in the implant cervical third (mean of 27.75 N), while the internal hexagon had the highest values (mean of 219.61 N). There was no immediate significant loss of preload after screw tightening. Tightening/untightening sequences, regardless of the implant/abutment interface design or type of screw used in the study, did not result in any significant loss of initial preload. Conical implant connections demonstrated greater structural reinforcement within the internal connections.

Stresses in Implant-Supported Fixed Complete Dentures with Different Screw-Tightening Sequences and Torque Application Modes.

PubMed

Barcellos, Leonardo H; Palmeiro, Marina Lobato; Naconecy, Marcos M; Geremia, Tomás; Cervieri, André; Shinkai, Rosemary S

2018-05-17

To compare the effects of different screw-tightening sequences and torque applications on stresses in implant-supported fixed complete dentures supported by five abutments. Strain gauges fixed to the abutments were used to test the sequences 2-4-3-1-5; 1-2-3-4-5; 3-2-4-1-5; and 2-5-4-1-3 with direct 10-Ncm torque or progressive torque (5 + 10 Ncm). Data were analyzed using analysis of variance and standardized effect size. No effects of tightening sequence or torque application were found except for the sequence 3-2-4-1-5 and some small to moderate effect sizes. Screw-tightening sequences and torque application modes have only a marginal effect on residual stresses.

Analysis of re-replication from deregulated origin licensing by DNA fiber spreading

PubMed Central

Dorn, Elizabeth S.; Chastain, Paul D.; Hall, Jonathan R.; Cook, Jeanette Gowen

2009-01-01

A major challenge each human cell-division cycle is to ensure that DNA replication origins do not initiate more than once, a phenomenon known as re-replication. Acute deregulation of replication control ultimately causes extensive DNA damage, cell-cycle checkpoint activation and cell death whereas moderate deregulation promotes genome instability and tumorigenesis. In the absence of detectable increases in cellular DNA content however, it has been difficult to directly demonstrate re-replication or to determine if the ability to re-replicate is restricted to a particular cell-cycle phase. Using an adaptation of DNA fiber spreading we report the direct detection of re-replication on single DNA molecules from human chromosomes. Using this method we demonstrate substantial re-replication within 1 h of S phase entry in cells overproducing the replication factor, Cdt1. Moreover, a comparison of the HeLa cancer cell line to untransformed fibroblasts suggests that HeLa cells produce replication signals consistent with low-level re-replication in otherwise unperturbed cell cycles. Re-replication after depletion of the Cdt1 inhibitor, geminin, in an untransformed fibroblast cell line is undetectable by standard assays but readily quantifiable by DNA fiber spreading analysis. Direct evaluation of re-replicated DNA molecules will promote increased understanding of events that promote or perturb genome stability. PMID:19010964

Air Force Dynamic Mechanical Analysis Testing of NATO Round Robin Propellant Testing for Development of AOP-4717

DTIC Science & Technology

2015-08-01

10 minutes. After this, the furnace was opened and the clamps were tightened to 6 in-lb of torque . At the end of the tests, we examined the specimens...to use a different procedure for tightening the clamps in the frequency sweep tests -- this is explained in the next section...procedure to tighten the clamps. This is described next. First, the test applies different frequencies at a large range of temperatures – from -110 C to 70

Methods of Measuring Stress Relaxation in Composite Tape Springs

DTIC Science & Technology

2015-03-26

plate in order to spread the load evenly and prevent excess torque . The plate also allows for force on the tape spring to be applied to the entire...aluminum squares that can be tightened to the base. The test fixture is secured to the marble base. The tape springs are folded in three locations with...top plate is pressed down by tightening the bolt on each nut. The tightening is complete when the tape spring just begins to create an M shape and

A Generalized Machine Fault Detection Method Using Unified Change Detection

DTIC Science & Technology

2014-10-02

SOCIETY 2014 11 of the extension shaft. It can be induced by a lack of tightening torque of the end-nut and consequently causes a load...Test Facility (HTTF). The objective of the study was to provide HUMS systems with the capability to detect the loss of tightening torque of the end...from pinion SSA (at Ring-Front sensor & cruise power) change signal with cross-over at 75th shaft order Ten end-nut tightening torques were used in

Update on Tissue Tightening

PubMed Central

2010-01-01

A variety of medical devices are described under the heading of tissue tightening devices. This article reviews the tissue tightening devices currently available in the United States and some that may receive clearance in the upcoming year. These include the various radiofrequency devices as well as the pulsed light devices that achieve similar end results. The one noticeable factor seen with this group of devices is the paucity of large, clinical, controlled trials that appear in the medical literature for this group of medical devices as a whole. PMID:20725568

Tissue tightening: a hot topic utilizing deep dermal heating.

PubMed

Gold, Michael H

2007-12-01

The US market has seen a rapid growth in new radiofrequency (RF) devices over the past several years, all for the benefit of our patients. This column will summarize the various types of RF devices currently available and review their technologies for a nonsurgical approach to tissue tightening. Further clinical trials are necessary to demonstrate the efficacy as well as safety of RF devices for tissue tightening so that we can treat our patients with devices that truly work and provide the desired results.

Hydrocortisone, Neomycin, and Polymyxin

MedlinePlus

... your pharmacist or doctor. Replace and tighten the cap or dropper right away. Wash your hands to ... instilling the next drop. Replace and tighten the cap on the dropper bottle. Do not wipe or ...

Mechanisms to Control Rereplication and Implications for Cancer

PubMed Central

Hook, Sara S.; Lin, Jie Jessie; Dutta, Anindya

2007-01-01

Recent advances in the replication field have highlighted how the replication initiator proteins are negatively regulated by inhibitor proteins and ubiquitin-mediated degradation in mammalian cells to prevent rereplication. When these regulatory pathways go awry, uncontrolled rereplication ensues and a G2/M checkpoint is evoked to prevent cellular death. Many components of the checkpoints activated by rereplicaton are important for cancer prevention by facilitating DNA damage repair processes. The pathways that prevent rereplication themselves have also recently been implicated in preventing tumorigenesis. Studies from patient tumors, genetically altered mice, and mammalian cell culture suggest that deregulation of replication licensing proteins results in an increase in aneuploidy, chromosomal fusions, and DNA breaks. These studies provide a framework to address how regulators of replication function to maintain genomic stability. PMID:18053699

Mechanics of the taper integrated screwed-in (TIS) abutments used in dental implants.

PubMed

Bozkaya, Dinçer; Müftü, Sinan

2005-01-01

The tapered implant-abutment interface is becoming more popular due to the mechanical reliability of retention it provides. Consequently, understanding the mechanical properties of the tapered interface with or without a screw at the bottom has been the subject of a considerable amount of studies involving experiments and finite element (FE) analysis. This paper focuses on the tapered implant-abutment interface with a screw integrated at the bottom of the abutment. The tightening and loosening torques are the main factors in determining the reliability and the stability of the attachment. Analytical formulas are developed to predict tightening and loosening torque values by combining the equations related to the tapered interface with screw mechanics equations. This enables the identification of the effects of the parameters such as friction, geometric properties of the screw, the taper angle, and the elastic properties of the materials on the mechanics of the system. In particular, a relation between the tightening torque and the screw pretension is identified. It was shown that the loosening torque is smaller than the tightening torque for typical values of the parameters. Most of the tightening load is carried by the tapered section of the abutment, and in certain combinations of the parameters the pretension in the screw may become zero. The calculations performed to determine the loosening torque as a percentage of tightening torque resulted in the range 85-137%, depending on the values of taper angle and the friction coefficient.

Assessment of cold welding properties of the internal conical interface of two commercially available implant systems.

PubMed

Norton, M R

1999-02-01

The cone-screw abutment has been shown to diminish micromovement by reducing the burden of component loosening and fracture. However, anecdotal concern for cold welding of cone-screw joints in implant design has been identified as a potential source for lack of retrievability. This comparative study evaluated the loosening torque, as a percentage of tightening torque, for the ITI Straumann and Astra Tech (3.5 and 4.0 mm diameters) implant systems, which use an 8-degree and 11-degree internal cone, respectively. Implants and abutments from each system were mounted in a torque device, and a range of tightening torques was applied. Loosening torques were then measured, and the influence of conus angle, interfacial surface area, saliva contamination, and time delay to loosening were all assessed. The loosening torque only exceeded tightening torque at the highest levels, just before component failure, when plastic deformation was expected. For all clinically relevant levels of torque, both in a dry environment and with components bathed in artificial saliva at 37 degrees C, loosening torque was always seen to be 80% to 90% of tightening torque, demonstrating that cold welding does not occur. There was a high correlation between loosening and tightening torque for all systems tested, but no statistical difference when comparing wet versus dry or comparing individual data for each system. It can be concluded that for clinically relevant levels of tightening torque, no problems are anticipated with respect to retrievability.

Influence of repeated screw tightening on bacterial leakage along the implant-abutment interface.

PubMed

do Nascimento, Cássio; Pedrazzi, Vinícius; Miani, Paola Kirsten; Moreira, Larissa Daher; de Albuquerque, Rubens Ferreira

2009-12-01

Bacterial penetration along the implant-abutment interface as a consequence of abutment screw loosening has been reported in a number of recent studies. The aim of this in vitro study was to investigate the influence of repeated tightening of the abutment screw on leakage of Streptococcus mutans along the interface between implants and pre-machined abutments. Twenty pre-machined abutments with a plastic sleeve were used. The abutment screws were tightened to 32 N cm in group 1 (n=10 - control) and to 32 N cm, loosened and re-tightened with the same torque twice in group 2 (n=10). The assemblies were completely immersed in 5 ml of Tryptic Soy Broth medium inoculated with S. mutans and incubated for 14 days. After this period, contamination of the implant internal threaded chamber was evaluated using the DNA Checkerboard method. Microorganisms were found on the internal surfaces of both groups evaluated. However, bacterial counts in group 2 were significantly higher than that in the control group (P<0.05). These results suggest that bacterial leakage between implants and abutments occurs even under unloaded conditions and at a higher intensity when the abutment screw is tightened and loosened repeatedly.

The Influence of Torque Tightening on the Position Stability of the Abutment in Conical Implant-Abutment Connections.

PubMed

Hogg, Wiebke Semper; Zulauf, Kris; Mehrhof, Jürgen; Nelson, Katja

2015-01-01

The influence of repeated system-specific torque tightening on the position stability of the abutment after de- and reassembly of the implant components was evaluated in six dental implant systems with a conical implant-abutment connection. An established experimental setup was used in this study. Rotation, vertical displacement, and canting moments of the abutment were observed; they depended on the implant system (P = .001, P < .001, P = .006, respectively). Repeated torque tightening of the abutment screw does not eliminate changes in position of the abutment.

Use of an Ethanol-Driven Pressure Cell to Measure Hydrostatic Pressure Response of Protein-Stabilized Gold Nanoclusters

DTIC Science & Technology

2016-01-01

the PC was then screwed into the PC and tightened to 50 ft-lb using a click-type torque wrench. It is important to ensure that a small amount of...ethanol from the PC leaks into the tightened top nut to ensure that no air is present in the cell. A connecting nut is then screwed into the top nut...and tightened ; again it is important to ensure that ethanol leaks into the connecting nut to ensure the absence of air pockets. A schematic of the

Effect of tightening torque on the marginal adaptation of cement-retained implant-supported fixed dental prostheses

PubMed Central

Ghanbarzadeh, Jalil; Dashti, Hossin; Karamad, Reza; Alikhasi, Marzieh; Nakhaei, Mohammadreza

2015-01-01

Background: The final position of the abutment changes with the amount of tightening torque. This could eventually lead to loss of passivity and marginal misfit of prostheses. The aim of this study was to evaluate the effect of three different tightening torques on the marginal adaptation of 3-unit cement-retained implant-supported fixed dental prostheses (FDPs). Materials and Methods: Two implants (Straumann) were inserted in an acrylic block so that one of the implants was placed vertically and the other at a 15° vertical angle. A straight abutment and a 15° angulated abutment were connected to the vertically and obliquely installed implants, respectively, so that the two abutments were parallel. Then, 10 cement-retained FDPs were waxed and cast. Abutments were tightened with 10, 20, and 35 Ncm torques, respectively. Following each tightening torque, FDPs were luted on respective abutments with temporary cement. The marginal adaptation of the retainers was evaluated using stereomicroscope. FDPs were then removed from the abutments and were sectioned at the connector sites. The retainers were luted again on their respective abutments. Luting procedures and marginal adaptation measurement were repeated. Data were analyzed by ANOVA and least significant difference tests (α = 0.05). After cutting the FDP connectors, the independent samples t-test was used to compare misfit values (α = 0.05). Results: Following 10, 20, and 35 Ncm tightening torques, the marginal discrepancy of the retainers of FDPs significantly increased (P < 0.05). There was no significant difference between the marginal discrepancies of these two retainers (P > 0.05). The marginal gap values of angulated abutment retainers (ANRs) were significantly higher than those of the straight abutment after cutting the connectors (P = 0.026). Conclusion: Within the limitations of this study, the marginal misfit of cement-retained FDPs increased continuously when the tightening torque increased. After cutting the connectors, the marginal misfit of the ANRs was higher than those of the straight abutment retainers. PMID:26288627

Effect of tightening torque on the marginal adaptation of cement-retained implant-supported fixed dental prostheses.

PubMed

Ghanbarzadeh, Jalil; Dashti, Hossin; Karamad, Reza; Alikhasi, Marzieh; Nakhaei, Mohammadreza

2015-01-01

The final position of the abutment changes with the amount of tightening torque. This could eventually lead to loss of passivity and marginal misfit of prostheses. The aim of this study was to evaluate the effect of three different tightening torques on the marginal adaptation of 3-unit cement-retained implant-supported fixed dental prostheses (FDPs). Two implants (Straumann) were inserted in an acrylic block so that one of the implants was placed vertically and the other at a 15° vertical angle. A straight abutment and a 15° angulated abutment were connected to the vertically and obliquely installed implants, respectively, so that the two abutments were parallel. Then, 10 cement-retained FDPs were waxed and cast. Abutments were tightened with 10, 20, and 35 Ncm torques, respectively. Following each tightening torque, FDPs were luted on respective abutments with temporary cement. The marginal adaptation of the retainers was evaluated using stereomicroscope. FDPs were then removed from the abutments and were sectioned at the connector sites. The retainers were luted again on their respective abutments. Luting procedures and marginal adaptation measurement were repeated. Data were analyzed by ANOVA and least significant difference tests (α = 0.05). After cutting the FDP connectors, the independent samples t-test was used to compare misfit values (α = 0.05). Following 10, 20, and 35 Ncm tightening torques, the marginal discrepancy of the retainers of FDPs significantly increased (P < 0.05). There was no significant difference between the marginal discrepancies of these two retainers (P > 0.05). The marginal gap values of angulated abutment retainers (ANRs) were significantly higher than those of the straight abutment after cutting the connectors (P = 0.026). Within the limitations of this study, the marginal misfit of cement-retained FDPs increased continuously when the tightening torque increased. After cutting the connectors, the marginal misfit of the ANRs was higher than those of the straight abutment retainers.

The influence of abutment screw tightening on screw joint configuration.

PubMed

Lang, Lisa A; Wang, Rui-Feng; May, Kenneth B

2002-01-01

Limiting abutment-to-implant hexagonal discrepancies and rotational movement of the abutment around the implant to less than 5 degrees would result in a more stable screw joint. However, the exact relationship after abutment screw tightening is unknown, as is the effect of a counter-torque device in limiting abutment movement during screw tightening. This study examined the orientation of the abutment hexagon to the implant hexagon after tightening of the abutment screw for several abutment systems with and without the use of a counter-torque device. Thirty conical self-tapping implants (3.75 x 10.0 mm) and 10 wide-platform Brånemark System implants (5.0 x 10.0 mm), along with 10 abutment specimens from the CeraOne, Estheticone, Procera, and AuraAdapt systems, were selected for this investigation. The implants were placed in a holding device prior to tightening of the abutments. When the tightening torque recommended for each abutment system was reached with the use of a torque controller, each implant abutment specimen was removed from the holding device and embedded in a hard resin medium. The specimens were sectioned in a horizontal direction at the level of the hexagons and cleansed of debris prior to examination. The hexagon orientations were assessed as the degree and direction of rotation of the abutment hexagon around the implant hexagon. The range of the maximum degrees of rotation for all 4 abutment groups tightened with or without the counter-torque device was slightly more than 3.53 degrees. The absolute degrees of rotation for all 4 abutment groups were less than 1.50 degrees with or without the use of the counter-torque device. The hexagon-to-hexagon orientation measured as rotational fit on all abutment systems was below the 5 degrees suggested as optimal for screw joint stability. The absolute degrees of rotation for all 4 abutment groups were less than 1.50 degrees regardless of whether the counter-torque device was used.

Bolt installation tool for tightening large nuts and bolts

NASA Technical Reports Server (NTRS)

Mcdougal, A. R.; Norman, R. M.

1974-01-01

Large bolts and nuts are accurately tightened to structures without damaging torque stresses. There are two models of bolt installation tool. One is rigidly mounted and one is hand held. Each model includes torque-multiplier unit.

Off Label Antiviral Therapeutics for Henipaviruses: New Light Through Old Windows

PubMed Central

Aljofan, Mohamad; Lo, Michael K.; Rota, Paul A.; Michalski, Wojtek P.; Mungall, Bruce A.

2010-01-01

Hendra and Nipah viruses are recently emerged zoonotic paramyxoviruses for which there is no vaccine or protective therapy available. While a number of experimental therapeutics and vaccines have recently been reported, all of these will require lengthy approval processes, limiting their usefulness in the short term. To address the urgent need for henipavirus therapeutics, a number of currently licensed pharmaceuticals have been evaluated for off label efficacy against henipavirus replication in vitro. Initially it was observed that compounds which released intracellular calcium stores induced a potent inhibition of henipaviruses replication, prompting the evaluation of known drugs with a similar effect on calcium mobilisation. Of the eight compounds randomly selected based on existing literature, seven inhibited virus replication in the micromolar range while the remaining compound also inhibited virus replication but only at millimolar concentrations. Pretreatment experiments with various calcium chelators, channel antagonists or endoplasmic reticulum release inhibitors supported a calcium mediated mechanism of action for five of these compounds. The mechanism of antiviral action for the remaining three compounds is currently unknown. Additionally, a number of other modulators of calcium flux, including calcium channel and calmodulin antagonists also exhibited potent antiviral activity in vitro providing a broad range of potential therapeutic options for the treatment of henipavirus infections. Importantly, as many of these compounds are currently licensed drugs, regulatory approval should be a much more streamlined process, with the caveat that appropriate in vivo efficacy can be demonstrated in animal models. PMID:20668647

Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton

PubMed Central

Parker, William H.; Rhea, Elizabeth Meredith; Qu, Zhi-Chao; Hecker, Morgan R.

2016-01-01

Vitamin C, or ascorbic acid, both tightens the endothelial permeability barrier in basal cells and also prevents barrier leak induced by inflammatory agents. Barrier tightening by ascorbate in basal endothelial cells requires nitric oxide derived from activation of nitric oxide synthase. Although ascorbate did not affect cyclic AMP levels in our previous study, there remains a question of whether it might activate downstream cyclic AMP-dependent pathways. In this work, we found in both primary and immortalized cultured endothelial cells that ascorbate tightened the endothelial permeability barrier by ∼30%. In human umbilical vein endothelial cells, this occurred at what are likely physiologic intracellular ascorbate concentrations. In so doing, ascorbate decreased measures of oxidative stress and also flattened the cells to increase cell-to-cell contact. Inhibition of downstream cyclic AMP-dependent proteins via protein kinase A did not prevent ascorbate from tightening the endothelial permeability barrier, whereas inhibition of Epac1 did block the ascorbate effect. Although Epac1 was required, its mediator Rap1 was not activated. Furthermore, ascorbate acutely stabilized microtubules during depolymerization induced by colchicine and nocodazole. Over several days in culture, ascorbate also increased the amount of stable acetylated α-tubulin. Microtubule stabilization was further suggested by the finding that ascorbate increased the amount of Epac1 bound to α-tubulin. These results suggest that physiologic ascorbate concentrations tighten the endothelial permeability barrier in unstimulated cells by stabilizing microtubules in a manner downstream of cyclic AMP that might be due both to increasing nitric oxide availability and to scavenging of reactive oxygen or nitrogen species. PMID:27605450

Effect of screw torque level on cortical bone pullout strength.

PubMed

Cleek, Tammy M; Reynolds, Karen J; Hearn, Trevor C

2007-02-01

The objectives of this study were 2-fold: (1) to perform detailed analysis of cortical screw tightening stiffness during automated insertion, and (2) to determine the effect of 3 torque levels on the holding strength of the bone surrounding the screw threads as assessed by screw pullout. Ten pairs of ovine tibiae were used with 3 test sites spaced 20 mm apart centered along the shaft. One side of each pair was used for measuring ultimate failure torque (Tmax). These Tmax and bone-density values were used to predict Tmax at contralateral tibia sites. Screws were inserted and tightened to 50%, 70%, and 90% of predicted Tmax at the contralateral sites to encompass the average clinical level of torque (86% Tmax). Pullout tests were performed and maximum force values were normalized by cortical thickness. Torque to failure tests indicated tightening to 86% Tmax occurs after yield and leads to an average 51% loss in stiffness. Normalized pullout strength for screws tightened to 50% Tmax, 70% Tmax, and 90% Tmax were 2525 +/- 244, 2707 +/- 280, and 2344 +/- 346 N, respectively, with a significant difference between 70% Tmax and 90% Tmax groups (P < 0.05). Within the limitations of our study involving the testing of 1 type of screw purchase in ovine tibiae, results demonstrate that clinical levels of lag screw tightening (86% Tmax) are past the yield point of bone. Tightening to these high torque levels can cause damage leading to compromised holding strength. Further research is still required to establish the appropriate level of torque required for achieving optimal fracture fixation and healing.

Investigation of high-strength bolt-tightening verification techniques.

DOT National Transportation Integrated Search

2016-03-01

The current means and methods of verifying that high-strength bolts have been properly tightened are very laborious and time : consuming. In some cases, the techniques require special equipment and, in other cases, the verification itself may be some...

Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing.

PubMed

Kim, Jin S; Nanfara, Michael T; Chodavarapu, Sundari; Jin, Kyeong S; Babu, Vignesh M P; Ghazy, Mohamed A; Chung, Scisung; Kaguni, Jon M; Sutton, Mark D; Cho, Yunje

2017-04-20

Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda-sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda-β clamp complex. This complex contains two pairs of Hda dimers sandwiched between two β clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the β clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda-β clamp complex indicate that the interaction of the β clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda-β clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing

PubMed Central

Kim, Jin S.; Nanfara, Michael T.; Chodavarapu, Sundari; Jin, Kyeong S.; Babu, Vignesh M. P.; Ghazy, Mohamed A.; Chung, Scisung

2017-01-01

Abstract Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda–sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda–β clamp complex. This complex contains two pairs of Hda dimers sandwiched between two β clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the β clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda–β clamp complex indicate that the interaction of the β clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda–β clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. PMID:28168278

Low-Thermal-Resistance Baseplate Mounting

NASA Technical Reports Server (NTRS)

Perreault, W. T.

1984-01-01

Low-thermal-resistance mounting achieved by preloading baseplate to slight convexity with screws threaded through beam. As mounting bolts around edge of base-place tightened, baseplate and cold plate contact first in center, with region of intimate contact spreading outward as bolts tightened.

Ultrasound skin tightening.

PubMed

Minkis, Kira; Alam, Murad

2014-01-01

Ultrasound skin tightening is a noninvasive, nonablative method that allows for energy deposition into the deep dermal and subcutaneous tissue while avoiding epidermal heating. Ultrasound coagulation is confined to arrays of 1-mm(3) zones that include the superficial musculoaponeurotic system and connective tissue. This technology gained approval from the Food and Drug Administration as the first energy-based skin "lifting" device, specifically for lifting lax tissue on the neck, submentum, and eyebrows. Ultrasound has the unique advantage of direct visualization of treated structures during treatment. Ultrasound is a safe and efficacious treatment for mild skin tightening and lifting. Copyright © 2014 Elsevier Inc. All rights reserved.

Non-surgical radiofrequency facelift.

PubMed

Narins, David J; Narins, Rhoda S

2003-10-01

There has been considerable interest in using non-ablative methods to rejuvenate the skin. The ThermaCool TC (Thermage Inc.) is a radiofrequency (RF) device that has been introduced to induce tightening of the address the problem of skin via a uniform volumetric heating into the deep dermis tightening, resulting in a 'non-surgical facelift'. Radiofrequency produces a uniform volumetric heating into the deep dermis. Twenty treatment areas in 17 patients were treated to evaluate the efficacy and safety of RF treatment to the brow and jowls. The technique was found to produce gradual tightening in most patients, and there were no adverse effects.

Implant abutment deformation during prosthetic cylinder screw tightening: an in vitro study.

PubMed

Neto, Rafael Tobias Moretti; Moura, Marcio Silva; Souza, Edson Antonio Capello; Rubo, José Henrique

2009-01-01

Nonpassive fit frameworks are believed to lead to implant overload and consequently loss of osseointegration. This is one of the most commonly reported failures of implant prostheses. In an ideal situation of passive fit, when torque is applied to bring the abutment-cylinder interface together some amount of deformation can be expected, and it should be homogeneous along the periphery of the abutment. The aim of this study was to verify the amount of abutment deformation that can be expected when a free-standing cylinder is screwed into place. This could give insight into what should be accepted as passive fit. Strain gauges were bonded to the sides of five standard abutments that had machined palladium-silver cylinders or cobalt-chromium cast cylinders screwed into place. Measurements were taken to verify the deformation at each site. Values of abutment deformation after abutment screw tightening ranged from -127.70 to -590.27 microepsilon. The deformation recorded for palladium-silver prosthetic cylinder tightening ranged from 56.905 to -381.50 microepsilon (mean: 173.298 microepsilon) and from -5.62638 to -383.86 microepsilon (mean: 200.474 microepsilon) for cobalt-chromium cylinders. There was no statistically significant difference among the two groups. Both abutment screw tightening and prosthetic cylinder screw tightening result in abutment deformation, which is compressive most of the time.

Loosening torque of Universal Abutment screws after cyclic loading: influence of tightening technique and screw coating.

PubMed

Bacchi, Atais; Regalin, Alexandre; Bhering, Claudia Lopes Brilhante; Alessandretti, Rodrigo; Spazzin, Aloisio Oro

2015-10-01

The purpose of this study was to evaluate the influence of tightening technique and the screw coating on the loosening torque of screws used for Universal Abutment fixation after cyclic loading. Forty implants (Titamax Ti Cortical, HE, Neodent) (n=10) were submerged in acrylic resin and four tightening techniques for Universal Abutment fixation were evaluated: A - torque with 32 Ncm (control); B - torque with 32 Ncm holding the torque meter for 20 seconds; C - torque with 32 Ncm and retorque after 10 minutes; D - torque (32 Ncm) holding the torque meter for 20 seconds and retorque after 10 minutes as initially. Samples were divided into subgroups according to the screw used: conventional titanium screw or diamond like carbon-coated (DLC) screw. Metallic crowns were fabricated for each abutment. Samples were submitted to cyclic loading at 10(6) cycles and 130 N of force. Data were analyzed by two-way ANOVA and Tukey's test (5%). The tightening technique did not show significant influence on the loosening torque of screws (P=.509). Conventional titanium screws showed significant higher loosening torque values than DLC (P=.000). The use of conventional titanium screw is more important than the tightening techniques employed in this study to provide long-term stability to Universal Abutment screws.

Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: implications from other RNA viruses

PubMed Central

Nishiyama, Shoko; Ikegami, Tetsuro

2015-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae). Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the U.S. MP-12 displays a temperature-sensitive (ts) phenotype and does not replicate at 41°C. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF. PMID:26322023

Transducer-Mounting Fixture

NASA Technical Reports Server (NTRS)

Spiegel, Kirk W.

1990-01-01

Transducer-mounting fixture holds transducer securely against stud. Projects only slightly beyond stud after installation. Flanged transducer fits into fixture when hinged halves open. When halves reclosed, fixture tightened onto threaded stud until stud makes contact with transducer. Knurled area on fixture aids in tightening fixture on stud.

Investigation of high-strength bolt-tightening verification techniques : tech transfer summary.

DOT National Transportation Integrated Search

2016-03-01

The primary objective of this project was to explore the current state-of-practice and the state-of-the-art techniques for high-strength bolt tightening and verification in structural steel connections. This project was completed so that insight coul...

An alternative section method for casting and posterior laser welding of metallic frameworks for an implant-supported prosthesis.

PubMed

de Aguiar, Fábio Afrânio; Tiossi, Rodrigo; Rodrigues, Renata Cristina Silveira; Mattos, Maria de Gloria Chiarello; Ribeiro, Ricardo Faria

2009-04-01

The aim of this study was to compare the accuracy of fit of three types of implant-supported frameworks cast in Ni-Cr alloy: specifically, a framework cast as one piece compared to frameworks cast separately in sections to the transverse or the diagonal axis, and later laser welded. Three sets of similar implant-supported frameworks were constructed. The first group of six 3-unit implant-supported frameworks were cast as one piece, the second group of six were sectioned in the transverse axis of the pontic region prior to casting, and the last group of six were sectioned in the diagonal axis of the pontic region prior to casting. The sectioned frameworks were positioned in the matrix (10 N.cm torque) and laser welded. To evaluate passive fit, readings were made with an optical microscope with both screws tightened and with only one-screw tightened. Data were submitted to ANOVA and Tukey-Kramer's test (p < 0.05). When both screws were tightened, no differences were found between the three groups (p > 0.05). In the single-screw-tightened test, with readings made opposite to the tightened side, the group cast as one piece (57.02 +/- 33.48 mum) was significantly different (p < 0.05) from the group sectioned diagonally (18.92 +/- 4.75 microm) but no different (p > 0.05) from the group transversally sectioned (31.42 +/- 20.68 microm). On the tightened side, no significant differences were found between the groups (p > 0.05). Results of this study showed that casting diagonally sectioned frameworks lowers misfit levels of prosthetic implant-supported frameworks and also improves the levels of passivity to the same frameworks when compared to structures cast as one piece.

Modified section method for laser-welding of ill-fitting cp Ti and Ni-Cr alloy one-piece cast implant-supported frameworks.

PubMed

Tiossi, R; Falcão-Filho, H; Aguiar Júnior, F A; Rodrigues, R C; Mattos, M da G; Ribeiro, R F

2010-05-01

This study aimed to verify the effect of modified section method and laser-welding on the accuracy of fit of ill-fitting commercially pure titanium (cp Ti) and Ni-Cr alloy one-piece cast frameworks. Two sets of similar implant-supported frameworks were constructed. Both groups of six 3-unit implant-supported fixed partial dentures were cast as one-piece [I: Ni-Cr (control) and II: cp Ti] and evaluated for passive fitting in an optical microscope with both screws tightened and with only one screw tightened. All frameworks were then sectioned in the diagonal axis at the pontic region (III: Ni-Cr and IV: cp Ti). Sectioned frameworks were positioned in the matrix (10-Ncm torque) and laser-welded. Passive fitting was evaluated for the second time. Data were submitted to anova and Tukey-Kramer honestly significant difference tests (P < 0.05). With both screws tightened, one-piece cp Ti group II showed significantly higher misfit values (27.57 +/- 5.06 microm) than other groups (I: 11.19 +/- 2.54 microm, III: 12.88 +/- 2.93 microm, IV: 13.77 +/- 1.51 microm) (P < 0.05). In the single-screw-tightened test, with readings on the opposite side to the tightened side, Ni-Cr cast as one-piece (I: 58.66 +/- 14.30 microm) was significantly different from cp Ti group after diagonal section (IV: 27.51 +/- 8.28 microm) (P < 0.05). On the tightened side, no significant differences were found between groups (P > 0.05). Results showed that diagonally sectioning ill-fitting cp Ti frameworks lowers misfit levels of prosthetic implant-supported frameworks and also improves passivity levels of the same frameworks when compared to one-piece cast structures.

Traffic safety for the cell: influence of cyclin-dependent kinase activity on genomic stability.

PubMed

Enders, Greg H; Maude, Shannon L

2006-04-12

Genomic instability has long been considered a key factor in tumorigenesis. Recent evidence suggests that DNA damage may be widespread in early pre-neoplastic states, with deregulation of cyclin-dependent kinase (Cdk) activity a driving force. Increased Cdk activity may critically reduce licensing of origins of DNA replication, drive re-replication, or mediate overexpression of checkpoint proteins, inducing deleterious cell cycle delay. Conversely, inhibition of Cdk activity may compromise replication efficiency, expression of checkpoint proteins, or activation of DNA repair proteins. These vital functions point to the impact of Cdk activity on the stability of the genome. Insight into these pathways may improve our understanding of tumorigenesis and lead to more rational cancer therapies.

Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression.

PubMed

Franz, André; Pirson, Paul A; Pilger, Domenic; Halder, Swagata; Achuthankutty, Divya; Kashkar, Hamid; Ramadan, Kristijan; Hoppe, Thorsten

2016-02-04

The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging.

Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression

PubMed Central

Franz, André; Pirson, Paul A.; Pilger, Domenic; Halder, Swagata; Achuthankutty, Divya; Kashkar, Hamid; Ramadan, Kristijan; Hoppe, Thorsten

2016-01-01

The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging. PMID:26842564

Energy Savings Analysis for Energy Monitoring and Control Systems

DTIC Science & Technology

1995-01-01

for evaluating design and construction a:-0 quality, and for studying the effectiveness of air - tightening AC retrofits. No simple relationship...Energy These models of residential infiltration are based on statistical "Resource Center (1983) include information on air tightening in fits of

In vitro comparative analysis of the fit of gold alloy or commercially pure titanium implant-supported prostheses before and after electroerosion.

PubMed

Sartori, Ivete Aparecida de Mattias; Ribeiro, Ricardo Faria; Francischone, Carlos Eduardo; de Mattos, Maria da Gloria Chiarello

2004-08-01

For implant-supported prostheses, passive fit is critical for the success of rehabilitation, especially when alternative materials are used. The purpose of this study was to compare interfacial fit of implant-supported prostheses cast in titanium to those cast in gold alloy. Five 3-unit fixed partial dentures were fabricated in gold alloy (Degudent U) as 1-piece castings, and 5 others were similarly cast in commercially pure titanium (Grade 1). The interfacial gaps between the prostheses and the abutments were evaluated with an optical microscope, before and after electroerosion. Readings were made with both screws tightened (10 N.cm torque), and with only 1 side tightened, so as to also evaluate the passive fit of the prostheses. Data were compared statistically by 2-way analysis of variance and the post hoc Tukey multiple range test (alpha=.05). Before electroerosion, the interfacial gaps for the 1-piece prostheses were significantly smaller (P<.001) in the gold alloy group when the screws were tightened (Au=12.6 +/- 3.0 microm, compared to Ti=30.1 +/- 6.4 microm). When the side opposite the tightened side was analyzed, there was no significant difference between the gold alloy and titanium groups (Au=69.2 +/- 24.9 microm and Ti=94.2 +/- 39.6 microm). The electroerosion procedure significantly (P<.001) reduced the gaps at the interfaces for both groups under all conditions. Comparison between groups after electroerosion did not present significant differences when the side opposite the tightened side was analyzed, but the gold alloy group showed better fit when the tightened side was analyzed (12.8 +/- 1.4 microm for gold alloy; 29.6 +/- 4.4 microm for titanium) and when both screws were tightened (5.4 +/- 2.3 microm for gold alloy; 16.1 +/- 5.5 microm for titanium). Cast titanium prostheses, despite showing larger interfacial gaps between the prosthesis and abutment than those obtained with gold alloy, had improved fit after being subjected to electroerosion.

Ways of Noninvasive Facial Skin Tightening and Fat Reduction.

PubMed

Fritz, Klaus; Salavastru, Carmen

2016-06-01

For skin tightening, ablative and nonablative lasers have been used with various parameters full or fractionated. Currently, other energy-based technologies have been developed such as radiofrequency (RF) from mono- to multipolar, microneedling RF, and high-intensity focused ultrasound. They heat up the tissue to a clinical endpoint. Temperatures above 42°C stimulate fibroblasts to produce more collagen and some technologies produce small coagulation points that allow to shrink and to tighten the tissue with less downtime or side effects. Alternative treatments not based on heat can be chemical peels from light to deep and microneedling without RF. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Peripheral Vascular Disease

MedlinePlus

... smokers aged 20 to 40. Smoking causes the blood vessels to tighten in everyone who smokes. But in people with Buerger’s disease, there is so much tightening in the vessels that a lack of oxygen to the cells (ischemia) or tissue death (necrosis) may result. The symptoms may be different for ...

Comparison of release torques of tightened bolts in vacuum and air

NASA Technical Reports Server (NTRS)

Demorest, K. E.

1970-01-01

Various combinations of stainless steel, mild steel, and aluminum bolt-nut couples are tightened to 60 lb-ft in partial vacuum and in air. Results are given for tests with and without two lubricants /a fluorosilicone and a sodium silicate bonded dry-film/.

Use of micro-focused ultrasound with visualization to lift and tighten lax knee skin (1.).

PubMed

Gold, Michael H; Sensing, Whitney; Biron, Julie

2014-10-01

Public interest in noninvasive, aesthetic treatments for the rejuvenation of appearance continues to grow. The following prospective, open-label, nonrandomized trial was conducted to evaluate the safety and efficacy of micro-focused ultrasound with visualization (MFU-V) for achieving lift and tightening of lax skin above the knee. Healthy adult women (N = 30) with mild- to moderate bilateral skin laxity above the knees were enrolled. MFU-V was applied to a grid of eight 25 mm(2) squares above each knee. MFU-V was first applied using a 4 MHz, 4.5 mm transducer followed by a 7 MHz, 3.0 mm transducer. Approximately 320 treatment lines applied to each knee [corrected]. The primary efficacy endpoint was lifting and tightening of lax skin above the knee as determined by the principle investigator using the Physician Global Aesthetic Improvement Scale (PGAIS). Among 28 evaluable subjects, 24 subjects (86%) showed improved lifting and tightening of knee skin laxity at 90- and 180-day follow-up visits. Three subjects showed no change and the appearance of one subject worsened. There were no adverse events or evidence of skin injury. Similar to its safety and efficacy for tightening facial skin and reducing wrinkles, MFU-V is an effective, noninvasive method for reducing skin laxity and improving the appearance of skin above the knee. ClinicalTrials.gov Identifier: NCT01708434.

Loosening torque of Universal Abutment screws after cyclic loading: influence of tightening technique and screw coating

PubMed Central

Regalin, Alexandre; Bhering, Claudia Lopes Brilhante; Alessandretti, Rodrigo; Spazzin, Aloisio Oro

2015-01-01

PURPOSE The purpose of this study was to evaluate the influence of tightening technique and the screw coating on the loosening torque of screws used for Universal Abutment fixation after cyclic loading. MATERIALS AND METHODS Forty implants (Titamax Ti Cortical, HE, Neodent) (n=10) were submerged in acrylic resin and four tightening techniques for Universal Abutment fixation were evaluated: A - torque with 32 Ncm (control); B - torque with 32 Ncm holding the torque meter for 20 seconds; C - torque with 32 Ncm and retorque after 10 minutes; D - torque (32 Ncm) holding the torque meter for 20 seconds and retorque after 10 minutes as initially. Samples were divided into subgroups according to the screw used: conventional titanium screw or diamond like carbon-coated (DLC) screw. Metallic crowns were fabricated for each abutment. Samples were submitted to cyclic loading at 106 cycles and 130 N of force. Data were analyzed by two-way ANOVA and Tukey's test (5%). RESULTS The tightening technique did not show significant influence on the loosening torque of screws (P=.509). Conventional titanium screws showed significant higher loosening torque values than DLC (P=.000). CONCLUSION The use of conventional titanium screw is more important than the tightening techniques employed in this study to provide long-term stability to Universal Abutment screws. PMID:26576253

Anchorage performance of a high-pressure pre-tightening resin anchor with a compressed grouting body

PubMed Central

Tian, Jiansheng; Hu, Li

2017-01-01

Supports for deep mine roadways located in soft surrounding rock face several problems: difficulty in applying pre-tightening force, low bearing capacity, and poor initial support. To solve these problems, this study proposes a high-pressure pre-tightening resin anchor with a compressed grouting body for use in soft and fractured rock surrounding a deep roadway. Using model experiments, we analyzed the anchorage performance of the proposed anchor and a conventional tensile-type anchor for three different values of the elastic modulus of the surrounding rock. The results showed that regardless of the surrounding rock type, the peak micro-strain (642–541) and displacement (6.09–6.5 mm) at the pull-out end of the proposed anchor were always smaller than the peak micro-strain (1433–1105) and displacement (8.77–9.2 mm) at the pull-out end of the conventional anchor. Furthermore, as the anchor’s pre-tightening force increased from 20 kN to 120 kN, the anchor’s strain remained concentrated over a length of 0.4 m from the bearing end. Compared with conventional tensile-type anchors, the proposed high-pressure pre-tightening resin anchor with a compressed grouting body has a higher ultimate bearing capacity, allows the grouting length to be decreased to 0.4 m, and provides initial support resistance. PMID:28196084

Multicenter clinical perspectives on a broadband infrared light device for skin tightening.

PubMed

Taub, Amy Forman; Battle, Eliot F; Nikolaidis, Gregory

2006-09-01

Modalities for skin tightening include radiofrequency (RF) energy, lasers, and combination RF and diode lasers. A new broadband infrared light device (BILD) (Titan, Cutera, Inc, Brisbane, CA) targets water to achieve dermal heating and collagen remodeling for skin tightening. Although thousands of procedures have been performed worldwide with this device, only one article (to the author's knowledge) describing its performance in skin tightening has been published. Three US dermatologists report their experience with and provide their perspective on facial skin tightening with the BILD system. As early adopters, they each have 12 to 18 months experience with this system. One author (A.F.T.) treated 42 patients twice at 1-month intervals over 18 months. The mean improvement score was 1.83 (scale 0 to 4, with 4 denoting maximum improvement) with an average follow-up time of 3.7 months. More than 90% of treated patients showed visible improvement. No complications were observed and patient satisfaction was high. This paper presents the general consensus of the authors on patient selection and treatment protocol, their modifications of the manufacturer's treatment protocol, and the outcomes of 42 patients treated by one author (A.F.T.). The observations were gathered separately and turned out to be very similar. The recommendations are presented to help practitioners achieve consistently good results and avoid complications with the BILD procedure.

Aspergillus section Versicolores: nine new species and multilocus DNA sequence based phylogeny

USDA-ARS?s Scientific Manuscript database

ß-tubulin, calmodulin, internal transcribed spacer and partial lsu-rDNA, RNA polymerase, DNA replication licensing factor Mcm7, and pre-rRNA processing protein Tsr1 were amplified and sequenced from 62 A. versicolor clade isolates and analyzed phylogenetically using the concordance model to establis...

Aspergillus section Versicolores, nine new species and multilocus DNA sequence based phylogeny

USDA-ARS?s Scientific Manuscript database

ß-tubulin, calmodulin, internal transcribed spacer and partial lsu-rDNA, RNA polymerase, DNA replication licensing factor Mcm7, and pre-rRNA processing protein Tsr1 were amplified and sequenced from 62 A. versicolor clade isolates and analyzed phylogenetically using the concordance model to establis...

Improved Screw-Thread Lock

NASA Technical Reports Server (NTRS)

Macmartin, Malcolm

1995-01-01

Improved screw-thread lock engaged after screw tightened in nut or other mating threaded part. Device does not release contaminating material during tightening of screw. Includes pellet of soft material encased in screw and retained by pin. Hammer blow on pin extrudes pellet into slot, engaging threads in threaded hole or in nut.

49 CFR 178.360-4 - Closure devices.

Code of Federal Regulations, 2010 CFR

2010-10-01

... threads when securely tightened. Pipe threads must be luted with an appropriate non-hardening compound which must be capable of withstanding up to 149 °C (300 °F) without loss of efficiency. Tightening torque must be adequate to maintain leak tightness with the specific luting compound. (2) An opening may...

Duplex Wrench

NASA Technical Reports Server (NTRS)

Canada, C. N.

1987-01-01

Special tool enables one worker to do two-worker job. Wrench holds two nuts in place while third nut, coaxial with others, turned. Developed for tightening delicate couplings on gas-supply panel. Single operator restrains coupling pressure cap and connector body nut with one hand. Other hand free to tighten coupling nut with torque wrench.

HPV-type-specific response of cervical cancer cells to cisplatin after silencing replication licensing factor MCM4.

PubMed

Das, Mitali; Prasad, Shyam Babu; Yadav, Suresh Singh; Modi, Arusha; Singh, Sunita; Pradhan, Satyajit; Narayan, Gopeshwar

2015-12-01

Minichoromosome maintenance (MCM) proteins play key role in cell cycle progression by licensing DNA replication only once per cell cycle. These proteins are found to be overexpressed in cervical cancer cells. In this study, we depleted MCM4, one of the MCM 2-7 complex components by RNA interference (RNAi) in four cervical cancer cell lines. The four cell lines were selected on the basis of their human papillomavirus (HPV) infection: HPV16-positive SiHa, HPV18-positive ME-180, HPV16- and HPV18-positive CaSki, and HPV-negative C-33A. The MCM4-deficient cells irrespective of their HPV status grow for several generations and maintain regular cell cycle. We did not find any evidence of augmented response to a short-term (48 h) cisplatin treatment in these MCM4-deficient cells. However, MCM4-/HPV16+ SiHa cells cannot withstand a prolonged treatment (up to 5 days) of even a sublethal dosage of cisplatin. They show increased chromosomal instability compared to their control counterparts. On the other hand, MCM4-deficient CaSki cells (both HPV16+ and 18+) remain resistant to a prolonged exposure to cisplatin. Our study indicates that cervical cancer cells may be using excess MCMs as a backup for replicative stress; however, its regulatory mechanism is dependent on the HPV status of the cells.

75 FR 32863 - Airworthiness Directives; PILATUS AIRCRAFT LTD. Model PC-12/47E Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

... describes the unsafe condition as: Reports have been received indicating that, if the power control friction...: Reports have been received indicating that, if the power control friction wheel is tightened, the reverse... indicating that, if the power control friction wheel is tightened, the reverse thrust latch may stick and...

49 CFR 178.360-4 - Closure devices.

Code of Federal Regulations, 2013 CFR

2013-10-01

... securely tightened. Pipe threads must be luted with an appropriate non-hardening compound which must be capable of withstanding up to 149 °C (300 °F) without loss of efficiency. Tightening torque must be... subchapter). A torque wrench must be used in securing the flange with a corresponding torque of no more than...

49 CFR 178.360-4 - Closure devices.

Code of Federal Regulations, 2012 CFR

2012-10-01

... securely tightened. Pipe threads must be luted with an appropriate non-hardening compound which must be capable of withstanding up to 149 °C (300 °F) without loss of efficiency. Tightening torque must be... subchapter). A torque wrench must be used in securing the flange with a corresponding torque of no more than...

76 FR 66618 - Airworthiness Directives; Eurocopter France (Eurocopter) Model EC225LP Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-27

... tightening torque of the screws which secure the assembly. Since then, Eurocopter has developed a.... EASB 05A005 specifies checking the dome fairing support for a crack and readjusting the tightening torque of the dome fairing-to-dome fairing support attachment screws. If a crack is found, the EASB...

49 CFR 178.360-4 - Closure devices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... securely tightened. Pipe threads must be luted with an appropriate non-hardening compound which must be capable of withstanding up to 149 °C (300 °F) without loss of efficiency. Tightening torque must be... subchapter). A torque wrench must be used in securing the flange with a corresponding torque of no more than...

Microfocused ultrasound for skin tightening.

PubMed

MacGregor, Jennifer L; Tanzi, Elizabeth L

2013-03-01

The demand for noninvasive skin tightening procedures is increasing as patients seek safe and effective alternatives to aesthetic surgical procedures of the face, neck, and body. Over the past decade, radiofrequency and infrared laser devices have been popularized owing to their ability to deliver controlled heat to the dermis, stimulate neocollagenesis, and effect modest tissue tightening with minimal recovery. However, these less invasive approaches are historically associated with inferior efficacy so that surgery still remains the treatment of choice to address moderate to severe tissue laxity. Microfocused ultrasound was recently introduced as a novel energy modality for transcutaneous heat delivery that reaches the deeper subdermal connective tissue in tightly focused zones at consistent programmed depths. The goal is to produce a deeper wound healing response at multiple levels with robust collagen remodeling and a more durable clinical response. The Ulthera device (Ulthera, Inc, Meza, AZ), with refined microfocused ultrasound technology, has been adapted specifically for skin tightening and lifting with little recovery or risk of complications since its introduction in 2009. As clinical parameters are studied and optimized, enhanced efficacy and consistency of clinical improvement is expected.

Cortical bone strains around straight and angulated immediate orthodontic microimplants: a pilot study.

PubMed

Cehreli, Secil; Yilmaz, Alev; Arman-Ozcirpici, Ayca

2013-04-01

To measure strains around orthodontic implants upon torque tightening and loading and to assess correlations between factors influencing primary stability. Self-drilling implants were placed into bovine iliac crest blocks after CT assessments. Upon bonding of strain gauges on bone adjacent to the implants, strain measurements were performed using a data acquisition system during torque tightening and 250 g orthodontic force application by elastic chains. The torque required to place straight implants (12.16 N.cm) was higher than 30- to 40-degree angulated implants (9.31 N.cm) (P < 0.05). Cortical bone strain amplitudes of both implant placements were comparable (P > 0.05). Strains during torque tightening of straight (196 με) and tilted (114 με) implants were higher than those obtained during orthodontic loading (20-30 με). Despite the positive and direct relationship found between torque and torque strain output, strong correlations between other parameters could not be detected. Vertically aligned and 30- to 40-degree angulated immediate orthodontic microimplants are associated with low amplitude strains upon torque tightening and orthodontic loading.

Effects of Screw Configuration on the Preload Force of Implant-Abutment Screws.

PubMed

Zipprich, Holger; Rathe, Florian; Pinz, Sören; Schlotmann, Luca; Lauer, Hans-Christoph; Ratka, Christoph

The aim of this study was to investigate the effects of tightening torque, screw head angle, and thread number on the preload force of abutment screws. The test specimens consisted of three self-manufactured components (ie, a thread sleeve serving as an implant analog, an abutment analog, and an abutment screw). The abutment screws were fabricated with metric M1.6 external threads. The thread number varied between one and seven threads. The screw head angles were produced in eight varying angles (30 to 180 degrees). A sensor unit simultaneously measured the preload force of the screw and the torsion moment inside the screw shank. The tightening of the screw with the torque wrench was performed in five steps (15 to 35 Ncm). The torque wrench was calibrated before each step. Only the tightening torque and screw head angle affected the resulting preload force of the implant-abutment connection. The thread number had no effect. There was an approximately linear correlation between tightening torque and preload force. The tightening torque and screw head angle were the only study parameters that affected the resulting preload force of the abutment screw. The results obtained from this experiment are valid only for a single torque condition. Further investigations are needed that analyze other parameters that affect preload force. Once these parameters are known, it will add value for a strong, but detachable connection between the implant and abutment. Short implants and flat-to-flat connections especially will benefit significantly from this knowledge.

Complementary clinical effects of topical tightening treatment in conjunction with a radiofrequency procedure.

PubMed

Goldberg, David J; Yatskayer, Margarita; Raab, Susana; Chen, Nannan; Krol, Yevgeniy; Oresajo, Christian

2014-10-01

Abstract Background: Skin laxity and cellulite on the buttocks and thighs are two common cosmetic concerns. Skin tightening with radiofrequency (RF) devices has become increasingly popular. The purpose of this study is to evaluate the efficacy and safety of a topical skin laxity tightening agent when used in combination with an RF device. A double-blinded, randomized clinical trial enrolled twenty females with mild-to-moderate skin laxity on the posterior thighs/buttocks. Each subject underwent two monthly treatments with an RF source (Alma Accent) to both legs. Subjects were then randomized to apply a topical agent (Skinceuticals Body Tightening Concentrate) twice daily to only one designated thigh/buttock throughout the eight-week duration of the study. All subjects were evaluated for improvement in lifting, skin tone, radiance, firmness/tightness, skin texture, and overall appearance based on photographic evaluation by blinded investigators at 12 weeks following the final RF treatment. A statistically significant improvement was found in the overall appearance on both sides treated with the RF device when compared to baseline. However, the area treated with the topical agent showed a statistically significantly greater degree of improvement than the side where no topical agent was applied. No adverse effects were reported. The use of a novel skin tightening agent used after RF procedures is both safe and effective for treatment of skin laxity on the buttocks and thighs. Combined therapy leads to a better result.

Cancer Imaging Phenomics Toolkit (CaPTK) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

CaPTk is a tool that facilitates translation of highly sophisticated methods that help us gain a comprehensive understanding of the underlying mechanisms of cancer from medical imaging research to the clinic. It replicates basic interactive functionalities of radiological workstations and is distributed under a BSD-style license.

Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome.

PubMed

Bicknell, Louise S; Walker, Sarah; Klingseisen, Anna; Stiff, Tom; Leitch, Andrea; Kerzendorfer, Claudia; Martin, Carol-Anne; Yeyati, Patricia; Al Sanna, Nouriya; Bober, Michael; Johnson, Diana; Wise, Carol; Jackson, Andrew P; O'Driscoll, Mark; Jeggo, Penny A

2011-02-27

Studies into disorders of extreme growth failure (for example, Seckel syndrome and Majewski osteodysplastic primordial dwarfism type II) have implicated fundamental cellular processes of DNA damage response signaling and centrosome function in the regulation of human growth. Here we report that mutations in ORC1, encoding a subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. We establish that these mutations disrupt known ORC1 functions including pre-replicative complex formation and origin activation. ORC1 deficiency perturbs S-phase entry and S-phase progression. Additionally, we show that Orc1 depletion in zebrafish is sufficient to markedly reduce body size during rapid embryonic growth. Our data suggest a model in which ORC1 mutations impair replication licensing, slowing cell cycle progression and consequently impeding growth during development, particularly at times of rapid proliferation. These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing.

Effect of force tightening on cable tension and displacement in greater trochanter reattachment.

PubMed

Canet, Fanny; Duke, Kajsa; Bourgeois, Yan; Laflamme, G-Yves; Brailovski, Vladimir; Petit, Yvan

2011-01-01

The purpose of this study was to evaluate cable tension during installation, and during loading similar to walking in a cable grip type greater trochanter (GT), reattachment system. A 4th generation Sawbones composite femur with osteotomised GT was reattached with four Cable-Ready® systems (Zimmer, Warsaw, IN). Cables were tightened at 3 different target installation forces (178, 356 and 534 N) and retightened once as recommended by the manufacturer. Cables tension was continuously monitored using in-situ load cells. To simulate walking, a custom frame was used to apply quasi static load on the head of a femoral stem implant (2340 N) and abductor pull (667 N) on the GT. GT displacement (gap and sliding) relative to the femur was measured using a 3D camera system. During installation, a drop in cable tension was observed when tightening subsequent cables: an average 40+12.2% and 11 ± 5.9% tension loss was measured in the first and second cable. Therefore, retightening the cables, as recommended by the manufacturer, is important. During simulated walking, the second cable additionally lost up to 12.2+3.6% of tension. No difference was observed between the GT-femur gaps measured with cables tightened at different installation forces (p=0.32). The GT sliding however was significantly greater (0.9 ± 0.3 mm) when target installation force was set to only 178 N compared to 356 N (0.2 ± 0.1 mm); p<0.001. There were no significant changes when initial tightening force was increased to 534 N (0.3 ± 0.1 mm); p=0.11. In conclusion, the cable tightening force should be as close as possible to that recommended by the manufacturer, because reducing it compromises the stability of the GT fragment, whereas increasing it does not improve this stability, but could lead to cable breakage.

Pre-load on oral implants after screw tightening fixed full prostheses: an in vivo study.

PubMed

Duyck, J; Van Oosterwyck, H; Vander Sloten, J; De Cooman, M; Puers, R; Naert, I

2001-03-01

The fit of implant supported fixed prostheses is said to be of clinical concern because of the rigid fixation of an oral implant in its surrounding bone. The influence of the torque sequence of the set screws during fixation of implant supported fixed full prostheses on the final pre-load was investigated in vitro. No significant effect of the torque sequence of the set screws on the final pre-load was observed. The main objective of this study was to quantify and qualify the pre-load in vivo on implants supporting a fixed full prosthesis. This was performed when the prostheses were supported by all five or six implants and was repeated when the prostheses were supported by only four and three implants. A total of 13 patients with a fixed full implant supported prosthesis were selected. The existing abutments were changed for strain gauged abutments. After tightening the set screws with a torque of 10 N cm, the pre-load conditions were registered. The average (SEM) axial forces and bending moments in case of five or six, four and three supporting implants were 323 N (43 N), 346 N (59 N), 307 N (60 N) 21 N cm (3 N cm) and 21 N cm (2 N cm), 23 N cm (5 N cm), respectively. In addition, the pre-load was registered after fixation of a machined gold cylinder, as delivered by the manufacturer, on each of the supporting implants, representing the 'optimal fit' situation. The corresponding average (SEM) axial forces and bending moments in case of five or six, four and three supporting implants were 426 N (36 N), 405 N (40 N), 413 N (46 N) and 8 N cm (1 N cm), 8 N cm (1 N cm), 8 N cm (1 N cm), respectively. The induced axial forces after tightening the prostheses were significantly lower then after tightening the gold cylinder in case of five or six supporting implants (P < 0.02). The induced bending moments after tightening the prostheses were statistically significantly higher (P < 0.0001) then after tightening the gold cylinder in all test conditions (five or six, four or three supporting implants). This study underlines the static load present after screw tightening implant supported fixed full prostheses.

The plant cell cycle: Pre-Replication complex formation and controls

PubMed Central

Brasil, Juliana Nogueira; Costa, Carinne N. Monteiro; Cabral, Luiz Mors; Ferreira, Paulo C. G.; Hemerly, Adriana S.

2017-01-01

Abstract The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes. PMID:28304073

Phosphopeptide binding by Sld3 links Dbf4-dependent kinase to MCM replicative helicase activation.

PubMed

Deegan, Tom D; Yeeles, Joseph Tp; Diffley, John Fx

2016-05-02

The initiation of eukaryotic DNA replication requires the assembly of active CMG (Cdc45-MCM-GINS) helicases at replication origins by a set of conserved and essential firing factors. This process is controlled during the cell cycle by cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK), and in response to DNA damage by the checkpoint kinase Rad53/Chk1. Here we show that Sld3, previously shown to be an essential CDK and Rad53 substrate, is recruited to the inactive MCM double hexamer in a DDK-dependent manner. Sld3 binds specifically to DDK-phosphorylated peptides from two MCM subunits (Mcm4, 6) and then recruits Cdc45. MCM mutants that cannot bind Sld3 or Sld3 mutants that cannot bind phospho-MCM or Cdc45 do not support replication. Moreover, phosphomimicking mutants in Mcm4 and Mcm6 bind Sld3 without DDK and facilitate DDK-independent replication. Thus, Sld3 is an essential "reader" of DDK phosphorylation, integrating signals from three distinct protein kinase pathways to coordinate DNA replication during S phase. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

RPA activates the XPF-ERCC1 endonuclease to initiate processing of DNA interstrand crosslinks.

PubMed

Abdullah, Ummi B; McGouran, Joanna F; Brolih, Sanja; Ptchelkine, Denis; El-Sagheer, Afaf H; Brown, Tom; McHugh, Peter J

2017-07-14

During replication-coupled DNA interstrand crosslink (ICL) repair, the XPF-ERCC1 endonuclease is required for the incisions that release, or "unhook", ICLs, but the mechanism of ICL unhooking remains largely unknown. Incisions are triggered when the nascent leading strand of a replication fork strikes the ICL Here, we report that while purified XPF-ERCC1 incises simple ICL-containing model replication fork structures, the presence of a nascent leading strand, modelling the effects of replication arrest, inhibits this activity. Strikingly, the addition of the single-stranded DNA (ssDNA)-binding replication protein A (RPA) selectively restores XPF-ERCC1 endonuclease activity on this structure. The 5'-3' exonuclease SNM1A can load from the XPF-ERCC1-RPA-induced incisions and digest past the crosslink to quantitatively complete the unhooking reaction. We postulate that these collaborative activities of XPF-ERCC1, RPA and SNM1A might explain how ICL unhooking is achieved in vivo . © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

ORC1 BAH domain links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome

PubMed Central

Kuo, Alex J.; Song, Jikui; Cheung, Peggie; Ishibe-Murakami, Satoko; Yamazoe, Sayumi; Chen, James K.; Patel, Dinshaw J.; Gozani, Or

2012-01-01

Recognition of distinctly modified histones by specialized “effector” proteins constitutes a key mechanism for transducing molecular events at chromatin to biological outcomes1. Effector proteins influence DNA-templated processes, including transcription, DNA recombination, and DNA repair; however, no effector functions have yet been identified within the mammalian machinery that regulates DNA replication. Here we show that ORC1 – a component of ORC (origin of replication complex), which mediates pre-DNA replication licensing2 – contains a BAH (bromo adjacent homology) domain that specifically recognizes histone H4 dimethylated at lysine 20 (H4K20me2). Recognition of H4K20me2 is a property common to BAH domains present within diverse metazoan ORC1 proteins. Structural studies reveal that the specificity of the BAH domain for H4K20me2 is mediated by a dynamic aromatic dimethyllysine-binding cage and multiple intermolecular contacts involving the bound peptide. H4K20me2 is enriched at replication origins and abrogating ORC1 recognition of H4K20me2 in cells impairs ORC1 occupancy at origins, ORC chromatin loading, and cell-cycle progression. Mutation of the ORC1 BAH domain has been implicated in the etiology of Meier-Gorlin syndrome (MGS)3,4, a form of primordial dwarfism5, and ORC1 depletion in zebrafish results in an MGS-like phenotype4. We find that wild-type human ORC1, but not ORC1 H4K20me2-binding mutants, rescues the growth retardation of orc1 morphants. Moreover, zebrafish depleted of H4K20me2 have diminished body size, mirroring the phenotype of orc1 morphants. Together, our results identify the BAH domain as a novel methyllysine-binding module, thereby establishing the first direct link between histone methylation and the metazoan DNA replication machinery, and defining a pivotal etiologic role for the canonical H4K20me2 mark, via ORC1, in primordial dwarfism. PMID:22398447

The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

PubMed

Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

2013-12-01

Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

49 CFR 572.86 - Test conditions and dummy adjustment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... lying on a horizontal surface and the neck assembly mounted and shoulders on the edge of the surface... surface with the shoulders on the edge of the surface, mount the head and tighten the head bolt and nut... upper arm and tighten firmly the adjustment bolts for the shoulder joint with the upper arm placed in a...

49 CFR 572.86 - Test conditions and dummy adjustment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... lying on a horizontal surface and the neck assembly mounted and shoulders on the edge of the surface... surface with the shoulders on the edge of the surface, mount the head and tighten the head bolt and nut... upper arm and tighten firmly the adjustment bolts for the shoulder joint with the upper arm placed in a...

49 CFR 572.86 - Test conditions and dummy adjustment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... lying on a horizontal surface and the neck assembly mounted and shoulders on the edge of the surface... surface with the shoulders on the edge of the surface, mount the head and tighten the head bolt and nut... upper arm and tighten firmly the adjustment bolts for the shoulder joint with the upper arm placed in a...

49 CFR 572.86 - Test conditions and dummy adjustment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... lying on a horizontal surface and the neck assembly mounted and shoulders on the edge of the surface... surface with the shoulders on the edge of the surface, mount the head and tighten the head bolt and nut... upper arm and tighten firmly the adjustment bolts for the shoulder joint with the upper arm placed in a...

49 CFR 572.86 - Test conditions and dummy adjustment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... lying on a horizontal surface and the neck assembly mounted and shoulders on the edge of the surface... surface with the shoulders on the edge of the surface, mount the head and tighten the head bolt and nut... upper arm and tighten firmly the adjustment bolts for the shoulder joint with the upper arm placed in a...

49 CFR 572.75 - Lumbar spine, abdomen, and pelvis assembly and test procedure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... specified in Figure 42. (2) Adjust the dummy by— (i) Tightening the femur ballflange screws at each hip socket joint to 50 inch-pounds torque; (ii) Attaching the pelvis to the seating surface by a bolt D/605... drawing Figure 42. (iv) Tightening the mountings so that the pelvis-lumbar joining surface is horizontal...

49 CFR 572.75 - Lumbar spine, abdomen, and pelvis assembly and test procedure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... specified in Figure 42. (2) Adjust the dummy by— (i) Tightening the femur ballflange screws at each hip socket joint to 50 inch-pounds torque; (ii) Attaching the pelvis to the seating surface by a bolt D/605... drawing Figure 42. (iv) Tightening the mountings so that the pelvis-lumbar joining surface is horizontal...

49 CFR 572.75 - Lumbar spine, abdomen, and pelvis assembly and test procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... specified in Figure 42. (2) Adjust the dummy by— (i) Tightening the femur ballflange screws at each hip socket joint to 50 inch-pounds torque; (ii) Attaching the pelvis to the seating surface by a bolt D/605... drawing Figure 42. (iv) Tightening the mountings so that the pelvis-lumbar joining surface is horizontal...

49 CFR 572.75 - Lumbar spine, abdomen, and pelvis assembly and test procedure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... specified in Figure 42. (2) Adjust the dummy by— (i) Tightening the femur ballflange screws at each hip socket joint to 50 inch-pounds torque; (ii) Attaching the pelvis to the seating surface by a bolt D/605... drawing Figure 42. (iv) Tightening the mountings so that the pelvis-lumbar joining surface is horizontal...

49 CFR 572.75 - Lumbar spine, abdomen, and pelvis assembly and test procedure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... specified in Figure 42. (2) Adjust the dummy by— (i) Tightening the femur ballflange screws at each hip socket joint to 50 inch-pounds torque; (ii) Attaching the pelvis to the seating surface by a bolt D/605... drawing Figure 42. (iv) Tightening the mountings so that the pelvis-lumbar joining surface is horizontal...

Tenured Faculty Members Are Spared in Latest Round of Belt Tightening.

ERIC Educational Resources Information Center

Mooney, Carolyn J.

1993-01-01

Although the 1980s period of belt-tightening in higher education meant layoff of many tenured professors, financially troubled colleges are trimming part-time and nontenured faculty jobs and offering encouraging early retirement in the current period of retrenchment. However, the proportion of tenured faculty has shrunk as the overall size of the…

Noninvasive Skin Tightening Treatment

PubMed Central

2015-01-01

Noninvasive skin tightening has become one of the most common cosmetic aesthetic procedures being performed today. The use of radiofrequency devices for these procedures has been at the forefront of this trend for the past several years. Newer and more sophisticated radiofrequency devices are being brought to the market and presented here are the Venus Freeze and Venus Legacy. PMID:26155322

Internal core tightener

DOEpatents

Brynsvold, Glen V.; Snyder, Jr., Harold J.

1976-06-22

An internal core tightener which is a linear actuated (vertical actuation motion) expanding device utilizing a minimum of moving parts to perform the lateral tightening function. The key features are: (1) large contact areas to transmit loads during reactor operation; (2) actuation cam surfaces loaded only during clamping and unclamping operation; (3) separation of the parts and internal operation involved in the holding function from those involved in the actuation function; and (4) preloaded pads with compliant travel at each face of the hexagonal assembly at the two clamping planes to accommodate thermal expansion and irradiation induced swelling. The latter feature enables use of a "fixed" outer core boundary, and thus eliminates the uncertainty in gross core dimensions, and potential for rapid core reactivity changes as a result of core dimensional change.

Trends in Residential Services for Mentally Retarded People: 1977-1982. Brief #23.

ERIC Educational Resources Information Center

Hill, B. K.; Lakin, K. C.

In 1977 a survey was conducted of all state-licensed, state-contracted, and state-operated residential facilities serving mentally retarded people in the United States. The survey was replicated in 1982 and this report summarizes and compares the results of the two surveys. Results indicate that the overall size of the residential service system…

Tightening the Purchasing Process: Superintendents Get More Involved in Buying Policies

ERIC Educational Resources Information Center

Rivero, Victor

2009-01-01

Over the last 18 months, school district purchasing offices across the country have been tightening the reins like never before while more top-level administrators get involved in the budget process. "When the economy really hit the skids, states got hit hard, so a lot of school districts were forced to make severe budget cuts," says John Musso,…

75 FR 3418 - Airworthiness Directives; British Aerospace Regional Aircraft Model HP.137 Jetstream Mk.1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-21

... tightening torque are contained in APPH SB 32-76 Revision 1. As a result, pistons which were previously... formula for calculating the piston safe life. This calculation and a revised end fitting tightening torque... piston rod adjacent to the eye-end. This was caused by excessive torque which had been applied to the eye...

String tightening as a self-organizing phenomenon.

PubMed

Banerjee, Bonny

2007-09-01

The phenomenon of self-organization has been of special interest to the neural network community throughout the last couple of decades. In this paper, we study a variant of the self-organizing map (SOM) that models the phenomenon of self-organization of the particles forming a string when the string is tightened from one or both of its ends. The proposed variant, called the string tightening self-organizing neural network (STON), can be used to solve certain practical problems, such as computation of shortest homotopic paths, smoothing paths to avoid sharp turns, computation of convex hull, etc. These problems are of considerable interest in computational geometry, robotics path-planning, artificial intelligence (AI) (diagrammatic reasoning), very large scale integration (VLSI) routing, and geographical information systems. Given a set of obstacles and a string with two fixed terminal points in a 2-D space, the STON model continuously tightens the given string until the unique shortest configuration in terms of the Euclidean metric is reached. The STON minimizes the total length of a string on convergence by dynamically creating and selecting feature vectors in a competitive manner. Proof of correctness of this anytime algorithm and experimental results obtained by its deployment have been presented in the paper.

In Vitro Evaluation of Manual Torque Values Applied to Implant-Abutment Complex by Different Clinicians and Abutment Screw Loosening.

PubMed

Dincer Kose, Onur; Karataslı, Burcin; Demircan, Sabit; Kose, Taha Emre; Cene, Erhan; Aya, Serhan Aydın; Erdem, Mehmet Ali; Cankaya, Abdulkadir Burak

2017-01-01

Preload is applied to screws manually or using a torque wrench in dental implant systems, and the preload applied must be appropriate for the purpose. The aim of this study was to assess screw loosening and bending/torsional moments applied by clinicians of various specialties following application of manual tightening torque to combinations of implants and abutments. Ten-millimeter implants of 3.7 and 4.1 mm diameters and standard or solid abutments were used. Each group contained five implant-abutment combinations. The control and experimental groups comprised 20 and 160 specimens, respectively. Implants in the experimental group were tightened by dentists of different specialties. Torsional and bending moments during tightening were measured using a strain gauge. Control group and implants with preload values close to the ideal preload were subjected to a dynamic loading test at 150 N, 15 Hz, and 85,000 cycles. The implants that deformed in this test were examined using an optical microscope to assess deformities. Manual tightening did not yield the manufacturer-recommended preload values. Dynamic loading testing suggested early screw loosening/fracture in samples with insufficient preload.

In Vitro Evaluation of Manual Torque Values Applied to Implant-Abutment Complex by Different Clinicians and Abutment Screw Loosening

PubMed Central

Demircan, Sabit; Cene, Erhan; Aya, Serhan Aydın; Erdem, Mehmet Ali; Cankaya, Abdulkadir Burak

2017-01-01

Preload is applied to screws manually or using a torque wrench in dental implant systems, and the preload applied must be appropriate for the purpose. The aim of this study was to assess screw loosening and bending/torsional moments applied by clinicians of various specialties following application of manual tightening torque to combinations of implants and abutments. Ten-millimeter implants of 3.7 and 4.1 mm diameters and standard or solid abutments were used. Each group contained five implant-abutment combinations. The control and experimental groups comprised 20 and 160 specimens, respectively. Implants in the experimental group were tightened by dentists of different specialties. Torsional and bending moments during tightening were measured using a strain gauge. Control group and implants with preload values close to the ideal preload were subjected to a dynamic loading test at 150 N, 15 Hz, and 85,000 cycles. The implants that deformed in this test were examined using an optical microscope to assess deformities. Manual tightening did not yield the manufacturer-recommended preload values. Dynamic loading testing suggested early screw loosening/fracture in samples with insufficient preload. PMID:28473988

Split-face histological and biochemical evaluation of tightening efficacy using temperature- and impedance-controlled continuous non-invasive radiofrequency energy.

PubMed

Boisnic, Sylvie; Divaris, Marc; Branchet, Marie-Christine; Nelson, Andrew A

2017-06-01

Bipolar radiofrequency (RF) is capable of heating dermal collagen fibers and inducing skin tightening by collagen remodeling. To substantiate safety and improvement of skin laxity following skin heating with a novel temperature- and impedance-controlled non-invasive radiofrequency (RF) device by histological and biochemical evaluations. A split-face study was performed on 4 subjects who underwent 8 weekly RF sessions on one side of their face, leaving the other side an untreated control and then underwent facelift procedure. Clinical evaluation by photographs was done prior to the surgical procedure. Ex vivo fragments were harvested from both sides and compared. Morphometric analysis of dermal collagen fibers, collagen synthesis, and elastin synthesis evaluations were compared in triplicates. Facial skin tightening was apparent in split-face photographs. A significant increase of 7.9% in dermal collagen content, and a significant increase of 34.7% in collagen synthesis were demonstrated in the treated samples. No statistically significant effect on elastin synthesis was detected. Skin tightening following treatment with non-invasive RF has proven histologically and biochemically to derive from increase in dermal collagen synthesis and content.

U.S. Air Force Live | The Official Blog of the United States Air Force

Science.gov Websites

. Christopher Uecker, 25th Aircraft Maintenance Unit weapons load crew team chief, tightens a guided bomb unit Uecker, 25th Aircraft Maintenance Unit weapons load crew team chief, tightens a guided bomb unit onto an Maintenance Unit load munitions onto an A-10 Thunderbolt II during the Vigilant Ace 16 exercise on Osan Air

Micro-leakage at the implant-abutment interface with different tightening torques in vitro.

PubMed

Silva-Neto, João Paulo da; Prudente, Marcel Santana; Carneiro, Thiago de Almeida Prado Naves; Nóbilo, Mauro Antônio de Arruda; Penatti, Mario Paulo Amante; Neves, Flávio Domingues das

2012-01-01

This study evaluated the microleakage at the implant/abutment interface of external hexagon (eH) implants and abutments with different amounts of bacteria and tightening torques. A bacterial suspension was prepared to inoculate the implants. The first phase of this study used nine EH implants and abutments that were divided into three groups with different amounts of bacterial suspension (n=3): V0.5: 0.5 µL; V1.0: 1.0 µL e V1.5: 1.5 µL, and tightened to the manufacturer's recommended torque. The second phase of this experiment used 27 assemblies that were similar to those used in the first phase. These samples were inoculated with 0.5 µL of bacterial suspension and divided into three groups (n=9). T10: 10 Ncm; T20: 20 Ncm and T32: 32 Ncm. The samples were evaluated according to the turbidity of the broth every 24 hours for 14 days, and the bacteria viability was tested after that period. The statistical evaluation was conducted by Kruskal-Wallis testing (p<.05). During the first phase, groups V1.0 and V1.5 was presented with bacterial contamination in all samples after 24 h. During the second phase, two samples from group T10 and one from T20 presented positive results for bacterial contamination. Different amounts of bacterial solution led to overflow and contamination during the first 24 h of the experiment. The tightening torques did not statistically affect the microleakage in the assemblies. However, the group that was tightened to 32 Ncm torque did not show any bacterial contamination. After 14 days of experimentation, the bacteria were proven to remain viable inside the implant internal cavity.

Micro-leakage at the implant-abutment interface with different tightening torques in vitro

PubMed Central

da SILVA-NETO, João Paulo; PRUDENTE, Marcel Santana; CARNEIRO, Thiago de Almeida Prado Naves; NÓBILO, Mauro Antônio de Arruda; PENATTI, Mario Paulo Amante; NEVES, Flávio Domingues das

2012-01-01

Objectives This study evaluated the microleakage at the implant/abutment interface of external hexagon (EH) implants and abutments with different amounts of bacteria and tightening torques. Material and Methods A bacterial suspension was prepared to inoculate the implants. The first phase of this study used nine EH implants and abutments that were divided into three groups with different amounts of bacterial suspension (n=3): V0.5: 0.5 µL; V1.0: 1.0 µL e V1.5: 1.5 µL, and tightened to the manufacturer's recommended torque. The second phase of this experiment used 27 assemblies that were similar to those used in the first phase. These samples were inoculated with 0.5 µL of bacterial suspension and divided into three groups (n=9). T10: 10 Ncm; T20: 20 Ncm and T32: 32 Ncm. The samples were evaluated according to the turbidity of the broth every 24 hours for 14 days, and the bacteria viability was tested after that period. The statistical evaluation was conducted by Kruskal-Wallis testing (p<.05). Results During the first phase, groups V1.0 and V1.5 was presented with bacterial contamination in all samples after 24 h. During the second phase, two samples from group T10 and one from T20 presented positive results for bacterial contamination. Different amounts of bacterial solution led to overflow and contamination during the first 24 h of the experiment. The tightening torques did not statistically affect the microleakage in the assemblies. However, the group that was tightened to 32 Ncm torque did not show any bacterial contamination. Conclusion After 14 days of experimentation, the bacteria were proven to remain viable inside the implant internal cavity. PMID:23138747

Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication.

PubMed

Brustel, Julien; Kirstein, Nina; Izard, Fanny; Grimaud, Charlotte; Prorok, Paulina; Cayrou, Christelle; Schotta, Gunnar; Abdelsamie, Alhassan F; Déjardin, Jérôme; Méchali, Marcel; Baldacci, Giuseppe; Sardet, Claude; Cadoret, Jean-Charles; Schepers, Aloys; Julien, Eric

2017-09-15

Among other targets, the protein lysine methyltransferase PR-Set7 induces histone H4 lysine 20 monomethylation (H4K20me1), which is the substrate for further methylation by the Suv4-20h methyltransferase. Although these enzymes have been implicated in control of replication origins, the specific contribution of H4K20 methylation to DNA replication remains unclear. Here, we show that H4K20 mutation in mammalian cells, unlike in Drosophila , partially impairs S-phase progression and protects from DNA re-replication induced by stabilization of PR-Set7. Using Epstein-Barr virus-derived episomes, we further demonstrate that conversion of H4K20me1 to higher H4K20me2/3 states by Suv4-20h is not sufficient to define an efficient origin per se , but rather serves as an enhancer for MCM2-7 helicase loading and replication activation at defined origins. Consistent with this, we find that Suv4-20h-mediated H4K20 tri-methylation (H4K20me3) is required to sustain the licensing and activity of a subset of ORCA/LRWD1-associated origins, which ensure proper replication timing of late-replicating heterochromatin domains. Altogether, these results reveal Suv4-20h-mediated H4K20 tri-methylation as a critical determinant in the selection of active replication initiation sites in heterochromatin regions of mammalian genomes. © 2017 The Authors.

ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells.

PubMed

Lewis, Samantha C; Uchiyama, Lauren F; Nunnari, Jodi

2016-07-15

Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood. Mitochondrial distribution depends on division, which occurs at endoplasmic reticulum (ER)-mitochondria contact sites. These sites were spatially linked to a subset of nucleoids selectively marked by mtDNA polymerase and engaged in mtDNA synthesis--events that occurred upstream of mitochondrial constriction and division machine assembly. Our data suggest that ER tubules proximal to nucleoids are necessary but not sufficient for mtDNA synthesis. Thus, ER-mitochondria contacts coordinate licensing of mtDNA synthesis with division to distribute newly replicated nucleoids to daughter mitochondria. Copyright © 2016, American Association for the Advancement of Science.

The cholesterol, fatty acid and triglyceride synthesis pathways regulated by site 1 protease (S1P) are required for efficient replication of severe fever with thrombocytopenia syndrome virus.

PubMed

Urata, Shuzo; Uno, Yukiko; Kurosaki, Yohei; Yasuda, Jiro

2018-06-12

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively. These results enhance our understanding of the SFTSV replication mechanism and may contribute to the development of novel therapies for SFTSV infection. Copyright © 2018. Published by Elsevier Inc.

Fractional nonablative laser resurfacing: is there a skin tightening effect?

PubMed

Kauvar, Arielle N B

2014-12-01

Fractional photothermolysis, an approach to laser skin resurfacing that creates microscopic thermal wounds in skin separated by islands of spared tissue, was developed to overcome the high incidence of adverse events and prolonged healing times associated with full coverage ablative laser procedures. To examine whether fractional nonablative laser resurfacing induces skin tightening. A literature review was performed to evaluate the clinical and histologic effects of fractional nonablative laser resurfacing and full coverage ablative resurfacing procedures. Fractional nonablative lasers produce excellent outcomes with minimal risk and morbidity for a variety of clinical conditions, including photodamaged skin, atrophic scars, surgical and burn scars. Efforts to induce robust fibroplasia in histologic specimens and skin tightening in the clinical setting have yielded inconsistent results. A better understanding of the histology of fractional laser resurfacing will help to optimize clinical outcomes.

Non-ablative skin tightening with radiofrequency in Asian skin.

PubMed

Kushikata, Nobuharu; Negishi, Kei; Tezuka, Yukiko; Takeuchi, Kaori; Wakamatsu, Shingo

2005-02-01

The recent successful application of radiofrequency (RF) in non-ablative skin tightening for skin laxity has attracted attention worldwide. The efficacy and clinical effect of RF were assessed in Asian skin, with additional study on the duration of the effect and any complications. Eighty-five Japanese females were enrolled in the study for treatment of nasolabial folds, marionette lines, and sagging jowls with 6-month follow-up. RF treatment was effective for nasolabial folds, marionette lines, and jowls. Objective physician evaluation found relatively good improvement at 3 months post-treatment, and even better improvement at the 6-month evaluation. RF treatment was very satisfactory for skin tightening in Asian facial skin. When compared with published literature from the United States, the results suggested that there might be race-related differences in the treatment parameters. (c) 2005 Wiley-Liss, Inc.

Adjustable-Torque Truss-Joint Mechanism

NASA Technical Reports Server (NTRS)

Bush, Harold G.; Wallsom, Richard E.

1993-01-01

Threaded pin tightened or loosened; tedious trial-and-error procedure shortened. Mechanism joining strut and node in truss structure preloaded to desired stress to ensure tight, compressive fit preventing motion of strut during loading or vibration. Preload stress on stack of Belleville spring washers adjusted by tightening or loosening threaded Belleville-washer-alignment pin. Pin turned, by use of allen wrench, to adjust compression preload on Belleville washers and adjusts joint-operating torque.

Changes in Financial Aid and Student Enrollment at Historically Black Colleges and Universities after the Tightening of PLUS Credit Standards: An Update for the 2013/14 School Year. REL 2017-254

ERIC Educational Resources Information Center

Johnson, Matthew; Bruch, Julie; Gill, Brian

2017-01-01

In 2011 the U.S. Department of Education tightened the credit standards for Parent Loans for Undergraduate Students (PLUS). Concerned about the possible effects of this change on historically Black colleges and universities (HBCUs), Regional Educational Laboratory Mid-Atlantic's Historically Black Colleges and Universities College Completion…

Home-use TriPollar RF device for facial skin tightening: Clinical study results.

PubMed

Beilin, Ghislaine

2011-04-01

Professional, non-invasive, anti-aging treatments based on radio-frequency (RF) technologies are popular for skin tightening and improvement of wrinkles. A new home-use RF device for facial treatments has recently been developed based on TriPollar™ technology. To evaluate the STOP™ home-use device for facial skin tightening using objective and subjective methods. Twenty-three female subjects used the STOP at home for a period of 6 weeks followed by a maintenance period of 6 weeks. Facial skin characteristics were objectively evaluated at baseline and at the end of the treatment and maintenance periods using a three-dimensional imaging system. Additionally, facial wrinkles were classified and subjects scored their satisfaction and sensations. Following STOP treatment, a statistically significant reduction of perioral and periorbital wrinkles was achieved in 90% and 95% of the patients, respectively, with an average periorbital wrinkle reduction of 41%. This objective result correlated well with the periorbital wrinkle classification result of 40%. All patients were satisfied to extremely satisfied with the treatments and all reported moderate to excellent visible results. The clinical study demonstrated the safety and efficacy of the STOP home-use device for facial skin tightening. Treatment can maintain a tighter and suppler skin with improvement of fine lines and wrinkles.

Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

PubMed

Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

2016-12-06

The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

New-generation radiofrequency technology.

PubMed

Krueger, Nils; Sadick, Neil S

2013-01-01

Radiofrequency (RF) technology has become a standard treatment in aesthetic medicine with many indications due to its versatility, efficacy, and safety. It is used worldwide for cellulite reduction; acne scar revision; and treatment of hypertrophic scars and keloids, rosacea, and inflammatory acne in all skin types. However, the most common indication for RF technology is the nonablative tightening of tissue to improve skin laxity and reduce wrinkles. Radiofrequency devices are classified as unipolar, bipolar, or multipolar depending on the number of electrodes used. Additional modalities include fractional RF; sublative RF; phase-controlled RF; and combination RF therapies that apply light, massage, or pulsed electromagnetic fields (PEMFs). This article reviews studies and case series on these devices. Radiofrequency technology for aesthetic medicine has seen rapid advancements since it was used for skin tightening in 2003. Future developments will continue to keep RF technology at the forefront of the dermatologist's armamentarium for skin tightening and rejuvenation.

Significance of DNA Replication Licensing Proteins (MCM2, MCM5 and CDC6), p16 and p63 as Markers of Premalignant Lesions of the Uterine Cervix: Its Usefulness to Predict Malignant Potential

PubMed Central

Saritha, VN; Veena, VS; Krishna, KM Jagathnath; Somanathan, Thara; Sujathan, K

2018-01-01

Cervical cancer continues to be a leading cancer among women in many parts of the world. Nation-wide screening with the Pap smear has not been implemented in India due to the lack of adequately trained cytologists. Identification of biomarkers to predict malignant potential of the identified low risk lesions is essential to avoid excessive retesting and follow up. The current study analyzed the expression patterns of DNA replication licensing proteins, proliferation inhibitor protein p16INK4A and tumor suppresser protein p63 in cervical tissues and smears to assess the ability of these proteins to predict progression. Methods: Cervical smears and corresponding tissues were immunostained using mouse monoclonal antibodies against MCM2, MCM5, CDC6, p16 and p63. Smears were treated with a non-ionic surfactant sodium deoxycholate prior to immuno-cytochemistry. The standard ABC method of immunohistochemistry was performed using DAB as the chromogen. The immunostained samples were scored on a 0-3+ scale and staining patterns of smears were compared with those of tissue sections. Sensitivity and specificity for each of these markers were calculated taking histopathology as the gold standard. Result: All the markers were positive in malignant and dysplastic cells. MCM protein expression was found to be up-regulated in LSIL, HSIL and in malignancies to a greater extent than p16 as well as p63. CDC6 protein was preferentially expressed in high grade lesions and in invasive squamous cell carcinomas. A progressive increase in the expression of DNA replication licensing proteins in accordance with the grades of cervical intraepithelial lesion suggests these markers as significant to predict malignant potential of low grade lesions in cervical smears. Conclusion: MCMs and CDC6 can be applied as biomarkers to predict malignant potential of low grade lesions identified in screening programmes and retesting / follow up might be confined to those with high risk lesions alone so that overuse of resources can be safely avoided. PMID:29373905

Novel features of ARS selection in budding yeast Lachancea kluyveri

PubMed Central

2011-01-01

Background The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined. Results In this study we have isolated and characterized autonomously replicating sequences (ARSs) in Lachancea kluyveri - a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that L. kluyveri ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in Saccharomyces cerevisiae. Moreover, compared with S. cerevisiae and K. lactis, the replication licensing machinery in L. kluyveri seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all S. cerevisiae ARSs tested and most Kluyveromyces lactis ARSs. In contrast, only about half of the L. kluyveri ARSs function in S. cerevisiae and less than 10% function in K. lactis. Conclusions Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs. PMID:22204614

Novel features of ARS selection in budding yeast Lachancea kluyveri.

PubMed

Liachko, Ivan; Tanaka, Emi; Cox, Katherine; Chung, Shau Chee Claire; Yang, Lu; Seher, Arael; Hallas, Lindsay; Cha, Eugene; Kang, Gina; Pace, Heather; Barrow, Jasmine; Inada, Maki; Tye, Bik-Kwoon; Keich, Uri

2011-12-28

The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined. In this study we have isolated and characterized autonomously replicating sequences (ARSs) in Lachancea kluyveri - a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that L. kluyveri ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in Saccharomyces cerevisiae. Moreover, compared with S. cerevisiae and K. lactis, the replication licensing machinery in L. kluyveri seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all S. cerevisiae ARSs tested and most Kluyveromyces lactis ARSs. In contrast, only about half of the L. kluyveri ARSs function in S. cerevisiae and less than 10% function in K. lactis. Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs.

Laser lipolysis: skin tightening in lipoplasty using a diode laser.

PubMed

Wolfenson, Moisés; Hochman, Bernardo; Ferreira, Lydia Massako

2015-05-01

New devices have been developed for surgical repair of deformities caused by localized fat deposits associated with skin laxity. The use of these devices requires the adoption of safety parameters. The aim of this study was to investigate skin tightening by laser lipolysis, using a dual-wavelength diode laser. This prospective, cross-sectional study was conducted between June of 2008 and July of 2010 with 41 consecutive patients who underwent laser lipolysis to correct contour deformities. Laser lipolysis was performed with a diode laser operating at two wavelengths (924 and 975 nm) controlled independently, and using three different tip lengths, allowing treatment of small, medium, and large areas of adipose tissue. The procedure was performed under local anesthesia in a surgical setting. To calculate the optimal cumulative energy, a total energy dose of 5 kJ/10 × 10-cm skin area was used as a safety parameter to prevent treatment complications. The circumferences of body regions were measured preoperatively, immediately after surgery, and 90 days later. Measurements were compared using the Wilcoxon test at a significance level of 0.05 (p < 0.05). A significant skin tightening was observed in all patients, regardless of the body site involved (i.e., face, breast, arms, or waist regions), and no complications occurred. Laser lipolysis results in progressive skin tightening over time. Therapeutic, IV.

Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria.

PubMed

Hoffman, Stephen L; Billingsley, Peter F; James, Eric; Richman, Adam; Loyevsky, Mark; Li, Tao; Chakravarty, Sumana; Gunasekera, Anusha; Chattopadhyay, Rana; Li, Minglin; Stafford, Richard; Ahumada, Adriana; Epstein, Judith E; Sedegah, Martha; Reyes, Sharina; Richie, Thomas L; Lyke, Kirsten E; Edelman, Robert; Laurens, Matthew B; Plowe, Christopher V; Sim, B Kim Lee

2010-01-01

Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.

Cytomegalovirus and polyomavirus BK posttransplant.

PubMed

Egli, Adrian; Binggeli, Simone; Bodaghi, Sohrab; Dumoulin, Alexis; Funk, Georg A; Khanna, Nina; Leuenberger, David; Gosert, Rainer; Hirsch, Hans H

2007-09-01

Virus replication and progression to disease in transplant patients is determined by patient-, graft- and virus-specific factors. This complex interaction is modulated by the net state of immunosuppression and its impact on virus-specific cellular immunity. Due to the increasing potency of immunosuppressive regimens, graft rejections have decreased, but susceptibility to infections has increased. Therefore, cytomegalovirus (CMV) remains the most important viral pathogen posttransplant despite availability of effective antiviral drugs and validated strategies for prophylactic, preemptive and therapeutic intervention. CMV replication can affect almost every organ system, with frequent recurrences and increasing rates of antiviral resistance. Together with indirect long-term effects, CMV significantly reduces graft and patient survival after solid organ and hematopoietic stem cell transplantation. The human polyomavirus called BK virus (BKV), on the other hand, only recently surfaced as pathogen with organ tropism largely limited to the reno-urinary tract, manifesting as polyomavirus-associated nephropathy in kidney transplant and hemorrhagic cystitis in hematopoetic stem cell transplant patients. No licensed anti-polyoma viral drugs are available, and treatment relies mainly on improving immune functions to regain control over BKV replication. In this review, we discuss diagnostic and therapeutic aspects of CMV and BKV replication and disease posttransplantation.

USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

PubMed

Hernández-Pérez, Santiago; Cabrera, Elisa; Amoedo, Hugo; Rodríguez-Acebes, Sara; Koundrioukoff, Stephane; Debatisse, Michelle; Méndez, Juan; Freire, Raimundo

2016-10-01

DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Efficacy and safety of non-invasive body tightening with high-intensity focused ultrasound (HIFU).

PubMed

Ko, E J; Hong, J Y; Kwon, T-R; Choi, E J; Jang, Y-J; Choi, S Y; Yoo, K H; Kim, S Y; Kim, B J

2017-11-01

Noninvasive skin-tightening devices have become increasingly popular in response to increasing demand for improvements in skin laxity and tightening with minimal risk and recovery time. We evaluated the efficacy and safety of HIFU for skin tightening in the face and body. A total of 32 Korean subjects enrolled in this prospective clinical trial. The subjects were treated with HIFU to both cheeks, lower abdomen, and thigh. Skin elasticity was measured before and after treatment using a Cutometer (CT575, Courage and Khazaka ® , Cologne, Germany). Three blinded, experienced dermatologists evaluated paired pre- and post-treatment (week 4 and 12) photographs according to the Global Aesthetic Improvement Scale (GAIS). Participants also completed self-assessments using GAIS. Subjects rated their pain on a numeric rating scale (NRS) immediately, 7 days, 4 weeks, and 12 weeks after treatment. Skin elasticity measured via a Cutometer was significantly improved 12 weeks after treatment at all treated sites (P<.05). Both IGAIS and SGAIS showed significant improvements 12 weeks after treatment. Immediately after treatment the mean NRS score was 3.00±1.586, but no pain was reported at 4 and 12 weeks post-treatment. No serious adverse effects were observed during the follow-up period. HIFU safely and effectively improves skin elasticity and clinical contouring of the face and body. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Progressive Tightening of Pulley Sutures for Primary Repair of Large Scalp Wounds

PubMed Central

McLaughlin, Jillian M.; Ross, Lindy S.; Phillips, Linda G.; Wagner, Richard F.

2017-01-01

Summary: Scalp defects greater than 2 cm in diameter are not usually amenable to primary closure and require local tissue rearrangement, grafting, tissue expansion, or prolonged second intention healing. Scalp flap reconstruction is a significant undertaking that requires elevation of a total flap surface area that is 3–6 times the size of the defect, often involves profuse bleeding, and can be challenging to perform without conscious sedation or general anesthesia. Anticoagulated and medically complex patients pose additional challenges and limit options for treatment. The pulley suture uses the mechanical advantage of the pulley to distribute tension across a wound and is useful in areas of high tension such as scalp wounds. For scalp wounds greater than 2 cm, pulley sutures are placed along the length of the wound. An assistant exerts equal tension on the pulley sutures, and the surgeon sequentially ties the sutures. The sutures are tightened and retied weekly until complete scalp closure is achieved. The pulley sutures can be used for rapid primary closure of scalp wounds up to 2.5–3.0 cm in diameter under local anesthesia. For scalp wounds larger than 3 cm, we have also found that pulley sutures can be progressively tightened yielding additional tissue expansion every week. Scalp wounds greater than 3.0 cm can be easily closed via primary repair and weekly tightening of pulley sutures without the need for flap reconstruction, traditional tissue expander placement, or second intention healing. PMID:29632771

A Preliminary Study of a Transdermal Radiofrequency Device for Body Slimming.

PubMed

Key, Douglas J

2015-11-01

The use and potential of radiofrequency energy for tissue contracture and body contouring has been established in the literature. Maximum reduction of laxity can be achieved by simultaneously tightening surface tissue and reducing unwanted fat below by the transdermal application of heat to reach and maintain tissue temperature targets within a well-defined range, inducing collagen remodeling in skin as well as apoptosis of fat cells and creating an overall slimming effect. A novel device utilizes transcutaneous monopolar RF for body slimming in this manner, employing a thermistor feedback control mechanism to safely manage energy delivery and tissue temperature. Subjects (n=14) presenting with abdominal laxity were treated up to four times using the transcutaneous monopolar RF device at one or two zones in the abdominal region (at operator's discretion). Non-expert blinded graders rated correction on an arbitrary scale (0=no laxity, 4=maximum laxity) after choosing the order of the before-and-after photo sets. A patient satisfaction survey was also administered. The two graders correctly ordered 10 of 14 photo sets in agreement. Average rated improvement was 0.75 and 0.80 for graders 1 and 2, respectively. Patient survey results revealed average perceived tightening of 2.14 points on a 0 to 4 scale (0=lowest tightening result, 4=highest tightening), and 8 of 14 subjects would recommend treatment to others. Transdermal monopolar RF is a safe and effective modality for non-invasive body slimming.

Comparison of 3D displacements of screw-retained zirconia implant crowns into implants with different internal connections with respect to screw tightening.

PubMed

Rebeeah, Hanadi A; Yilmaz, Burak; Seidt, Jeremy D; McGlumphy, Edwin; Clelland, Nancy; Brantley, William

2018-01-01

Internal conical implant-abutment connections without horizontal platforms may lead to crown displacement during screw tightening and torque application. This displacement may affect the proximal contacts and occlusion of the definitive prosthesis. The purpose of this in vitro study was to evaluate the displacement of custom screw-retained zirconia single crowns into a recently introduced internal conical seal implant-abutment connection in 3D during hand and torque driver screw tightening. Stereolithic acrylic resin models were printed using computed tomography data from a patient missing the maxillary right central incisor. Two different internal connection implant systems (both ∼11.5 mm) were placed in the edentulous site in each model using a surgical guide. Five screw-retained single zirconia computer-aided design and computer-aided manufacturing (CAD-CAM) crowns were fabricated for each system. A pair of high-resolution digital cameras was used to record the relationship of the crown to the model. The crowns were tightened according to the manufacturers' specifications using a torque driver, and the cameras recorded their relative position again. Three-dimensional image correlation was used to measure and compare crown positions, first hand tightened and then torque driven. The displacement test was repeated 3 times for each crown. Commercial image correlation software was used to extract the data and compare the amount of displacement vertically, mesiodistally, and buccolingually. Repeated-measures ANOVA calculated the relative displacements for all 5 specimens for each implant for both crown screw hand tightening and after applied torque. A Student t test with Bonferroni correction was used for pairwise comparison of interest to determine statistical differences between the 2 implants (α=.05). The mean vertical displacements were statistically higher than the mean displacements in the mesiodistal and buccolingual directions for both implants (P<.001). Mean displacements in all directions were statistically significant between iterations for both implants (P<.001). No statistically significant differences were found for displacements between implants at different directions and at different iterations (P>.05). Within the limitations of this in vitro study, screw-retained zirconia crowns tended to displace in all 3 directions, with the highest mean displacement in the vertical direction at iteration 1. However, the amount of displacement of crowns between the 2 different implants was statistically insignificant for all directions and iterations. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Virus-Like Particles That Can Deliver Proteins and RNA | NCI Technology Transfer Center | TTC

Cancer.gov

The present invention describes novel virus-like particles (VLPs) that are capable of binding to and replicating within a target mammalian cell, including human cells. The claimed VLPs are safer than viral delivery because they are incapable of re-infecting target cells. The National Cancer Institute's Protein Expression Laboratory seeks parties interested in licensing the novel delivery of RNA to mammalian cells using virus-like particles.

Worldwide Emerging Environmental Issues Affecting the U.S. Military. September 2008 Report

DTIC Science & Technology

2008-09-01

Anticipation and Response System…………………………………………..1 Item 3. First EU-Central Asia Security Forum Included Environmental Security………….2 Item 4. Indonesian ...back seat at EU-Central Asia talks http://euobserver.com/9/26778/?rk=1 Item 4. Indonesian Navy to Tighten Security in Sea Border Areas The... Indonesian Navy announced that it will tighten security in its eastern and western sea border areas to support law enforcement efforts at sea for

APC/C--the master controller of origin licensing?

PubMed

Sivaprasad, Umasundari; Machida, Yuichi J; Dutta, Anindya

2007-02-23

DNA replication must be tightly controlled to prevent initiation of a second round of replication until mitosis is complete. So far, components of the pre-replicative complex (Cdt1, Cdc6 and geminin) were considered key players in this regulation. In a new study, Machida and Dutta have shown that depletion of Emi1 caused cells to replicate their DNA more than once per cell cycle 1. This effect was dependent on the ability of Emi1 to inhibit the APC/C. In addition to its role in regulating entry into mitosis, oscillation of APC/C activity regulates pre-RC formation: high APC/C activity in late M/G1 allows pre-RC formation and low APC/C activity in S/G2 prevents pre-RC formation for a second time thereby preventing rereplication. Each redundant pathway to prevent rereplication is dependent on regulating one of the pre-RC components, and all of the pathways are co-regulated by Emi1 through the APC/C. In this commentary we discuss how this new role of Emi1 adds to our understanding of the regulation of replication initiation. We also review the literature to analyze whether APC/C has a role in regulating endoreduplication (a normal state of polyploidy in some differentiated cells). Similarly a role of premature APC/C activation in genomic instability of tumors is discussed.

MCM-BP regulates unloading of the MCM2–7 helicase in late S phase

PubMed Central

Nishiyama, Atsuya; Frappier, Lori; Méchali, Marcel

2011-01-01

Origins of DNA replication are licensed by recruiting MCM2–7 to assemble the prereplicative complex (pre-RC). How MCM2–7 is inactivated or removed from chromatin at the end of S phase is still unclear. Here, we show that MCM-BP can disassemble the MCM2–7 complex and might function as an unloader of MCM2–7 from chromatin. In Xenopus egg extracts, MCM-BP exists in a stable complex with MCM7, but is not associated with the MCM2–7 hexameric complex. MCM-BP accumulates in nuclei in late S phase, well after the loading of MCM2–7 onto chromatin. MCM-BP immunodepletion in Xenopus egg extracts inhibits replication-dependent MCM dissociation without affecting pre-RC formation and DNA replication. When excess MCM-BP is incubated with Xenopus egg extracts or immunopurified MCM2–7, it binds to MCM proteins and promotes disassembly of the MCM2–7 complex. Recombinant MCM-BP also releases MCM2–7 from isolated late-S-phase chromatin, but this activity is abolished when DNA replication is blocked. MCM-BP silencing in human cells also delays MCM dissociation in late S phase. We propose that MCM-BP plays a key role in the mechanism by which pre-RC is cleared from replicated DNA in vertebrate cells. PMID:21196493

Long-term three-dimensional volumetric assessment of skin tightening using a sharply tapered non-insulated microneedle radiofrequency applicator with novel fractionated pulse mode in asians.

PubMed

Tanaka, Yohei

2015-10-01

Non-insulated microneedle radiofrequency (NIMNRF) is a novel method that allows non-thermal penetration of the epidermis followed by radiofrequency (RF) coagulation at selected depths of the dermis that are surrounded by a zone of non-coagulative volumetric heating. The objective of this study was to investigate subjectively and objectively the efficacy of a single fractional NIMNRF treatment. Twenty Japanese patients underwent full face skin tightening using a sharply tapered NIMNRF applicator with a novel fractionated pulse mode. The system platform (1MHZ) incorporated six independent phase controlled RF generators coupled to RF microneedles that induced skin remodeling via controlled dermal coagulation. Patients received from 500 to 1000 pulses that were 80-110 milliseconds in duration at a power of 10-14 W, and a 1.5-2.5 mm penetration depth. Topical anesthetic cream was applied before the treatment. Monthly three-dimensional (3-D) volumetric assessments were performed for 6 months after treatment. Patients rated their satisfaction using a 5-point scale. During the study patients showed significant skin tightening on the lower two-thirds of the face. Objective assessments with superimposed 3-D color images showed significant median volumetric reduction of 12.1 ml at 6 months post-treatment. Ninety percent of the patients were either "satisfied" or "very satisfied" with the treatment results. The treatments were well tolerated with minimal discomfort. Complications included a slight burning sensation and mild erythema that were minor and transitory; both resolved within 5 hours. Side effects such as post-inflammatory hyperpigmentation, epidermal burns, and scar formation were not observed. The advantages of this NIMNRF treatment for skin tightening are its long-lasting high efficacy as shown through 3-D volumetric assessments. Moreover, NIMNRF produced minimal complications and downtime as well as few side effects. This non-invasive novel fractional NIMNRF approach provides safe and effective treatment of skin tightening in Asian patients. © 2015 Wiley Periodicals, Inc.

Novel Acylguanidine-Based Inhibitor of HIV-1

PubMed Central

Mwimanzi, Philip; Tietjen, Ian; Miller, Scott C.; Shahid, Aniqa; Cobarrubias, Kyle; Kinloch, Natalie N.; Baraki, Bemuluyigza; Richard, Jonathan; Finzi, Andrés; Fedida, David; Brumme, Zabrina L.

2016-01-01

ABSTRACT The emergence of transmissible HIV-1 strains with resistance to antiretroviral drugs highlights a continual need for new therapies. Here we describe a novel acylguanidine-containing compound, 1-(2-(azepan-1-yl)nicotinoyl)guanidine (or SM111), that inhibits in vitro replication of HIV-1, including strains resistant to licensed protease, reverse transcriptase, and integrase inhibitors, without major cellular toxicity. At inhibitory concentrations, intracellular p24Gag production was unaffected, but virion release (measured as extracellular p24Gag) was reduced and virion infectivity was substantially impaired, suggesting that SM111 acts at a late stage of viral replication. SM111-mediated inhibition of HIV-1 was partially overcome by a Vpu I17R mutation alone or a Vpu W22* truncation in combination with Env N136Y. These mutations enhanced virion infectivity and Env expression on the surface of infected cells in the absence and presence of SM111 but also impaired Vpu's ability to downregulate CD4 and BST2/tetherin. Taken together, our results support acylguanidines as a class of HIV-1 inhibitors with a distinct mechanism of action compared to that of licensed antiretrovirals. Further research on SM111 and similar compounds may help to elucidate knowledge gaps related to Vpu's role in promoting viral egress and infectivity. IMPORTANCE New inhibitors of HIV-1 replication may be useful as therapeutics to counteract drug resistance and as reagents to perform more detailed studies of viral pathogenesis. SM111 is a small molecule that blocks the replication of wild-type and drug-resistant HIV-1 strains by impairing viral release and substantially reducing virion infectivity, most likely through its ability to prevent Env expression at the infected cell surface. Partial resistance to SM111 is mediated by mutations in Vpu and/or Env, suggesting that the compound affects host/viral protein interactions that are important during viral egress. Further characterization of SM111 and similar compounds may allow more detailed pharmacological studies of HIV-1 egress and provide opportunities to develop new treatments for HIV-1. PMID:27512074

Influence of different tightening forces before laser welding to the implant/framework fit.

PubMed

da Silveira-Júnior, Clebio Domingues; Neves, Flávio Domingues; Fernandes-Neto, Alfredo Júlio; Prado, Célio Jesus; Simamoto-Júnior, Paulo César

2009-06-01

The aim of the present study was to evaluate the influence of abutment screw tightening force before laser welding procedures on the vertical fit of metal frameworks over four implants. To construct the frameworks, prefabricated titanium abutments and cylindrical titanium bars were joined by laser welding to compose three groups: group of manual torque (GMT), GT10 and GT20. Before welding, manual torque simulating routine laboratory procedure was applied to GTM. In GT10 and GT20, the abutment screws received 10 and 20 Ncm torque, respectively. After welding, the implant/framework interfaces were assessed by optical comparator microscope using two methods. First, the single screw test (SST) was used, in which the interfaces of the screwed and non-screwed abutments were assessed, considering only the abutments at the framework extremities. Second, the interfaces of all the abutments were evaluated when they were screwed. In the SST, intergroup analysis (Kruskal Wallis) showed no significant difference among the three conditions of tightening force; that is, the different tightening force before welding did not guarantee smaller distortions. Intragroup analysis (Wilcoxon) showed that for all groups, the interfaces of the non-screwed abutments were statistically greater than the interfaces of the screwed abutments, evidencing distortions in all the frameworks. ANOVA was applied for the comparison of interfaces when all the abutments were screwed and showed no significant difference among the groups. Under the conditions of this study, pre-welding tightness on abutment screws did not influence the vertical fit of implant-supported metal frameworks.

Ultrasound biomechanical anatomy of the soft structures in relation to the ulnar nerve in the cubital tunnel of the elbow.

PubMed

Michelin, Paul; Leleup, Grégoire; Ould-Slimane, Mourad; Merlet, Marie Caroline; Dubourg, Benjamin; Duparc, Fabrice

2017-11-01

Chronic ulnar nerve entrapment worsened by elbow flexion is the most common injury, but rare painful conditions may also be related to ulnar nerve instability. The posterior bundle of the medial collateral ligament (pMCL) and the retinaculum, respectively form a soft floor and a ceiling for the cubital tunnel. The aim of our study was to dynamically assess these soft structures of the cubital tunnel focusing on those involved in the biomechanics of the ulnar nerve. Forty healthy volunteers had a bilateral ultrasonography of the cubital tunnel. Elbows were scanned in full extension, 45° and 90°, and maximal passive flexion. Morphological changes of the nerve and related structures were dynamically assessed on transverse views. Both the pMCL and the retinaculum tightened with flexion. During elbow flexion, the tightening of the pMCL superficially moved the ulnar nerve remote from the osseous floor of the retroepicondylar groove. A retinaculum was visible in all 69 tunnels with stable nerves (86.3%), tightened in flexion, but absent in 11 tunnels with unstable nerves (13.7%). The retinaculum was fibrous in 60 elbows and muscular in nine, the nine muscular variants did not significantly influence the biomechanics of stable nerves. Stable nerves flattened in late flexion between the tightened pMCL and retinaculum, whereas unstable nerves transiently flattened when translating against the anterior osseous edge of the groove. The retinaculum and the pMCL are key structures in the biomechanics of the ulnar nerve in the cubital tunnel of the elbow.

Axial displacements in external and internal implant-abutment connection.

PubMed

Lee, Ji-Hye; Kim, Dae-Gon; Park, Chan-Jin; Cho, Lee-Ra

2014-02-01

The purpose of this study was to evaluate the axial displacement of the abutments during clinical procedures by the tightening torque and cyclic loading. Two different implant-abutment connection systems were used (external butt joint connection [EXT]; internal tapered conical connection [INT]). The master casts with two implant replicas, angulated 10° from each other, were fabricated for each implant connection system. Four types of impression copings were assembled and tightened with the corresponding implants (hex transfer impression coping, non-hex transfer impression coping, hex pick-up impression coping, non-hex pick-up impression coping). Resin splinted abutments and final prosthesis were assembled. The axial displacement was measured from the length of each assembly, which was evaluated repeatedly, after 30 Ncm torque tightening. After 250 N cyclic loading of final prosthesis for 1,000,000 cycles, additional axial displacement was recorded. The mean axial displacement was statistically analyzed (repeated measured ANOVA). There was more axial displacement in the INT group than that of the EXT group in impression copings, resin splinted abutments, and final prosthesis. Less axial displacement was found at 1-piece non-hex transfer type impression coping than other type of impression copings in the INT group. There was more axial displacement at the final prosthesis than resin splinted abutments in the INT and the EXT groups. After 250 N cyclic loading of final prosthesis, the INT group showed more axial displacement than that of the EXT group. Internal tapered conical connection demonstrated a varying amount of axial displacement with tightening torque and cyclic loading. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Evaluating the bending response of two osseointegrated transfemoral implant systems using 3D digital image correlation.

PubMed

Thompson, Melanie L; Backman, David; Branemark, Rickard; Mechefske, Chris K

2011-05-01

Osseointegrated transfemoral implants have been introduced as a prosthetic solution for above knee amputees. They have shown great promise, providing an alternative for individuals who could not be accommodated by conventional, socket-based prostheses; however, the occurrence of device failures is of concern. In an effort to improve the strength and longevity of the device, a new design has been proposed. This study investigates the mechanical behavior of the new taper-based assembly in comparison to the current hex-based connection for osseointegrated transfemoral implant systems. This was done to better understand the behavior of components under loading, in order to optimize the assembly specifications and improve the useful life of the system. Digital image correlation was used to measure surface strains on two assemblies during static loading in bending. This provided a means to measure deformation over the entire sample and identify critical locations as the assembly was subjected to a series of loading conditions. It provided a means to determine the effects of tightening specifications and connection geometry on the material response and mechanical behavior of the assemblies. Both osseoinegrated assemblies exhibited improved strength and mechanical performance when tightened to a level beyond the current specified tightening torque of 12 N m. This was shown by decreased strain concentration values and improved distribution of tensile strain. Increased tightening torque provides an improved connection between components regardless of design, leading to increased torque retention, decreased peak tensile strain values, and a more gradual, primarily compressive distribution of strains throughout the assembly.

Mechanical stability of a novel screw design after repeated insertion: can the double-thread screw serve as a back up?

PubMed

Wiendieck, Kurt; Müller, Helge; Buchfelder, Michael; Sommer, Björn

2018-06-01

We investigated mechanical pull-out behavior and tightening torque of a novel dual-core pedicle "6T screw" (6T). The aim of this study was to test if these changes in screw geometry are increasing the strength of the pedicle screw fixation after repeated insertion. Three different types of pedicle screws were inserted in rigid foam blocks. Tightening torque and pull-out strength were measured during two repetitive insertions of a standard 6.5×45-mm conical screw. The third insertion into the pilot hole was performed using either standard 6.5×45-mm or 7.2×45-mm conical screws or the novel 6.5×45-mm (6T) screw. Additionally, we performed a surface analysis to investigate the bone/screw interface. The maximal tightening torque at the third insertion of the novel 6T screw was 194% higher compared to the standard 6.5×45-mm conical screw and 135% higher compared to the standard 7.2×45-mm conical screw. The pull-out strength of the 6T screw showed no significant changes, and surface analysis revealed a compression of the screw-foam interface due to the different internal diameters. The modified geometrical design of the 6T screw seems to have no statistically significant effect on the pull-out strength, although it achieved a higher tightening torque. This might be due to the different pitch angle cutting a new thread into the material and also to the enlarged inner diameter.

Detection of Small Stress Relaxation in Tightened Metallic Structures by Ultrasounds

NASA Astrophysics Data System (ADS)

Augereau, F.; Portal, A.

Experimental data are presented here to highlight the performances of ultrasounds for the control or the better understanding of the quality of the mechanical contact between tightened plates. Thus, variations of the mechanical load as small as those induced by creep or stress relaxation are potentially detectable by simply monitoring the amplitude of the reflected acoustic plane wave reflected at this interface. To illustrate this, two 3 cm thick aluminium plates are firstly tightened with a given torque and next, the amplitude of the acoustic wave is monitored for several days. All long this test, the temperature of the sample is controlled as well as the compression load applied to the plates using a thermocouple and a bolt gauge sensor. The reflected amplitude decreases quickly during first hours and then stabilises after a week approximately. The total variation reaches -28% of the initial value of the reflected amplitude. During this test, temperature is remained almost constant and its fluctuation around the ambient temperature is not correlated with the reflected amplitude. As expected from classic stress relaxation tests, the compression load has slowly decreased by an amount of only -1% but this should have logically increased the reflected amplitude. Further investigations have shown that instrumentation drift were negligible. Consequently, this large decrease of the reflected amplitude has been interpreted as the indication of the increase of the contact area between the two tightened plates. This test attests the high sensitivity of ultrasonic reflection measurement to investigate quality of mechanical contacts for non destructive testing.

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

Prodan, V.D.

The working load on the fastening parts of a permanent tight joint, which determines the strength, and on the gasket, which determines the hermeticity of the joint, depends on the stress of preliminary tightening. This stress must be determined when calculating the force distribution of the joint, since it depends on the magnitude of the stress whether the joint is capable of withstanding the internal pressure of the medium in the vessel without disturbing the tightness of the joint and strength of its parts. The seal will be hermetic when the specific load on the sealing surfaces of the lenticularmore » gasket becomes equal to or higher than the specific load established for given conditions of pressure and properties of the sealing medium. The recommended specific load was calculated for nitrogen as the working medium. The required tightening stress was calculated for standard flange joints with a lenticular gasket of nominal diameter 25-200mm at a working pressure of 32 MPa. The equations given can also be used to calculate the stress of preliminary tightening of the fastening parts and of other types of permanent tight joints with partial radial self-sealing.« less

The effect of 3 torque delivery systems on gold screw preload at the gold cylinder-abutment screw joint.

PubMed

Tan, Keson B; Nicholls, Jack I

2002-01-01

This study measured the gold screw preload at the gold cylinder-abutment screw joint interface obtained by 3 torque delivery systems. Using a precalibrated, strain-gauged standard abutment as the load cell, 3 torque delivery systems tested were shown to have significant differences in gold screw preload when a gold cylinder was attached. Mean preloads measured were 291.2 N for hand torque drivers set at 10 Ncm, 340.3 N for electronic torque controllers at low setting/10 Ncm, 384.4 N for electronic torque controllers at high setting/10 Ncm; and 140.8 N for hand-tightening with a prosthetic slot screwdriver. Significant differences in screw preload were also found between operators using a hand torque driver. Hand-tightening delivered insufficient preload and cannot be recommended for final gold screw tightening. Different electronic torque controller units set at 10 Ncm induced mean gold screw preloads that ranged from 264.1 N to as high as 501.2 N. Electronic torque controllers should be regularly recalibrated to ensure optimal output.

Tilted orthodontic micro implants: a photoelastic stress analysis.

PubMed

Çehreli, Seçil; Özçırpıcı, Ayça Arman; Yılmaz, Alev

2013-10-01

The aim of this study was to examine peri-implant stresses around orthodontic micro implants upon torque-tightening and static load application by quasi-three-dimensional photoelastic stress analysis. Self-tapping orthodontic micro implants were progressively inserted into photoelastic models at 30, 45, 70, and 90 degrees and insertion torques were measured. Stress patterns (isochromatic fringe orders) were recorded by the quasi-three-dimensional photoelastic method using a circular polariscope after insertion and 250 g static force application. Torque-tightening of implants generated peri-implant stresses. Upon insertion, 90 degree placed implants displayed the lowest and homogeneous stress distribution followed by 30, 70, and 45 degree tilted implants. Static loading did not dramatically alter stress fields around the implants tested. The highest alteration in stress distribution was observed for the 90 degree placed implant, while 70 degree tilted implant had the lowest stresses among tilted implants. Torque-tightening of orthodontic micro implants creates a stress field that is not dramatically altered after application of static lateral moderate orthodontic loads, particularly at the cervical region of tilted implants.

Nonsurgical tightening of skin laxity: a new radiofrequency approach.

PubMed

Rusciani, Antonio; Curinga, Giuseppe; Menichini, Giulio; Alfano, Carmine; Rusciani, Luigi

2007-04-01

Improvement in skin laxity can be difficult to achieve without invasive surgical procedures. Monopolar radiofrequency (RF) treatment is used by physicians to heat skin and promote tissue tightening and contouring. RF technology produces an electric current that generates heat through resistance in the dermis and subcutaneous tissue. The thermal effect depends on the conductivity features of the treated tissue. When heated, collagen fibrils will denature and contract, which is believed to lead to the observed tissue tightening. Ninety-three consecutive patients with mild to moderate laxity were included in the study. The Surgitron Dual Frequency RF (Radiowave technology, Ellman International) was used to treat skin laxity. The application of RF energy took place in an ambulatory setting with no need for skin sterilization or anesthesia. Patients immediately noticed a microlifting retraction in the treated tissues according to the vectors mapped in the area. There were no significant complications and the majority of patients were satisfied with the procedure and able to return to their daily routine after leaving the office, thereby substantiating the popularity of noninvasive rejuvenating procedures.

All-Wales licensed premises intervention (AWLPI): a randomised controlled trial to reduce alcohol-related violence

PubMed Central

2014-01-01

Background Alcohol-related violence in and in the vicinity of licensed premises continues to place a considerable burden on the United Kingdom’s (UK) health services. Robust interventions targeted at licensed premises are therefore required to reduce the costs of alcohol-related harm. Previous evaluations of interventions in licensed premises have a number of methodological limitations and none have been conducted in the UK. The aim of the trial was to determine the effectiveness of the Safety Management in Licensed Environments intervention designed to reduce alcohol-related violence in licensed premises, delivered by Environmental Health Officers, under their statutory authority to intervene in cases of violence in the workplace. Methods/Design A national randomised controlled trial, with licensed premises as the unit of allocation. Premises were identified from all 22 Local Authorities in Wales. Eligible premises were those with identifiable violent incidents on premises, using police recorded violence data. Premises were allocated to intervention or control by optimally balancing by Environmental Health Officer capacity in each Local Authority, number of violent incidents in the 12 months leading up to the start of the project and opening hours. The primary outcome measure is the difference in frequency of violence between intervention and control premises over a 12 month follow-up period, based on a recurrent event model. The trial incorporates an embedded process evaluation to assess intervention implementation, fidelity, reach and reception, and to interpret outcome effects, as well as investigate its economic impact. Discussion The results of the trial will be applicable to all statutory authorities directly involved with managing violence in the night time economy and will provide the first formal test of Health and Safety policy in this environment. If successful, opportunities for replication and generalisation will be considered. Trial registration UKCRN 14077; ISRCTN78924818. PMID:24405575

Antiviral activity of silymarin against chikungunya virus

PubMed Central

Lani, Rafidah; Hassandarvish, Pouya; Chiam, Chun Wei; Moghaddam, Ehsan; Chu, Justin Jang Hann; Rausalu, Kai; Merits, Andres; Higgs, Stephen; Vanlandingham, Dana; Abu Bakar, Sazaly; Zandi, Keivan

2015-01-01

The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection. PMID:26078201

Inactivation of Hepatitis B Virus Replication in Cultured Cells and In Vivo with Engineered Transcription Activator-Like Effector Nucleases

PubMed Central

Bloom, Kristie; Ely, Abdullah; Mussolino, Claudio; Cathomen, Toni; Arbuthnot, Patrick

2013-01-01

Chronic hepatitis B virus (HBV) infection remains an important global health problem. Stability of the episomal covalently closed circular HBV DNA (cccDNA) is largely responsible for the modest curative efficacy of available therapy. Since licensed anti-HBV drugs have a post-transcriptional mechanism of action, disabling cccDNA is potentially of therapeutic benefit. To develop this approach, we engineered mutagenic transcription activator-like effector nucleases (TALENs) that target four HBV-specific sites within the viral genome. TALENs with cognate sequences in the S or C open-reading frames (ORFs) efficiently disrupted sequences at the intended sites and suppressed markers of viral replication. Following triple transfection of cultured HepG2.2.15 cells under mildly hypothermic conditions, the S TALEN caused targeted mutation in ~35% of cccDNA molecules. Markers of viral replication were also inhibited in vivo in a murine hydrodynamic injection model of HBV replication. HBV target sites within S and C ORFs of the injected HBV DNA were mutated without evidence of toxicity. These findings are the first to demonstrate a targeted nuclease-mediated disruption of HBV cccDNA. Efficacy in vivo also indicates that these engineered nucleases have potential for use in treatment of chronic HBV infection. PMID:23883864

European emission, fuel quality regs tighten--

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

Not Available

1989-12-18

Emission regulations and fuel quality requirements will tighten as Europe enters the 1990s. The stiffer emission regulations, particularly in those nations in the European Economic Community (EEC), will more closely resemble those already in effect in the U.S. and Japan. Nations not in the EEC, particularly Austria, Switzerland, Norway, Sweden, and Finland, are also formulating rules that adopt the 1983 U.S. emission standards. Rules and tax incentives have also been introduced to encourage the use of unleaded gasoline in EEC member countries. Details of some of the emission rules for both EEC member and non-member countries are discussed.

Ebola virus vaccines: an overview of current approaches

PubMed Central

Marzi, Andrea; Feldmann, Heinz

2016-01-01

Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. PMID:24575870

Displacement comparison of CAD-CAM titanium and zirconia abutments to implants with different conical connections.

PubMed

Yilmaz, Burak; Hashemzadeh, Shervin; Seidt, Jeremy D; Clelland, Nancy L

2018-04-01

To compare the displacements of CAD-CAM zirconia and titanium abutments into different internal connection systems after torquing. OsseoSpeed EV and OsseoSpeed TX implants (n=10) were placed in resin blocks. Zirconia and titanium abutments (n=5) were first hand tightened and then tightened to the recommended torque (20Ncm for TX and 25Ncm for EV). Displacements of abutments between screw tightening by hand and torque driver was measured using three-dimensional digital image correlation (3D DIC) technique. Displacements were measured in U (front/back), V (into/outward), W (right/left) directions and 3-dimensionally (3D). ANOVA with restricted maximum likelihood estimation method was used to analyze the data. Bonferroni-corrected t tests was used to determine the statistical differences (α=0.05). 3D displacement of zirconia and titanium abutments was significantly greater in OsseoSpeed EV implant (P<0.001). Displacement of zirconia and titanium abutments was not significantly different within implant systems, 3D (P≥0.386) and in each direction (P≥0.382). In U and V directions, zirconia and titanium abutments displaced significantly more towards negative in OsseoSpeed EV implant (P<0.019). Within the OsseoSpeed TX system, abutments displaced significantly more in V direction compared to the U and W (P≤0.005), and within the Osseospeed EV system, abutment displacements were significantly different amongst directions and displacements in V were the greatest (P<0.001). Abutments displaced more in the implant that required higher torque values to tighten the abutment. The amount of displacement in both systems was clinically small. Abutment material did not affect the magnitude of displacement. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

A novel method for real-time skin impedance measurement during radiofrequency skin tightening treatments.

PubMed

Harth, Yoram; Lischinsky, Daniel

2011-03-01

The thermal effects of monopolar and bipolar radiofrequency (RF) have been proven to be beneficial in skin tightening. Nevertheless, these effects were frequently partial or unpredictable because of the uncontrolled nature of monopolar or unipolar RF and the superficial nature of energy flow for bipolar or tripolar configurations. One of the hypotheses for lack or predictability of efficacy of the first-generation RF therapy skin tightening systems is lack of adaptation of delivered power to differences in individual skin impedance. A novel multisource phase-controlled system was used (1 MHz, power range 0-65 W) for treatment and real-time skin impedance measurements in 24 patients (EndyMed PRO™; EndyMed, Cesarea, Israel). This system allows continuous real-time measurement of skin impedance delivering constant energy to the patient skin independent of changes in its impedance. More than 6000 unique skin impedance measurements on 22 patients showed an average session impedance range was 215-584 Ohm with an average of 369 Ohm (standard deviation of 49 Ohm). Analyzing individual pulses (total of 600 readings) showed a significant decrease in impedance during the pulse. These findings validate the expected differences in skin impedance between individual patients and in the same patients during the treatment pulse. Clinical study on 30 patients with facial skin aging using the device has shown high predictability of efficacy (86.7% of patients had good results or better at 3 months' follow-up [decrease of 2 or more grades in Fitzpatrick's wrinkle scale]). The real-time customization of energy according to skin impedance allows a significantly more accurate and safe method of nonablative skin tightening with more consistent and predictable results. © 2011 Wiley Periodicals, Inc.

Axial displacement of abutments into implants and implant replicas, with the tapered cone-screw internal connection, as a function of tightening torque.

PubMed

Dailey, Bruno; Jordan, Laurence; Blind, Olivier; Tavernier, Bruno

2009-01-01

The passive fit of a superstructure on implant abutments is essential to success. One source of error when using a tapered cone-screw internal connection may be the difference between the tightening torque level applied to the abutments by the laboratory technician compared to that applied by the treating clinician. The purpose of this study was to measure the axial displacement of tapered cone-screw abutments into implants and their replicas as a function of the tightening torque level. Twenty tapered cone-screw abutments were selected. Two groups were created: 10 abutments were secured into 10 implants, and 10 abutments were secured into 10 corresponding implant replicas. Each abutment was tightened in increasing increments of 5 Ncm, from 0 Ncm to 45 Ncm, with a torque controller. The length of each sample was measured repeatedly with an Electronic Digital Micrometer. The mean axial displacement for the implant group and the replica group was calculated. The data were analyzed by the Mann-Whitney and Spearman tests. For both groups, there was always an axial displacement of the abutment upon each incremental application of torque. The mean axial displacement values varied between 7 and 12 microm for the implant group and between 6 and 21 microm for the replica group at each 5-Ncm increment. From 0 to 45 Ncm, the total mean axial displacement values were 89 microm for the implant group and 122 microm for the replica group. There was a continuous axial displacement of the abutments into implants and implant replicas when the applied torque was raised from 0 to 45 Ncm. Torque applied above the level recommended by the manufacturer increased the difference in displacement between the two groups.

Three-Dimensional Displacement of Nine Different Abutments for an Implant with an Internal Hexagon Platform.

PubMed

Gilbert, Andy B; Yilmaz, Burak; Seidt, Jeremy D; McGlumphy, Edwin A; Clelland, Nancy L; Chien, Hua-Hong

2015-01-01

Clinicians need to know whether there are any differences among the many abutment options available for restoring a particular implant. This study aims to compare nine abutments for one implant system for positional changes between hand tightening and torqueing. Nine Tapered Screw-Vent (TSV) implants were placed into a resin block. Five specimens of nine different abutments (n = 45) were tried in one of the nine implants. Initially, the abutments were torqued to 20 Ncm to represent hand tightening. Abutments were tightened to 30 Ncm using a torque driver as recommended by the manufacturer for final seating. Images were recorded in 12-second intervals for approximately 10 minutes after the torque was applied. The spatial relationship of the abutments to the resin block was determined using three-dimensional digital image correlation. Commercial image correlation software was used to analyze the displacements. Mean displacements for the nine different abutments were calculated in all three dimensions and for overall displacement in space. A t test with a step-down Bonferroni correction was used for a pairwise comparison of each abutment's mean displacements to the other abutments to determine statistical differences (α = .05). The Atlantis titanium, Inclusive titanium, and Legacy zirconia abutments showed mean displacements that were statistically significantly higher than other abutments in the horizontal direction. The overall three-dimensional displacement of the Atlantis titanium abutment after an applied 30-Ncm torque was significantly higher than that of six of the other eight abutments (P < .0144). Within the limitations of this in vitro study, the Zimmer PSA demonstrated less displacement between hand tightening and torqueing than the Atlantis titanium or Inclusive titanium abutments when used to restore a TSV implant.

Spline-Screw Payload-Fastening System

NASA Technical Reports Server (NTRS)

Vranish, John M.

1994-01-01

Payload handed off securely between robot and vehicle or structure. Spline-screw payload-fastening system includes mating female and male connector mechanisms. Clockwise (or counter-clockwise) rotation of splined male driver on robotic end effector causes connection between robot and payload to tighten (or loosen) and simultaneously causes connection between payload and structure to loosen (or tighten). Includes mechanisms like those described in "Tool-Changing Mechanism for Robot" (GSC-13435) and "Self-Aligning Mechanical and Electrical Coupling" (GSC-13430). Designed for use in outer space, also useful on Earth in applications needed for secure handling and secure mounting of equipment modules during storage, transport, and/or operation. Particularly useful in machine or robotic applications.

Evidence-based medicine: liposuction.

PubMed

Matarasso, Alan; Levine, Steven M

2013-12-01

After reading this article, the participant should be able to: 1. Perform preoperative assessment and patient selection for liposuction surgeries. 2. Explain the differences among the various types of anesthesia and wetting solutions used in liposuction. 3. Identify the available literature about skin-tightening procedures. 4. Convey to patients the complication profile for various modalities of liposuction. 5. Recall important ASPS consensus guidelines when discussing liposuction. The article was prepared to feature recent evidence-based publications pertaining to liposuction. The authors placed special emphasis on the most clinically relevant data. In addition, they highlighted current data regarding liposuction-related fields, including autologous fat transfer and minimally invasive skin tightening.

Scleroderma-like Disorders.

PubMed

Sharma, Amit

2018-04-20

Scleroderma is a term used to describe diseases that involve hardening and tightening of the skin and the underlying subcutaneous connective tissue. It could be localized to skin and subcutaneous tissue, or may involve the internal organs too in systemic sclerosis. There are disorders that can cause hardening and tightening of skin and mimic scleroderma but are rarely associated with Raynaud phenomenon, sclerodactyly, and autoantibodies in the serum, features specific to scleroderma/systemic sclerosis. These are termed as "scleroderma variants" or "scleroderma like disorders". This review discusses the various "scleroderma variants" e.g. scleromyxedema, scleredema, nephrogenic systemic fibrosis, and eosinophilic fasciitis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Analysis of Electrical Energy Consumption of the Impact Screwdriver During Assembly of Fixed Threaded Joints

NASA Astrophysics Data System (ADS)

Grinevich, I.; Nikishin, Vl.; Mozga, N.; Laitans, M.

2017-06-01

The paper deals with the possibilities of reducing the consumption of electrical energy of the impact screwdriver during the assembly of fixed threaded joints. The recommendations related to a decrease in electrical energy consumption would allow reducing product costs but so far there have been no such recommendations from the producers of the tool as to the effective operating regimes of the impact screwdrivers in relation to electrical energy consumption and necessary tightening moment of the nut. The aim of the study is to find out the economical operating mode of the electrical impact screwdriver when assembling fixed threaded joints. By varying the set speed of the rotor head and working time of the impact mechanism, there is an opportunity to determine electrical energy consumption of the tool for the given tightening moment. The results of the experiment show that at the same tightening moment obtained the electrical energy consumption of the impact screwdriver is less at a higher starting set speed of the rotor head but shorter operating time of the impact mechanism than at a lower speed of the rotor head and longer operating time of the impact mechanism.

3D finite element analysis of tightening process of bolt and nut connections with pitch difference

NASA Astrophysics Data System (ADS)

Liu, X.; Noda, N.-A.; Sano, Y.; Huang, Y. T.; Takase, Y.

2018-06-01

In a wide industrial field, the bolt-nut joint is unitized as an important machine element and anti-loosening performance is always required. In this paper, the effect of a slight pitch difference between a bolt and nut is studied. Firstly, by varying the pitch difference, the prevailing torque required for the nut rotation, before the nut touches the clamped body, is measured experimentally. Secondly, the tightening torque is determined as a function of the axial force of the bolt after the nut touches the clamped body. The results show that a large value of pitch difference may provide large prevailing torque that causes an anti-loosening effect although a very large pitch difference may deteriorate the bolt axial force under a certain tightening torque. Thirdly, a suitable pitch difference is determined taking into account the anti-loosening and clamping abilities. Furthermore, the chamfered corners at nut ends are considered, and it is found that the 3D finite element analysis with considering the chamfered nut threads has a good agreement with the experimental observation. Finally, the most desirable pitch difference required for improving anti-loosening is proposed.

Efficacy of diode laser (810 and 940 nm) for facial skin tightening.

PubMed

Voravutinon, Nataya; Seawthaweesin, Kanikar; Bureethan, Apron; Srivipatana, Anchisa; Vejanurug, Patnapa

2015-12-01

Laser treatment has been introduced for facial skin tightening. However, no prior study has used a diode laser to treat facial skin laxity. To evaluate the efficacy and safety of a 810- and 940-nm diode laser (MeDioStarNeXT) for treating facial skin laxity. Thirty patients, with facial skin laxity grading scale II-IV, were enrolled in this study. Each patient underwent four sessions with a 810- and 940-nm diode laser (MeDioStarNeXT) treatment over 3-week intervals. Improvement in the laxity of facial skin was evaluated using a Cutometer MPA 580, spectrophotometer, and a grading scale. Significant improvement was observed with the Cutometer F3 and R7 parameters at 1 and 3 months after complete treatment, respectively. Physician assessment showed significant improvement in the laxity scale at 1 and 6 months after treatment. Approximately 10% of the patients reported mild pain or minor adverse events. Ninety-eight percent of the patients were satisfied with the treatments. Treatment with a diode laser (810 and 940 nm) is safe and may be effective for facial skin tightening. Maintenance treatment is necessary to sustain the effect of treatment. © 2015 Wiley Periodicals, Inc.

Evaluation of screw loosening on new abutment screws and after successive tightening.

PubMed

Barbosa, Gustavo Seabra; Silva-Neto, João Paulo da; Simamoto-Júnior, Paulo Cezar; Neves, Flávio Domingues das; Mattos, Maria da Gloria Chiarello de; Ribeiro, Ricardo Faria

2011-01-01

This study evaluated the loss of the torque applied after use of new screws and after successive tightening. Four infrastructures (IE), using UCLA castable abutment type, were cast in cobalt-chromium alloy and new abutment screws (G1) were used in a first moment. Subsequently, the same abutment screws were used a second time (G2) and more than two times (G3). The values of the torques applied and detorques were measured with a digital torque wrench to obtain the values of initial tightening loss (%). Data were analyzed by ANOVA and Tukey's test (?=0.05). Significant differences were observed between the G1 (50.71% ± 11.36) and G2 (24.01% ± 3.33) (p=0.000) and between G1 (50.71% ± 11.36) and G3 (25.60% ± 4.64) (p=0.000). There was no significant difference between G2 and G3 (p=0.774). Within the limitations of the study, it may be concluded that the percentage of the initial torque loss is lower when screws that already suffered the application of an initial torque were used, remaining stable after application of successive torques.

Claudin-31 contributes to corticosteroid-induced alterations in the barrier properties of the gill epithelium.

PubMed

Kolosov, Dennis; Donini, Andrew; Kelly, Scott P

2017-01-05

The contribution of Claudin-31 (Cldn-31) to corticosteroid-induced tightening of the trout gill epithelium was examined using a primary cultured model preparation. Cldn-31 is a ∼23 kDa protein that localizes to the periphery of gill epithelial cells and diffusely in select gill cells that are Na + -K + -ATPase-immunoreactive. Transcriptional knockdown (KD) of cldn-31 reduced Cldn-31 abundance and increased epithelium permeability. Under simulated in vivo conditions (apical freshwater), cldn-31 KD increased net ion flux rates (≡ efflux). Cortisol treatment increased Cldn-31 abundance and decreased epithelium permeability. This tightening effect was diminished, but not eliminated, by cldn-31 KD, most likely due to other cortisol-sensitive TJ proteins that were transcriptionally unperturbed or enhanced in cortisol-treated cldn-31 KD preparations. However, cldn-31 KD abolished a cortisol-induced increase in Cldn-8d abundance, which may contribute to compromised cldn-31 KD epithelium permeability. Data suggest an important barrier function for Cldn-31 and an integral role for Cldn-31 in corticosteroid-induced gill epithelium tightening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Accelerated testing of an optimized closing system for automotive fuel tank

NASA Astrophysics Data System (ADS)

Gligor, A.; Ilie, S.; Nicolae, V.; Mitran, G.

2015-11-01

Taking into account the legal prescriptions which are in force and the new regulatory requirements that will be mandatory to implement in the near future regarding testing characteristics of automotive fuel tanks, resulted the necessity to develop a new testing methodology which allows to estimate the behaviour of the closing system of automotive fuel tank over a long period of time (10-15 years). Thus, were designed and conducted accelerated tests under extreme assembling and testing conditions (high values for initial tightening torques, extreme values of temperature and pressure). In this paper are presented two of durability tests which were performed on an optimized closing system of fuel tank: (i) the test of exposure to temperature with cyclical variation and (ii) the test of continuous exposure to elevated temperature. In these experimental tests have been used main components of the closing system manufactured of two materials variants, both based on the polyoxymethylene, material that provides higher mechanical stiffness and strength in a wide temperature range, as well as showing increased resistance to the action of chemical agents and fuels. The tested sample included a total of 16 optimized locking systems, 8 of each of 2 versions of material. Over deploying the experiments were determined various parameters such as: the initial tightening torque, the tightening torque at different time points during measurements, the residual tightening torque, defects occurred in the system components (fissures, cracks, ruptures), the sealing conditions of system at the beginning and at the end of test. Based on obtained data were plotted the time evolution diagrams of considered parameter (the residual tightening torque of the system consisting of locking nut and threaded ring), in different temperature conditions, becoming possible to make pertinent assessments on the choice between the two types of materials. By conducting these tests and interpreting the obtained results, it can be created a clear picture of the capacity of closing system of fuel tank to fulfil the functional requirements following the exposure to values of testing parameters significantly above the values that may appear throughout the entire service life of the vehicle. The proposed accelerated testing method shows the main advantage of simulation in a limited time all the situations which may be encountered in a much longer period of time, namely the service life of the vehicle.

The DNA replication licensing factor miniature chromosome maintenance 7 is essential for RNA splicing of epidermal growth factor receptor, c-Met, and platelet-derived growth factor receptor.

PubMed

Chen, Zhang-Hui; Yu, Yan P; Michalopoulos, George; Nelson, Joel; Luo, Jian-Hua

2015-01-16

Miniature chromosome maintenance 7 (MCM7) is an essential component of DNA replication licensing complex. Recent studies indicate that MCM7 is amplified and overexpressed in a variety of human malignancies. In this report, we show that MCM7 binds SF3B3. The binding motif is located in the N terminus (amino acids 221-248) of MCM7. Knockdown of MCM7 or SF3B3 significantly increased unspliced RNA of epidermal growth factor receptor, platelet-derived growth factor receptor, and c-Met. A dramatic drop of reporter gene expression of the oxytocin exon 1-intron-exon 2-EGFP construct was also identified in SF3B3 and MCM7 knockdown PC3 and DU145 cells. The MCM7 or SF3B3 depleted cell extract failed to splice reporter RNA in in vitro RNA splicing analyses. Knockdown of SF3B3 and MCM7 leads to an increase of cell death of both PC3 and DU145 cells. Such cell death induction is partially rescued by expressing spliced c-Met. To our knowledge, this is the first report suggesting that MCM7 is a critical RNA splicing factor, thus giving significant new insight into the oncogenic activity of this protein. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.

PubMed

Ly, Tony; Endo, Aki; Lamond, Angus I

2015-01-02

Previously, we analyzed protein abundance changes across a 'minimally perturbed' cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (

Expression of the p12 subunit of human DNA polymerase δ (Pol δ), CDK inhibitor p21(WAF1), Cdt1, cyclin A, PCNA and Ki-67 in relation to DNA replication in individual cells.

PubMed

Zhao, Hong; Zhang, Sufang; Xu, Dazhong; Lee, Marietta Ywt; Zhang, Zhongtao; Lee, Ernest Yc; Darzynkiewicz, Zbigniew

2014-01-01

We recently reported that the p12 subunit of human DNA polymerase δ (Pol δ4) is degraded by CRL4(Cdt2) which regulates the licensing factor Cdt1 and p21(WAF1) during the G1 to S transition. Presently, we performed multiparameter laser scanning cytometric analyses of changes in levels of p12, Cdt1 and p21(WAF1), detected immunocytochemically in individual cells, vis-à-vis the initiation and completion of DNA replication. The latter was assessed by pulse-labeling A549 cells with the DNA precursor ethynyl-2'-deoxyribose (EdU). The loss of p12 preceded the initiation of DNA replication and essentially all cells incorporating EdU were p12 negative. Completion of DNA replication and transition to G2 phase coincided with the re-appearance and rapid rise of p12 levels. Similar to p12 a decline of p21(WAF1) and Cdt1 was seen at the end of G1 phase and all DNA replicating cells were p21(WAF1) and Cdt1 negative. The loss of p21(WAF1) preceded that of Cdt1 and p12 and the disappearance of the latter coincided with the onset of DNA replication. Loss of p12 leads to conversion of Pol δ4 to its trimeric form, Pol δ3, so that the results provide strong support to the notion that Pol δ3 is engaged in DNA replication during unperturbed progression through the S phase of cell cycle. Also assessed was a correlation between EdU incorporation, likely reflecting the rate of DNA replication in individual cells, and the level of expression of positive biomarkers of replication cyclin A, PCNA and Ki-67 in these cells. Of interest was the observation of stronger correlation between EdU incorporation and expression of PCNA (r = 0.73) than expression of cyclin A (r = 0.47) or Ki-67 (r = 0.47).

Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication.

PubMed

Hossain, Manzar; Stillman, Bruce

2012-08-15

Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.

Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex

PubMed Central

Liu, Jun; McConnell, Kristopher; Dixon, Michael; Calvi, Brian R.

2012-01-01

Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. PMID:22049023

Two Geminin homologs regulate DNA replication in silkworm, Bombyx mori.

PubMed

Tang, Xiao-Fang; Chen, Xiang-Yun; Zhang, Chun-Dong; Li, Yao-Feng; Liu, Tai-Hang; Zhou, Xiao-Lin; Wang, La; Zhang, Qian; Chen, Peng; Lu, Cheng; Pan, Min-Hui

2017-05-03

DNA replication is rigorously controlled in cells to ensure that the genome duplicates exactly once per cell cycle. Geminin is a small nucleoprotein, which prevents DNA rereplication by directly binding to and inhibiting the DNA replication licensing factor, Cdt1. In this study, we have identified 2 Geminin genes, BmGeminin1 and BmGeminn2, in silkworm, Bombyx mori. These genes contain the Geminin conserved coiled-coil domain and are periodically localized in the nucleus during the S-G2 phase but are degraded at anaphase in mitosis. Both BmGeminin1 and BmGeminin2 are able to homodimerize and interact with BmCdt1 in cells. In addition, BmGeminin1 and BmGeminin2 can interact with each other. Overexpression of BmGeminin1 affects cell cycle progression: cell cycle is arrested in S phase, and RNA interference of BmGeminin1 leads to rereplication. In contrast, overexpression or knockdown of BmGeminin2 with RNAi did not significantly affect cell cycle, while more rereplication occurred when BmGeminin1 and BmGeminin2 together were knocked down in cells than when only BmGeminin1 was knocked down. These data suggest that both BmGeminin1 and BmGeminin2 are involved in the regulation of DNA replication. These findings provide insight into the function of Geminin and contribute to our understanding of the regulation mechanism of cell cycle in silkworm.

Flexible DNA Path in the MCM Double Hexamer Loaded on DNA.

PubMed

Hizume, Kohji; Kominami, Hiroaki; Kobayashi, Kei; Yamada, Hirofumi; Araki, Hiroyuki

2017-05-16

The formation of the pre-replicative complex (pre-RC) during the G1 phase, which is also called the licensing of DNA replication, is the initial and essential step of faithful DNA replication during the subsequent S phase. It is widely accepted that in the pre-RC, double-stranded DNA passes through the holes of two ring-shaped minichromosome maintenance (MCM) 2-7 hexamers; however, the spatial organization of the DNA and proteins involved in pre-RC formation is unclear. Here we reconstituted the pre-RC from purified DNA and proteins and visualized the complex using atomic force microscopy (AFM). AFM revealed that the MCM double hexamers formed elliptical particles on DNA. Analysis of the angle of binding of DNA to the MCM double hexamer suggests that the DNA does not completely pass through both holes of the MCM hexamers, possibly because the DNA exited from the gap between Mcm2 and Mcm5. A DNA loop fastened by the MCM double hexamer was detected in pre-RC samples reconstituted from purified proteins as well as those purified from yeast cells, suggesting a higher-order architecture of the loaded MCM hexamers and DNA strands.

Characterization of the catalytic center of the Ebola virus L polymerase.

PubMed

Schmidt, Marie Luisa; Hoenen, Thomas

2017-10-01

Ebola virus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates. While no licensed therapeutics are available, recently there has been tremendous progress in developing antivirals. Targeting the ribonucleoprotein complex (RNP) proteins, which facilitate genome replication and transcription, and particularly the polymerase L, is a promising antiviral approach since these processes are essential for the virus life cycle. However, until now little is known about L in terms of its structure and function, and in particular the catalytic center of the RNA-dependent RNA polymerase (RdRp) of L, which is one of the most promising molecular targets, has never been experimentally characterized. Using multiple sequence alignments with other negative sense single-stranded RNA viruses we identified the putative catalytic center of the EBOV RdRp. An L protein with mutations in this center was then generated and characterized using various life cycle modelling systems. These systems are based on minigenomes, i.e. miniature versions of the viral genome, in which the viral genes are exchanged against a reporter gene. When such minigenomes are coexpressed with RNP proteins in mammalian cells, the RNP proteins recognize them as authentic templates for replication and transcription, resulting in reporter activity reflecting these processes. Replication-competent minigenome systems indicated that our L catalytic domain mutant was impaired in genome replication and/or transcription, and by using replication-deficient minigenome systems, as well as a novel RT-qPCR-based genome replication assay, we showed that it indeed no longer supported either of these processes. However, it still showed similar expression to wild-type L, and retained its ability to be incorporated into inclusion bodies, which are the sites of EBOV genome replication. We have experimentally defined the catalytic center of the EBOV RdRp, and thus a promising antiviral target regulating an essential aspect of the EBOV life cycle.

Zileuton

MedlinePlus

... class of medications called leukotriene synthesis inhibitors. It works by stopping the formation of certain natural substances that cause swelling, tightening, and mucus production in the airways.

Tool For Driving Many Fasteners Simultaneously

NASA Technical Reports Server (NTRS)

Cook, Joseph S., Jr.

1995-01-01

Proposed tool tightens or loosens several bolts, screws, nuts, or other threaded fasteners arranged in circle on compressor head, automotive wheel, pipe-end flange, or similar object. Enables assembly or disassembly in fraction of time needed to tighten fasteners one at a time. Simultaneously applies same torque to all fasteners, preventing distortion and enhancing reliability. Concept not limited to circular fastener patterns. Adapted to rectangular configurations like on engine intake manifolds, by adding gears to drive train to provide proper spacing. Designed to deliver fixed or adjustable maximum torque. To ensure even seal loading, piston pressure simultaneously ramped from initial to final values to maintain relatively constant torque loading on all fasteners until final specifications limit achieved.

Tightening the focus: moral panic, moral regulation and liberal government.

PubMed

Hier, Sean P

2011-09-01

The purpose of this article is to tighten the focus of moral panic studies by clarifying and elaborating on an analytical framework that conceptualizes moral panic as a form of moral regulation. The first part of the article explains why moral panic should be conceptualized as a form of moral regulation. The second part presents a rejoinder to Critcher's (2009) critique of the widening focus of moral panic studies. The third part elaborates on the conceptual relationship between the sociologies of moral panic and moral regulation by offering fresh insights into the sociological and political importance of moral panic as a technique of liberal government. © London School of Economics and Political Science 2011.

Painless, safe, and efficacious noninvasive skin tightening, body contouring, and cellulite reduction using multisource 3DEEP radiofrequency.

PubMed

Harth, Yoram

2015-03-01

In the last decade, Radiofrequency (RF) energy has proven to be safe and highly efficacious for face and neck skin tightening, body contouring, and cellulite reduction. In contrast to first-generation Monopolar/Bipolar and "X -Polar" RF systems which use one RF generator connected to one or more skin electrodes, multisource radiofrequency devices use six independent RF generators allowing efficient dermal heating to 52-55°C, with no pain or risk of other side effects. In this review, the basic science and clinical results of body contouring and cellulite treatment using multisource radiofrequency system (Endymed PRO, Endymed, Cesarea, Israel) will be discussed and analyzed. © 2015 Wiley Periodicals, Inc.

The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses.

PubMed

Broadbent, Andrew J; Santos, Celia P; Godbout, Rachel A; Subbarao, Kanta

2014-11-01

Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥ 100-fold) replication at 39 °C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP (34 G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 °C, but the replication of WSN(ts sig) was restricted ≥ 100-fold compared to that at 33 °C. Reassortant CA07(ts sig) viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥ 100-fold at 39 °C. In ferrets, the CA07(ts sig) virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our data indicate this is associated with the presence of a PB2 gene segment derived from an avian influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the ts signature from a licensed LAIV donor virus is ts in vitro and attenuated in vivo when the PB2 gene is derived from a human origin virus but not from an avian virus. Our study provides information that could benefit the rational design of alternative LAIV backbones against animal origin influenza viruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The Temperature-Sensitive and Attenuation Phenotypes Conferred by Mutations in the Influenza Virus PB2, PB1, and NP Genes Are Influenced by the Species of Origin of the PB2 Gene in Reassortant Viruses Derived from Influenza A/California/07/2009 and A/WSN/33 Viruses

PubMed Central

Broadbent, Andrew J.; Santos, Celia P.; Godbout, Rachel A.

2014-01-01

ABSTRACT Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥100-fold) replication at 39°C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391E, 581G, and 661T), PB2 (265S), and NP (34G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04ts sig and CA07ts sig viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39°C, but the replication of WSNts sig was restricted ≥100-fold compared to that at 33°C. Reassortant CA07ts sig viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥100-fold at 39°C. In ferrets, the CA07ts sig virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07ts sig virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. IMPORTANCE Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our data indicate this is associated with the presence of a PB2 gene segment derived from an avian influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the ts signature from a licensed LAIV donor virus is ts in vitro and attenuated in vivo when the PB2 gene is derived from a human origin virus but not from an avian virus. Our study provides information that could benefit the rational design of alternative LAIV backbones against animal origin influenza viruses. PMID:25122786

A pilot study of the efficacy of the POLARGEN® ultrahigh-frequency electric field (40.68 MHz) radiofrequency device in the treatment of facial contouring.

PubMed

Kim, Miri; Lim, Jihong; Bae, Jung Min; Park, Hyun Jeong

2017-11-01

Various radiofrequency (RF) devices are used to treat skin laxity and face contouring, but few studies have examined ultrahigh-frequency (UHF) electric field (40.68 MHz) RF devices. To evaluate the efficacy and safety of a UHF electric field (40.68 MHz) RF device for skin tightening and face contouring. Ten patients each underwent four sessions of UHF electric field RF device treatment at 2-week intervals. Clinical improvement was evaluated with the patient satisfaction score using a six-point scale, and clinical photographs taken at every visit and 2 months after the RF treatment were assessed. Skin biopsies were obtained from one patient before the first treatment and immediately after the last treatment. Adverse reactions were recorded at every follow-up visit. All patients were women with a mean age of 51.7 ± 7.2 years. The mean satisfaction score was 4.5 ± 0.9 immediately after the last treatment session. Cheek, jawline, and neck enhancement and tightening were apparent in all patients. Side effects were minimal, and there were no burns or major complications. The UHF electric field RF device was effective for skin tightening and facial contouring, without significant adverse reactions.

Single-treatment skin tightening by radiofrequency and long-pulsed, 1064-nm Nd: YAG laser compared.

PubMed

Key, Douglas J

2007-02-01

To compare single-treatment facial skin tightening achieved with the current radiofrequency (RF) protocol with single-treatment tightening achieved with the long-pulsed, 1064-nm Nd:YAG laser. A total of 12 patients were treated with RF energy on one side of the face and laser energy on the other. Results were evaluated on a numerical scale (0-12 with 12 = greatest enhancement) from pre- and posttreatment photographs by a blinded panel. Upper face improvement (posttreatment score minus pretreatment score) was essentially the same on both sides (30.2 and 31.3% improvement for laser and RF, respectively, P=0.89). Lower face improvement was greater in the laser-treated side (35.7 and 23.8% improvement for laser and RF, respectively), but the difference was not significant (P=0.074). Overall face improvement was significantly greater on the laser-treated side (47.5 and 29.8% improvement for laser and RF, respectively, P=0.028). A single high-fluence treatment with the long-pulse 1064-nm Nd:YAG laser may improve skin laxity more than a single treatment with the RF device. Further controlled split-face or very large non-self controlled studies are needed to conclusively determine the relative efficacies of the two technologies. (c) 2007 Wiley-Liss, Inc.

Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma.

PubMed

Prevost, Luanna B; Smith, Michelle K; Knight, Jennifer K

2016-01-01

Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon mutation potentially impacts replication, transcription, and translation. We then used computer-assisted lexical analysis combined with human scoring to categorize student responses. The lexical analysis models showed high agreement with human scoring, demonstrating that this approach can be successfully used to analyze large numbers of student written responses. The results of this analysis show that students' ideas about one process in the central dogma can affect their thinking about subsequent and previous processes, leading to mixed models of conceptual understanding. © 2016 L. B. Prevost et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The composition and initial evaluation of a grimace scale in ferrets after surgical implantation of a telemetry probe.

PubMed

Reijgwart, Marsinah L; Schoemaker, Nico J; Pascuzzo, Riccardo; Leach, Matthew C; Stodel, Melanie; de Nies, Loes; Hendriksen, Coenraad F M; van der Meer, Miriam; Vinke, Claudia M; van Zeeland, Yvonne R A

2017-01-01

Reliable recognition of pain is difficult in ferrets as many currently available parameters are non-specific, inconsistent and/or impractical. Grimace scales have successfully been applied to assess pain in different animal species and might also be applicable to ferrets. To compose a Ferret Grimace Scale (FGS), we studied the facial musculature of ferrets and compared lateral photographs of 19 ferret faces at six time points before and after intraperitoneal telemetry probe implantation. We identified the Action Units (AUs) orbital tightening, nose bulging, cheek bulging, ear changes and whisker retraction as potential indicators of pain in ferrets. To evaluate whether these AUs could reliably be used to identify photographs taken before and after surgery, the photographs were scored 0, 1 or 2 (not, moderately or obviously present) by 11 observers that were blinded to the treatment and timing of the photographs. All AU-scores assigned to the photographs taken five hours after surgery were significantly higher compared to their time-matched baseline scores. Further analysis using the weights that were obtained using a Linear Discriminant Analysis revealed that scoring orbital tightening alone was sufficient to make this distinction with high sensitivity, specificity and accuracy. Including weighted scores for nose bulging, cheek bulging and ear change did not change this. As these AUs had more missing values than orbital tightening, their descriptions should be re-evaluated. Including whisker retraction, which had a negative weight, resulted in lower accuracy and should therefore in its current form be left out of the FGS. Overall, the results of this study suggest that the FGS and the AU orbital tightening in particular could be useful in a multifactorial pain assessment protocol for ferrets. However, before applying the FGS in practice, it should be further validated by incorporating more time points before and after applying (different) painful stimuli, and different levels of analgesia.

Influence of Diamondlike Carbon Coating of Screws on Axial Tightening Force and Stress Distribution on Overdenture Bar Frameworks with Different Fit Levels and Materials.

PubMed

dos Santos, Mateus Bertolini Fernandes; Bacchi, Atais; Consani, Rafael Leonardo Xediek; Correr-Sobrinho, Lourenço

2015-01-01

The aim of this study was to evaluate the axial tightening force applied by conventional and diamondlike carbon (DLC)-coated screws and to verify, through three-dimensional finite element analysis (FEA), the stress distribution caused by different framework materials and prosthetic screws in overdenture frameworks with different misfit levels. The axial tightening force applied by the screw was evaluated by means of a titanium matrix connected to a load cell. Conventional titanium or DLC-coated screws were tightened with a digital torque wrench, and the load values were recorded. The values were applied in an FEA to a bar-clip attachment system connected to two 4.0 × 11-mm external-hexagon titanium implants placed in an anterior edentulous arch. DLC-coated and conventional screws were modeled with their respective axial forces obtained on the experimental evaluation for three bar framework materials (titanium, nickel-chromium, and cobalt-chromium) and three levels of misfit (100, 150, and 200 μm). Von Mises stresses for prosthetic components and maximum principal stress and microstrains (maximum principal strains) for bone tissue were measured. The mean force applied by the conventional screw was 25.55 N (± 1.78); the prosthetic screw coated with a DLC layer applied a mean force of 31.44 N (± 2.11), a statistically significant difference. In the FEA, the DLC screw led to higher stresses on the framework; however, the prosthetic screw suffered lower stress. No influence of screw type was seen in the bone tissue. Titanium frameworks reduced the stress transmitted to the bone tissue and the bar framework but had no influence on the screws. Higher misfit values resulted in an increased stress/strain in bone tissue and bar framework, which was not the case for retention screws.

Effect of Repeated Screw Joint Closing and Opening Cycles and Cyclic Loading on Abutment Screw Removal Torque and Screw Thread Morphology: Scanning Electron Microscopy Evaluation.

PubMed

Arshad, Mahnaz; Mahgoli, Hosseinali; Payaminia, Leila

To evaluate the effect of repeated screw joint closing and opening cycles and cyclic loading on abutment screw removal torque and screw thread morphology using scanning electron microscopy (SEM). Three groups (n = 10 in each group) of implant-abutment-abutment screw assemblies were created. There were also 10 extra abutment screws as new screws in group 3. The abutment screws were tightened to 12 Ncm with an electronic torque meter; then they were removed and removal torque values were recorded. This sequence was repeated 5 times for group 1 and 15 times for groups 2 and 3. The same screws in groups 1 and 2 and the new screws in group 3 were then tightened to 12 Ncm; this was also followed by screw tightening to 30 Ncm and retightening to 30 Ncm 15 minutes later. Removal torque measurements were performed after screws were subjected to cyclic loading (0.5 × 10⁶ cycles; 1 Hz; 75 N). Moreover, the surface topography of one screw from each group before and after cyclic loading was evaluated with SEM and compared with an unused screw. All groups exhibited reduced removal torque values in comparison to insertion torque in each cycle. However, there was a steady trend of torque loss in each group. A comparison of the last cycle of the groups before loading showed significantly greater torque loss value in the 15th cycle of groups 2 and 3 compared with the fifth cycle of group 1 (P < .05). Nonetheless, torque loss values after loading were not shown to be significantly different from each other. Using a new screw could not significantly increase the value of removal torque. It was concluded that restricting the amount of screw tightening is more important than replacing the screw with a new one when an abutment is definitively placed.

Influence of Different Screw Torque Levels on the Biomechanical Behavior of Tapered Prosthetic Abutments.

PubMed

Herbst, Paulo Eduardo; de Carvalho, Eduardo Bortolas; Salatti, Rafael C; Valgas, Laiz; Tiossi, Rodrigo

To study the force used for tightening tapered one-piece prosthetic abutments and their influence on the removal torque value and stress level of the prosthetic abutment after cyclic loading. Fourteen implants and prosthetic abutments were divided into two groups (n = 7): G1, 20 Ncm; and G2, 32 Ncm (manufacturer recommended). A 20-mm T-shaped horizontal bar was adapted to the abutments. A 12-Hz cyclic loading was applied to the specimens in an electrodynamic testing system with the maximum number of cycles set to 10 6 . Specimens were inclined by 15 degrees from the vertical axis, and a 5-mm off-center vertical load was applied to generate a combination of bending and torquing moments on the tapered connections. Progressive loads (from 164.85 to 362.85 N) were applied when the previous sample survived 10 6 cycles. The paired t test compared the screw removal torque with the initial tightening torque for each group (α = .05). A finite element analysis (FEA) of the mechanical testing analyzed the regions of stress concentration. No specimens failed after 10 6 cyclic loadings. The mean screw removal torque for both groups was similar to the initial abutment torque value applied for each group (G1, 20.36 ± 8.73 Ncm; and G2, 35.61 ± 6.99 Ncm) (P > .05). FEA showed similar stress behavior for both groups in the study despite the different simulated screw preloads (G1: 200 N; G2: 320 N). The coronal region of the implant body presented the highest strain values in both groups. Tightening tapered one-piece prosthetic abutments at 20 and 32 Ncm maintains a stable connection after cyclic loading. The stresses generated by the different tightening forces during cyclic loading are highest at the coronal level of the connection.

Objective assessment of skin tightening in Asians using a water-filtered near-infrared (1,000–1,800 nm) device with contact-cooling and freezer-stored gel

PubMed Central

Tanaka, Yohei; Tsunemi, Yuichiro; Kawashima, Makoto; Tatewaki, Naoto; Nishida, Hiroshi

2013-01-01

Background Near-infrared has been shown to penetrate deeper than optical light sources independent of skin color, allowing safer treatment for the Asian skin type. Many studies have indicated the efficacy of various types of devices, but have not included a sufficiently objective evaluation. In this study, we used three-dimensional imaging for objective evaluation of facial skin tightening using a water-filtered near-infrared device. Methods Twenty Japanese patients were treated with the water-filtered near-infrared (1,000–1,800 nm) device using a contact-cooling and nonfreezing gel stored in a freezer. Three-dimensional imaging was performed, and quantitative volume measurements were taken to evaluate the change in post-treatment volume. The patients then provided their subjective assessments. Results Objective assessments of the treated cheek volume evaluated by a three-dimensional color schematic representation with quantitative volume measurements showed significant improvement 3 months after treatment. The mean volume reduction at the last post-treatment visit was 2.554 ± 0.999 mL. The post-treatment volume was significantly reduced compared with the pretreatment volume in all patients (P < 0.0001). Eighty-five percent of patients reported satisfaction with the improvement of skin laxity, and 80% of patients reported satisfaction with improvement of rhytids, such as the nasolabial folds. Side effects, such as epidermal burns and scar formation, were not observed throughout the study. Conclusion The advantages of this water-filtered near-infrared treatment are its high efficacy for skin tightening, associated with a minimal level of discomfort and minimal side effects. Together, these characteristics facilitate our ability to administer repeated treatments and provide alternative or adjunctive treatment for patients, with improved results. This study provides a qualitative and quantitative volumetric assessment, establishing the ability of this technology to reduce volume through noninvasive skin tightening. PMID:23837000

The composition and initial evaluation of a grimace scale in ferrets after surgical implantation of a telemetry probe

PubMed Central

Schoemaker, Nico J.; Pascuzzo, Riccardo; Leach, Matthew C.; Stodel, Melanie; de Nies, Loes; Hendriksen, Coenraad F. M.; van der Meer, Miriam; Vinke, Claudia M.; van Zeeland, Yvonne R. A.

2017-01-01

Reliable recognition of pain is difficult in ferrets as many currently available parameters are non-specific, inconsistent and/or impractical. Grimace scales have successfully been applied to assess pain in different animal species and might also be applicable to ferrets. To compose a Ferret Grimace Scale (FGS), we studied the facial musculature of ferrets and compared lateral photographs of 19 ferret faces at six time points before and after intraperitoneal telemetry probe implantation. We identified the Action Units (AUs) orbital tightening, nose bulging, cheek bulging, ear changes and whisker retraction as potential indicators of pain in ferrets. To evaluate whether these AUs could reliably be used to identify photographs taken before and after surgery, the photographs were scored 0, 1 or 2 (not, moderately or obviously present) by 11 observers that were blinded to the treatment and timing of the photographs. All AU-scores assigned to the photographs taken five hours after surgery were significantly higher compared to their time-matched baseline scores. Further analysis using the weights that were obtained using a Linear Discriminant Analysis revealed that scoring orbital tightening alone was sufficient to make this distinction with high sensitivity, specificity and accuracy. Including weighted scores for nose bulging, cheek bulging and ear change did not change this. As these AUs had more missing values than orbital tightening, their descriptions should be re-evaluated. Including whisker retraction, which had a negative weight, resulted in lower accuracy and should therefore in its current form be left out of the FGS. Overall, the results of this study suggest that the FGS and the AU orbital tightening in particular could be useful in a multifactorial pain assessment protocol for ferrets. However, before applying the FGS in practice, it should be further validated by incorporating more time points before and after applying (different) painful stimuli, and different levels of analgesia. PMID:29131858

Significant skin-tightening by closure of fractional ablative laser holes.

PubMed

Russe, Elisabeth; Purschke, Martin; Limpiangkanan, Wikunda; Farinelli, William A; Wang, Ying; Doukas, Apostolos G; Sakamoto, Fernanda H; Wechselberger, Gottfried; Anderson, Richard Rox

2018-01-01

Ablative fractional laser treatment uses thousands of very small laser beam wounds to damage a fraction of the skin, which stimulates tissue remodeling. Each open micro-wound heals without scarring, but the amount of skin tightening achieved is limited. This animal study was performed to test the hypothesis that immediate temporary closure of fractional laser wounds could increase skin tightening after fractional ablative laser treatment. Four adult swine were used for the study; 98 square test sites (3 × 3 cm) were tattooed on the abdomen and flanks of each pig. An ablative fractional Erbium:YAG laser (Sciton Profile, Sciton Inc, Palo Alto, CA) was used to treat the test areas. A laser micro-spot fluence of 375 J/cm 2 was delivered in 150-250 microseconds pulses, resulting in an array of ablation channels extending 1.5 mm deep into the skin, with a spot size of 250 µm, with 10% treatment density. Immediately following laser exposure the resulting holes were closed using a stretched elastic adhesive dressing, which, when applied, recoiled and compressed the diameter of the ablation holes. The compressive dressings were removed after 7 days. This procedure was compared to removing the same amount of skin (10%) mechanically by specially designed 19 gauge coring needles, as well as to the same laser and coring methods without compression closure. Area and shape of test sites were measured by digital photography before and 28 days after treatment. Data analysis included compensation for animal growth, as measured by increase in the area of the untreated control sites. All treated and control sites healed within a week, without scarring evident at 28 days. Laser treatment combined with compressive wound closure caused significant shrinkage at 28 days compared with untreated control sites. The treated skin area was reduced by 11.5% (P = 0.0001). Needle coring with wound closure produced similar, significant shrinkage (8%, P < 0.0021), whereas laser and needle coring treatment without closure did not result in significant area reduction (P = 0.1289) compared with untreated control sites. Significant skin tightening can be achieved by immediate temporary non-invasive wound closure after short pulse Er:YAG fractional ablative laser treatment, as well as after mechanically removing skin with a coring needle. This approach may improve skin tightening after ablative laser treatments. Further clinical studies are necessary to confirm successful application in humans. Lasers Surg. Med. 50:64-69, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

PubMed

Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng

2018-02-14

The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

Tightening slip knots in raw and degummed silk to increase toughness without losing strength.

PubMed

Pantano, Maria F; Berardo, Alice; Pugno, Nicola M

2016-02-12

Knots are fascinating topological elements, which can be found in both natural and artificial systems. While in most of the cases, knots cannot be loosened without breaking the strand where they are tightened, herein, attention is focused on slip or running knots, which on the contrary can be unfastened without compromising the structural integrity of their hosting material. Two different topologies are considered, involving opposite unfastening mechanisms, and their influence on the mechanical properties of natural fibers, as silkworm silk raw and degummed single fibers, is investigated and quantified. Slip knots with optimized shape and size result in a significant enhancement of fibers energy dissipation capability, up to 300-400%, without affecting their load bearing capacity.

Tightening slip knots in raw and degummed silk to increase toughness without losing strength

PubMed Central

Pantano, Maria F.; Berardo, Alice; Pugno, Nicola M.

2016-01-01

Knots are fascinating topological elements, which can be found in both natural and artificial systems. While in most of the cases, knots cannot be loosened without breaking the strand where they are tightened, herein, attention is focused on slip or running knots, which on the contrary can be unfastened without compromising the structural integrity of their hosting material. Two different topologies are considered, involving opposite unfastening mechanisms, and their influence on the mechanical properties of natural fibers, as silkworm silk raw and degummed single fibers, is investigated and quantified. Slip knots with optimized shape and size result in a significant enhancement of fibers energy dissipation capability, up to 300–400%, without affecting their load bearing capacity. PMID:26868855

Do Sealing Materials Influence Superstructure Attachment in Implants?

PubMed

Biscoping, Stephanie; Ruttmann, Esther; Rehmann, Peter; Wöstmann, Bernd

This study aimed to evaluate the possible effect of sealing materials on superstructure attachment (ie, tightening/loosening torque and implant-abutment gap) in two different implant systems. A silicone, a chlorhexidine gel, and an industrial lubricant were tested. A 3D microscope was used for assessment of the implant-abutment gap, and the abutment screw was tightened and loosened with a digital torque screwdriver. A total of 20 implants per test group (10 BEGO Semados RI and 10 Nobel Biocare Replace Select Straight) were evaluated. The tested sealing materials did not influence the gap between implant and abutment, but the force necessary for loosening the abutment screws decreased significantly. Sealing materials may be useful against bacteria, but probably influence torque negatively.

Experimental investigation of residual stress distribution during turning of weak stiffness revolving parts

NASA Astrophysics Data System (ADS)

Jiao, Sicheng; Zhang, Chengyan; Liu, Guancheng; Lu, Jiping; Tang, Shuiyuan

2017-08-01

A series of turning experiments have been carried out to study the effect of different cutting speed, feed rate and pre-tightening torque on residual stress distribution during turning of weak stiffness revolving parts. Surface residual stress and the peak residual compressive stress are selected from the typical residual stress distribution profile. The residual stress by turning was measured by X-ray diffraction method. In order to get the distribution of residual stress along depth direction, the specimens need to be etched layer by layer. From this investigation, it can be concluded that it is practicable to control the distribution of residual stress by changing the pre-tightening torque and cutting parameters during turning of weak stiffness revolving parts.

Pathogenic effects of Rift Valley fever virus NSs gene are alleviated in cultured cells by expressed antiviral short hairpin RNAs.

PubMed

Scott, Tristan; Paweska, Janusz T; Arbuthnot, Patrick; Weinberg, Marc S

2012-01-01

Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, may cause severe hepatitis, encephalitis and haemorrhagic fever in humans. There are currently no available licensed vaccines or therapies to treat the viral infection in humans. RNA interference (RNAi)-based viral gene silencing offers a promising approach to inhibiting replication of this highly pathogenic virus. The small (S) segment of the RVFV tripartite genome carries the genetic determinates for pathogenicity during infection. This segment encodes the non-structural S (NSs) and essential nucleocapsid (N) genes. To advance RNAi-based inhibition of RVFV replication, we designed several Pol III short hairpin RNA (shRNA) expression cassettes against the NSs and N genes, including a multimerized plasmid vector that included four shRNA expression cassettes. Effective target silencing was demonstrated using full- and partial-length target reporter assays, and confirmed by western blot analysis of exogenous N and NSs expression. Small RNA northern blots showed detectable RNAi guide strand formation from single and multimerized shRNA constructs. Using a cell culture model of RVFV replication, shRNAs targeting the N gene decreased intracellular nucleocapsid protein concentration and viral replication. The shRNAs directed against the NSs gene reduced NSs protein concentrations and alleviated NSs-mediated cytotoxicity, which may be caused by host transcription suppression. These data are the first demonstration that RNAi activators have a potential therapeutic benefit for countering RVFV infection.

Two Geminin homologs regulate DNA replication in silkworm, Bombyx mori

PubMed Central

Tang, Xiao-Fang; Chen, Xiang-Yun; Zhang, Chun-Dong; Li, Yao-Feng; Liu, Tai-Hang; Zhou, Xiao-Lin; Wang, La; Zhang, Qian; Chen, Peng; Lu, Cheng; Pan, Min-Hui

2017-01-01

ABSTRACT DNA replication is rigorously controlled in cells to ensure that the genome duplicates exactly once per cell cycle. Geminin is a small nucleoprotein, which prevents DNA rereplication by directly binding to and inhibiting the DNA replication licensing factor, Cdt1. In this study, we have identified 2 Geminin genes, BmGeminin1 and BmGeminn2, in silkworm, Bombyx mori. These genes contain the Geminin conserved coiled-coil domain and are periodically localized in the nucleus during the S-G2 phase but are degraded at anaphase in mitosis. Both BmGeminin1 and BmGeminin2 are able to homodimerize and interact with BmCdt1 in cells. In addition, BmGeminin1 and BmGeminin2 can interact with each other. Overexpression of BmGeminin1 affects cell cycle progression: cell cycle is arrested in S phase, and RNA interference of BmGeminin1 leads to rereplication. In contrast, overexpression or knockdown of BmGeminin2 with RNAi did not significantly affect cell cycle, while more rereplication occurred when BmGeminin1 and BmGeminin2 together were knocked down in cells than when only BmGeminin1 was knocked down. These data suggest that both BmGeminin1 and BmGeminin2 are involved in the regulation of DNA replication. These findings provide insight into the function of Geminin and contribute to our understanding of the regulation mechanism of cell cycle in silkworm. PMID:28379781

Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

PubMed

Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

2013-12-05

Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

An orc1 allele with a mutated APC motif is female sterile with amplification defects.

PubMed

Park, So Young; Asano, Maki

2012-08-01

The origin recognition complex 1 (ORC1) is the largest subunit of the ORC, the heteromeric hexamer. ORC1 is an essential component of the pre-replicative complex (pre-RC) that licenses eukaryote DNA replication origins. The levels of ORC1 fluctuate during the mitotic cell cycle in Drosophila as well as in some human cells. Proteolysis of ORC1 occurs at the end of M phase in Drosophila, which is mediated by the anaphase-promoting complex (APC), and in late S phase in human cells by Skip-Cullin-F box (SCF). Previously we showed that proteolysis of ORC1 by APC is mediated by the ORC1 destruction box (the O-box), an APC motif conserved among species yet distinct from the D-box or KEN-box. Recently we showed that replacing the O-box with the D-box (ORC1O→D) changes the degradation profile of ORC1 during a canonical cell cycle. Here we report further characterization of the ORC1O→D allele that turned out to be a useful tool to examine the function of ORC1 in other modes of DNA replication during oogenesis. In endoreplication stages ORC1O→D does not change any DNA content profiles, consistent with our previous finding that ORC is dispensable for endoreplication. However, in amplification stage replication efficiency of ORC1O→D is drastically reduced, which resulted in amplification defects that led to thin egg shell phenotype. Taken together, our analyses show that orc1 allele newly identified is female sterile and possesses a unique feature of phenotypes that are distinct in different modes of DNA replication.

Genome-wide association study of sporadic brain arteriovenous malformations.

PubMed

Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G; Sidney, Stephen; McCulloch, Charles E; Al-Shahi Salman, Rustam; Berg, Jonathan N; Koeleman, Bobby P C; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto; Puca, Alfredo; Lawton, Michael T; Young, William L; Pawlikowska, Ludmila; Klijn, Catharina J M; Kim, Helen

2016-09-01

The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Ebola Virus Vaccines – reality or fiction?

PubMed Central

Mire, Chad E.; Geisbert, Thomas W.; Feldmann, Heinz

2016-01-01

For 40 years ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates. In December 2013 an unprecedented Zaire ebolavirus epidemic began in West Africa. Although “patient zero” has finally been reached after 2 years, the virus is again causing disease in the region. Currently there are no licensed vaccines or therapeutic countermeasures against ebolaviruses; however, the epidemic in West Africa has focused attention on the potential vaccine platforms developed over the past 15 years. There has been remarkable progress using a variety of platforms including DNA, subunit, and several viral vector approaches, replicating and non-replicating, which have shown varying degrees of protective efficacy in the “gold-standard” nonhuman primate models for Ebolavirus infections. A number of these vaccine platforms have moved into clinical trials over the past year with the hope of finding an efficacious vaccine to prevent future outbreaks/epidemics of Ebola hemorrhagic fever on the scale of the West African epidemic. PMID:27078187

Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells

PubMed Central

Ly, Tony; Endo, Aki; Lamond, Angus I

2015-01-01

Abstract Previously, we analyzed protein abundance changes across a ‘minimally perturbed’ cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/), an online, searchable resource. DOI: http://dx.doi.org/10.7554/eLife.04534.001 PMID:25555159

Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards practical application for treating herpes zoster.

PubMed

Shiraki, K

2017-11-01

Valacyclovir and famciclovir enabled successful systemic therapy for treating herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their phosphorylation with viral thymidine kinase. Helicase-primase inhibitors (HPIs) inhibit the progression of the replication fork, an initial step in DNA synthesis to separate the double strand into two single strands. The HPIs amenamevir and pritelivir have a novel mechanism of action, once-daily administration with nonrenal excretory characteristics, and clinical efficacy for genital herpes. Amenamevir exhibits anti-VZV and anti-HSV activity while pritelivir only has anti-HSV activity. A clinical trial of amenamevir for herpes zoster has been completed, and amenamevir has been licensed and successfully used in 20,000 patients with herpes zoster so far in Japan. We have characterized the features of the antiviral action of amenamevir and, unlike acyclovir, the drug's antiviral activity is not influenced by the viral replication cycle. Amenamevir is opening a new era of antiherpes therapy. Copyright 2017 Clarivate Analytics.

Darunavir concentrations in cerebrospinal fluid and blood in HIV-1-infected individuals.

PubMed

Yilmaz, Aylin; Izadkhashti, Arash; Price, Richard W; Mallon, Patrick W; De Meulder, Marc; Timmerman, Philip; Gisslén, Magnus

2009-04-01

Darunavir is the most recently licensed protease inhibitor currently used in treatment-experienced HIV-infected individuals. Our objective was to determine darunavir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing ritonavir-boosted darunavir. Darunavir concentrations were determined by liquid chromatography tandem mass spectrometry in 14 paired CSF and plasma samples from eight HIV-1-infected individuals. The lower limit of quantification was 5.0 ng/ml. All of the 14 CSF samples had detectable darunavir concentrations with a median darunavir concentration of 34.2 ng/ml (range 15.9-212.0 ng/ml). The median (range) plasma darunavir concentration was 3930 (1800-12900) ng/ml. All CSF samples had detectable darunavir concentrations. Most of them exceeded or were in the same range as levels needed to inhibit replication of wild type virus, making it probable that darunavir, at least to some extent, contributes to the suppression of HIV replication in the central nervous system.

Identification of a small molecule inhibitor of Ebola virus genome replication and transcription using in silico screening.

PubMed

Easton, Victoria; McPhillie, Martin; Garcia-Dorival, Isabel; Barr, John N; Edwards, Thomas A; Foster, Richard; Fishwick, Colin; Harris, Mark

2018-06-02

Ebola virus (EBOV) causes a severe haemorrhagic fever in humans and has a mortality rate over 50%. With no licensed drug treatments available, EBOV poses a significant threat. Investigations into possible therapeutics have been severely hampered by the classification of EBOV as a BSL4 pathogen. Here, we describe a drug discovery pathway combining in silico screening of compounds predicted to bind to a hydrophobic pocket on the nucleoprotein (NP); with a robust and rapid EBOV minigenome assay for inhibitor validation at BSL2. One compound (MCCB4) was efficacious (EC 50 4.8 μM), exhibited low cytotoxicity (CC 50  > 100 μM) and was specific, with no effect on either a T7 RNA polymerase driven firefly luciferase or a Bunyamwera virus minigenome. Further investigations revealed that this small molecule inhibitor was able to outcompete established replication complexes, an essential aspect for a potential EBOV treatment. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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

Kuo, Alex J; Song, Jikui; Cheung, Peggie

The recognition of distinctly modified histones by specialized 'effector' proteins constitutes a key mechanism for transducing molecular events at chromatin to biological outcomes. Effector proteins influence DNA-templated processes, including transcription, DNA recombination and DNA repair; however, no effector functions have yet been identified within the mammalian machinery that regulate DNA replication. Here we show that ORC1 - a component of ORC (origin of replication complex), which mediates pre-DNA replication licensing - contains a bromo adjacent homology (BAH) domain that specifically recognizes histone H4 dimethylated at lysine 20 (H4K20me2). Recognition of H4K20me2 is a property common to BAH domains present withinmore » diverse metazoan ORC1 proteins. Structural studies reveal that the specificity of the BAH domain for H4K20me2 is mediated by a dynamic aromatic dimethyl-lysine-binding cage and multiple intermolecular contacts involving the bound peptide. H4K20me2 is enriched at replication origins, and abrogating ORC1 recognition of H4K20me2 in cells impairs ORC1 occupancy at replication origins, ORC chromatin loading and cell-cycle progression. Mutation of the ORC1 BAH domain has been implicated in the aetiology of Meier-Gorlin syndrome (MGS), a form of primordial dwarfism, and ORC1 depletion in zebrafish results in an MGS-like phenotype. We find that wild-type human ORC1, but not ORC1-H4K20me2-binding mutants, rescues the growth retardation of orc1 morphants. Moreover, zebrafish depleted of H4K20me2 have diminished body size, mirroring the phenotype of orc1 morphants. Together, our results identify the BAH domain as a novel methyl-lysine-binding module, thereby establishing the first direct link between histone methylation and the metazoan DNA replication machinery, and defining a pivotal aetiological role for the canonical H4K20me2 mark, via ORC1, in primordial dwarfism.« less

DNA Replication and Cell Cycle Progression Regulatedby Long Range Interaction between Protein Complexes bound to DNA.

PubMed

Matsson, L

2001-12-01

A nonstationary interaction that controlsDNA replication and the cell cycle isderived from many-body physics in achemically open T cell. The model predictsa long range force F'(ξ) =- (κ/2) ξ(1 - ξ)(2 - ξ)between thepre-replication complexes (pre-RCs) boundby the origins in DNA, ξ = ϕ/N being the relativedisplacement of pre-RCs, ϕ the number of pre-RCs, N the number of replicons to be replicated,and κ the compressibilitymodulus in the lattice of pre-RCs whichbehaves dynamically like an elasticallybraced string. Initiation of DNAreplication is induced at the thresholdϕ = N by a switch ofsign of F''(ξ), fromattraction (-) and assembly in the G(1) phase (0<ϕ

Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability

PubMed Central

Pozo, Pedro N.; Cook, Jeanette Gowen

2016-01-01

Successful cell proliferation requires efficient and precise genome duplication followed by accurate chromosome segregation. The Cdc10-dependent transcript 1 protein (Cdt1) is required for the first step in DNA replication, and in human cells Cdt1 is also required during mitosis. Tight cell cycle controls over Cdt1 abundance and activity are critical to normal development and genome stability. We review here recent advances in elucidating Cdt1 molecular functions in both origin licensing and kinetochore–microtubule attachment, and we describe the current understanding of human Cdt1 regulation. PMID:28025526

Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.

PubMed

Pannekoek, Willem-Jan; Vliem, Marjolein J; Bos, Johannes L

2018-02-17

Epac1 and Rap1 mediate cAMP-induced tightening of endothelial junctions. We have previously found that one of the mechanisms is the inhibition of Rho-mediated tension in radial stress fibers by recruiting the RhoGAP ArhGAP29 in a complex containing the Rap1 effectors Rasip1 and Radil. However, other mechanisms have been proposed as well, most notably the induction of tension in circumferential actin cables by Cdc42 and its GEF FGD5. Here, we have investigated how Rap1 controls FGD5/Cdc42 and how this interconnects with Radil/Rasip1/ArhGAP29. Using endothelial barrier measurements, we show that Rho inhibition is not sufficient to explain the barrier stimulating effect of Rap1. Indeed, Cdc42-mediated tension is induced at cell-cell contacts upon Rap1 activation and this is required for endothelial barrier function. Depletion of potential Rap1 effectors identifies AF6 to mediate Rap1 enhanced tension and concomitant Rho-independent barrier function. When overexpressed in HEK293T cells, AF6 is found in a complex with FGD5 and Radil. From these results we conclude that Rap1 utilizes multiple pathways to control tightening of endothelial junctions, possibly through a multiprotein effector complex, in which AF6 functions to induce tension in circumferential actin cables.

Behaviour of Frictional Joints in Steel Arch Yielding Supports

NASA Astrophysics Data System (ADS)

Horyl, Petr; Šňupárek, Richard; Maršálek, Pavel

2014-10-01

The loading capacity and ability of steel arch supports to accept deformations from the surrounding rock mass is influenced significantly by the function of the connections and in particular, the tightening of the bolts. This contribution deals with computer modelling of the yielding bolt connections for different torques to determine the load-bearing capacity of the connections. Another parameter that affects the loading capacity significantly is the value of the friction coefficient of the contacts between the elements of the joints. The authors investigated both the behaviour and conditions of the individual parts for three values of tightening moment and the relation between the value of screw tightening and load-bearing capacity of the connections for different friction coefficients. ANSYS software and the finite element method were used for the computer modelling. The solution is nonlinear because of the bi-linear material properties of steel and the large deformations. The geometry of the computer model was created from designs of all four parts of the structure. The calculation also defines the weakest part of the joint's structure based on stress analysis. The load was divided into two loading steps: the pre-tensioning of connecting bolts and the deformation loading corresponding to 50-mm slip of one support. The full Newton-Raphson method was chosen for the solution. The calculations were carried out on a computer at the Supercomputing Centre VSB-Technical University of Ostrava.

Short time efficacy and safety of focused monopolar radiofrequency device for labial laxity improvement-noninvasive labia tissue tightening. A prospective cohort study.

PubMed

Fistonić, Ivan; Sorta Bilajac Turina, Iva; Fistonić, Nikola; Marton, Ingrid

2016-03-01

To evaluate safety and efficacy of focused monopolar radio frequency (RF) device for non-invasive labia tissue tightening and improvement of labial laxity. This prospective cohort study participants were 17 female subjects aged between 27 and 56 years with lax skin at the labia area. All subjects received four consecutive treatments at 7-day intervals with RF device (Exilis Protege IntimaR, BTL Industries Inc., Boston, MA). The primary efficacy outcome measure was defined as one or more point improvement on 1-4 scale for vulva appearance determined by three blinded evaluators. Digital photographs were taken at the baseline and 1 month after the last treatment. Sexual gratification was assessed with Female Sexual Functioning Index (FSFI) and patient discomfort by Visual Analogue Scale (VAS). An average 2.9 (of maximum 4) points improvement rate in vulvar appearance was observed (P < 0.01). Mean of the total FSFI score enhanced from initial 75-87% (P < 0.001). Resultant 4.7 (18%) points increase was achieved. Ninety four percent of subjects reported mild to none discomfort during the treatment. No adverse events during the study course were reported. The present study demonstrates the positive effect of focused monopolar RF device for non-invasive labia tissue tightening. The treatment is effective and safe with high patient satisfaction. © 2016 Wiley Periodicals, Inc.

Transboundary hazardous waste management. Part I: Waste management policy of importing countries.

PubMed

Fan, Kuo-Shuh; Chang, Tien Chin; Ni, Shih-Piao; Lee, Ching-Hwa

2005-12-01

Mixed metal-containing waste, polychlorinated biphenyls (PCB) containing capacitors, printed circuit boards, steel mill dust and metal sludge were among the most common wastes exported from Taiwan. Before the implementation of the self-monitoring model programme of the Basel Convention (secretariat of the Basel Convention 2001) in the Asia region, Taiwan conducted a comprehensive 4-year follow-up project involving government authorities and the waste disposal facilities of the importing countries. A total of five countries and nine plants were visited in 2001-2002. The following outcomes can be drawn from these investigations. The Chinese government adopts the strategies of 'on-site processing' and 'relative centralization' on the waste management by tightening permitting and increasing site inspection. A three-level reviewing system is adopted for the import application. The United States have not signed the Basel Convention yet; the procedures of hazardous waste import rely on bilateral agreements. Importers are not required to provide official notification from the waste exporting countries. The operation, administration, monitoring and licensing of waste treatment plants are governed by the state environmental bureau. Finland, France and Belgium are members of the European Union. The procedures and policies of waste import are similar. All of the documents associated with transboundary movement require the approval of each government involved. Practically, the notification forms and tracking forms effectively manage the waste movement.

Contractions

MedlinePlus

... feel tightening of your uterus muscles at irregular intervals or a squeezing sensation in your lower abdomen ... beginning of childbirth. These contractions come at regular intervals, usually move from the back to the lower ...

Pilocarpine Ophthalmic

MedlinePlus

... instilling the next drop. Replace and tighten the cap on the dropper bottle. Do not wipe or ... someone else apply the gel. Remove the protective cap. Avoid touching the tip of the tube against ...

Defensive Driving.

ERIC Educational Resources Information Center

Sutton, Judy

1997-01-01

Discusses management issues surrounding school busing operations within the context of tightening budgets while simultaneously serving the growing number of students with special needs. The debate on bus use for advertising is highlighted. (GR)

The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype

PubMed Central

Nishiyama, Shoko; Lokugamage, Nandadeva

2016-01-01

ABSTRACT Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by “abortion storms” in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. IMPORTANCE Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12 vaccine to understand virologic characteristics. Our study revealed that MP-12 vaccine contains ts mutations independently in the L, M, and S segments and that MP-12 displays a restrictive replication at 38°C. PMID:26819307

The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype.

PubMed

Nishiyama, Shoko; Lokugamage, Nandadeva; Ikegami, Tetsuro

2016-01-27

Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12 vaccine to understand virologic characteristics. Our study revealed that MP-12 vaccine contains ts mutations independently in the L, M, and S segments and that MP-12 displays a restrictive replication at 38°C. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Azilsartan

MedlinePlus

... It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the ... Advil, Motrin) and naproxen (Aleve, Naprosyn) and selective COX-2 inhibitors such as celecoxib (Celebrex); diuretics ('water pills'); lithium ( ...

Ultrasonic extensometer measures bolt preload

NASA Technical Reports Server (NTRS)

Daniels, C. M., Jr.

1978-01-01

Extensometer using ultrasonic pulse reflections to measure elongations in tightened belts and studs is much more accurate than conventional torque wrenches in application of specified preload to bolts and other threaded fasteners.

Collagenase Clostridium Histolyticum Injection

MedlinePlus

Collagenase Clostridium histolyticum injection is used to treat Dupuytren's contracture (a painless thickening and tightening of tissue [ ... class of medications called enzymes. In people with Dupuytren's contracture, it works by helping to break down ...

IncobotulinumtoxinA Injection

MedlinePlus

... tightening of the neck muscles that may cause neck pain and abnormal head positions) in adults and blepharospasm ( ... vision changes eyelid swelling eye pain or irritation neck pain shortness of breath fainting dizziness rash hives itching ...

Eldercare at Home: Mobility Problems

MedlinePlus

... your shoulders back. You should feel your shoulder blades pull together. Cervical Range of Motion Purpose: To ... ahead. Keep your chin tucked and your shoulder blades back. Tighten your stomach muscles. First, rise up ...

7 CFR 42.110 - Sampling plans for tightened condition of container inspection; Tables II and II-A.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS STANDARDS FOR CONDITION OF FOOD CONTAINERS...

The Fall of the Flagships.

ERIC Educational Resources Information Center

Gose, Ben

2002-01-01

Describes how, with budgets tightening, the University of Texas at Austin and Texas A&M University at College Station are among the elite public institutions wondering if they should trade state money for greater autonomy. (EV)

Semilocal density functional obeying a strongly tightened bound for exchange

PubMed Central

Sun, Jianwei; Perdew, John P.; Ruzsinszky, Adrienn

2015-01-01

Because of its useful accuracy and efficiency, density functional theory (DFT) is one of the most widely used electronic structure theories in physics, materials science, and chemistry. Only the exchange-correlation energy is unknown, and needs to be approximated in practice. Exact constraints provide useful information about this functional. The local spin-density approximation (LSDA) was the first constraint-based density functional. The Lieb–Oxford lower bound on the exchange-correlation energy for any density is another constraint that plays an important role in the development of generalized gradient approximations (GGAs) and meta-GGAs. Recently, a strongly and optimally tightened lower bound on the exchange energy was proved for one- and two-electron densities, and conjectured for all densities. In this article, we present a realistic “meta-GGA made very simple” (MGGA-MVS) for exchange that respects this optimal bound, which no previous beyond-LSDA approximation satisfies. This constraint might have been expected to worsen predicted thermochemical properties, but in fact they are improved over those of the Perdew–Burke–Ernzerhof GGA, which has nearly the same correlation part. MVS exchange is however radically different from that of other GGAs and meta-GGAs. Its exchange enhancement factor has a very strong dependence upon the orbital kinetic energy density, which permits accurate energies even with the drastically tightened bound. When this nonempirical MVS meta-GGA is hybridized with 25% of exact exchange, the resulting global hybrid gives excellent predictions for atomization energies, reaction barriers, and weak interactions of molecules. PMID:25561554

Traditional Lower Blepharoplasty: Is Additional Support Necessary? A 30-Year Review.

PubMed

Maffi, Terry R; Chang, Shiliang; Friedland, Jack A

2011-07-01

Several refinements have been made in lower eyelid rejuvenation, and there is now strong belief that the traditional approach places too little emphasis on lower eyelid support. The purpose of this study was to retrospectively review the 30-year experience of the senior author (J.A.F.) performing primary lower blepharoplasty by the traditional approach and to determine the complication rate when lower lid-tightening procedures were not performed concomitantly. A retrospective chart review of all traditional blepharoplasties performed by the senior author over the past 30 years was performed. The traditional approach was performed through an external, subciliary incision. Concomitant lower lid-tightening procedures were not performed. The authors determined the complication rate of the procedure, such as symptomatic lower eyelid malposition and chemosis. A total of 3014 patients underwent traditional lower blepharoplasties and, after applying the exclusion criteria, 2007 patients were studied. A postoperative complication was defined as the development of either chemosis or symptomatic lower eyelid malposition. Chemosis developed in only 1.2 percent of the patients (24 of 2007). Eight of the 2007 patients (0.4 percent) developed symptomatic lower eyelid malposition. This study proves that when performed meticulously and precisely, traditional lower blepharoplasty is safe and effective. Correction of preoperatively diagnosed lower lid laxity is essential; however, when lower eyelid tone is adequate, the authors believe that the routine addition of a tightening procedure for support or the routine use of combined internal and external approaches is unnecessary. Therapeutic, IV.

Semilocal density functional obeying a strongly tightened bound for exchange.

PubMed

Sun, Jianwei; Perdew, John P; Ruzsinszky, Adrienn

2015-01-20

Because of its useful accuracy and efficiency, density functional theory (DFT) is one of the most widely used electronic structure theories in physics, materials science, and chemistry. Only the exchange-correlation energy is unknown, and needs to be approximated in practice. Exact constraints provide useful information about this functional. The local spin-density approximation (LSDA) was the first constraint-based density functional. The Lieb-Oxford lower bound on the exchange-correlation energy for any density is another constraint that plays an important role in the development of generalized gradient approximations (GGAs) and meta-GGAs. Recently, a strongly and optimally tightened lower bound on the exchange energy was proved for one- and two-electron densities, and conjectured for all densities. In this article, we present a realistic "meta-GGA made very simple" (MGGA-MVS) for exchange that respects this optimal bound, which no previous beyond-LSDA approximation satisfies. This constraint might have been expected to worsen predicted thermochemical properties, but in fact they are improved over those of the Perdew-Burke-Ernzerhof GGA, which has nearly the same correlation part. MVS exchange is however radically different from that of other GGAs and meta-GGAs. Its exchange enhancement factor has a very strong dependence upon the orbital kinetic energy density, which permits accurate energies even with the drastically tightened bound. When this nonempirical MVS meta-GGA is hybridized with 25% of exact exchange, the resulting global hybrid gives excellent predictions for atomization energies, reaction barriers, and weak interactions of molecules.

Does maximum torque mean optimal pullout strength of screws?

PubMed

Tankard, Sara E; Mears, Simon C; Marsland, Daniel; Langdale, Evan R; Belkoff, Stephen M

2013-04-01

To determine the relationship between insertion torque and pullout strength of 3.5-mm-diameter cortical screws in cadaveric humeri with different bone mineral densities (BMDs). Five pairs of human humeri from each of 3 BMD groups (normal, osteopenic, and osteoporotic) were used. Holes were drilled in each humerus, and maximum insertion torque (T(max)) was measured by tightening a screw until stripping occurred. In the remaining holes, screws were tightened to 50%, 70%, or 90% of the T(max). A servohydraulic testing machine pulled each screw out at 1 mm/s while resulting force and axial displacement were recorded at 10 Hz. The authors checked for an effect of insertion torque (percent T(max)) on pullout strength using a general linearized and latent mixed model (Stata10), controlling for cortical thickness and BMD (T-score). Pullout strength for normal and osteoporotic bone was greatest for screws inserted to 50% T(max) and was significantly greater than that at T(max) but not significantly different from that at 70% or 90% T(max). For osteopenic bone, pullout strength was greatest at 70% peak torque, but it was not significantly different from the pullout strength at the 50% or 90% T(max) levels. Tightening screws beyond 50% T(max) does not increase pullout strength of the screw and may place bone at risk for damage that might result in loss of fixation. Even after adjusting for bone thickness and density, there is no clear relationship between pullout strength and screw torque.

[Intradiscal temperature variation resulting from radiofrequency thermal therapy. Cadaver study].

PubMed

Ramírez-León, J F; Rugeles-Ortiz, J G; Barreto-perea, J A; Alonso-cuéllar, G O

2014-01-01

Disc disease is one of the most common causes of lumbar pain. The new era of treatments for degenerative disc disease involves the use of minimally-invasive thermal technologies allowing for collagen remodeling and destruction of nociceptors in the annulus. However, a better understanding of the treatment pathophysiology is needed. The purpose of this study was to measure intradiscal temperature variation after thermodiscoplasty. A human cadaver spine specimen was obtained and divided into blocks, each composed of two intervertebral plates and an intact disc. Radio frequency was applied at five spots with three different time intervals. Temperature was measured in each of the combinations. Units were weighed before and after treatment. Finally, the disc was exposed and the tightening achieved with each radio frequency application was measured. Data were analyzed with the SPSS software. The mean weight reduction obtained was 1.4 g on average (SD 0.599), with values between 0.5 and 2.6 grams. Mean temperature in the posterior rim of the annulus was 37.6 degrees C and mean temperature variation was 3.0 degrees C (SD 6.407). Mean tightening achieved in all blocks overall was 1.4 mm. The results obtained show the effectiveness of radio frequency thermodiscoplasty when performed within the safety parameters. Temperature values with radio frequency were lower than those found in comparable studies. The weight and the tightening show the effect of disc shrinking and dehydration. This report is an effective tool to define time parameters for the application of this technology.

Antiviral properties of deazaadenine nucleoside derivatives.

PubMed

Vittori, S; Dal Ben, D; Lambertucci, C; Marucci, G; Volpini, R; Cristalli, G

2006-01-01

Viral infections have menaced human beings since time immemorial, and even today new viral strains that cause lethal diseases are being discovered with alarming frequency. One major example is HIV, the etiological agent of AIDS, which spread up in the last two decades. Very recently, other virus based diseases such as avian flu have spread fear around the world, and hemorrhagic fevers from central Africa serious threaten human health because of their very deadly effects. New antiviral agents are still greatly needed to counter these menaces. Many scientists are involved in this field of research, and many of the recently discovered effective antiviral compounds are nucleoside analogues. Among those derivatives, deazapurine nucleoside analogues have demonstrated potent inhibitory effect of viral replication. This review reports on recently generated data from preparing and testing deazapurine nucleoside derivatives as inhibitors in virus replication systems. Although most of the reported data have been produced in antiHIV, antiHCMV, and antiHSV biological testing, very recently other new important fields of application have been discovered, all in topical subjects of strong interest. In fact, deazapurine nucleosides have been found to be active as chemotherapeutics for some veterinary systemic viral infections, for which no antiviral drugs are licensed yet. Furthermore, they demonstrated efficacy in the inhibition of Hepatitis C virus replication. Finally, these compounds showed high potency as virucides against Ebola Virus, curing Ebola infected mice with a single dose administration.

ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication

PubMed Central

Iwahori, Satoko; Kohmon, Daisuke; Kobayashi, Junya; Tani, Yuhei; Yugawa, Takashi; Komatsu, Kenshi; Kiyono, Tohru; Sugimoto, Nozomi; Fujita, Masatoshi

2014-01-01

Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to DNA double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also by some changes in chromatin architecture, suggesting potential ATM function in cell cycle control. Here, we found that ATM is involved in timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least in certain cell types, degradation of p27Kip1 was also impaired by ATM inhibition. The novel ATM function for Cdt1 regulation was dependent on its kinase activity and NBS1. Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S phase. ATM silencing induced partial reduction in levels of Skp2, a component of SCFSkp2 ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2 silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as reported previously, ATM silencing partially prevented Akt phosphorylation at Ser473, indicative of its activation, and Akt inhibition led to modest stabilization of Cdt1. Therefore, the ATM-Akt-SCFSkp2 pathway may partly contribute to the novel ATM function. Finally, ATM inhibition rendered cells hypersensitive to induction of re-replication, indicating importance for maintenance of genome stability. PMID:24280901

Analysis of Published Hydrogen Vehicle Safety Research

DOT National Transportation Integrated Search

2010-02-01

Hydrogen-fueled vehicles (HFVs) offer the promise of providing safe, clean, and efficient transportation in a setting of rising fuel prices and tightening environmental regulations. However, the technologies needed to store or manufacture hydrogen on...

RimabotulinumtoxinB Injection

MedlinePlus

... tightening of the neck muscles that may cause neck pain and abnormal head positions). RimabotulinumtoxinB injection is in ... cannot be substituted for another.RimabotulinumtoxinB injection controls ... longer before you feel the full benefit of rimabotulinumtoxinB injection.

Adjustable gastric banding (image)

MedlinePlus

... pouch and causes a feeling of fullness. The band can be tightened or loosened over time to change the size of the passage. Initially, the pouch holds about 1 ounce of food and later expands to 2-3 ounces.

Extra-strong "floating nut"

NASA Technical Reports Server (NTRS)

Charles, J. F.; Theakston, H.

1979-01-01

Increased bearing area withstands much higher torque than previous designs. Floating nut makes it possible to fasten parts on heavy-duty equipment, such as tractors and cranes, even though they can be reached for tightening from one side only.

Regulation of leaf organ size by the Arabidopsis RPT2a 19S proteasome subunit.

PubMed

Sonoda, Yutaka; Sako, Kaori; Maki, Yuko; Yamazaki, Naoko; Yamamoto, Hiroko; Ikeda, Akira; Yamaguchi, Junji

2009-10-01

The ubiquitin/26S proteasome pathway plays a central role in the degradation of short-lived regulatory proteins, to control many cellular events. To further understand this pathway, we focused on the RPT2 subunit of the 26S proteasome regulatory particle. The Arabidopsis genome contains two genes, AtRPT2a and AtRPT2b, which encode paralog molecules of the RPT2 subunit, with a difference of only three amino acids in the protein sequences. Both genes showed similar mRNA accumulation patterns. However, the rpt2a mutant showed a specific phenotype of enlarged leaves caused by increased cell size, in correlation with increased ploidy. Detailed analyses revealed that cell expansion is increased in the rpt2a mutant by extended endoreduplication early in leaf development. The transcription of genes encoding cell cycle-related components, for DNA replication licensing and the G2/M phase, was also promoted in the rpt2a mutant, suggesting that extended endoreduplication was caused by increased DNA replication, and disrupted regulation of the G2/M checkpoint, at the proliferation stage of leaf development.

Olean-18-ene triterpenoids from Celastraceae species inhibit HIV replication targeting NF-kB and Sp1 dependent transcription.

PubMed

Osorio, Alex A; Muñóz, Alejandro; Torres-Romero, David; Bedoya, Luis M; Perestelo, Nayra R; Jiménez, Ignacio A; Alcamí, José; Bazzocchi, Isabel L

2012-06-01

In the present study we report the isolation of nine new olean-18-ene triterpenes (1-9), along with three known ones (10-12), from Cassine xylocarpa and Maytenus jelskii. Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques (COSY, ROESY, HSQC and HMBC), and spectrometric methods. The natural compounds and derivatives 13-15 have been tested for their potential as inhibitors of human immunodeficiency virus type 1 replication. Five compounds from this series displayed potent antiviral activity with IC(50)s in the micromolar range (1, 3, 4, 7 and 8) being 1 and 8 the most active compounds. The target of these compounds was different from antiretroviral drugs currently licensed as they act as inhibitors of enhancer-dependent transcription. The structure-activity relationships were established based on the regiosubstitution and oxidation degree of the triterpene scaffold, revealing that these aspects were able to modulate the selectivity and intensity of HIV inhibition. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

A HTML5 open source tool to conduct studies based on Libet’s clock paradigm

PubMed Central

Garaizar, Pablo; Cubillas, Carmelo P.; Matute, Helena

2016-01-01

Libet’s clock is a well-known procedure in experiments in psychology and neuroscience. Examples of its use include experiments exploring the subjective sense of agency, action-effect binding, and subjective timing of conscious decisions and perceptions. However, the technical details of the apparatus used to conduct these types of experiments are complex, and are rarely explained in sufficient detail as to guarantee an exact replication of the procedure. With this in mind, we developed Labclock Web, a web tool designed to conduct online and offline experiments using Libet’s clock. After describing its technical features, we explain how to configure specific experiments using this tool. Its degree of accuracy and precision in the presentation of stimuli has been technically validated, including the use of two cognitive experiments conducted with voluntary participants who performed the experiment both in our laboratory and via the Internet. Labclock Web is distributed without charge under a free software license (GPLv3) since one of our main objectives is to facilitate the replication of experiments and hence the advancement of knowledge in this area. PMID:27623167

A HTML5 open source tool to conduct studies based on Libet's clock paradigm.

PubMed

Garaizar, Pablo; Cubillas, Carmelo P; Matute, Helena

2016-09-13

Libet's clock is a well-known procedure in experiments in psychology and neuroscience. Examples of its use include experiments exploring the subjective sense of agency, action-effect binding, and subjective timing of conscious decisions and perceptions. However, the technical details of the apparatus used to conduct these types of experiments are complex, and are rarely explained in sufficient detail as to guarantee an exact replication of the procedure. With this in mind, we developed Labclock Web, a web tool designed to conduct online and offline experiments using Libet's clock. After describing its technical features, we explain how to configure specific experiments using this tool. Its degree of accuracy and precision in the presentation of stimuli has been technically validated, including the use of two cognitive experiments conducted with voluntary participants who performed the experiment both in our laboratory and via the Internet. Labclock Web is distributed without charge under a free software license (GPLv3) since one of our main objectives is to facilitate the replication of experiments and hence the advancement of knowledge in this area.

Experimental testing of a new integrated model of the budding yeast Start transition.

PubMed

Adames, Neil R; Schuck, P Logan; Chen, Katherine C; Murali, T M; Tyson, John J; Peccoud, Jean

2015-11-05

The cell cycle is composed of bistable molecular switches that govern the transitions between gap phases (G1 and G2) and the phases in which DNA is replicated (S) and partitioned between daughter cells (M). Many molecular details of the budding yeast G1-S transition (Start) have been elucidated in recent years, especially with regard to its switch-like behavior due to positive feedback mechanisms. These results led us to reevaluate and expand a previous mathematical model of the yeast cell cycle. The new model incorporates Whi3 inhibition of Cln3 activity, Whi5 inhibition of SBF and MBF transcription factors, and feedback inhibition of Whi5 by G1-S cyclins. We tested the accuracy of the model by simulating various mutants not described in the literature. We then constructed these novel mutant strains and compared their observed phenotypes to the model's simulations. The experimental results reported here led to further changes of the model, which will be fully described in a later article. Our study demonstrates the advantages of combining model design, simulation, and testing in a coordinated effort to better understand a complex biological network. © 2015 Adames et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

PubMed

Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

2016-01-01

Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. © 2016 K. Southard et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

49 CFR 572.19 - Lumbar spine, abdomen and pelvis.

Code of Federal Regulations, 2014 CFR

2014-10-01

... rotation joints by the attachments shown in Figure 18. Tighten the mountings so that the pelvis-lumbar... pounds torque. Remove the head and the neck and install a cylindrical aluminum adapter 2.0 inches in...

49 CFR 572.19 - Lumbar spine, abdomen and pelvis.

Code of Federal Regulations, 2011 CFR

2011-10-01

... rotation joints by the attachments shown in Figure 18. Tighten the mountings so that the pelvis-lumbar... pounds torque. Remove the head and the neck and install a cylindrical aluminum adapter 2.0 inches in...

49 CFR 572.19 - Lumbar spine, abdomen and pelvis.

Code of Federal Regulations, 2012 CFR

2012-10-01

... rotation joints by the attachments shown in Figure 18. Tighten the mountings so that the pelvis-lumbar... pounds torque. Remove the head and the neck and install a cylindrical aluminum adapter 2.0 inches in...

49 CFR 572.19 - Lumbar spine, abdomen and pelvis.

Code of Federal Regulations, 2013 CFR

2013-10-01

... rotation joints by the attachments shown in Figure 18. Tighten the mountings so that the pelvis-lumbar... pounds torque. Remove the head and the neck and install a cylindrical aluminum adapter 2.0 inches in...

49 CFR 572.19 - Lumbar spine, abdomen and pelvis.

Code of Federal Regulations, 2010 CFR

2010-10-01

... rotation joints by the attachments shown in Figure 18. Tighten the mountings so that the pelvis-lumbar... pounds torque. Remove the head and the neck and install a cylindrical aluminum adapter 2.0 inches in...

Methods for removing concrete decks from bridge girders.

DOT National Transportation Integrated Search

2014-08-01

With ever tightening budgets and limitations of demolition equipment, states are looking for cost-effective, reliable, and : sustainable methods for removing concrete decks from bridges. : The goal of this research was to explore such methods. The re...

Adapter plate assembly for adjustable mounting of objects

DOEpatents

Blackburn, R.S.

1986-05-02

An adapter plate and two locking discs are together affixed to an optic table with machine screws or bolts threaded into a fixed array of internally threaded holes provided in the table surface. The adapter plate preferably has two, and preferably parallel, elongated locating slots each freely receiving a portion of one of the locking discs for secure affixation of the adapter plate to the optic table. A plurality of threaded apertures provided in the adapter plate are available to attach optical mounts or other devices onto the adapter plate in an orientation not limited by the disposition of the array of threaded holes in the table surface. An axially aligned but radially offset hole through each locking disc receives a screw that tightens onto the table, such that prior to tightening of the screw the locking disc may rotate and translate within each locating slot of the adapter plate for maximum flexibility of the orientation thereof.

Pull-pull position control of dual motor wire rope transmission.

PubMed

Guo, Quan; Jiao, Zongxia; Yan, Liang; Yu, Qian; Shang, Yaoxing

2016-08-01

Wire rope transmission is very efficient because of the small total moving object mass. The wire rope could only transmit pulling force. Therefore it has to be kept in a tightened state during transmission; in high speed applications the dynamic performance depends on the rope's stiffness, which can be adjusted by the wire rope tension. To improve the system dynamic performance output, this paper proposes a novel pull-pull method based on dual motors connected by wire ropes, for precise, high speed position control applications. The method can regulate target position and wire rope tension simultaneously. Wire ropes remain in a pre-tightening state at all times, which prevents the influence of elasticity and reduces the position tracking error in the changing direction process. Simulations and experiments were conducted; the results indicate that both position precision and superior dynamic performance can be synchronously achieved. The research is relevant to space craft precision pointing instruments.

Adapter plate assembly for adjustable mounting of objects

DOEpatents

Blackburn, Robert S.

1987-01-01

An adapter plate and two locking discs are together affixed to an optic table with machine screws or bolts threaded into a fixed array of internally threaded holes provided in the table surface. The adapter plate preferably has two, and preferably parallel, elongated locating slots each freely receiving a portion of one of the locking discs for secure affixation of the adapter plate to the optic table. A plurality of threaded apertures provided in the adapter plate are available to attach optical mounts or other devices onto the adapter plate in an orientation not limited by the disposition of the array of threaded holes in the table surface. An axially aligned but radially offset hole through each locking disc receives a screw that tightens onto the table, such that prior to tightening of the screw the locking disc may rotate and translate within each locating slot of the adapter plate for maximum flexibility of the orientation thereof.

Split spline screw

NASA Technical Reports Server (NTRS)

Vranish, John M. (Inventor)

1993-01-01

A split spline screw type payload fastener assembly, including three identical male and female type split spline sections, is discussed. The male spline sections are formed on the head of a male type spline driver. Each of the split male type spline sections has an outwardly projecting load baring segment including a convex upper surface which is adapted to engage a complementary concave surface of a female spline receptor in the form of a hollow bolt head. Additionally, the male spline section also includes a horizontal spline releasing segment and a spline tightening segment below each load bearing segment. The spline tightening segment consists of a vertical web of constant thickness. The web has at least one flat vertical wall surface which is designed to contact a generally flat vertically extending wall surface tab of the bolt head. Mutual interlocking and unlocking of the male and female splines results upon clockwise and counter clockwise turning of the driver element.

Simulation and Experiment Research on Fatigue Life of High Pressure Air Pipeline Joint

NASA Astrophysics Data System (ADS)

Shang, Jin; Xie, Jianghui; Yu, Jian; Zhang, Deman

2017-12-01

High pressure air pipeline joint is important part of high pressure air system, whose reliability is related to the safety and stability of the system. This thesis developed a new type-high pressure air pipeline joint, carried out dynamics research on CB316-1995 and new type-high pressure air pipeline joint with finite element method, deeply analysed the join forms of different design schemes and effect of materials on stress, tightening torque and fatigue life of joint. Research team set up vibration/pulse test bench, carried out joint fatigue life contrast test. The result shows: the maximum stress of the joint is inverted in the inner side of the outer sleeve nut, which is consistent with the failure mode of the crack on the outer sleeve nut in practice. Simulation and experiment of fatigue life and tightening torque of new type-high pressure air pipeline joint are better than CB316-1995 joint.

[Calcaneo-fibular ligament surgery for chronic lateral instability of the upper ankle : Broström technique with modification by Wille. Video article].

PubMed

Kosiol, J; Wille, M; Putzer, D; Biedermann, R

2015-11-01

An acute ligament rupture of the lateral ligament complex of the ankle joint is treated without surgery. Treatment failure may lead to a chronically unstable situation of the ankle joint, in which case surgery is an effective procedure for stabilizing the ruptured ligaments. Anatomical reconstruction is the best operative technique if the ligament tissue is of good quality. In our video we demonstrate a new possibility for the positioning of an anchor to tighten the calcaneo-fibular ligament. Modified Broström repairs are described in the literature in which the calcaneo-fibular ligament is released and reattached to the fibula to tighten it. We present the option to release the ligament at the calcaneus and reattach it using a suture anchor. This offers the advantage of preventing the possible dislocation of the peroneal tendons.

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle

PubMed Central

Serre, Stéphanie B. N.; Jensen, Sanne B.; Ghanem, Lubna; Humes, Daryl G.; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens

2016-01-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. PMID:27021330

Sensing small molecule interactions with lipid membranes by local pH modulation.

PubMed

Huang, Da; Zhao, Tao; Xu, Wei; Yang, Tinglu; Cremer, Paul S

2013-11-05

Herein, we utilized a label-free sensing platform based on pH modulation to detect the interactions between tetracaine, a positively charged small molecule used as a local anesthetic, and planar supported lipid bilayers (SLBs). The SLBs were patterned inside a flow cell, allowing for various concentrations of tetracaine to be introduced over the surface in a buffer solution. Studies with membranes containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) yielded an equilibrium dissociation constant value of Kd = 180 ± 47 μm for this small molecule-membrane interaction. Adding cholesterol to the SLBs decreased the affinity between tetracaine and the bilayers, while this interaction tightened when POPE (1-hexadecanoyl-2-(9-Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine) was added. Studies were also conducted with three negatively charged membrane lipids, POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt)), POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (sodium salt)), and ganglioside GM1. All three measurements gave rise to a similar tightening of the apparent Kd value compared with pure POPC membranes. The lack of chemical specificity with the identity of the negatively charged lipid indicated that the tightening was largely electrostatic. Through a direct comparison with ITC measurements, it was found that the pH modulation sensor platform offers a facile, inexpensive, highly sensitive, and rapid method for the detection of interactions between putative drug candidates and lipid bilayers. As such, this technique may potentially be exploited as a screen for drug development and analysis.

Torque removal evaluation of prosthetic screws after tightening and loosening cycles: an in vitro study.

PubMed

Cardoso, Mayra; Torres, Marcelo Ferreira; Lourenço, Eduardo José Veras; de Moraes Telles, Daniel; Rodrigues, Renata Cristina Silveira; Ribeiro, Ricardo Faria

2012-04-01

The aim of this study was to evaluate the variation in removal torque of implant prosthetic abutment screws after successive tightening and loosening cycles, in addition to evaluating the influence of the hexagon at the abutment base on screw removal torque. Twenty hexagonal abutments were tightened to 20 regular external hex implants with a titanium alloy screw, with an insertion torque of 32 N cm, measured with a digital torque gauge. The implant/abutment/screw assemblies were divided into two groups: (1) abutments without hexagon at the base and (2) abutments with a hexagon at the base. Each assembly received a provisional restoration and was submitted to mechanical loading cycles. After this, the screws were removed and the removal torque was measured. This sequence was repeated 10 times, then the screw was replaced by a new one, and another cycle was performed. Linear regression analysis was performed. Removal torque values tended to decrease as the number of insertion/removal cycles increased, for both groups. Comparisons of the slopes and the intercepts between groups showed no statistical difference. There was no significant difference between the mean values of last five cycles and the 11th cycle. Within the limitations of this in vitro study, it was concluded that (1) repeated insertion/removal cycles promoted gradual reduction in removal torque of screws, (2) replacing the screw with a new one after 10 cycles did not increase resistance to loosening, and (3) removal of the hexagon from the abutment base had no effect on the removal torque of the screws. © 2011 John Wiley & Sons A/S.

Effect of retorque on loosening torque of prosthetic screws under two levels of fit of implant-supported dentures.

PubMed

Spazzin, Aloísio Oro; Henrique, Guilherme Elias Pessanha; Nóbilo, Mauro Antônio de Arruda; Consani, Rafael Leonardo Xediek; Correr-Sobrinho, Lourenço; Mesquita, Marcelo Ferraz

2010-01-01

This study evaluated the influence of retorque on loosening torque (Lt) of prosthetic screws in implant-supported dentures with different fit levels. Ten mandibular implant-supported dentures were fabricated and then 20 cast models were then prepared using prosthetic structures to create 2 fit levels: passive fit (Pf) and misfit (Mf). Two tightening techniques were also evaluated: initial torque only (T1); and initial torque and retorque after 10 min (T2). Gold or titanium screws were used, resulting in 4 groups to each one: Pf/T1, Pf/T2, Mf/T1, Mf/T2. The Lt was measured 24 h after the tightening torque using digital torque meter. Data were analyzed statistically by two-way ANOVA and Tukey's test (alpha=0.05), separately for each screw material. For titanium screws, no significant difference (p>0.05) was found between Pf/T1 and Pf/T2, or between Pf/T2 and Mf/T2. However, statistically significant difference (p<0.05) was found between Pf/T1 and Mf/T1, and between Mf/T1 and Mf/T2. Mf reduced the Lt using T1, while and T2 increased the Lt for Mf. Retorque and fit were shown to have no significant influence on the Lt of the gold screws. Retorque application made insignificant the misfit effect on the Lt of the titanium screws, suggesting that this procedure should be performed routinely during the screw tightening in multi-unit dentures.

Claudin-8d is a cortisol-responsive barrier protein in the gill epithelium of trout.

PubMed

Kolosov, Dennis; Kelly, Scott P

2017-10-01

The influence of claudin (Cldn) 8 tight junction (TJ) proteins on cortisol-mediated alterations in gill epithelium permeability was examined using a primary cultured trout gill epithelium model. Genes encoding three Cldn-8 proteins ( cldn-8b, -8c and -8d ) have been identified in trout and all are expressed in the model gill epithelium. Cortisol treatment 'tightened' the gill epithelium, as indicated by increased transepithelial resistance (TER) and reduced paracellular [ 3 H]polyethylene glycol (MW 400 Da; PEG-400) flux. This occurred in association with elevated cldn-8d mRNA abundance, but no alterations in cldn-8b and -8c mRNA abundance were observed. Transcriptional knockdown (KD) of cldn-8d inhibited a cortisol-induced increase in Cldn-8d abundance and reduced the 'epithelium tightening' effect of cortisol in association with increased paracellular PEG-400 flux. Under simulated in vivo conditions (i.e. apical freshwater), cldn-8d KD hindered a cortisol-mediated reduction in basolateral to apical Na + and Cl - flux (i.e. reduced the ability of cortisol to mitigate ion loss). However, cldn-8d KD did not abolish the tightening effect of cortisol on the gill epithelium. This is likely due, in part, to the effect of cortisol on genes encoding other TJ proteins, which in some cases appeared to exhibit a compensatory response. Data support the idea that Cldn-8d is a barrier protein of the gill epithelium TJ that contributes significantly to corticosteroid-mediated alterations in gill epithelium permeability. © 2017 Society for Endocrinology.

Engineering Temperature Sensitive Live Attenuated Influenza Vaccines from Emerging Viruses

PubMed Central

Zhou, Bin; Li, Yan; Speer, Scott D.; Subba, Anju; Lin, Xudong; Wentworth, David E.

2012-01-01

The licensed live attenuated influenza A vaccine (LAIV) in the United States is created by making a reassortant containing six internal genes from a cold-adapted master donor strain (ca A/AA/6/60) and two surface glycoprotein genes from a circulating/emerging strain (e.g., A/CA/7/09 for the 2009/2010 H1N1 pandemic). Technologies to rapidly create recombinant viruses directly from patient specimens were used to engineer alternative LAIV candidates that have genomes composed entirely of vRNAs from pandemic or seasonal strains. Multiple mutations involved in the temperature-sensitive (ts) phenotype of the ca A/AA/6/60 master donor strain were introduced into a 2009 H1N1 pandemic strain rA/New York/1682/2009 (rNY1682-WT) to create rNY1682-TS1, and additional mutations identified in other ts viruses were added to rNY1682-TS1 to create rNY1682-TS2. Both rNY1682-TS1 and rNY1682-TS2 replicated efficiently at 30°C and 33°C. However, rNY1682-TS1 was partially restricted, and rNY1682-TS2 was completely restricted at 39°C. Additionally, engineering the TS1 or TS2 mutations into a distantly related human seasonal H1N1 influenza A virus also resulted pronounced restriction of replication in vitro. Clinical symptoms and virus replication in the lungs of mice showed that although rNY1682-TS2 and the licensed FluMist®-H1N1pdm LAIV that was used to combat the 2009/2010 pandemic were similarly attenuated, the rNY1682-TS2 was more protective upon challenge with a virulent mutant of pandemic H1N1 virus or a heterologous H1N1 (A/PR/8/1934) virus. This study demonstrates that engineering key temperature sensitive mutations (PB1-K391E, D581G, A661T; PB2-P112S, N265S, N556D, Y658H) into the genomes of influenza A viruses attenuates divergent human virus lineages and provides an alternative strategy for the generation of LAIVs. PMID:22449422

7 CFR 42.108 - Normal, tightened, or reduced inspection.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 42.108 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS STANDARDS FOR CONDITION OF FOOD CONTAINERS Procedures for Stationary Lot Sampling and...

Be on the lookout.

PubMed

Hudson, T

1999-04-01

The cost coil tightens. The Net widens. Alternative care booms. And higher tech means more trade-offs. These and other trends play out in a new health care environmental assessment created by VHA and Deloitte & Touche--an Executive Chartbook exclusive to H&HN.

A Polyhedral Outer-approximation, Dynamic-discretization optimization solver, 1.x

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

Bent, Rusell; Nagarajan, Harsha; Sundar, Kaarthik

2017-09-25

In this software, we implement an adaptive, multivariate partitioning algorithm for solving mixed-integer nonlinear programs (MINLP) to global optimality. The algorithm combines ideas that exploit the structure of convex relaxations to MINLPs and bound tightening procedures

49 CFR 572.175 - Upper and lower torso assemblies and torso flexion test procedure.

Code of Federal Regulations, 2012 CFR

2012-10-01

.../lower torso assembly is as follows: (1) Torque the lumbar cable (drawing 420-4130) (incorporated by... threaded attachment holes. Tighten the mountings so that the test material is rigidly affixed to the test...

49 CFR 572.9 - Lumbar spine, abdomen, and pelvis.

Code of Federal Regulations, 2013 CFR

2013-10-01

...″ cap screw holes and attach the front mounting at the femur axial rotation joint. Tighten the mountings... socket joint to 240 inch-pounds torque. (3) Flex the thorax forward 50° and then rearward as necessary to...

49 CFR 572.9 - Lumbar spine, abdomen, and pelvis.

Code of Federal Regulations, 2010 CFR

2010-10-01

...″ cap screw holes and attach the front mounting at the femur axial rotation joint. Tighten the mountings... socket joint to 240 inch-pounds torque. (3) Flex the thorax forward 50° and then rearward as necessary to...

49 CFR 572.175 - Upper and lower torso assemblies and torso flexion test procedure.

Code of Federal Regulations, 2013 CFR

2013-10-01

.../lower torso assembly is as follows: (1) Torque the lumbar cable (drawing 420-4130) (incorporated by... threaded attachment holes. Tighten the mountings so that the test material is rigidly affixed to the test...

49 CFR 572.9 - Lumbar spine, abdomen, and pelvis.

Code of Federal Regulations, 2012 CFR

2012-10-01

...″ cap screw holes and attach the front mounting at the femur axial rotation joint. Tighten the mountings... socket joint to 240 inch-pounds torque. (3) Flex the thorax forward 50° and then rearward as necessary to...

49 CFR 572.9 - Lumbar spine, abdomen, and pelvis.

Code of Federal Regulations, 2011 CFR

2011-10-01

...″ cap screw holes and attach the front mounting at the femur axial rotation joint. Tighten the mountings... socket joint to 240 inch-pounds torque. (3) Flex the thorax forward 50° and then rearward as necessary to...

49 CFR 572.9 - Lumbar spine, abdomen, and pelvis.

Code of Federal Regulations, 2014 CFR

2014-10-01

...″ cap screw holes and attach the front mounting at the femur axial rotation joint. Tighten the mountings... socket joint to 240 inch-pounds torque. (3) Flex the thorax forward 50° and then rearward as necessary to...

49 CFR 572.175 - Upper and lower torso assemblies and torso flexion test procedure.

Code of Federal Regulations, 2014 CFR

2014-10-01

.../lower torso assembly is as follows: (1) Torque the lumbar cable (drawing 420-4130) (incorporated by... threaded attachment holes. Tighten the mountings so that the test material is rigidly affixed to the test...

Characterization of host immune responses in Ebola virus infections.

PubMed

Wong, Gary; Kobinger, Gary P; Qiu, Xiangguo

2014-06-01

Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics.

7 CFR 42.135 - Normal, tightened or reduced on-line inspection.

Code of Federal Regulations, 2010 CFR

2010-01-01

....135 Section 42.135 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS STANDARDS FOR CONDITION OF FOOD CONTAINERS On-Line Sampling and Inspection...

76 FR 5494 - Pipeline Safety: Mechanical Fitting Failure Reporting Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-01

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration 49 CFR Part... Safety: Mechanical Fitting Failure Reporting Requirements AGENCY: Pipeline and Hazardous Materials Safety... tightening. A widely accepted industry guidance document, Gas Pipeline Technical Committee (GPTC) Guide, does...

A Database and Tool for Boundary Conditions for Regional Air Quality Modeling: Description and Evaluation

EPA Science Inventory

Transported air pollutants receive increasing attention as regulations tighten and global concentrations increase. The need to represent international transport in regional air quality assessments requires improved representation of boundary concentrations. Currently available ob...

Negative Rotation Cinch Strap.

DTIC Science & Technology

This project discloses an improved unitary parachute torso harness, having a single fastening means, wherein an auxillary tightening strap is...attached to the groin straps of said harness. Said auxillary straps are used to prevent torso rotation or harness slippage and to prevent harness elongation

MODELING AND MEASUREMENT OF REAL-TIME CO CONCENTRATIONS IN ROADWAY MICROENVIRONMENTS

EPA Science Inventory

Although emission standards for motor vehicles continue to be tightened, tailpipe emissions continue to be a major source of human exposure to air toxics. The United States Environmental protection Agency's national Exposure Research laboratory has initiated a project to impro...

"Tighten-up" on Prosecution of Vandals

ERIC Educational Resources Information Center

Hill, Frederick W.

1974-01-01

The author feels that vandals should feel the full weight of social disapproval of their acts, that equipment and facilities designed to guard confidential material must be given greater consideration, and that school business officials should speed up bill payments to vendors. (Author/MLF)

Analysis of transit contracting models and proper incentives for long-term success : [summary].

DOT National Transportation Integrated Search

2013-11-01

In many locales, transit budgets are beng tightened, and transit systems are being challenged to operate more costeffectively. At the same time, demand for services is increasing. This has renewed interest in contracting fixed route service. Howev...

Special wrench for B-nuts reduces torque stress in tubing

NASA Technical Reports Server (NTRS)

Stein, J. A.

1970-01-01

Gear-driven torque wrench with bearing support is used to tighten B-nut connection of partially supported fluid line with minimum stress to adjacent tubing and fittings. Wrench is useful for working with weak or brittle lines such as glass tubing.

How We Snatched Our Schools from the Brink of Financial Ruin.

ERIC Educational Resources Information Center

Jones, Mike M.

1981-01-01

The Waycross (Georgia) school system retired its debt and reduced its tax rates, without reducing educational quality, by budgeting for an operating reserve, carefully reviewing programs, reducing its fiscal responsibilities for special programs, and tightening its budget management techniques. (RW)

Power-Tool Adapter For T-Handle Screws

NASA Technical Reports Server (NTRS)

Deloach, Stephen R.

1992-01-01

Proposed adapter enables use of pneumatic drill, electric drill, electric screwdriver, or similar power tool to tighten or loosen T-handled screws. Notched tube with perpendicular rod welded to it inserted in chuck of tool. Notched end of tube slipped over screw handle.

AbobotulinumtoxinA Injection

MedlinePlus

... tightening of the neck muscles that may cause neck pain and abnormal head positions). AbobotulinumtoxinA injection is also ... it. If you are using abobotulinumtoxinA to treat cervical dystonia, it may take 2 weeks or longer before you feel the full benefit of abobotulinumtoxinA injection.

Corporate Speak and "Collateral Recruitment": Surfing the Student Body

ERIC Educational Resources Information Center

McGloin, Colleen

2015-01-01

Academic practice is scrutinized and regulated with such "Corporate speak" terms as "performance indicators," "benchmarking," "service providers" and "clients." As part of a field where ideological shifts continue to apply marketized frames of reference as neoliberalism tightens its grip, new terms…

What web browsing reveals about your health.

PubMed

Libert, Timothy; Grande, David; Asch, David A

2015-11-16

Advertisers can learn a lot from our digital footprints, including about our health. Timothy Libert and colleagues argue that we need to tighten restrictions on such data for marketing purposes while looking at their potential to improve health. © BMJ Publishing Group Ltd 2015.

49 CFR 173.227 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone B.

Code of Federal Regulations, 2013 CFR

2013-10-01

... are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in place by any means capable of...

49 CFR 173.226 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone A.

Code of Federal Regulations, 2011 CFR

2011-10-01

...; (3) Have screw-type closures that are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in...

49 CFR 173.227 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone B.

Code of Federal Regulations, 2010 CFR

2010-10-01

... are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in place by any means capable of...

49 CFR 173.226 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone A.

Code of Federal Regulations, 2012 CFR

2012-10-01

...; (3) Have screw-type closures that are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in...

49 CFR 173.226 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone A.

Code of Federal Regulations, 2013 CFR

2013-10-01

...; (3) Have screw-type closures that are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in...

49 CFR 173.226 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone A.

Code of Federal Regulations, 2010 CFR

2010-10-01

...; (3) Have screw-type closures that are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in...

49 CFR 173.227 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone B.

Code of Federal Regulations, 2014 CFR

2014-10-01

... are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in place by any means capable of...

49 CFR 173.227 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone B.

Code of Federal Regulations, 2011 CFR

2011-10-01

... are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in place by any means capable of...

49 CFR 173.226 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone A.

Code of Federal Regulations, 2014 CFR

2014-10-01

...; (3) Have screw-type closures that are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in...

49 CFR 173.227 - Materials poisonous by inhalation, Division 6.1, Packing Group I, Hazard Zone B.

Code of Federal Regulations, 2012 CFR

2012-10-01

... are— (i) Closed and tightened to a torque prescribed by the closure manufacturer, using a properly calibrated device that is capable of measuring torque; (ii) Physically held in place by any means capable of...

Some Moral Dimensions of Administrative Theory and Practice.

ERIC Educational Resources Information Center

Raywid, Mary Anne

1986-01-01

Examines management approaches in ethical terms, arriving at numerous criteria applicable to educational administration. Discusses scientific management, morally neutral concepts, hyperrationalization, tightening of controls, and the business/industry model as having eclipsed or confused the moral dimensions of education. Calls for enlarged moral…

Marketing in Higher Education.

ERIC Educational Resources Information Center

Hockenberger, Susan J.

Educational institutions must seek new approaches to institutional planning because of such factors as shrinking traditional college age populations, eroding grants, governmental and judicial incursion, the tightening economic belt, and concern over the relevance of education to modern day needs. The concept of marketing higher education is…

Trading Spaces

ERIC Educational Resources Information Center

Cort, Cliff

2006-01-01

Education administrators face the dual dilemma of crowded, aging facilities and tightening capital budgets. The challenge is to build the necessary classroom, laboratory and activity space while minimizing the length and expense of the construction process. One solution that offers an affordable alternative is modular construction, a method that…

A method for independent modelling in support of regulatory review of dose assessments.

PubMed

Dverstorp, Björn; Xu, Shulan

2017-11-01

Several countries consider geological disposal facilities as the preferred option for spent nuclear fuel due to their potential to provide isolation from the surface environment on very long timescales. In 2011 the Swedish Nuclear Fuel & Waste Management Co. (SKB) submitted a license application for construction of a spent nuclear fuel repository. The disposal method involves disposing spent fuel in copper canisters with a cast iron insert at about 500 m depth in crystalline basement rock, and each canister is surrounded by a buffer of swelling bentonite clay. SKB's license application is supported by a post-closure safety assessment, SR-Site. SR-Site has been reviewed by the Swedish Radiation Safety Authority (SSM) for five years. The main method for review of SKB's license application is document review, which is carried out by SSM's staff and supported by SSM's external experts. The review has proven a challenging task due to its broad scope, complexity and multidisciplinary nature. SSM and its predecessors have, for several decades, been developing independent models to support regulatory reviews of post-closure safety assessments for geological repositories. For the review of SR-Site, SSM has developed a modelling approach with a structured application of independent modelling activities, including replication modelling, use of alternative conceptual models and bounding calculations, to complement the traditional document review. This paper describes this scheme and its application to biosphere and dose assessment modelling. SSM's independent modelling has provided important insights regarding quality and reasonableness of SKB's rather complex biosphere modelling and has helped quantifying conservatisms and highlighting conceptual uncertainty. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comprehensive protein-protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1.

PubMed

DeMille, Desiree; Bikman, Benjamin T; Mathis, Andrew D; Prince, John T; Mackay, Jordan T; Sowa, Steven W; Hall, Tacie D; Grose, Julianne H

2014-07-15

Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose homeostasis in yeast, mice, and humans, yet little is known about the molecular mechanisms of its function. Using both yeast two-hybrid and copurification approaches, we identified the protein-protein interactome for yeast PAS kinase 1 (Psk1), revealing 93 novel putative protein binding partners. Several of the Psk1 binding partners expand the role of PAS kinase in glucose homeostasis, including new pathways involved in mitochondrial metabolism. In addition, the interactome suggests novel roles for PAS kinase in cell growth (gene/protein expression, replication/cell division, and protein modification and degradation), vacuole function, and stress tolerance. In vitro kinase studies using a subset of 25 of these binding partners identified Mot3, Zds1, Utr1, and Cbf1 as substrates. Further evidence is provided for the in vivo phosphorylation of Cbf1 at T211/T212 and for the subsequent inhibition of respiration. This respiratory role of PAS kinase is consistent with the reported hypermetabolism of PAS kinase-deficient mice, identifying a possible molecular mechanism and solidifying the evolutionary importance of PAS kinase in the regulation of glucose homeostasis. © 2014 DeMille et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Current role of resurfacing lasers.

PubMed

Hantash, B M; Gladstone, H B

2009-06-01

Resurfacing lasers have been the treatment of choice for diminishing rhytids and tightening skin. The carbon dioxide and erbium lasers have been the gold and silver standards. Despite their effectiveness, these resurfacing lasers have a very high risk profile including scarring, hyperpigmentation and hypopigmentation. Because of these side effects, various practitioners have tried alternative settings for these lasers as well as alternative wavelengths, particularly in the infrared spectrum. These devices have had less downtime, but their effectiveness has been limited to fine wrinkles. As with selective photothemolysis, a major advance in the field has been fractionated resurfacing which incorporates grids of microthermal zones that spares islands of skin. This concept permits less tissue damage and quicker tissue regeneration. Initially, fractionated resurfacing was limited to the nonablative mid-infrared spectrum. These resurfacing lasers is appropriate for those patients with acne scars, uneven skin tone, mild to moderate photodamage, and is somewhat effective for melasma. Importantly, because there is less overall tissue damage and stimulation of melanocytes, these lasers can be used in darker skin types. Downtime is 2-4 days of erythema and scaling. Yet, these nonablative fractionated devices required 5-6 treatments to achieve a moderate effect. Logically, the fractionated resurfacing has now been applied to the CO2 and the Erbium:Yag lasers. These devices can treat deeper wrinkles and tighten skin. Downtime appears to be 5-7 days. The long term effectiveness and the question of whether these fractionated devices will approach the efficacy of the standard resurfacing lasers is still in question. Ultimately either integrated devices which may use fractionated resurfacing, radiofrequency and a sensitizer, or combining different lasers in a single treatment may prove to be the most effective in reducing rhtyides, smoothing the skin topography and tightening the skin envelope.

Nonablative lasers and nonlaser systems in dermatology: current status.

PubMed

Sachdev, Mukta; Hameed, Sunaina; Mysore, Venkataram

2011-01-01

Nonablative lasers and nonlaser systems are newer systems used for skin rejuvenation, tightening, body sculpting, and scar remodeling. Different technologies such as lasers, Intense Pulsed Light (IPL), and radiofrequency have been introduced. Most nonablative laser systems emit light within the infrared portion of the electromagnetic spectrum (1000-1500 nm). At these wavelengths, absorption by superficial water containing tissue is relatively weak, thereby effecting deeper tissue penetration. A detailed understanding of the device being used is recommended. Nonablative technology have been used for several indications such as skin tightening, periorbital tissue tightening, treatment of nasolabial lines and jowl, body sculpting/remodeling, cellulite reduction, scar revision and remodeling and for the treatment of photodamaged skin. Nonablative laser and light modalities can be carried out in a physician treatment room or hospital setting or a nursing home with a small operation theater. The dermatologic consultation should include detailed assessment of the patient's skin condition and skin type. An informed consent is mandatory to protect the rights of the patient as well as the practitioner. All patients must have carefully taken preoperative and postoperative pictures. Depends on the indication, the area to be treated, the acceptable downtime for the desired correction, and to an extent the skin color. These lasers are mostly pain-free and tolerated well by patients but may require topical anesthesia. In most cases, topical cooling and numbing using icepacks is sufficient, even in an apprehensive patient. The nonablative lasers, light sources and radiofrequency systems are safe, even in darker skin types, and postoperative care is minimal. Proper postoperative care is important in avoiding complications. Post-treatment edema and redness settle in a few hours to a few days. Postoperative sun avoidance and use of sunscreen is mandatory.

The Role of Direct and Visual Force Feedback in Suturing Using a 7-DOF Dual-Arm Teleoperated System.

PubMed

Talasaz, Ali; Trejos, Ana Luisa; Patel, Rajni V

2017-01-01

The lack of haptic feedback in robotics-assisted surgery can result in tissue damage or accidental tool-tissue hits. This paper focuses on exploring the effect of haptic feedback via direct force reflection and visual presentation of force magnitudes on performance during suturing in robotics-assisted minimally invasive surgery (RAMIS). For this purpose, a haptics-enabled dual-arm master-slave teleoperation system capable of measuring tool-tissue interaction forces in all seven Degrees-of-Freedom (DOFs) was used. Two suturing tasks, tissue puncturing and knot-tightening, were chosen to assess user skills when suturing on phantom tissue. Sixteen subjects participated in the trials and their performance was evaluated from various points of view: force consistency, number of accidental hits with tissue, amount of tissue damage, quality of the suture knot, and the time required to accomplish the task. According to the results, visual force feedback was not very useful during the tissue puncturing task as different users needed different amounts of force depending on the penetration of the needle into the tissue. Direct force feedback, however, was more useful for this task to apply less force and to minimize the amount of damage to the tissue. Statistical results also reveal that both visual and direct force feedback were required for effective knot tightening: direct force feedback could reduce the number of accidental hits with the tissue and also the amount of tissue damage, while visual force feedback could help to securely tighten the suture knots and maintain force consistency among different trials/users. These results provide evidence of the importance of 7-DOF force reflection when performing complex tasks in a RAMIS setting.

The influence of different screw tightening forces on the vertical misfit of implant-supported frameworks.

PubMed

Vasconcellos, Diego Klee de; Bottino, Marco Antonio; Nishioka, Renato Sussumu; Valandro, Luiz Felipe; Costa, Elza Maria Valadares da

2005-06-01

The present in vitro study was designed to compare the differences in the vertical misfit of implant-supported frameworks using three different forces for tightening the bridge locking screws: fastening by hand until first resistance, and using torque drivers with 10 and 20Ncm. The investigation was conducted based on the results given by 9 six-unit nickel-chromium (2 abutments/ 4 pontics) screw-retained implant-supported frameworks. The structures were exposed to simulated porcelain firings. The marginal misfit measurements were made using a traveling measuring microscope at selected screw tightening forces: fastening by hand until first resistance, and using torque drivers with 10 and 20Ncm. The results were submitted to one-way ANOVA with repeated measures on one factor, and post hoc pairwise comparisons using Tukey test (5%). The mean marginal misfit of the frameworks, fastening the screws by hand until first resistance, was 41.56µm (SD±12.45µm). The use of torque driver devices caused a significant reduction in marginal opening (p<0.05). With the lowest torque available (10Ncm), the mean marginal discrepancy at the abutment-framework interface was reduced an average of 52% to a mean marginal opening of 19.71µm (SD±2.97µm). After the use of the 20Ncm torque driver, the mean marginal discrepancy of the frameworks was reduced an average of 69% to a mean marginal opening of 12.82µm (SD±4.0µm). Comparing the use of torque drivers with 10 and 20 Ncm torque, the means are not significantly different from one another. The seating force has an important effect on the vertical misfit measurements, once it may considerably narrow the vertical misfit gaps at the abutment-framework interface, thus leading to a misjudgment of the real marginal situation.

"Turn-of-the-Nut" Method Is Not Appropriate for Use in Cancellous Bone.

PubMed

Ryan, Melissa K; Mohtar, Aaron A; Costi, John J; Reynolds, Karen J

2015-11-01

The level to which bone screws are tightened is determined subjectively by the operating surgeon. It is likely that the tactile feedback that surgeons rely on is based on localized tissue yielding, which may predispose the screw-bone interface to failure. A limited number of studies have investigated the ratio between clinical tightening torque and stripping torque. The purpose of this study was to measure, for the first time, the ratio between yield torque (T yield) and stripping torque (T max) during screw insertion into the cancellous bone and to compare these torques with clinical levels of tightening reported in the literature. Additionally, a rotational limit was investigated as a potential end point for screw insertion in cancellous bone. A 6.5-mm outer diameter commercial cancellous bone screw was inserted into human femoral head specimens (n = 89). Screws were inserted to failure, while recording insertion torque, compression under the screw head, and rotation angle. The median, interquartile ranges, and coefficient of variation were calculated for each of the following parameters: T yield, T max, T yield/T max, slope, T plateau, and rotation angle. The median ratio of T yield/T max and rotation angle was 85.45% and 96.5 degrees, respectively. The coefficient of variation was greatest for the rotation angle compared with the ratio of T yield/T max (0.37 vs. 0.12). The detection of yield may be a more precise method than the rotation angle in cancellous bone; however, bone-screw constructs that exhibit a T yield close to T max may be more susceptible to stripping during insertion. Future work can identify factors that influence the ratio of T yield/T max may help to reduce the incidence of screw stripping.

Pullout strength of cancellous screws in human femoral heads depends on applied insertion torque, trabecular bone microarchitecture and areal bone mineral density.

PubMed

Ab-Lazid, Rosidah; Perilli, Egon; Ryan, Melissa K; Costi, John J; Reynolds, Karen J

2014-12-01

For cancellous bone screws, the respective roles of the applied insertion torque (TInsert) and of the quality of the host bone (microarchitecture, areal bone mineral density (aBMD)), in contributing to the mechanical holding strength of the bone-screw construct (FPullout), are still unclear. During orthopaedic surgery screws are tightened, typically manually, until adequate compression is attained, depending on surgeons' manual feel. This corresponds to a subjective insertion torque control, and can lead to variable levels of tightening, including screw stripping. The aim of this study, performed on cancellous screws inserted in human femoral heads, was to investigate which, among the measurements of aBMD, bone microarchitecture, and the applied TInsert, has the strongest correlation with FPullout. Forty six femoral heads were obtained, over which microarchitecture and aBMD were evaluated using micro-computed tomography and dual X-ray absorptiometry. Using an automated micro-mechanical test device, a cancellous screw was inserted in the femoral heads at TInsert set to 55% to 99% of the predicted stripping torque beyond screw head contact, after which FPullout was measured. FPullout exhibited strongest correlations with TInsert (R=0.88, p<0.001), followed by structure model index (SMI, R=-0.81, p<0.001), bone volume fraction (BV/TV, R=0.73, p<0.001) and aBMD (R=0.66, p<0.01). Combinations of TInsert with microarchitectural parameters and/or aBMD did not improve the prediction of FPullout. These results indicate that, for cancellous screws, FPullout depends most strongly on the applied TInsert, followed by microarchitecture and aBMD of the host bone. In trabecular bone, screw tightening increases the holding strength of the screw-bone construct. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical efficacy and safety evaluation of a novel fractional unipolar radiofrequency device on facial tightening: A preliminary report.

PubMed

Suh, Dong Hye; Byun, Eun Jung; Lee, Sang Jun; Song, Kye Yong; Kim, Hei Sung

2017-06-01

Previous studies have shown that radiofrequency (RF) energy is safe and effective for improving skin laxity. Unlike monopolar and bipolar devices, little has been studied with the unipolar hand piece. We sought to evaluate the safety and efficacy of a novel fractional unipolar RF device on facial tightening. This was a retrospective, single-center study of 14 subjects with age-related facial laxity who underwent five sessions of fractional unipolar RF at an interval of 2 weeks, and then followed-up for 3 months. Standardized photos were taken at baseline and at 3-months follow-up, and were assessed by two independent dermatologists using a 4-point scale (0=no improvement, 1=mild improvement, 2=moderate improvement, 3=significant improvement). Punch biopsies (2 mm) were performed and a questionnaire was used to evaluate the patient's satisfaction and the incidence of adverse reactions. Fourteen subjects with mild to moderate age-related facial laxity were included in the study. The mean age of the subjects was 49.7 years (range 32-80). 35.7% of the subjects showed significant improvement, 50% moderate improvement, and 14.3% slight improvement of facial laxity in their follow-up photos. About 85.7% of the patients replied that they were either greatly satisfied or satisfied with the results at 3-months follow-up. Skin biopsies revealed an increase in collagen in the dermis. None of the subjects experienced any serious adverse events during or after the procedure. Our findings suggest that fractional Unipolar RF can be safely performed on the face and is effective in skin tightening. It has a great advantage over other forms of RF by being entirely painless. © 2017 Wiley Periodicals, Inc.

Lockwasher Strongly Resists Disassembly

NASA Technical Reports Server (NTRS)

Jeffers, Stephanie Z.

1991-01-01

Lockwasher designed to prevent counter-rotation and loosening of machine screw once screw tightened. Tabs engage slots in pawl-and-ratchet fashion. Features similar to those of "childproof" cap on pill bottle. Intended to replace cup-washer-and-screwhead combination exposed to high-speed, turbulent flow in turbomachinery.

Preparing Alumni for Student Recruitment.

ERIC Educational Resources Information Center

Mount, Brian

As recruitment budgets continue to tighten and with fewer colleges reporting application increases for their freshmen classes, enrollment managers must continue to explore all potential sources of recruitment talent. Alumni are often an underutilized or sometimes poorly utilized resource in recruitment efforts. Younger alumni, for example, may…

Passive ammonia monitoring in the United States: Comparing three different sampling devices

EPA Science Inventory

The need for ambient gaseous ammonia (NH3) measurements has increased in the last decade as reactive nitrogen concentrations and deposition fluxes show little change even with tightening standards on nitrogen oxides (NOx) emissions. Currently, there are several networks developin...

Analysis of transit contracting models and proper incentives for long-term success.

DOT National Transportation Integrated Search

2013-11-01

As transit systems are being challenged to operate in the most cost-effective manner, and budgets are being tightened and demand for services increases, there has been renewed interest in the area of contracting for fixed route service in the United ...

Cashing in

ERIC Educational Resources Information Center

Villano, Matt

2009-01-01

To say the American economy is in a precarious mode would be the understatement of the century. Banks have foundered, American industry is looking for federal bailouts, and belts are tightening everywhere. Not surprisingly, higher education officials at private institutions are wondering which students will be able to afford ever-escalating…

Cool Shelter

ERIC Educational Resources Information Center

Praeger, Charles E.

2005-01-01

Amid climbing energy costs and tightening budgets, administrators at school districts, colleges and universities are looking for all avenues of potential savings while promoting sustainable communities. Cool metal roofing can save schools money and promote sustainable design at the same time. Cool metal roofing keeps the sun's heat from collecting…

Do School Uniforms Fit?

ERIC Educational Resources Information Center

White, Kerry A.

2000-01-01

In 1994, Long Beach (California) Unified School District began requiring uniforms in all elementary and middle schools. Now, half of all urban school systems and many suburban schools have uniform policies. Research on uniforms' effectiveness is mixed. Tightened dress codes may be just as effective and less litigious. (MLH)

Tool enables proper mating of accelerometer and cable connector

NASA Technical Reports Server (NTRS)

Steed, C. N.

1966-01-01

Tool supports accelerometer in axial alignment with an accelerometer cable connector and permits tightening of the accelerometer to the cable connector with a torque wrench. This is done without damaging the components or permitting them to work loose under sustained, high-level vibrations.

Focus on Wage and Salary Programs.

ERIC Educational Resources Information Center

Risher, Howard W.

1989-01-01

Budget pressures, tightening labor markets, and increasing public interest should prompt colleges and universities to review their wage and salary programs. Many administrators have never been exposed to practices other than those common to higher education, and trustees with corporate experience may provide some insight. (Author/MSE)

Marketers hone their skills to reach target markets.

PubMed

White, D; Christensen, M

1990-08-05

New challenges lie ahead for health care marketers. Marketers must communicate with several important groups: their own administration, the general public, employers, hospital employees, and, of course, physicians. And as budgets tighten, the methods used to communicate must become more creative and more efficient.

DEVELOPMENT OF A MODEL FOR REAL TIME CO CONCENTRATIONS NEAR ROADWAYS

EPA Science Inventory

Although emission standards for mobile sources continue to be tightened, tailpipe emissions in urban areas continue to be a major source of human exposure to air toxics. Current human exposure models using simplified assumptions based on fixed air monitoring stations and region...

Comparative analysis of the fit of 3-unit implant-supported frameworks cast in nickel-chromium and cobalt-chromium alloys and commercially pure titanium after casting, laser welding, and simulated porcelain firings.

PubMed

Tiossi, Rodrigo; Rodrigues, Renata Cristina Silveira; de Mattos, Maria da Glória Chiarello; Ribeiro, Ricardo Faria

2008-01-01

This study compared the vertical misfit of 3-unit implant-supported nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) alloy and commercially pure titanium (cpTi) frameworks after casting as 1 piece, after sectioning and laser welding, and after simulated porcelain firings. The results on the tightened side showed no statistically significant differences. On the opposite side, statistically significant differences were found for Co-Cr alloy (118.64 microm [SD: 91.48] to 39.90 microm [SD: 27.13]) and cpTi (118.56 microm [51.35] to 27.87 microm [12.71]) when comparing 1-piece to laser-welded frameworks. With both sides tightened, only Co-Cr alloy showed statistically significant differences after laser welding. Ni-Cr alloy showed the lowest misfit values, though the differences were not statistically significantly different. Simulated porcelain firings revealed no significant differences.

Method and apparatus for animal positioning in imaging systems

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

Hadjioannou, Arion-Xenofon; Stout, David B.; Silverman, Robert W.

An apparatus for imaging an animal includes a first mounting surface, a bed sized to support the animal and releasably secured to or integral with the first mounting surface. The apparatus also includes a plurality of straps, each having a first end in a fixed position relative to the bed and a second end for tightening around a limb of the animal. A method for in-vivo imaging of an animal includes providing an animal that has limbs, providing a first mounting surface, and providing a bed removably secured to or integral with the mounting surface and sized to support themore » animal as well as being coupled to a plurality of straps. The method also includes placing the animal on the bed between the plurality of straps and tightening at least two of the plurality of straps around at least two of the limbs such that the animal is substantially secured in place relative to the bed.« less

Manual Torque Data Study

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

Mundt, Mark Osroe; Martinez, Matthew Ronald; Varela, Jeanette Judith

At the Pantex Plant in Amarillo, TX, Production Technicians (PTs) build and disassemble nuclear weapon systems. The weapons are held in an integrated work stand for stability and to increase the safety environment for the workers and for the materials being processed. There are many occasions in which a knob must be turned to tighten an assembly part. This can help to secure or manipulate pieces of the system. As there are so many knobs to turn, the instructions given to the PTs are to twist the knob to a hand-tight setting, without the aid of a torque wrench. Theremore » are inherent risks in this procedure as the knobs can be tightened too loosely such that the apparatus falls apart or too tightly such that the force can crush or pinch components in the system that contain energetic materials. We want to study these operations at Pantex. Our goal is to collect torque data to assess the safety and reliability of humantooling interfaces.« less

Experimental and numerical analysis of clamped joints in front motorbike suspensions

NASA Astrophysics Data System (ADS)

Croccolo, D.; de Agostinis, M.; Vincenzi, N.

2010-06-01

Clamped joints are shaft-hub connections used, as an instance, in front motorbike suspensions to lock the steering plates with the legs and the legs with the wheel pin, by means of one or two bolts. The preloading force, produced during the tightening process, should be evaluated accurately, since it must lock safely the shaft, without overcoming the yielding point of the hub. Firstly, friction coefficients have been evaluated on “ad-hoc designed” specimens, by applying the Design of Experiment approach: the applied tightening torque has been precisely related to the imposed preloading force. Then, the tensile state of clamps have been evaluated both via FEM and by leveraging some design formulae proposed by the Authors as function of the preloading force and of the clamp geometry. Finally, the results have been compared to those given by some strain gauges applied on the tested clamps: the discrepancies between numerical analyses, the design formulae and the experimental results remains under a threshold of 10%.

Noninvasive radio frequency for skin tightening and body contouring.

PubMed

Weiss, Robert A

2013-03-01

The medical use of radio frequency (RF) is based on an oscillating electrical current forcing collisions between charged molecules and ions, which are then transformed into heat. RF heating occurs irrespective of chromophore or skin type and is not dependent on selective photothermolysis. RF can be delivered using monopolar, bipolar, and unipolar devices, and each method has theoretical limits of depth penetration. A variant of bipolar delivery is fractional RF delivery. In monopolar configurations, RF will penetrate deeply and return via a grounding electrode. Multiple devices are available and are detailed later in the text. RF thermal stimulation is believed to result in a microinflammatory process that promotes new collagen. By manipulating skin cooling, RF can also be used for heating and reduction of fat. Currently, the most common uses of RF-based devices are to noninvasively manage and treat skin tightening of lax skin (including sagging jowls, abdomen, thighs, and arms), as well as wrinkle reduction, cellulite improvement, and body contouring.

Immunogenicity and protective efficacy of a replication-defective infectious bronchitis virus vaccine using an adenovirus vector and administered in ovo.

PubMed

Zeshan, Basit; Zhang, Lili; Bai, Juan; Wang, Xinglong; Xu, Jiarong; Jiang, Ping

2010-06-01

In ovo vaccination remains an attractive option for a cost effective, uniform and mass application of vaccines for commercial poultry. However, the vaccines which can be delivered safely by this method are limited and there is no currently licensed embryo-safe vaccine against infectious bronchitis virus (IBV). In this study, a recombinant adenovirus expressing the S1 gene of nephropathogenic IBV (rAd-S1) was constructed and the immune responses and protective efficacy against homologous challenge were evaluated after in ovo vaccination. The results showed that the rAd-S1 led to dramatic augmentation of humoral and cellular responses in birds vaccinated in ovo followed by an intramuscular inoculation. Both IFN-gamma and IL-4 in chicken's lymphocytes were produced by this strategy. Following challenge with IBV, the chickens vaccinated with recombinant adenovirus showed fewer nephropathic lesions and less severe clinical signs as compared to those receiving wild-type adenovirus or PBS. The construction of non-replicating human adenovirus vector encoding S1 gene of IBV and its in ovo delivery demonstrated the potential of an alternative vaccination strategy against IBV. Copyright 2010 Elsevier B.V. All rights reserved.

Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever.

PubMed

Warimwe, George M; Gesharisha, Joseph; Carr, B Veronica; Otieno, Simeon; Otingah, Kennedy; Wright, Danny; Charleston, Bryan; Okoth, Edward; Elena, Lopez-Gil; Lorenzo, Gema; Ayman, El-Behiry; Alharbi, Naif K; Al-dubaib, Musaad A; Brun, Alejandro; Gilbert, Sarah C; Nene, Vishvanath; Hill, Adrian V S

2016-02-05

Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.

Good Performers

ERIC Educational Resources Information Center

Bennett, Bob

2009-01-01

Soaring energy prices and tightening school budgets don't mix well. In fact, millions of children across the United States are being educated in energy-leaking, unhealthful facilities in dire need of physical upgrade and systems modernization. Increasing numbers of K-12 districts and institutions of higher learning are turning to performance-based…

Busting Bolts

ERIC Educational Resources Information Center

Scott, Alan

2013-01-01

A simple apparatus is described which serves as a materials testing laboratory. Bolts are placed in it and subjected to tensile and torsional stress while being tightened. The tensile and torsional stress and strain can be measured, which enables the determination of several mechanical properties of the bolt material, including Young's…

Two Crowd Control Case Studies

DTIC Science & Technology

2007-08-01

Soldiers shine powerful lights into the detox center from 110-foot towers. The army steadily pushes its side of the barriers forward, tightening their...for Mo- hawks. Water fight - not effective for either side. Army locks and loads - effective for Army 26 Sep 90 At the local detox center in

Critical Mass: Education and the Economy.

ERIC Educational Resources Information Center

Groff, Warren H.

1984-01-01

Underscores the importance of strategic planning and management in higher education in the future, emphasizing the need to develop the intellectual capital necessary to implement planning and management systems to tighten the relationship between education and the economy. Discusses selected facts about the economy and the challenges facing…

Where the Money Is

ERIC Educational Resources Information Center

Miller, Kurtz

2018-01-01

This article describes a grantmanship framework for high school science educators. The scenario described illustrates the importance of grant writing in an era of increased school accountability and tightened purse strings. The framework presented can be used for most STEM-related projects and can guide educators toward high-quality instruction…

The Illusion of the Instructional Biology Laboratory.

ERIC Educational Resources Information Center

Ralph, Charles L.

1996-01-01

Argues that the changing informational content of biology, tightening cost constraints, improving electronic media, increasing pressures from advocates of animal rights, and the growing evidence of the effectiveness of electronic modes of instruction are undermining the traditional belief that all students in biology should have the benefit of…

Five Components to Consider for BYOT/BYOD

ERIC Educational Resources Information Center

Ackerman, Amy S.; Krupp, Melissa L.

2012-01-01

Although school budgets have plummeted due to federal and state funding reductions, adopting Bring Your Own Technology (BYOT), may address monetary tightening while simultaneously infusing 21st century learning. Implementing BYOT may provide real, rigorous, and relevant learning for the students while posing higher-order thinking questions from…

Automatic, computerized testing of bolts

NASA Technical Reports Server (NTRS)

Carlucci, J., Jr.; Lobb, V. B.; Stoller, F. W.

1970-01-01

System for testing bolts with various platings, lubricants, nuts, and tightening procedures tests 200 fasteners, and processes and summarizes the results, within one month. System measures input torque, nut rotation, bolt clamping force, bolt shank twist, and bolt elongation, data is printed in report form. Test apparatus is described.

Tightening the Corn Belt.

ERIC Educational Resources Information Center

Trisler, Carmen E.

1995-01-01

Presents an activity in which students: identify agricultural crops that are grown in Great Lakes states, understand how global climate change will affect these crops, hypothesize about crops that could replace these, compare the current crops' economic value with projected replacement crops, and analyze the impact of global climate on the…

Showcasing Unsung Heroes: Positive PR/Positive Relationships

ERIC Educational Resources Information Center

Ruder, Robert

2009-01-01

Despite the budgetary belt-tightening and what appears to be a gloomy financial future for many of the nation's school districts, south Florida's "Sun Sentinel" recently showcased five noninstructional employees from the Broward County school district. The "Sun Sentinel" chose to provide readers with a comprehensive look at…

76 FR 19719 - Airworthiness Directives; Saab AB, Saab Aerosystems Model SAAB 2000 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-08

... fretting corrosion; a detailed inspection of the actuator mounting bracket and shock struts for damage, cracks, and signs of corrosion; and doing corrective actions if necessary. Corrective actions include removing corrosion, replacing affected bolts with new bolts, tightening loose nuts, repairing, and...

Monopolar radiofrequency facial tightening: a retrospective analysis of efficacy and safety in over 600 treatments.

PubMed

Weiss, Robert A; Weiss, Margaret A; Munavalli, Girish; Beasley, Karen L

2006-09-01

Monopolar radiofrequency skin heating coupled with cryogen cooling of facial skin for skin tightening has been utilized on over 10,000 patients since 2002. In order to establish the actual rate and degree of side effects in our clinical experience, a retrospective chart review was performed. Charts and clinical images of over 600 consecutive patient treatments between May 2002 and June 2006 using a monopolar radiofrequency device (Thermacool, Thermage, Haywood, CA) for skin tightening at the Maryland Laser, Skin and Vein Institute were retrospectively reviewed. The primary presentation for treatment was skin laxity of the lower face. Treatment was delivered with a 1-cm2 standard tip at fluences of 81 to 124 J/cm2 (level of 12.5 to 15), a 1-cm2 "fast" tip at fluences of 62 to 109 J/cm2 (level of 72.0 to 76.0), a 1.5-cm2 "big fast" tip at fluences of 75 to 130 J/cm2 (level of 61.5 to 65), and a 3-cm2 "bigger" tip at equivalent fluences as each became available. As treatment algorithms evolved over 4 years, the algorithm of multiple passes at lower fluence associated with better clinical outcomes and greater patient acceptance has been adopted. The most common immediate and expected clinical effects were erythema and edema lasting less than 24 hours, although 6 patients reported edema lasting for up to 1 week. There were no permanent side effects. In total, 2.7% of treatments resulted in temporary side effects, the most significant of which was a slight depression on the cheek (n = 1), which completely resolved within 3.5 months. Other side effects included localized areas of acneiform subcutaneous erythematous papules (n = 4) and a linear superficial crust (n = 1) with the original tip, all of which resolved within 1 week. One patient reported small erythematous subcutaneous nodules resolving in 17 days. Tenderness of the neck lasting from 2 weeks (n = 2) to 3 weeks (n = 1) was also reported. Our data, obtained in an office setting without injectable anesthetic or i.v. sedation, indicate that monopolar RF for skin tightening is a very safe procedure. The treatment algorithm and tips have evolved over several years leading to increased safety and efficacy. Side effects are infrequent, self-limited, and minor, comparing favorably to other nonablative devices utilized for facial rejuvenation.

Exploring channeling optimized radiofrequency energy: a review of radiofrequency history and applications in esthetic fields.

PubMed

Belenky, Inna; Margulis, Ariel; Elman, Monica; Bar-Yosef, Udi; Paun, Silviu D

2012-03-01

Because of its high efficiency and safety, radiofrequency (RF) energy is widely used in the dermatological field for heating biological tissue in various esthetic applications, including skin tightening, skin lifting, body contouring, and cellulite reduction. This paper reviews the literature on the use of nonablative RF energy in the esthetic field and its scientific background. The purpose of this article is to describe in detail the extensive use of medical devices based on RF technology, the development of these medical devices over the years, and recent developments and trends in RF technology. The authors conducted a systematic search of publications that address safety and efficacy issues, technical system specifications, and clinical techniques. Finally, the authors focused on their own clinical experiences with the use of patented Channeling Optimized RF Energy technique and mechanical massage. An in-vivo study was conducted in domestic pigs, with a thermal video camera. Twenty-seven female patients participated in a cellulite and body shaping study. The treatments were conducted according to a three-phase protocol. An additional 16 females participated in a skin tightening case study. All of the patients underwent three treatment sessions at 3-week intervals, each according to a protocol specific to the area being treated. The review of the literature on RF-based systems revealed that these systems are safe, with low risks for potential side effects, and effective for cellulite, body contouring, and skin tightening procedures. The in-vivo measurements confirmed the theory that the penetration depth of RF is an inverse function of its frequency, and using a vacuum mechanism makes an additional contribution to the RF energy penetration. The heating effect of RF was also found to increase blood circulation and to induce collagen remodeling. The results from the cellulite and body shaping treatments showed an overall average improvement of 55% in the appearance of cellulite, with an average circumferential reduction of 3.31 cm in the buttocks, 2.94 cm in the thighs, and 2.14 cm in the abdomen. The results from the skin tightening procedure showed moderate improvement of skin appearance in 50% and significant improvement in 31%. At the follow-up visits the results were found to be sustained without any significant side effects. Of all tissue heating techniques, RF-based technologies appear to be the most established and clinically proven. The design and specifications of the described vacuumassisted bipolar RF device fall within the range of the specifications currently prescribed for esthetic, nonablative RF systems.

46 CFR 160.115-7 - Design, construction, and performance of winches.

Code of Federal Regulations, 2013 CFR

2013-10-01

... materials. Provisions must also be made to prevent loosening or tightening resulting from differences of... which disconnects all electrical potential to the winch, must be provided. This switch must be located... switch will disconnect all electrical potential of the circuit in which the switches are connected; (B...

46 CFR 160.115-7 - Design, construction, and performance of winches.

Code of Federal Regulations, 2014 CFR

2014-10-01

... materials. Provisions must also be made to prevent loosening or tightening resulting from differences of... opening of which disconnects all electrical potential to the winch, must be provided. This switch must be... either switch will disconnect all electrical potential of the circuit in which the switches are connected...

Push/Push Fastener

NASA Technical Reports Server (NTRS)

Jackson, Steven A.

1996-01-01

Modified version of Nylatch (or equivalent) commerical quick-connect/quick-disconnect fastener for joining flat panels. Fastener tightened by pushing on knob on one side and loosened by pushing on knob on other side. Push/push operation of fastener advantageous in cold or otherwise hostile environments where gloves worn, in underwater operations, or if person handicapped.

Food Preservation Mini-Modules Offer Options for Learners and Extension Staff

ERIC Educational Resources Information Center

Driessen, Suzanne

2013-01-01

Renewed interest in growing and purchasing locally grown foods quadrupled requests for food preservation classes. Economic times tightened budgets, decreasing staffing levels of Extension educators. Offering options via the Internet was a natural progression to meet the increased demand. Extension educators created 20 5-minute online video--like…

Aero dopes and varnishes

NASA Technical Reports Server (NTRS)

Britton, H T S

1927-01-01

Before proceeding to discuss the preparation of dope solutions, it will be necessary to consider some of the essential properties which should be possessed of a dope film, deposited in and on the surface of an aero fabric. The first is that it should tighten the material and second it should withstand weathering.

Disinterested, Disengaged, Useless: Conservative or Progressive Idea of the University?

ERIC Educational Resources Information Center

McLennan, Gregor

2008-01-01

There is evidence aplenty of academics' increasing incorporation into the life and fate of their university's brand, just as it is clear that university structures and incentives generally are dependent upon increasingly competitive resource capture under tightened managerial ideologies of institutional commitment (albeit by way of innumerable…

Converge & Conquer

ERIC Educational Resources Information Center

Korzeniowski, Paul

2008-01-01

State-of-the-art, energy-efficient facilities are now emerging on campuses across the US, and for a variety of reasons: One practical consideration is that such buildings bring down energy costs, which are now soaring. Facing rising expenditures and a tightening of potential revenue, universities are looking for ways to reduce operating costs, and…

Ending the Tech Refresh Nightmare

ERIC Educational Resources Information Center

Demski, Jennifer

2010-01-01

As higher education budgets tighten in the ongoing recession, colleges and universities have found themselves questioning, lengthening, and even eliminating tech refresh cycles. Yet how deep an institution cuts into its refresh program can compromise its ability to provide an up-to-date and competitive computing environment for students and a…

Virtual Reference, Real Money: Modeling Costs in Virtual Reference Services

ERIC Educational Resources Information Center

Eakin, Lori; Pomerantz, Jeffrey

2009-01-01

Libraries nationwide are in yet another phase of belt tightening. Without an understanding of the economic factors that influence library operations, however, controlling costs and performing cost-benefit analyses on services is difficult. This paper describes a project to develop a cost model for collaborative virtual reference services. This…

16 CFR 1616.4 - Sampling and acceptance procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... a suitable thread and stitch. The specimen shall include each of the components over its entire... fabric in Tightened Sampling must be discontinued until that part of the process or component which is... otherwise attaching the trim shall be done with thread or fastening material of the same composition and...

Gas pressure in sealed electrochemical cells measured externally

NASA Technical Reports Server (NTRS)

Sherfey, J. M.

1967-01-01

Piezoresistive transducer measures gas pressure inside sealed secondary electrochemical cells without breaking the seal. This method is based on the observed fact that the force exerted by the cell faces on the clamp tightening them against the transducer is a function of the gas pressure inside the cell.

Hiring Seniors: Everybody Gives, Everybody Benefits

ERIC Educational Resources Information Center

Ruder, Robert

2011-01-01

Living on fixed incomes and faced with increasing taxes, senior citizens frequently feel the squeeze of a tightening economy more than other populations. Their retirement dollars buy less as their property taxes inch upward, despite the fact that they don't have school-age children. The Hempfield and Manheim Township School Districts in…

Impact of enhanced ozone deposition and halogen chemistry on tropospheric ozone over the Northern Hemisphere

EPA Science Inventory

Fate of ozone in marine environments has been receiving increased attention due to the tightening of ambient air quality standards. The role of deposition and halogen chemistry is examined through incorporation of an enhanced ozone deposition algorithm and inclusion of halogen ch...

Supporting Families in a Time of Fear

ERIC Educational Resources Information Center

Kugler, Eileen Gale

2017-01-01

With U.S. immigration policies tightening, many teachers find students from immigrant backgrounds are worried about families or friends facing harsh consequences--or are suffering from losing a family member to deportation. Some students and families are disengaging from school, and kids are even being bullied about their backgrounds. Kugler shows…

78 FR 34288 - Airworthiness Directives; Eurocopter France Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

... attaching fittings. If more than a 20 percent tightening torque load loss is discovered, the ASBs require... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 [Docket No. FAA-2013... detect the torque loss of the bolts that secure the MGB bar attaching fittings and to prevent cracks that...

A decision-support framework for using value capture to fund public transit : lessons from project-specific analyses [research brief].

DOT National Transportation Integrated Search

2012-05-01

Fiscal belt-tightening at all levels of government has lent urgency to identifying alternate sources of funding for public transportation. Value capture (VC) is one such source. Based on the benefits received principle, VC captures public infra...

Comparing District Achievement to Improve Decision Making in Clark County, Nevada. Vignette

ERIC Educational Resources Information Center

American Institutes for Research, 2012

2012-01-01

In response to changing demographics, a tightening budget, and drastic achievement gaps (white students outperform Latino students on standardized tests) the Clark County School District in Nevada (the fifth largest district in the country) commissioned, in 2011, an educational and operational efficiency review. The district commissioned the…

Your School Needs a Frugal Librarian!

ERIC Educational Resources Information Center

Johns, Sara Kelly

2011-01-01

School libraries are crucial to learning, but need resources to close the digital and print divide that widens as school budgets shrink. In this article, the author shares her perspective on stretching the library dollar. As budgets tighten and the use of library resources increases, school librarian's ingenuity, skill, and planning can ensure…

Universal Service Brings Fiber to Their Doorsteps.

ERIC Educational Resources Information Center

Vedro, Steven

1996-01-01

In a time of fiscal belt tightening, many states will hesitate to launch new multimillion-dollar distance education network projects. Instead they will concentrate on regulatory initiatives to stimulate the development of affordable advanced universal service by the private sector. Discusses the limitations of state regulatory strategies in the…

What Influences Spending on Education? Education Indicators in Focus. No. 46

ERIC Educational Resources Information Center

OECD Publishing, 2016

2016-01-01

The challenge of providing more and better education with tightening public budgets has made governments increasingly interested in the efficient allocation of education resources. Results from the OECD Programme for International Student Assessment (PISA) show that, among countries with a comparatively high gross domestic product (GDP) per…

Occupational Mobility of Low Income Workers.

ERIC Educational Resources Information Center

Slifman, Lawrence

This dissertation is primarily concerned with assessing the impact of changes in the aggregate labor supply-demand balance on the upward occupational mobility of lower income workers. The empirical analysis indicates that the size of inter-occupational flows is cyclically sensitive, given relative wages. As the labor market tightens, the…

Colorblindness: The New Racism?

ERIC Educational Resources Information Center

Scruggs, Afi-Odelia E.

2009-01-01

Kawania Wooten's voice tightens when she describes the struggle she's having at the school her son attends. When his class created a timeline of civilization, Wooten saw the Greeks, the Romans and the Incas. Nothing was said about Africa, even though the class has several African American students. This article discusses racial…

30 CFR 7.308 - Lockwasher equivalency test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... hole and continuously and uniformly tightened at a speed not to exceed 30 rpm until the fastening's... cycles. (b) Acceptable performance. The minimum torque value required to start removal of the fastening from the installed position (minimum breakway torque) for any cycle of any test sample shall be greater...

30 CFR 7.308 - Lockwasher equivalency test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... hole and continuously and uniformly tightened at a speed not to exceed 30 rpm until the fastening's... cycles. (b) Acceptable performance. The minimum torque value required to start removal of the fastening from the installed position (minimum breakway torque) for any cycle of any test sample shall be greater...

30 CFR 7.308 - Lockwasher equivalency test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... hole and continuously and uniformly tightened at a speed not to exceed 30 rpm until the fastening's... cycles. (b) Acceptable performance. The minimum torque value required to start removal of the fastening from the installed position (minimum breakway torque) for any cycle of any test sample shall be greater...

30 CFR 7.308 - Lockwasher equivalency test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... hole and continuously and uniformly tightened at a speed not to exceed 30 rpm until the fastening's... cycles. (b) Acceptable performance. The minimum torque value required to start removal of the fastening from the installed position (minimum breakway torque) for any cycle of any test sample shall be greater...

30 CFR 7.308 - Lockwasher equivalency test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... hole and continuously and uniformly tightened at a speed not to exceed 30 rpm until the fastening's... cycles. (b) Acceptable performance. The minimum torque value required to start removal of the fastening from the installed position (minimum breakway torque) for any cycle of any test sample shall be greater...

Pivoting-Head Wrench

NASA Technical Reports Server (NTRS)

Bradley, Glen L.

1993-01-01

Wrench ends pivot so it can be used to loosen or tighten nuts or bolts in confined spaces. One end equipped with open-end socket; other end, with double-hexagon socket. Heads pivot on pins. Pins fit tightly so heads do not flop; friction on pins sufficient to hold heads in positions until rotated intentionally.

Social Responsibility and the Result of Experiments

ERIC Educational Resources Information Center

Lester, David

1970-01-01

Stresses the danger in the publication of premature or nonreplicable research findings in psychology, especially in the creation of public myths, and advises that the psychological profession (1) tighten standards for analysis and presentation of data in published research papers (2) establish communication between the profession and the news…

Successful foaling by a Standardbred mare with a ruptured prepubic tendon.

PubMed

Schutten, Kerry J V

2016-12-01

A 12-year-old Standardbred mare was diagnosed with a ruptured prepubic tendon 1 month prepartum. The mare was treated with analgesia, stall rest, and an abdominal support wrap that was tightened daily. Both a live foal born 1 month later and the mare are doing well.

Methamphetamine: Putting the Brakes on Speed

ERIC Educational Resources Information Center

Gettig, Jacob P.; Grady, Sarah E.; Nowosadzka, Izabella

2006-01-01

In only recent history, illicit use of methamphetamine, once isolated to urban areas on the West Coast, has spread into rural areas of the Midwest and southern United States. Although past and current methamphetamine legislation has increased penalties for methamphetamine manufacturers and tightened restrictions on sales of known precursors, the…

Tightening the Iron Cage: Concertive Control in Self-Managing Teams.

ERIC Educational Resources Information Center

Barker, James R.

1993-01-01

Describes how an (industrial) organization's control system evolved in response to a managerial change from hierarchical, bureaucratic control to concertive control via self-management teams. The organization's members developed a system of value-based normative rules that controlled their actions more powerfully and completely than did the former…

Curriculum Consonance and Dissonance in Technology Education Classrooms

ERIC Educational Resources Information Center

Brown, Ryan A.

2009-01-01

In a time of increased accountability, a tightened curriculum, and fewer curricular choices for students, technology education in the United States is in the position of defending itself by "carving a niche" in the school curriculum. Justifying the place of technology education is becoming increasingly difficult, as there has been little…

Radio-Frequency Identification: Asset Control at Your Fingertips

ERIC Educational Resources Information Center

Scholes, Marcus

2009-01-01

Times are tough for everyone, including public school districts. During the past decade, school districts have faced the dual challenges of tightening budgets and increasing fiscal responsibility and oversight. Many school districts have found a way to manage their assets, reduce staff requirements, increase accountability, and save money on…

Database Marketplace 2010: Feast and Famine

ERIC Educational Resources Information Center

Tenopir, Carol; Baker, Gayle; Grogg, Jill

2010-01-01

With fancy new software developments and growth in both the richness of content and delivery options for information resources, the Database Marketplace 2010 is a feast for buyers. Unfortunately, institutional budget cuts may force more of a famine mentality--with belt-tightening for most, and only purchases that are life-sustaining being served…

Reliable Wiring Harness

NASA Technical Reports Server (NTRS)

Gaspar, Kenneth C.

1987-01-01

New harness for electrical wiring includes plugs that do not loosen from vibration. Ground braids prevented from detaching from connectors and constrained so braids do not open into swollen "birdcage" sections. Spring of stainless steel encircles ground braid. Self-locking connector contains ratchet not only preventing connector from opening, but tightens when vibrated.

How to Pay for Public Education

ERIC Educational Resources Information Center

Reiff, Mark R.

2014-01-01

For years now, public education, and especially public higher education, has been under attack. Funding has been drastically reduced, fees increased, and the seemingly irresistible political force of ever-tightening austerity budgets threatens to cut it even more. But I am not going to take the standard line that government financial support for…

Mcm2 deficiency results in short deletions allowing high resolution identification of genes contributing to lymphoblastic lymphoma

PubMed Central

Rusiniak, Michael E.; Kunnev, Dimiter; Freeland, Amy; Cady, Gillian K.; Pruitt, Steven C.

2011-01-01

Mini-chromosome maintenance (Mcm) proteins are part of the replication licensing complex that is loaded onto chromatin during the G1-phase of the cell cycle and required for initiation of DNA replication in the subsequent S-phase. Mcm proteins are typically loaded in excess of the number of locations that are utilized during S-phase. Nonetheless, partial depletion of Mcm proteins leads to cancers and stem cell deficiencies. Mcm2 deficient mice, on a 129Sv genetic background, display a high rate of thymic lymphoblastic lymphoma. Here array comparative genomic hybridization (aCGH) is utilized to characterize the genetic damage accruing in these tumors. The predominant events are deletions averaging less than 0.5 Mb, considerably shorter than observed in prior studies using alternative mouse lymphoma models or human tumors. Such deletions facilitate identification of specific genes and pathways responsible for the tumors. Mutations in many genes that have been implicated in human lymphomas are recapitulated in this mouse model. These features, and the fact that the mutation underlying the accelerated genetic damage does not target a specific gene or pathway a priori, are valuable features of this mouse model for identification of tumor suppressor genes. Genes affected in all tumors include Pten, Tcfe2a, Mbd3 and Setd1b. Notch1 and additional genes are affected in subsets of tumors. The high frequency of relatively short deletions is consistent with elevated recombination between nearby stalled replication forks in Mcm2 deficient mice. PMID:22158038

Advances with using CRISPR/Cas-mediated gene editing to treat infections with hepatitis B virus and hepatitis C virus.

PubMed

Moyo, Buhle; Bloom, Kristie; Scott, Tristan; Ely, Abdullah; Arbuthnot, Patrick

2018-01-15

Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal. Disabling cccDNA is thus key to curing HBV infections and application of gene editing technology, such as harnessing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has curative potential. Several studies have reported good efficacy when employing CRISPR/Cas technologies to disable HBV replication in cultured cells and in hydrodynamically injected mice. Recent advances with HCV drug development have revolutionized treatment of the infection. Nevertheless, individuals may be refractory to treatment. Targeting RNA from HCV with CRISPR/Cas isolated from Francisella novicida may have therapeutic utility. Although preclinical work shows that CRISPR/Cas technology has potential to overcome infection with HBV and HCV, significant challenges need to be met. Ensuring specificity for viral targets and efficient delivery of the gene editing sequences to virus-infected cells are particularly important. The field is at an interesting stage and the future of curative antiviral drug regimens, particularly for treatment of chronic HBV infection, may well entail use of combinations that include derivatives of CRISPR/Cas. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle.

PubMed

Serre, Stéphanie B N; Jensen, Sanne B; Ghanem, Lubna; Humes, Daryl G; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens; Gottwein, Judith M

2016-06-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Distinct self-interaction domains promote Multi Sex Combs accumulation in and formation of the Drosophila histone locus body.

PubMed

Terzo, Esteban A; Lyons, Shawn M; Poulton, John S; Temple, Brenda R S; Marzluff, William F; Duronio, Robert J

2015-04-15

Nuclear bodies (NBs) are structures that concentrate proteins, RNAs, and ribonucleoproteins that perform functions essential to gene expression. How NBs assemble is not well understood. We studied the Drosophila histone locus body (HLB), a NB that concentrates factors required for histone mRNA biosynthesis at the replication-dependent histone gene locus. We coupled biochemical analysis with confocal imaging of both fixed and live tissues to demonstrate that the Drosophila Multi Sex Combs (Mxc) protein contains multiple domains necessary for HLB assembly. An important feature of this assembly process is the self-interaction of Mxc via two conserved N-terminal domains: a LisH domain and a novel self-interaction facilitator (SIF) domain immediately downstream of the LisH domain. Molecular modeling suggests that the LisH and SIF domains directly interact, and mutation of either the LisH or the SIF domain severely impairs Mxc function in vivo, resulting in reduced histone mRNA accumulation. A region of Mxc between amino acids 721 and 1481 is also necessary for HLB assembly independent of the LisH and SIF domains. Finally, the C-terminal 195 amino acids of Mxc are required for recruiting FLASH, an essential histone mRNA-processing factor, to the HLB. We conclude that multiple domains of the Mxc protein promote HLB assembly in order to concentrate factors required for histone mRNA biosynthesis. © 2015 Terzo et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Trouble in paradise: The crime and health outcomes of the Surfers Paradise licensed venue lockout.

PubMed

de Andrade, Dominique; Homel, Ross; Townsley, Michael

2016-09-01

The lockout intervention has become embedded in Australian alcohol policy with little scientific evidence of its effectiveness in reducing violence and disorder. This paper reports an evaluation of the Queensland lockout pilot in Surfers Paradise. Patrons could not enter or re-enter licensed venues after 3 am, while patrons inside at this time could stay until close. Using police and ambulance data, time series analyses examined the impact of tourism seasons and the lockout on rates of crime, violence, injury and intoxication. Additional analyses were also conducted to show spatial and temporal changes in crime over time. Both police and ambulance data showed that the lockout introduction had no statistically significant impact on rates of crime, violence, head and neck injuries, and intoxication over the 2 years following lockout. Hot spot maps indicated limited spatial shift of crime within Surfers Paradise following the lockout introduction, with evidence of a temporary intensification of crime in already established hot spots. We found a moderate statistically significant change in the 24 h distribution of crime after the lockout implementation, suggesting temporal displacement of crime. Results support the small existing body of evidence on lockouts that indicates they are largely ineffective in reducing crime and injuries in entertainment districts. As multi-pronged strategies that include a lockout gain in popularity, further investigation should focus on identifying the key drivers of successful interventions such as the Newcastle strategy, to better refine these interventions for replication and evaluation elsewhere. [De Andrade D, Homel R, Townsley M. Trouble in paradise: The crime and health outcomes of the Surfers Paradise licensed venue lockout. Drug Alcohol Rev 2016;35:564-572]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Mitochondrial anchorage and fusion contribute to mitochondrial inheritance and quality control in the budding yeast Saccharomyces cerevisiae.

PubMed

Higuchi-Sanabria, Ryo; Charalel, Joseph K; Viana, Matheus P; Garcia, Enrique J; Sing, Cierra N; Koenigsberg, Andrea; Swayne, Theresa C; Vevea, Jason D; Boldogh, Istvan R; Rafelski, Susanne M; Pon, Liza A

2016-03-01

Higher-functioning mitochondria that are more reduced and have less ROS are anchored in the yeast bud tip by the Dsl1-family protein Mmr1p. Here we report a role for mitochondrial fusion in bud-tip anchorage of mitochondria. Fluorescence loss in photobleaching (FLIP) and network analysis experiments revealed that mitochondria in large buds are a continuous reticulum that is physically distinct from mitochondria in mother cells. FLIP studies also showed that mitochondria that enter the bud can fuse with mitochondria that are anchored in the bud tip. In addition, loss of fusion and mitochondrial DNA (mtDNA) by deletion of mitochondrial outer or inner membrane fusion proteins (Fzo1p or Mgm1p) leads to decreased accumulation of mitochondria at the bud tip and inheritance of fitter mitochondria by buds compared with cells with no mtDNA. Conversely, increasing the accumulation and anchorage of mitochondria in the bud tip by overexpression of MMR1 results in inheritance of less-fit mitochondria by buds and decreased replicative lifespan and healthspan. Thus quantity and quality of mitochondrial inheritance are ensured by two opposing processes: bud-tip anchorage by mitochondrial fusion and Mmr1p, which favors bulk inheritance; and quality control mechanisms that promote segregation of fitter mitochondria to the bud. © 2016 Higuchi-Sanabria et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Vaccines licensed and in clinical trials for the prevention of dengue.

PubMed

Torresi, J; Ebert, G; Pellegrini, M

2017-05-04

Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.

Development of a domain-specific genetic language to design Chlamydomonas reinhardtii expression vectors.

PubMed

Wilson, Mandy L; Okumoto, Sakiko; Adam, Laura; Peccoud, Jean

2014-01-15

Expression vectors used in different biotechnology applications are designed with domain-specific rules. For instance, promoters, origins of replication or homologous recombination sites are host-specific. Similarly, chromosomal integration or viral delivery of an expression cassette imposes specific structural constraints. As de novo gene synthesis and synthetic biology methods permeate many biotechnology specialties, the design of application-specific expression vectors becomes the new norm. In this context, it is desirable to formalize vector design strategies applicable in different domains. Using the design of constructs to express genes in the chloroplast of Chlamydomonas reinhardtii as an example, we show that a vector design strategy can be formalized as a domain-specific language. We have developed a graphical editor of context-free grammars usable by biologists without prior exposure to language theory. This environment makes it possible for biologists to iteratively improve their design strategies throughout the course of a project. It is also possible to ensure that vectors designed with early iterations of the language are consistent with the latest iteration of the language. The context-free grammar editor is part of the GenoCAD application. A public instance of GenoCAD is available at http://www.genocad.org. GenoCAD source code is available from SourceForge and licensed under the Apache v2.0 open source license.

Vaccines licensed and in clinical trials for the prevention of dengue

PubMed Central

Torresi, J.; Ebert, G.; Pellegrini, M.

2017-01-01

ABSTRACT Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1–80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans. PMID:28281864

Higher Education Reform in Italy: Tightening Regulation Instead of Steering at a Distance

ERIC Educational Resources Information Center

Donina, Davide; Meoli, Michele; Paleari, Stefano

2015-01-01

In December 2010, a comprehensive reform (Law 240/2010, or "Gelmini reform") changed the institutional governance and internal organization of Italian state universities. This paper investigates the redefinition of the state role in the light of public management reform narratives, linking them to the Governance Equalizer Model to…

Analysis of Numerical Models for Dispersion of Chemical/Biological Agents in Complex Building Environments

DTIC Science & Technology

2004-11-01

variation in ventilation rates over time and the distribution of ventilation air within a building, and to estimate the impact of envelope air ... tightening efforts on infiltration rates. • It may be used to determine the indoor air quality performance of a building before construction, and to

Counterbalancing Student Debt with "Asset Empowerment" and Economic Mobility

ERIC Educational Resources Information Center

Elliott, William; Chan, Monnica; Poore, Anthony

2015-01-01

Education provides one of the best opportunities for American children to build the capacity to climb up the economic ladder. It has even been called the "great equalizer" in American society. In today's tightened labor market, providing equal access to postsecondary education is more critical than ever. The Georgetown Center on…

21 CFR 884.5960 - Genital vibrator for therapeutic use.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Genital vibrator for therapeutic use. 884.5960 Section 884.5960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... of sexual dysfunction or as an adjunct to Kegel's exercise (tightening of the muscles of the pelvic...

21 CFR 884.5960 - Genital vibrator for therapeutic use.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Genital vibrator for therapeutic use. 884.5960 Section 884.5960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... of sexual dysfunction or as an adjunct to Kegel's exercise (tightening of the muscles of the pelvic...

21 CFR 884.5960 - Genital vibrator for therapeutic use.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Genital vibrator for therapeutic use. 884.5960 Section 884.5960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... of sexual dysfunction or as an adjunct to Kegel's exercise (tightening of the muscles of the pelvic...

21 CFR 884.5960 - Genital vibrator for therapeutic use.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Genital vibrator for therapeutic use. 884.5960 Section 884.5960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... of sexual dysfunction or as an adjunct to Kegel's exercise (tightening of the muscles of the pelvic...

21 CFR 884.5960 - Genital vibrator for therapeutic use.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Genital vibrator for therapeutic use. 884.5960 Section 884.5960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... of sexual dysfunction or as an adjunct to Kegel's exercise (tightening of the muscles of the pelvic...

The Changing UK Careers Landscape: Tidal Waves, Turbulence and Transformation

ERIC Educational Resources Information Center

Hughes, Deirdre

2013-01-01

This article explores how the UK careers landscape in each of the four home nations is changing in response to neo-liberal policies. In this context, careers services are increasingly under pressure to demonstrate their added value, impact and returns on investment. As fiscal arrangements tighten and governments state their preferences and…

Sino-Indian War 1962 -- Where do India and China Stand Today?

DTIC Science & Technology

2013-06-14

interests in Nepal stem from its concerns over movement of large numbers of Tibetans into Nepal . Therefore, India is not only concerned with growing...Tibetan refugee community. Beijing has been pressing Nepal to tighten its borders with Tibet, which has led to a major decrease in the number of

29 CFR 1915.134 - Abrasive wheels.

Code of Federal Regulations, 2012 CFR

2012-07-01

... shall be so mounted as to maintain proper alignment with the wheel, and the guard and its fastenings... safety flanges are required, they shall be used only with wheels designed to fit the flanges. Only safety... wheels shall fit freely on the spindle and shall not be forced on. The spindle nut shall be tightened...

29 CFR 1915.134 - Abrasive wheels.

Code of Federal Regulations, 2013 CFR

2013-07-01

... shall be so mounted as to maintain proper alignment with the wheel, and the guard and its fastenings... safety flanges are required, they shall be used only with wheels designed to fit the flanges. Only safety... wheels shall fit freely on the spindle and shall not be forced on. The spindle nut shall be tightened...

29 CFR 1915.134 - Abrasive wheels.

Code of Federal Regulations, 2014 CFR

2014-07-01

... shall be so mounted as to maintain proper alignment with the wheel, and the guard and its fastenings... safety flanges are required, they shall be used only with wheels designed to fit the flanges. Only safety... wheels shall fit freely on the spindle and shall not be forced on. The spindle nut shall be tightened...

Computers and the supply of radiology services: anatomy of a disruptive technology.

PubMed

Levy, Frank

2008-10-01

Over the next decade, computers will augment the supply of radiology services at a time when reimbursement rules are likely to tighten. Increased supply and slower growing demand will result in a radiology market that is more competitive, with less income growth, than the market of the past 15 years.

Contemporary Issues in Community Colleges: A Synopsis.

ERIC Educational Resources Information Center

Cohen, Arthur M.

This report presents background on community college development and discusses four areas of concern. The first area is maintaining access for all students. Trends are toward tightening criteria for attendance. Colleges in some states will be forced to make clearer distinctions among the student groups they serve and for whom they expect to…

Ground water and surface water: the linkage tightens, but challenges remain

USGS Publications Warehouse

Winter, Thomas C.

2001-01-01

Hydrologists have recognized for more than a century that groundwater and surface water are closely linked, but for most of that timestudies of their interaction were carried out largely by single disci-plines. This is slowly changing, however, as the need for integratedstudies involving many disciplines is becoming more evident.

Keeping the Arts Alive: Fine Arts Databases

ERIC Educational Resources Information Center

Young, Terrence E., Jr.

2005-01-01

When budgets are tightened, the school library media specialists and/or the arts programs are often considered expendable. No Child Left Behind legislation means increasing academic time for core subjects, which translates into cutting time for arts education. As money becomes tight, frills are cut (i.e., the arts). Schools don't seem able to fill…

46 CFR 160.062-3 - Materials, construction, workmanship, and performance requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... effects as galvanic corrosion, freezing, or buckling of moving parts, or loosening and tightening of... 15 feet prior to being tested for either the temperature or the corrosion resistance tests of 160.062-4(c)(2). After exposure to these temperature and corrosion tests, a hydraulic release shall release...

Private-Loan Reliance Worries Colleges

ERIC Educational Resources Information Center

Basken, Paul

2008-01-01

At many colleges across the nation, as administrators fret about the effects of a worsening economy, students arriving this fall will get more help securing jobs and more advice on paying for their educations. Some students will even find colleges willing to cut their tuition bills. This article reports that as banks tighten standards for private…

Following the Cuts: How Is the Recession Affecting Faculty Work?

ERIC Educational Resources Information Center

Lounder, Andrew; Waugaman, Chelsea; Kenyon, Mark; Levine, Amy; Meekins, Matthew; O'Meara, KerryAnn

2011-01-01

The recession of 2008-2009 and the continuing decline in local, state, and federal funds available to support higher education have resulted in serious budget cuts and belt-tightening. Given that faculty constitute an institution's most costly resource, it was not surprising, though it is nonetheless disheartening, to learn of the University of…

Using Minds to Command the Logic of Things: A Response to Case and Wright.

ERIC Educational Resources Information Center

Paul, Richard

1997-01-01

Reviews some of the basic tenets of critical thinking as it applies to social studies, especially those articulated in Roland Case's and Ian Wright's article, "Taking Seriously the Teaching of Critical Thinking." Praises the article but suggests that it would be improved by tightening the central focus. (MJP)

The Intellectual Landscape of Critical Policy Analysis

ERIC Educational Resources Information Center

Diem, Sarah; Young, Michelle D.; Welton, Anjalé D.; Mansfield, Katherine Cumings; Lee, Pei-Ling

2014-01-01

What counts as critical policy analysis in education? Over the past 30 years, a tightening of national educational policies can be seen in the USA and across the globe. Over this same period of time, a growing number of educational policy scholars, dissatisfied with traditional frameworks, have used critical frameworks in their analyses. Their…

The influence of opening windows and doors on the natural ventilation rate of a residential building

EPA Science Inventory

An analysis of air exchange rates due to intentional window and door openings in a research test house located in a residential environment is presented. These data inform the development of ventilation rate control strategies as building envelopes are tightened to improve the e...

Staff Perceptions of E-Learning in a Community Health Care Organization

ERIC Educational Resources Information Center

Gabriel, Monica; Longman, Sandra

2004-01-01

How do organizations cope with the increased speed of technological change? How do leaders optimize resources with tightened budgets? How do staff and students acquire the necessary knowledge and skills in the midst of constant change? Electronic learning (e-learning) is one form of learning that utilizes technology to deliver, interact or…

Evaluating the War on Drugs: US and Colombian Interdiction Efforts

DTIC Science & Technology

1994-03-01

market remained in the hands of Mexican traffickers.3 When, in the early 1970’s, the US tightened drug enforcement along the border with Mexico and the...US Senate, September 12-13, 1989. Tokatlian, J. , Bagley, B., Eds., Economia y Politica del Narcotraffico, CEI, Bogota, 1990. U.S. Congress. Senate

Integrating Algorithm Visualization Video into a First-Year Algorithm and Data Structure Course

ERIC Educational Resources Information Center

Crescenzi, Pilu; Malizia, Alessio; Verri, M. Cecilia; Diaz, Paloma; Aedo, Ignacio

2012-01-01

In this paper we describe the results that we have obtained while integrating algorithm visualization (AV) movies (strongly tightened with the other teaching material), within a first-year undergraduate course on algorithms and data structures. Our experimental results seem to support the hypothesis that making these movies available significantly…

75 FR 17887 - Airworthiness Directives; The Boeing Company Model 767 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-08

... torque to the nut and bolt of the main track downstop assembly. The corrective actions include: Installing a bolt and spacer with a new nut (including applying torque to make sure that it has been.... Tightening the existing nut. Boeing Special Attention Service Bulletin 767-57-0118, dated October 8, 2009...

78 FR 40956 - Airworthiness Directives; Eurocopter Deutschland (Eurocopter) Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

... compressor pulley to the rotor brake disc lost torque and allowed the pulley to separate. After the... installed in a tightening direction, or if the pulley is loose, remove and inspect the pulley as described.... (ii) Install the pulley and torque each mount bolt to 90 inch- pounds. After torqueing, determine...

Facilities Financing: Monetizing Education's Untapped Resource. Working Paper 2011-04

ERIC Educational Resources Information Center

Kothari, Himanshu

2011-01-01

Like most everyone, schools have been forced to tighten their belts to survive in today's economic downturn. School leaders have been cutting budgets for afterschool activities, classroom equipment, and staff, all in an era of increasing academic expectations. It is little surprise, then, that facilities issues have been relegated to the bottom of…

School Shootings in Policy Spotlight

ERIC Educational Resources Information Center

Maxwell, Lesli A.

2006-01-01

The three school shootings that left a principal and six students dead in less than a week have sparked a barrage of pledges from national and state political leaders to tighten campus security. School safety experts urged caution against overreacting to the horrific, but rare, incidents in rural schools in Colorado, Pennsylvania, and Wisconsin.…

38th Annual Maintenance & Operations Cost Study for Schools

ERIC Educational Resources Information Center

Agron, Joe

2009-01-01

Despite the worst economic environment in generations, spending by K-12 institutions on maintenance and operations (M&O) held its own--defying historical trends that have shown M&O spending among the most affected in times of budget tightening. This article presents data from the 38th annual Maintenance & Operations Cost Study for…

Changes to Tensile Strength and Electromagnetic Shielding Effectiveness in Neutron Irradiated Carbon Nanocomposites

DTIC Science & Technology

2013-03-01

3 II. Background ...Agilent Technologies E8362B PNA Series Microwave Network Analyzer. The waveguide is secured by hex cap screws and nuts tightened to the torque...believed to result in a reduction in tensile strength of the composite. 5 II. Background Chapter Overview This chapter describes the

Thoreau's Pencil and Baumol's Cost Disease

ERIC Educational Resources Information Center

Buxton, Bruce E.

2004-01-01

Everyone knows perfectly well that tuitions have outpaced inflation every year since Homer was a pup. Tuition sticker shock, that ineluctable annual rise in school costs, causes the nation sporadic fits of hand wringing, belt tightening, and taxpayer revolt. Most troubling of all, it has inspired an industry of policy wonks, efficiency experts,…

Exploding Boxes

ERIC Educational Resources Information Center

Kinney; Jan

2011-01-01

How do you teach the "same old, same old" in an interesting and inexpensive way? Art teachers are forever looking for new angles on the good-old elements and principles. And, as budgets tighten, they are trying to be as frugal as possible while still holding their students' attention. Enter exploding boxes! In conceptualizing the three types of…

New Frontiers: Training Forensic Accountants within the Accounting Program

ERIC Educational Resources Information Center

Ramaswamy, Vinita

2007-01-01

Accountants have recently been subject to very unpleasant publicity following the collapse of Enron and other major companies. There has been a plethora of accounting failures and accounting restatements of falsified earnings, with litigations and prosecutions taking place every day. As the FASB struggles to tighten the loopholes in accounting,…

Afterschool Programs: A Wise Public Investment. Afterschool Alert. Issue Brief No.22

ERIC Educational Resources Information Center

Afterschool Alliance, 2005

2005-01-01

After-school advocates and practitioners face a seemingly continual struggle for adequate funding. While there have been successes, budgets have tightened at all levels of government, and advocates must be prepared to demonstrate that after-school programs are a worthy investment. This report highlights benefits of these programs by pointing out…

Lower energy and pulse stacking. A safer alternative for skin tightening using fractional CO2 laser.

PubMed

Motta, Marcos Matias; Stelini, Rafael Fantelli; Calderoni, Davi Reis; Gilioli, Rovilson; Kharmandayan, Paulo

2016-01-01

To evaluate the effect of different energies and stacking in skin shrinkage. Three decreasing settings of a fractional CO2 laser were applied to the abdomen of Twenty five Wistar rats divided into three groups. Group I (n=5) was histologically evaluated for microthermal zones dimensions. Groups II and III (n=10 each) were macroscopic evaluated with freeware ImageJ for area contraction immediately and after 30 and 60 days. No statistical significance was found within microthermal zone histological dimensions (Group I) in all settings studied. (Ablation depth: 76.90 to 97.18µm; Coagulation depth: 186.01 to 219.84 µm). In Group II, macroscopic evaluation showed that all settings cause significant immediate skin contraction. The highest setting cause significant more intense tightening effect initially, contracting skin area from 258.65 to 179.09 mm2. The same pattern was observed in Group III. At 30 and 60 days, the lowest setting significantly sustained contraction. Lower fractional CO2 laser energies associated to pulse stacking could cause consistent and long lasting tissue contraction in rats.

Body-contouring with radiofrequency-assisted liposuction.

PubMed

Ion, Lucian; Raveendran, Sherine S; Fu, Brian

2011-12-01

Liposculpturing is the most frequently performed procedure in the aesthetic clinical practice. The techniques have evolved into significant modification during the past few decades with introduction of several new devices, leading to superior outcome. Radiofrequency-assisted liposuction (RFAL) have revolutionised body contouring techniques by providing simultaneous fat liquefaction, coagulation of blood vessels, and skin tightening in the tissues. In this study we discuss our preliminary experience with RFAL in treating patients for aesthetic body contouring and patients with HIV-related lipohypertrophy. Forty-two patients were treated with RFAL for cosmetic concerns, and eight were treated for HIV-related lipohypertrophy after unsuccessful outcome with other techniques. Significant reduction of adipose tissue with marked tightening of the skin was noted in all the patients. Clinical results were impressive in terms of pain, recovery, and patient satisfaction. Remarkable improvement was observed in patients with HIV-related cervical lipohypertrophy and gynaecomastia with fibrous fatty tissue. Two patients suffered superficial burns and were managed conservatively. Our experience suggests that controlled application of radiofrequency power for liposculpturing may open up a new horizon of non-excisional lipectomy in the future.

Relationship between locking-bolt torque and load pre-tension in the Ilizarov frame.

PubMed

Osei, N A; Bradley, B M; Culpan, P; Mitchell, J B; Barry, M; Tanner, K E

2006-10-01

The wire-bolt interface in an Ilizarov frame has been mechanically tested. The optimal torque to be applied to the frame locking-bolts during physiological loading has been defined. The set-up configuration was as is used clinically except a copper tube was used to simulate bone. The force-displacement curves of the Ilizarov wires are not altered by locking-bolt torque. The force in the bone model at which pre-tension is lost increases as the locking-bolts are tightened to 14 Nm torque, but decreases if torque exceeds 14 Nm. Thus, 14 Nm is the optimal locking-bolt torque in frame. The relationship between pre-tension versus load for different locking-bolt torques arises because at low and high clamping torques poor wire holding and plastic deformation respectively occur. Wire damage was seen under light and electron microscopy. Clinically, over or under-tightening locking-bolts will cause loss of pre-tension, reduction in frame stiffness and excessive movement at the fracture site, which may be associated with delayed union.

Tightening the entropic uncertainty bound in the presence of quantum memory

NASA Astrophysics Data System (ADS)

Adabi, F.; Salimi, S.; Haseli, S.

2016-06-01

The uncertainty principle is a fundamental principle in quantum physics. It implies that the measurement outcomes of two incompatible observables cannot be predicted simultaneously. In quantum information theory, this principle can be expressed in terms of entropic measures. M. Berta et al. [Nat. Phys. 6, 659 (2010), 10.1038/nphys1734] have indicated that uncertainty bound can be altered by considering a particle as a quantum memory correlating with the primary particle. In this article, we obtain a lower bound for entropic uncertainty in the presence of a quantum memory by adding an additional term depending on the Holevo quantity and mutual information. We conclude that our lower bound will be tightened with respect to that of Berta et al. when the accessible information about measurements outcomes is less than the mutual information about the joint state. Some examples have been investigated for which our lower bound is tighter than Berta et al.'s lower bound. Using our lower bound, a lower bound for the entanglement of formation of bipartite quantum states has been obtained, as well as an upper bound for the regularized distillable common randomness.

Observational Evidence of the "Tightening of Hadley Ascent"

NASA Astrophysics Data System (ADS)

Su, H.; Wu, L.; Jiang, J. H.

2017-12-01

Recent studies show that the Hadley Circulation undergoes complicated structure changes under global warming (e.g., Su et al., 2014; Lau and Kim 2015; Byrne and Schneider 2016; Su et al., 2017)). Accompanied by the widening of the descent zone, a narrowing of the ascending branch of the Hadley Circulation is simulated in most climate models. The magnitude of the tightening of Hadley ascent (THA) in the models is found to be highly correlated with the decrease of tropical high cloud fraction, which is a major contributor to the inter-model spread of the longwave radiative cooling rate and the global-mean precipitation change per degree of surface warming (Su et al. 2017). While the THA is a common feature in the models, its observational evidence is limited. We have examined a number of reanalyses and satellite datasets to identify the indicators of the THA in terms of large-scale winds, water vapor, cloud and precipitation changes in the past decades. The robustness of the THA in the observations and the differences between various datasets will be presented.

Ex vivo study of the home-use TriPollar RF device using an experimental human skin model.

PubMed

Boisnic, Sylvie; Branchet, Marie Christine

2010-09-01

A wide variety of professional radio frequency (RF) aesthetic treatments for anti-aging are available aiming at skin tightening. A new home-use RF device for facial treatments has recently been developed based on TriPollar technology. To evaluate the mechanism of the new home-use device, in the process of collagen remodeling, using an ex vivo skin model. Human skin samples were collected in order to evaluate the anti-aging effect of a home-use device for facial treatments on an ex vivo human skin model. Skin tightening was evaluated by dermal histology, quantitative analysis of collagen fibers and dosage of collagen synthesis. Significant collagen remodeling following RF treatment with the device was found in the superficial and mid-deep dermis. Biochemical measurement of newly synthesized collagen showed an increase of 41% in the treated samples as compared to UV-aged control samples. The new home-use device has been demonstrated to affect significant collagen remodeling, in terms of the structural and biochemical improvement of dermal collagen on treated skin samples.

Monopolar radiofrequency treatment of the eyelids: a safety evaluation.

PubMed

Biesman, Brian S; Pope, Karl

2007-07-01

Monopolar radiofrequency (RF) energy has been used to successfully accomplish noninvasive skin tightening of the face, abdomen, and extremities. Owing to concerns about injury to the eye itself, monopolar RF treatment of the eyelids has not been feasible. The objective was to evaluate the safety of a novel 0.25-cm(2)"shallow" treatment tip for noninvasive tightening of eyelid skin. This was a tripartite study that began with an animal model to evaluate soft tissue effects and temperature change at the ocular surface. Findings were then extrapolated to ex vivo evaluation of human eyelids and ultimately to an in vivo human eyelid safety study. The animal studies demonstrated that the 0.25-cm(2) treatment tip could be used safely on eyelids in conjunction with appropriate ocular protection. The ex vivo human eyelid studies confirmed that, at typical treatment settings, the shallow treatment tip did not produce frank eyelid injury. The in vivo human studies confirmed that, at the tested settings, the novel treatment tip did not injure the eyelids or eyes. If used properly, the 0.25-cm(2) treatment tip can be safely used on human eyelids.

Tightening of tropical ascent and high clouds key to precipitation change in a warmer climate

PubMed Central

Su, Hui; Jiang, Jonathan H.; Neelin, J. David; Shen, T. Janice; Zhai, Chengxing; Yue, Qing; Wang, Zhien; Huang, Lei; Choi, Yong-Sang; Stephens, Graeme L.; Yung, Yuk L.

2017-01-01

The change of global-mean precipitation under global warming and interannual variability is predominantly controlled by the change of atmospheric longwave radiative cooling. Here we show that tightening of the ascending branch of the Hadley Circulation coupled with a decrease in tropical high cloud fraction is key in modulating precipitation response to surface warming. The magnitude of high cloud shrinkage is a primary contributor to the intermodel spread in the changes of tropical-mean outgoing longwave radiation (OLR) and global-mean precipitation per unit surface warming (dP/dTs) for both interannual variability and global warming. Compared to observations, most Coupled Model Inter-comparison Project Phase 5 models underestimate the rates of interannual tropical-mean dOLR/dTs and global-mean dP/dTs, consistent with the muted tropical high cloud shrinkage. We find that the five models that agree with the observation-based interannual dP/dTs all predict dP/dTs under global warming higher than the ensemble mean dP/dTs from the ∼20 models analysed in this study. PMID:28589940

Progress towards the treatment of Ebola haemorrhagic fever.

PubMed

Ströher, Ute; Feldmann, Heinz

2006-12-01

Being highly pathogenic for human and nonhuman primates and the subject of former weapon programmes makes Ebola virus one of the most feared pathogens worldwide today. Due to a lack of licensed pre- and postexposure intervention, the current response depends on rapid diagnostics, proper isolation procedures and supportive care of case patients. Consequently, the development of more specific countermeasures is of high priority for the preparedness of many nations. Over the past years, enhanced research efforts directed to better understand virus replication and pathogenesis have identified potential new targets for intervention strategies. The authors discuss the most promising therapeutic approaches for Ebola haemorrhagic fever as judged by their efficacy in animal models. The current development in this field encourages discussions on how to move some of the experimental approaches towards clinical application.

Tightening the Dutch coffee shop policy: Evaluation of the private club and the residence criterion.

PubMed

van Ooyen-Houben, Marianne M J; Bieleman, Bert; Korf, Dirk J

2016-05-01

The Dutch coffee shop policy was tightened in 2012. Two additional criteria that coffee shops must adhere to in order for them to be tolerated came into force: the private club and the residence criterion. Coffee shops were only permitted to give access to members and only residents of the Netherlands were permitted to become a member. This tightened policy sought to make coffee shops smaller and more controllable, to reduce the nuisance associated with coffee shops and to reduce the number of foreign visitors attracted by the coffee shops. Enforcement began in the southern provinces. The private club criterion was abolished at the end of 2012. A sample of fourteen municipalities with coffee shops was drawn. Seven in the south were treated as an 'experimental group' and the others as 'comparison group'. A baseline assessment and follow-ups at six and 18 months were performed. A combination of methods was applied: interviews with local experts, surveys with neighbourhood residents, coffee shop visitors and cannabis users, and ethnographic field work. Drugs tourism to coffee shops swiftly declined in 2012. The coffee shops also lost a large portion of their local customers, since users did not want to register as a member. The illegal market expanded. Neighbourhood residents experienced a greater amount of nuisance caused by dealer activities. After abolishment of the private club criterion, residents of the Netherlands largely returned to the coffee shops. Drug tourists still remained largely absent. Neighbourhood residents experienced more nuisance from coffee shops again. Illegal cannabis sale was tempered. No effect on cannabis use was found. The quick and robust shifts in the users' market in reaction to the policy changes illustrate the power of policy, but also the limitations caused by the dynamic and resilient nature of the Dutch cannabis supply market. Copyright © 2016 Elsevier B.V. All rights reserved.

Redox Regulation of Cell Contacts by Tricellulin and Occludin: Redox-Sensitive Cysteine Sites in Tricellulin Regulate Both Tri- and Bicellular Junctions in Tissue Barriers as Shown in Hypoxia and Ischemia.

PubMed

Cording, Jimmi; Günther, Ramona; Vigolo, Emilia; Tscheik, Christian; Winkler, Lars; Schlattner, Isabella; Lorenz, Dorothea; Haseloff, Reiner F; Schmidt-Ott, Kai M; Wolburg, Hartwig; Blasig, Ingolf E

2015-11-01

Tight junctions (TJs) seal paracellular clefts in epithelia/endothelia and form tissue barriers for proper organ function. TJ-associated marvel proteins (TAMPs; tricellulin, occludin, marvelD3) are thought to be relevant to regulation. Under normal conditions, tricellulin tightens tricellular junctions against macromolecules. Traces of tricellulin occur in bicellular junctions. As pathological disturbances have not been analyzed, the structure and function of human tricellulin, including potentially redox-sensitive Cys sites, were investigated under reducing/oxidizing conditions at 3- and 2-cell contacts. Ischemia, hypoxia, and reductants redistributed tricellulin from 3- to 2-cell contacts. The extracellular loop 2 (ECL2; conserved Cys321, Cys335) trans-oligomerized between three opposing cells. Substitutions of these residues caused bicellular localization. Cys362 in transmembrane domain 4 contributed to bicellular heterophilic cis-interactions along the cell membrane with claudin-1 and marvelD3, while Cys395 in the cytosolic C-terminal tail promoted homophilic tricellullar cis-interactions. The Cys sites included in homo-/heterophilic bi-/tricellular cis-/trans-interactions contributed to cell barrier tightness for small/large molecules. Tricellulin forms TJs via trans- and cis-association in 3-cell contacts, as demonstrated electron and quantified fluorescence microscopically; it tightens 3- and 2-cell contacts. Tricellulin's ECL2 specifically seals 3-cell contacts redox dependently; a structural model is proposed. TAMP ECL2 and claudins' ECL1 share functionally and structurally similar features involved in homo-/heterophilic tightening of cell-cell contacts. Tricellulin is a specific redox sensor and sealing element at 3-cell contacts and may compensate as a redox mediator for occludin loss at 2-cell contacts in vivo and in vitro. Molecular interaction mechanisms were proposed that contribute to tricellulin's function. In conclusion, tricellulin is a junctional redox regulator for ischemia-related alterations.

Influence of bolt tightening torque, wire size, and component reuse on wire fixation in circular external fixation.

PubMed

Wosar, Marc A; Marcellin-Little, Denis J; Roe, Simon C

2002-01-01

To evaluate the effects of bolt torque, wire size, and component reuse on the ability to maintain wire tension in 3 external skeletal fixation systems. Biomechanical study. Yield strength in tension of 1.0-, 1.2-, 1.5-, and 1.6-mm-diameter wires, and yield strength in torque of Hofmann Small Bone Fixation (SBF) cannulated and slotted bolts and IMEX regular and miniature bolts were determined on a testing machine. The minimum bolt tightening torque needed to prevent wire slippage at clinically recommended wire tensions was determined. Components were tested 10 times, and loads at slippage were recorded. The IMEX system required a mean of 8 Nm of bolt tightening torque to maintain 900 N (1.6-mm wires). The SBF system required a mean of 3 Nm bolt torque to maintain 300 N (1.0-mm wires) and 5 Nm to maintain 600 N (1.2-mm wires). The SBF cannulated bolt required 9 Nm of torque to maintain 900 N (1.5-mm wires). The SBF slotted bolts could only maintain 800 N before yield. The IMEX miniature system required a mean bolt torque of 1.1 Nm to maintain 300 N. The cannulated and slotted bolts from both manufacturers failed to maintain 70% of initial wire tension after 7 and 4 uses, respectively. The IMEX systems and the SBF system using 1.0- and 1.2-mm wires could maintain clinically recommended wire tension safely. Only the IMEX system could maintain clinically recommended wire tension safely using 1.5- or 1.6-mm wires. The SBF system using 1.0- and 1.2-mm wires and the IMEX system using all wire sizes can maintain clinically relevant wire tension. The SBF system using 1.5-mm wires could not. Cannulated and slotted bolts should not be used more than 6 and 3 times, respectively. Nuts should not be reused. Copyright 2002 by The American College of Veterinary Surgeons

Tighter accuracy standards within point-of-care blood glucose monitoring: how six commonly used systems compare.

PubMed

Robinson, Charlotte S; Sharp, Patrick

2012-05-01

Blood glucose monitoring systems (BGMS) are used in the hospital environment to manage blood glucose levels in patients at the bedside. The International Organization for Standardization (ISO) 15197:2003 standard is currently used by regulatory bodies as a minimum requirement for the performance of BGMS, specific to self-testing. There are calls for the tightening of accuracy requirements and implementation of a standard specifically for point-of-care (POC) BGMS. The accuracy of six commonly used BGMS was assessed in a clinical setting, with 108 patients' finger stick capillary samples. Using the accuracy criteria from the existing standard and a range of tightened accuracy criteria, system performance was compared. Other contributors to system performance have been measured, including hematocrit sensitivity and meter error rates encountered in the clinical setting. Five of the six BGMS evaluated met current accuracy criteria within the ISO 15197 standard. Only the Optium Xceed system had >95% of all readings within a tightened criteria of ±12.5% from the reference at glucose levels ≥72 mg/dl (4 mmol/liter) and ±9 mg/dl (0.5 mmol/liter) at glucose levels <72 mg/dl (4 mmol/liter). The Nova StatStrip Xpress had the greatest number of error messages observed; Optium Xceed the least. OneTouch Ultra2, Nova StatStrip Xpress, Accu-Chek Performa, and Contour TS products were all significantly influenced by blood hematocrit levels. From evidence obtained during this clinical evaluation, the Optium Xceed system is most likely to meet future anticipated accuracy standards for POC BGMS. In this clinical study, the results demonstrated the Optium Xceed product to have the highest level of accuracy, to have the lowest occurrence of error messages, and to be least influenced by blood hematocrit levels. © 2012 Diabetes Technology Society.

Body Contouring and Skin Tightening Using a Unique Novel Multisource Radiofrequency Energy Delivery Method

PubMed Central

Robson, Sam

2017-01-01

Objective: The objective of this study was to examine the efficacy and safety of the latest multisource radiofrequency handpiece, specially designed for body area skin treatments. The new handpiece features six concentric electrodes, each connected to an independently controlled radiofrequency generator. Design and settings: This was an international multicenter study across two sites. Twenty-five patients were enrolled into the study. Patients underwent at least five sessions of body skin tightening and circumference reduction. The first four sessions were held at one-week intervals and the other 1 to 4 remaining sessions, at two-week intervals. Participants: Twenty-five patients (23 women and 2 men). Measurements: Overall change was graded by the physicians using the global aesthetic improvement scale. Patients were asked to complete satisfaction questionnaires at the end of the treatment sessions. Images were taken prior to the treatments, before every treatment session, and at the follow-up visit. Results: No adverse events were reported as a result of the treatment. Measured body weight of the patients, as monitored during the study period, was stable (±2kg). Ninety-two percent of the patients were pleased with the results and finished all the treatment sessions. Twenty-four patients (96%) saw an improvement in body shape. Ninety-two percent of the patients would recommend the treatment to others. Overall change graded by the physician by the global aesthetic improvement scale provided the following results: 44 percent of the patients had more than 75-percent improvement, 32 percent of the patients between 50- to 75-percent improvement, 20 percent of the patients had between 25- to 50-percent improvement and only four percent had less than 25-percent improvement. Conclusion: The authors’ data show that the handpiece examined provides high efficacy in skin tightening and body contouring after 5 to 8 painless treatments. Patient subjective questionnaires show very high satisfaction rates. PMID:28458771

Activating the innate immune response to counter chronic hepatitis B virus infection.

PubMed

Lamb, Camilla; Arbuthnot, Patrick

2016-12-01

Chronic infection with hepatitis B virus (HBV) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. Licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of HBV is a priority. Areas covered: The recent demonstration that the activation of the innate immune response may eradicate HBV from infected hepatocytes has a promising therapeutic application. Small molecule stimulators of Toll-like receptors (TLRs) inhibit replication of woodchuck hepatitis virus in woodchucks and HBV in chimpanzees and mice. Early stage clinical trials using GS-9620, a TLR7 agonist, indicate that this candidate antiviral is well tolerated in humans. Using an alternative approach, triggering the innate immune response with agonists of lymphotoxin-β receptor caused efficient APOBEC-mediated deamination and degradation of viral covalently closed circular DNA. Expert opinion: Eliminating HBV cccDNA from infected individuals would constitute a cure, and has become the focus of intensive research that employs various therapeutic approaches, including gene therapy. Immunomodulation through innate immune activation shows promise for the treatment of chronic infection of HBV (CHB) and, used in combination with other therapeutics, may contribute to the global control of infections and ultimately to the eradication of HBV.

Flavivirus Infection of Ixodes scapularis (Black-Legged Tick) Ex Vivo Organotypic Cultures and Applications for Disease Control.

PubMed

Grabowski, Jeffrey M; Tsetsarkin, Konstantin A; Long, Dan; Scott, Dana P; Rosenke, Rebecca; Schwan, Tom G; Mlera, Luwanika; Offerdahl, Danielle K; Pletnev, Alexander G; Bloom, Marshall E

2017-08-22

Ixodes scapularis ticks transmit many infectious agents that cause disease, including tick-borne flaviviruses (TBFVs). TBFV infections cause thousands of human encephalitis cases worldwide annually. In the United States, human TBFV infections with Powassan virus (POWV) are increasing and have a fatality rate of 10 to 30%. Additionally, Langat virus (LGTV) is a TBFV of low neurovirulence and is used as a model TBFV. TBFV replication and dissemination within I. scapularis organs are poorly characterized, and a deeper understanding of virus biology in this vector may inform effective countermeasures to reduce TBFV transmission. Here, we describe short-term, I. scapularis organ culture models of TBFV infection. Ex vivo organs were metabolically active for 9 to 10 days and were permissive to LGTV and POWV replication. Imaging and videography demonstrated replication and spread of green fluorescent protein-expressing LGTV in the organs. Immunohistochemical staining confirmed LGTV envelope and POWV protein synthesis within the infected organs. LGTV- and POWV-infected organs produced infectious LGTV and POWV; thus, the ex vivo cultures were suitable for study of virus replication in individual organs. LGTV- and POWV-infected midgut and salivary glands were subjected to double-stranded RNA (dsRNA) transfection with dsRNA to the LGTV 3' untranslated region (UTR), which reduced infectious LGTV and POWV replication, providing a proof-of-concept use of RNA interference in I. scapularis organ cultures to study the effects on TBFV replication. The results contribute important information on TBFV localization within ex vivo I. scapularis organs and provide a significant translational tool for evaluating recombinant, live vaccine candidates and potential tick transcripts and proteins for possible therapeutic use and vaccine development to reduce TBFV transmission. IMPORTANCE Tick-borne flavivirus (TBFV) infections cause neurological and/or hemorrhagic disease in humans worldwide. There are currently no licensed therapeutics or vaccines against Powassan virus (POWV), the only TBFV known to circulate in North America. Evaluating tick vector targets for antitick vaccines directed at reducing TBFV infection within the arthropod vector is a critical step in identifying efficient approaches to controlling TBFV transmission. This study characterized infection of female Ixodes scapularis tick organ cultures of midgut, salivary glands, and synganglion with the low-neurovirulence Langat virus (LGTV) and the more pathogenic POWV. Cell types of specific organs were susceptible to TBFV infection, and a difference in LGTV and POWV replication was noted in TBFV-infected organs. This tick organ culture model of TBFV infection will be useful for various applications, such as screening of tick endogenous dsRNA corresponding to potential control targets within midgut and salivary glands to confirm restriction of TBFV infection.

The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication.

PubMed

Bharaj, Preeti; Atkins, Colm; Luthra, Priya; Giraldo, Maria Isabel; Dawes, Brian E; Miorin, Lisa; Johnson, Jeffrey R; Krogan, Nevan J; Basler, Christopher F; Freiberg, Alexander N; Rajsbaum, Ricardo

2017-09-15

Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection. IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP35 protein contributes to pathogenesis, because it serves as an essential cofactor of the viral polymerase as well as a potent antagonist of innate immunity. However, how VP35 function is regulated by host cellular factors is poorly understood. Here, we report that the host E3-ubiquitin ligase TRIM6 promotes VP35 ubiquitination and is important for efficient virus replication. Therefore, our study identifies a new host factor, TRIM6, as a potential target in the development of antiviral drugs against EBOV. Copyright © 2017 American Society for Microbiology.

The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication

PubMed Central

Bharaj, Preeti; Atkins, Colm; Luthra, Priya; Giraldo, Maria Isabel; Dawes, Brian E.; Miorin, Lisa; Johnson, Jeffrey R.; Krogan, Nevan J.; Basler, Christopher F.; Freiberg, Alexander N.

2017-01-01

ABSTRACT Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection. IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP35 protein contributes to pathogenesis, because it serves as an essential cofactor of the viral polymerase as well as a potent antagonist of innate immunity. However, how VP35 function is regulated by host cellular factors is poorly understood. Here, we report that the host E3-ubiquitin ligase TRIM6 promotes VP35 ubiquitination and is important for efficient virus replication. Therefore, our study identifies a new host factor, TRIM6, as a potential target in the development of antiviral drugs against EBOV. PMID:28679761

Prokaryotic and eukaryotic DNA helicases. Essential molecular motor proteins for cellular machinery.

PubMed

Tuteja, Narendra; Tuteja, Renu

2004-05-01

DNA helicases are ubiquitous molecular motor proteins which harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of energetically stable duplex DNA, and thus play important roles in nearly all aspects of nucleic acid metabolism, including replication, repair, recombination, and transcription. They break the hydrogen bonds between the duplex helix and move unidirectionally along the bound strand. All helicases are also translocases and DNA-dependent ATPases. Most contain conserved helicase motifs that act as an engine to power DNA unwinding. All DNA helicases share some common properties, including nucleic acid binding, NTP binding and hydrolysis, and unwinding of duplex DNA in the 3' to 5' or 5' to 3' direction. The minichromosome maintenance (Mcm) protein complex (Mcm4/6/7) provides a DNA-unwinding function at the origin of replication in all eukaryotes and may act as a licensing factor for DNA replication. The RecQ family of helicases is highly conserved from bacteria to humans and is required for the maintenance of genome integrity. They have also been implicated in a variety of human genetic disorders. Since the discovery of the first DNA helicase in Escherichia coli in 1976, and the first eukaryotic one in the lily in 1978, a large number of these enzymes have been isolated from both prokaryotic and eukaryotic systems, and the number is still growing. In this review we cover the historical background of DNA helicases, helicase assays, biochemical properties, prokaryotic and eukaryotic DNA helicases including Mcm proteins and the RecQ family of helicases. The properties of most of the known DNA helicases from prokaryotic and eukaryotic systems, including viruses and bacteriophages, are summarized in tables.

A Genome-Wide RNA Interference Screen Identifies a Role for Wnt/β-Catenin Signaling during Rift Valley Fever Virus Infection.

PubMed

Harmon, Brooke; Bird, Sara W; Schudel, Benjamin R; Hatch, Anson V; Rasley, Amy; Negrete, Oscar A

2016-08-15

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses La Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. These studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses. Copyright © 2016 Harmon et al.

Acquiring Data by Mining the Past: Pairing Communities with Environmental Monitoring Methods through Open Online Collaborative Replication

NASA Astrophysics Data System (ADS)

Lippincott, M.; Lewis, E. S.; Gehrke, G. E.; Wise, A.; Pyle, S.; Sinatra, V.; Bland, G.; Bydlowski, D.; Henry, A.; Gilberts, P. A.

2016-12-01

Community groups are interested in low-cost sensors to monitor their environment. However, many new commercial sensors are unknown devices without peer-reviewed evaluations of data quality or pathways to regulatory acceptance, and the time to achieve these outcomes may be beyond a community's patience and attention. Rather than developing a device from scratch or validating a new commercial product, a workflow is presented whereby existing technologies, especially those that are out of patent, are replicated through open online collaboration between communities affected by environmental pollution, volunteers, academic institutions, and existing open hardware and open source software projects. Technology case studies will be presented, focusing primarily on a passive PM monitor based on the UNC Passive Monitor. Stages of the project will be detailed moving from identifying community needs, reviewing existing technology, partnership development, technology replication, IP review and licensing, data quality assurance (in process), and field evaluation with community partners (in process), with special attention to partnership development and technology review. We have leveraged open hardware and open source software to lower the cost and access barriers of existing technologies for PM10-2.5 and other atmospheric measures that have already been validated through peer review. Existing validation of and regulatory familiarity with a technology enables a rapid pathway towards collecting data, shortening the time it takes for communities to leverage data in environmental management decisions. Online collaboration requires rigorous documentation that aids in spreading research methods and promoting deep engagement by interested community researchers outside academia. At the same time, careful choice of technology and the use of small-scale fabrication through laser cutting, 3D printing, and open, shared repositories of plans and software enables educational engagement that broadens a project's reach.

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

DOE PAGES

Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.; ...

2016-05-25

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

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

Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

Rationale and Suggestions for Emphasizing Afrocentricity in the Public Schools.

ERIC Educational Resources Information Center

Honeman, Bob

Public schools are facing the largest crisis in American educational history. More and more minority students are attending public schools, and traditional methods of instruction are failing to meet their needs. The back-to-basics and belt-tightening movements within public schooling are part of a last-ditch effort to support an elitist education…

Three Worlds: New Directions in Participant Development in Sport and Physical Activity

ERIC Educational Resources Information Center

Collins, Dave; Bailey, Richard; Ford, Paul A.; MacNamara, Aine; Toms, Martin; Pearce, Gemma

2012-01-01

The twin challenges of inactivity and the 2012 Olympics have tightened the focus in UK sport promotion. However, the twin track approach which treats these challenges as distinct concerns may limit the efficacy of interventions in either area. We propose that a continuum between participation, performance sport and elite achievement represents the…

Urban Poverty and the Welfare State: Comparative Reflections on Scandinavia and the U.S. Working Paper No. 481.

ERIC Educational Resources Information Center

Abrahamson, Peter

Scandinavian welfare states are developing a growing new middle class and a growing marginalized, poverty-threatened underclass, reproducing the societal duality caused by labor market structuring. Tightening labor markets, increased dependency on welfare benefits, and substantial decreases in public transfers have combined to create a growing…

Modeling Carbon Exchange

NASA Technical Reports Server (NTRS)

Sellers, Piers

2012-01-01

Model results will be reviewed to assess different methods for bounding the terrestrial role in the global carbon cycle. It is proposed that a series of climate model runs could be scoped that would tighten the limits on the "missing sink" of terrestrial carbon and could also direct future satellite image analyses to search for its geographical location and understand its seasonal dynamics.

How Can Only 18 Black Teachers Working in Liverpool Represent a Diverse Teaching Workforce? A Critical Narrative

ERIC Educational Resources Information Center

Boyle, William; Charles, Marie

2016-01-01

This paper follows on from the authors' previous research into minimal Black teacher representation in Liverpool schools [Boyle, B., and M. Charles. 2010. "Tightening the Shackles: The Continued Invisibility of Liverpool's British African Caribbean Teachers." "Journal of Black Studies" 42 (3): 427-435]. It is based on a…

Do Cyborg Dreams Emancipate Sheep? (with Apologies to Philip K. Dick).

ERIC Educational Resources Information Center

Bromley, Hank

A full investigation into how and why the expression of potential benefits of computers in schools is hindered would need to consider many aspects, but one point that should be considered is the ever-tightening integration of educational institutions into the global economy. Evidence of the accelerating assimilation of schools into the economy…

Understanding the challenges of municipal tree planting

Treesearch

E.G. McPherson; R. Young

2010-01-01

Nine of the twelve largest cities in the U.S. have mayoral tree planting initiatives (TPIs), with pledges to plant nearly 20 million trees. Although executive-level support for trees has never been this widespread, many wonder if this support will endure as administrations change and budgets tighten. In an effort to share lessons learned from successes and setbacks, a...

The Liability of Colleges and Universities for Fraud, Waste, and Abuse in Federally Funded Grants and Projects.

ERIC Educational Resources Information Center

Gordon, Steven D.

1996-01-01

The federal government's war on fraud, waste, and abuse in expenditure of federal funds has reached college campuses. Institutions that fail to heed this development are vulnerable to harsh sanctions. They must tighten accounting practices and recognize their liability for fraudulent practices of faculty and students. Internal investigations and…