Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair.

Science.gov (United States)

Nakanishi, Koji; Yang, Yun-Gui; Pierce, Andrew J; Taniguchi, Toshiyasu; Digweed, Martin; D'Andrea, Alan D; Wang, Zhao-Qi; Jasin, Maria

2005-01-25

Fanconi anemia (FA) is a recessive disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. Cells from FA patients are hypersensitive to agents that produce DNA crosslinks and, after treatment with these agents, have pronounced chromosome breakage and other cytogenetic abnormalities. Eight FANC genes have been cloned, and the encoded proteins interact in a common cellular pathway. DNA-damaging agents activate the monoubiquitination of FANCD2, resulting in its targeting to nuclear foci that also contain BRCA1 and BRCA2/FANCD1, proteins involved in homology-directed DNA repair. Given the interaction of the FANC proteins with BRCA1 and BRCA2, we tested whether cells from FA patients (groups A, G, and D2) and mouse Fanca-/- cells with a targeted mutation are impaired for this repair pathway. We find that both the upstream (FANCA and FANCG) and downstream (FANCD2) FA pathway components promote homology-directed repair of chromosomal double-strand breaks (DSBs). The FANCD2 monoubiquitination site is critical for normal levels of repair, whereas the ATM phosphorylation site is not. The defect in these cells, however, is mild, differentiating them from BRCA1 and BRCA2 mutant cells. Surprisingly, we provide evidence that these proteins, like BRCA1 but unlike BRCA2, promote a second DSB repair pathway involving homology, i.e., single-strand annealing. These results suggest an early role for the FANC proteins in homologous DSB repair pathway choice.

Inguinal hernia repair with tension-free hernioplasty under local anesthesia

International Nuclear Information System (INIS)

Gao, Jia-Sen; Wang, Zhen-Jun; Zhao, Bo; Ma Song Zhang; Pang, Guo-Yi; Na, Dong-Ming; Zhang Yu-Dong

2009-01-01

To evaluate the use of local anesthesia in tension-free hernioplasty in a local hospital. The study took place at Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China during the period from January 2007 to May 2008. All 110 patients who had undergone inguinal hernia repair with mesh under local anesthesia were included in the study. To increase the homogeneity of the sample, we excluded umbilical hernia repairs, parastomal hernia repairs, non-elective procedures, procedures not involving mesh, and repairs performed concurrently with another surgical procedure. We performed a retrospective review of all 110 patients' data. The average operating time was 45 minutes (30-70 minutes), and the average hospital stay was 3-4 days. There was no postoperative mortality in this study. No surgical site infection occurred. Two patients (18%) that suffered from a moderate scrotal hematoma had recovered after extract injection therapy was applied. The duration of incisional pain was 2-3 days, and no patient required post-operative analgesia. During the follow-up, no recurrence occurred. The use of local anesthesia in inguinal hernia repair with tension-free hernioplasty is a safe and effective alternative for inpatient treatment. (aothor)

A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year.

Science.gov (United States)

Siclari, Alberto; Mascaro, Gennaro; Gentili, Chiara; Cancedda, Ranieri; Boux, Eugenio

2012-03-01

Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Inducible DNA-repair systems in yeast: competition for lesions.

Science.gov (United States)

Mitchel, R E; Morrison, D P

1987-03-01

DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate

EXPERIENCE WITH THE OPEN TENSION-FREE HERNIA REPAIR

Directory of Open Access Journals (Sweden)

Slavko Rakovec

2002-03-01

Full Text Available Background. All old techniques of herniorrhaphy involve approximation of tissues under tension, which accounts for their unreliability. Therefore the recovery time is long and the recurrence rate unacceptably high. The new methods using a mesh patch of polypropylene allow for a tensionfree repair, which is much more reliable. So they are associated with a shorter recovery time and carry a low probability of recurrence. The tension-free repair can be accomplished in an open manner, by placing the mesh through an open incision, or by the endoscopic technique, which involves placing the mesh from within by laparoscopic instruments. The open tension-free procedures can be performed with the use of stitches (according to Lichtenstein or without them (sutureless techniques. Stitching the mesh may cause problems due to maldistribution of tension between the mesh and the patient’s tissues, the occurrence of neuralgia or the development of inflammatory granuloma. Therefore sutureless procedures are increasingly performed. They usually require, besides the use of a mesh patch, also the use of a dart plug made of the same material.Methods. The open tension-free methods of hernia repair have been used at our Department since 1994. The first 77 operations were performed by Lichtenstein technique. The mean postoperative hospital stay was 3.4 days and the mean work restriction period was 3 weeks. In the middle of the year 1995, we shifted to suturless technique. By the end of the year 2000, we had performed 768 operations. The average postoperative hospital stay was 1.2 days and the average recovery time was 10 days.Results. In the first group of 77 hernia repairs performed by the Lichtenstein procedure serious complications were noted in six patients: bleeding in one, long-lasting neuralgia in two, and purulent granuloma, appearing long after discharge from the hospital, in three. There were no recurrences. In the second group of 768 hernia repairs

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

Science.gov (United States)

Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

2014-01-01

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

On failure of the pruning technique in "error repair in shift-reduce parsers"

NARCIS (Netherlands)

Bertsch, E; Nederhof, MJ

A previous article presented a technique to compute the least-cost error repair by incrementally generating configurations that result from inserting and deleting tokens in a syntactically incorrect input. An additional mechanism to improve the run-time efficiency of this algorithm by pruning some

Understanding the dynamics of correct and error responses in free recall: evidence from externalized free recall.

Science.gov (United States)

Unsworth, Nash; Brewer, Gene A; Spillers, Gregory J

2010-06-01

The dynamics of correct and error responses in a variant of delayed free recall were examined in the present study. In the externalized free recall paradigm, participants were presented with lists of words and were instructed to subsequently recall not only the words that they could remember from the most recently presented list, but also any other words that came to mind during the recall period. Externalized free recall is useful for elucidating both sampling and postretrieval editing processes, thereby yielding more accurate estimates of the total number of error responses, which are typically sampled and subsequently edited during free recall. The results indicated that the participants generally sampled correct items early in the recall period and then transitioned to sampling more erroneous responses. Furthermore, the participants generally terminated their search after sampling too many errors. An examination of editing processes suggested that the participants were quite good at identifying errors, but this varied systematically on the basis of a number of factors. The results from the present study are framed in terms of generate-edit models of free recall.

Uracil excision repair in Mycobacterium tuberculosis cell-free extracts.

Science.gov (United States)

Kumar, Pradeep; Bharti, Sanjay Kumar; Varshney, Umesh

2011-05-01

Uracil excision repair is ubiquitous in all domains of life and initiated by uracil DNA glycosylases (UDGs) which excise the promutagenic base, uracil, from DNA to leave behind an abasic site (AP-site). Repair of the resulting AP-sites requires an AP-endonuclease, a DNA polymerase, and a DNA ligase whose combined activities result in either short-patch or long-patch repair. Mycobacterium tuberculosis, the causative agent of tuberculosis, has an increased risk of accumulating uracils because of its G + C-rich genome, and its niche inside host macrophages where it is exposed to reactive nitrogen and oxygen species, two major causes of cytosine deamination (to uracil) in DNA. In vitro assays to study DNA repair in this important human pathogen are limited. To study uracil excision repair in mycobacteria, we have established assay conditions using cell-free extracts of M. tuberculosis and M. smegmatis (a fast-growing mycobacterium) and oligomer or plasmid DNA substrates. We show that in mycobacteria, uracil excision repair is completed primarily via long-patch repair. In addition, we show that M. tuberculosis UdgB, a newly characterized family 5 UDG, substitutes for the highly conserved family 1 UDG, Ung, thereby suggesting that UdgB might function as backup enzyme for uracil excision repair in mycobacteria. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mouse RAD54 affects DNA double-strand break repair and sister chromatid exchange

NARCIS (Netherlands)

H.B. Beverloo (Berna); R.D. Johnson (Roger); M. Jasin (Maria); R. Kanaar (Roland); J.H.J. Hoeijmakers (Jan); M.L.G. Dronkert (Mies)

2000-01-01

textabstractCells can achieve error-free repair of DNA double-strand breaks (DSBs) by homologous recombination through gene conversion with or without crossover. In contrast, an alternative homology-dependent DSB repair pathway, single-strand annealing (SSA), results in deletions. In this study, we

DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice.

Science.gov (United States)

Schipler, Agnes; Iliakis, George

2013-09-01

Although the DNA double-strand break (DSB) is defined as a rupture in the double-stranded DNA molecule that can occur without chemical modification in any of the constituent building blocks, it is recognized that this form is restricted to enzyme-induced DSBs. DSBs generated by physical or chemical agents can include at the break site a spectrum of base alterations (lesions). The nature and number of such chemical alterations define the complexity of the DSB and are considered putative determinants for repair pathway choice and the probability that errors will occur during this processing. As the pathways engaged in DSB processing show distinct and frequently inherent propensities for errors, pathway choice also defines the error-levels cells opt to accept. Here, we present a classification of DSBs on the basis of increasing complexity and discuss how complexity may affect processing, as well as how it may cause lethal or carcinogenic processing errors. By critically analyzing the characteristics of DSB repair pathways, we suggest that all repair pathways can in principle remove lesions clustering at the DSB but are likely to fail when they encounter clusters of DSBs that cause a local form of chromothripsis. In the same framework, we also analyze the rational of DSB repair pathway choice.

LAPAROSCOPIC TEP VERSUS OPEN HERNIOPLASTY: A COMPARATIVE STUDY OF EXTRAPERITONEAL TENSION FREE MESH REPAIRS IN INGUINAL HERNIA

OpenAIRE

Rehan Sabir; Sadiq; Shadan

2015-01-01

Inguinal hernia repair is now one of the most commonly performed general surgical procedures in practice. 'Tension - free repair' is the procedure of choice . [ 1 ] due to its low recurrence rate, these tension - free repair procedures can be roughly categorized into two groups: laparoscopic and open anterior approach. TEP is accepted as the most ideal method because it can avoid entry into the peritoneal cavity, which can cause intraperitoneal compli...

Implication of the E. coli K12 uvrA and recA genes in the repair of 8-methoxypsoralen-induced mono adducts and crosslinks on plasmid DNA

International Nuclear Information System (INIS)

Paramio, J.M.; Bauluz, C.; Vidania, R. de

1986-01-01

Genotoxicity of psoralen damages on plasmid DNA has been studied. pBR322 DNA was randomly modified with several concentrations of 8-methoxypsoralen plus 365 nm-UV light. After transformation into E. coli strains (wild-type, uvrA and recA) plasmid survival and mutagenesis were analyzed. To study the influence of the SOS response on plasmid recovery, preirradiation of the cells was performed. In absence of cell preirradiation, crosslinks were not repaired in any strain. Mono adducts were also lethal but in part removed by the excision-repair pathway. Preirradiation of the cells significantly. increased plasmid recovery in recA+ celia. In uvrA- only the mutagenic pathway seemed to be involved in the repair of the damaged DNA. Wild type strain showed the highest increase in plasmid survival, involving the repair of mono adducts and some fraction of crosslinks mainly through an error-free repair pathway. This suggests an enhancement of the excision repair promoted by the induction of SOS functions. (Author) 32 refs

Repair for scattering expansion truncation errors in transport calculations

International Nuclear Information System (INIS)

Emmett, M.B.; Childs, R.L.; Rhoades, W.A.

1980-01-01

Legendre expansion of angular scattering distributions is usually limited to P 3 in practical transport calculations. This truncation often results in non-trivial errors, especially alternating negative and positive lateral scattering peaks. The effect is especially prominent in forward-peaked situations such as the within-group component of the Compton Scattering of gammas. Increasing the expansion to P 7 often makes the peaks larger and narrower. Ward demonstrated an accurate repair, but his method requires special cross section sets and codes. The DOT IV code provides fully-compatible, but heuristic, repair of the erroneous scattering. An analytical Klein-Nishina estimator, newly available in the MORSE code, allows a test of this method. In the MORSE calculation, particle scattering histories are calculated in the usual way, with scoring by an estimator routine at each collision site. Results for both the conventional P 3 estimator and the analytical estimator were obtained. In the DOT calculation, the source moments are expanded into the directional representation at each iteration. Optionally a sorting procedure removes all negatives, and removes enough small positive values to restore particle conservation. The effect of this is to replace the alternating positive and negative values with positive values of plausible magnitude. The accuracy of those values is examined herein

SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination

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Waaqo Daddacha

2017-08-01

Full Text Available DNA double-strand break (DSB repair by homologous recombination (HR is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs. SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs to facilitate end resection and HR. Significantly, a cancer-associated mutant with impaired CtIP interaction, but not dNTPase-inactive SAMHD1, fails to rescue the end resection impairment of SAMHD1 depletion. Our findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.

A robust network of double-strand break repair pathways governs genome integrity during C. elegans development.

NARCIS (Netherlands)

Pontier, D.B.; Tijsterman, M.

2009-01-01

To preserve genomic integrity, various mechanisms have evolved to repair DNA double-strand breaks (DSBs). Depending on cell type or cell cycle phase, DSBs can be repaired error-free, by homologous recombination, or with concomitant loss of sequence information, via nonhomologous end-joining (NHEJ)

Topical erythropoietin promotes wound repair in diabetic rats.

Science.gov (United States)

Hamed, Saher; Ullmann, Yehuda; Masoud, Muhannad; Hellou, Elias; Khamaysi, Ziad; Teot, Luc

2010-01-01

Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

Protecting DNA from errors and damage: an overview of DNA repair mechanisms in plants compared to mammals.

Science.gov (United States)

Spampinato, Claudia P

2017-05-01

The genome integrity of all organisms is constantly threatened by replication errors and DNA damage arising from endogenous and exogenous sources. Such base pair anomalies must be accurately repaired to prevent mutagenesis and/or lethality. Thus, it is not surprising that cells have evolved multiple and partially overlapping DNA repair pathways to correct specific types of DNA errors and lesions. Great progress in unraveling these repair mechanisms at the molecular level has been made by several talented researchers, among them Tomas Lindahl, Aziz Sancar, and Paul Modrich, all three Nobel laureates in Chemistry for 2015. Much of this knowledge comes from studies performed in bacteria, yeast, and mammals and has impacted research in plant systems. Two plant features should be mentioned. Plants differ from higher eukaryotes in that they lack a reserve germline and cannot avoid environmental stresses. Therefore, plants have evolved different strategies to sustain genome fidelity through generations and continuous exposure to genotoxic stresses. These strategies include the presence of unique or multiple paralogous genes with partially overlapping DNA repair activities. Yet, in spite (or because) of these differences, plants, especially Arabidopsis thaliana, can be used as a model organism for functional studies. Some advantages of this model system are worth mentioning: short life cycle, availability of both homozygous and heterozygous lines for many genes, plant transformation techniques, tissue culture methods and reporter systems for gene expression and function studies. Here, I provide a current understanding of DNA repair genes in plants, with a special focus on A. thaliana. It is expected that this review will be a valuable resource for future functional studies in the DNA repair field, both in plants and animals.

Nucleotide-excision repair of DNA in cell-free extracts of the yeast Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Wang, Z.; Wu, X.; Friedberg, E.C.

1993-01-01

A wide spectrum of DNA lesions are repaired by the nucleotide-excision repair (NER) pathway in both eukaryotic and prokaryotic cells. We have developed a cell-free system in Saccharomyces cerevisiae that supports NER. NER was monitored by measuring repair synthesis in DNA treated with cisplatin or with UV radiation. Repair synthesis in vitro was defective in extracts of rad1, rad2, and rad10 mutant cells, all of which have mutations in genes whose products are known to be required for NER in vivo. Additionally, repair synthesis was complemented by mixing different mutant extracts, or by adding purified Rad1 or Rad10 protein to rad1 or rad10 mutant extracts, respectively. The latter observation demonstrates that the Rad1 and Rad10 proteins directly participate in the biochemical pathway of NER. NER supported by nuclear extracts requires ATP and Mg 2+ and is stimulated by polyethylene glycol and by small amounts of whole cell extract containing overexpressed Rad2 protein. The nuclear extracts also contain base-excision repair activity that is present at wild-type levels in rad mutant extracts. This cell-free system is expected to facilitate studies on the biochemical pathway of NER in S. cerevisiae

Optimization of Trade-offs in Error-free Image Transmission

Science.gov (United States)

Cox, Jerome R.; Moore, Stephen M.; Blaine, G. James; Zimmerman, John B.; Wallace, Gregory K.

1989-05-01

The availability of ubiquitous wide-area channels of both modest cost and higher transmission rate than voice-grade lines promises to allow the expansion of electronic radiology services to a larger community. The band-widths of the new services becoming available from the Integrated Services Digital Network (ISDN) are typically limited to 128 Kb/s, almost two orders of magnitude lower than popular LANs can support. Using Discrete Cosine Transform (DCT) techniques, a compressed approximation to an image may be rapidly transmitted. However, intensity or resampling transformations of the reconstructed image may reveal otherwise invisible artifacts of the approximate encoding. A progressive transmission scheme reported in ISO Working Paper N800 offers an attractive solution to this problem by rapidly reconstructing an apparently undistorted image from the DCT coefficients and then subse-quently transmitting the error image corresponding to the difference between the original and the reconstructed images. This approach achieves an error-free transmission without sacrificing the perception of rapid image delivery. Furthermore, subsequent intensity and resampling manipulations can be carried out with confidence. DCT coefficient precision affects the amount of error information that must be transmitted and, hence the delivery speed of error-free images. This study calculates the overall information coding rate for six radiographic images as a function of DCT coefficient precision. The results demonstrate that a minimum occurs for each of the six images at an average coefficient precision of between 0.5 and 1.0 bits per pixel (b/p). Apparently undistorted versions of these six images can be transmitted with a coding rate of between 0.25 and 0.75 b/p while error-free versions can be transmitted with an overall coding rate between 4.5 and 6.5 b/p.

Chromosomal Bands Affected by Acute Oil Exposure and DNA Repair Errors

Science.gov (United States)

Zock, Jan-Paul; Giraldo, Jesús; Pozo-Rodríguez, Francisco; Espinosa, Ana; Rodríguez-Trigo, Gema; Verea, Hector; Castaño-Vinyals, Gemma; Gómez, Federico P.; Antó, Josep M.; Coll, Maria Dolors; Barberà, Joan Albert; Fuster, Carme

2013-01-01

Background In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. Objectives We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. Methods Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. Results Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016). Conclusion The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas) reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure. PMID:24303039

PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair

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Meimei Zhao

2017-08-01

Full Text Available The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway. DNA-PK phosphorylates and activates PCAF upon UV damage and consequently promotes the acetylation of RPA1. Moreover, the acetylation of RPA1 is tightly regulated by HDAC6 and SIRT1. Together, our results demonstrate that the K163 acetylation of RPA1 plays a key role in the repair of UV-induced DNA damage and reveal how the specific RPA1 modification modulates the choice of distinct DNA repair pathways.

Discretization errors at free boundaries of the Grad-Schlueter-Shafranov equation

International Nuclear Information System (INIS)

Meyer-Spasche, R.; Fornberg, B.

1990-10-01

The numerical error of standard finite-difference schemes is analyzed at free boundaries of the Grad-Schlueter-Shafranov equation of plasma physics. A simple correction strategy is devised to eliminate (to leading order) the errors which arise as the free boundary crosses the rectangular grid at irregular locations. The resulting scheme can be solved by Gauss-Newton or Inverse iterations, or by multigrid iterations. Extrapolation (from 2nd to 3rd order of accuracy) is possible for the new scheme. (orig.)

The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair.

Science.gov (United States)

Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

2016-10-01

USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1.

Capacity of oscillatory associative-memory networks with error-free retrieval

International Nuclear Information System (INIS)

Nishikawa, Takashi; Lai Yingcheng; Hoppensteadt, Frank C.

2004-01-01

Networks of coupled periodic oscillators (similar to the Kuramoto model) have been proposed as models of associative memory. However, error-free retrieval states of such oscillatory networks are typically unstable, resulting in a near zero capacity. This puts the networks at disadvantage as compared with the classical Hopfield network. Here we propose a simple remedy for this undesirable property and show rigorously that the error-free capacity of our oscillatory, associative-memory networks can be made as high as that of the Hopfield network. They can thus not only provide insights into the origin of biological memory, but can also be potentially useful for applications in information science and engineering

Repair of radiation damage in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Setlow, R.B.

1981-01-01

The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

Repair of radiation damage in mammalian cells

International Nuclear Information System (INIS)

Setlow, R.B.

1981-01-01

The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

Multiconfiguration Pair-Density Functional Theory Is Free From Delocalization Error.

Science.gov (United States)

Bao, Junwei Lucas; Wang, Ying; He, Xiao; Gagliardi, Laura; Truhlar, Donald G

2017-11-16

Delocalization error has been singled out by Yang and co-workers as the dominant error in Kohn-Sham density functional theory (KS-DFT) with conventional approximate functionals. In this Letter, by computing the vertical first ionization energy for well separated He clusters, we show that multiconfiguration pair-density functional theory (MC-PDFT) is free from delocalization error. To put MC-PDFT in perspective, we also compare it with some Kohn-Sham density functionals, including both traditional and modern functionals. Whereas large delocalization errors are almost universal in KS-DFT (the only exception being the very recent corrected functionals of Yang and co-workers), delocalization error is removed by MC-PDFT, which bodes well for its future as a step forward from KS-DFT.

Gene promoter methylation and DNA repair capacity in monozygotic twins with discordant smoking habits.

Science.gov (United States)

Ottini, Laura; Rizzolo, Piera; Siniscalchi, Ester; Zijno, Andrea; Silvestri, Valentina; Crebelli, Riccardo; Marcon, Francesca

2015-02-01

The influence of DNA repair capacity, plasma nutrients and tobacco smoke exposure on DNA methylation was investigated in blood cells of twenty-one couples of monozygotic twins with discordant smoking habits. All study subjects had previously been characterized for mutagen sensitivity with challenge assays with ionizing radiation in peripheral blood lymphocytes. Plasma levels of folic acid, vitamin B12 and homocysteine were also available from a previous investigation. In this work DNA methylation in the promoter region of a panel of ten genes involved in cell cycle control, differentiation, apoptosis and DNA repair (p16, FHIT, RAR, CDH1, DAPK1, hTERT, RASSF1A, MGMT, BRCA1 and PALB2) was assessed in the same batches of cells isolated for previous studies, using the methylation-sensitive high-resolution melting technique. Fairly similar profiles of gene promoter methylation were observed within co-twins compared to unrelated subjects (p= 1.23 × 10(-7)), with no significant difference related to smoking habits (p = 0.23). In a regression analysis the methylation index of study subjects, used as synthetic descriptor of overall promoter methylation, displayed a significant inverse correlation with radiation-induced micronuclei (p = 0.021) and plasma folic acid level (p = 0.007) both in smokers and in non-smokers. The observed association between repair of radiation-induced DNA damage and promoter methylation suggests the involvement of the DNA repair machinery in DNA modification. Data also highlight the possible modulating effect of folate deficiency on DNA methylation and the strong influence of familiarity on the individual epigenetic profile. Copyright © 2015 Elsevier B.V. All rights reserved.

Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

OpenAIRE

Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

2015-01-01

Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-l...

The preliminary study on the inductory signal triggering the error-prone DNA repair function in mammalian cells

International Nuclear Information System (INIS)

Su Zaozhong; Luo Zuyu

1989-01-01

The nature of the signal triggering error-prone DNA repair function in mammalian cells was studied from two notions: (1) Does the inducing signal result from the direct hitting the cellular targets by DNA-damaging agents? (2) Is inhibition of DNA replication a prerequisite condition for the triggering effect? Thus, the ultraviolet (UV)-irradiated exogenous DNAs were introduced into human and rat cells by transfection. The results showed that this transfection was able to induce the error-prone repair as efficient as direct UV-irradiation to cells. Moreover, the two inductory treaetments expressed similar kinetics and dose-responses. No matter whether the introduced DNAs initiated replication, they exhibited the incuctory activity. Therefore, it can be considered that DNA lesions itself, not the direct interaction of DNA-damaging agents with specific cellular targets, serve as a triggering signal for the inductory process. Inhibition of DNA replication is not a prerequisite for the inductory signal

Error-free 320 Gb/s simultaneous add-drop multiplexing

DEFF Research Database (Denmark)

Mulvad, Hans Christian Hansen; Oxenløwe, Leif Katsuo; Clausen, Anders

2007-01-01

We report on the first demonstration of error-free time-division add-drop multiplexing at 320 Gb/s. The add- and drop-operations are performed simultaneously in a non-linear optical loop mirror with only 100 m of highly non-linear fibre....

The effect of low radiation doses on DNA repair processes

International Nuclear Information System (INIS)

Tuschl, H.

1978-08-01

Error free DNA repair processes are an important preprequisite for the maintenance of genetic integrity of cells. They are of special importance for persons therapeutically or occupationally exposed to radiation. Therefore the effect of radiation therapy and elevated natural background radiation on unscheduled DNA synthesis was tested in peripheral lymphocytes of exposed persons. Both, autoradiographic studies of unscheduled DNA synthesis and measurement of 3 H-thymidine uptake into double stranded and single-strand containing DNA fractions revealed an increase of capacity for DNA repair. (author)

Error amplification to promote motor learning and motivation in therapy robotics.

Science.gov (United States)

Shirzad, Navid; Van der Loos, H F Machiel

2012-01-01

To study the effects of different feedback error amplification methods on a subject's upper-limb motor learning and affect during a point-to-point reaching exercise, we developed a real-time controller for a robotic manipulandum. The reaching environment was visually distorted by implementing a thirty degrees rotation between the coordinate systems of the robot's end-effector and the visual display. Feedback error amplification was provided to subjects as they trained to learn reaching within the visually rotated environment. Error amplification was provided either visually or through both haptic and visual means, each method with two different amplification gains. Subjects' performance (i.e., trajectory error) and self-reports to a questionnaire were used to study the speed and amount of adaptation promoted by each error amplification method and subjects' emotional changes. We found that providing haptic and visual feedback promotes faster adaptation to the distortion and increases subjects' satisfaction with the task, leading to a higher level of attentiveness during the exercise. This finding can be used to design a novel exercise regimen, where alternating between error amplification methods is used to both increase a subject's motor learning and maintain a minimum level of motivational engagement in the exercise. In future experiments, we will test whether such exercise methods will lead to a faster learning time and greater motivation to pursue a therapy exercise regimen.

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

Science.gov (United States)

Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

2016-02-01

Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

Science.gov (United States)

Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

2016-01-01

Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

SCAI promotes DNA double-strand break repair in distinct chromosomal contexts

DEFF Research Database (Denmark)

Hansen, Rebecca Kring; Mund, Andreas; Poulsen, Sara Lund

2016-01-01

cell invasion) as a 53BP1-interacting chromatin-associated protein that promotes the functionality of several DSB repair pathways in mammalian cells. SCAI undergoes prominent enrichment at DSB sites through dual mechanisms involving 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1...... in repressive chromatin environments. Moreover, we establish an important role of SCAI in meiotic recombination, as SCAI deficiency in mice leads to germ cell loss and subfertility associated with impaired retention of the DMC1 recombinase on meiotic chromosomes. Collectively, our findings uncover SCAI...... as a physiologically important component of both NHEJ- and HR-mediated pathways that potentiates DSB repair efficiency in specific chromatin contexts....

FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.

Science.gov (United States)

Liu, Ting; Ghosal, Gargi; Yuan, Jingsong; Chen, Junjie; Huang, Jun

2010-08-06

Fanconi anemia (FA) is caused by mutations in 13 Fanc genes and renders cells hypersensitive to DNA interstrand cross-linking (ICL) agents. A central event in the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex. Here, we characterize a previously unrecognized nuclease, Fanconi anemia-associated nuclease 1 (FAN1), that promotes ICL repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex. Thus, the mono-ubiquitylated ID complex recruits the downstream repair protein FAN1 and facilitates the repair of DNA interstrand cross-links.

Modes of DNA repair and replication

International Nuclear Information System (INIS)

Hanawalt, P.; Kondo, S.

1979-01-01

Modes of DNA repair and replication require close coordination as well as some overlap of enzyme functions. Some classes of recovery deficient mutants may have defects in replication rather than repair modes. Lesions such as the pyrimidine dimers produced by ultraviolet light irradiation are the blocks to normal DNA replication in vivo and in vitro. The DNA synthesis by the DNA polymerase 1 of E. coli is blocked at one nucleotide away from the dimerized pyrimidines in template strands. Thus, some DNA polymerases seem to be unable to incorporate nucleotides opposite to the non-pairing lesions in template DNA strands. The lesions in template DNA strands may block the sequential addition of nucleotides in the synthesis of daughter strands. Normal replication utilizes a constitutive ''error-free'' mode that copies DNA templates with high fidelity, but which may be totally blocked at a lesion that obscures the appropriate base pairing specificity. It might be expected that modified replication system exhibits generally high error frequency. The error rate of DNA polymerases may be controlled by the degree of phosphorylation of the enzyme. Inducible SOS system is controlled by recA genes that also control the pathways for recombination. It is possible that SOS system involves some process other than the modification of a blocked replication apparatus to permit error-prone transdimer synthesis. (Yamashita, S.)

Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

Science.gov (United States)

Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

2012-09-01

UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

Mycobacteria exploit three genetically distinct DNA double-strand break repair pathways.

Science.gov (United States)

Gupta, Richa; Barkan, Daniel; Redelman-Sidi, Gil; Shuman, Stewart; Glickman, Michael S

2011-01-01

Bacterial pathogens rely on their DNA repair pathways to resist genomic damage inflicted by the host. DNA double-strand breaks (DSBs) are especially threatening to bacterial viability. DSB repair by homologous recombination (HR) requires nucleases that resect DSB ends and a strand exchange protein that facilitates homology search. RecBCD and RecA perform these functions in Escherichia coli and constitute the major pathway of error-free DSB repair. Mycobacteria, including the human pathogen M. tuberculosis, elaborate an additional error-prone pathway of DSB repair via non-homologous end-joining (NHEJ) catalysed by Ku and DNA ligase D (LigD). Little is known about the relative contributions of HR and NHEJ to mycobacterial chromosome repair, the factors that dictate pathway choice, or the existence of additional DSB repair pathways. Here we demonstrate that Mycobacterium smegmatis has three DSB repair pathway options: HR, NHEJ and a novel mechanism of single-strand annealing (SSA). Inactivation of NHEJ or SSA is compensated by elevated HR. We find that mycobacterial RecBCD does not participate in HR or confer resistance to ionizing radiation (IR), but is required for the RecA-independent SSA pathway. In contrast, the mycobacterial helicase-nuclease AdnAB participates in the RecA-dependent HR pathway, and is a major determinant of resistance to IR and oxidative DNA damage. These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase-nuclease machines to distinct repair pathways. © 2010 Blackwell Publishing Ltd.

The effects of field errors on low-gain free-electron lasers

International Nuclear Information System (INIS)

Esarey, E.; Tang, C.M.; Marable, W.P.

1991-01-01

This paper reports on the effects of random wiggler magnetic field errors on low-gain free-electron lasers that are examined analytically and numerically through the use of ensemble averaging techniques. Wiggler field errors perturb the electron beam as it propagates and lead to a random walk of the beam centroid δx, variations in the axial beam energy δ γz and deviations in the relative phase of the electrons in the ponderomotive wave δψ. In principle, the random walk may be kept as small as desired through the use of transverse focusing and beam steering. Transverse focusing of the electron beam is shown to be ineffective in reducing the phase deviation. Furthermore, it is shown that beam steering at the wiggler entrance reduces the average phase deviation at the end of the wiggler by 1/3. The effect of the field errors (via the phase deviation) on the gain in the low-gain regime is calculated. To avoid significant reduction in gain it is necessary for the phase deviation to be small compared to 2π. The detrimental effects of wiggler errors on low-gain free-electron lasers may be reduced by arranging the magnet poles in an optimal ordering such that the magnitude of the phase deviation is minimized

Corpus-Based Websites to Promote Learner Autonomy in Correcting Writing Collocation Errors

Directory of Open Access Journals (Sweden)

Pham Thuy Dung

2016-12-01

Full Text Available The recent yet powerful emergence of E-learning and using online resources in learning EFL (English as a Foreign Language has helped promote learner autonomy in language acquisition including self-correcting their mistakes. This pilot study despite conducted on a modest sample of 25 second year students majoring in Business English at Hanoi Foreign Trade University is an initial attempt to investigate the feasibility of using corpus-based websites to promote learner autonomy in correcting collocation errors in EFL writing. The data is collected using a pre-questionnaire and a post-interview aiming to find out the participants’ change in belief and attitude toward learner autonomy in collocation errors in writing, the extent of their success in using the corpus-based websites to self-correct the errors and the change in their confidence in self-correcting the errors using the websites. The findings show that a significant majority of students have shifted their belief and attitude toward a more autonomous mode of learning, enjoyed a fair success of using the websites to self-correct the errors and become more confident. The study also yields an implication that a face-to-face training of how to use these online tools is vital to the later confidence and success of the learners

UV-inducible DNA repair in Acinetobacter calcoaceticus

International Nuclear Information System (INIS)

Berenstein, D.

1987-01-01

Bacterial mutation frequency after UV irradiation and phage mutation frequency under conditions of W-reactivation were determined in A. calcoaceticus. With the exception of streptomycin resistance, there was no increase in the frequency of the assayed markers above the background level. The increased survival of phage during W-reactivation was not followed by an increase in the frequency of mutation from turbid to clear plaque formers among phage survivors. The findings suggested that the UV-inducible repair pathway in A. calcoaceticus was error free. Post-irradiation incubation of UV-treated culture before phage infection resulted in a further increase of W-reactivation. As chloramphenicol inhibited this response, it was concluded that de novo protein synthesis was involved in the UV-inducible repair pathway in A. calcoaceticus. (Auth.)

Using Authentic Medication Errors to Promote Pharmacy Student Critical Thinking and Active Learning

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Reza Karimi

2018-01-01

Full Text Available Objective: To promote first year (P1 pharmacy students’ awareness of medication error prevention and to support student learning in biomedical and pharmaceutical sciences. Innovation: A novel curricular activity was created and referred to as “Medication Errors and Sciences Applications (MESA”. The MESA activity encouraged discussions of patient safety among students and faculty to link medication errors to biomedical and pharmaceutical sciences, which ultimately reinforced student learning in P1 curricular topics.   Critical Analysis: Three P1 cohorts implemented the MESA activity and approximately 75% of students from each cohort completed a reliable assessment instrument. Each P1 cohort had at least 14 student teams who generated professional reports analyzing authentic medication errors. The quantitative assessment results indicated that 70-85% of students believed that the MESA activity improved student learning in biomedical and pharmaceutical sciences. More than 95% of students agreed that the MESA activity introduced them to medication errors. Approximately 90% of students agreed that the MESA activity integrated the knowledge and skills they developed through the P1 curriculum, promoted active learning and critical thinking, and encouraged students to be self-directed learners. Furthermore, our data indicated that approximately 90% of students stated that the achievement of Bloom’s taxonomy's six learning objectives was promoted by completing the MESA activity. Next Steps: Pharmacy students’ awareness of medication errors is a critical component of pharmacy education, which pharmacy educators can integrate with biomedical and pharmaceutical sciences to enhance student learning in the P1 year. Treatment of Human Subjects: IRB exemption granted   Type: Note License: CC BY

EGR1 induces tenogenic differentiation of tendon stem cells and promotes rabbit rotator cuff repair.

Science.gov (United States)

Tao, Xu; Liu, Junpeng; Chen, Lei; Zhou, You; Tang, Kanglai

2015-01-01

The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries. © 2015 S. Karger AG, Basel.

EGR1 Induces Tenogenic Differentiation of Tendon Stem Cells and Promotes Rabbit Rotator Cuff Repair

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Xu Tao

2015-01-01

Full Text Available Background/Aims: The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1 in the differentiation of tendon stem cells (TSCs and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Methods: Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. Results: EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. Conclusion: EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries.

CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer.

Science.gov (United States)

Stefansson, Olafur Andri; Hermanowicz, Stefan; van der Horst, Jasper; Hilmarsdottir, Holmfridur; Staszczak, Zuzanna; Jonasson, Jon Gunnlaugur; Tryggvadottir, Laufey; Gudjonsson, Thorkell; Sigurdsson, Stefan

2017-07-05

DNA repair of alkylation damage is defective in various cancers. This occurs through somatically acquired inactivation of the MGMT gene in various cancer types, including breast cancers. In addition to MGMT, the two E. coli AlkB homologs ALKBH2 and ALKBH3 have also been linked to direct reversal of alkylation damage. However, it is currently unknown whether ALKBH2 or ALKBH3 are found inactivated in cancer. Methylome datasets (GSE52865, GSE20713, GSE69914), available through Omnibus, were used to determine whether ALKBH2 or ALKBH3 are found inactivated by CpG promoter methylation. TCGA dataset enabled us to then assess the impact of CpG promoter methylation on mRNA expression for both ALKBH2 and ALKBH3. DNA methylation analysis for the ALKBH3 promoter region was carried out by pyrosequencing (PyroMark Q24) in 265 primary breast tumours and 30 proximal normal breast tissue samples along with 8 breast-derived cell lines. ALKBH3 mRNA and protein expression were analysed in cell lines using RT-PCR and Western blotting, respectively. DNA alkylation damage assay was carried out in cell lines based on immunofluorescence and confocal imaging. Data on clinical parameters and survival outcomes in patients were obtained and assessed in relation to ALKBH3 promoter methylation. The ALKBH3 gene, but not ALKBH2, undergoes CpG promoter methylation and transcriptional silencing in breast cancer. We developed a quantitative alkylation DNA damage assay based on immunofluorescence and confocal imaging revealing higher levels of alkylation damage in association with epigenetic inactivation of the ALKBH3 gene (P = 0.029). In our cohort of 265 primary breast cancer, we found 72 cases showing aberrantly high CpG promoter methylation over the ALKBH3 promoter (27%; 72 out of 265). We further show that increasingly higher degree of ALKBH3 promoter methylation is associated with reduced breast-cancer specific survival times in patients. In this analysis, ALKBH3 promoter methylation at >20

Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation

International Nuclear Information System (INIS)

Taioli, Emanuela; Ragin, Camille; Wang, Xiao-hong; Chen, Jiangying; Langevin, Scott M; Brown, Ashley R; Gollin, Susanne M; Garte, Seymour; Sobol, Robert W

2009-01-01

Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer. The promoter methylation status of the DNA repair gene MGMT and the tumor suppressor genes CDKN2A and RASSF1 were evaluated by methylation-specific PCR in 88 primary oral and pharyngeal tumors and correlated with survival and tumor recurrence. Quantitative MGMT methylation was also assessed. 29.6% of the tumors presented with MGMT methylation, 11.5% with CDKN2A methylation and 12.1% with RASSF1 methylation. MGMT promoter methylation was significantly associated with poorer overall and disease-free survival. No differences in methylation status of MGMT and RASSF1 with HPV infection, smoking or drinking habits were observed. A significant inverse trend with the amount of MGMT methylation and overall and disease-free survival was observed (p trend = 0.002 and 0.001 respectively). These results implicate MGMT promoter methylation as a possible biomarker for oral and pharyngeal cancer prognosis. The critical role of MGMT in DNA repair suggests that defective DNA repair may be correlative in the observed association between MGMT promoter methylation and tumor recurrence. Follow-up studies should include further quantitative MSP-PCR measurement, global methylation profiling and detailed analysis of downstream DNA repair genes regulated by promoter methylation

Threats to repair injury caused by judicial errors and criminal damage

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Muntean Vasilisa

2017-12-01

Full Text Available The grounds for the occurrence of punitive damages are related to the illicit actions of the persons with responsibilities in the courts and the criminal prosecution bodies. In order to provide protection against such unfair situations, there are a number of legal guarantees. The legislator has highlighted both the specific circle of reasons (illegal detention, unlawful criminal prosecution, unlawful sentencing, etc. necessary to ensure that the damage caused to the person can be repaired, as well as the circle of conditions for the right to reparation (the acquittal, the order for termination of the criminal proceedings or for the prosecution, etc.. The reparation of the damage caused by judicial and criminal prosecution errors arises at the time when the act whereby the person was convicted or illegally arrested, ie at the time when the rehabilitation act became irrevocable, was found to be illegal.

[Effect of simvastatin on inducing endothelial progenitor cells homing and promoting bone defect repair].

Science.gov (United States)

Song, Quansheng; Wang, Lingying; Zhu, Jinglin; Han, Xiaoguang; Li, Xu; Yang, Yanlin; Sun, Yan; Song, Chunli

2010-09-01

To investigate the effect of simvastatin on inducing endothelial progenitor cells (EPCs) homing and promoting bone defect repair, and to explore the mechanism of local implanting simvastatin in promoting bone formation. Simvastatin (50 mg) compounded with polylactic acid (PLA, 200 mg) or only PLA (200 mg) was dissolved in acetone (1 mL) to prepare implanted materials (Simvastatin-PLA material, PLA material). EPCs were harvested from bone marrow of 2 male rabbits and cultured with M199; after identified by immunohistochemistry, the cell suspension of EPCs at the 3rd generation (2 x 10(6) cells/mL) was prepared and transplanted into 12 female rabbits through auricular veins (2 mL). After 3 days, the models of cranial defect with 15 cm diameter were made in the 12 female rabbits. And the defects were repaired with Simvastatin-PLA materials (experimental group, n=6) and PLA materials (control group, n=6), respectively. The bone repair was observed after 8 weeks of operation by gross appearance, X-ray film, and histology; gelatin-ink perfusion and HE staining were used to show the new vessels formation in the defect. Fluorescence in situ hybridization (FISH) was performed to show the EPCs homing at the defect site. All experimental animals of 2 groups survived to the end of the experiment. After 8 weeks in experimental group, new bone formation was observed in the bone defect by gross and histology, and an irregular, hyperdense shadow by X-ray film; no similar changes were observed in control group. FISH showed that the male EPC containing Y chromosome was found in the wall of new vessels in the defect of experimental group, while no male EPC containing Y chromosome was found in control group. The percentage of new bone formation in defect area was 91.63% +/- 4.07% in experimental group and 59.45% +/- 5.43% in control group, showing significant difference (P < 0.05). Simvastatin can promote bone defect repair, and its mechanism is probably associated with inducing EPCs

Separable and Error-Free Reversible Data Hiding in Encrypted Image with High Payload

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Zhaoxia Yin

2014-01-01

Full Text Available This paper proposes a separable reversible data-hiding scheme in encrypted image which offers high payload and error-free data extraction. The cover image is partitioned into nonoverlapping blocks and multigranularity encryption is applied to obtain the encrypted image. The data hider preprocesses the encrypted image and randomly selects two basic pixels in each block to estimate the block smoothness and indicate peak points. Additional data are embedded into blocks in the sorted order of block smoothness by using local histogram shifting under the guidance of the peak points. At the receiver side, image decryption and data extraction are separable and can be free to choose. Compared to previous approaches, the proposed method is simpler in calculation while offering better performance: larger payload, better embedding quality, and error-free data extraction, as well as image recovery.

Mesenchymal stem cells overexpressing Ihh promote bone repair.

Science.gov (United States)

Zou, Shasha; Chen, Tingting; Wang, Yanan; Tian, Ruhui; Zhang, Lingling; Song, Pingping; Yang, Shi; Zhu, Yong; Guo, Xizhi; Huang, Yiran; Li, Zheng; Kan, Lixin; Hu, Hongliang

2014-10-28

Indian hedgehog (Ihh) signaling pathway is known to play key roles in various aspects of normal endochondral bone development. This study tested the potential roles of high Ihh signaling in the context of injury-induced bone regeneration. A rabbit tibia defect model was established to test the effects of the implant of Ihh/mesenchymal stem cells (MSCs)/scaffold complex. Computed tomography (CT), gross observation, and standard histological and immunohistological techniques were used to evaluate the effectiveness of the treatment. In vitro studies with MSCs and C3H10T1/2 cells were also employed to further understand the cellular and molecular mechanisms. We found that the implanted Ihh/MSCs/scaffold complex promoted bone repair. Consistently, in vitro study found that Ihh induced the upregulation of chondrocytic, osteogenic, and vascular cell markers, both in C3H10T1/2 cells and MSCs. Our study has demonstrated that high Ihh signaling in a complex with MSCs enhanced bone regeneration effectively in a clinically relevant acute injury model. Even though the exact underlying mechanisms are still far from clear, our primary data suggested that enhanced chondrogenesis, osteogenesis, and angiogenesis of MSCs at least partially contribute to the process. This study not only has implications for basic research of MSCs and Ihh signaling pathway but also points to the possibility of direct application of this specific paradigm to clinical bone repair.

Implication of the E. coli K12 uvrA and recA genes in the repair of 8-methoxypsoralen-induced mono adducts and crosslinks on plasmid DNA; Implicacion de los genes uvrA de E. coli K12 en la reparacion de monoaductos y entrecruzamien tos inducidos en DNA plasmidico por 8-metoxipso raleno mas luz ultravioleta A

Energy Technology Data Exchange (ETDEWEB)

Paramio, J M; Bauluz, C; Vidania, R de

1986-07-01

Genotoxicity of psoralen damages on plasmid DNA has been studied. pBR322 DNA was randomly modified with several concentrations of 8-methoxypsoralen plus 365 nm-UV light. After transformation into E. coli strains (wild-type, uvrA and recA) plasmid survival and mutagenesis were analyzed. To study the influence of the SOS response on plasmid recovery, preirradiation of the cells was performed. In absence of cell preirradiation, crosslinks were not repaired in any strain. Mono adducts were also lethal but in part removed by the excision-repair pathway. Preirradiation of the cells significantly. increased plasmid recovery in recA+ celia. In uvrA- only the mutagenic pathway seemed to be involved in the repair of the damaged DNA. Wild type strain showed the highest increase in plasmid survival, involving the repair of mono adducts and some fraction of crosslinks mainly through an error-free repair pathway. This suggests an enhancement of the excision repair promoted by the induction of SOS functions. (Author) 32 refs.

Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

Directory of Open Access Journals (Sweden)

Jianfeng Zhang

2015-06-01

Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.

Science.gov (United States)

Berghoff, Stefan A; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M; Saher, Gesine

2017-01-24

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.

The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.

Science.gov (United States)

Knipscheer, Puck; Räschle, Markus; Smogorzewska, Agata; Enoiu, Milica; Ho, The Vinh; Schärer, Orlando D; Elledge, Stephen J; Walter, Johannes C

2009-12-18

Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.

Inducible error-prone repair in B. subtilis. Progress report, September 1, 1981-April 30, 1985

Energy Technology Data Exchange (ETDEWEB)

Yasbin, R.E.

1984-12-01

The objective was to investigate and elucidate the molecular mechanisms responsible for (i) inducible DNA repair system(s) and for (ii) error-prone repair in the gram positive bacterium Bacillus subtilis. The SOS-like system of Bacillus subtilis consists of several coordinately induced phenomena (e.g., cellular filamentation, prophage induction, and Weigle reactivation of uv-damaged bacteriophage) which are expressed after cellular insult such as DNA damage or inhibition of DNA replication. Mutagenesis of the bacterial chromosome and the development or maintenance of competence also appear to be involved in the SOS-like response in this bacterium. The genetic characterization of the SOS-like system has involved an analysis of (i) the effects of various DNA repair mutations on the expression of inducible phenomena and (ii) the tsi-23 mutation, which renders host strains thermally inducible for each of the SOS-like functions. Bacterial filamentation was unaffected by any of the DNA repair mutations studied. In contrast, the induction of prophage after thermal or uv pretreatment was abolished in strains carrying the recE4, recA1, recB2, or recG13 mutation. Weigle reactivation was also inhibited by the recE4, recA1, recB2, or recG13 mutation, whereas levels of W-reactivation were lower in strains which carried the uvrA42, polA5, or rec-961 mutation than in the DNA repair-proficient strain. Strains which carried the recE4 allele were incapable of chromosomal DNA-mediated transformation, and the frequency of this event was decreased in strains carrying the recA1, recB2, or tsi-23 mutation. Plasmid DNA transformation efficiency was decreased only in strains carrying the tsi-23 mutation in addition to the recE4, recA1, recB2, mutation. The results indicate that the SOS-like or SOB system of B. subtilis is regulated at different levels by two or more gene products.

HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis

DEFF Research Database (Denmark)

Adelman, Carrie A.; Lolo, Rafal L.; Birkbak, Nicolai Juul

2013-01-01

Repair of interstrand crosslinks (ICLs) requires the coordinated action of the intra-S-phase checkpoint and the Fanconi anaemia pathway, which promote ICL incision, translesion synthesis and homologous recombination (reviewed in refs 1, 2). Previous studies have implicated the 3'-5' superfamily 2......, phenotype than the null, indicative of haploinsufficiency. We establish that HELQ interacts directly with the RAD51 paralogue complex BCDX2 and functions in parallel to the Fanconi anaemia pathway to promote efficient homologous recombination at damaged replication forks. Thus, our results reveal a critical...

Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea.

Science.gov (United States)

Fukushima, Takao; Katayama, Yoichi; Watanabe, Takao; Yoshino, Atsuo; Ogino, Akiyoshi; Ohta, Takashi; Komine, Chiaki

2005-02-15

In certain types of human cancers, transcriptional inactivation of hMLH1 by promoter hypermethylation plays a causal role in the loss of mismatch repair functions that modulate cytotoxic pathways in response to DNA-damaging agents. The aim of the present study was to investigate the role of promoter methylation of the hMLH1 gene in malignant astrocytomas. We examined the hMLH1 promoter methylation in a homogeneous cohort of patients with 41 malignant astrocytomas treated by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea chemotherapy in combination with radiation and interferon therapy, and assessed the correlation of such methylation with clinical outcome. hMLH1 promoter methylation was found in 6 (15%) of the 41 newly diagnosed malignant astrocytomas. Hypermethylation of the hMLH1 promoter corresponded closely with a loss of immunohistochemical staining for hMLH1 protein (P = 0.0013). Patients with hMLH1-methylated tumors displayed a greater chance of responding to adjuvant therapy as compared with those with hMLH1-unmethylated tumors (P = 0.0150). The presence of hMLH1 hypermethylation was significantly associated with a longer progression-free survival on both univariate analysis (P = 0.0340) and multivariate analysis (P = 0.0161). The present study identified hMLH1 methylation status as a predictor of the clinical response of malignant astrocytomas to chloroethylnitrosourea-based adjuvant therapy. The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis.

Enhancement of excision-repair efficiency by conditioned medium from density-inhibited cultures in V79 Chinese hamster cells

International Nuclear Information System (INIS)

Nakano, S.

1979-01-01

Conditioned medium from density-inhibited V79 Chinese hamster cell cultures, given as a post-treatment to UV-irradiated homologous cells, was demonstrated to reduce the lethal action of ultraviolet light by temporarily blocking DNA replication. Since the increased survival was not affected by various nontoxic concentrations of caffeine, such protective effect would be attributable to the prolonged intervention of excision repair before DNA replication during the post-treatment period. The influence of conditioned medium on the UV-induced mutation at the ouabain-resistance locus was also examined and a significant decrease in mutation frequecy was noted. The observed reduction in killing and mutation as a result of post-incubation in conditioned medium, which delays DNA replication, would be interpreted as evidence that conditioned medium provides a longer period of time for an error-free excision-repair process, leaving lesion in DNA available for error-prone post-replication repair. (Auth.)

Emergency repair of upper extremity large soft tissue and vascular injuries with flow-through anterolateral thigh free flaps.

Science.gov (United States)

Zhan, Yi; Fu, Guo; Zhou, Xiang; He, Bo; Yan, Li-Wei; Zhu, Qing-Tang; Gu, Li-Qiang; Liu, Xiao-Lin; Qi, Jian

2017-12-01

Complex extremity trauma commonly involves both soft tissue and vascular injuries. Traditional two-stage surgical repair may delay rehabilitation and functional recovery, as well as increase the risk of infections. We report a single-stage reconstructive surgical method that repairs soft tissue defects and vascular injuries with flow-through free flaps to improve functional outcomes. Between March 2010 and December 2016 in our hospital, 5 patients with severe upper extremity trauma received single-stage reconstructive surgery, in which a flow-through anterolateral thigh free flap was applied to repair soft tissue defects and vascular injuries simultaneously. Cases of injured artery were reconstructed with the distal trunk of the descending branch of the lateral circumflex femoral artery. A segment of adjacent vein was used if there was a second artery injury. Patients were followed to evaluate their functional recoveries, and received computed tomography angiography examinations to assess peripheral circulation. Two patients had post-operative thumb necrosis; one required amputation, and the other was healed after debridement and abdominal pedicle flap repair. The other 3 patients had no major complications (infection, necrosis) to the recipient or donor sites after surgery. All the patients had achieved satisfactory functional recovery by the end of the follow-up period. Computed tomography angiography showed adequate circulation in the peripheral vessels. The success of these cases shows that one-step reconstructive surgery with flow-through anterolateral thigh free flaps can be a safe and effective treatment option for patients with complex upper extremity trauma with soft tissue defects and vascular injuries. Copyright © 2017. Published by Elsevier Ltd.

The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate

International Nuclear Information System (INIS)

Bajinskis, Ainars; Olsson, Gunilla; Harms-Ringdahl, Mats

2012-01-01

The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO 3 ). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure.

The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate.

Science.gov (United States)

Bajinskis, Ainars; Olsson, Gunilla; Harms-Ringdahl, Mats

2012-03-01

The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO(3)). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure. Copyright © 2011 Elsevier B.V. All rights reserved.

The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate

Energy Technology Data Exchange (ETDEWEB)

Bajinskis, Ainars, E-mail: ainars.bajinskis@gmt.su.se [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden); Olsson, Gunilla; Harms-Ringdahl, Mats [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden)

2012-03-01

The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO{sub 3}). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure.

Role of DNA lesions and repair in the transformation of human cells

International Nuclear Information System (INIS)

Maher, V.M.; McCormick, J.J.

1987-01-01

Results of studies on the transformation of diploid human fibroblasts in culture into tumor-forming cells by exposure to chemical carcinogens or radiation indicate that such transformation is multi-stepped process that at least one step, acquisition of anchorage independence, occurs as a mutagenic event. Studies comparing normal-repairing human cells with DNA repair-deficient cells, such as those derived from cancer-prone xeroderma pigmentosum patients, indicate that excision repair in human fibroblasts is essentially an error-free process that the ability to excise potentially cytotoxic, mutagenic, or transforming lesions induced DNA by carcinogens determines their ultimate biological consequences. Cells deficient in excision repair are abnormally sensitive to these agents. Studies with cells treated at various times in the cell cycle show that there is a certain limited amount of time available for DNA repair between the initial exposure and the onset of the cellular event responsible for mutation induction and transformation to anchorage independence. The data suggest that DNA replication on a template containing unexcised lesions (photoproducts, adducts) is the critical event

Microwave-assisted silica-promoted solvent-free synthesis of ...

Indian Academy of Sciences (India)

method using microwave irradiation with an excellent yield. The newly ... Table 1. Silica promoted microwave-assisted solvent-free synthesis of quinazolinone ... Time (min). Yield (%)a ..... thanks SC/ST cell of Bangalore University for research.

Ergodic Capacity Analysis of Free-Space Optical Links with Nonzero Boresight Pointing Errors

KAUST Repository

Ansari, Imran Shafique; Alouini, Mohamed-Slim; Cheng, Julian

2015-01-01

A unified capacity analysis of a free-space optical (FSO) link that accounts for nonzero boresight pointing errors and both types of detection techniques (i.e. intensity modulation/ direct detection as well as heterodyne detection) is addressed

Radiobiological significance of DNA repair

International Nuclear Information System (INIS)

Kuzin, A.M.

1978-01-01

A short outline is given on the history of the problem relating to the repair of radiation injuries, specifically its molecular mechanisms. The most urgent problems which currently confront the researchers are noted. This is a further study on the role of DNA repair in post-radiation recovery, search for ways to activate and suppress DNA repair, investigations into the activity balance of various repair enzymes as well as the problem of errors in the structure of repairing DNA. An important role is attached to the investigations of DNA repair in solving a number of practical problems

Free radical scavenging and the expression of potentially lethal damage in X-irradiated repair-deficient Escherichia coli

International Nuclear Information System (INIS)

Billen, D.

1987-01-01

When cells are exposed to ionizing radiation, they suffer lethal damage (LD), potentially lethal damage (PLD), and sublethal damage (SLD). All three forms of damage may be caused by direct or indirect radiation action or by the interaction of indirect radiation products with direct DNA damage. In this report I examine the expression of LD and PLD caused by the indirect action of X rays in isogenic, repair-deficient Escherichia coli. The radiosensitivity of a recA mutant, deficient both in pre- and post replication recombination repair and SOS induction (inducible error-prone repair), was compared to that of a recB mutant which is recombination deficient but SOS proficient and to a previously studied DNA polymerase 1-deficient mutant (polA) which lacks the excision repair pathway. Indirect damage by water radicals (primarily OH radicals) was circumvented by the presence of 2 M glycerol during irradiation. Indirect X-ray damage by water radicals accounts for at least 85% of the PLD found in exposed repair-deficient cells. The DNA polymerase 1-deficient mutant is most sensitive to indirect damage with the order of sensitivity polA1 greater than recB greater than or equal to recA greater than wild type. For the direct effects of X rays the order of sensitivity is recA greater than recB greater than polA1 greater than wild type. The significance of the various repair pathways in mitigating PLD by direct and indirect damage is discussed

Mutagenic DNA repair in Escherichia coli. Pt. 2

International Nuclear Information System (INIS)

Doubleday, O.P.; Bridges, B.A.; Green, M.H.L.

1975-01-01

The photoreversibility of UV-induced mutations to Trp + in strain Escherichia coli WP2 uvr A trp (unable to excise pyrimidine dimers) was lost at different rates during incubation in different media. In Casamino acids medium after a short initial lag, photoreversibility was lost over about one generation time; in minimal medium with tryptophan, photoreversibility persisted for more than two generations; in Casamino acids medium with pantoyl lactone photoreversibility was lost extremely slowly. The rate of loss of photoreversibility was unaffected by UV dose in either Casamino acids medium or in minimal medium. The same eventual number of induced mutants was obtained when cells were incubated for two generations in any of the three media before being transferred to selective plates supplemented with Casamino acids. Thus in each the proportion of cells capable of giving rise to a mutant was the same and only the rate at which these cells did so during post-irradiation growth varied, suggesting that there might be a specific fraction of pyrimidine dimers at a given site capable of initiating a mutagenic repair event, and that the size of this fraction is dose dependent. Segregation experiments have shown that error-prone repair appears to occur once only and is not repeated in subsequent replication cycles, in contrast to (presumed error-free) recombination repair. The results are discussed in the light of current models of UV mutagenesis. (orig.) [de

Evaluation of Cinnamomum osmophloeum Kanehira Extracts on Tyrosinase Suppressor, Wound Repair Promoter, and Antioxidant

Directory of Open Access Journals (Sweden)

Man-Gang Lee

2015-01-01

Full Text Available Cinnamomum osmophloeum Kanehira belongs to the Lauraceae family of Taiwan’s endemic plants. In this study, C. osmophloeum Kanehira extract has shown inhibition of tyrosinase activity on B16-F10 cellular system first. Whether extracts inhibited mushroom tyrosinase activity was tested, and a considerable inhibition of mushroom tyrosinase activity by in vitro assays was presented. Animal experiments of C. osmophloeum Kanehira were carried out by observing animal wound repair, and the extracts had greater wound healing power than the vehicle control group (petroleum jelly with 8% DMSO, w/v. In addition, the antioxidant capacity of C. osmophloeum Kanehira extracts in vitro was evaluated. We measured C. osmophloeum Kanehira extract’s free radical scavenging capability, metal chelating, and reduction power, such as biochemical activity analysis. The results showed that a high concentration of C. osmophloeum Kanehira extract had a significant scavenging capability of free radical, a minor effect of chelating ability, and moderate reducing power. Further exploration of the possible physiological mechanisms and the ingredient components of skincare product for skin-whitening, wound repair, or antioxidative agents are to be done.

Promoting peripheral myelin repair.

Science.gov (United States)

Zhou, Ye; Notterpek, Lucia

2016-09-01

Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

A Human Amnion-Derived Extracellular Matrix-Coated Cell-Free Scaffold for Cartilage Repair: In Vitro and In Vivo Studies.

Science.gov (United States)

Nogami, Makiko; Kimura, Tomoatsu; Seki, Shoji; Matsui, Yoshito; Yoshida, Toshiko; Koike-Soko, Chika; Okabe, Motonori; Motomura, Hiraku; Gejo, Ryuichi; Nikaido, Toshio

2016-04-01

Extracellular matrix (ECM) derived from human amniotic mesenchymal cells (HAMs) has various biological activities. In this study, we developed a novel HAM-derived ECM-coated polylactic-co-glycolic acid (ECM-PLGA) scaffold, examined its property on mesenchymal cells, and investigated its potential as a cell-free scaffold for cartilage repair. ECM-PLGA scaffolds were developed by inoculating HAM on a PLGA. After decellularization by irradiation, accumulated ECM was examined. Exogenous cell growth and differentiation of rat mesenchymal stem cells (MSCs) on the ECM-PLGA were analyzed in vitro by cell attachment/proliferation assay and reverse transcription-polymerase chain reaction. The cell-free ECM-PLGA scaffolds were implanted into osteochondral defects in the trochlear groove of rat knees. After 4, 12, or 24 weeks, the animals were sacrificed and the harvested tissues were examined histologically. The ECM-PLGA contained ECM that mimicked natural amniotic stroma that contains type I collagen, fibronectin, hyaluronic acid, and chondroitin sulfates. The ECM-PLGA showed excellent properties of cell attachment and proliferation. MSCs inoculated on the ECM-PLGA scaffold showed accelerated type II collagen mRNA expression after 3 weeks in culture. The ECM-PLGA implanted into an osteochondral defect in rat knees induced gradual tissue regeneration and resulted in hyaline cartilage repair, which was better than that in the empty control group. These in vitro and in vivo experiments show that the cell-free scaffold composed of HAM-derived ECM and PLGA provides a favorable growth environment for MSCs and facilitates the cartilage repair process. The ECM-PLGA may become a "ready-made" biomaterial for cartilage repair therapy.

Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

Energy Technology Data Exchange (ETDEWEB)

Dong, Hui; Shi, Qiong; Song, Xiufang; Fu, Juanli; Hu, Lihua; Xu, Demei; Su, Chuanyang; Xia, Xiaomin; Song, Erqun; Song, Yang, E-mail: songyangwenrong@hotmail.com

2015-07-01

Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observed phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.

Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

Science.gov (United States)

Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

2015-01-01

Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats. PMID:26487860

Neurotrophin-3 Induces BMP-2 and VEGF Activities and Promotes the Bony Repair of Injured Growth Plate Cartilage and Bone in Rats.

Science.gov (United States)

Su, Yu-Wen; Chung, Rosa; Ruan, Chun-Sheng; Chim, Shek Man; Kuek, Vincent; Dwivedi, Prem P; Hassanshahi, Mohammadhossein; Chen, Ke-Ming; Xie, Yangli; Chen, Lin; Foster, Bruce K; Rosen, Vicki; Zhou, Xin-Fu; Xu, Jiake; Xian, Cory J

2016-06-01

Injured growth plate is often repaired by bony tissue causing bone growth defects, for which the mechanisms remain unclear. Because neurotrophins have been implicated in bone fracture repair, here we investigated their potential roles in growth plate bony repair in rats. After a drill-hole injury was made in the tibial growth plate and bone, increased injury site mRNA expression was observed for neurotrophins NGF, BDNF, NT-3, and NT-4 and their Trk receptors. NT-3 and its receptor TrkC showed the highest induction. NT-3 was localized to repairing cells, whereas TrkC was observed in stromal cells, osteoblasts, and blood vessel cells at the injury site. Moreover, systemic NT-3 immunoneutralization reduced bone volume at injury sites and also reduced vascularization at the injured growth plate, whereas recombinant NT-3 treatment promoted bony repair with elevated levels of mRNA for osteogenic markers and bone morphogenetic protein (BMP-2) and increased vascularization and mRNA for vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 at the injured growth plate. When examined in vitro, NT-3 promoted osteogenesis in rat bone marrow stromal cells, induced Erk1/2 and Akt phosphorylation, and enhanced expression of BMPs (particularly BMP-2) and VEGF in the mineralizing cells. It also induced CD31 and VEGF mRNA in rat primary endothelial cell culture. BMP activity appears critical for NT-3 osteogenic effect in vitro because it can be almost completely abrogated by co-addition of the BMP inhibitor noggin. Consistent with its angiogenic effect in vivo, NT-3 promoted angiogenesis in metatarsal bone explants, an effect abolished by co-treatment with anti-VEGF. This study suggests that NT-3 may be an osteogenic and angiogenic factor upstream of BMP-2 and VEGF in bony repair, and further studies are required to investigate whether NT-3 may be a potential target for preventing growth plate faulty bony repair or for promoting bone fracture healing. © 2016

IPTV multicast with peer-assisted lossy error control

Science.gov (United States)

Li, Zhi; Zhu, Xiaoqing; Begen, Ali C.; Girod, Bernd

2010-07-01

Emerging IPTV technology uses source-specific IP multicast to deliver television programs to end-users. To provide reliable IPTV services over the error-prone DSL access networks, a combination of multicast forward error correction (FEC) and unicast retransmissions is employed to mitigate the impulse noises in DSL links. In existing systems, the retransmission function is provided by the Retransmission Servers sitting at the edge of the core network. In this work, we propose an alternative distributed solution where the burden of packet loss repair is partially shifted to the peer IP set-top boxes. Through Peer-Assisted Repair (PAR) protocol, we demonstrate how the packet repairs can be delivered in a timely, reliable and decentralized manner using the combination of server-peer coordination and redundancy of repairs. We also show that this distributed protocol can be seamlessly integrated with an application-layer source-aware error protection mechanism called forward and retransmitted Systematic Lossy Error Protection (SLEP/SLEPr). Simulations show that this joint PARSLEP/ SLEPr framework not only effectively mitigates the bottleneck experienced by the Retransmission Servers, thus greatly enhancing the scalability of the system, but also efficiently improves the resistance to the impulse noise.

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

Science.gov (United States)

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

2017-12-01

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

Error Modelling for Multi-Sensor Measurements in Infrastructure-Free Indoor Navigation

Directory of Open Access Journals (Sweden)

Laura Ruotsalainen

2018-02-01

Full Text Available The long-term objective of our research is to develop a method for infrastructure-free simultaneous localization and mapping (SLAM and context recognition for tactical situational awareness. Localization will be realized by propagating motion measurements obtained using a monocular camera, a foot-mounted Inertial Measurement Unit (IMU, sonar, and a barometer. Due to the size and weight requirements set by tactical applications, Micro-Electro-Mechanical (MEMS sensors will be used. However, MEMS sensors suffer from biases and drift errors that may substantially decrease the position accuracy. Therefore, sophisticated error modelling and implementation of integration algorithms are key for providing a viable result. Algorithms used for multi-sensor fusion have traditionally been different versions of Kalman filters. However, Kalman filters are based on the assumptions that the state propagation and measurement models are linear with additive Gaussian noise. Neither of the assumptions is correct for tactical applications, especially for dismounted soldiers, or rescue personnel. Therefore, error modelling and implementation of advanced fusion algorithms are essential for providing a viable result. Our approach is to use particle filtering (PF, which is a sophisticated option for integrating measurements emerging from pedestrian motion having non-Gaussian error characteristics. This paper discusses the statistical modelling of the measurement errors from inertial sensors and vision based heading and translation measurements to include the correct error probability density functions (pdf in the particle filter implementation. Then, model fitting is used to verify the pdfs of the measurement errors. Based on the deduced error models of the measurements, particle filtering method is developed to fuse all this information, where the weights of each particle are computed based on the specific models derived. The performance of the developed method is

ATR-p53 restricts homologous recombination in response to replicative stress but does not limit DNA interstrand crosslink repair in lung cancer cells.

Directory of Open Access Journals (Sweden)

Bianca M Sirbu

Full Text Available Homologous recombination (HR is required for the restart of collapsed DNA replication forks and error-free repair of DNA double-strand breaks (DSB. However, unscheduled or hyperactive HR may lead to genomic instability and promote cancer development. The cellular factors that restrict HR processes in mammalian cells are only beginning to be elucidated. The tumor suppressor p53 has been implicated in the suppression of HR though it has remained unclear why p53, as the guardian of the genome, would impair an error-free repair process. Here, we show for the first time that p53 downregulates foci formation of the RAD51 recombinase in response to replicative stress in H1299 lung cancer cells in a manner that is independent of its role as a transcription factor. We find that this downregulation of HR is not only completely dependent on the binding site of p53 with replication protein A but also the ATR/ATM serine 15 phosphorylation site. Genetic analysis suggests that ATR but not ATM kinase modulates p53's function in HR. The suppression of HR by p53 can be bypassed under experimental conditions that cause DSB either directly or indirectly, in line with p53's role as a guardian of the genome. As a result, transactivation-inactive p53 does not compromise the resistance of H1299 cells to the interstrand crosslinking agent mitomycin C. Altogether, our data support a model in which p53 plays an anti-recombinogenic role in the ATR-dependent mammalian replication checkpoint but does not impair a cell's ability to use HR for the removal of DSB induced by cytotoxic agents.

Arab Researchers Promotions of Open Archives and Free

Directory of Open Access Journals (Sweden)

Abd Al-Majid Salih Bu Azza

2006-09-01

Full Text Available A study aiming at measuring the promotion of Arab researches for Open Archives and Free Electronic Journal, contained 60 researches in Sultan Qabus university in Oman, and discovered their opinion about open access resources. It found that 78.8 % of researchers did not publish articles in Free Electronic Journals, and 77.8 % do not aware about the international imitative of Open Access. Also discovered that researchers refuse publishing their articles in e-journals because of electronic articles are not considered in their universities.

Near-Infrared Free-Radical and Free-Radical-Promoted Cationic Photopolymerizations by In-Source Lighting Using Upconverting Glass.

Science.gov (United States)

Kocaarslan, Azra; Tabanli, Sevcan; Eryurek, Gonul; Yagci, Yusuf

2017-11-13

A method is presented for the initiation of free-radical and free-radical-promoted cationic photopolymerizations by in-source lighting in the near-infrared (NIR) region using upconverting glass (UCG). This approach utilizes laser irradiation of UCG at 975 nm in the presence of fluorescein (FL) and pentamethyldiethylene triamine (PMDETA). FL excited by light emitted from the UCG undergoes electron-transfer reactions with PMDETA to form free radicals capable of initiating polymerization of methyl methacrylate. To execute the corresponding free-radical-promoted cationic polymerization of cyclohexene oxide, isobutyl vinyl ether, and N-vinyl carbazole, it was necessary to use FL, dimethyl aniline (DMA), and diphenyliodonium hexafluorophosphate as sensitizer, coinitiator, and oxidant, respectively. Iodonium ions promptly oxidize DMA radicals formed to the corresponding cations. Thus, cationic polymerization with efficiency comparable to the conventional irradiation source was achieved. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas.

Science.gov (United States)

Felsberg, Jörg; Thon, Niklas; Eigenbrod, Sabina; Hentschel, Bettina; Sabel, Michael C; Westphal, Manfred; Schackert, Gabriele; Kreth, Friedrich Wilhelm; Pietsch, Torsten; Löffler, Markus; Weller, Michael; Reifenberger, Guido; Tonn, Jörg C

2011-08-01

Epigenetic silencing of the O(6) -methylguanine-DNA methyltransferase (MGMT) gene promoter is associated with prolonged survival in glioblastoma patients treated with temozolomide (TMZ). We investigated whether glioblastoma recurrence is associated with changes in the promoter methylation status and the expression of MGMT and the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 in pairs of primary and recurrent glioblastomas of 80 patients, including 64 patients treated with radiotherapy and TMZ after the first operation. Among the primary tumors, the MGMT promoter was methylated in 31 patients and unmethylated in 49 patients. In 71 patients (89%), the MGMT promoter methylation status of the primary tumor was retained at recurrence. MGMT promoter methylation, but not MGMT protein expression, was associated with longer progression-free survival, overall survival and postrecurrence survival (PRS). Moreover, PRS was increased under salvage chemotherapy. Investigation of primary and recurrent glioblastomas of 43 patients did not identify promoter methylation in any of the four MMR genes. However, recurrent glioblastomas demonstrated significantly lower MSH2, MSH6 and PMS2 protein expression as detected by immunohistochemistry. In conclusion, reduced expression of MMR proteins, but not changes in MGMT promoter methylation, is characteristic of glioblastomas recurring after the current standards of care. Copyright © 2011 UICC.

Possible error-prone repair of neoplastic transformation induced by fission-spectrum neutrons

Energy Technology Data Exchange (ETDEWEB)

Hill, C K; Han, A; Elkind, M M

1948-01-01

An examination was made of the effect of fission-spectrum neutrons from the JANUS reactor at Argonne National Laboratory, delivered either as acute or protracted irradiation, on the incidence of neoplastic transformation in the C3H 10T1/2 mouse embryo cell line. Acute exposures were delivered at 10-38 cGy min/sup -1/, protracted exposures at 0.086 or 0.43 cGy min/sup -1/. The total doses for both ranged from 2.4 to 350 cGy. In the low dose region (2.4-80 cGy), there was a large enhancement in transformation frequency when the neutrons were delivered at the low dose rates compared with the high dose rates, but the survival of the cells was not significantly different between the two exposures conditions. Analysis of the intial parts of the curves shows that the regression line for protracted doses is about 9 times steeper than that for single acute exposures. Finally, the possibility is discussed that an ''error-prone'' repair process may be causing the enhanced transformation frequency by protracted neutron exposures.

Error-Free Text Typing Performance of an Inductive Intra-Oral Tongue Computer Interface for Severely Disabled Individuals.

Science.gov (United States)

Andreasen Struijk, Lotte N S; Bentsen, Bo; Gaihede, Michael; Lontis, Eugen R

2017-11-01

For severely paralyzed individuals, alternative computer interfaces are becoming increasingly essential for everyday life as social and vocational activities are facilitated by information technology and as the environment becomes more automatic and remotely controllable. Tongue computer interfaces have proven to be desirable by the users partly due to their high degree of aesthetic acceptability, but so far the mature systems have shown a relatively low error-free text typing efficiency. This paper evaluated the intra-oral inductive tongue computer interface (ITCI) in its intended use: Error-free text typing in a generally available text editing system, Word. Individuals with tetraplegia and able bodied individuals used the ITCI for typing using a MATLAB interface and for Word typing for 4 to 5 experimental days, and the results showed an average error-free text typing rate in Word of 11.6 correct characters/min across all participants and of 15.5 correct characters/min for participants familiar with tongue piercings. Improvements in typing rates between the sessions suggest that typing ratescan be improved further through long-term use of the ITCI.

Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization.

Science.gov (United States)

Zhao, Zhiwei; Li, Xiaoling; Li, Qing

2017-08-01

Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days. The phosphorylation of Erk1/2 and Akt, and the expression of LC3-II, Beclin 1 and p62 were measured using western blotting. After treatment for 60days, myelination of the injured sciatic nerve was evaluated by MBP immunohistochemical staining and the expression of PMP22, Fibrin and S100 were determined using qRT-PCR and western blotting. In vitro, RSC96 cells were starved for 12h to induce autophagy, and received DMSO, curcumin, PD98059+curcumin, IGF-1+curcumin and BFA1 respectively. The phosphorylation of Erk1/2、Akt and the expression of LC3-II, Beclin 1, p62, PMP22, Fibrin and S100 were measured using western blotting, and the cell apoptosis was detected by flow cytometry. Curcumin could promote injury-induced cell autophagy, remyelination and axon regeneration in sciatic nerve of rats. In vitro, curcumin could accelerate cell autophagy through regulating autophagy related Erk1/2 and Akt pathway, prevent cell apoptosis and promote expression of PMP22 and S100, and reduced deposition of Fibrin in cultured RSC96 SCs. Curcumin could accelerate injured sciatic nerve repair in rats through reducing SCs apoptosis and promoting myelinization. Copyright © 2017. Published by Elsevier Masson SAS.

FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair

Directory of Open Access Journals (Sweden)

Zeina Kais

2016-06-01

Full Text Available BRCA1/2 proteins function in homologous recombination (HR-mediated DNA repair and cooperate with Fanconi anemia (FA proteins to maintain genomic integrity through replication fork stabilization. Loss of BRCA1/2 proteins results in DNA repair deficiency and replicative stress, leading to genomic instability and enhanced sensitivity to DNA-damaging agents. Recent studies have shown that BRCA1/2-deficient tumors upregulate Polθ-mediated alternative end-joining (alt-EJ repair as a survival mechanism. Whether other mechanisms maintain genomic integrity upon loss of BRCA1/2 proteins is currently unknown. Here we show that BRCA1/2-deficient tumors also upregulate FANCD2 activity. FANCD2 is required for fork protection and fork restart in BRCA1/2-deficient tumors. Moreover, FANCD2 promotes Polθ recruitment at sites of damage and alt-EJ repair. Finally, loss of FANCD2 in BRCA1/2-deficient tumors enhances cell death. These results reveal a synthetic lethal relationship between FANCD2 and BRCA1/2, and they identify FANCD2 as a central player orchestrating DNA repair pathway choice at the replication fork.

Fibronectin Extra Domain A Promotes Liver Sinusoid Repair following Hepatectomy.

Directory of Open Access Journals (Sweden)

Bridget Sackey-Aboagye

Full Text Available Liver sinusoidal endothelial cells (LSECs are the main endothelial cells in the liver and are important for maintaining liver homeostasis as well as responding to injury. LSECs express cellular fibronectin containing the alternatively spliced extra domain A (EIIIA-cFN and increase expression of this isoform after liver injury, although its function is not well understood. Here, we examined the role of EIIIA-cFN in liver regeneration following partial hepatectomy. We carried out two-thirds partial hepatectomies in mice lacking EIIIA-cFN and in their wild type littermates, studied liver endothelial cell adhesion on decellularized, EIIIA-cFN-containing matrices and investigated the role of cellular fibronectins in liver endothelial cell tubulogenesis. We found that liver weight recovery following hepatectomy was significantly delayed and that sinusoidal repair was impaired in EIIIA-cFN null mice, especially females, as was the lipid accumulation typical of the post-hepatectomy liver. In vitro, we found that liver endothelial cells were more adhesive to cell-deposited matrices containing the EIIIA domain and that cellular fibronectin enhanced tubulogenesis and vascular cord formation. The integrin α9β1, which specifically binds EIIIA-cFN, promoted tubulogenesis and adhesion of liver endothelial cells to EIIIA-cFN. Our findings identify a role for EIIIA-cFN in liver regeneration and tubulogenesis. We suggest that sinusoidal repair is enhanced by increased LSEC adhesion, which is mediated by EIIIA-cFN.

Error-free 5.1 Tbit/s data generation on a single-wavelength channel using a 1.28 Tbaud symbol rate

DEFF Research Database (Denmark)

Mulvad, Hans Christian Hansen; Galili, Michael; Oxenløwe, Leif Katsuo

2009-01-01

We demonstrate a record bit rate of 5.1 Tbit/s on a single wavelength using a 1.28 Tbaud OTDM symbol rate, DQPSK data-modulation, and polarisation-multiplexing. Error-free performance (BER......We demonstrate a record bit rate of 5.1 Tbit/s on a single wavelength using a 1.28 Tbaud OTDM symbol rate, DQPSK data-modulation, and polarisation-multiplexing. Error-free performance (BER...

DNA Repair Systems

Indian Academy of Sciences (India)

DNA molecule which makes it ideal for storage and propagation of genetic information. ... of these errors are broadly referred to as DNA repair. DNA can ... changes occur in the human genome per day. ..... nails, frequent physical and mental.

[The effectiveness of error reporting promoting strategy on nurse's attitude, patient safety culture, intention to report and reporting rate].

Science.gov (United States)

Kim, Myoungsoo

2010-04-01

The purpose of this study was to examine the impact of strategies to promote reporting of errors on nurses' attitude to reporting errors, organizational culture related to patient safety, intention to report and reporting rate in hospital nurses. A nonequivalent control group non-synchronized design was used for this study. The program was developed and then administered to the experimental group for 12 weeks. Data were analyzed using descriptive analysis, X(2)-test, t-test, and ANCOVA with the SPSS 12.0 program. After the intervention, the experimental group showed significantly higher scores for nurses' attitude to reporting errors (experimental: 20.73 vs control: 20.52, F=5.483, p=.021) and reporting rate (experimental: 3.40 vs control: 1.33, F=1998.083, porganizational culture and intention to report. The study findings indicate that strategies that promote reporting of errors play an important role in producing positive attitudes to reporting errors and improving behavior of reporting. Further advanced strategies for reporting errors that can lead to improved patient safety should be developed and applied in a broad range of hospitals.

A community-wide school health project for the promotion of smoke-free homes.

Science.gov (United States)

Loke, Alice Yuen; Mak, Y W

2015-11-26

A community-wide school health project for the promotion of smoke-free homes was launched in June 2010 with the aim of promoting the benefits of smoke-free homes to all school-aged children (aged 6-18), and indirectly to their parents and family members. The 1-year project included health talks on a smoke-free life; the distribution of educational leaflets; slogan and visual art competitions; and a health fair held in June 2011. Two sets of questionnaires were developed to solicit a resolution and action from the participants regarding the establishment of a smoke-free home, and their decision to stay smoke-free. This is a paper to report on the activities of this project, the attempts to reach out to school-aged children, and their indications of agreement with, support for, and commitment to promoting smoke-free homes. The project reached an estimated 12,800 school-aged children in Hong Kong. A large proportion of those received educational leaflets (69.6-88.2 %). Of those who participated in the health fair, 69.7-87.6 % agreed to promote the concept of smoke-free homes to friends and family. More primary than secondary students pledged to not take up smoking (90.8 vs 85.8 %). About 82 % of those who had experimented with smoking pledged to stop. A small proportion of them reported already having established a smoke-free policy at home (14.9 %), placed a 'No Smoking' sign at home (16.4 %), informed visitors of their smoke-free policy at home (12.9 %), and asked visitors to dispose of lit cigarettes before entering their home (15.9 %). This community-wide school health project on the benefits of smoke-free homes reached a large number of students, and indirectly to family members, and home visitors. Public health efforts of this kind should be continued to reach younger generations and the general public.

Transplantation of bone marrow derived cells promotes pancreatic islet repair in diabetic mice

International Nuclear Information System (INIS)

Gao Xiaodong; Song Lujun; Shen Kuntang; Wang Hongshan; Niu Weixin; Qin Xinyu

2008-01-01

The transplantation of bone marrow (BM) derived cells to initiate pancreatic regeneration is an attractive but as-yet unrealized strategy. Presently, BM derived cells from green fluorescent protein transgenic mice were transplanted into diabetic mice. Repair of diabetic islets was evidenced by reduction of hyperglycemia, increase in number of islets, and altered pancreatic histology. Cells in the pancreata of recipient mice co-expressed BrdU and insulin. Double staining revealed β cells were in the process of proliferation. BrdU + insulin - PDX-1 + cells, Ngn3 + cells and insulin + glucagon + cells, which showed stem cells, were also found during β-cell regeneration. The majority of transplanted cells were mobilized to the islet and ductal regions. In recipient pancreas, transplanted cells simultaneously expressed CD34 but did not express insulin, PDX-1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and CD45. It is concluded that BM derived cells especially CD34 + cells can promote repair of pancreatic islets. Moreover, both proliferation of β cells and differentiation of pancreatic stem cells contribute to the regeneration of β cells

Cellular heredity in haploid cultures of somatic cells. Progress report, August 1977--August 1978. [Role of DNA repair mechanisms in uv mutagenesis in cultured frog and fish cells

Energy Technology Data Exchange (ETDEWEB)

Freed, J.J.

1978-09-01

Studies in progress on cultured frog and fish cells, exploring the relation between the frequency of mutation after ultraviolet irradiation and the pathway through which DNA repair takes place are reported. The rationale is that the mutation frequency induced by a uv exposure is determined not only by the dose delivered but by the fidelity of the DNA repair process. Since frog cells express photoreversal enzyme, whether repair takes place by error-free photoreversal or by other, error-prone, mechanisms can be determined experimentally. An important question is whether an inducible, error-prone mutagenic form of repair is demonstrable. During the past year, methods necessary to determine uv survival and mutation frequency over a range of uv exposures were worked out. Using these methods, we have tested for alteration of the uv survival curve by previous conditioning exposures in frog cells was studied and uv survival and photoreversal capacity in fish cells were determined. The relation between uv survival and induction of ouabain resistance by an alkylating agent (MNNG) was examined as a background for further studies with uv. A procedure intended to accomplish DNA-mediated transfer of frog DNA photolyase enzyme to Chinese hamster cells is described.

Enhanced error related negativity amplitude in medication-naïve, comorbidity-free obsessive compulsive disorder.

Science.gov (United States)

Nawani, Hema; Narayanaswamy, Janardhanan C; Basavaraju, Shrinivasa; Bose, Anushree; Mahavir Agarwal, Sri; Venkatasubramanian, Ganesan; Janardhan Reddy, Y C

2018-04-01

Error monitoring and response inhibition is a key cognitive deficit in obsessive-compulsive disorder (OCD). Frontal midline regions such as the cingulate cortex and pre-supplementary motor area are considered critical brain substrates of this deficit. Electrophysiological equivalent of the above dysfunction is a fronto-central event related potential (ERP) which occurs after an error called the error related negativity (ERN). In this study, we sought to compare the ERN parameters between medication-naïve, comorbidity-free subjects with OCD and healthy controls (HC). Age, sex and handedness matched subjects with medication-naïve, comorbidity-free OCD (N = 16) and Healthy Controls (N = 17) performed a modified version of the flanker task while EEG was acquired for ERN. EEG signals were recorded from the electrodes FCz and Cz. Clinical severity of OCD was assessed using the Yale Brown Obsessive Compulsive Scale. The subjects with OCD had significantly greater ERN amplitude at Cz and FCz. There were no significant correlations between ERN measures and illness severity measures. Overactive performance monitoring as evidenced by enhanced ERN amplitude could be considered as a biomarker for OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanoparticles carrying neurotrophin-3-modified Schwann cells promote repair of sciatic nerve defects.

Science.gov (United States)

Zong, Haibin; Zhao, Hongxing; Zhao, Yilei; Jia, Jingling; Yang, Libin; Ma, Chao; Zhang, Yang; Dong, Yuzhen

2013-05-15

Schwann cells and neurotrophin-3 play an important role in neural regeneration, but the secretion of neurotrophin-3 from Schwann cells is limited, and exogenous neurotrophin-3 is inactived easily in vivo. In this study, we have transfected neurotrophin-3 into Schwann cells cultured in vitro using nanoparticle liposomes. Results showed that neurotrophin-3 was successfully transfected into Schwann cells, where it was expressed effectively and steadily. A composite of Schwann cells transfected with neurotrophin-3 and poly(lactic-co-glycolic acid) biodegradable conduits was transplanted into rats to repair 10-mm sciatic nerve defects. Transplantation of the composite scaffold could restore the myoelectricity and wave amplitude of the sciatic nerve by electrophysiological examination, promote nerve axonal and myelin regeneration, and delay apoptosis of spinal motor neurons. Experimental findings indicate that neurotrophin-3 transfected Schwann cells combined with bridge grafting can promote neural regeneration and functional recovery after nerve injury.

Optical waveform sampling and error-free demultiplexing of 1.28 Tbit/s serial data in a silicon nanowire

DEFF Research Database (Denmark)

Ji, Hua; Hu, Hao; Galili, Michael

2010-01-01

We experimentally demonstrate 640 Gbit/s and 1.28 Tbit/s serial data optical waveform sampling and 640-to-10 Gbit/s and 1.28 Tbit/s-to-10 Gbit/s error-free demultiplexing using four-wave mixing in a 300nm$$450nm$$5mm silicon nanowire.......We experimentally demonstrate 640 Gbit/s and 1.28 Tbit/s serial data optical waveform sampling and 640-to-10 Gbit/s and 1.28 Tbit/s-to-10 Gbit/s error-free demultiplexing using four-wave mixing in a 300nm$$450nm$$5mm silicon nanowire....

Cell-free assay measuring repair DNA synthesis in human fibroblasts

International Nuclear Information System (INIS)

Ciarrocchi, G.; Linn, S.

1978-01-01

Osmotic disruption of confluent cultured human fibroblasts that have been irradiated or exposed to chemical carcinogens allows the specific measurement of repair DNA synthesis using dTTP as a precursor. Fibroblasts similarly prepared from various xeroderma pigmentosum cell lines show the deficiencies of uv-induced DNA synthesis predicted from in vivo studies, while giving normal responses to methylmethanesulfonate. A pyrimidine-dimer-specific enzyme, T4 endonuclease V, stimulated the rate of uv-induced repair synthesis with normal and xeroderma pigmentosum cell lines. This system should prove useful for identifying agents that induce DNA repair, and cells that respond abnormally to such induction. It should also be applicable to an in vitro complementation assay with repair-defective cells and proteins obtained from repair-proficient cells. Finally, by using actively growing fibroblasts and thymidine in the system, DNA replication can be measured and studied in vitro

Additive manufacturing for in situ repair of osteochondral defects

International Nuclear Information System (INIS)

Cohen, Daniel L; Lipton, Jeffrey I; Bonassar, Lawrence J; Lipson, Hod

2010-01-01

Tissue engineering holds great promise for injury repair and replacement of defective body parts. While a number of techniques exist for creating living biological constructs in vitro, none have been demonstrated for in situ repair. Using novel geometric feedback-based approaches and through development of appropriate printing-material combinations, we demonstrate the in situ repair of both chondral and osteochondral defects that mimic naturally occurring pathologies. A calf femur was mounted in a custom jig and held within a robocasting-based additive manufacturing (AM) system. Two defects were induced: one a cartilage-only representation of a grade IV chondral lesion and the other a two-material bone and cartilage fracture of the femoral condyle. Alginate hydrogel was used for the repair of cartilage; a novel formulation of demineralized bone matrix was used for bone repair. Repair prints for both defects had mean surface errors less than 0.1 mm. For the chondral defect, 42.8 ± 2.6% of the surface points had errors that were within a clinically acceptable error range; however, with 1 mm path planning shift, an estimated ∼75% of surface points could likely fall within the benchmark envelope. For the osteochondral defect, 83.6 ± 2.7% of surface points had errors that were within clinically acceptable limits. In addition to implications for minimally invasive AM-based clinical treatments, these proof-of-concept prints are some of the only in situ demonstrations to-date, wherein the substrate geometry was unknown a priori. The work presented herein demonstrates in situ AM, suggests potential biomedical applications and also explores in situ-specific issues, including geometric feedback, material selection and novel path planning techniques.

DNA repair in human cells

International Nuclear Information System (INIS)

Regan, J.D.; Carrier, W.L.; Kusano, I.; Furuno-Fukushi, I.; Dunn, W.C. Jr.; Francis, A.A.; Lee, W.H.

1982-01-01

Our primary objective is to elucidate the molecular events in human cells when cellular macromolecules such as DNA are damaged by radiation or chemical agents. We study and characterize (i) the sequence of DNA repair events, (ii) the various modalities of repair, (iii) the genetic inhibition of repair due to mutation, (iv) the physiological inhibition of repair due to mutation, (v) the physiological inhibition of repair due to biochemical inhibitors, and (vi) the genetic basis of repair. Our ultimate goals are to (i) isolate and analyze the repair component of the mutagenic and/or carcinogenic event in human cells, and (ii) elucidate the magnitude and significance of this repair component as it impinges on the practical problems of human irradiation or exposure to actual or potential chemical mutagens and carcinogens. The significance of these studies lies in (i) the ubiquitousness of repair (most organisms, including man, have several complex repair systems), (ii) the belief that mutagenic and carcinogenic events may arise only from residual (nonrepaired) lesions or that error-prone repair systems may be the major induction mechanisms of the mutagenic or carcinogenic event, and (iii) the clear association of repair defects and highly carcinogenic disease states in man [xeroderma pigmentosum (XP)

Distinct roles of FANCO/RAD51C in DNA damage signaling and repair: implications for fanconi anemia and breast cancer susceptibility

International Nuclear Information System (INIS)

Nagaraju, G.; Somyajit, K.; Subramanya, S.

2012-01-01

Unrepaired or misrepaired chromosomal double-strand breaks (DSBs) can cause gross chromosomal rearrangements which eventually can lead to tumorigenesis through inactivation of tumor suppressor genes or activation of oncogenes. There are two major mechanisms of DSB repair: non-homologous end joining (NHEJ) and homologous recombination (HR). DSBs that are generated during S and G2 phase of the cell are preferentially repaired by sister chromatid recombination (SCR), an HR pathway that utilizes neighboring sister chromatid as a template. Since the copied information is accurate, SCR is potentially an error-free pathway. HR also plays a critical role in the repair of daughter strand gaps (DSGs) that arise as a result of replication fork stalling and facilitates replication fork recovery. Furthermore, in collaboration with nucleotide excision repair and translesion synthesis, HR is involved in the repair of DNA interstrand cross-links (ICLs). Thus, HR is important for the maintenance of genome integrity and its dysfunction can lead to various genetic disorders and cancer

Free Biceps Tendon Autograft to Augment Arthroscopic Rotator Cuff Repair

OpenAIRE

Obma, Padraic R.

2013-01-01

Arthroscopic rotator cuff repairs have become the standard of treatment for all sizes of tears over the past several years. Current healing rates reported in the literature are quite good, but improving the healing potential of rotator cuff repairs remains a challenging problem. There has been an increase recently in the use of augmentation of rotator cuff repairs with xenografts or synthetics for large and massive tears. Biceps tenodesis is often indicated as part of the treatment plan while...

Optical Waveform Sampling and Error-Free Demultiplexing of 1.28 Tb/s Serial Data in a Nanoengineered Silicon Waveguide

DEFF Research Database (Denmark)

Ji, Hua; Pu, Minhao; Hu, Hao

2011-01-01

This paper presents the experimental demonstrations of using a pure nanoengineered silicon waveguide for 1.28 Tb/s serial data optical waveform sampling and 1.28 Tb/s–10 Gb/s error free demultiplexing. The 330-fs pulses are resolved in each 780-fs time slot in waveform sampling. Error...

A history of the DNA repair and mutagenesis field: The discovery of base excision repair.

Science.gov (United States)

Friedberg, Errol C

2016-01-01

This article reviews the early history of the discovery of an DNA repair pathway designated as base excision repair (BER), since in contrast to the enzyme-catalyzed removal of damaged bases from DNA as nucleotides [called nucleotide excision repair (NER)], BER involves the removal of damaged or inappropriate bases, such as the presence of uracil instead of thymine, from DNA as free bases. Copyright © 2015. Published by Elsevier B.V.

Constitutive error based parameter estimation technique for plate structures using free vibration signatures

Science.gov (United States)

Guchhait, Shyamal; Banerjee, Biswanath

2018-04-01

In this paper, a variant of constitutive equation error based material parameter estimation procedure for linear elastic plates is developed from partially measured free vibration sig-natures. It has been reported in many research articles that the mode shape curvatures are much more sensitive compared to mode shape themselves to localize inhomogeneity. Complying with this idea, an identification procedure is framed as an optimization problem where the proposed cost function measures the error in constitutive relation due to incompatible curvature/strain and moment/stress fields. Unlike standard constitutive equation error based procedure wherein a solution of a couple system is unavoidable in each iteration, we generate these incompatible fields via two linear solves. A simple, yet effective, penalty based approach is followed to incorporate measured data. The penalization parameter not only helps in incorporating corrupted measurement data weakly but also acts as a regularizer against the ill-posedness of the inverse problem. Explicit linear update formulas are then developed for anisotropic linear elastic material. Numerical examples are provided to show the applicability of the proposed technique. Finally, an experimental validation is also provided.

Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

Science.gov (United States)

Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

2013-10-29

Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

Aging impairs double-strand break repair by homologous recombination in Drosophila germ cells.

Science.gov (United States)

Delabaere, Laetitia; Ertl, Henry A; Massey, Dashiell J; Hofley, Carolyn M; Sohail, Faraz; Bienenstock, Elisa J; Sebastian, Hans; Chiolo, Irene; LaRocque, Jeannine R

2017-04-01

Aging is characterized by genome instability, which contributes to cancer formation and cell lethality leading to organismal decline. The high levels of DNA double-strand breaks (DSBs) observed in old cells and premature aging syndromes are likely a primary source of genome instability, but the underlying cause of their formation is still unclear. DSBs might result from higher levels of damage or repair defects emerging with advancing age, but repair pathways in old organisms are still poorly understood. Here, we show that premeiotic germline cells of young and old flies have distinct differences in their ability to repair DSBs by the error-free pathway homologous recombination (HR). Repair of DSBs induced by either ionizing radiation (IR) or the endonuclease I-SceI is markedly defective in older flies. This correlates with a remarkable reduction in HR repair measured with the DR-white DSB repair reporter assay. Strikingly, most of this repair defect is already present at 8 days of age. Finally, HR defects correlate with increased expression of early HR components and increased recruitment of Rad51 to damage in older organisms. Thus, we propose that the defect in the HR pathway for germ cells in older flies occurs following Rad51 recruitment. These data reveal that DSB repair defects arise early in the aging process and suggest that HR deficiencies are a leading cause of genome instability in germ cells of older animals. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Atypical Role for PhoU in Mutagenic Break Repair under Stress in Escherichia coli.

Directory of Open Access Journals (Sweden)

Janet L Gibson

Full Text Available Mechanisms of mutagenesis activated by stress responses drive pathogen/host adaptation, antibiotic and anti-fungal-drug resistance, and perhaps much of evolution generally. In Escherichia coli, repair of double-strand breaks (DSBs by homologous recombination is high fidelity in unstressed cells, but switches to a mutagenic mode using error-prone DNA polymerases when the both the SOS and general (σS stress responses are activated. Additionally, the σE response promotes spontaneous DNA breakage that leads to mutagenic break repair (MBR. We identified the regulatory protein PhoU in a genetic screen for functions required for MBR. PhoU negatively regulates the phosphate-transport and utilization (Pho regulon when phosphate is in excess, including the PstB and PstC subunits of the phosphate-specific ABC transporter PstSCAB. Here, we characterize the PhoU mutation-promoting role. First, some mutations that affect phosphate transport and Pho transcriptional regulation decrease mutagenesis. Second, the mutagenesis and regulon-expression phenotypes do not correspond, revealing an apparent new function(s for PhoU. Third, the PhoU mutagenic role is not via activation of the σS, SOS or σE responses, because mutations (or DSBs that restore mutagenesis to cells defective in these stress responses do not restore mutagenesis to phoU cells. Fourth, the mutagenesis defect in phoU-mutant cells is partially restored by deletion of arcA, a gene normally repressed by PhoU, implying that a gene(s repressed by ArcA promotes mutagenic break repair. The data show a new role for PhoU in regulation, and a new regulatory branch of the stress-response signaling web that activates mutagenic break repair in E. coli.

Designer bFGF-incorporated D-form self-assembly peptide nanofiber scaffolds to promote bone repair

Energy Technology Data Exchange (ETDEWEB)

He, Bin, E-mail: binheing@163.com [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Ou, Yunsheng; Chen, Shuo; Zhao, Weikang; Zhou, Ao [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Zhao, Jinqiu [Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Li, Hong [School of Physical Science and Technology, Sichuan University, Chengdu 610000 (China); Jiang, Dianming [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Zhu, Yong, E-mail: 568731668@qq.com [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China)

2017-05-01

D-Form and L-form peptide nanofiber scaffolds can spontaneously form stable β-sheet secondary structures and nanofiber hydrogel scaffolds, and hold some promise in hemostasis and wound healing. We report here on the synthetic self-assembling peptide D-RADA16 and L-RADA16 are both found to produce stable β-sheet secondary structure and nanofiber hydrogel scaffolds based on circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM) and rheology analysis etc. D-RADA16 hydrogel and L-RADA16 hydrogel can enhance obvious bone repair in femoral condyle defects of the Sprague-Dawley (SD) rat model compared to PBS treatment. Based on micro-computed tomography (CT), it was revealed that D-RADA16 hydrogel and L-RADA16 hydrogel were capable to obtain the extensive bone healing. Histological evaluation also found that these two hydrogels facilitate the presence of more mature bone tissue within the femoral condyle defects. Additionally, D-RADA16 hydrogel showed some potential in storing and releasing basic-fibroblast growth factor (bFGF) which was able to further promote bone regeneration based on micro-CT analysis. These results indicate that D-form peptide nanofiber hydrogel have some special capacity for bone repair. - Highlights: • Peptide D-RADA16 and L-RADA16 can form stable hydrogels. • D-RADA16 hydrogel can obtain the comparable and extensive promotion to bone healing compared to L-RADA16 hydrogel. • L-RADA16 hydrogel allows for slow release of bFGF.

How consumers respond to the behavior of missing a free gift promotion: inaction inertia effect on products offered as free gifts.

Science.gov (United States)

Liu, Tsung-Chi; Cheng, Ti; Ni, Feng-Yu

2011-01-01

Inaction inertia describes the phenomenon that an individual is unlikely to act on an attractive opportunity after having bypassed an even more attractive one. The results of two experiments indicate that after missing an initial opportunity to obtain a product as a free gift during a promotional period, the inaction inertia effect reduces the likelihood of consumers buying the product at a discounted price (second, inferior opportunity), particularly if the free gift has a high regular price. Additionally, according to the results of Experiment 2, those consumers are less likely to buy a product that has been offered previously as a free gift when a greater total quantity of the free gift is offered during a promotional period. Moreover, the mediation analysis results indicate that anticipated regret and valuation significantly impact the mediating role of inaction inertia.

Emerging Importance of Helicases in Plant Stress Tolerance: Characterization of Oryza sativa Repair Helicase XPB2 Promoter and Its Functional Validation in Tobacco under Multiple Stresses.

Science.gov (United States)

Raikwar, Shailendra; Srivastava, Vineet K; Gill, Sarvajeet S; Tuteja, Renu; Tuteja, Narendra

2015-01-01

Genetic material always remains at the risk of spontaneous or induced damage which challenges the normal functioning of DNA molecule, thus, DNA repair is vital to protect the organisms against genetic damage. Helicases, the unique molecular motors, are emerged as prospective molecules to engineer stress tolerance in plants and are involved in nucleic acid metabolism including DNA repair. The repair helicase, XPB is an evolutionary conserved protein present in different organisms, including plants. Availability of few efficient promoters for gene expression in plants provoked us to study the promoter of XPB for better understanding of gene regulation under stress conditions. Here, we report the in silico analysis of novel stress inducible promoter of Oryza sativa XPB2 (OsXPB2). The in vivo validation of functionality/activity of OsXPB2 promoter under abiotic and hormonal stress conditions was performed by Agrobacterium-mediated transient assay in tobacco leaves using OsXPB2::GUS chimeric construct. The present research revealed that OsXPB2 promoter contains cis-elements accounting for various abiotic stresses (salt, dehydration, or cold) and hormone (Auxin, ABA, or MeJA) induced GUS expression/activity in the promoter-reporter assay. The promoter region of OsXPB2 contains CACG, GTAACG, CACGTG, CGTCA CCGCCGCGCT cis acting-elements which are reported to be salt, dehydration, cold, MeJA, or ABA responsive, respectively. Functional analysis was done by Agrobacterium-mediated transient assay using agroinfiltration in tobacco leaves, followed by GUS staining and fluorescence quantitative analyses. The results revealed high induction of GUS activity under multiple abiotic stresses as compared to mock treated control. The present findings suggest that OsXPB2 promoter is a multi-stress inducible promoter and has potential applications in sustainable crop production under abiotic stresses by regulating desirable pattern of gene expression.

Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-ι

Energy Technology Data Exchange (ETDEWEB)

Jain, Rinku; Choudhury, Jayati Roy; Buku, Angeliki; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

2017-03-08

N1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-ι (Polι) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Polι is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Polι bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the syn conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a “foothold” and is largely disordered. Together, our kinetic and structural studies show how Polι maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity.

Improved children's motor learning of the basketball free shooting pattern by associating subjective error estimation and extrinsic feedback.

Science.gov (United States)

Silva, Leandro de Carvalho da; Pereira-Monfredini, Carla Ferro; Teixeira, Luis Augusto

2017-09-01

This study aimed at assessing the interaction between subjective error estimation and frequency of extrinsic feedback in the learning of the basketball free shooting pattern by children. 10- to 12-year olds were assigned to 1 of 4 groups combining subjective error estimation and relative frequency of extrinsic feedback (33% × 100%). Analysis of performance was based on quality of movement pattern. Analysis showed superior learning of the group combining error estimation and 100% feedback frequency, both groups receiving feedback on 33% of trials achieved intermediate results, and the group combining no requirement of error estimation and 100% feedback frequency had the poorest learning. Our results show the benefit of subjective error estimation in association with high frequency of extrinsic feedback in children's motor learning of a sport motor pattern.

Development of inducer-free expression plasmids based on IPTG-inducible promoters for Bacillus subtilis.

Science.gov (United States)

Tran, Dinh Thi Minh; Phan, Trang Thi Phuong; Huynh, Thanh Kieu; Dang, Ngan Thi Kim; Huynh, Phuong Thi Kim; Nguyen, Tri Minh; Truong, Tuom Thi Tinh; Tran, Thuoc Linh; Schumann, Wolfgang; Nguyen, Hoang Duc

2017-07-25

Besides Escherichia coli, Bacillus subtilis is an important bacterial species for the production of recombinant proteins. Recombinant genes are inserted into shuttle expression vectors which replicate in both E. coli and in B. subtilis. The ligation products are first transformed into E. coli cells, analyzed for correct insertions, and the correct recombinant plasmids are then transformed into B. subtilis. A major problem using E. coli cells can be the strong basal level of expression of the recombinant protein which may interfere with the stability of the cells. To minimize this problem, we developed strong expression vectors being repressed in E. coli and inducer-free in B. subtilis. In general, induction of IPTG-inducible expression vectors is determined by the regulatory lacI gene encoding the LacI repressor in combination with the lacO operator on the promoter. To investigate the inducer-free properties of the vectors, we constructed inducer-free expression plasmids by removing the lacI gene and characterized their properties. First, we examined the ability to repress a reporter gene in E. coli, which is a prominent property facilitating the construction of the expression vectors carrying a target gene. The β-galactosidase (bgaB gene) basal levels expressed from Pgrac01-bgaB could be repressed at least twice in the E. coli cloning strain. Second, the inducer-free production of BgaB from four different plasmids with the Pgrac01 promoter in B. subtilis was investigated. As expected, BgaB expression levels of inducer-free constructs are at least 37 times higher than that of the inducible constructs in the absence of IPTG, and comparable to those in the presence of the inducer. Third, using efficient IPTG-inducible expression vectors containing the strong promoter Pgrac100, we could convert them into inducer-free expression plasmids. The BgaB production levels from the inducer-free plasmid in the absence of the inducer were at least 4.5 times higher than that of

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors.

Science.gov (United States)

Butler, Jason M; Kobayashi, Hideki; Rafii, Shahin

2010-02-01

The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.

Radiation damage and its repair in non-sporulating bacteria

International Nuclear Information System (INIS)

Moseley, B.E.B.

1984-01-01

A review is given of radiation damage and its repair in non-sporulating bacteria. The identification and measurement of radiation damage in the DNA of the bacteria after exposure to ultraviolet radiation and ionizing radiation is described. Measuring the extent of DNA repair and ways of isolating repair mutants are also described. The DNA repair mechanisms for UV-induced damage are discussed including photoreactivation repair, excision repair, post-replication recombination repair and induced error-prone repair. The DNA repair mechanisms for ionizing radiation damage are also discussed including the repair of both single and double-strand breaks. Other aspects discussed include the effects of growth, irradiation medium and recovery medium on survival, DNA repair in humans, the commercial use of UV and ionizing radiations and the future of ionizing irradiation as a food treatment process. (U.K.)

An improved estimator for the hydration of fat-free mass from in vivo measurements subject to additive technical errors

International Nuclear Information System (INIS)

Kinnamon, Daniel D; Ludwig, David A; Lipshultz, Steven E; Miller, Tracie L; Lipsitz, Stuart R

2010-01-01

The hydration of fat-free mass, or hydration fraction (HF), is often defined as a constant body composition parameter in a two-compartment model and then estimated from in vivo measurements. We showed that the widely used estimator for the HF parameter in this model, the mean of the ratios of measured total body water (TBW) to fat-free mass (FFM) in individual subjects, can be inaccurate in the presence of additive technical errors. We then proposed a new instrumental variables estimator that accurately estimates the HF parameter in the presence of such errors. In Monte Carlo simulations, the mean of the ratios of TBW to FFM was an inaccurate estimator of the HF parameter, and inferences based on it had actual type I error rates more than 13 times the nominal 0.05 level under certain conditions. The instrumental variables estimator was accurate and maintained an actual type I error rate close to the nominal level in all simulations. When estimating and performing inference on the HF parameter, the proposed instrumental variables estimator should yield accurate estimates and correct inferences in the presence of additive technical errors, but the mean of the ratios of TBW to FFM in individual subjects may not

Emerging importance of helicases in plant stress tolerance: characterization of Oryza sativa repair helicase XPB2 promoter and its functional validation in tobacco under multiple stresses

Directory of Open Access Journals (Sweden)

Shailendra eRaikwar

2015-12-01

Full Text Available Genetic material always remains at the risk of spontaneous or induced damage which challenges the normal functioning of DNA molecule, thus, DNA repair is vital to protect the organisms against genetic damage. DNA hHelicases, the unique molecular motors, are emerged as potentialprospective molecules to engineer stress tolerance in plants and are involved in a variety of DNA nucleic acid metabolismc processes including DNA repair. The DNA repair helicase, OsXPB2 is an evolutionary conserved protein present in different organisms, including plants. Availability of few efficient promoters for gene expression in plants provoked us to study the promoter of XPB for better understanding of gene regulation under stress The analysis of promoter sequence from plant genome is important in understanding the gene regulation. Hereconditions. Here, we report the in silico analysis of novel stress inducible promoter of rice Oryza sativa OsXPB2 (OsXPB2. gene is reported. The in vivo validation of functionality/activity of novel stress inducible promoter of rice OsXPB2 gene promoter under abiotic and hormonal stress conditions was performed by Agrobacterium-mediated transient assay in tobacco leaves using OsXPB2::GUS chimeric construct. Our resultsThe present research revealed that OsXPB2 promoter contains cis-elements accounting for various abiotic stresses (salt, dehydration or cold and hormone (Auxin, ABA or MeJA induced GUS expression/activity in the promoter-reporter assay. The promoter region of OsXPB2 contains CACG, GTAACG, CACGTG, CGTCA CCGCCGCGCT cis acting-elements which are reported to be salt, dehydration, cold, MeJA or ABA responsive, respectively. Functional analysis was done by Agrobacterium-transient assays using agroinfiltration in tobacco leaves, followed by GUS staining and fluorescence quantitative analyses. The results revealed high induction of GUS activity under multiple abiotic stresses as compared to mock treated control. The present

p53 regulates the repair of DNA double-strand breaks by both homologous and non-homologous recombination

International Nuclear Information System (INIS)

Willers, H.; Powell, S.N.; Dahm-Daphi, J.

2003-01-01

Full text: p53 is known to suppress spontaneous homologous recombination (HR), while its role in non-homologous recombination (NHR) remains to be clarified. Here, we sought to determine the influence of p53 on the repair of chromosomal double-strand breaks (DSBs) by HR or NHR using specially designed recombination substrates that integrate into the genome. Isogenic mouse fibroblast pairs with or without expression of exogenous p53 protein were utilized. A reporter plasmid carrying a mutated XGPRT gene was chromosomally integrated and DSBs were generated within the plasmid by the I-SceI endonuclease. Subsequent homology-mediated repair from an episomal donor resulted in XGPRT reconstitution and cellular resistance to a selection antibiotic. Analogously, the repair of chromosomal I-SceI breaks by NHR using another novel reporter plasmid restored XGPRT translation. For p53-null cells, the mean frequency of I-SceI break repair via HR was 5.5 x 10 -4 . The p53-Val135 mutant, which previously has been shown to suppress spontaneous HR by 14-fold employing the same cell system and reporter gene, only caused a 2- to 3-fold suppression of break-induced HR. In contrast, a dramatic effect of p53 on repair via NHR was found. Preliminary sequence analysis indicated that there was at least a 1000-fold reduction of illegitimate repair events resulting in loss of sequence at the break sites. The observed effects were mediated by p53 mutants defective in regulation of the cell-cycle and apoptosis. The main findings were: (1) p53 virtually blocked illegitimate rejoining of chromosomal ends. (2) The suppression of homologous DSB repair was less pronounced than the inhibition of spontaneous HR. We hypothesize that p53 allows to a certain extent error-free homology-dependent repair to proceed, while blocking error-prone NHR. The data support and extent a previous model, in which p53 maintains genomic stability by regulating recombination independently of its transactivation function

Tif-stimulated deoxyribonucleic acid repair in Escherichia coli K-12

International Nuclear Information System (INIS)

Castellazzi, M.; Jacques, M.; George, J.

1980-01-01

Bacterial survival is significantly increased after ultraviolet irradiation in tif sfi cells, provided that the thermosensitive tif mutation has been expressed at 41 0 C before irradiation. This tif-mediated reactivation of ultraviolet irradiated bacteria needs de novo protein synthesis, as is the case for the tif-mediated reactivation of ultraviolet-irradiated phage lambda. However, in striking contrast to the phage reactivation process, this tif-mediated reactivation is no longer associated with mutagenesis. It also requires the presence of the uvrA + excision function. These results strongly suggest the existence in Escherichia coli K-12 of a repair pathway acting on bacterial deoxyribonucleic acid which is inducible, error free, and uvr dependent

Effect of slope errors on the performance of mirrors for x-ray free electron laser applications.

Science.gov (United States)

Pardini, Tom; Cocco, Daniele; Hau-Riege, Stefan P

2015-12-14

In this work we point out that slope errors play only a minor role in the performance of a certain class of x-ray optics for X-ray Free Electron Laser (XFEL) applications. Using physical optics propagation simulations and the formalism of Church and Takacs [Opt. Eng. 34, 353 (1995)], we show that diffraction limited optics commonly found at XFEL facilities posses a critical spatial wavelength that makes them less sensitive to slope errors, and more sensitive to height error. Given the number of XFELs currently operating or under construction across the world, we hope that this simple observation will help to correctly define specifications for x-ray optics to be deployed at XFELs, possibly reducing the budget and the timeframe needed to complete the optical manufacturing and metrology.

Roles of neural stem cells in the repair of peripheral nerve injury.

Science.gov (United States)

Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

2017-12-01

Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1

Directory of Open Access Journals (Sweden)

Dan He

2018-05-01

Full Text Available Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL oxidized by heme enzyme myeloperoxidase (MPO is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1 using human aorta endothelial cells (HAEC and SR-B1 (-/- mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/- mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.

Promotion of accelerated repair in a radiation impaired wound healing model in murine skin

International Nuclear Information System (INIS)

Walker, M.D.

2000-02-01

therapeutic modalities investigated were unable to counteract any radiation damage and promote acceleration of repair in this impaired wound healing model. (author)

Maintenance and Repair of Concrete Structures

NARCIS (Netherlands)

Bijen, J.M.J.M.

1989-01-01

In 1987 and 1988 a series of articles was published in the Dutchjournal "Cement" about maintenance and repair of concrete structures. The series was written to promote the transfer of know-how concerning maintenance and repair of concrete structures. Use has been made of know-how developed in the

Fixation free femoral hernia repair with a 3D dynamic responsive implant. A case series report.

Science.gov (United States)

Amato, G; Romano, G; Agrusa, A; Gordini, L; Gulotta, E; Erdas, E; Calò, P G

2018-04-23

To date, no gold standard for the surgical treatment of femoral hernia exists. Pure tissue repair as well as mesh/plug implantation, open or laparoscopic, are the most performed methods. Nevertheless, all these techniques need sutures or mesh fixation. This implies the risk of damaging sensitive structures of the femoral area, along with complications related to tissue tear and postoperative discomfort consequent to poor quality mesh incorporation. The present retrospective multicenter case series highlights the results of femoral hernia repair procedures performed with a 3D dynamic responsive implant in a cohort of 32 patients during a mean follow up of 27 months. Aiming to simplify the surgical procedure and reduce complications, a 3D dynamic responsive implant was delivered for femoral hernia repair, in a patient cohort. After returning the hernia sack to the abdominal cavity, the implant was simply delivered into the hernia defect where it remained, thanks to its inherent centrifugal expansion, obliterating the hernia opening without need of fixation. Postoperative pain assessment was determined using the VAS score system. The use of the 3D prosthetic device allowed for easier and faster surgical repair in a fixation free fashion. None of the typical fixation related complications occurred in the examined patients. Postoperative pain assessment with VAS score showed a very low level of pain, allowing the return of patients to normal activities in extremely reduced times. In the late postoperative period, no discomfort or chronic pain was reported. Femoral hernia repair with the 3D dynamic revealed a quick and safe placement procedure. The reduced pain intensity, as well as the absence of adverse events consequent to sutures or mesh fixation, seems to be a significant benefit of the motile compliance of the device. Furthermore, this 3D prosthesis has already proven to induce an enhanced probiotic response showing ingrowth in the implant of the typical tissue

Promoting free online CME for intimate partner violence: what works at what cost?

Science.gov (United States)

Harris, John M; Novalis-Marine, Cheryl; Amend, Robert W; Surprenant, Zita J

2009-01-01

There is a need to provide practicing physicians with training on the recognition and management of intimate partner violence (IPV). Online continuing medical education (CME) could help meet this need, but there is little information on the costs and effectiveness of promoting online CME to physicians. This lack of information may discourage IPV training efforts and the use of online CME in general. We promoted an interactive, multimedia, online IPV CME program, which offered free CME credit, to 92,000 California physicians for 24 months. We collected data on user satisfaction, the costs of different promotional strategies, and self-reported user referral source. We evaluated California physician awareness of the promotion via telephone surveys. Over 2 years, the CME program was used by 1869 California physicians (2% of market), who rated the program's overall quality highly (4.52 on a 1-5 scale; 5 = excellent). The average promotional cost per physician user was $75. Direct mail was the most effective strategy, costing $143 each for 821 users. E-promotion via search engine advertising and e-mail solicitation had less reach, but was more cost efficient ($30-$80 per user). Strategies with no direct cost, such as notices in professional newsletters, accounted for 31% (578) of physician users. Phone surveys found that 24% of California physicians were aware of the online IPV CME program after 18 months of promotion. Promoting online CME, even well-received free CME, to busy community physicians requires resources, in this case at least $75 per physician reached. The effective use of promotional resources needs to be considered when developing social marketing strategies to improve community physician practices. Organizations with an interest in promoting online training might consider the use of e-promotion techniques along with conventional promotion strategies.

Comparison of shrinkage related properties of various patch repair materials

Science.gov (United States)

Kristiawan, S. A.; Fitrianto, R. S.

2017-02-01

A patch repair material has been developed in the form of unsaturated polyester resin (UPR)-mortar. The performance and durability of this material are governed by its compatibility with the concrete being repaired. One of the compatibility issue that should be tackled is the dimensional compatibility as a result of differential shrinkage between the repair material and the concrete substrate. This research aims to evaluate such shrinkage related properties of UPR-mortar and to compare with those of other patch repair materials. The investigation includes the following aspects: free shrinkage, resistance to delamination and cracking. The results indicate that UPR-mortar poses a lower free shrinkage, lower risk of both delamination and cracking tendency in comparison to other repair materials.

The transcription fidelity factor GreA impedes DNA break repair.

Science.gov (United States)

Sivaramakrishnan, Priya; Sepúlveda, Leonardo A; Halliday, Jennifer A; Liu, Jingjing; Núñez, María Angélica Bravo; Golding, Ido; Rosenberg, Susan M; Herman, Christophe

2017-10-12

Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor that compromises genomic integrity.

Placental promoter methylation of DNA repair genes and prenatal exposure to particulate air pollution: an ENVIRONAGE cohort study

Directory of Open Access Journals (Sweden)

Kristof Y Neven, MSc

2018-04-01

Full Text Available Summary: Background: Exposure to particulate air pollution has been linked with risk of carcinogenesis. Damage to repair pathways might have long-term adverse health effects. We aimed to investigate the association of prenatal exposure to air pollution with placental mutation rate and the DNA methylation of key placental DNA repair genes. Methods: This cohort study used data from the ongoing ENVironmental Influence ON early AGEing (ENVIRONAGE birth cohort, which enrols pairs of mothers and neonates (singleton births only at the East-Limburg Hospital (Genk, Belgium. Placental DNA samples were collected after birth. We used bisulfite-PCR-pyrosequencing to investigate the mutation rate of Alu (a marker for overall DNA mutation and DNA methylation in the promoter genes of key DNA repair and tumour suppressor genes (APEX1, OGG1, PARP1, ERCC1, ERCC4, p53, and DAPK1. We used a high-resolution air pollution model to estimate exposure to particulate matter with a diameter less than 2·5 μm (PM2·5, black carbon, and NO2 over the entire pregnancy on the basis of maternal address. Alu mutation was analysed with a linear regression model, and methylation values of the selected genes were analysed in mixed-effects models. Effect estimates are presented as the relative percentage change in methylation for an ambient air pollution increment of one IQR (ie, the difference between the first and third quartiles of exposure in the entire cohort. Findings: 500 biobanked placental DNA samples were randomly selected from 814 pairs of mothers and neonates who were recruited to the cohort between Feb 1, 2010, and Dec 31, 2014, of which 463 samples met the pyrosequencing quality control criteria. IQR exposure increments were 3·84 μg/m3 for PM2·5, 0·36 μg/m3 for black carbon, and 5·34 μg/m3 for NO2. Among these samples, increased Alu mutation rate was associated with greater exposure to PM2·5 (r=0·26, p<0·0001 and black carbon (r=0·33, p<0·0001, but not NO2

Visualization of DNA double-strand break repair: From molecules to cells

NARCIS (Netherlands)

Krawczyk, Przemek M.; Stap, Jan; Aten, Jacob A.

2008-01-01

DNA double-strand break (DSB) signaling and repair processes are positioned at the crossroad of nuclear pathways that regulate DNA replication, cell division, senescence and apoptosis. Importantly, errors in DSB repair may lead to lethal or potentially tumorigenic chromosome rearrangements.

Promoting public transport as a subscription service: Effects of a free month travel card

DEFF Research Database (Denmark)

Thøgersen, John

2009-01-01

Newspapers, book clubs, telephone services and many other subscription services are often marketed to new customers by means of a free or substantially discounted trial period. This article evaluates this method as a means to promote commuting by public transport in a field experiment and based...... that had an effect was the free month travel card, which led to a significant increase in commuting by public transport.As expected, the effect was mediated through a change in behavioural intentions rather than a change in perceived constraints. As expected, the effect became weaker when the promotion...

Error Free Quantum Reading by Quasi Bell State of Entangled Coherent States

Science.gov (United States)

Hirota, Osamu

2017-12-01

Nonclassical states of light field have been exploited to provide marvellous results in quantum information science. Usefulness of nonclassical states in quantum information science depends on whether a physical parameter as a signal is continuous or discrete. Here we present an investigation of the potential of quasi Bell states of entangled coherent states in quantum reading of the classical digital memory which was pioneered by Pirandola (Phys.Rev.Lett.,106,090504,2011). This is a typical example of discrimination for discrete quantum parameters. We show that the quasi Bell state gives the error free performance in the quantum reading that cannot be obtained by any classical state.

Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration.

Science.gov (United States)

Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

2012-12-15

Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7-21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy.

Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration☆

Science.gov (United States)

Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

2012-01-01

Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7–21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy. PMID:25317130

Switching between chewing-gum and no-gum at learning and retrieval does not accentuate error production in free recall

OpenAIRE

Miles, C.; Johnson, A.J.

2010-01-01

Three experiments compared chewing gum to a no gum condition to examine further the finding (Anderson, Berry, Morse & Diotte, 2005) that switching flavour between learning and recall encourages error production independently of free recall. In order to encourage error production, participants in Experiment 1 were told to guess responses at recall, participants in Experiment 2 were required to recall categorised word lists and in Experiment 3 participants repeated the same learning-recall comb...

Induction and repair of DNA double strand breaks: The increasing spectrum of non-homologous end joining pathways

International Nuclear Information System (INIS)

Mladenov, Emil; Iliakis, George

2011-01-01

A defining characteristic of damage induced in the DNA by ionizing radiation (IR) is its clustered character that leads to the formation of complex lesions challenging the cellular repair mechanisms. The most widely investigated such complex lesion is the DNA double strand break (DSB). DSBs undermine chromatin stability and challenge the repair machinery because an intact template strand is lacking to assist restoration of integrity and sequence in the DNA molecule. Therefore, cells have evolved a sophisticated machinery to detect DSBs and coordinate a response on the basis of inputs from various sources. A central function of cellular responses to DSBs is the coordination of DSB repair. Two conceptually different mechanisms can in principle remove DSBs from the genome of cells of higher eukaryotes. Homologous recombination repair (HRR) uses as template a homologous DNA molecule and is therefore error-free; it functions preferentially in the S and G2 phases. Non-homologous end joining (NHEJ), on the other hand, simply restores DNA integrity by joining the two ends, is error prone as sequence is only fortuitously preserved and active throughout the cell cycle. The basis of DSB repair pathway choice remains unknown, but cells of higher eukaryotes appear programmed to utilize preferentially NHEJ. Recent work suggests that when the canonical DNA-PK dependent pathway of NHEJ (D-NHEJ), becomes compromised an alternative NHEJ pathway and not HRR substitutes in a quasi-backup function (B-NHEJ). Here, we outline aspects of DSB induction by IR and review the mechanisms of their processing in cells of higher eukaryotes. We place particular emphasis on backup pathways of NHEJ and summarize their increasing significance in various cellular processes, as well as their potential contribution to carcinogenesis.

Recall and Effectiveness of Messages Promoting Smoke-Free Policies in Rural Communities

Science.gov (United States)

Butler, Karen M.; Wiggins, Amanda T.; Kostygina, Ganna; Langley, Ronald E.; Hahn, Ellen J.

2016-01-01

Abstract Introduction: Low-cost media campaigns increase demand for smoke-free policies in underserved rural areas. The study examined the impact of loss- and gain-framed smoke-free print ads on recall and perceived effectiveness in rural communities, controlling for personal characteristics. Methods: Following 6- to 9-month print media campaigns in three rural counties, recall and perceived effectiveness of loss-framed (ie, targeting dangers of secondhand smoke [SHS]) and gain-framed (ie, highlighting positive aspects of smoke-free air) ads were assessed using random-digit-dial phone surveys. Respondents were asked if they remembered each ad, whether they liked it, whether they were prompted to contact a smoke-free coalition, whether the ad made them think, and whether it prompted emotion. Mixed modeling assessed whether personal factors predicted ad recall or perceived effectiveness. Results: Loss-framed ads were less likely to be recalled but more likely to prompt emotion. For ads of both frame types, females reported greater recall and perceived effectiveness than males. Those with less education reported higher perceived effectiveness of the ads but lower recall. Nonsmokers were more likely than smokers to perceive the ads as effective. Knowledge of SHS risk and support for smoke-free workplaces were positively associated with recall and effectiveness. Conclusions: Ad recall and perceived effectiveness were associated with framing and demographic and personal characteristics. Smoke-free efforts in rural areas may be bolstered by continuing to promote benefits of smoke-free workplace policies and educate on SHS risks. Rural areas may need to provide a combination of ad types and framing strategies to appeal to a wide audience. Implications: Rural communities are disproportionately affected by SHS and less likely to be protected by smoke-free policies. This study adds evidence-based guidance for tailoring rural smoke-free media campaigns using different framing

The cAMP signaling system inhibits the repair of {gamma}-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells

Energy Technology Data Exchange (ETDEWEB)

Cho, Eun-Ah [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

2012-06-01

Highlights: Black-Right-Pointing-Pointer cAMP signaling system inhibits repair of {gamma}-ray-induced DNA damage. Black-Right-Pointing-Pointer cAMP signaling system inhibits DNA damage repair by decreasing XRCC1 expression. Black-Right-Pointing-Pointer cAMP signaling system decreases XRCC1 expression by promoting its proteasomal degradation. Black-Right-Pointing-Pointer The promotion of XRCC1 degradation by cAMP signaling system is mediated by Epac1. -- Abstract: Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on {gamma}-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (G{alpha}sQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of G{alpha}sQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after {gamma}-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2 Prime -O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2 Prime -O-Me-cAMP and restored XRCC1 protein level following {gamma}-ray irradiation. From

Translesion synthesis DNA polymerases promote error-free replication through the minor-groove DNA adduct 3-deaza-3-methyladenine.

Science.gov (United States)

Yoon, Jung-Hoon; Roy Choudhury, Jayati; Park, Jeseong; Prakash, Satya; Prakash, Louise

2017-11-10

N3-Methyladenine (3-MeA) is formed in DNA by reaction with S -adenosylmethionine, the reactive methyl donor, and by reaction with alkylating agents. 3-MeA protrudes into the DNA minor groove and strongly blocks synthesis by replicative DNA polymerases (Pols). However, the mechanisms for replicating through this lesion in human cells remain unidentified. Here we analyzed the roles of translesion synthesis (TLS) Pols in the replication of 3-MeA-damaged DNA in human cells. Because 3-MeA has a short half-life in vitro , we used the stable 3-deaza analog, 3-deaza-3-methyladenine (3-dMeA), which blocks the DNA minor groove similarly to 3-MeA. We found that replication through the 3-dMeA adduct is mediated via three different pathways, dependent upon Polι/Polκ, Polθ, and Polζ. As inferred from biochemical studies, in the Polι/Polκ pathway, Polι inserts a nucleotide (nt) opposite 3-dMeA and Polκ extends synthesis from the inserted nt. In the Polθ pathway, Polθ carries out both the insertion and extension steps of TLS opposite 3-dMeA, and in the Polζ pathway, Polζ extends synthesis following nt insertion by an as yet unidentified Pol. Steady-state kinetic analyses indicated that Polι and Polθ insert the correct nt T opposite 3-dMeA with a much reduced catalytic efficiency and that both Pols exhibit a high propensity for inserting a wrong nt opposite this adduct. However, despite their low fidelity of synthesis opposite 3-dMeA, TLS opposite this lesion replicates DNA in a highly error-free manner in human cells. We discuss the implications of these observations for TLS mechanisms in human cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Error management for musicians: an interdisciplinary conceptual framework.

Science.gov (United States)

Kruse-Weber, Silke; Parncutt, Richard

2014-01-01

Musicians tend to strive for flawless performance and perfection, avoiding errors at all costs. Dealing with errors while practicing or performing is often frustrating and can lead to anger and despair, which can explain musicians' generally negative attitude toward errors and the tendency to aim for flawless learning in instrumental music education. But even the best performances are rarely error-free, and research in general pedagogy and psychology has shown that errors provide useful information for the learning process. Research in instrumental pedagogy is still neglecting error issues; the benefits of risk management (before the error) and error management (during and after the error) are still underestimated. It follows that dealing with errors is a key aspect of music practice at home, teaching, and performance in public. And yet, to be innovative, or to make their performance extraordinary, musicians need to risk errors. Currently, most music students only acquire the ability to manage errors implicitly - or not at all. A more constructive, creative, and differentiated culture of errors would balance error tolerance and risk-taking against error prevention in ways that enhance music practice and music performance. The teaching environment should lay the foundation for the development of such an approach. In this contribution, we survey recent research in aviation, medicine, economics, psychology, and interdisciplinary decision theory that has demonstrated that specific error-management training can promote metacognitive skills that lead to better adaptive transfer and better performance skills. We summarize how this research can be applied to music, and survey-relevant research that is specifically tailored to the needs of musicians, including generic guidelines for risk and error management in music teaching and performance. On this basis, we develop a conceptual framework for risk management that can provide orientation for further music education and

Error management for musicians: an interdisciplinary conceptual framework

Directory of Open Access Journals (Sweden)

Silke eKruse-Weber

2014-07-01

Full Text Available Musicians tend to strive for flawless performance and perfection, avoiding errors at all costs. Dealing with errors while practicing or performing is often frustrating and can lead to anger and despair, which can explain musicians’ generally negative attitude toward errors and the tendency to aim for errorless learning in instrumental music education. But even the best performances are rarely error-free, and research in general pedagogy and psychology has shown that errors provide useful information for the learning process. Research in instrumental pedagogy is still neglecting error issues; the benefits of risk management (before the error and error management (during and after the error are still underestimated. It follows that dealing with errors is a key aspect of music practice at home, teaching, and performance in public. And yet, to be innovative, or to make their performance extraordinary, musicians need to risk errors. Currently, most music students only acquire the ability to manage errors implicitly - or not at all. A more constructive, creative and differentiated culture of errors would balance error tolerance and risk-taking against error prevention in ways that enhance music practice and music performance. The teaching environment should lay the foundation for the development of these abilities. In this contribution, we survey recent research in aviation, medicine, economics, psychology, and interdisciplinary decision theory that has demonstrated that specific error-management training can promote metacognitive skills that lead to better adaptive transfer and better performance skills. We summarize how this research can be applied to music, and survey relevant research that is specifically tailored to the needs of musicians, including generic guidelines for risk and error management in music teaching and performance. On this basis, we develop a conceptual framework for risk management that can provide orientation for further

Delayed peripheral nerve repair: methods, including surgical 'cross-bridging' to promote nerve regeneration.

Science.gov (United States)

Gordon, Tessa; Eva, Placheta; Borschel, Gregory H

2015-10-01

Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges) into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to 'protect' chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.

SU-E-T-377: Inaccurate Positioning Might Introduce Significant MapCheck Calibration Error in Flatten Filter Free Beams

International Nuclear Information System (INIS)

Wang, S; Chao, C; Chang, J

2014-01-01

Purpose: This study investigates the calibration error of detector sensitivity for MapCheck due to inaccurate positioning of the device, which is not taken into account by the current commercial iterative calibration algorithm. We hypothesize the calibration is more vulnerable to the positioning error for the flatten filter free (FFF) beams than the conventional flatten filter flattened beams. Methods: MapCheck2 was calibrated with 10MV conventional and FFF beams, with careful alignment and with 1cm positioning error during calibration, respectively. Open fields of 37cmx37cm were delivered to gauge the impact of resultant calibration errors. The local calibration error was modeled as a detector independent multiplication factor, with which propagation error was estimated with positioning error from 1mm to 1cm. The calibrated sensitivities, without positioning error, were compared between the conventional and FFF beams to evaluate the dependence on the beam type. Results: The 1cm positioning error leads to 0.39% and 5.24% local calibration error in the conventional and FFF beams respectively. After propagating to the edges of MapCheck, the calibration errors become 6.5% and 57.7%, respectively. The propagation error increases almost linearly with respect to the positioning error. The difference of sensitivities between the conventional and FFF beams was small (0.11 ± 0.49%). Conclusion: The results demonstrate that the positioning error is not handled by the current commercial calibration algorithm of MapCheck. Particularly, the calibration errors for the FFF beams are ~9 times greater than those for the conventional beams with identical positioning error, and a small 1mm positioning error might lead to up to 8% calibration error. Since the sensitivities are only slightly dependent of the beam type and the conventional beam is less affected by the positioning error, it is advisable to cross-check the sensitivities between the conventional and FFF beams to detect

Mutagenic DNA repair in Escherichia coli. Pt. 2. Factors affecting loss of photoreversibility of UV induced mutations

Energy Technology Data Exchange (ETDEWEB)

Doubleday, O P; Bridges, B A; Green, M H.L. [Medical Research Council, Brighton (UK). Cell Mutation Unit

1975-01-01

The photoreversibility of UV-induced mutations to Trp/sup +/ in strain Escherichia coli WP2 uvr A trp (unable to excise pyrimidine dimers) was lost at different rates during incubation in different media. In Casamino acids medium after a short initial lag, photoreversibility was lost over about one generation time; in minimal medium with tryptophan, photoreversibility persisted for more than two generations; in Casamino acids medium with pantoyl lactone photoreversibility was lost extremely slowly. The rate of loss of photoreversibility was unaffected by UV dose in either Casamino acids medium or in minimal medium. The same eventual number of induced mutants was obtained when cells were incubated for two generations in any of the three media before being transferred to selective plates supplemented with Casamino acids. Thus in each the proportion of cells capable of giving rise to a mutant was the same and only the rate at which these cells did so during post-irradiation growth varied, suggesting that there might be a specific fraction of pyrimidine dimers at a given site capable of initiating a mutagenic repair event, and that the size of this fraction is dose dependent. Segregation experiments have shown that error-prone repair appears to occur once only and is not repeated in subsequent replication cycles, in contrast to (presumed error-free) recombination repair. The results are discussed in the light of current models of UV mutagenesis.

Investigating the effects of sales promotions on customer behavioral intentions at duty-free shops: An Incheon International Airport case study

Directory of Open Access Journals (Sweden)

Jin-Woo Park

2013-09-01

Full Text Available Purpose: This paper seeks to investigate the effects of sales promotions at airport duty-free shops by testing a conceptual model that considers price, coupons, free gifts, points, satisfaction, value, image, and behavioral intentions simultaneously.Design/methodology/approach: For this testing, structural equation modeling was applied to data collected from duty-free shop users at Incheon International Airport.Findings: Price and coupons were found as significant drivers of customer satisfaction, which was directly related to customer value, image, and behavioral intentions.Originality/value: This paper is the first research that examines the effects of sales promotions at the duty-free shops of Incheon International Airport. The identified sales promotion factors that influence the behavioral intentions of customers at duty-free shops are potentially useful for analyzing the possible trends and changes in duty-free shop customer buying behavior.

Studies of DNA repair in saccharomyces cerevisiae. I. Characterization of a new allele of RAD6. II. Investigation of events in the first cell cycle after DNA damage

International Nuclear Information System (INIS)

Douthwright-Fasse, J.A.

1979-01-01

Studies in two independent, but related, areas of DNA repair have been carried out in Saccharomyces cerevisiae; characterization of a new allele in the RAD6 gene which suggests that the gene is multifunctional, and utilization of photoreactivation as a probe of events occurring during the first cell cycle after DNA damage. Strains carrying the new allele, designated rad6-4, are as sensitive to uv and ionizing radiation as those carrying rad6-1 or rad6-3 but, unlike them, are capable of induced mutagenesis and sporulation. Although rad6-4 may well be a missense mutation, the evidence shows that it is unlikely that this phenotype is due to leakiness. Instead, the data suggest that the RAD6 gene is multifunctional. One function is necessary to recover from DNA damage in an error-free manner, and the other is concerned with mutagenic processes and sporulation. Rad6-1 and rad6-3 strains are deficient in both of these functions, while rad6-4 strains are deficient only in the error-free function. The loss of photoreversibility (LOP) of ultraviolet induced mutations to arginine independence in an excision defective strain carrying arg4-17 examines the events occurring in the first cell cycle after DNA damage. LOP is dependent upon de novo protein synthesis. LOP begins immediately after UV irradiation, before semiconservative DNA synthesis takes place, and is complete after four hours in growth medium.There is no evidence indicating whether the normal function of the protein is involved in excision repair, or in one of the two repair processes believed to be inducible; induced mutagenesis or recombinational repair

Recall and Effectiveness of Messages Promoting Smoke-Free Policies in Rural Communities.

Science.gov (United States)

Rayens, Mary Kay; Butler, Karen M; Wiggins, Amanda T; Kostygina, Ganna; Langley, Ronald E; Hahn, Ellen J

2016-05-01

Low-cost media campaigns increase demand for smoke-free policies in underserved rural areas. The study examined the impact of loss- and gain-framed smoke-free print ads on recall and perceived effectiveness in rural communities, controlling for personal characteristics. Following 6- to 9-month print media campaigns in three rural counties, recall and perceived effectiveness of loss-framed (ie, targeting dangers of secondhand smoke [SHS]) and gain-framed (ie, highlighting positive aspects of smoke-free air) ads were assessed using random-digit-dial phone surveys. Respondents were asked if they remembered each ad, whether they liked it, whether they were prompted to contact a smoke-free coalition, whether the ad made them think, and whether it prompted emotion. Mixed modeling assessed whether personal factors predicted ad recall or perceived effectiveness. Loss-framed ads were less likely to be recalled but more likely to prompt emotion. For ads of both frame types, females reported greater recall and perceived effectiveness than males. Those with less education reported higher perceived effectiveness of the ads but lower recall. Nonsmokers were more likely than smokers to perceive the ads as effective. Knowledge of SHS risk and support for smoke-free workplaces were positively associated with recall and effectiveness. Ad recall and perceived effectiveness were associated with framing and demographic and personal characteristics. Smoke-free efforts in rural areas may be bolstered by continuing to promote benefits of smoke-free workplace policies and educate on SHS risks. Rural areas may need to provide a combination of ad types and framing strategies to appeal to a wide audience. Rural communities are disproportionately affected by SHS and less likely to be protected by smoke-free policies. This study adds evidence-based guidance for tailoring rural smoke-free media campaigns using different framing: gain-framed messages (ie, benefits of smoke-free environments) to

Systems Maintenance Automated Repair Tasks (SMART)

Science.gov (United States)

Schuh, Joseph; Mitchell, Brent; Locklear, Louis; Belson, Martin A.; Al-Shihabi, Mary Jo Y.; King, Nadean; Norena, Elkin; Hardin, Derek

2010-01-01

SMART is a uniform automated discrepancy analysis and repair-authoring platform that improves technical accuracy and timely delivery of repair procedures for a given discrepancy (see figure a). SMART will minimize data errors, create uniform repair processes, and enhance the existing knowledge base of engineering repair processes. This innovation is the first tool developed that links the hardware specification requirements with the actual repair methods, sequences, and required equipment. SMART is flexibly designed to be useable by multiple engineering groups requiring decision analysis, and by any work authorization and disposition platform (see figure b). The organizational logic creates the link between specification requirements of the hardware, and specific procedures required to repair discrepancies. The first segment in the SMART process uses a decision analysis tree to define all the permutations between component/ subcomponent/discrepancy/repair on the hardware. The second segment uses a repair matrix to define what the steps and sequences are for any repair defined in the decision tree. This segment also allows for the selection of specific steps from multivariable steps. SMART will also be able to interface with outside databases and to store information from them to be inserted into the repair-procedure document. Some of the steps will be identified as optional, and would only be used based on the location and the current configuration of the hardware. The output from this analysis would be sent to a work authoring system in the form of a predefined sequence of steps containing required actions, tools, parts, materials, certifications, and specific requirements controlling quality, functional requirements, and limitations.

Ergodic Capacity Analysis of Free-Space Optical Links with Nonzero Boresight Pointing Errors

KAUST Repository

Ansari, Imran Shafique

2015-04-01

A unified capacity analysis of a free-space optical (FSO) link that accounts for nonzero boresight pointing errors and both types of detection techniques (i.e. intensity modulation/ direct detection as well as heterodyne detection) is addressed in this work. More specifically, an exact closed-form expression for the moments of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system is presented in terms of well-known elementary functions. Capitalizing on these new moments expressions, we present approximate and simple closedform results for the ergodic capacity at high and low SNR regimes. All the presented results are verified via computer-based Monte-Carlo simulations.

Nucleation theory - Is replacement free energy needed?. [error analysis of capillary approximation

Science.gov (United States)

Doremus, R. H.

1982-01-01

It has been suggested that the classical theory of nucleation of liquid from its vapor as developed by Volmer and Weber (1926) needs modification with a factor referred to as the replacement free energy and that the capillary approximation underlying the classical theory is in error. Here, the classical nucleation equation is derived from fluctuation theory, Gibb's result for the reversible work to form a critical nucleus, and the rate of collision of gas molecules with a surface. The capillary approximation is not used in the derivation. The chemical potential of small drops is then considered, and it is shown that the capillary approximation can be derived from thermodynamic equations. The results show that no corrections to Volmer's equation are needed.

The role of undifferentiated adipose-derived stem cells in peripheral nerve repair.

Science.gov (United States)

Zhang, Rui; Rosen, Joseph M

2018-05-01

Peripheral nerve injuries impose significant health and economic consequences, yet no surgical repair can deliver a complete recovery of sensory or motor function. Traditional methods of repair are less than ideal: direct coaptation can only be performed when tension-free repair is possible, and transplantation of nerve autograft can cause donor-site morbidity and neuroma formation. Cell-based therapy delivered via nerve conduits has thus been explored as an alternative method of nerve repair in recent years. Stem cells are promising sources of the regenerative core material in a nerve conduit because stem cells are multipotent in function, abundant in supply, and more accessible than the myelinating Schwann cells. Among different types of stem cells, undifferentiated adipose-derived stem cell (uASC), which can be processed from adipose tissue in less than two hours, is a promising yet underexplored cell type. Studies of uASC have emerged in the past decade and have shown that autologous uASCs are non-immunogenic, easy to access, abundant in supply, and efficacious at promoting nerve regeneration. Two theories have been proposed as the primary regenerative mechanisms of uASC: in situ trans-differentiation towards Schwann cells, and secretion of trophic and anti-inflammatory factors. Future studies need to fully elucidate the mechanisms, side effects, and efficacy of uASC-based nerve regeneration so that uASCs can be utilized in clinical settings.

Shining Light on Nanotechnology to Help Repair and Regeneration

Science.gov (United States)

Gupta, Asheesh; Avci, Pinar; Sadasivam, Magesh; Chandran, Rakkiyappan; Parizotto, Nivaldo; Vecchio, Daniela; Antunes-Melo, Wanessa C; Dai, Tianhong; Chiang, Long Y.; Hamblin, Michael R.

2012-01-01

Phototherapy can be used in two completely different but complementary therapeutic applications. While low level laser (or light) therapy (LLLT) uses red or near-infrared light alone to reduce inflammation, pain and stimulate tissue repair and regeneration, photodynamic therapy (PDT) uses the combination of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen species that can kill infectious microorganisms and cancer cells or destroy unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in the arteries). The recent development of nanotechnology applied to medicine (nanomedicine) has opened a new front of advancement in the field of phototherapy and has provided hope for the development of nanoscale drug delivery platforms for effective killing of pathological cells and to promote repair and regeneration. Despite the well-known beneficial effects of phototherapy and nanomaterials in producing the killing of unwanted cells and promoting repair and regeneration, there are few reports that combine all three elements i.e. phototherapy, nanotechnology and, tissue repair and regeneration. However, these areas in all possible binary combinations have been addressed by many workers. The present review aims at highlighting the combined multi-model applications of phototherapy, nanotechnology and, reparative and regeneration medicine and outlines current strategies, future applications and limitations of nanoscale-assisted phototherapy for the management of cancers, microbial infections and other diseases, and to promote tissue repair and regeneration. PMID:22951919

OPTIMUM DISTRIBUTION OF REPAIRS IN ТS-8 OF ELECTRIC LOCOMOTIVES VL80С BETWEEN REPAIR DEPOTS IN THE REPUBLIC OF KAZAKHSTAN

Directory of Open Access Journals (Sweden)

Seidulla ABDULLAYEV

2017-06-01

Full Text Available The article presents the solution for the problem of optimal distribution of electric locomotives in repair enterprises for carrying out repairs in the frame of technical service - 8 (ТS-8 and increased technical service - 8 (ITS-8. The aim of the study is to improve the efficacy of a rolling stock with a simultaneous decrease in the total expenses connected with the repair of locomotives and their transportation in repair enterprises. This is possible due to a reduction in the requirement for repairs by optimization of a resource before change of wheel bandages in electric locomotives VL80С that promotes an increase in their between-repairs run.

Comparison between single-row and double-row rotator cuff repair: a biomechanical study.

Science.gov (United States)

Milano, Giuseppe; Grasso, Andrea; Zarelli, Donatella; Deriu, Laura; Cillo, Mario; Fabbriciani, Carlo

2008-01-01

The aim of this study was to compare the mechanical behavior under cyclic loading test of single-row and double-row rotator cuff repair with suture anchors in an ex-vivo animal model. For the present study, 50 fresh porcine shoulders were used. On each shoulder, a crescent-shaped full-thickness tear of the infraspinatus was performed. Width of the tendon tear was 2 cm. The lesion was repaired using metal suture anchors. Shoulders were divided in four groups, according the type of repair: single-row tension-free repair (Group 1); single-row tension repair (Group 2); double-row tension-free repair (Group 3); double-row tension repair (Group 4); and a control group. Specimens were subjected to a cyclic loading test. Number of cycles at 5 mm of elongation and at failure, and total elongation were calculated. Single-row tension repair showed significantly poorest results for all the variables considered, when compared with the other groups. Regarding the mean number of cycles at 5 mm of elongation and at failure, there was a nonsignificant difference between Groups 3 and 4, and both of them were significantly greater than Group 1. For mean total elongation, the difference between Groups 1, 3, and 4 was not significant, but all of them were significantly lower than the control group. A single-row repair is particularly weak when performed under tension. Double-row repair is significantly more resistant to cyclic displacement than single-row repair in both tension-free and tension repair. Double-row repair technique can be primarily considered for large, unstable rotator cuff tears to improve mechanical strength of primary fixation of tendons to bone.

Primary unilateral cleft lip repair

OpenAIRE

Adenwalla, H. S.; Narayanan, P. V.

2009-01-01

The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform clos...

DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers.

Science.gov (United States)

Javid, Mahsa; Sasanakietkul, Thanyawat; Nicolson, Norman G; Gibson, Courtney E; Callender, Glenda G; Korah, Reju; Carling, Tobias

2018-02-01

Efficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity. We hypothesized that persistent oxidative stress and consequent transcriptional dysregulation observed in thyroid follicles will lead to MMR deficiency and potentiate papillary thyroid tumorigenesis. MMR gene expression was analyzed by targeted microarray in 18 papillary thyroid cancer (PTC), 9 paracarcinoma normal thyroid (PCNT) and 10 normal thyroid (NT) samples. The findings were validated by qRT-PCR, and in follicular thyroid cancers (FTC) and follicular thyroid adenomas (FTA) for comparison. FOXO transcription factor expression was also analyzed. Protein expression was assessed by immunohistochemistry. Genomic integrity was evaluated by whole-exome sequencing-derived read-depth analysis and Mann-Whitney U test. Clinical correlations were assessed using Fisher's exact and t tests. Microarray and qRT-PCR revealed reduced expression of all four MMR genes in PTC compared with PCNT and of PMS2 compared with NT. FTC and FTA showed upregulation in MLH1, MLH3 and PMS2. PMS2 protein expression correlated with the mRNA expression pattern. FOXO1 showed lower expression in PMS2-deficient PTCs (log2-fold change -1.72 vs. -0.55, U = 11, p clinical characteristics. MMR deficiency, potentially promoted by FOXO1 suppression, may explain the etiology for PTC development in some patients. FTC and FTA retain MMR activity and are likely caused by a different tumorigenic pathway.

Repair-modification of radiodamaged genes

International Nuclear Information System (INIS)

Volpe, P.; Institute of Experimental Medicine, Rome; Eremenko, T.

1995-01-01

It is proposed that through repair-modification, the modified base 5mC may have facilitated the divergent evolution of coding (hypomethylated exon) and uncoding (hypermethylated promoter and intron) sequences in eukaryotic genes. The radioinduced repair patches appearing in regions lacking 5mC are fully reconstructed by excision-repair, whereas those appearing in regions containing 5mC are incompletely reconstructed by this conventional mechanism. Such a second class of repair patches may, however, become fully reconstructed, in the S phase, by repair-modification. In fact, while DNA polymerase β - which is a key enzyme of excision-repair - is active through the whole interphase. DNA methylase - which is responsible for post-synthetic DNA modification - is essentially active in S. Uncoupling of these two enzyme systems, outside S, might explain why in unsynchronised cells repair patches of non-replicating strands are hypomethylated when compared with specific methylation of replicating strands. In other words, excision-repair would always be able to re-establish the primary ATGC language of both damaged unmethylated and methylated regions, while repair-modification would be able to re-establish the modified ATGC(5mC) language of the damaged methylated regions, only in S, but not in G 1 or G 2 . In these two phases, when DNA methylation is inversely correlated with pre-mRNA transcription (as in the case of many tissue-specific genes), such demethylation might induce a silent transcriptional unit to become active. (Author)

A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study.

Science.gov (United States)

Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V N; Poh, Chueh Loo; Wang, Dong-An

2015-11-09

In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.

Delayed peripheral nerve repair: methods, including surgical ′cross-bridging′ to promote nerve regeneration

Directory of Open Access Journals (Sweden)

Tessa Gordon

2015-01-01

Full Text Available Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to ′protect′ chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.

Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11-mutant mouse meiocytes, and is altered in the absence of HORMAD1.

Science.gov (United States)

Carofiglio, Fabrizia; Sleddens-Linkels, Esther; Wassenaar, Evelyne; Inagaki, Akiko; van Cappellen, Wiggert A; Grootegoed, J Anton; Toth, Attila; Baarends, Willy M

2018-03-01

Repair of SPO11-dependent DNA double-strand breaks (DSBs) via homologous recombination (HR) is essential for stable homologous chromosome pairing and synapsis during meiotic prophase. Here, we induced radiation-induced DSBs to study meiotic recombination and homologous chromosome pairing in mouse meiocytes in the absence of SPO11 activity (Spo11 YF/YF model), and in the absence of both SPO11 and HORMAD1 (Spo11/Hormad1 dko). Within 30 min after 5 Gy irradiation of Spo11 YF/YF mice, 140-160 DSB repair foci were detected, which specifically localized to the synaptonemal complex axes. Repair of radiation-induced DSBs was incomplete in Spo11 YF/YF compared to Spo11 +/YF meiocytes. Still, repair of exogenous DSBs promoted partial recovery of chromosome pairing and synapsis in Spo11 YF/YF meiocytes. This indicates that at least part of the exogenous DSBs can be processed in an interhomolog recombination repair pathway. Interestingly, in a seperate experiment, using 3 Gy of irradiation, we observed that Spo11/Hormad1 dko spermatocytes contained fewer remaining DSB repair foci at 48 h after irradiation compared to irradiated Spo11 knockout spermatocytes. Together, these results show that recruitment of exogenous DSBs to the synaptonemal complex, in conjunction with repair of exogenous DSBs via the homologous chromosome, contributes to homology recognition. In addition, the data suggest a role for HORMAD1 in DNA repair pathway choice in mouse meiocytes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms

Directory of Open Access Journals (Sweden)

Zhi-yuan Guo

2015-01-01

Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

APOBEC3 cytidine deaminases in double-strand DNA break repair and cancer promotion.

Science.gov (United States)

Nowarski, Roni; Kotler, Moshe

2013-06-15

High frequency of cytidine to thymidine conversions was identified in the genome of several types of cancer cells. In breast cancer cells, these mutations are clustered in long DNA regions associated with single-strand DNA (ssDNA), double-strand DNA breaks (DSB), and genomic rearrangements. The observed mutational pattern resembles the deamination signature of cytidine to uridine carried out by members of the APOBEC3 family of cellular deaminases. Consistently, APOBEC3B (A3B) was recently identified as the mutational source in breast cancer cells. A3G is another member of the cytidine deaminases family predominantly expressed in lymphoma cells, where it is involved in mutational DSB repair following ionizing radiation treatments. This activity provides us with a new paradigm for cancer cell survival and tumor promotion and a mechanistic link between ssDNA, DSBs, and clustered mutations. Cancer Res; 73(12); 3494-8. ©2013 AACR. ©2013 AACR.

A recursive framework for time-dependent characteristics of tested and maintained standby units with arbitrary distributions for failures and repairs

International Nuclear Information System (INIS)

Vaurio, Jussi K.

2015-01-01

The time-dependent unavailability and the failure and repair intensities of periodically tested aging standby system components are solved with recursive equations under three categories of testing and repair policies. In these policies, tests or repairs or both can be minimal or perfect renewals. Arbitrary distributions are allowed to times to failure as well as to repair and renewal durations. Major preventive maintenance is done periodically or at random times, e.g. when a true demand occurs. In the third option process renewal is done if a true demand occurs or when a certain mission time has expired since the previous maintenance, whichever occurs first. A practical feature is that even if a repair can renew the unit, it does not generally renew the alternating process. The formalism updates and extends earlier results by using a special backward-renewal equation method, by allowing scheduled tests not limited to equal intervals and accepting arbitrary distributions and multiple failure types and causes, including failures caused by tests, human errors and true demands. Explicit solutions are produced to integral equations associated with an age-renewal maintenance policy. - Highlights: • Time-dependent unavailability, failure count and repair count for a standby system. • Free testing schedule and distributions for times to failure, repair and maintenance. • Multiple failure modes; tests or repairs or both can be minimal or perfect renewals. • Process renewals periodically, randomly or based on the process age or an initiator. • Backward renewal equations as explicit solutions to Volterra-type integral equations

G9a coordinates with the RPA complex to promote DNA damage repair and cell survival.

Science.gov (United States)

Yang, Qiaoyan; Zhu, Qian; Lu, Xiaopeng; Du, Yipeng; Cao, Linlin; Shen, Changchun; Hou, Tianyun; Li, Meiting; Li, Zhiming; Liu, Chaohua; Wu, Di; Xu, Xingzhi; Wang, Lina; Wang, Haiying; Zhao, Ying; Yang, Yang; Zhu, Wei-Guo

2017-07-25

Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This mechanism facilitates homologous recombination (HR) and cell survival. We confirmed the interaction between RPA and G9a to be critical for RPA foci formation and HR upon DNA damage. Collectively, our findings demonstrate a regulatory pathway based on CK2-G9a-RPA that permits HR in cancer cells and provide further rationale for the use of G9a inhibitors as a cancer therapeutic.

Performance analysis of multihop heterodyne free-space optical communication over general Malaga turbulence channels with pointing error

KAUST Repository

Alheadary, Wael Ghazy

2017-09-21

This work investigates the end-to-end performance of a free space optical amplify-and-forward (AF) channel-state-information (CSI)-assisted relaying system using heterodyne detection over Malaga turbulence channels at the presence of pointing error employing rectangular quadrature amplitude modulation (R-QAM). More specifically, we present exact closed-form expressions for average bit-error rate for adaptive/non-adaptive modulation, achievable spectral efficiency, and ergodic capacity by utilizing generalized power series of Meijer\\'s G-function. Moreover, asymptotic closed form expressions are provided to validate our work at high power regime. In addition, all the presented analytical results are illustrated using a selected set of numerical results. Moreover, we applied the bisection method to find the optimum beam width for the proposed FSO system.

Inducible error-prone repair in B. subtilis. Progress report, September 1, 1978-August 31, 1979

International Nuclear Information System (INIS)

Yasbin, R.E.

1979-01-01

The mechanism of activation and the mode of action of the SOS system in the bacterium Bacillus subtilis is under study. Interesting aspects of the SOS system in B. subtilis are: (1) the differences between SOS functions in this bacterium and in the enteric bacteria; (2) the spontaneous activation of SOS functions in component cells; and (3) the difficulty in obtaining consistent results for mutation studies in this bacterium. In order to characterize the SOS system of B. subtilis, it was proposed to: (1) isolate bacteria mutated in genes controlling various repair function; (2) investigate inducible repair; (3) determine the role of endogeneous Bacillus prophages in SOS functions; and (4) develop a tester system for potential carcinogens from competent Bacillus subtilis cells. Research has been able to: (1) isolate strains of B. subtilis in which the endogeneous prophages have been removed or neutralized; (2) demonstrate the association of one SOS function with prophage SPB; (3) demonstrate that the survival of uv-irradiated B. subtilis is not significantly altered by the removal and neutralization of the endogeneous prophages; (4) develop competant B. subtilis into a tester system; and (5) show that DNA polymerase III is absolutely necessary for W reactivation. In addition, uv and mitomycin C resistant mutants have been isolated and inducible postreplication repair in excision-repair deficient mutants of B. subtilis has been studied. The last two results are somewaht confusing but highly exciting in regards to DNA repair mechanisms in B. subtilis

Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.

Science.gov (United States)

Esteller, M; Garcia-Foncillas, J; Andion, E; Goodman, S N; Hidalgo, O F; Vanaclocha, V; Baylin, S B; Herman, J G

2000-11-09

The DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumor to alkylating agents. We analyzed the MGMT promoter in tumor DNA by a methylation-specific polymerase-chain-reaction assay. The gliomas were obtained from patients who had been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU). The molecular data were correlated with the clinical outcome. The MGMT promoter was methylated in gliomas from 19 of 47 patients (40 percent). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status. Methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents.

Collaborative Repair in EFL Classroom Talk.

Science.gov (United States)

Iles, Zara

1996-01-01

Drawing data from audiotaped lessons with 10 native-speaker English-as-a-Foreign-Language (EFL) teachers and 12 EFL learners of varied linguistic backgrounds, a study explored some of the ways in which classroom talk by learners is collaboratively built to repair errors, misunderstandings, and non-communication. Focus is on both explicit and…

Oxidative DNA damage & repair: An introduction.

Science.gov (United States)

Cadet, Jean; Davies, Kelvin J A

2017-06-01

This introductory article should be viewed as a prologue to the Free Radical Biology & Medicine Special Issue devoted to the important topic of Oxidatively Damaged DNA and its Repair. This special issue is dedicated to Professor Tomas Lindahl, co-winner of the 2015 Nobel Prize in Chemistry for his seminal discoveries in the area repair of oxidatively damaged DNA. In the past several years it has become abundantly clear that DNA oxidation is a major consequence of life in an oxygen-rich environment. Concomitantly, survival in the presence of oxygen, with the constant threat of deleterious DNA mutations and deletions, has largely been made possible through the evolution of a vast array of DNA repair enzymes. The articles in this Oxidatively Damaged DNA & Repair special issue detail the reactions by which intracellular DNA is oxidatively damaged, and the enzymatic reactions and pathways by which living organisms survive such assaults by repair processes. Copyright © 2017 Elsevier Inc. All rights reserved.

[Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

Science.gov (United States)

Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

2018-02-01

The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

Epigenetic changes of DNA repair genes in cancer.

Science.gov (United States)

Lahtz, Christoph; Pfeifer, Gerd P

2011-02-01

'Every Hour Hurts, The Last One Kills'. That is an old saying about getting old. Every day, thousands of DNA damaging events take place in each cell of our body, but efficient DNA repair systems have evolved to prevent that. However, our DNA repair system and that of most other organisms are not as perfect as that of Deinococcus radiodurans, for example, which is able to repair massive amounts of DNA damage at one time. In many instances, accumulation of DNA damage has been linked to cancer, and genetic deficiencies in specific DNA repair genes are associated with tumor-prone phenotypes. In addition to mutations, which can be either inherited or somatically acquired, epigenetic silencing of DNA repair genes may promote tumorigenesis. This review will summarize current knowledge of the epigenetic inactivation of different DNA repair components in human cancer.

Repair of a mandibular defect with a free vascularized coccygeal vertebra transfer in a dog.

Science.gov (United States)

Yeh, L S; Hou, S M

1994-01-01

Bilateral mandibular defects in a male mongrel dog were repaired. On the left side, a free vascularized coccygeal bone graft that included the median caudal artery and caudal vein was used to correct the defect. On the right side, the defect was bridged with a bone plate and screws. For further immobilization, the muzzle was temporarily taped for 3 weeks and a pharyngostomy tube was used for nutritional support. The dog was able to eat dry commercial food satisfactorily within 2 months of surgery despite mild malocclusion. Radiographs taken 2 months and 18 months postoperatively showed bony union with graft hypertrophy in the left mandible, whereas the right mandibular defect showed protracted nonunion. The results indicate that vascularized coccygeal vertebra transfer provides an alternative for the management of canine mandibular defects.

Genomic Instability Promoted by Overexpression of Mismatch Repair Factors in Yeast: A Model for Understanding Cancer Progression.

Science.gov (United States)

Chakraborty, Ujani; Dinh, Timothy A; Alani, Eric

2018-04-13

Mismatch repair (MMR) proteins act in spellchecker roles to excise misincorporation errors that occur during DNA replication. Curiously, large-scale analyses of a variety of cancers showed that increased expression of MMR proteins often correlated with tumor aggressiveness, metastasis, and early recurrence. To better understand these observations, we used the TCGA and GENT databases to analyze MMR protein expression in cancers. We found that the MMR genes MSH2 and MSH6 are overexpressed more frequently than MSH3 , and that MSH2 and MSH6 are often co-overexpressed as a result of copy number amplifications of these genes. These observations encouraged us to test the effects of upregulating MMR protein levels in baker's yeast, where we can sensitively monitor genome instability phenotypes associated with cancer initiation and progression. Msh6 overexpression (2 to 4-fold) almost completely disrupted mechanisms that prevent recombination between divergent DNA sequences by interacting with the DNA polymerase processivity clamp PCNA and by sequestering the Sgs1 helicase. Importantly, co-overexpression of Msh2 and Msh6 (∼8-fold) conferred, in a PCNA interaction dependent manner, several genome instability phenotypes including increased mutation rate, increased sensitivity to the DNA replication inhibitor hydroxyurea and the DNA damaging agents methyl methanesulfonate and 4-nitroquinoline N-oxide, and elevated loss of heterozygosity. Msh2 and Msh6 co-overexpression also altered the cell cycle distribution of exponentially growing cells, resulting in an increased fraction of unbudded cells, consistent with a larger percentage of cells in G1. These novel observations suggested that overexpression of MSH factors affected the integrity of the DNA replication fork, causing genome instability phenotypes that could be important for promoting cancer progression. Copyright © 2018, Genetics.

Relay-aided free-space optical communications using α - μ distribution over atmospheric turbulence channels with misalignment errors

Science.gov (United States)

Upadhya, Abhijeet; Dwivedi, Vivek K.; Singh, G.

2018-06-01

In this paper, we have analyzed the performance of dual hop radio frequency (RF)/free-space optical (FSO) fixed gain relay environment confined by atmospheric turbulence induced fading channel over FSO link and modeled using α - μ distribution. The RF hop of the amplify-and-forward scheme undergoes the Rayleigh fading and the proposed system model also considers the pointing error effect on the FSO link. A novel and accurate mathematical expression of the probability density function for a FSO link experiencing α - μ distributed atmospheric turbulence in the presence of pointing error is derived. Further, we have presented analytical expressions of outage probability and bit error rate in terms of Meijer-G function. In addition to this, a useful and mathematically tractable closed-form expression for the end-to-end ergodic capacity of the dual hop scheme in terms of bivariate Fox's H function is derived. The atmospheric turbulence, misalignment errors and various binary modulation schemes for intensity modulation on optical wireless link are considered to yield the results. Finally, we have analyzed each of the three performance metrics for high SNR in order to represent them in terms of elementary functions and the achieved analytical results are supported by computer-based simulations.

Video Error Correction Using Steganography

Science.gov (United States)

Robie, David L.; Mersereau, Russell M.

2002-12-01

The transmission of any data is always subject to corruption due to errors, but video transmission, because of its real time nature must deal with these errors without retransmission of the corrupted data. The error can be handled using forward error correction in the encoder or error concealment techniques in the decoder. This MPEG-2 compliant codec uses data hiding to transmit error correction information and several error concealment techniques in the decoder. The decoder resynchronizes more quickly with fewer errors than traditional resynchronization techniques. It also allows for perfect recovery of differentially encoded DCT-DC components and motion vectors. This provides for a much higher quality picture in an error-prone environment while creating an almost imperceptible degradation of the picture in an error-free environment.

True Lies: The Double Life of the Nucleotide Excision Repair Factors in Transcription and DNA Repair

Directory of Open Access Journals (Sweden)

Nicolas Le May

2010-01-01

Full Text Available Nucleotide excision repair (NER is a major DNA repair pathway in eukaryotic cells. NER removes structurally diverse lesions such as pyrimidine dimers, arising upon UV irradiation or bulky chemical adducts, arising upon exposure to carcinogens and some chemotherapeutic drugs. NER defects lead to three genetic disorders that result in predisposition to cancers, accelerated aging, neurological and developmental defects. During NER, more than 30 polypeptides cooperate to recognize, incise, and excise a damaged oligonucleotide from the genomic DNA. Recent papers reveal an additional and unexpected role for the NER factors. In the absence of a genotoxic attack, the promoters of RNA polymerases I- and II-dependent genes recruit XPA, XPC, XPG, and XPF to initiate gene expression. A model that includes the growth arrest and DNA damage 45α protein (Gadd45α and the NER factors, in order to maintain the promoter of active genes under a hypomethylated state, has been proposed but remains controversial. This paper focuses on the double life of the NER factors in DNA repair and transcription and describes the possible roles of these factors in the RNA synthesis process.

Repair and mutagenesis of herpes simplex virus in UV-irradiated monkey cells

International Nuclear Information System (INIS)

Lytle, C.D.; Goddard, J.G.; Lin, C.H.

1980-01-01

Mutagenic repair in mammalian cells was investigated by determining the mutagenesis of UV-irradiated or unirradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cells. These results were compared with the results for UV-enhanced virus reactivation (UVER) in the same experimental situation. High and low multiplicities of infection were used to determine the effects of multiplicity reactivation (MR). UVER and MR were readily demonstrable and were approximately equal in amount in an infectious center assay. For this study, a forward-mutation assay was developed to detect virus mutants resistant to iododeoxycytidine (ICdR), probably an indication of the mutant virus being defective at its thymidine kinase locus. ICdR-resistant mutants did not have a growth advantage over wild-type virus in irradiated or unirradiated cells. Thus, higher fractions of mutant virus indicated greater mutagenesis during virus repair and/or replication. The data showed that: (1) unirradiated virus was mutated in unirradiated cells, providing a background level of mutagenesis; (2) unirradiated virus was mutated about 40% more in irradiated cells, indicating that virus replication (DNA synthesis) became more mutagenic as a result of cell irradiation; (3) irradiated virus was mutated much more (about 6-fold) than unirradiated virus, even in unirradiated cells; (4) cell irradiation did not change the mutagenesis of irradiated virus except at high multiplicity of infection. High multiplicity of infection did not demonstrate UVER or MR alone to be either error-free or error-prone. When the two processes were present simultaneously, they were mutagenic. (orig.)

Turbine repair process, repaired coating, and repaired turbine component

Science.gov (United States)

Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose

2015-11-03

A turbine repair process, a repaired coating, and a repaired turbine component are disclosed. The turbine repair process includes providing a turbine component having a higher-pressure region and a lower-pressure region, introducing particles into the higher-pressure region, and at least partially repairing an opening between the higher-pressure region and the lower-pressure region with at least one of the particles to form a repaired turbine component. The repaired coating includes a silicon material, a ceramic matrix composite material, and a repaired region having the silicon material deposited on and surrounded by the ceramic matrix composite material. The repaired turbine component a ceramic matrix composite layer and a repaired region having silicon material deposited on and surrounded by the ceramic matrix composite material.

Field error lottery

Energy Technology Data Exchange (ETDEWEB)

Elliott, C.J.; McVey, B. (Los Alamos National Lab., NM (USA)); Quimby, D.C. (Spectra Technology, Inc., Bellevue, WA (USA))

1990-01-01

The level of field errors in an FEL is an important determinant of its performance. We have computed 3D performance of a large laser subsystem subjected to field errors of various types. These calculations have been guided by simple models such as SWOOP. The technique of choice is utilization of the FELEX free electron laser code that now possesses extensive engineering capabilities. Modeling includes the ability to establish tolerances of various types: fast and slow scale field bowing, field error level, beam position monitor error level, gap errors, defocusing errors, energy slew, displacement and pointing errors. Many effects of these errors on relative gain and relative power extraction are displayed and are the essential elements of determining an error budget. The random errors also depend on the particular random number seed used in the calculation. The simultaneous display of the performance versus error level of cases with multiple seeds illustrates the variations attributable to stochasticity of this model. All these errors are evaluated numerically for comprehensive engineering of the system. In particular, gap errors are found to place requirements beyond mechanical tolerances of {plus minus}25{mu}m, and amelioration of these may occur by a procedure utilizing direct measurement of the magnetic fields at assembly time. 4 refs., 12 figs.

Role for Artemis nuclease in the repair of radiation-induced DNA double strand breaks by alternative end joining.

Science.gov (United States)

Moscariello, Mario; Wieloch, Radi; Kurosawa, Aya; Li, Fanghua; Adachi, Noritaka; Mladenov, Emil; Iliakis, George

2015-07-01

Exposure of cells to ionizing radiation or radiomimetic drugs generates DNA double-strand breaks that are processed either by homologous recombination repair (HRR), or by canonical, DNA-PKcs-dependent non-homologous end-joining (C-NHEJ). Chemical or genetic inactivation of factors involved in C-NHEJ or HRR, but also their local failure in repair proficient cells, promotes an alternative, error-prone end-joining pathway that serves as backup (A-EJ). There is evidence for the involvement of Artemis endonuclease, a protein deficient in a human radiosensitivity syndrome associated with severe immunodeficiency (RS-SCID), in the processing of subsets of DSBs by HRR or C-NHEJ. It is thought that within HRR or C-NHEJ Artemis processes DNA termini at complex DSBs. Whether Artemis has a role in A-EJ remains unknown. Here, we analyze using pulsed-field gel electrophoresis (PFGE) and specialized reporter assays, DSB repair in wild-type pre-B NALM-6 lymphocytes, as well as in their Artemis(-/-), DNA ligase 4(-/-) (LIG4(-/-)), and LIG4(-/-)/Artemis(-/-) double mutant counterparts, under conditions allowing evaluation of A-EJ. Our results substantiate the suggested roles of Artemis in C-NHEJ and HRR, but also demonstrate a role for the protein in A-EJ that is confirmed in Artemis deficient normal human fibroblasts. We conclude that Artemis is a nuclease participating in DSB repair by all major repair pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of outcome of totally extra peritoneal laparoscopic inguinal hernia repair with lichtenstein open repair

International Nuclear Information System (INIS)

Ahmed, I.; Dian, A.; Azam, U.F.; Khan, M.

2015-01-01

The objective of this study was to evaluate outcome of total extraperitoneal laparoscopic inguinal hernia repair with Lichtenstein open repair in terms of postoperative pain. Study Design: Quasi experimental study. Place and Duration of Study: Surgical unit l Rawalpindi and Allied hospitals from January to June 2012. Patients and Methods: Sixty patients, with unilateral, primary, inguinal hernia were alternately allocated to undergo either total extraperitoneal (TEP) laparoscopic repair of inguinal hernia or Lichtenstein tension free, mesh repair of inguinal hernia. Pain scores at 12, 24, and 48 hours and at 7 days of follow up were noted using a visual analogue scale. Total number of intravenous injections of Diclofenac Sodium requested by the patient for pain relief was also noted. Results: At 12 hours after surgery, the mean pain scores in the TEP group were 3.1 ± 1.8 and in the Lichtenstein group they were 4.2 ± 2.1 (p 0.031). At 24 hours after surgery, the scores were 2.3 ± 1.5 and 3.1 ± 1.9 for the TEP and Lichtenstein groups, respectively (p = 0.026). At 48 hours after surgery, the mean pain scores in the TEP group were 1.5 ± 1.1 while in the Lichtenstein group they were 2.0 ± 1.6 (p = 0.041). At 7 days after surgery, the scores were 0.3 ± 0.5 in the TEP group and 0.4 ± 0.8 in the Lichtenstein group (0.137). The mean number of injection of Diclofenac Sodium required by the TEP and Lichtenstein groups was 3.1 ± 1.6 and 5.8 ± 2.2, respectively (p = 0.011). Conclusion: Less postoperative pain and requirement for analgesics were reported by patients who underwent total extraperitoneal laparoscopic repair of inguinal hernia as compared to those who underwent inguinal hernia repair by Lichtenstein tension free mesh hernioplasty. (author)

Aspects of DNA repair and nucleotide pool imbalance

Energy Technology Data Exchange (ETDEWEB)

Holliday, R.

1985-01-01

Evidence that optimum repair depends on adequate pools of deoxynucleotide triphosphates (dNTPs) comes from the study of pyrimidine auxotrophs of Ustilago maydis. These strains are sensitive to UV light and X-rays, and for pyr1-1 it has been shown that the intracellular concentration of dTTP is reduced about 7-fold. The survival curve of pyr1-1 after UV-treatment, and split dose experiments with wild-type cells, provide evidence for an inducible repair mechanism, which probably depends on genetic recombination. Although inducible repair saves cellular resources, it has the disadvantage of becoming ineffective at doses which are high enough to inactivate the repressed structural gene(s) for repair enzymes. It is clear that a wide variety of repair mechanisms have evolved to remove lesions which arise either spontaneously or as a result of damage from external agents. Nevertheless, it would be incorrect to assume that all species require all possible pathways of repair. It is now well established that the accuracy of DNA and protein synthesis depends on proof-reading or editing mechanisms. Optimum accuracy levels will evolve from the balance between error avoidance in macromolecular synthesis and physiological efficiency in growth and propagation.

Video Error Correction Using Steganography

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Robie David L

2002-01-01

Full Text Available The transmission of any data is always subject to corruption due to errors, but video transmission, because of its real time nature must deal with these errors without retransmission of the corrupted data. The error can be handled using forward error correction in the encoder or error concealment techniques in the decoder. This MPEG-2 compliant codec uses data hiding to transmit error correction information and several error concealment techniques in the decoder. The decoder resynchronizes more quickly with fewer errors than traditional resynchronization techniques. It also allows for perfect recovery of differentially encoded DCT-DC components and motion vectors. This provides for a much higher quality picture in an error-prone environment while creating an almost imperceptible degradation of the picture in an error-free environment.

My journey to DNA repair.

Science.gov (United States)

Lindahl, Tomas

2013-02-01

I completed my medical studies at the Karolinska Institute in Stockholm but have always been devoted to basic research. My longstanding interest is to understand fundamental DNA repair mechanisms in the fields of cancer therapy, inherited human genetic disorders and ancient DNA. I initially measured DNA decay, including rates of base loss and cytosine deamination. I have discovered several important DNA repair proteins and determined their mechanisms of action. The discovery of uracil-DNA glycosylase defined a new category of repair enzymes with each specialized for different types of DNA damage. The base excision repair pathway was first reconstituted with human proteins in my group. Cell-free analysis for mammalian nucleotide excision repair of DNA was also developed in my laboratory. I found multiple distinct DNA ligases in mammalian cells, and led the first genetic and biochemical work on DNA ligases I, III and IV. I discovered the mammalian exonucleases DNase III (TREX1) and IV (FEN1). Interestingly, expression of TREX1 was altered in some human autoimmune diseases. I also showed that the mutagenic DNA adduct O(6)-methylguanine (O(6)mG) is repaired without removing the guanine from DNA, identifying a surprising mechanism by which the methyl group is transferred to a residue in the repair protein itself. A further novel process of DNA repair discovered by my research group is the action of AlkB as an iron-dependent enzyme carrying out oxidative demethylation. Copyright © 2013. Production and hosting by Elsevier Ltd.

Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.

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Christos Rammos

Full Text Available Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO. NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%. Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03 and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001. PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02 and improved endothelial functions (FMD 4.8±1.0%, p<0.0001.We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.

Effects of whole body γ irradiation on skin wound cells and the repaired-promoting action of W11-a12

International Nuclear Information System (INIS)

Shu Chongxiang; Cheng Tianmin; Yan Guohe; Ran Xinze

2002-01-01

Objective: To study the effects of 6 Gy whole body γ irradiation on components of wound cells and the repair-promoting action of W 11 -a 12 , an extract from Periplaneta americana. Methods: After mice were received 6 Gy gamma ray irradiation, the area of healing range in wound cross section, the cellular infiltration of wound and the content of basic fibroblast growth factor (bFGF) in wound epithelial cells were observed and the healing-promoting effect of W 11 -a 12 on the radiation-impaired wound was investigated. Results: The area of healing range in cross section was decreased, various infiltrated cells were all inhibited by radiation, but the range of inhibition was more or less different, and the descending order of severity was as follows: macrophages, vascular endothelial cells, fibroblasts and epithelial cells. The content of bFGF in epithelial cells was decreased. W 11 -a 12 had beneficial heal-promoting effect on radiation-impaired wound: it increased cellular infiltration and promoted synthesis and secretion of bFGF in epithelial cells. Conclusion: The depletion of wound cells is mainly responsible for the healing deficits of radiation-impaired skin wound and W 11 -a 12 enhances cell migration and proliferation and promotes synthesis and secretion of bFGF in epithelial cells

Crystal Structures of DNA-Whirly Complexes and Their Role in Arabidopsis Organelle Genome Repair

Energy Technology Data Exchange (ETDEWEB)

Cappadocia, Laurent; Maréchal, Alexandre; Parent, Jean-Sébastien; Lepage, Étienne; Sygusch, Jurgen; Brisson, Normand (Montreal)

2010-09-07

DNA double-strand breaks are highly detrimental to all organisms and need to be quickly and accurately repaired. Although several proteins are known to maintain plastid and mitochondrial genome stability in plants, little is known about the mechanisms of DNA repair in these organelles and the roles of specific proteins. Here, using ciprofloxacin as a DNA damaging agent specific to the organelles, we show that plastids and mitochondria can repair DNA double-strand breaks through an error-prone pathway similar to the microhomology-mediated break-induced replication observed in humans, yeast, and bacteria. This pathway is negatively regulated by the single-stranded DNA (ssDNA) binding proteins from the Whirly family, thus indicating that these proteins could contribute to the accurate repair of plant organelle genomes. To understand the role of Whirly proteins in this process, we solved the crystal structures of several Whirly-DNA complexes. These reveal a nonsequence-specific ssDNA binding mechanism in which DNA is stabilized between domains of adjacent subunits and rendered unavailable for duplex formation and/or protein interactions. Our results suggest a model in which the binding of Whirly proteins to ssDNA would favor accurate repair of DNA double-strand breaks over an error-prone microhomology-mediated break-induced replication repair pathway.

The DNA translocase RAD5A acts independently of the other main DNA repair pathways, and requires both its ATPase and RING domain for activity in Arabidopsis thaliana.

Science.gov (United States)

Klemm, Tobias; Mannuß, Anja; Kobbe, Daniela; Knoll, Alexander; Trapp, Oliver; Dorn, Annika; Puchta, Holger

2017-08-01

Multiple pathways exist to repair DNA damage induced by methylating and crosslinking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the functional homolog of budding yeast Rad5 that is required for the error-free branch of post-replicative repair, plays a surprisingly prominent role in the repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase domain and the ubiquitination function of the RING domain of the Arabidopsis protein are essential for the cellular response to different forms of DNA damage. To define the exact role of RAD5A within the complex network of DNA repair pathways, we crossed the rad5a mutant line with mutants of different known repair factors of Arabidopsis. We had previously shown that RAD5A acts independently of two main pathways of replication-associated DNA repair defined by the helicase RECQ4A and the endonuclease MUS81. The enhanced sensitivity of all double mutants tested in this study indicates that the repair of damaged DNA by RAD5A also occurs independently of nucleotide excision repair (AtRAD1), single-strand break repair (AtPARP1), as well as microhomology-mediated double-strand break repair (AtTEB). Moreover, RAD5A can partially complement for a deficient AtATM-mediated DNA damage response in plants, as the double mutant shows phenotypic growth defects. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Friendship at work and error disclosure

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Hsiao-Yen Mao

2017-10-01

Full Text Available Organizations rely on contextual factors to promote employee disclosure of self-made errors, which induces a resource dilemma (i.e., disclosure entails costing one's own resources to bring others resources and a friendship dilemma (i.e., disclosure is seemingly easier through friendship, yet the cost of friendship is embedded. This study proposes that friendship at work enhances error disclosure and uses conservation of resources theory as underlying explanation. A three-wave survey collected data from 274 full-time employees with a variety of occupational backgrounds. Empirical results indicated that friendship enhanced error disclosure partially through relational mechanisms of employees’ attitudes toward coworkers (i.e., employee engagement and of coworkers’ attitudes toward employees (i.e., perceived social worth. Such effects hold when controlling for established predictors of error disclosure. This study expands extant perspectives on employee error and the theoretical lenses used to explain the influence of friendship at work. We propose that, while promoting error disclosure through both contextual and relational approaches, organizations should be vigilant about potential incongruence.

Advanced repair solution of clear defects on HTPSM by using nanomachining tool

Science.gov (United States)

Lee, Hyemi; Kim, Munsik; Jung, Hoyong; Kim, Sangpyo; Yim, Donggyu

2015-10-01

As the mask specifications become tighter for low k1 lithography, more aggressive repair accuracy is required below sub 20nm tech. node. To meet tight defect specifications, many maskshops select effective repair tools according to defect types. Normally, pattern defects are repaired by the e-beam repair tool and soft defects such as particles are repaired by the nanomachining tool. It is difficult for an e-beam repair tool to remove particle defects because it uses chemical reaction between gas and electron, and a nanomachining tool, which uses physical reaction between a nano-tip and defects, cannot be applied for repairing clear defects. Generally, film deposition process is widely used for repairing clear defects. However, the deposited film has weak cleaning durability, so it is easily removed by accumulated cleaning process. Although the deposited film is strongly attached on MoSiN(or Qz) film, the adhesive strength between deposited Cr film and MoSiN(or Qz) film becomes weaker and weaker by the accumulated energy when masks are exposed in a scanner tool due to the different coefficient of thermal expansion of each materials. Therefore, whenever a re-pellicle process is needed to a mask, all deposited repair points have to be confirmed whether those deposition film are damaged or not. And if a deposition point is damaged, repair process is needed again. This process causes longer and more complex process. In this paper, the basic theory and the principle are introduced to recover clear defects by using nanomachining tool, and the evaluated results are reviewed at dense line (L/S) patterns and contact hole (C/H) patterns. Also, the results using a nanomachining were compared with those using an e-beam repair tool, including the cleaning durability evaluated by the accumulated cleaning process. Besides, we discuss the phase shift issue and the solution about the image placement error caused by phase error.

Radiative flux and forcing parameterization error in aerosol-free clear skies.

Science.gov (United States)

Pincus, Robert; Mlawer, Eli J; Oreopoulos, Lazaros; Ackerman, Andrew S; Baek, Sunghye; Brath, Manfred; Buehler, Stefan A; Cady-Pereira, Karen E; Cole, Jason N S; Dufresne, Jean-Louis; Kelley, Maxwell; Li, Jiangnan; Manners, James; Paynter, David J; Roehrig, Romain; Sekiguchi, Miho; Schwarzkopf, Daniel M

2015-07-16

Radiation parameterizations in GCMs are more accurate than their predecessorsErrors in estimates of 4 ×CO 2 forcing are large, especially for solar radiationErrors depend on atmospheric state, so global mean error is unknown.

The nature of articulation errors in Egyptian Arabic-speaking children with velopharyngeal insufficiency due to cleft palate.

Science.gov (United States)

Abou-Elsaad, Tamer; Baz, Hemmat; Afsah, Omayma; Mansy, Alzahraa

2015-09-01

Even with early surgical repair, the majority of cleft palate children demonstrate articulation errors and have typical cleft palate speech. Was to determine the nature of articulation errors of Arabic consonants in Egyptian Arabic-speaking children with velopharyngeal insufficiency (VPI). Thirty Egyptian Arabic-speaking children with VPI due to cleft palate (whether primary repaired or secondary repaired) were studied. Auditory perceptual assessment (APA) of children speech was conducted. Nasopharyngoscopy was done to assess the velopharyngeal port (VPP) movements while the child was repeating speech tasks. Mansoura Arabic Articulation test (MAAT) was performed to analyze the consonants articulation of these children. The most frequent type of articulatory errors observed was substitution, more specifically, backing. Pharyngealization of anterior fricatives was the most frequent substitution, especially for the /s/ sound. The most frequent substituting sounds for other sounds were /ʔ/ followed by /k/ and /n/ sounds. Significant correlations were found between the degrees of the open nasality and VPP closure and the articulation errors. On the other hand, the sounds (/ʔ/,/ħ/,/ʕ/,/n/,/w/,/j/) were normally articulated in all studied group. The determination of articulation errors in VPI children could guide the therapists for designing appropriate speech therapy programs for these cases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Regulation of DNA repair by parkin

International Nuclear Information System (INIS)

Kao, Shyan-Yuan

2009-01-01

Mutation of parkin is one of the most prevalent causes of autosomal recessive Parkinson's disease (PD). Parkin is an E3 ubiquitin ligase that acts on a variety of substrates, resulting in polyubiquitination and degradation by the proteasome or monoubiquitination and regulation of biological activity. However, the cellular functions of parkin that relate to its pathological involvement in PD are not well understood. Here we show that parkin is essential for optimal repair of DNA damage. Parkin-deficient cells exhibit reduced DNA excision repair that can be restored by transfection of wild-type parkin, but not by transfection of a pathological parkin mutant. Parkin also protects against DNA damage-induced cell death, an activity that is largely lost in the pathological mutant. Moreover, parkin interacts with the proliferating cell nuclear antigen (PCNA), a protein that coordinates DNA excision repair. These results suggest that parkin promotes DNA repair and protects against genotoxicity, and implicate DNA damage as a potential pathogenic mechanism in PD.

Chemical repair of trypsin-histidinyl radical

International Nuclear Information System (INIS)

Jovanovic, S.V.; Ruvarac, I.; Jankovic, I.; Josimovic, L.

1991-01-01

Oxyl radicals, such as hydroxyl, alkoxyl and peroxyl, react with biomolecules to produce bioradicals. Unless chemically repaired by suitable antioxidants, these bioradicals form stable products. This leads to loss of biological function of parent biomolecules with deleterious biological results, such as mutagenesis and cancer. Consequently, the understanding of the mechanisms of oxyl radical damage to biomolecules and chemical repair of such damage is crucial for the development of strategies for anticarcinogenesis and radioprotection. In this study the chemical repair of the histidinyl radical generated upon the trichloromethylperoxyl radical reaction with trypsin vas investigated by gamma radiolysis. The trypsin histidinyl radical is a resonance-stabilized heterocyclic free radical which was found to be unreactive with oxygen. The efficacy of the chemical repair of the trypsin-histidinyl radical by endogenous antioxidants which are electron donors (e.g. 5-hydroxytryptophan, uric acid) is compared to that of antioxidants which are H-atom donors (e. g. glutathione). 9 refs., 2 figs., 1 tab

On-bead fluorescent DNA nanoprobes to analyze base excision repair activities

International Nuclear Information System (INIS)

Gines, Guillaume; Saint-Pierre, Christine; Gasparutto, Didier

2014-01-01

Graphical abstract: -- Highlights: •On magnetic beads fluorescent enzymatic assays. •Simple, easy, non-radioactive and electrophoresis-free functional assay. •Lesion-containing hairpin DNA probes are selective for repair enzymes. •The biosensing platform allows the measurement of DNA repair activities from purified enzymes or within cell free extracts. -- Abstract: DNA integrity is constantly threatened by endogenous and exogenous agents that can modify its physical and chemical structure. Changes in DNA sequence can cause mutations sparked by some genetic diseases or cancers. Organisms have developed efficient defense mechanisms able to specifically repair each kind of lesion (alkylation, oxidation, single or double strand break, mismatch, etc). Here we report the adjustment of an original assay to detect enzymes’ activity of base excision repair (BER), that supports a set of lesions including abasic sites, alkylation, oxidation or deamination products of bases. The biosensor is characterized by a set of fluorescent hairpin-shaped nucleic acid probes supported on magnetic beads, each containing a selective lesion targeting a specific BER enzyme. We have studied the DNA glycosylase alkyl-adenine glycosylase (AAG) and the human AP-endonuclease (APE1) by incorporating within the DNA probe a hypoxanthine lesion or an abasic site analog (tetrahydrofuran), respectively. Enzymatic repair activity induces the formation of a nick in the damaged strand, leading to probe's break, that is detected in the supernatant by fluorescence. The functional assay allows the measurement of DNA repair activities from purified enzymes or in cell-free extracts in a fast, specific, quantitative and sensitive way, using only 1 pmol of probe for a test. We recorded a detection limit of 1 μg mL −1 and 50 μg mL −1 of HeLa nuclear extracts for APE1 and AAG enzymes, respectively. Finally, the on-bead assay should be useful to screen inhibitors of DNA repair activities

Reprogramming Cells for Brain Repair

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Randall D. McKinnon

2013-08-01

Full Text Available At present there are no clinical therapies that can repair traumatic brain injury, spinal cord injury or degenerative brain disease. While redundancy and rewiring of surviving circuits can recover some lost function, the brain and spinal column lack sufficient endogenous stem cells to replace lost neurons or their supporting glia. In contrast, pre-clinical studies have demonstrated that exogenous transplants can have remarkable efficacy for brain repair in animal models. Mesenchymal stromal cells (MSCs can provide paracrine factors that repair damage caused by ischemic injury, and oligodendrocyte progenitor cell (OPC grafts give dramatic functional recovery from spinal cord injury. These studies have progressed to clinical trials, including human embryonic stem cell (hESC-derived OPCs for spinal cord repair. However, ESC-derived allografts are less than optimal, and we need to identify a more appropriate donor graft population. The cell reprogramming field has developed the ability to trans-differentiate somatic cells into distinct cell types, a technology that has the potential to generate autologous neurons and glia which address the histocompatibility concerns of allografts and the tumorigenicity concerns of ESC-derived grafts. Further clarifying how cell reprogramming works may lead to more efficient direct reprogram approaches, and possibly in vivo reprogramming, in order to promote brain and spinal cord repair.

Renal Tubule Repair: Is Wnt/β-Catenin a Friend or Foe?

Science.gov (United States)

Gewin, Leslie S

2018-01-24

Wnt/β-catenin signaling is extremely important for proper kidney development. This pathway is also upregulated in injured renal tubular epithelia, both in acute kidney injury and chronic kidney disease. The renal tubular epithelium is an important target of kidney injury, and its response (repair versus persistent injury) is critical for determining whether tubulointerstitial fibrosis, the hallmark of chronic kidney disease, develops. This review discusses how Wnt/β-catenin signaling in the injured tubular epithelia promotes either repair or fibrosis after kidney injury. There is data suggesting that epithelial Wnt/β-catenin signaling is beneficial in acute kidney injury and important in tubular progenitors responsible for epithelial repair. The role of Wnt/β-catenin signaling in chronically injured epithelia is less clear. There is convincing data that Wnt/β-catenin signaling in interstitial fibroblasts and pericytes contributes to the extracellular matrix accumulation that defines fibrosis. However, some recent studies question whether Wnt/β-catenin signaling in chronically injured epithelia actually promotes fibrosis or repair.

The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair.

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Inna Maltseva

Full Text Available Corneal epithelial wound repair involves the migration of epithelial cells to cover the defect followed by the proliferation of the cells to restore thickness. Heparan sulfate proteoglycans (HSPGs are ubiquitous extracellular molecules that bind to a plethora of growth factors, cytokines, and morphogens and thereby regulate their signaling functions. Ligand binding by HS chains depends on the pattern of four sulfation modifications, one of which is 6-O-sulfation of glucosamine (6OS. SULF1 and SULF2 are highly homologous, extracellular endosulfatases, which post-synthetically edit the sulfation status of HS by removing 6OS from intact chains. The SULFs thereby modulate multiple signaling pathways including the augmentation of Wnt/ß-catenin signaling. We found that wounding of mouse corneal epithelium stimulated SULF1 expression in superficial epithelial cells proximal to the wound edge. Sulf1⁻/⁻, but not Sulf2⁻/⁻, mice, exhibited a marked delay in healing. Furthermore, corneal epithelial cells derived from Sulf1⁻/⁻ mice exhibited a reduced rate of migration in repair of a scratched monolayer compared to wild-type cells. In contrast, human primary corneal epithelial cells expressed SULF2, as did a human corneal epithelial cell line (THCE. Knockdown of SULF2 in THCE cells also slowed migration, which was restored by overexpression of either mouse SULF2 or human SULF1. The interchangeability of the two SULFs establishes their capacity for functional redundancy. Knockdown of SULF2 decreased Wnt/ß-catenin signaling in THCE cells. Extracellular antagonists of Wnt signaling reduced migration of THCE cells. However in SULF2- knockdown cells, these antagonists exerted no further effects on migration, consistent with the SULF functioning as an upstream regulator of Wnt signaling. Further understanding of the mechanistic action of the SULFs in promoting corneal repair may lead to new therapeutic approaches for the treatment of corneal injuries.

Moving toward people's needs for smoke-free restaurants: before and after a national promotion program in Taiwan, 2003-2005.

Science.gov (United States)

Chen, Yi-Hua; Yeh, Ching-Ying; Chen, Ruey-Yu; Chien, Ling-Chu; Yu, Po-Tswen; Chao, Kun-Yu; Han, Bor-Cheng

2009-05-01

In Taiwan, the Smoke-Free Restaurant Program (SFRP) was implemented from 2003 to 2005 as an initial phase before the introduction of restrictive legislation promoting smoke-free restaurants (SFRs). No studies have evaluated trends in public opinion before and after a national health promotion campaign for the introduction of SFRs on a voluntary basis. The present study investigated whether public opinion with respect to eliminating environmental tobacco smoke (ETS) in restaurants changed after implementation of the SFRP. Data were obtained from four large-scale, nationally representative surveys conducted in 2003-2005 before and after implementation of the SFRP. Weighted analyses were performed to obtain nationally representative results. After a series of SFRP campaigns, reported exposure to ETS in restaurants by survey participants decreased by approximately 14%. Approximately 20% more people had heard of SFRs, and approximately 25% more had chosen to dine in a smoke-free restaurant. We found consistently high community support for SFRs (ca. 95%), and approximately 80% supported smoke-free restaurant legislation, although both rates dropped slightly in 2005. People aged 60 years or more, nonsmokers, and those who had greater knowledge of ETS hazards were more likely to support smoke-free restaurant legislation. The SFRP was effective at promoting SFRs on a voluntary basis. Strong community endorsement has major implications for legislators who are considering the nature and extent of further smoke-free restaurant legislation in Taiwan and other countries.

Repair process and a repaired component

Energy Technology Data Exchange (ETDEWEB)

Roberts, III, Herbert Chidsey; Simpson, Stanley F.

2018-02-20

Matrix composite component repair processes are disclosed. The matrix composite repair process includes applying a repair material to a matrix composite component, securing the repair material to the matrix composite component with an external securing mechanism and curing the repair material to bond the repair material to the matrix composite component during the securing by the external securing mechanism. The matrix composite component is selected from the group consisting of a ceramic matrix composite, a polymer matrix composite, and a metal matrix composite. In another embodiment, the repair process includes applying a partially-cured repair material to a matrix composite component, and curing the repair material to bond the repair material to the matrix composite component, an external securing mechanism securing the repair material throughout a curing period, In another embodiment, the external securing mechanism is consumed or decomposed during the repair process.

Comparative Study of Inguinal Hernia Repair Rates After Radical Prostatectomy or External Beam Radiotherapy

International Nuclear Information System (INIS)

Lughezzani, Giovanni; Sun, Maxine; Perrotte, Paul; Alasker, Ahmed; Jeldres, Claudio; Isbarn, Hendrik; Budaeus, Lars; Lattouf, Jean-Baptiste; Valiquette, Luc; Benard, Francois; Saad, Fred; Graefen, Markus; Montorsi, Francesco; Karakiewicz, Pierre I.

2010-01-01

Purpose: We tested the hypothesis that patients treated for localized prostate cancer with radical prostatectomy (RP) have a higher risk of requiring an inguinal hernia (IH) repair than their counterparts treated with external beam radiotherapy (EBRT). Methods and Materials: Within the Quebec Health Plan database, we identified 6,422 men treated with RP and 4,685 men treated with EBRT for localized prostate cancer between 1990 and 2000, in addition to 6,933 control patients who underwent a prostate biopsy. From among that population, we identified patients who underwent a unilateral or bilateral hernia repair after either RP or EBRT. Kaplan-Meier plots showed IH repair-free survival rates. Univariable and multivariable Cox regression models tested the predictors of IH repair after RP or EBRT. Covariates consisted of age, year of surgery, and Charlson Comorbidity Index. Results: IH repair-free survival rates at 1, 2, 5, and 10 years were 96.8, 94.3, 90.5, and 86.2% vs. 98.9, 98.0, 95.4, and 92.2%, respectively, in RP vs. EBRT patients (log-rank test, p < 0.001). IH repair-free survival rates in the biopsy population were 98.3, 97.1, 94.9, and 90.2% at the same four time points. In multivariable Cox regression models, RP predisposed to a 2.3-fold higher risk of IH repair than EBRT (p < 0.001). Besides therapy type, patient age (p < 0.001) represented the only other independent predictor of IH repair. Conclusions: RP predisposes to a higher rate of IH repair relative to EBRT. This observation should be considered at informed consent.

DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

OpenAIRE

Poulogiannis , George; Frayling , Ian; Arends , Mark

2009-01-01

Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

A measurement strategy and an error-compensation model for the on-machine laser measurement of large-scale free-form surfaces

International Nuclear Information System (INIS)

Li, Bin; Li, Feng; Liu, Hongqi; Cai, Hui; Mao, Xinyong; Peng, Fangyu

2014-01-01

This study presents a novel measurement strategy and an error-compensation model for the measurement of large-scale free-form surfaces in on-machine laser measurement systems. To improve the measurement accuracy, the effects of the scan depth, surface roughness, incident angle and azimuth angle on the measurement results were investigated experimentally, and a practical measurement strategy considering the position and orientation of the sensor is presented. Also, a semi-quantitative model based on geometrical optics is proposed to compensate for the measurement error associated with the incident angle. The normal vector of the measurement point is determined using a cross-curve method from the acquired surface data. Then, the azimuth angle and incident angle are calculated to inform the measurement strategy and error-compensation model, respectively. The measurement strategy and error-compensation model are verified through the measurement of a large propeller blade on a heavy machine tool in a factory environment. The results demonstrate that the strategy and the model are effective in increasing the measurement accuracy. (paper)

Error-free Dispersion-uncompensated Transmission at 20 Gb/s over SSMF using a Hybrid III-V/SOI DML with MRR Filtering

DEFF Research Database (Denmark)

Cristofori, Valentina; Kamchevska, Valerija; Ding, Yunhong

2016-01-01

Error-free 20-Gb/s directly-modulated transmission is achieved by enhancing the dispersion tolerance of a III-V/SOI DFB laser with a silicon micro-ring resonator. Low (∼0.4 dB) penalty compared to back-to-back without ring is demonstrated after 5-km SSMF....

Inducible error-prone repair in B. subtilis. Progress report, May 1, 1983-April 30, 1984

International Nuclear Information System (INIS)

Yasbin, R.E.

1983-12-01

DNA repair mechanisms in Bacillus subtilis were investigated following mutagenesis via ultraviolet radiation or by chemical mutagens. A bioassay is described whereby the efficiency of repair mechanisms can be measured. DNA cloning studies to transfer the photoreactivation gene from E. coli to B. subtilis are reported. The mutation, which induces the SOS-like system in B. subtilis when grown at 45 0 C, was characterized in order to begin delineation of the genes controlling this system, efforts directed at isolation and cloning of a DNA Polymerase III gene of B. subtilis are related. (DT)

Laparoscopic totally extraperitoneal inguinal hernia repair: lessons learned from 3,100 hernia repairs over 15 years.

Science.gov (United States)

Dulucq, Jean-Louis; Wintringer, Pascal; Mahajna, Ahmad

2009-03-01

Two revolutions in inguinal hernia repair surgery have occurred during the last two decades. The first was the introduction of tension-free hernia repair by Liechtenstein in 1989 and the second was the application of laparoscopic surgery to the treatment of inguinal hernia in the early 1990s. The purposes of this study were to assess the safety and effectiveness of laparoscopic totally extraperitoneal (TEP) repair and to discuss the technical changes that we faced on the basis of our accumulative experience. Patients who underwent an elective inguinal hernia repair at the Department of Abdominal Surgery at the Institute of Laparoscopic Surgery (ILS), Bordeaux, between June 1990 and May 2005 were enrolled retrospectively in this study. Patient demographic data, operative and postoperative course, and outpatient follow-up were studied. A total of 3,100 hernia repairs were included in the study. The majority of the hernias were repaired by TEP technique; the repair was done by transabdominal preperitoneal (TAPP) repair in only 3%. Eleven percent of the hernias were recurrences after conventional repair. Mean operative time was 17 min in unilateral hernia and 24 min in bilateral hernia. There were 36 hernias (1.2%) that required conversion: 12 hernias were converted to open anterior Liechtenstein and 24 to laparoscopic TAPP technique. The incidence of intraoperative complications was low. Most of the patients were discharged at the second day of the surgery. The overall postoperative morbidity rate was 2.2%. The incidence of recurrence rate was 0.35%. The recurrence rate for the first 200 repairs was 2.5%, but it decreased to 0.47% for the subsequent 1,254 hernia repairs According to our experience, in the hands of experienced laparoscopic surgeons, laparoscopic hernia repair seems to be the favored approach for most types of inguinal hernias. TEP is preferred over TAPP as the peritoneum is not violated and there are fewer intra-abdominal complications.

Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

Science.gov (United States)

Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

2017-06-01

Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

Repair capability and the cellular age response for killing and mutation induction after UV

International Nuclear Information System (INIS)

Wood, R.D.; Burki, H.J.; California Univ., Berkeley

1982-01-01

The cell-cycle response for killing and mutation induction by ultraviolet irradiation was measured in synchronous Chinese hamster ovary cells (CHO wild-type) and in a UV-hypersensitive mutant (43-3B) derived from this line. The CHO 43-3B line shows a greatly enhanced sensitivity to killing (D 0 of 0.3 as compared to 3.2 J/m 2 for the wild-type), is hypermutable, and deficient in DNA repair. For the wild-type, a characteristic age response is seen for killing by UV, with maximum sensitivity in early-S and resistance increasing through the S-phase. There is also a life-cycle specificity for induction of diphtheria-toxin resistance in late-G 1 and early-S. Relatively little variation is seen through the cell cycle for induced 6-thioguanine and ouabain resistance. In contrast, the 43-3B cell line shows a relatively 'flat' response to UV throughout the cell cycle, for both killing and mutation induction. Therefore it appears that the characteristic age responses seen in the wild-type CHO are associated with the function of an essentially error-free repair process. (orig./AJ)

Teacher-Student Development in Mathematics Classrooms: Interrelated Zones of Free Movement and Promoted Actions

Science.gov (United States)

Hussain, Mohammed Abdul; Monaghan, John; Threlfall, John

2013-01-01

This paper applies and extends Valsiner's "zone theory" (zones of free movement and promoted actions) through an examination of an intervention to establish inquiry communities in primary mathematics classrooms. Valsiner's zone theory, in a classroom setting, views students' freedom of choice of action and thought as mediated by the teacher. The…

Approaching Error-Free Customer Satisfaction through Process Change and Feedback Systems

Science.gov (United States)

Berglund, Kristin M.; Ludwig, Timothy D.

2009-01-01

Employee-based errors result in quality defects that can often impact customer satisfaction. This study examined the effects of a process change and feedback system intervention on error rates of 3 teams of retail furniture distribution warehouse workers. Archival records of error codes were analyzed and aggregated as the measure of quality. The…

Molecular mechanisms of DNA repair inhibition by caffeine

Energy Technology Data Exchange (ETDEWEB)

Selby, C.P.; Sancar, A. (Univ. of North Carolina School of Medicine, Chapel Hill (USA))

1990-05-01

Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.

Indications for an inducible component of error-prone DNA repair in yeast

International Nuclear Information System (INIS)

Siede, W.; Eckardt, F.

1984-01-01

In a thermoconditional mutant of mutagenic DNA repair (rev 2sup(ts) = rad5-8) of Saccharomyces cerevisiae recovery of survival and mutation frequencies can be monitored by incubating UV-irradiated cells in growth medium at a permissive temperature (23 0 C) before plating and a shift to restrictive temperature (36 0 C). Inhibition of protein synthesis with cycloheximide during incubation at permissive conditions blocks this REV 2 dependent recovery process in stationary phase rev 2sup(ts) cells, whereas it can be reduced but not totally abolished in exponentially growing cells. These results indicate a strict dependence on post-irradiation protein synthesis in stationary phase cells and argue for a considerable constitutive level and only limited inducibility in logarithmic phase cells. The UV inducibility of the REV 2 coded function in stationary phase cells could be confirmed by analysis of dose-response pattern of the his 5-2 reversion: in stationary phase rev 2sup(ts) cells, the quadratic component of the biphasic linear-quadratic induction kinetics found at 23 0 C, which is interpreted as the consequence of induction of mutagenic repair, is eliminated at 36 0 C. (author)

Indications for an inducible component of error-prone DNA repair in yeast.

Science.gov (United States)

Siede, W; Eckardt, F

1984-01-01

In a thermoconditional mutant of mutagenic DNA repair (rev 2ts = rad 5-8) of Saccharomyces cerevisiae recovery of survival and mutation frequencies can be monitored by incubating UV-irradiated cells in growth medium at a permissive temperature (23 degrees C) before plating and a shift to restrictive temperature (36 degrees C). Inhibition of protein synthesis with cycloheximide during incubation at permissive conditions blocks this REV 2 dependent recovery process in stationary phase rev 2ts cells, whereas it can be reduced but not totally abolished in exponentially growing cells. These results indicate a strict dependence on post-irradiation protein synthesis in stationary phase cells and argue for a considerable constitutive level and only limited inducibility in logarithmic phase cells. The UV inducibility of the REV 2 coded function in stationary phase cells could be confirmed by analysis of the dose-response pattern of the his 5-2 reversion: in stationary phase rev 2ts cells, the quadratic component of the biphasic linear-quadratic induction kinetics found at 23 degrees C, which is interpreted as the consequence of induction of mutagenic repair, is eliminated at 36 degrees C.

Lichtenstein Mesh Repair (LMR) v/s Modified Bassini's Repair (MBR) + Lichtenstein Mesh Repair of Direct Inguinal Hernias in Rural Population - A Comparative Study.

Science.gov (United States)

Patil, Santosh M; Gurujala, Avinash; Kumar, Ashok; Kumar, Kuthadi Sravan; Mithun, Gorre

2016-02-01

Lichtenstein's tension free mesh hernioplasty is the commonly done open technique for inguinal hernias. As our hospital is in rural area, majority of patients are labourers, open hernias are commonly done. The present study was done by comparing Lichtenstein Mesh Repair (LMR) v/s Modified Bassini's repair (MBR) + Lichtenstein mesh repair (LMR) of direct Inguinal Hernias to compare the technique of both surgeries and its outcome like postoperative complications and recurrence rate. A comparative randomized study was conducted on patients reporting to MNR hospital, sangareddy with direct inguinal hernias. A total of fifty consecutive patients were included in this study of which, 25 patients were operated by LMR and 25 patients were operated by MBR+LMR and followed up for a period of two years. The outcomes of the both techniques were compared. Study involved 25 each of Lichtenstein's mesh repair (LMR) and modified bassini's repair (MBR) + LMR, over a period of 2 years. The duration of surgery for lichtenstein mesh repair is around 34.56 min compared to LMR+MBR, which is 47.56 min which was statistically significant (p-value is MBR group in POD 1, but not statistically significant (p-value is 0.0949) and from POD 7 the pain was almost similar in both groups. The recurrence rate is 2% for LMR and 0% for MBR+LMR. LMR+MBR was comparatively better than only LMR in all direct inguinal hernias because of low recurrence rate (0%) and low postoperative complications, which showed in our present study.

DNA repair in cancer: emerging targets for personalized therapy

International Nuclear Information System (INIS)

Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan

2014-01-01

Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer

Metabolite damage and repair in metabolic engineering design

Energy Technology Data Exchange (ETDEWEB)

Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.; Bruner, Steven D.; Hanson, Andrew D.

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.

Philosophy of weld repair of steam turbine rotors

International Nuclear Information System (INIS)

Bertilsson, J.E.; Scarlin, R.B.; Faber, G.

1987-01-01

Weld repair of a cracked rotor should never be limited to simply grinding out cracks and filling up with weld metal. It is essential to know where and why a crack appeared. In several instances in the past weld repairs have been made of fatigue cracked rotors which have been placed successfully into service. Prolonged further operation can be assured only if the cause of cracking is known and if the design weakness demonstrated in this way is eliminated. However, in cases where creep cracking is encountered or where the creep life is approaching exhaustion, a local repair even if achieved crack-free, cannot ensure successful long-term further operation. The decision must be made to replace a major section of the rotor. The paper describes weld repair trials performed on an HP rotor after 100,000 hours of operation. The results demonstrate the feasibility of making weld repairs of low-toughness CrMoV rotors according to this philosophy

Free microvascular rotationplasty with nerve repair for rhabdomyosarcoma in a 18-month-old patient.

Science.gov (United States)

Pérez-García, Alberto; Salom, Marta; Villaverde-Doménech, María Eloísa; Baixauli, Francisco; Simón-Sanz, Eduardo

2017-05-01

Rotationplasty is a limb-sparing surgical option in lower limb malignancies. Sciatic or tibial nerve encasement has been considered an absolute contraindication to this procedure. We report a case of an 18-month-old girl with a rhabdomyosarcoma that affected the leg and popliteal fossa, with neurovascular involvement. Knee and proximal leg intercalary resection was performed followed by reconstruction with free microvascular rotationplasty and neurorraphy from tibial division of sciatic nerve to sural and tibial nerves, and from saphenous nerve to superficial peroneal nerve. Postoperative course was uneventful and ambulation with a provisional prosthesis was restarted during the sixth week after surgery. Bone consolidation was observed after two months. Eighteen months later, the patient had a good gait pattern with a below-knee prosthesis and had recovered sensation in the whole foot and ankle area. This case shows that rotationplasty with nerve repair may provide a sensate stump, which is vital for successful prosthetic adaptation. We believe it may be considered as an alternative to above-knee amputation in tumors with sciatic involvement. © 2017 Wiley Periodicals, Inc.

Repair of X-ray-induced single-strand breaks by a cell-free system

International Nuclear Information System (INIS)

Seki, Shuji; Ikeda, Shogo; Tsutui, Ken; Teraoka, Hirobumi

1990-01-01

Repair of X-ray-induced single-strand breaks of DNA was studied in vitro using an exonuclease purified from mouse ascites sarcoma (SR-C3H/He) cells. X-ray-dose-dependent unscheduled DNA synthesis was primed by the exonuclease. Repair of X-ray-induced single-strand breaks in pUC19 plasmid DNA was demonstrated by agarose gel electrophoresis after incubating the damaged DNA with the exonuclease, DNA polymerase (Klenow fragment of DNA polymerase I or DNA polymerase β purified from SR-C3H/He cells), four deoxynucleoside triphosphates, ATP and DNA ligase (T4 DNA ligase or DNA ligase I purified from calf thymus). The present results suggested that the exonuclease is involved in the initiation of repair of X-ray-induced single-strand breaks in removing 3' ends of X-ray-damaged DNA. (author)

Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

DEFF Research Database (Denmark)

Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

2015-01-01

Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... in the form of oxidative stress, has been linked to a wide variety of diseases including inborn errors of metabolism. In this review we will summarize how the functional state of mitochondria -- and especially the concentration of reactive oxygen species (ROS), produced in connection with the respiratory...... chain -- regulates cellular stress responses by redox regulation of nuclear gene networks involved in repair systems to maintain cellular homeostasis and health. Based on our own and other's studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism...

Exploring Senior Residents' Intraoperative Error Management Strategies: A Potential Measure of Performance Improvement.

Science.gov (United States)

Law, Katherine E; Ray, Rebecca D; D'Angelo, Anne-Lise D; Cohen, Elaine R; DiMarco, Shannon M; Linsmeier, Elyse; Wiegmann, Douglas A; Pugh, Carla M

The study aim was to determine whether residents' error management strategies changed across 2 simulated laparoscopic ventral hernia (LVH) repair procedures after receiving feedback on their initial performance. We hypothesize that error detection and recovery strategies would improve during the second procedure without hands-on practice. Retrospective review of participant procedural performances of simulated laparoscopic ventral herniorrhaphy. A total of 3 investigators reviewed procedure videos to identify surgical errors. Errors were deconstructed. Error management events were noted, including error identification and recovery. Residents performed the simulated LVH procedures during a course on advanced laparoscopy. Participants had 30 minutes to complete a LVH procedure. After verbal and simulator feedback, residents returned 24 hours later to perform a different, more difficult simulated LVH repair. Senior (N = 7; postgraduate year 4-5) residents in attendance at the course participated in this study. In the first LVH procedure, residents committed 121 errors (M = 17.14, standard deviation = 4.38). Although the number of errors increased to 146 (M = 20.86, standard deviation = 6.15) during the second procedure, residents progressed further in the second procedure. There was no significant difference in the number of errors committed for both procedures, but errors shifted to the late stage of the second procedure. Residents changed the error types that they attempted to recover (χ 2 5 =24.96, perrors, but decreased for strategy errors. Residents also recovered the most errors in the late stage of the second procedure (p error management strategies changed between procedures following verbal feedback on their initial performance and feedback from the simulator. Errors and recovery attempts shifted to later steps during the second procedure. This may reflect residents' error management success in the earlier stages, which allowed further progression in the

APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

Science.gov (United States)

Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

2012-07-12

APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

Design of an error-free nondestructive plutonium assay facility

International Nuclear Information System (INIS)

Moore, C.B.; Steward, W.E.

1987-01-01

An automated, at-line nondestructive assay (NDA) laboratory is installed in facilities recently constructed at the Savannah River Plant. The laboratory will enhance nuclear materials accounting in new plutonium scrap and waste recovery facilities. The advantages of at-line NDA operations will not be realized if results are clouded by errors in analytical procedures, sample identification, record keeping, or techniques for extracting samples from process streams. Minimization of such errors has been a primary design objective for the new facility. Concepts for achieving that objective include mechanizing the administrative tasks of scheduling activities in the laboratory, identifying samples, recording and storing assay data, and transmitting results information to process control and materials accounting functions. These concepts have been implemented in an analytical computer system that is programmed to avoid the obvious sources of error encountered in laboratory operations. The laboratory computer exchanges information with process control and materials accounting computers, transmitting results information and obtaining process data and accounting information as required to guide process operations and maintain current records of materials flow through the new facility

Nonhomologous DNA End Joining in Cell-Free Extracts

Directory of Open Access Journals (Sweden)

Sheetal Sharma

2010-01-01

Full Text Available Among various DNA damages, double-strand breaks (DSBs are considered as most deleterious, as they may lead to chromosomal rearrangements and cancer when unrepaired. Nonhomologous DNA end joining (NHEJ is one of the major DSB repair pathways in higher organisms. A large number of studies on NHEJ are based on in vitro systems using cell-free extracts. In this paper, we summarize the studies on NHEJ performed by various groups in different cell-free repair systems.

Development of an Abbe Error Free Micro Coordinate Measuring Machine

Directory of Open Access Journals (Sweden)

Qiangxian Huang

2016-04-01

Full Text Available A micro Coordinate Measuring Machine (CMM with the measurement volume of 50 mm × 50 mm × 50 mm and measuring accuracy of about 100 nm (2σ has been developed. In this new micro CMM, an XYZ stage, which is driven by three piezo-motors in X, Y and Z directions, can achieve the drive resolution of about 1 nm and the stroke of more than 50 mm. In order to reduce the crosstalk among X-, Y- and Z-stages, a special mechanical structure, which is called co-planar stage, is introduced. The movement of the stage in each direction is detected by a laser interferometer. A contact type of probe is adopted for measurement. The center of the probe ball coincides with the intersection point of the measuring axes of the three laser interferometers. Therefore, the metrological system of the CMM obeys the Abbe principle in three directions and is free from Abbe error. The CMM is placed in an anti-vibration and thermostatic chamber for avoiding the influence of vibration and temperature fluctuation. A series of experimental results show that the measurement uncertainty within 40 mm among X, Y and Z directions is about 100 nm (2σ. The flatness of measuring face of the gauge block is also measured and verified the performance of the developed micro CMM.

Assessment of repair welding technologies of irradiated materials

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-08-15

Damages on reactor internals of stainless steels caused by stress corrosion cracking and fatigue were identified in aged BWR plants. Repair-welding is one of the practical countermeasure candidates to restore the soundness of components and structures. The project of 'Assessment of Repair welding Technologies of Irradiated Materials' has been carried out to develop the technical guideline regarding the repair-welding of reactor internals. In FY 2011, we investigated the fatigue strength of stainless steel SUS316L irradiated by YAG laser welding. Furthermore, revision of the technical guideline regarding the repair-welding of reactor internals was discussed. Diagram of tungsten inert gas (TIG) weld cracking caused by entrapped Helium was modified. Helium concentration for evaluation-free of TIG weld cracking caused by entrapped Helium was revised to 0.007appm from 0.01appm. (author)

Error analysis and assessment of unsteady forces acting on a flapping wing micro air vehicle: free flight versus wind-tunnel experimental methods.

Science.gov (United States)

Caetano, J V; Percin, M; van Oudheusden, B W; Remes, B; de Wagter, C; de Croon, G C H E; de Visser, C C

2015-08-20

An accurate knowledge of the unsteady aerodynamic forces acting on a bio-inspired, flapping-wing micro air vehicle (FWMAV) is crucial in the design development and optimization cycle. Two different types of experimental approaches are often used: determination of forces from position data obtained from external optical tracking during free flight, or direct measurements of forces by attaching the FWMAV to a force transducer in a wind-tunnel. This study compares the quality of the forces obtained from both methods as applied to a 17.4 gram FWMAV capable of controlled flight. A comprehensive analysis of various error sources is performed. The effects of different factors, e.g., measurement errors, error propagation, numerical differentiation, filtering frequency selection, and structural eigenmode interference, are assessed. For the forces obtained from free flight experiments it is shown that a data acquisition frequency below 200 Hz and an accuracy in the position measurements lower than ± 0.2 mm may considerably hinder determination of the unsteady forces. In general, the force component parallel to the fuselage determined by the two methods compares well for identical flight conditions; however, a significant difference was observed for the forces along the stroke plane of the wings. This was found to originate from the restrictions applied by the clamp to the dynamic oscillations observed in free flight and from the structural resonance of the clamped FWMAV structure, which generates loads that cannot be distinguished from the external forces. Furthermore, the clamping position was found to have a pronounced influence on the eigenmodes of the structure, and this effect should be taken into account for accurate force measurements.

On-bead fluorescent DNA nanoprobes to analyze base excision repair activities

Energy Technology Data Exchange (ETDEWEB)

Gines, Guillaume; Saint-Pierre, Christine; Gasparutto, Didier, E-mail: didier.gasparutto@cea.fr

2014-02-17

Graphical abstract: -- Highlights: •On magnetic beads fluorescent enzymatic assays. •Simple, easy, non-radioactive and electrophoresis-free functional assay. •Lesion-containing hairpin DNA probes are selective for repair enzymes. •The biosensing platform allows the measurement of DNA repair activities from purified enzymes or within cell free extracts. -- Abstract: DNA integrity is constantly threatened by endogenous and exogenous agents that can modify its physical and chemical structure. Changes in DNA sequence can cause mutations sparked by some genetic diseases or cancers. Organisms have developed efficient defense mechanisms able to specifically repair each kind of lesion (alkylation, oxidation, single or double strand break, mismatch, etc). Here we report the adjustment of an original assay to detect enzymes’ activity of base excision repair (BER), that supports a set of lesions including abasic sites, alkylation, oxidation or deamination products of bases. The biosensor is characterized by a set of fluorescent hairpin-shaped nucleic acid probes supported on magnetic beads, each containing a selective lesion targeting a specific BER enzyme. We have studied the DNA glycosylase alkyl-adenine glycosylase (AAG) and the human AP-endonuclease (APE1) by incorporating within the DNA probe a hypoxanthine lesion or an abasic site analog (tetrahydrofuran), respectively. Enzymatic repair activity induces the formation of a nick in the damaged strand, leading to probe's break, that is detected in the supernatant by fluorescence. The functional assay allows the measurement of DNA repair activities from purified enzymes or in cell-free extracts in a fast, specific, quantitative and sensitive way, using only 1 pmol of probe for a test. We recorded a detection limit of 1 μg mL{sup −1} and 50 μg mL{sup −1} of HeLa nuclear extracts for APE1 and AAG enzymes, respectively. Finally, the on-bead assay should be useful to screen inhibitors of DNA repair

Lichtenstein Mesh Repair (LMR) v/s Modified Bassini’s Repair (MBR) + Lichtenstein Mesh Repair of Direct Inguinal Hernias in Rural Population – A Comparative Study

Science.gov (United States)

Patil, Santosh M; Kumar, Ashok; Kumar, Kuthadi Sravan; Mithun, Gorre

2016-01-01

Introduction Lichtenstein’s tension free mesh hernioplasty is the commonly done open technique for inguinal hernias. As our hospital is in rural area, majority of patients are labourers, open hernias are commonly done. The present study was done by comparing Lichtenstein Mesh Repair (LMR) v/s Modified Bassini’s repair (MBR) + Lichtenstein mesh repair (LMR) of direct Inguinal Hernias to compare the technique of both surgeries and its outcome like postoperative complications and recurrence rate. Materials and Methods A comparative randomized study was conducted on patients reporting to MNR hospital, sangareddy with direct inguinal hernias. A total of fifty consecutive patients were included in this study of which, 25 patients were operated by LMR and 25 patients were operated by MBR+LMR and followed up for a period of two years. The outcomes of the both techniques were compared. Results Study involved 25 each of Lichtenstein’s mesh repair (LMR) and modified bassini’s repair (MBR) + LMR, over a period of 2 years. The duration of surgery for lichtenstein mesh repair is around 34.56 min compared to LMR+MBR, which is 47.56 min which was statistically significant (p-value is MBR group in POD 1, but not statistically significant (p-value is 0.0949) and from POD 7 the pain was almost similar in both groups. The recurrence rate is 2% for LMR and 0% for MBR+LMR. Conclusion LMR+MBR was comparatively better than only LMR in all direct inguinal hernias because of low recurrence rate (0%) and low postoperative complications, which showed in our present study. PMID:27042517

Specificity and completeness of inhibition of DNA repair by novobiocin and aphidicolin

International Nuclear Information System (INIS)

Cleaver, J.E.

1982-01-01

Novobiocin and aphidicolin were both potent inhibitors of excision repair of u.v.-induced damage to DNA in human embryonic fibroblasts, and both also inhibited semiconservative DNA replication even more strongly. The mechanism of action of these two drugs is, however, different. Novobiocin inhibited repair replication without accumulating single-strand breaks, but aphidicolin inhibited repair replication with the accumulation of numerous single-strand breaks. Novobiocin appears to inhibit repair at an earlier stage than aphidicolin, which may indicate that DNA topoisomerases play a role in eukaryotic DNA repair. Digestion of DNA by exonuclease III indicated that repair patches in novobiocin-treated cells contained no excess 3'OH termini, whereas up to 40% of the repaired DNA in aphidicolin-treated cells had free 3'OH termini. Therefore, although aphidicolin resulted in the accumulation of single-strand breaks, many of the repair events escaped inhibition and the number of breaks is an underestimate of the true number of repair events

Metabolite damage and repair in metabolic engineering design.

Science.gov (United States)

Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture

Energy Technology Data Exchange (ETDEWEB)

Cho, Yun Kyung; Kim, Gunha; Park, Serah; Sim, Ju Hee; Won, You Jin [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hwang, Chang Ho [Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714 (Korea, Republic of); Yoo, Jong Yoon, E-mail: jyyoo@amc.seoul.kr [Department of Rehabilitation Medicine, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hong, Hea Nam, E-mail: hnhong@amc.seoul.kr [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of)

2012-01-13

Highlights: Black-Right-Pointing-Pointer Lysolecithin-induced demyelination elevated EpoR expression in OPCs. Black-Right-Pointing-Pointer In association with elevated EpoR, EPO increased OPCs proliferation. Black-Right-Pointing-Pointer EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. Black-Right-Pointing-Pointer EPO promoted myelin repair following lysolecithin-induced demyelination. -- Abstract: Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to a limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.

Mutator suppression and escape from replication error-induced extinction in yeast.

Directory of Open Access Journals (Sweden)

Alan J Herr

2011-10-01

Full Text Available Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10⁻³ inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer.

Nanopolymers Delivery of the Bone Morphogenetic Protein-4 Plasmid to Mesenchymal Stem Cells Promotes Articular Cartilage Repair In Vitro and In Vivo

Directory of Open Access Journals (Sweden)

Junjun Shi

2012-01-01

Full Text Available The clinical application of viral vectors for gene therapy is limited for biosafety consideration. In this study, to promote articular cartilage repair, poly (lactic-co glycolic acid (PLGA nanopolymers were used as non-viral vectors to transfect rabbit mesenchymal stem cells (MSCs with the pDC316-BMP4-EGFP plasmid. The cytotoxicity and transfection efficiency in vitro were acceptable measuring by CCK-8 and flow cytometry. After transfection, Chondrogenic markers (mRNA of Col2a1, Sox9, Bmp4, and Agg of experimental cells (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers were increased more than those of control cells (MSCs being transfected with naked BMP-4 plasmid alone. In vivo study, twelve rabbits (24 knees with large full thickness articular cartilage defects were randomly divided into the experimental group (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers and the control group (MSCs being transfected with naked BMP-4 plasmid. The experimental group showed better regeneration than the control group 6 and 12 weeks postoperatively. Hyaline-like cartilage formed at week 12 in the experimental group, indicating the local delivery of BMP-4 plasmid to MSCs by PLGA nanopolymers improved articular cartilage repair significantly. PLGA nanopolymers could be a promising and effective non-viral vector for gene therapy in cartilage repair.

Indications for an inducible component of error-prone DNA repair in yeast.

OpenAIRE

Siede, W.; Eckardt, F.

1984-01-01

In a thermoconditional mutant of mutagenic DNA repair (rev 2ts = rad 5-8) of Saccharomyces cerevisiae recovery of survival and mutation frequencies can be monitored by incubating UV-irradiated cells in growth medium at a permissive temperature (23 degrees C) before plating and a shift to restrictive temperature (36 degrees C). Inhibition of protein synthesis with cycloheximide during incubation at permissive conditions blocks this REV 2 dependent recovery process in stationary phase rev 2ts c...

MGMT promoter methylation determined by HRM in comparison to MSP and pyrosequencing for predicting high-grade glioma response.

Science.gov (United States)

Switzeny, Olivier J; Christmann, Markus; Renovanz, Mirjam; Giese, Alf; Sommer, Clemens; Kaina, Bernd

2016-01-01

The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with alkylating drugs. Since MGMT is highly epigenetically regulated, the MGMT promoter methylation status is taken as an indicator of MGMT silencing, predicting the outcome of glioma therapy. MGMT promoter methylation is usually determined by methylation specific PCR (MSP), which is a labor intensive and error-prone method often used semi-quantitatively. Searching for alternatives, we used closed-tube high resolution melt (HRM) analysis, which is a quantitative method, and compared it with MSP and pyrosequencing regarding its predictive value. We analyzed glioblastoma cell lines with known MGMT activity and formalin-fixed samples from IDH1 wild-type high-grade glioma patients (WHO grade III/IV) treated with radiation and temozolomide by HRM, MSP, and pyrosequencing. The data were compared as to progression-free survival (PFS) and overall survival (OS) of patients exhibiting the methylated and unmethylated MGMT status. A promoter methylation cut-off level relevant for PFS and OS was determined. In a multivariate Cox regression model, methylation of MGMT promoter of high-grade gliomas analyzed by HRM, but not MSP, was found to be an independent predictive marker for OS. Univariate Kaplan-Meier analyses revealed for PFS and OS a significant and better discrimination between methylated and unmethylated tumors when quantitative HRM was used instead of MSP. Compared to MSP and pyrosequencing, the HRM method is simple, cost effective, highly accurate and fast. HRM is at least equivalent to pyrosequencing in quantifying the methylation level. It is superior in predicting PFS and OS of high-grade glioma patients compared to MSP and, therefore, can be recommended being used routinely for determination of the MGMT status of gliomas.

Applying a biodeposition layer to increase the bond of a repair mortar on a mortar substrate

OpenAIRE

Snoeck, Didier; Wang, Jianyun; Bentz, D. P.; De Belie, Nele

2018-01-01

One of the major concerns in infrastructure repair is a sufficient bond between the substrate and the repair material, especially for the long-term performance and durability of the repaired structure. In this study, the bond of the repair material on the mortar substrate is promoted via the biodeposition of a calcium carbonate layer by a ureolytic bacterium. X-ray diffraction and scanning electron microscopy were used to examine the interfaces between the repair material and the substrate, a...

Direct electron transfer of glucose oxidase promoted by carbon nanotubes is without value in certain mediator-free applications

International Nuclear Information System (INIS)

Wang, Y.; Yao, Y.

2012-01-01

We have investigated the direct electron transfer (DET) promoted by carbon nanotubes (CNTs) on an electrode containing immobilized glucose oxidase (GOx) with the aim to develop a third-generation glucose biosensor and a mediator-free glucose biofuel cell anode. GOx was immobilized via chitosan (CS) on a glassy carbon electrode (GCE) modified with multi-walled carbon nanotubes (MWCNTs). Cyclic voltammetric revealed that the GOx on the surface of such an electrode is unable to simultaneously demonstrate DET with the electrode and to retain its catalytic activity towards glucose, although the MWCNTs alone can promote electron transfer between GOx and electrode. This is interpreted in terms of two types of GOx on the surface, the distribution and properties of which are quite different. The first type exhibits DET capability that results from the collaboration of MWCNTs and metal impurities, but is unable to catalyze the oxidation of glucose. The second type maintains its glucose-specific catalytic capability in the presence of a mediator, which can be enhanced by MWCNTs, but cannot undergo DET with the electrode. As a result, the MWCNTs are capable of promoting the electron transfer, but this is without value in some mediator-free applications such as in third-generation glucose biosensors and in mediator-free anodes for glucose biofuel cells. (author)

“Direct modulation of a hybrid III-V/Si DFB laser with MRR filtering for 22.5-Gb/s error-free dispersion-uncompensated transmission over 2.5-km SSMF

DEFF Research Database (Denmark)

Cristofori, Valentina; Da Ros, Francesco; Ding, Yunhong

2016-01-01

Error-free and penalty-free transmission over 2.5 km SSMF of a 22.5 Gb/s data signal from a directly modulated hybrid III-V/Si DFB laser is achieved by enhancing the dispersion tolerance using a silicon micro-ring resonator....

Substrate overlap and functional competition between human nucleotide excision repair and Escherichia coli photolyase and (A)BC excision nuclease

International Nuclear Information System (INIS)

Sibghat-Ullah; Sancar, Z.

1990-01-01

Human cell free extract prepared by the method of Manley et al. carries out repair synthesis on UV-irradiated DNA. Removal of pyrimidine dimers by photoreactivation with DNA photolyase reduces repair synthesis by about 50%. With excess enzyme in the reaction mixture photolyase reduced the repair signal by the same amount even in the absence of photoreactivating light, presumably by binding to pyrimidine dimers and interfering with the binding of human damage recognition protein. Similarly, the UvrB subunit of Escherichia coli (A)BC excinuclease when loaded onto UV-irradiated or psoralen-adducted DNA inhibited repair synthesis by cell-free extract by 75-80%. The opposite was true also as HeLa cell free extract specifically inhibited the photorepair of a thymine dimer by DNA photolyase and its removal by (A)BC excinuclease. Cell-free extracts from xeroderma pigmentosum (XP) complementation groups A and C were equally effective in blocking the E. coli repair proteins, while extracts from complementation groups D and E were ineffective in blocking the E. coli enzyme. These results suggest that XP-D and XP-E cells are defective in the damage recognition subunits(s) of human excision nuclease

The conditions that promote fear learning: prediction error and Pavlovian fear conditioning.

Science.gov (United States)

Li, Susan Shi Yuan; McNally, Gavan P

2014-02-01

A key insight of associative learning theory is that learning depends on the actions of prediction error: a discrepancy between the actual and expected outcomes of a conditioning trial. When positive, such error causes increments in associative strength and, when negative, such error causes decrements in associative strength. Prediction error can act directly on fear learning by determining the effectiveness of the aversive unconditioned stimulus or indirectly by determining the effectiveness, or associability, of the conditioned stimulus. Evidence from a variety of experimental preparations in human and non-human animals suggest that discrete neural circuits code for these actions of prediction error during fear learning. Here we review the circuits and brain regions contributing to the neural coding of prediction error during fear learning and highlight areas of research (safety learning, extinction, and reconsolidation) that may profit from this approach to understanding learning. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

Science.gov (United States)

Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki

2014-12-01

Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

A 3D nanofibrous hydrogel and collagen sponge scaffold promotes locomotor functional recovery, spinal repair, and neuronal regeneration after complete transection of the spinal cord in adult rats

International Nuclear Information System (INIS)

Kaneko, Ai; Matsushita, Akira; Sankai, Yoshiyuki

2015-01-01

Central nervous system neurons in adult mammals display limited regeneration after injury, and functional recovery is poor following complete transection (>4 mm gap) of a rat spinal cord. A novel combination scaffold composed of 3D nanofibrous hydrogel PuraMatrix and a honeycomb collagen sponge was used to promote spinal repair and locomotor functional recovery following complete transection of the spinal cord in rats. We transplanted this scaffold into 5 mm spinal cord gaps and assessed spinal repair and functional recovery using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. The BBB score of the scaffold-transplanted group was significantly higher than that of the PBS-injected control group from 24 d to 4 months after the operation (P < 0.001–0.01), reaching 6.0  ±  0.75 (mean ± SEM) in the transplant and 0.70  ±  0.46 in the control groups. Neuronal regeneration and spinal repair were examined histologically using Pan Neuronal Marker, glial fibrillary acidic protein, growth-associated protein 43, and DAPI. The scaffolds were well integrated into the spinal cords, filling the 5 mm gaps with higher numbers of regenerated and migrated neurons, astrocytes, and other cells than in the control group. Mature and immature neurons and astrocytes in the scaffolds became colocalized and aligned longitudinally over >2 mm, suggesting their differentiation, maturation, and function. The spinal cord NF200 content of the transplant group, analyzed by western blot, was more than twice that of the control group, supporting the histological results. Transplantation of this novel scaffold promoted functional recovery, spinal repair, and neuronal regeneration. (paper)

Ontology Alignment Repair through Modularization and Confidence-Based Heuristics.

Directory of Open Access Journals (Sweden)

Emanuel Santos

Full Text Available Ontology Matching aims at identifying a set of semantic correspondences, called an alignment, between related ontologies. In recent years, there has been a growing interest in efficient and effective matching methods for large ontologies. However, alignments produced for large ontologies are often logically incoherent. It was only recently that the use of repair techniques to improve the coherence of ontology alignments began to be explored. This paper presents a novel modularization technique for ontology alignment repair which extracts fragments of the input ontologies that only contain the necessary classes and relations to resolve all detectable incoherences. The paper presents also an alignment repair algorithm that uses a global repair strategy to minimize both the degree of incoherence and the number of mappings removed from the alignment, while overcoming the scalability problem by employing the proposed modularization technique. Our evaluation shows that our modularization technique produces significantly small fragments of the ontologies and that our repair algorithm produces more complete alignments than other current alignment repair systems, while obtaining an equivalent degree of incoherence. Additionally, we also present a variant of our repair algorithm that makes use of the confidence values of the mappings to improve alignment repair. Our repair algorithm was implemented as part of AgreementMakerLight, a free and open-source ontology matching system.

Ontology Alignment Repair through Modularization and Confidence-Based Heuristics.

Science.gov (United States)

Santos, Emanuel; Faria, Daniel; Pesquita, Catia; Couto, Francisco M

2015-01-01

Ontology Matching aims at identifying a set of semantic correspondences, called an alignment, between related ontologies. In recent years, there has been a growing interest in efficient and effective matching methods for large ontologies. However, alignments produced for large ontologies are often logically incoherent. It was only recently that the use of repair techniques to improve the coherence of ontology alignments began to be explored. This paper presents a novel modularization technique for ontology alignment repair which extracts fragments of the input ontologies that only contain the necessary classes and relations to resolve all detectable incoherences. The paper presents also an alignment repair algorithm that uses a global repair strategy to minimize both the degree of incoherence and the number of mappings removed from the alignment, while overcoming the scalability problem by employing the proposed modularization technique. Our evaluation shows that our modularization technique produces significantly small fragments of the ontologies and that our repair algorithm produces more complete alignments than other current alignment repair systems, while obtaining an equivalent degree of incoherence. Additionally, we also present a variant of our repair algorithm that makes use of the confidence values of the mappings to improve alignment repair. Our repair algorithm was implemented as part of AgreementMakerLight, a free and open-source ontology matching system.

Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair.

Science.gov (United States)

Dupont, Kenneth M; Boerckel, Joel D; Stevens, Hazel Y; Diab, Tamim; Kolambkar, Yash M; Takahata, Masahiko; Schwarz, Edward M; Guldberg, Robert E

2012-03-01

Biomaterial scaffolds functionalized to stimulate endogenous repair mechanisms via the incorporation of osteogenic cues offer a potential alternative to bone grafting for the treatment of large bone defects. We first quantified the ability of a self-complementary adeno-associated viral vector encoding bone morphogenetic protein 2 (scAAV2.5-BMP2) to enhance human stem cell osteogenic differentiation in vitro. In two-dimensional culture, scAAV2.5-BMP2-transduced human mesenchymal stem cells (hMSCs) displayed significant increases in BMP2 production and alkaline phosphatase activity compared with controls. hMSCs and human amniotic-fluid-derived stem cells (hAFS cells) seeded on scAAV2.5-BMP2-coated three-dimensional porous polymer Poly(ε-caprolactone) (PCL) scaffolds also displayed significant increases in BMP2 production compared with controls during 12 weeks of culture, although only hMSC-seeded scaffolds displayed significantly increased mineral formation. PCL scaffolds coated with scAAV2.5-BMP2 were implanted into critically sized immunocompromised rat femoral defects, both with or without pre-seeding of hMSCs, representing ex vivo and in vivo gene therapy treatments, respectively. After 12 weeks, defects treated with acellular scAAV2.5-BMP2-coated scaffolds displayed increased bony bridging and had significantly higher bone ingrowth and mechanical properties compared with controls, whereas defects treated with scAAV2.5-BMP2 scaffolds pre-seeded with hMSCs failed to display significant differences relative to controls. When pooled, defect treatment with scAAV2.5-BMP2-coated scaffolds, both with or without inclusion of pre-seeded hMSCs, led to significant increases in defect mineral formation at all time points and increased mechanical properties compared with controls. This study thus presents a novel acellular bone-graft-free endogenous repair therapy for orthotopic tissue-engineered bone regeneration.

Use of hydroxyurea in the measurement of DNA repair by the BND cellulose method

International Nuclear Information System (INIS)

Irwin, J.; Strauss, B.

1980-01-01

Hydroxyurea inhibition is a convenient method of suppressing replicative DNA synthesis for DNA excision-repair measurement by the BND cellulose technique. Nonetheless, hydroxyurea can introduce artefacts by direct reaction with repair-inducing compounds and by long-term inhibition of the overall repair process. A simple technique of overcoming these problems is described. Cells are reacted with repair-inducing compounds in the absence of hydroxyurea, the cells are washed free of inducer, hydroxyurea is added to 2 mM, and after a short period to establish replication inhibition, 3 H dThd is added and repair measured over a one-hour incubation period

Influence of material surface on the scanning error of a powder-free 3D measuring system.

Science.gov (United States)

Kurz, Michael; Attin, Thomas; Mehl, Albert

2015-11-01

This study aims to evaluate the accuracy of a powder-free three-dimensional (3D) measuring system (CEREC Omnicam, Sirona), when scanning the surface of a material at different angles. Additionally, the influence of water was investigated. Nine different materials were combined with human tooth surface (enamel) to create n = 27 specimens. These materials were: Controls (InCoris TZI and Cerec Guide Bloc), ceramics (Vitablocs® Mark II and IPS Empress CAD), metals (gold and amalgam) and composites (Tetric Ceram, Filtek Supreme A2B and A2E). The highly polished samples were scanned at different angles with and without water. The 216 scans were then analyzed and descriptive statistics were obtained. The height difference between the tooth and material surfaces, as measured with the 3D scans, ranged from 0.83 μm (±2.58 μm) to -14.79 μm (±3.45 μm), while the scan noise on the materials was between 3.23 μm (±0.79 μm) and 14.24 μm (±6.79 μm) without considering the control groups. Depending on the thickness of the water film, measurement errors in the order of 300-1,600 μm could be observed. The inaccuracies between the tooth and material surfaces, as well as the scan noise for the materials, were within the range of error for measurements used for conventional impressions and are therefore negligible. The presence of water, however, greatly affects the scan. The tested powder-free 3D measuring system can safely be used to scan different material surfaces without the prior application of a powder, although drying of the surface prior to scanning is highly advisable.

The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

Institute of Scientific and Technical Information of China (English)

Dong Sun

2016-01-01

Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent de-velopment in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury.

The identification and repair of anomalous measurements in the measurement of big diameter based on rolling-wheel method

Science.gov (United States)

Chen, Haiou; Yu, Xiaofen

2011-05-01

Rolling-wheel method is an effective way of measuring big diameter. After amending the temperature error and pressure error, the uncertainty of measurement can not be φ =5um/m stably because of the influence of skid. The traditional method of identifying skid loses sight of the influences of the unstable motor speed, the appearance form error and the eccentric of installation of the big axis and rolling wheel and so on, so the method has its limitation. In this paper, a new method of multiple identification and repair is introduced, namely n diameters are measured and Chauvenet standard is used for identifying the anomalous measurements one by one, and then the average value of the remaining data is used for repairing identified anomalous measurements, and the next round identification and repair is carried out until the accuracy requirement of the measurement is satisfied. The result of experiments indicates that the method can identify anomalous measurements whose offsets caused by the skid are greater than 0.2φ , and the uncertainty of measurement has improved substantially.

The carboxyl terminus of FANCE recruits FANCD2 to the Fanconi Anemia (FA) E3 ligase complex to promote the FA DNA repair pathway.

Science.gov (United States)

Polito, David; Cukras, Scott; Wang, Xiaozhe; Spence, Paige; Moreau, Lisa; D'Andrea, Alan D; Kee, Younghoon

2014-03-07

Fanconi anemia (FA) is a genome instability syndrome characterized by bone marrow failure and cellular hypersensitivity to DNA cross-linking agents. In response to DNA damage, the FA pathway is activated through the cooperation of 16 FA proteins. A central player in the pathway is a multisubunit E3 ubiquitin ligase complex or the FA core complex, which monoubiquitinates its substrates FANCD2 and FANCI. FANCE, a subunit of the FA core complex, plays an essential role by promoting the integrity of the complex and by directly recognizing FANCD2. To delineate its role in substrate ubiquitination from the core complex assembly, we analyzed a series of mutations within FANCE. We report that a phenylalanine located at the highly conserved extreme C terminus, referred to as Phe-522, is a critical residue for mediating the monoubiquitination of the FANCD2-FANCI complex. Using the FANCE mutant that specifically disrupts the FANCE-FANCD2 interaction as a tool, we found that the interaction-deficient mutant conferred cellular sensitivity in reconstituted FANCE-deficient cells to a similar degree as FANCE null cells, suggesting the significance of the FANCE-FANCD2 interaction in promoting cisplatin resistance. Intriguingly, ectopic expression of the FANCE C terminus fragment alone in FA normal cells disrupts DNA repair, consolidating the importance of the FANCE-FANCD2 interaction in the DNA cross-link repair.

The Carboxyl Terminus of FANCE Recruits FANCD2 to the Fanconi Anemia (FA) E3 Ligase Complex to Promote the FA DNA Repair Pathway*

Science.gov (United States)

Polito, David; Cukras, Scott; Wang, Xiaozhe; Spence, Paige; Moreau, Lisa; D'Andrea, Alan D.; Kee, Younghoon

2014-01-01

Fanconi anemia (FA) is a genome instability syndrome characterized by bone marrow failure and cellular hypersensitivity to DNA cross-linking agents. In response to DNA damage, the FA pathway is activated through the cooperation of 16 FA proteins. A central player in the pathway is a multisubunit E3 ubiquitin ligase complex or the FA core complex, which monoubiquitinates its substrates FANCD2 and FANCI. FANCE, a subunit of the FA core complex, plays an essential role by promoting the integrity of the complex and by directly recognizing FANCD2. To delineate its role in substrate ubiquitination from the core complex assembly, we analyzed a series of mutations within FANCE. We report that a phenylalanine located at the highly conserved extreme C terminus, referred to as Phe-522, is a critical residue for mediating the monoubiquitination of the FANCD2-FANCI complex. Using the FANCE mutant that specifically disrupts the FANCE-FANCD2 interaction as a tool, we found that the interaction-deficient mutant conferred cellular sensitivity in reconstituted FANCE-deficient cells to a similar degree as FANCE null cells, suggesting the significance of the FANCE-FANCD2 interaction in promoting cisplatin resistance. Intriguingly, ectopic expression of the FANCE C terminus fragment alone in FA normal cells disrupts DNA repair, consolidating the importance of the FANCE-FANCD2 interaction in the DNA cross-link repair. PMID:24451376

STAT3 Controls the Long-Term Survival and Phenotype of Repair Schwann Cells during Nerve Regeneration.

Science.gov (United States)

Benito, Cristina; Davis, Catherine M; Gomez-Sanchez, Jose A; Turmaine, Mark; Meijer, Dies; Poli, Valeria; Mirsky, Rhona; Jessen, Kristjan R

2017-04-19

After nerve injury, Schwann cells convert to a phenotype specialized to promote repair. But during the slow process of axonal regrowth, these repair Schwann cells gradually lose their regeneration-supportive features and eventually die. Although this is a key reason for the frequent regeneration failures in humans, the transcriptional mechanisms that control long-term survival and phenotype of repair cells have not been studied, and the molecular signaling underlying their decline is obscure. We show, in mice, that Schwann cell STAT3 has a dual role. It supports the long-term survival of repair Schwann cells and is required for the maintenance of repair Schwann cell properties. In contrast, STAT3 is less important for the initial generation of repair Schwann cells after injury. In repair Schwann cells, we find that Schwann cell STAT3 activation by Tyr705 phosphorylation is sustained during long-term denervation. STAT3 is required for maintaining autocrine Schwann cell survival signaling, and inactivation of Schwann cell STAT3 results in a striking loss of repair cells from chronically denervated distal stumps. STAT3 inactivation also results in abnormal morphology of repair cells and regeneration tracks, and failure to sustain expression of repair cell markers, including Shh, GDNF, and BDNF. Because Schwann cell development proceeds normally without STAT3, the function of this factor appears restricted to Schwann cells after injury. This identification of transcriptional mechanisms that support long-term survival and differentiation of repair cells will help identify, and eventually correct, the failures that lead to the deterioration of this important cell population. SIGNIFICANCE STATEMENT Although injured peripheral nerves contain repair Schwann cells that provide signals and spatial clues for promoting regeneration, the clinical outcome after nerve damage is frequently poor. A key reason for this is that, during the slow growth of axons through the proximal

DNA repair and longevity in three species of cold-blooded vertebrates. [uv, turtle, fish

Energy Technology Data Exchange (ETDEWEB)

Woodhead, A.D.; Setlow, R.B.; Grist, E.

1980-01-01

The error catastrophe mechanism of ageing proposes that senescence results from the progressive accumulation of unrepaired damage to DNA throughout the life span. Studies of the changes in DNA repair capability in ageing cells both in vivo and in vitro have given ambiguous results, but a clear relation has been demonstrated in mammals between the DNA repair capacity and potential longevity. We have found no difference in excision repair capacity in cultured cells from three species of cold-blooded vertebrates, the long-lived turtle, with a potential life span of 118+ yr, the rainbow trout, 8 yr, and Amazon molly, with 3 yr.

19 CFR 10.787 - Goods re-entered after repair or alteration in Morocco.

Science.gov (United States)

2010-04-01

... Morocco. 10.787 Section 10.787 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... States-Morocco Free Trade Agreement Goods Returned After Repair Or Alteration § 10.787 Goods re-entered after repair or alteration in Morocco. (a) General. This section sets forth the rules that apply for...

19 CFR 10.570 - Goods re-entered after repair or alteration in Singapore.

Science.gov (United States)

2010-04-01

... Singapore. 10.570 Section 10.570 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... States-Singapore Free Trade Agreement Goods Returned After Repair Or Alteration § 10.570 Goods re-entered after repair or alteration in Singapore. (a) General. This section sets forth the rules which apply for...

Chemical determination of free radical-induced damage to DNA.

Science.gov (United States)

Dizdaroglu, M

1991-01-01

Free radical-induced damage to DNA in vivo can result in deleterious biological consequences such as the initiation and promotion of cancer. Chemical characterization and quantitation of such DNA damage is essential for an understanding of its biological consequences and cellular repair. Methodologies incorporating the technique of gas chromatography/mass spectrometry (GC/MS) have been developed in recent years for measurement of free radical-induced DNA damage. The use of GC/MS with selected-ion monitoring (SIM) facilitates unequivocal identification and quantitation of a large number of products of all four DNA bases produced in DNA by reactions with hydroxyl radical, hydrated electron, and H atom. Hydroxyl radical-induced DNA-protein cross-links in mammalian chromatin, and products of the sugar moiety in DNA are also unequivocally identified and quantitated. The sensitivity and selectivity of the GC/MS-SIM technique enables the measurement of DNA base products even in isolated mammalian chromatin without the necessity of first isolating DNA, and despite the presence of histones. Recent results reviewed in this article demonstrate the usefulness of the GC/MS technique for chemical determination of free radical-induced DNA damage in DNA as well as in mammalian chromatin under a vast variety of conditions of free radical production.

[Monitoring of Crack Propagation in Repaired Structures Based on Characteristics of FBG Sensors Reflecting Spectra].

Science.gov (United States)

Yuan, Shen-fang; Jin, Xin; Qiu, Lei; Huang, Hong-mei

2015-03-01

In order to improve the security of aircraft repaired structures, a method of crack propagation monitoring in repaired structures is put forward basing on characteristics of Fiber Bragg Grating (FBG) reflecting spectra in this article. With the cyclic loading effecting on repaired structure, cracks propagate, while non-uniform strain field appears nearby the tip of crack which leads to the FBG sensors' reflecting spectra deformations. The crack propagating can be monitored by extracting the characteristics of FBG sensors' reflecting spectral deformations. A finite element model (FEM) of the specimen is established. Meanwhile, the distributions of strains which are under the action of cracks of different angles and lengths are obtained. The characteristics, such as main peak wavelength shift, area of reflecting spectra, second and third peak value and so on, are extracted from the FBGs' reflecting spectral which are calculated by transfer matrix algorithm. An artificial neural network is built to act as the model between the characteristics of the reflecting spectral and the propagation of crack. As a result, the crack propagation of repaired structures is monitored accurately and the error of crack length is less than 0.5 mm, the error of crack angle is less than 5 degree. The accurately monitoring problem of crack propagation of repaired structures is solved by taking use of this method. It has important significance in aircrafts safety improvement and maintenance cost reducing.

DNA N-glycosylases and uv repair

Energy Technology Data Exchange (ETDEWEB)

Demple, B; Linn, S

1980-09-18

Repair of some DNA photoproducts can be mediated by glycosylic bond hydrolysis. Thus, Escherichia coli endonuclease III releases 5,6-hydrated thymines as free bases, while T4 uv endonuclease releases one of two glycosylic bonds holding pyrimidine dimers in DNA. In contrast, uninfected E. coli apparently does not excise pyrimidine dimers via a DNA glycosylase.

DNA excision repair in permeable human fibroblasts

International Nuclear Information System (INIS)

Kaufmann, W.K.; Bodell, W.J.; Cleaver, J.E.

1983-01-01

U.v. irradiation of confluent human fibroblasts activated DNA repair, aspects of which were characterized in the cells after they were permeabilized. Incubation of intact cells for 20 min between irradiation and harvesting was necessary to obtain a maximum rate of reparative DNA synthesis. Cells harvested immediately after irradiation before repair was initiated displayed only a small stimulation of DNA synthesis, indicating that permeable cells have a reduced capacity to recognize pyrimidine dimers and activate repair. The distribution of sizes of DNA strands labeled during 10 min of reparative DNA synthesis resembled that of parental DNA. However, during a 60-min incubation of permeable cells at 37 degrees C, parental DNA and DNA labeled by reparative DNA synthesis were both cleaved to smaller sizes. Cleavage also occurred in unirradiated cells, indicating that endogenous nuclease was active during incubation. Repair patches synthesized in permeable cells displayed increased sensitivity to digestion by micrococcal nuclease. However, the change in sensitivity during a chase with unlabeled DNA precursors was small, suggesting that reassembly of nucleosome structure at sites of repair was impaired. To examine whether this deficiency was due to a preponderance of incomplete or unligated repair patches, 3H-labeled (repaired) DNA was purified, then digested with exonuclease III and nuclease S1 to probe for free 3' ends and single-stranded regions. About 85% of the [3H]DNA synthesized during a 10-min pulse resisted digestion, suggesting that a major fraction of the repair patches that were filled were also ligated. U.v. light-activated DNA synthesis in permeable cells, therefore, appears to represent the continuation of reparative gap-filling at sites of excision repair activated within intact cells. Gap-filling and ligation were comparatively efficient processes in permeable cells

A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice

Directory of Open Access Journals (Sweden)

Liang Dong

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.

Primary unilateral cleft lip repair.

Science.gov (United States)

Adenwalla, H S; Narayanan, P V

2009-10-01

The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web.

Can We Fix This? Parent-Child Repair Processes and Preschoolers' Regulatory Skills.

Science.gov (United States)

Kemp, Christine J; Lunkenheimer, Erika; Albrecht, Erin C; Chen, Deborah

2016-10-01

The repair of difficult parent-child interactions is a marker of healthy functioning in infancy, but less is known about repair processes during early childhood. We used dynamic systems methods to investigate dyadic repair in mothers and their 3-year-old children ( N = 96) and its prediction of children's emotion regulation and behavior problems at a four-month follow-up. Mothers and children completed free play and challenging puzzle tasks. Repair was operationalized as the conditional probability of moving into a dyadic adaptive behavior region after individual or dyadic maladaptive behavior (e.g., child noncompliance, parental criticism). Overall, dyads repaired approximately half their maladaptive behaviors. A greater likelihood of repair during the puzzle task predicted better child emotion regulation and fewer behavior problems in preschool. Results suggest dyadic repair is an important process in early childhood and provide further evidence for the connection between parent-child coregulation and children's developing regulatory capacities. Implications for family-based interventions are discussed.

Implementation of an audit with feedback knowledge translation intervention to promote medication error reporting in health care: a protocol.

Science.gov (United States)

Hutchinson, Alison M; Sales, Anne E; Brotto, Vanessa; Bucknall, Tracey K

2015-05-19

their reporting behaviour. To assess sustainability of the intervention, at 6 months following completion of the intervention a point-prevalence chart audit is undertaken and a report of routinely collected medication errors for the previous 6 months is obtained. This intervention will have wider application for delivery of feedback to promote behaviour change for other areas of preventable error and adverse events.

Fanconi anaemia and the repair of Watson and Crick DNA crosslinks.

Science.gov (United States)

Kottemann, Molly C; Smogorzewska, Agata

2013-01-17

The function of Fanconi anaemia proteins is to maintain genomic stability. Their main role is in the repair of DNA interstrand crosslinks, which, by covalently binding the Watson and the Crick strands of DNA, impede replication and transcription. Inappropriate repair of interstrand crosslinks causes genomic instability, leading to cancer; conversely, the toxicity of crosslinking agents makes them a powerful chemotherapeutic. Fanconi anaemia proteins can promote stem-cell function, prevent tumorigenesis, stabilize replication forks and inhibit inaccurate repair. Recent advances have identified endogenous aldehydes as possible culprits of DNA damage that may induce the phenotypes seen in patients with Fanconi anaemia.

In-plant reliability data base for nuclear plant components: a feasibility study on human error information

International Nuclear Information System (INIS)

Borkowski, R.J.; Fragola, J.R.; Schurman, D.L.; Johnson, J.W.

1984-03-01

This report documents the procedure and final results of a feasibility study which examined the usefulness of nuclear plant maintenance work requests in the IPRDS as tools for understanding human error and its influence on component failure and repair. Developed in this study were (1) a set of criteria for judging the quality of a plant maintenance record set for studying human error; (2) a scheme for identifying human errors in the maintenance records; and (3) two taxonomies (engineering-based and psychology-based) for categorizing and coding human error-related events

EFL LEARNERS REPAIR SEQUENCE TYPES ANALYSIS AS PEER- ASSESSMENT IN ORAL PERFORMANCE

Directory of Open Access Journals (Sweden)

Novia Trisanti

2017-04-01

Full Text Available There are certain concerns that EFL teacher needs to observe in assessing students oral performance, such as the amount of words which the learners utter, the grammatical errors that they make, the hesitation and certain expression that they produce. This paper attempts to give overview of research results using qualitative method which show the impacts of repair sequence types analysis on those elements needed to be observed as students peer and self-assessment to enhance their speaking ability. The subject was tertiary level learners of English Department, State University of Semarang, Indonesia in 2012. Concerning the repair types, there are four repair sequences as reviewed by Buckwalter (2001, they are Self-Initiated Self Repair (SISR, Self-Initiated Other Repair (SIOR, Other-Initiated Self Repair (OISR, and Other-Initiated Other Repair (OIOR. Having the repair sequences types anaysis, the students investigated the repair sequence of their peers while they performed in class conversation. The modified peer- assessment guideline as proposed by Brown (2004 was used in identifying, categorizing and classifying the types of repair sequences in their peers oral performance. While, the peer-assessment can be a valuable additional means to improve students speaking since it is one of the motives that drive peer- evaluation, along with peer- verification, also peer and self- enhancement. The analysis results were then interpreted to see whether there was significant finding related to the students’ oral performance enhancement.

CRISPR Technology Reveals RAD(51)-ical Mechanisms of Repair in Roundworms: An Educational Primer for Use with "Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans".

Science.gov (United States)

Turcotte, Carolyn A; Andrews, Nicolas P; Sloat, Solomon A; Checchi, Paula M

2016-11-01

The mechanisms cells use to maintain genetic fidelity via DNA repair and the accuracy of these processes have garnered interest from scientists engaged in basic research to clinicians seeking improved treatment for cancer patients. Despite the continued advances, many details of DNA repair are still incompletely understood. In addition, the inherent complexity of DNA repair processes, even at the most fundamental level, makes it a challenging topic. This primer is meant to assist both educators and students in using a recent paper, "Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in Caenorhabditis elegans," to understand mechanisms of DNA repair. The goals of this primer are to highlight and clarify several key techniques utilized, with special emphasis on the clustered, regularly interspaced, short palindromic repeats technique and the ways in which it has revolutionized genetics research, as well as to provide questions for deeper in-class discussion. Copyright © 2016 by the Genetics Society of America.

rhPDGF-BB promotes early healing in a rat rotator cuff repair model.

Science.gov (United States)

Kovacevic, David; Gulotta, Lawrence V; Ying, Liang; Ehteshami, John R; Deng, Xiang-Hua; Rodeo, Scott A

2015-05-01

Tendon-bone healing after rotator cuff repair occurs by fibrovascular scar tissue formation, which is weaker than a normal tendon-bone insertion site. Growth factors play a role in tissue formation and have the potential to augment soft tissue healing in the perioperative period. Our study aim was to determine if rhPDGF-BB delivery on a collagen scaffold can improve tendon-to-bone healing after supraspinatus tendon repair compared with no growth factor in rats as measured by (1) gross observations; (2) histologic analysis; and (3) biomechanical testing. Ninety-five male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon. Rats were randomized into one of five groups: control (ie, repair only), scaffold only, and three different platelet-derived growth factor (PDGF) doses on the collagen scaffold. Animals were euthanized 5 days after surgery to assess cellular proliferation and angiogenesis. The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization, fibrocartilage formation with safranin-O staining, and collagen fiber organization with picrosirius red staining, and to determine the biomechanical properties (ie, load-to-failure testing) of the supraspinatus tendon-bone construct. The repaired supraspinatus tendon was in continuity with the bone in all animals. At 5 days, rhPDGF-BB delivery on a scaffold demonstrated a dose-dependent response in cellular proliferation and angiogenesis compared with the control and scaffold groups. At 28 days, with the numbers available, rhPDGF-BB had no effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls. The control group had higher tensile loads to failure and stiffness (35.5 ± 8.8 N and 20.3 ± 4.5 N/mm) than all the groups receiving the scaffold, including the PDGF groups (scaffold: 27 ± 6.4 N, p = 0.021 and 13 ± 5.7 N/mm, p = 0.01; 30 µg/mL PDGF: 26.5 ± 7.5 N, p = 0.014 and 13

The selective power of causality on memory errors.

Science.gov (United States)

Marsh, Jessecae K; Kulkofsky, Sarah

2015-01-01

We tested the influence of causal links on the production of memory errors in a misinformation paradigm. Participants studied a set of statements about a person, which were presented as either individual statements or pairs of causally linked statements. Participants were then provided with causally plausible and causally implausible misinformation. We hypothesised that studying information connected with causal links would promote representing information in a more abstract manner. As such, we predicted that causal information would not provide an overall protection against memory errors, but rather would preferentially help in the rejection of misinformation that was causally implausible, given the learned causal links. In two experiments, we measured whether the causal linkage of information would be generally protective against all memory errors or only selectively protective against certain types of memory errors. Causal links helped participants reject implausible memory lures, but did not protect against plausible lures. Our results suggest that causal information may promote an abstract storage of information that helps prevent only specific types of memory errors.

Cyclin A2 promotes DNA repair in the brain during both development and aging.

Science.gov (United States)

Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

2016-07-01

Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.

Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

Directory of Open Access Journals (Sweden)

Cornelia Tolg

Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

Effect of Different Surface Treatments on the Bond Strength of Repaired Resin Restorations

International Nuclear Information System (INIS)

Engy Fahmy Ismaiel Fekry Abaza

2010-01-01

In the last decade, growing demands by patients for mercury-free esthetic restorations had markedly increased the use of resin composites in restorative dentistry. However, despite the continuing development of resin composites with improved properties, several factors, such as discoloration, color mismatch, wear; chipping or bulk fracture might present clinical problems (Mjor and Gordan. 2002, Vichi et al. 2004 and Kolbeck et al. 2006). As a result, the clinician should decide whether to replace or simply repair these restorations. Total replacement of the restoration might be regarded as over-treatment since in most cases, large portions of the restorations might be clinically and radio graphically considered free of failure. Moreover, complete removal of the restoration inevitably resulted in weakening of the tooth, unnecessary removal of intact dental tissues, more money and time consuming. For these reasons, the repair of the restoration instead of its removal would be a favorable procedure (Lucena-Martin et al. 2001, Frankenberger et al. 2003 a and Oztas et al. 2003). The key element in the determination of successful repair procedures was the adequate bond strength between the existing resin composite and the new one. Various methods have been suggested to improve the bond strength of the repaired resin restorations (Tezvergil et al. 2003 and Bonstein et al. 2005). Mechanical and/or chemical treatments had been investigated for preparation of the aged resin restorations to be repaired (Tezvergil et al. 2003, Ozcan et al. 2005 and Hannig et al. 2006). These treatments were introduced to counteract the problems of aged resin restorations which were limited amount of residual free radicals available for reaction with the repair material, contaminated surface, and highly cross-linked resin matrix ( Dall Oca et al. 2006 and Papacchini et al. 2007 a) Previous studies emphasized that mechanical treatments are the most important factor in obtaining optimal repair

Base-oxidant promoted metal-free N-demethylation of arylamines

Indian Academy of Sciences (India)

alkylation damage repair, cancer metastatic chemopre- vention and also for drug metabolism.3 In classical methods, enzymatic processes are mostly responsible for this conversion in which metal complexes4 and various oxidases or peroxidases, like horseradish per- oxidase, lipogenase, cytochrome P-450, bleomycin,.

[SOS-repair--60 years].

Science.gov (United States)

Zavil'gel'skiĭ, G B

2013-01-01

This review integrates 60 years of research on SOS-repair and SOS-mutagenesis in procaryotes and eucaryotes, from Jean Weigle experiment in 1953 year (mutagenesis of lambda bacteriophage in UV-irradiated bacteria) to the latest achievements in studying SOS-mutagenesis on all living organisms--Eukarya, Archaea and Bacteria. A key role in establishing of a biochemical basis for SOS-mutagenesis belonges to the finding in 1998-1999 years that specific error-prone DNA polymerases (PolV and others) catalysed translesion synthesis on damaged DNA. This review focuses on recent studies addressing the new models for SOS-induced mutagenesis in Escherichia coli and Home sapiens cells.

Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

International Nuclear Information System (INIS)

Wei, Y T; Tian, W M; Yu, X; Cui, F Z; Hou, S P; Xu, Q Y; Lee, In-Seop

2007-01-01

A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue

Error analysis to improve the speech recognition accuracy on ...

Indian Academy of Sciences (India)

dictionary plays a key role in the speech recognition accuracy. .... Sophisticated microphone is used for the recording speech corpus in a noise free environment. .... values, word error rate (WER) and error-rate will be calculated as follows:.

Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.

Science.gov (United States)

Hiu, Takeshi; Farzampour, Zoya; Paz, Jeanne T; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D; Wang, Gordon; Lemmens, Robin; Tran, Kevin V; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A; O'Rourke, Nancy; Smith, Stephen J; Huguenard, John R; Bliss, Tonya M; Steinberg, Gary K

2016-02-01

Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

DNA repair , cell repair and radiosensitivity

International Nuclear Information System (INIS)

Zhestyanikov, V.D.

1983-01-01

Data obtained in laboratory of radiation cytology and literature data testifying to a considerable role of DNA repair in cell sensitivity to radiation and chemical DNA-tropic agents have been considered. Data pointing to the probability of contribution of inducible repair of DNA into plant cells sensitivity to X-rays are obtained. Certain violations of DNA repair do not result in the increase of radiosensitivity. It is assumed that in the cases unknown mechanisms of DNA repair operate

Implementing parallel spreadsheet models for health policy decisions: The impact of unintentional errors on model projections.

Science.gov (United States)

Bailey, Stephanie L; Bono, Rose S; Nash, Denis; Kimmel, April D

2018-01-01

Spreadsheet software is increasingly used to implement systems science models informing health policy decisions, both in academia and in practice where technical capacity may be limited. However, spreadsheet models are prone to unintentional errors that may not always be identified using standard error-checking techniques. Our objective was to illustrate, through a methodologic case study analysis, the impact of unintentional errors on model projections by implementing parallel model versions. We leveraged a real-world need to revise an existing spreadsheet model designed to inform HIV policy. We developed three parallel versions of a previously validated spreadsheet-based model; versions differed by the spreadsheet cell-referencing approach (named single cells; column/row references; named matrices). For each version, we implemented three model revisions (re-entry into care; guideline-concordant treatment initiation; immediate treatment initiation). After standard error-checking, we identified unintentional errors by comparing model output across the three versions. Concordant model output across all versions was considered error-free. We calculated the impact of unintentional errors as the percentage difference in model projections between model versions with and without unintentional errors, using +/-5% difference to define a material error. We identified 58 original and 4,331 propagated unintentional errors across all model versions and revisions. Over 40% (24/58) of original unintentional errors occurred in the column/row reference model version; most (23/24) were due to incorrect cell references. Overall, >20% of model spreadsheet cells had material unintentional errors. When examining error impact along the HIV care continuum, the percentage difference between versions with and without unintentional errors ranged from +3% to +16% (named single cells), +26% to +76% (column/row reference), and 0% (named matrices). Standard error-checking techniques may not

Bit error rate analysis of free-space optical communication over general Malaga turbulence channels with pointing error

KAUST Repository

Alheadary, Wael Ghazy

2016-12-24

In this work, we present a bit error rate (BER) and achievable spectral efficiency (ASE) performance of a freespace optical (FSO) link with pointing errors based on intensity modulation/direct detection (IM/DD) and heterodyne detection over general Malaga turbulence channel. More specifically, we present exact closed-form expressions for adaptive and non-adaptive transmission. The closed form expressions are presented in terms of generalized power series of the Meijer\\'s G-function. Moreover, asymptotic closed form expressions are provided to validate our work. In addition, all the presented analytical results are illustrated using a selected set of numerical results.

Primary unilateral cleft lip repair

Directory of Open Access Journals (Sweden)

Adenwalla H

2009-10-01

Full Text Available The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web.

Texture Repairing by Unified Low Rank Optimization

Institute of Scientific and Technical Information of China (English)

Xiao Liang; Xiang Ren; Zhengdong Zhang; Yi Ma

2016-01-01

In this paper, we show how to harness both low-rank and sparse structures in regular or near-regular textures for image completion. Our method is based on a unified formulation for both random and contiguous corruption. In addition to the low rank property of texture, the algorithm also uses the sparse assumption of the natural image: because the natural image is piecewise smooth, it is sparse in certain transformed domain (such as Fourier or wavelet transform). We combine low-rank and sparsity properties of the texture image together in the proposed algorithm. Our algorithm based on convex optimization can automatically and correctly repair the global structure of a corrupted texture, even without precise information about the regions to be completed. This algorithm integrates texture rectification and repairing into one optimization problem. Through extensive simulations, we show our method can complete and repair textures corrupted by errors with both random and contiguous supports better than existing low-rank matrix recovery methods. Our method demonstrates significant advantage over local patch based texture synthesis techniques in dealing with large corruption, non-uniform texture, and large perspective deformation.

Role of DNA repair in repair of cytogenetic damages. Slowly repaired DNA injuries involved in cytogenetic damages repair

International Nuclear Information System (INIS)

Zaichkina, S.I.; Rozanova, O.M.; Aptikaev, G.F.; Ganassi, E.Eh.

1989-01-01

Caffeine was used to study the kinetics of cytogenetic damages repair in Chinese hamster fibroblasts. Its half-time (90 min) was shown to correlate with that of repair of slowly repaired DNA damages. The caffeine-induced increase in the number of irreparable DNA damages, attributed to inhibition of double-strand break repair, is in a quantitative correlation with the effect of the cytogenetic damage modification

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

Science.gov (United States)

Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

2013-02-01

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy

NARCIS (Netherlands)

Vollebergh, Marieke A.; Lips, Esther H.; Nederlof, Petra M.; Wessels, Lodewyk F. A.; Wesseling, Jelle; Vijver, Marc J. vd; de Vries, Elisabeth G. E.; van Tinteren, Harm; Jonkers, Jos; Hauptmann, Michael; Rodenhuis, Sjoerd; Linn, Sabine C.

2014-01-01

Introduction: BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating

Writers, Readers, and Erasers of Histone Ubiquitylation in DNA Double-Strand Break Repair

DEFF Research Database (Denmark)

Smeenk, Godelieve; Mailand, Niels

2016-01-01

accurate lesion repair and restoration of genome integrity. In vertebrate cells, ubiquitin-dependent modifications of histones adjacent to DSBs by RNF8, RNF168, and other ubiquitin ligases have a key role in promoting the assembly of repair protein complexes, serving as direct recruitment platforms...... for a range of genome caretaker proteins and their associated factors. These DNA damage-induced chromatin ubiquitylation marks provide an essential component of a histone code for DSB repair that is controlled by multifaceted regulatory circuits, underscoring its importance for genome stability maintenance....... In this review, we provide a comprehensive account of how DSB-induced histone ubiquitylation is sensed, decoded and modulated by an elaborate array of repair factors and regulators. We discuss how these mechanisms impact DSB repair pathway choice and functionality for optimal protection of genome integrity...

Repair of DNA damage in the human metallothionein gene family

International Nuclear Information System (INIS)

Leadon, S.A.; Snowden, M.M.

1987-01-01

In order to distinguish enhanced repair of a sequence due to its transcriptional activity from enhanced repair due to chromatin alterations brought about by integration of a sequence into the genome, we have investigated the repair of damage both in endogenous genes and in cell lines that contain an integrated gene with an inducible promoter. The endogenous genes we are studying are the metallothioneins (MTs), a multigene family in man consisting of about 10-12 members. Cultured cells were exposed to 10-J/m 2 uv light and allowed to repair in the presence of bromodeoxyuridine. The DNA was then isolated, digested with Eco RI, and fully hybrid density DNA made by semiconservative synthesis was separated from unreplicated DNA by centrifugation in CsCl density gradients. Unreplicated, parental-density DNA was then reacted with a monoclonal antibody against bromouracil. 1 ref., 1 fig., 1 tab

Lead exposure in radiator repair workers: a survey of Washington State radiator repair shops and review of occupational lead exposure registry data.

Science.gov (United States)

Whittaker, Stephen G

2003-07-01

Radiator repair workers in Washington State have the greatest number of very elevated (> or =60 microg/dL) blood lead levels of any other worker population. The goals of this study were to determine the number of radiator repair workers potentially exposed to lead; estimate the extent of blood lead data underreporting to the Occupational Lead Exposure Registry; describe current safety and health practices in radiator repair shops; and determine appropriate intervention strategies to reduce exposure and increase employer and worker awareness. Lead exposure in Washington State's radiator repair workers was assessed by reviewing Registry data and conducting a statewide survey of radiator repair businesses. This study revealed that a total of 226 workers in Washington State (including owner-operators and all employees) conduct repair activities that could potentially result in excessive exposures to lead. Approximately 26% of radiator repair workers with elevated blood lead levels (> or =25 microg/dL) were determined to report to Washington State's Registry. This study also revealed a lack of awareness of lead's health effects, appropriate industrial hygiene controls, and the requirements of the Lead Standard. Survey respondents requested information on a variety of workplace health and safety issues and waste management; 80% requested a confidential, free-of-charge consultation. Combining data derived from an occupational health surveillance system and a statewide mail survey proved effective at characterizing lead exposures and directing public health intervention in Washington State.

The response of tenocytes to commercial scaffolds used for rotator cuff repair

Directory of Open Access Journals (Sweden)

RDJ Smith

2017-01-01

Full Text Available Surgical repairs of rotator cuff tears have high re-tear rates and many scaffolds have been developed to augment the repair. Understanding the interaction between patients’ cells and scaffolds is important for improving scaffold performance and tendon healing. In this in vitro study, we investigated the response of patient-derived tenocytes to eight different scaffolds. Tested scaffolds included X-Repair, Poly-Tape, LARS Ligament, BioFiber (synthetic scaffolds, BioFiber-CM (biosynthetic scaffold, GraftJacket, Permacol, and Conexa (biological scaffolds. Cell attachment, proliferation, gene expression, and morphology were assessed. After one day, more cells attached to synthetic scaffolds with dense, fine and aligned fibres (X-Repair and Poly-Tape. Despite low initial cell attachment, the human dermal scaffold (GraftJacket promoted the greatest proliferation of cells over 13 days. Expression of collagen types I and III were upregulated in cells grown on non-cross-linked porcine dermis (Conexa. Interestingly, the ratio of collagen I to collagen III mRNA was lower on all dermal scaffolds compared to synthetic and biosynthetic scaffolds. These findings demonstrate significant differences in the response of patient-derived tendon cells to scaffolds that are routinely used for rotator cuff surgery. Synthetic scaffolds promoted increased cell adhesion and a tendon-like cellular phenotype, while biological scaffolds promoted cell proliferation and expression of collagen genes. However, no single scaffold was superior. Our results may help understand the way that patients’ cells interact with scaffolds and guide the development of new scaffolds in the future.

Are Fruits of Free Normal Education Policy Real or Mythical? "A Critical Appraisal of the Free Teacher Education Policy Meant to Promote Rural Education in China"

Science.gov (United States)

Luo, Zubing; Mkandawire, Matthews Tiwaone

2015-01-01

Since September 2007, the Ministry of Education of China has been implementing a policy called "Free Normal Education" (FNE) for college students majoring in education in normal universities. The central goal for FNE is to promote quality of education by providing rural areas with high quality teachers who are bonded through their…

Frequency of oronasal fistulae in complete cleft palate repair

International Nuclear Information System (INIS)

Aslam, M.

2015-01-01

To determine the frequency of oro-nasal fistula in patients undergoing complete cleft palate repair by two flappalatoplasty. Study Design: Case series. Place and Duration of Study: Department of Plastic Surgery, Services Hospital, Lahore, from January to December 2013. Methodology: Patients admitted to the study place for repair of cleft palate after informed consent obtained were included. Cleft palate was repaired by two-flap palatoplasty, using Bardach technique. Patients were discharged on the second postoperative day and followed-up at third week postoperatively. During follow-up visits, fistulae formation and their sites were recorded on pre-designed proforma. Results: Among the total 90 patients, 40 patients (44.4%) were male and 50 patients (55.6%) were female. The mean age was 6.4 +- 5.7 years ranging from 9 months to 20 years. At third week follow-up, 5 patients (5.6%) had fistulae formation. Four patients (80%) had anterior fistulae and one patient (20%) had posterior fistula. Conclusion: With two-flap palatoplasty Bardach procedure for repair of cleft palate, the complication of fistula formation was uncommon at 5.6%, provided the repair was tension free and multi-layered. (author)

Medical Error Avoidance in Intraoperative Neurophysiological Monitoring: The Communication Imperative.

Science.gov (United States)

Skinner, Stan; Holdefer, Robert; McAuliffe, John J; Sala, Francesco

2017-11-01

Error avoidance in medicine follows similar rules that apply within the design and operation of other complex systems. The error-reduction concepts that best fit the conduct of testing during intraoperative neuromonitoring are forgiving design (reversibility of signal loss to avoid/prevent injury) and system redundancy (reduction of false reports by the multiplication of the error rate of tests independently assessing the same structure). However, error reduction in intraoperative neuromonitoring is complicated by the dichotomous roles (and biases) of the neurophysiologist (test recording and interpretation) and surgeon (intervention). This "interventional cascade" can be given as follows: test → interpretation → communication → intervention → outcome. Observational and controlled trials within operating rooms demonstrate that optimized communication, collaboration, and situational awareness result in fewer errors. Well-functioning operating room collaboration depends on familiarity and trust among colleagues. Checklists represent one method to initially enhance communication and avoid obvious errors. All intraoperative neuromonitoring supervisors should strive to use sufficient means to secure situational awareness and trusted communication/collaboration. Face-to-face audiovisual teleconnections may help repair deficiencies when a particular practice model disallows personal operating room availability. All supervising intraoperative neurophysiologists need to reject an insular or deferential or distant mindset.

Carbon nanotubes in neuroregeneration and repair.

Science.gov (United States)

Fabbro, Alessandra; Prato, Maurizio; Ballerini, Laura

2013-12-01

In the last decade, we have experienced an increasing interest and an improved understanding of the application of nanotechnology to the nervous system. The aim of such studies is that of developing future strategies for tissue repair to promote functional recovery after brain damage. In this framework, carbon nanotube based technologies are emerging as particularly innovative tools due to the outstanding physical properties of these nanomaterials together with their recently documented ability to interface neuronal circuits, synapses and membranes. This review will discuss the state of the art in carbon nanotube technology applied to the development of devices able to drive nerve tissue repair; we will highlight the most exciting findings addressing the impact of carbon nanotubes in nerve tissue engineering, focusing in particular on neuronal differentiation, growth and network reconstruction. © 2013.

Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

Energy Technology Data Exchange (ETDEWEB)

Jayakumar, Sundarraj; Pal, Debojyoti; Sandur, Santosh K., E-mail: sskumar@barc.gov.in

2015-09-15

Highlights: • Nrf2 inhibition in A549 cells led to attenuated DNA repair and radiosensitization. • Influence of Nrf2 on DNA repair is not linked to its antioxidant function. • Nrf2 influences DNA repair through homologous recombination (HR) repair pathway. • Many genes involved in HR pathway show ARE sequences in their upstream region. - Abstract: Nrf2 is a redox sensitive transcription factor that is involved in the co-ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by γH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non-homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA-PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2

Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

KAUST Repository

Takahashi, Yuta

2017-05-05

CpG islands (CGIs) are primarily promoter-associated genomic regions and are mostly unmethylated within highly methylated mammalian genomes. The mechanisms by which CGIs are protected from de novo methylation remain elusive. Here we show that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation. By targeting the DNA mismatch repair gene MLH1 CGI, we could generate a PSC model of a cancer-related epimutation. Furthermore, we successfully corrected aberrant imprinting in induced PSCs derived from an Angelman syndrome patient. Our results provide insights into how CpG-free DNA induces de novo CGI methylation and broaden the application of targeted epigenome editing for a better understanding of human development and disease.

Mutagenic DNA repair in Escherichia coli. VII

International Nuclear Information System (INIS)

Bridges, B.A.; Mottershead, R.P.

1978-01-01

Incubation of E. coli WP2 in the presence of chloramphenicol (CAP) for 90 min before and 60 min after γ-irradiation had no effect on the induction of Trp + mutations. Bacteria that had been treated with CAP for 90 min prior to UV irradiation showed normal or near normal yields of induced mutations to streptomycin or colicin E2 resistance. Most of these mutations lost their photoreversibility (indicating 'fixation') during continued incubation with CAP for a further 60 min after irradiation, during which time neither protein nor DNA synthesis was detectable. It is suggested that CAP-sensitive protein synthesis is not required for mutagenic (error-prone) repair of lesions in pre-existing DNA, arguing against an inducible component in this repair. In contrast the frequency of UV-induced mutations to Trp + (largely at suppressor loci) was drastically reduced by CAP pretreatment, confirming the need for an active replication fork for UV-mutagenesis at these loci. It is known from the work of others that CAP given after UV abolishes mutagenesis at these loci. It is concluded that CAP-sensitive protein synthesis (consistent with a requirement for an inducible function) is necessary for mutagenic repair only in newly-replicated DNA (presumably at daughter strand gaps) and not in pre-existing DNA. The data are consistent with but do not prove the hypothesis that CAP-sensitive and insensitive modes of mutagenesis reflect minor differences in the operation of a single basic mutagenic repair system. (Auth.)

Nerve transection repair using laser-activated chitosan in a rat model.

Science.gov (United States)

Bhatt, Neel K; Khan, Taleef R; Mejias, Christopher; Paniello, Randal C

2017-08-01

Cranial nerve transection during head and neck surgery is conventionally repaired with microsuture. Previous studies have demonstrated recovery with laser nerve welding (LNW), a novel alternative to microsuture. LNW has been reported to have poorer tensile strength, however. Laser-activated chitosan, an adhesive biopolymer, may promote nerve recovery while enhancing the tensile strength of the repair. Using a rat posterior tibial nerve injury model, we compared four different methods of nerve repair in this pilot study. Animal study. Animals underwent unilateral posterior tibial nerve transection. The injury was repaired by potassium titanyl phosphate (KTP) laser alone (n = 20), KTP + chitosan (n = 12), microsuture + chitosan (n = 12), and chitosan alone (n = 14). Weekly walking tracks were conducted to measure functional recovery (FR). Tensile strength (TS) was measured at 6 weeks. At 6 weeks, KTP laser alone had the best recovery (FR = 93.4% ± 8.3%). Microsuture + chitosan, KTP + chitosan, and chitosan alone all showed good FR (87.4% ± 13.5%, 84.6% ± 13.0%, and 84.1% ± 10.0%, respectively). One-way analysis of variance was performed (F(3,56) = 2.6, P = .061). A TS threshold of 3.8 N was selected as a control mean recovery. Three groups-KTP alone, KTP + chitosan, and microsuture + chitosan-were found to meet threshold 60% (95% confidence interval [CI]: 23.1%-88.3%), 75% (95% CI: 46.8%-91.1%), and 100% (95% CI: 75.8%-100.0%), respectively. In the posterior tibial nerve model, all repair methods promoted nerve recovery. Laser-activated chitosan as a biopolymer anchor provided good TS and appears to be a novel alternative to microsuture. This repair method may have surgical utility following cranial nerve injury during head and neck surgery. NA Laryngoscope, 127:E253-E257, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy

NARCIS (Netherlands)

Vollebergh, Marieke A.; Lips, Esther H.; Nederlof, Petra M.; Wessels, Lodewyk F. A.; Wesseling, Jelle; Vd Vijver, Marc J.; de Vries, Elisabeth G. E.; van Tinteren, Harm; Jonkers, Jos; Hauptmann, Michael; Rodenhuis, Sjoerd; Linn, Sabine C.

2014-01-01

BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and

Identification and estimation of nonlinear models using two samples with nonclassical measurement errors

KAUST Repository

Carroll, Raymond J.

2010-05-01

This paper considers identification and estimation of a general nonlinear Errors-in-Variables (EIV) model using two samples. Both samples consist of a dependent variable, some error-free covariates, and an error-prone covariate, for which the measurement error has unknown distribution and could be arbitrarily correlated with the latent true values; and neither sample contains an accurate measurement of the corresponding true variable. We assume that the regression model of interest - the conditional distribution of the dependent variable given the latent true covariate and the error-free covariates - is the same in both samples, but the distributions of the latent true covariates vary with observed error-free discrete covariates. We first show that the general latent nonlinear model is nonparametrically identified using the two samples when both could have nonclassical errors, without either instrumental variables or independence between the two samples. When the two samples are independent and the nonlinear regression model is parameterized, we propose sieve Quasi Maximum Likelihood Estimation (Q-MLE) for the parameter of interest, and establish its root-n consistency and asymptotic normality under possible misspecification, and its semiparametric efficiency under correct specification, with easily estimated standard errors. A Monte Carlo simulation and a data application are presented to show the power of the approach.

The dual nature of mismatch repair as antimutator and mutator: for better or for worse

Directory of Open Access Journals (Sweden)

Sara Thornby Bak

2014-08-01

Full Text Available DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.

Magnox Electric Littlebrook reactor inspection and repair rehearsal facility

International Nuclear Information System (INIS)

Barnes, S.A.; Clayton, R.; Gaydon, B.G.; Ramsey, B.H.

1996-01-01

Magnox reactors, although designed to be maintenance free during their operational life, have nevertheless highlighted the need for test rig facilities to train operators in the methods and techniques of reactor inspection and repair. The history of the facility for reactor engineering development (FRED) is described and its present role as a repair rehearsal facility noted. Advances in computer graphics may, in future, mean that such operator training will be virtual reality rather than analog reality based; however the need for such rigs to commission techniques and equipment and to establish performance and reliability is likely to continue. (UK)

Role of DNA repair in repair of cytogenetic damages. Contribution of repair of single-strand DNA breaks to cytogenetic damages repair

International Nuclear Information System (INIS)

Rozanova, O.M.; Zaichkina, S.I.; Aptikaev, G.F.; Ganassi, E.Eh.

1989-01-01

The comparison was made between the results of the effect of poly(ADP-ribosylation) ingibitors (e.g. nicotinamide and 3-aminobenzamide) and a chromatin proteinase ingibitor, phenylmethylsulfonylfluoride, on the cytogenetic damages repair, by a micronuclear test, and DNA repair in Chinese hamster fibroblasts. The values of the repair half-periods (5-7 min for the cytogenetic damages and 5 min for the rapidly repaired DNA damages) and a similar modyfying effect with regard to radiation cytogenetic damages and kynetics of DNA damages repair were found to be close. This confirms the contribution of repair of DNA single-strand breaks in the initiation of structural damages to chromosomes

Vector-free and transgene-free human iPS cells differentiate into functional neurons and enhance functional recovery after ischemic stroke in mice.

Directory of Open Access Journals (Sweden)

Osama Mohamad

Full Text Available Stroke is a leading cause of human death and disability in the adult population in the United States and around the world. While stroke treatment is limited, stem cell transplantation has emerged as a promising regenerative therapy to replace or repair damaged tissues and enhance functional recovery after stroke. Recently, the creation of induced pluripotent stem (iPS cells through reprogramming of somatic cells has revolutionized cell therapy by providing an unlimited source of autologous cells for transplantation. In addition, the creation of vector-free and transgene-free human iPS (hiPS cells provides a new generation of stem cells with a reduced risk of tumor formation that was associated with the random integration of viral vectors seen with previous techniques. However, the potential use of these cells in the treatment of ischemic stroke has not been explored. In the present investigation, we examined the neuronal differentiation of vector-free and transgene-free hiPS cells and the transplantation of hiPS cell-derived neural progenitor cells (hiPS-NPCs in an ischemic stroke model in mice. Vector-free hiPS cells were maintained in feeder-free and serum-free conditions and differentiated into functional neurons in vitro using a newly developed differentiation protocol. Twenty eight days after transplantation in stroke mice, hiPS-NPCs showed mature neuronal markers in vivo. No tumor formation was seen up to 12 months after transplantation. Transplantation of hiPS-NPCs restored neurovascular coupling, increased trophic support and promoted behavioral recovery after stroke. These data suggest that using vector-free and transgene-free hiPS cells in stem cell therapy are safe and efficacious in enhancing recovery after focal ischemic stroke in mice.

Use of high-dose erythropoietin for repair after injury: A comparison of outcomes in heart and kidney.

Science.gov (United States)

Gobe, Glenda C; Morais, Christudas; Vesey, David A; Johnson, David W

2013-07-01

There is a need to define the exact benefits and contraindications of use of high-dose recombinant human erythropoietin (EPO) for its non-hematopoietic function as a cytokine that enhances tissue repair after injury. This review compares the outcomes from use of EPO in the injured heart and kidney, two organs that are thought, traditionally, to have intrinsically-different repair mechanisms. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Ongoing work by us on EPO protection of ischemia-reperfusion-injured kidneys indicated, first, that EPO acutely enhanced kidney repair via anti-apoptotic, pro-regenerative mechanisms, and second, that EPO may promote chronic fibrosis in the long term. Work by others on the ischaemia-injured heart has also indicated that EPO promotes repair. Although myocardial infarcts are made up mostly of necrotic tissue, many publications state EPO is anti-apoptotic in the heart, as well as promoting healing via cell differentiation and stimulation of granulation tissue. In the case of the heart, promotion of fibrosis may be advantageous where an infarct has destroyed a zone of cardiomyocytes, but if EPO stimulates progressive fibrosis in the heart, this may promote cardiac failure. A major concern in relation to the use of EPO in a cytoprotective role is its stimulation of long-term inflammation and fibrosis. EPO usage for cytoprotection is undoubtedly advantageous, but it may need to be offset with an anti-inflammatory agent in some organs, like kidney and heart, where progression to chronic fibrosis after acute injury is often recorded.

Cetuximab Induces Eme1-Mediated DNA Repair: a Novel Mechanism for Cetuximab Resistance

Directory of Open Access Journals (Sweden)

Agnieszka Weinandy

2014-03-01

Full Text Available Overexpression of the epidermal growth factor receptor (EGFR is observed in a large number of neoplasms. The monoclonal antibody cetuximab/Erbitux is frequently applied to treat EGFR-expressing tumors. However, the application of cetuximab alone or in combination with radio- and/or chemotherapy often yields only little benefit for patients. In the present study, we describe a mechanism that explains resistance of both tumor cell lines and cultured primary human glioma cells to cetuximab. Treatment of these cells with cetuximab promoted DNA synthesis in the absence of increased proliferation, suggesting that DNA repair pathways were activated. Indeed, we observed that cetuximab promoted the activation of the DNA damage response pathway and prevented the degradation of essential meiotic endonuclease 1 homolog 1 (Eme1, a heterodimeric endonuclease involved in DNA repair. The increased levels of Eme1 were necessary for enhanced DNA repair, and the knockdown of Eme1 was sufficient to prevent efficient DNA repair in response to ultraviolet-C light or megavoltage irradiation. These treatments reduced the survival of tumor cells, an effect that was reversed by cetuximab application. Again, this protection was dependent on Eme1. Taken together, these results suggest that cetuximab initiates pathways that result in the stabilization of Eme1, thereby resulting in enhanced DNA repair. Accordingly, cetuximab enhances DNA repair, reducing the effectiveness of DNA-damaging therapies. This aspect should be considered when using cetuximab as an antitumor agent and suggests that Eme1 is a negative predictive marker.

Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

Science.gov (United States)

Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

2017-11-01

The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature

DNA repair

International Nuclear Information System (INIS)

Setlow, R.

1978-01-01

Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals

Studies of DNA repair in Saccharomyces cerevisiae. I. Characterization of a new allele of RAD6. II. Investigation of events in the first cell cycle after DNA damage

International Nuclear Information System (INIS)

Dolthwright-Fasse, J.A.

1980-01-01

Studies in two independent, but related, areas of DNA repair have been carried out in the eucaryotic yeast, Saccharomyces cerevisiae. The first is the characterization of a new allele in the RAD6 gene suggesting that the gene is multifunctional. The second is the utilization of photoreactivation as a probe of events occurring during the first cell cycle after DNA damage. Strains carrying the new allele, designated rad6-4, of the RAD6 locus are about as sensitive to uv and ionizing radiation as those carrying rad6-1 or rad6-3. Although rad6-4 may well be a missense mutation, the data suggest that the RAD6 gene is multifunctional. One function is necessary to recover from DNA damage in an error-free manner, and the other is concerned with mutagenic processes and sporulation. The loss of photoreversibility (LOP) of ultraviolet induced mutations to arginine independence in an excision defective strain carrying arg4-17 examines the events occurring in the first cell cycle. The post uv protein synthesis causes pyrimidine dimmers to become inaccessible to the photoreactivating enzyme in some unknown manner. There is no evidence indicating whether the normal function of the protein is involved in excision repair, or in one of the two repair processes believed to be inducible; induced mutagenesis or recombinational repair

HDAC4 and HDAC6 sustain DNA double strand break repair and stem-like phenotype by promoting radioresistance in glioblastoma cells.

Science.gov (United States)

Marampon, Francesco; Megiorni, Francesca; Camero, Simona; Crescioli, Clara; McDowell, Heather P; Sferra, Roberta; Vetuschi, Antonella; Pompili, Simona; Ventura, Luca; De Felice, Francesca; Tombolini, Vincenzo; Dominici, Carlo; Maggio, Roberto; Festuccia, Claudio; Gravina, Giovanni Luca

2017-07-01

The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery. We found that HDAC6 knock-down predisposes to radiation therapy-induced U251MG apoptosis- and U87MG autophagy-mediated cell death. HDAC4 silencing promoted radiation therapy-induced senescence, independently by the cellular context. Finally, we showed that p53 WT expression contributed to the radiotherapy lethal effects and that HDAC4 or HDAC6 sustained GBM stem-like radioresistant phenotype. Altogether, these observations suggest that HDAC4 and HDAC6 are guardians of irradiation-induced DNA damages and stemness, thus promoting radioresistance, and may represent potential prognostic markers and therapeutic targets in GBM. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomaterial applications in neural therapy and repair

Institute of Scientific and Technical Information of China (English)

Harmanvir Ghuman; Michel Modo

2017-01-01

The use of biomaterials,such as hydrogels,as a scaffold to deliver cells and drugs is becoming increasingly common to treat neurological conditions,including stroke.With a limited intrinsic ability to regenerate after injury,innovative tissue engineering strategies have shown the potential of biomaterials in facilitating neural tissue regeneration and functional recovery.Using biomaterials can not only promote the survival and integration of transplanted cells in the existing circuitry,but also support controlled site specific delivery of therapeutic drugs.This review aims to provide the reader an understanding of the brain tissue microenvironment after injury,biomaterial criteria that support tissue repair,commonly used natural and synthetic biomaterials,benefits of incorporating cells and neurotrophic factors,as well as the potential of endogenous neurogenesis in repairing the injured brain.

The importance of intra-hospital pharmacovigilance in the detection of medication errors

Science.gov (United States)

Villegas, Francisco; Figueroa-Montero, David; Barbero-Becerra, Varenka; Juárez-Hernández, Eva; Uribe, Misael; Chávez-Tapia, Norberto; González-Chon, Octavio

2018-01-01

Hospitalized patients are susceptible to medication errors, which represent between the fourth and the sixth cause of death. The department of intra-hospital pharmacovigilance intervenes in the entire process of medication with the purpose to prevent, repair and assess damages. To analyze medication errors reported by Mexican Fundación Clínica Médica Sur pharmacovigilance system and their impact on patients. Prospective study carried out from 2012 to 2015, where medication prescriptions given to patients were recorded. Owing to heterogeneity, data were described as absolute numbers in a logarithmic scale. 292 932 prescriptions of 56 368 patients were analyzed, and 8.9% of medication errors were identified. The treating physician was responsible of 83.32% of medication errors, residents of 6.71% and interns of 0.09%. No error caused permanent damage or death. This is the pharmacovigilance study with the largest sample size reported. Copyright: © 2018 SecretarÍa de Salud.

Two sides of the same coin: TFIIH complexes in transcription and DNA repair.

Science.gov (United States)

Zhovmer, Alexander; Oksenych, Valentyn; Coin, Frédéric

2010-04-13

TFIIH is organized into a seven-subunit core associated with a three-subunit Cdk-activating kinase (CAK) module. TFIIH has roles in both transcription initiation and DNA repair. During the last 15 years, several studies have been conducted to identify the composition of the TFIIH complex involved in DNA repair. Recently, a new technique combining chromatin immunoprecipitation and western blotting resolved the hidden nature of the TFIIH complex participating in DNA repair. Following the recruitment of TFIIH to the damaged site, the CAK module is released from the core TFIIH, and the core subsequently associates with DNA repair factors. The release of the CAK is specifically driven by the recruitment of the DNA repair factor XPA and is required to promote the incision/excision of the damaged DNA. Once the DNA lesions have been repaired, the CAK module returns to the core TFIIH on the chromatin, together with the release of the repair factors. These data highlight the dynamic composition of a fundamental cellular factor that adapts its subunit composition to the cell needs.

Two Sides of the Same Coin: TFIIH Complexes in Transcription and DNA Repair

Directory of Open Access Journals (Sweden)

Alexander Zhovmer

2010-01-01

Full Text Available TFIIH is organized into a seven-subunit core associated with a three-subunit Cdk-activating kinase (CAK module. TFIIH has roles in both transcription initiation and DNA repair. During the last 15 years, several studies have been conducted to identify the composition of the TFIIH complex involved in DNA repair. Recently, a new technique combining chromatin immunoprecipitation and western blotting resolved the hidden nature of the TFIIH complex participating in DNA repair. Following the recruitment of TFIIH to the damaged site, the CAK module is released from the core TFIIH, and the core subsequently associates with DNA repair factors. The release of the CAK is specifically driven by the recruitment of the DNA repair factor XPA and is required to promote the incision/excision of the damaged DNA. Once the DNA lesions have been repaired, the CAK module returns to the core TFIIH on the chromatin, together with the release of the repair factors. These data highlight the dynamic composition of a fundamental cellular factor that adapts its subunit composition to the cell needs.

Performance Analysis of Free-Space Optical Links Over Malaga (M) Turbulence Channels with Pointing Errors

KAUST Repository

Ansari, Imran Shafique

2015-08-12

In this work, we present a unified performance analysis of a free-space optical (FSO) link that accounts for pointing errors and both types of detection techniques (i.e. intensity modulation/direct detection (IM/DD) as well as heterodyne detection). More specifically, we present unified exact closedform expressions for the cumulative distribution function, the probability density function, the moment generating function, and the moments of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system, all in terms of the Meijer’s G function except for the moments that is in terms of simple elementary functions. We then capitalize on these unified results to offer unified exact closed-form expressions for various performance metrics of FSO link transmission systems, such as, the outage probability, the scintillation index (SI), the average error rate for binary and M-ary modulation schemes, and the ergodic capacity (except for IM/DD technique, where we present closed-form lower bound results), all in terms of Meijer’s G functions except for the SI that is in terms of simple elementary functions. Additionally, we derive the asymptotic results for all the expressions derived earlier in terms of Meijer’s G function in the high SNR regime in terms of simple elementary functions via an asymptotic expansion of the Meijer’s G function. We also derive new asymptotic expressions for the ergodic capacity in the low as well as high SNR regimes in terms of simple elementary functions via utilizing moments. All the presented results are verified via computer-based Monte-Carlo simulations.

Performance Analysis of Free-Space Optical Links Over Malaga (M) Turbulence Channels with Pointing Errors

KAUST Repository

Ansari, Imran Shafique; Yilmaz, Ferkan; Alouini, Mohamed-Slim

2015-01-01

In this work, we present a unified performance analysis of a free-space optical (FSO) link that accounts for pointing errors and both types of detection techniques (i.e. intensity modulation/direct detection (IM/DD) as well as heterodyne detection). More specifically, we present unified exact closedform expressions for the cumulative distribution function, the probability density function, the moment generating function, and the moments of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system, all in terms of the Meijer’s G function except for the moments that is in terms of simple elementary functions. We then capitalize on these unified results to offer unified exact closed-form expressions for various performance metrics of FSO link transmission systems, such as, the outage probability, the scintillation index (SI), the average error rate for binary and M-ary modulation schemes, and the ergodic capacity (except for IM/DD technique, where we present closed-form lower bound results), all in terms of Meijer’s G functions except for the SI that is in terms of simple elementary functions. Additionally, we derive the asymptotic results for all the expressions derived earlier in terms of Meijer’s G function in the high SNR regime in terms of simple elementary functions via an asymptotic expansion of the Meijer’s G function. We also derive new asymptotic expressions for the ergodic capacity in the low as well as high SNR regimes in terms of simple elementary functions via utilizing moments. All the presented results are verified via computer-based Monte-Carlo simulations.

A controlled community-based trial to promote smoke-free policy in rural communities.

Science.gov (United States)

Hahn, Ellen J; Rayens, Mary Kay; Adkins, Sarah; Begley, Kathy; York, Nancy

2015-01-01

Rural, tobacco-growing areas are disproportionately affected by tobacco use, secondhand smoke, and weak tobacco control policies. The purpose was to test the effects of a stage-specific, tailored policy-focused intervention on readiness for smoke-free policy, and policy outcomes in rural underserved communities. A controlled community-based trial including 37 rural counties. Data were collected annually with community advocates (n = 330) and elected officials (n = 158) in 19 intervention counties and 18 comparison counties over 5 years (average response rate = 68%). Intervention communities received policy development strategies from community advisors tailored to their stage of readiness and designed to build capacity, build demand, and translate and disseminate science. Policy outcomes were tracked over 5 years. Communities receiving the stage-specific, tailored intervention had higher overall community readiness scores and better policy outcomes than the comparison counties, controlling for county-level smoking rate, population size, and education. Nearly one-third of the intervention counties adopted smoke-free laws covering restaurants, bars, and all workplaces compared to none of the comparison counties. The stage-specific, tailored policy-focused intervention acted as a value-added resource to local smoke-free campaigns by promoting readiness for policy, as well as actual policy change in rural communities. Although actual policy change and percent covered by the policies were modest, these areas need additional resources and efforts to build capacity, build demand, and translate and disseminate science in order to accelerate smoke-free policy change and reduce the enormous toll from tobacco in these high-risk communities. © 2014 National Rural Health Association.

DC cancellation as a method of generating a t2-response and of solving the radial position error in a concentric free-falling two-sphere equivalence-principle experiment in a drag-free satellite

International Nuclear Information System (INIS)

Lange, Benjamin

2010-01-01

This paper presents a new method for doing a free-fall equivalence-principle (EP) experiment in a satellite at ambient temperature which solves two problems that have previously blocked this approach. By using large masses to change the gravity gradient at the proof masses, the orbit dynamics of a drag-free satellite may be changed in such a way that the experiment can mimic a free-fall experiment in a constant gravitational field on the earth. An experiment using a sphere surrounded by a spherical shell both completely unsupported and free falling has previously been impractical because (1) it is not possible to distinguish between a small EP violation and a slight difference in the semi-major axes of the orbits of the two proof masses and (2) the position difference in the orbit due to an EP violation only grows as t whereas the largest disturbance grows as t 3/2 . Furthermore, it has not been known how to independently measure the positions of a shell and a solid sphere with sufficient accuracy. The measurement problem can be solved by using a two-color transcollimator (see the main text), and since the radial-position-error and t-response problems arise from the earth's gravity gradient and not from its gravity field, one solution is to modify the earth's gravity gradient with local masses fixed in the satellite. Since the gravity gradient at the surface of a sphere, for example, depends only on its density, the gravity gradients of laboratory masses and of the earth unlike their fields are of the same order of magnitude. In a drag-free satellite spinning perpendicular to the orbit plane, two fixed spherical masses whose connecting line parallels the satellite spin axis can generate a dc gravity gradient at test masses located between them which cancels the combined gravity gradient of the earth and differential centrifugal force. With perfect cancellation, the position-error problem vanishes and the response grows as t 2 along a line which always points toward

Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

Directory of Open Access Journals (Sweden)

Xian-bin Kong

2017-01-01

Full Text Available Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compelling findings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels: (1 polyethylene glycol as an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury. (2 Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers. (3 Polyethylene glycol hydrogels have been used as supporting substrates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury

Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

Institute of Scientific and Technical Information of China (English)

Xian-bin Kong; Qiu-yan Tang; Xu-yi Chen; Yue Tu; Shi-zhong Sun; Zhong-lei Sun

2017-01-01

Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compellingfindings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels: (1) polyethylene glycol as an adjustable bio-molecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury. (2) Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers. (3) Polyethylene glycol hydrogels have been used as supporting sub-strates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury.

Triple negative breast cancers have a reduced expression of DNA repair genes.

Directory of Open Access Journals (Sweden)

Enilze Ribeiro

Full Text Available DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia in paraffin embedded samples of triple negative breast cancer (TNBC compared to luminal A breast cancer (LABC. Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.

Using Tourism Free-Choice Learning Experiences to Promote Environmentally Sustainable Behaviour: The Role of Post-Visit "Action Resources"

Science.gov (United States)

Ballantyne, Roy; Packer, Jan

2011-01-01

This paper argues the need for the providers of ecotourism and other free-choice environmental learning experiences to promote the adoption of environmentally sustainable actions beyond their own sites, when visitors return to their home environments. Previous research indicates that although visitors often leave such experiences with a heightened…

Repair of damaged DNA in-vivo. Comprehensive progress report, August 1980-August 1983

International Nuclear Information System (INIS)

Hanawalt, P.C.

1983-07-01

We have extended our characterization of long patch excision repair (LPER) and have demonstrated that LPER is not mutagenic (or error-prone); that the recA function is required for LPER, at least for its regulation; that the substrate for LPER is produced as a linear (not an exponential) function of uv (254 nm) dose; and that LPER can occur in uvr - cells treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG). We have developed 3 methods for measuring the frequency of interstrand crosslinks in DNA and are now applying these methods to the study of the formation and repair of DNA crosslinks in E.Coli. We have developed a monoclonal antibody specific for thymine glycol in DNA, and are using it to study the repair of thymine glycol in E. coli

Putative Enzymes of UV Photoproduct Repair

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Cynthia J. Sakofsky

2011-01-01

Full Text Available In order to determine the biological relevance of two S. acidocaldarius proteins to the repair of UV photoproducts, the corresponding genes (Saci_1227 and Saci_1096 were disrupted, and the phenotypes of the resulting mutants were examined by various genetic assays. The disruption used integration by homologous recombination of a functional but heterologous pyrE gene, promoted by short sequences attached to both ends via PCR. The phenotypic analyses of the disruptants confirmed that ORF Saci_1227 encodes a DNA photolyase which functions in vivo, but they could not implicate ORF Saci_1096 in repair of UV- or other externally induced DNA damage despite its similarity to genes encoding UV damage endonucleases. The success of the gene-disruption strategy, which used 5′ extensions of PCR primers to target cassette integration, suggests potential advantages for routine construction of Sulfolobus strains.

Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

Science.gov (United States)

Metcalf, Alexander M; Spurdle, Amanda B

2014-03-01

Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

DNA mismatch repair deficiency accelerates lung neoplasm development in K-rasLA1/+ mice: a brief report

International Nuclear Information System (INIS)

Downey, Charlene M; Jirik, Frank R

2015-01-01

Inherited as well as acquired deficiencies in specific DNA mismatch repair (MMR) components are associated with the development of a wide range of benign and malignant neoplasms. Loss of key members such as MSH2 and MLH1 severely cripples the ability of the cell to recognize and correct such lesions as base:base mismatches and replicative DNA polymerase errors such as slippages at repetitive sequences. Genomic instability resulting from MMR deficiency not only predisposes cells to malignant transformation but may also promote tumor progression. To test the latter, we interbred Msh2 −/− mice with the K-ras LA1/+ transgenic line that spontaneously develops a range of premalignant and malignant lung lesions. Compared to K-ras LA1/+ mice, K-ras LA1/+ ; Msh2 −/− mice developed lung adenomas and adenocarcinomas at an increased frequency and also demonstrated evidence of accelerated adenocarcinoma growth. Since MMR defects have been identified in some human lung cancers, the mutant mice may not only be of preclinical utility but they will also be useful in identifying gene alterations able to act in concert with Kras mutants to promote tumor progression

Nrf1 CNC-bZIP protein promotes cell survival and nucleotide excision repair through maintaining glutathione homeostasis.

Science.gov (United States)

Han, Weinong; Ming, Mei; Zhao, Rui; Pi, Jingbo; Wu, Chunli; He, Yu-Ying

2012-05-25

Skin cancer is the most common cancer in the United States. Its major environmental risk factor is UVB radiation in sunlight. In response to UVB damage, epidermal keratinocytes activate a specific repair pathway, i.e. nucleotide excision repair, to remove UVB-induced DNA lesions. However, the regulation of UVB response is not fully understood. Here we show that the long isoform of the nuclear factor erythroid 2-related factor 1 (Nrf1, also called NFE2L1), a cytoprotective transcription factor critical for the expression of multiple antioxidant response element-dependent genes, plays an important role in the response of keratinocytes to UVB. Nrf1 loss sensitized keratinocytes to UVB-induced apoptosis by up-regulating the expression of the proapoptotic Bcl-2 family member Bik through reducing glutathione levels. Knocking down Bik reduced UVB-induced apoptosis in Nrf1-inhibited cells. In UVB-irradiated surviving cells, however, disruption of Nrf1 impaired nucleotide excision repair through suppressing the transcription of xeroderma pigmentosum C (XPC), a factor essential for initiating the global genome nucleotide excision repair by recognizing the DNA lesion and recruiting downstream factors. Nrf1 enhanced XPC expression by increasing glutathione availability but was independent of the transcription repressor of XPC. Adding XPC or glutathione restored the DNA repair capacity in Nrf1-inhibited cells. Finally, we demonstrate that Nrf1 levels are significantly reduced by UVB radiation in mouse skin and are lower in human skin tumors than in normal skin. These results indicate a novel role of Nrf1 in UVB-induced DNA damage repair and suggest Nrf1 as a tumor suppressor in the skin.

Tension (re)builds: Biophysical mechanisms of embryonic wound repair.

Science.gov (United States)

Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo

2017-04-01

Embryonic tissues display an outstanding ability to rapidly repair wounds. Epithelia, in particular, serve as protective layers that line internal organs and form the skin. Thus, maintenance of epithelial integrity is of utmost importance for animal survival, particularly at embryonic stages, when an immune system has not yet fully developed. Rapid embryonic repair of epithelial tissues is conserved across species, and involves the collective migration of the cells around the wound. The migratory cell behaviours associated with wound repair require the generation and transmission of mechanical forces, not only for the cells to move, but also to coordinate their movements. Here, we review the forces involved in embryonic wound repair. We discuss how different force-generating structures are assembled at the molecular level, and the mechanisms that maintain the balance between force-generating structures as wounds close. Finally, we describe the mechanisms that cells use to coordinate the generation of mechanical forces around the wound. Collective cell movements and their misregulation have been associated with defective tissue repair, developmental abnormalities and cancer metastasis. Thus, we propose that understanding the role of mechanical forces during embryonic wound closure will be crucial to develop therapeutic interventions that promote or prevent collective cell movements under pathological conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Homologous Recombination DNA Repair Genes Play a Critical Role in Reprogramming to a Pluripotent State

Directory of Open Access Journals (Sweden)

Federico González

2013-03-01

Full Text Available Induced pluripotent stem cells (iPSCs hold great promise for personalized regenerative medicine. However, recent studies show that iPSC lines carry genetic abnormalities, suggesting that reprogramming may be mutagenic. Here, we show that the ectopic expression of reprogramming factors increases the level of phosphorylated histone H2AX, one of the earliest cellular responses to DNA double-strand breaks (DSBs. Additional mechanistic studies uncover a direct role of the homologous recombination (HR pathway, a pathway essential for error-free repair of DNA DSBs, in reprogramming. This role is independent of the use of integrative or nonintegrative methods in introducing reprogramming factors, despite the latter being considered a safer approach that circumvents genetic modifications. Finally, deletion of the tumor suppressor p53 rescues the reprogramming phenotype in HR-deficient cells primarily through the restoration of reprogramming-dependent defects in cell proliferation and apoptosis. These mechanistic insights have important implications for the design of safer approaches to creating iPSCs.

CORRECTING ERRORS: THE RELATIVE EFFICACY OF DIFFERENT FORMS OF ERROR FEEDBACK IN SECOND LANGUAGE WRITING

Directory of Open Access Journals (Sweden)

Chitra Jayathilake

2013-01-01

Full Text Available Error correction in ESL (English as a Second Language classes has been a focal phenomenon in SLA (Second Language Acquisition research due to some controversial research results and diverse feedback practices. This paper presents a study which explored the relative efficacy of three forms of error correction employed in ESL writing classes: focusing on the acquisition of one grammar element both for immediate and delayed language contexts, and collecting data from university undergraduates, this study employed an experimental research design with a pretest-treatment-posttests structure. The research revealed that the degree of success in acquiring L2 (Second Language grammar through error correction differs according to the form of the correction and to learning contexts. While the findings are discussed in relation to the previous literature, this paper concludes creating a cline of error correction forms to be promoted in Sri Lankan L2 writing contexts, particularly in ESL contexts in Universities.

On the Performance of Free-Space Optical Systems over Generalized Atmospheric Turbulence Channels with Pointing Errors

KAUST Repository

Ansari, Imran Shafique

2015-03-01

Generalized fading has been an imminent part and parcel of wireless communications. It not only characterizes the wireless channel appropriately but also allows its utilization for further performance analysis of various types of wireless communication systems. Under the umbrella of generalized fading channels, a unified performance analysis of a free-space optical (FSO) link over the Malaga (M) atmospheric turbulence channel that accounts for pointing errors and both types of detection techniques (i.e. indirect modulation/direct detection (IM/DD) as well as heterodyne detection) is presented. Specifically, unified exact closed-form expressions for the probability density function (PDF), the cumulative distribution function (CDF), the moment generating function (MGF), and the moments of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system are presented, all in terms of the Meijer\\'s G function except for the moments that is in terms of simple elementary functions. Then capitalizing on these unified results, unified exact closed-form expressions for various performance metrics of FSO link transmission systems are offered, such as, the outage probability (OP), the higher-order amount of fading (AF), the average error rate for binary and M-ary modulation schemes, and the ergodic capacity (except for IM/DD technique, where closed-form lower bound results are presented), all in terms of Meijer\\'s G functions except for the higher-order AF that is in terms of simple elementary functions. Additionally, the asymptotic results are derived for all the expressions derived earlier in terms of the Meijer\\'s G function in the high SNR regime in terms of simple elementary functions via an asymptotic expansion of the Meijer\\'s G function. Furthermore, new asymptotic expressions for the ergodic capacity in the low as well as high SNR regimes are derived in terms of simple elementary functions via utilizing moments. All the presented results are

CrowdAidRepair: A Crowd-Aided Interactive Data Repairing Method

KAUST Repository

Zhou, Jian

2016-03-25

Data repairing aims at discovering and correcting erroneous data in databases. Traditional methods relying on predefined quality rules to detect the conflict between data may fail to choose the right way to fix the detected conflict. Recent efforts turn to use the power of crowd in data repairing, but the crowd power has its own drawbacks such as high human intervention cost and inevitable low efficiency. In this paper, we propose a crowd-aided interactive data repairing method which takes the advantages of both rule-based method and crowd-based method. Particularly, we investigate the interaction between crowd-based repairing and rule-based repairing, and show that by doing crowd-based repairing to a small portion of values, we can greatly improve the repairing quality of the rule-based repairing method. Although we prove that the optimal interaction scheme using the least number of values for crowd-based repairing to maximize the imputation recall is not feasible to be achieved, still, our proposed solution identifies an efficient scheme through investigating the inconsistencies and the dependencies between values in the repairing process. Our empirical study on three data collections demonstrates the high repairing quality of CrowdAidRepair, as well as the efficiency of the generated interaction scheme over baselines.

DNA repair: Dynamic defenders against cancer and aging

Energy Technology Data Exchange (ETDEWEB)

Fuss, Jill O.; Cooper, Priscilla K.

2006-04-01

(UV) component of sunlight. NER can be divided into two classes based on where the repair occurs. NER occurring in DNA that is not undergoing transcription (i.e., most of the genome) is called global genome repair (GGR or GGNER), while NER taking place in the transcribed strand of active genes is called transcription-coupled repair (TCR or TC-NER). We will explore NER in more detail below. Mismatch repair (MMR) is another type of excision repair that specifically removes mispaired bases resulting from replication errors. DNA damage can also result in breaks in the DNA backbone, in one or both strands. Single-strand breaks (SSBs) are efficiently repaired by a mechanism that shares common features with the later steps in BER. Double-strand breaks (DSBs) are especially devastating since by definition there is no intact complementary strand to serve as a template for repair, and even one unrepaired DSB can be lethal [3]. In cells that have replicated their DNA prior to cell division, the missing information can be supplied by the duplicate copy, or sister chromatid, and DSBs in these cells are faithfully repaired by homologous recombination involving the exchange of strands of DNA between the two copies. However, most cells in the body are non-dividing, and in these cells the major mechanism for repairing DSBs is by non-homologous end joining (NHEJ), which as the name implies involves joining two broken DNA ends together without a requirement for homologous sequence and which therefore has a high potential for loss of genetic information.

SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair

DEFF Research Database (Denmark)

Van Cuijk, Loes; Van Belle, Gijsbert J.; Turkyilmaz, Yasemin

2015-01-01

XPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have shown that the SUMO-targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation o...

Moderating Argos location errors in animal tracking data

Science.gov (United States)

Douglas, David C.; Weinziert, Rolf; Davidson, Sarah C.; Kays, Roland; Wikelski, Martin; Bohrer, Gil

2012-01-01

1. The Argos System is used worldwide to satellite-track free-ranging animals, but location errors can range from tens of metres to hundreds of kilometres. Low-quality locations (Argos classes A, 0, B and Z) dominate animal tracking data. Standard-quality animal tracking locations (Argos classes 3, 2 and 1) have larger errors than those reported in Argos manuals.

Comparison of orthogonal kilovolt X-ray images and cone-beam CT matching results in setup error assessment and correction for EB-PBI during free breathing

International Nuclear Information System (INIS)

Wang Wei; Li Jianbin; Hu Hongguang; Ma Zhifang; Xu Min; Fan Tingyong; Shao Qian; Ding Yun

2014-01-01

Objective: To compare the differences in setup error (SE) assessment and correction between the orthogonal kilovolt X-ray images and CBCT in EB-PBI patients during free breathing. Methods: Nineteen patients after breast conserving surgery EB-PBI were recruited. Interfraction SE was acquired using orthogonal kilovolt X-ray setup images and CBCT, after on-line setup correction,calculate the residual error and compare the SE, residual error and setup margin (SM) quantified for orthogonal kilovolt X-ray images and CBCT. Wilcoxon sign-rank test was used to evaluate the differences. Results: The CBCT based SE (systematic error, ∑) was smaller than the orthogonal kilovolt X-ray images based ∑ in AP direction (-1.2 mm vs 2.00 mm; P=0.005), and there was no statistically significant differences for three dimensional directions in random error (σ) (P=0.948, 0.376, 0.314). After on-line setup correction,CBCT decreases setup residual error than the orthogonal kilovolt X-ray images in AP direction (Σ: -0.20 mm vs 0.50 mm, P=0.008; σ: 0.45 mm vs 1.34 mm, P=0.002). And also the CBCT based SM was smaller than orthogonal kilovolt X-ray images based SM in AP direction (Σ: -1.39 mm vs 5.57 mm, P=0.003; σ: 0.00 mm vs 3.2 mm, P=0.003). Conclusions: Compared with kilovolt X-ray images, CBCT underestimate the setup error in the AP direction, but decreases setup residual error significantly.An image-guided radiotherapy and setup error assessment using kilovolt X-ray images for EB-PBI plans was feasible. (authors)

Laparoscopic Hernia Repair in Infancy and Childhood; Evaluation of ...

African Journals Online (AJOL)

Materials & Methods: A prospective randomized controlled study was carried out in the ... Group B was subjected to laparoscopic hernia repair of inguinal hernia by ... Inclusion criteria included; bilateral inguinal hernia, recurrent hernia, hernia in ... By Country · List All Titles · Free To Read Titles This Journal is Open Access.

Is bone transplantation the gold standard for repair of alveolar bone defects?

Directory of Open Access Journals (Sweden)

Cassio Eduardo Raposo-Amaral

2014-01-01

Full Text Available New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate, compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7 defects were repaired with autogenous bone grafts; Group 2 (n = 5 defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5 defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5 defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6 defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2–5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01 and 38.35% ± 19.59% (p = 0.06 of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30 and 61.80% ± 2.14% (p = 0.88 of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone.

Mutagenic and epigenetic influence of caffeine on the frequencies of UV-induced ouabain-resistant Chinese hamster cells

International Nuclear Information System (INIS)

Chang, Chia-Cheng; Philipps, C.; Trosko, J.E.; Hart, R.W.

1977-01-01

Caffeine, given as a post-treatment to UV-irradiated Chinese hamster cells in vitro, modified the frequency of induced mutations at the ouabain resistance locus. Mutation frequencies were increased when caffeine was added only for the DNA repair and mutation fixation period. When caffeine was added after the DNA repair and mutation fixation period, or immediately after DNA damage and for the entire repair and selection period, mutation frequencies were reduced. A hypothesis, given to explain both results, is that caffeine, by blocking a constitutive 'error-free' postreplication repair process, allows an 'error-prone' DNA repair process to produce many mutations. Moreover, caffeine, possibly by modifying C-AMP metabolism, causes a repression of induced mutations which, in effect, explains its anti-mutagenic and anti-carcinogenic properties

Higher plants and UV-B radiation: balancing damage, repair and acclimation

International Nuclear Information System (INIS)

Jansen, M.A.K.; Gaba, V.; Greenberg, B.M.

1998-01-01

Although UV-B is a minor component of sunlight, it has a disproportionately damaging effect on higher plants. Ultraviolet-sensitive targets include DNA, proteins and membranes, and these must be protected for normal growth and development. DNA repair and secondary metabolite accumulation during exposure to UV-B have been characterized in considerable detail, but little is known about the recovery of photosynthesis, induction of free-radical scavenging and morphogenic changes. A future challenge is to elucidate how UV-B-exposed plants balance damage, repair, acclimation and adaptation responses in a photobiologically dynamic environment. (author)

Chloro-benquinone Modified on Graphene Oxide as Metal-free Catalyst: Strong Promotion of Hydroxyl Radical and Generation of Ultra-Small Graphene Oxide

Science.gov (United States)

Zhao, He; Wang, Juehua; Zhang, Di; Dai, Qin; Han, Qingzhen; Du, Penghui; Liu, Chenming; Xie, Yongbing; Zhang, Yi; Cao, Hongbin; Fan, Zhuangjun

2017-03-01

Carbon-based metal-free catalyst has attracted more and more attention. It is a big challenge to improve catalytic activity of metal-free catalyst for decomposition of H2O2 to produce hydroxyl radical (HO•). Here, we report chloro-benquinone (TCBQ) modified on graphene oxide (GO) as metal-free catalyst for strong promotion of HO•. By the incorporation of GO, the HO• production by H2O2 and TCBQ is significantly promoted. Based on density functional theory, TCBQ modified GO (GO-TCBQ) is more prone to be nucleophilic attacked by H2O2 to yield HO• via electron transfer acceleration. Furthermore, the generated HO• can cut GO nanosheets into uniform ultra-small graphene oxide (USGO) through the cleavage of epoxy and C-C bonds. Interestingly, the damaged GO and in situ formed GO fragments can further enhance decomposition of H2O2 to produce HO•. Different from other catalytic processes, the GO-TCBQ metal-free catalysis process can be enhanced by GO itself, producing more HO•, and uniform USGO also can be generated. Thus, the metal free catalysis will be considered a fabrication method for uniform USGO, and may be extended to other fields including detoxifying organic pollutants and the application as disinfectants.

[SOS response of DNA repair and genetic cell instability under hypoxic conditions].

Science.gov (United States)

Vasil'eva, S V; Strel'tsova, D A

2011-01-01

The SOS DNA repair pathway is induced in E. coli as a multifunctional cell response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or nalidixic acid treatment, thymine starvation, etc. Triggering of the system can be used as a general and early sign of DNA damage. Additionally, the SOS-response is known to be an "error-prone" DNA repair pathway and one of the sources of genetic instability. Hypoxic conditions are established to be the major factor of genetic instability as well. In this paper we for the first time studied the SOS DNA repair response under hypoxic conditions induced by the well known aerobic SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide evidence that those agents were able to induce the SOS DNA repair response in E. coli at anaerobic growth conditions. The process does not depend on the transcriptional activity of the universal protein of E. col anaerobic growth Fnr [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in hypoxic conditions.

Rectifying calibration error of Goldmann applanation tonometer is easy!

Directory of Open Access Journals (Sweden)

Nikhil S Choudhari

2014-01-01

Full Text Available Purpose: Goldmann applanation tonometer (GAT is the current Gold standard tonometer. However, its calibration error is common and can go unnoticed in clinics. Its company repair has limitations. The purpose of this report is to describe a self-taught technique of rectifying calibration error of GAT. Materials and Methods: Twenty-nine slit-lamp-mounted Haag-Streit Goldmann tonometers (Model AT 900 C/M; Haag-Streit, Switzerland were included in this cross-sectional interventional pilot study. The technique of rectification of calibration error of the tonometer involved cleaning and lubrication of the instrument followed by alignment of weights when lubrication alone didn′t suffice. We followed the South East Asia Glaucoma Interest Group′s definition of calibration error tolerance (acceptable GAT calibration error within ±2, ±3 and ±4 mm Hg at the 0, 20 and 60-mm Hg testing levels, respectively. Results: Twelve out of 29 (41.3% GATs were out of calibration. The range of positive and negative calibration error at the clinically most important 20-mm Hg testing level was 0.5 to 20 mm Hg and -0.5 to -18 mm Hg, respectively. Cleaning and lubrication alone sufficed to rectify calibration error of 11 (91.6% faulty instruments. Only one (8.3% faulty GAT required alignment of the counter-weight. Conclusions: Rectification of calibration error of GAT is possible in-house. Cleaning and lubrication of GAT can be carried out even by eye care professionals and may suffice to rectify calibration error in the majority of faulty instruments. Such an exercise may drastically reduce the downtime of the Gold standard tonometer.

Triple-Loaded Suture Anchors Versus a Knotless Rip Stop Construct in a Single-Row Rotator Cuff Repair Model.

Science.gov (United States)

Noyes, Matthew P; Lederman, Evan; Adams, Christopher R; Denard, Patrick J

2018-05-01

To compare the biomechanical properties of single-row repair with triple-loaded (TL) anchor repair versus a knotless rip stop (KRS) repair in a rotator cuff repair model. Rotator cuff tears were created in 8 cadaveric matched-pair specimens and repaired with a TL anchor or KRS construct. In the TL construct, anchors were placed in the greater tuberosity and then all suture limbs were passed through the rotator cuff as simple sutures and tied. In the KRS construct, a 2-mm suture tape was passed through the tendon in an inverted mattress fashion, and a free suture was passed medial to the suture tape to create a rip-stop. Then, the suture tape and free suture were secured with knotless anchors. Displacement was observed with video tracking after cyclic loading, and specimens were loaded to failure. The mean load to failure was 438 ± 59 N in TL anchor repairs compared with 457 ± 110 N in KRS repairs (P = .582). The mean displacement with cyclic loading was 3.8 ± 1.6 mm in TL anchor repairs versus 4.3 ± 1.8 mm in the KRS group (P = .297). Mode of failure was consistent in both groups, with 6 of 8 failures in the TL anchor group and 7 of 8 failures in KRS group occurring from anchor pullout. There is no statistical difference in load to failure and cyclic loading between TL anchor and KRS single-row repair techniques. KRS repair technique may be an alternative method of repairing full-thickness supraspinatus tendon tears with a single-row construct. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

REV7 counteracts DNA double-strand break resection and affects PARP inhibition

NARCIS (Netherlands)

Xu, Guotai; Chapman, J. Ross; Brandsma, Inger; Yuan, Jingsong; Mistrik, Martin; Bouwman, Peter; Bartkova, Jirina; Gogola, Ewa; Warmerdam, Daniël; Barazas, Marco; Jaspers, Janneke E.; Watanabe, Kenji; Pieterse, Mark; Kersbergen, Ariena; Sol, Wendy; Celie, Patrick H. N.; Schouten, Philip C.; van den Broek, Bram; Salman, Ahmed; Nieuwland, Marja; de Rink, Iris; de Ronde, Jorma; Jalink, Kees; Boulton, Simon J.; Chen, Junjie; van Gent, Dik C.; Bartek, Jiri; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

2015-01-01

Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway(1). In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with

Mitral valve repair. Quadrangular resection of the posterior leaflet in patients with myxomatous degeneration

Directory of Open Access Journals (Sweden)

Pablo Maria Alberto Pomerantzeff

1999-09-01

Full Text Available OBJECTIVE - To analyze the immediate and late results of mitral valve repair with quadrangular resection of the posterior leaflet without the use of a prosthetic ring annuloplasty. METHODS - Using this technique, 118 patients with mitral valve prolapse who underwent mitral repair from January '84 through December '96 were studied. Age ranged from 30 to 86 (mean = 59.1±11.8 years and 62.7% were males. An associated surgery was performed in 22% of the patients, and coronary artery bypass graft was the most frequently performed surgery (15 patients - 12.7%. In 20 (16.9% patients other associated techniques of mitral valve repair were used and shortening of elongated chordae tendineae was the most frequent one (6 patients. RESULTS - Immediate mortality was 0.9% (one patient. Long-term rates for thromboembolism, endocarditis, re-operation and death in the late postoperative period were 0.4%, 0.4%, 1.7% and 2.2% patients/year, respectively. The actuarial curve of survival was 83.8±8.6% over 12 years; survival free from re-operation was 91.8±4.3%, free from endocarditis was 99.2±0.8% and free from thromboembolism was 99.2±0.8%. In the late postoperative period, 93.8% of the patients were in functional class 1 (NYHA, with a complete follow-up in 89.7% of the patients. CONCLUSION - Patients with mitral valve prolapse who undergo mitral valve repair using this technique have a satisfactory prognosis over 12 years.

Defining near misses : towards a sharpened definition based on empirical data about error handling processes

NARCIS (Netherlands)

Kessels-Habraken, M.M.P.; Schaaf, van der T.W.; Jonge, de J.; Rutte, C.G.

2010-01-01

Medical errors in health care still occur frequently. Unfortunately, errors cannot be completely prevented and 100% safety can never be achieved. Therefore, in addition to error reduction strategies, health care organisations could also implement strategies that promote timely error detection and

DNA repair and cytokines: TGF-beta, IL-6, and thrombopoietin as different biomarkers of radioresistance

Directory of Open Access Journals (Sweden)

Francesca Bianca Aiello

2016-07-01

Full Text Available Double strand breaks (DSBs induced by radiotherapy are highly cytotoxic lesions, leading to chromosomal aberrations and cell death. ATM-dependent DNA-damage response, non-homologous end joining, and homologous recombination pathways coordinately contribute to repairing DSBs in higher eukaryotes. It is known that the expression of DSB repair genes is increased in tumors which is one of the main reasons for radioresistance. The inhibition of DSB repair pathways may be useful to increase tumor cell radiosensitivity and may target stem cell-like cancer cells, known to be the most radioresistant tumor components. Commonly overexpressed in neoplastic cells, cytokines confer radioresistance by promoting proliferation, survival, invasion, and angiogenesis. Unfortunately, tumor irradiation increases the expression of various cytokines displaying these effects, including transforming growth factor-beta and interlukin-6. Recently the capabilities of these cytokines to support DNA repair pathways and the ATM-dependent DNA response have been demonstrated. Thrombopoietin, essential for megakaryopoiesis and very important for hematopoietic stem cell homeostasis, has also been found to promote DNA repair in a highly selective manner. These findings reveal a novel mechanism underlying cytokine-related radioresistance, which may be clinically relevant. Therapies targeting specific cytokines may be used to improve radiosensitivity. Specific inhibitors may be chosen in consideration of different tumor microenvironments. Thrombopoietin may be useful in fending off irradiation-induced loss of hematopoietic stem cells.

Computer-Assisted Detection of 90% of EFL Student Errors

Science.gov (United States)

Harvey-Scholes, Calum

2018-01-01

Software can facilitate English as a Foreign Language (EFL) students' self-correction of their free-form writing by detecting errors; this article examines the proportion of errors which software can detect. A corpus of 13,644 words of written English was created, comprising 90 compositions written by Spanish-speaking students at levels A2-B2…

Electroacupuncture in the repair of spinal cord injury: inhibiting the Notch signaling pathway and promoting neural stem cell proliferation

Directory of Open Access Journals (Sweden)

Xin Geng

2015-01-01

Full Text Available Electroacupuncture for the treatment of spinal cord injury has a good clinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Dawley rats was clamped for 60 seconds. Dazhui (GV14 and Mingmen (GV4 acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expression of serum inflammatory factors was apparently downregulated in rat models of spinal cord injury after electroacupuncture. Hematoxylin-eosin staining and immunohistochemistry results demonstrated that electroacupuncture contributed to the proliferation of neural stem cells in rat injured spinal cord, and suppressed their differentiation into astrocytes. Real-time quantitative PCR and western blot assays showed that electroacupuncture inhibited activation of the Notch signaling pathway induced by spinal cord injury. These findings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem cells.

Arthroscopic suture anchor repair of the lateral ligament ankle complex: a cadaveric study.

Science.gov (United States)

Giza, Eric; Shin, Edward C; Wong, Stephanie E; Acevedo, Jorge I; Mangone, Peter G; Olson, Kirstina; Anderson, Matthew J

2013-11-01

Operative treatment of mechanical ankle instability is indicated for patients with multiple sprains and continued episodes of instability. Open repair of the lateral ankle ligaments involves exposure of the attenuated ligaments and advancement back to their anatomic insertions on the fibula using bone tunnels or suture implants. Open and arthroscopic fixation are equal in strength to failure for anatomic Broström repair. Controlled laboratory study. Seven matched pairs of human cadaveric ankle specimens were randomized into 2 groups of anatomic Broström repair: open or arthroscopic. The calcaneofibular ligament and anterior talofibular ligament were excised from their origin on the fibula. In the open repair group, 2 suture anchors were used to reattach the ligaments to their anatomic origins. In the arthroscopic repair group, identical suture anchors were used for repair via an arthroscopic technique. The ligaments were cyclically loaded 20 times and then tested to failure. Torque to failure, degrees to failure, initial stiffness, and working stiffness were measured. A matched-pair analysis was performed. Power analysis of 0.8 demonstrated that 7 pairs needed to show a difference of 30%, with a 15% standard error at a significance level of α = .05. There was no difference in the degrees to failure, torque to failure, or stiffness for the repaired ligament complex. Nine of 14 specimens failed at the suture anchor. There is no statistical difference in strength or stiffness of a traditional open repair as compared with an arthroscopic anatomic repair of the lateral ligaments of the ankle. An arthroscopic technique can be considered for lateral ligament stabilization in patients with mild to moderate mechanical instability.

Human errors related to maintenance and modifications

International Nuclear Information System (INIS)

Laakso, K.; Pyy, P.; Reiman, L.

1998-01-01

The focus in human reliability analysis (HRA) relating to nuclear power plants has traditionally been on human performance in disturbance conditions. On the other hand, some studies and incidents have shown that also maintenance errors, which have taken place earlier in plant history, may have an impact on the severity of a disturbance, e.g. if they disable safety related equipment. Especially common cause and other dependent failures of safety systems may significantly contribute to the core damage risk. The first aim of the study was to identify and give examples of multiple human errors which have penetrated the various error detection and inspection processes of plant safety barriers. Another objective was to generate numerical safety indicators to describe and forecast the effectiveness of maintenance. A more general objective was to identify needs for further development of maintenance quality and planning. In the first phase of this operational experience feedback analysis, human errors recognisable in connection with maintenance were looked for by reviewing about 4400 failure and repair reports and some special reports which cover two nuclear power plant units on the same site during 1992-94. A special effort was made to study dependent human errors since they are generally the most serious ones. An in-depth root cause analysis was made for 14 dependent errors by interviewing plant maintenance foremen and by thoroughly analysing the errors. A more simple treatment was given to maintenance-related single errors. The results were shown as a distribution of errors among operating states i.a. as regards the following matters: in what operational state the errors were committed and detected; in what operational and working condition the errors were detected, and what component and error type they were related to. These results were presented separately for single and dependent maintenance-related errors. As regards dependent errors, observations were also made

Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells.

Science.gov (United States)

Scanlon, Susan E; Scanlon, Christine D; Hegan, Denise C; Sulkowski, Parker L; Glazer, Peter M

2017-06-01

The heavy metal nickel is a known carcinogen, and occupational exposure to nickel compounds has been implicated in human lung and nasal cancers. Unlike many other environmental carcinogens, however, nickel does not directly induce DNA mutagenesis, and the mechanism of nickel-related carcinogenesis remains incompletely understood. Cellular nickel exposure leads to signaling pathway activation, transcriptional changes and epigenetic remodeling, processes also impacted by hypoxia, which itself promotes tumor growth without causing direct DNA damage. One of the mechanisms by which hypoxia contributes to tumor growth is the generation of genomic instability via down-regulation of high-fidelity DNA repair pathways. Here, we find that nickel exposure similarly leads to down-regulation of DNA repair proteins involved in homology-dependent DNA double-strand break repair (HDR) and mismatch repair (MMR) in tumorigenic and non-tumorigenic human lung cells. Functionally, nickel induces a defect in HDR capacity, as determined by plasmid-based host cell reactivation assays, persistence of ionizing radiation-induced DNA double-strand breaks and cellular hypersensitivity to ionizing radiation. Mechanistically, we find that nickel, in contrast to the metalloid arsenic, acutely induces transcriptional repression of HDR and MMR genes as part of a global transcriptional pattern similar to that seen with hypoxia. Finally, we find that exposure to low-dose nickel reduces the activity of the MLH1 promoter, but only arsenic leads to long-term MLH1 promoter silencing. Together, our data elucidate novel mechanisms of heavy metal carcinogenesis and contribute to our understanding of the influence of the microenvironment on the regulation of DNA repair pathways. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Arrest of irradiated G1, S, or G2 cells at mitosis using nocodazole promotes repair of potentially lethal damage

International Nuclear Information System (INIS)

Iliakis, G.; Nuesse, M.

1984-01-01

The ability of synchronized Ehrlich ascites tumor cells, irradiated in G1, S, and G2 phases, to repair potentially lethal damage when arrested at mitosis by using 0.4 μg/ml nocodazole, a specific inhibitor of microtubule polymerization, has been studied. Cells irradiated in these phases were found to repair potentially lethal damage at mitosis. The extent of this repair was similar to that observed for cells irradiated at the same stages in the cell cycle but allowed to repair potentially lethal damage by incubating in balanced salt solution for 6 hr after X irradiation

The role of non-protein sulphydryls in determining the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells

International Nuclear Information System (INIS)

Prise, K.M.; Davies, S.; Stratford, M.R.L.; Michael, B.D.

1992-01-01

Chinese hamster V79 fibroblasts were irradiated in the gas explosion apparatus and the chemical repair rates of the oxygen-dependent free radical precursors of DNA double-strand breaks (dsb) and lethal lesions measured using filter elution (pH 9.6) and a clonogenic assay. Depletion of cellular GSH levels, from 4.16 fmol/cell to 0.05 fmol/cell, by treatment with buthionine sulphoximine (50 μmol dm -3 ; 18 h), led to sensitization as regards DNA dsb induction and cell killing. This was evident at all time settings but was particularly pronounced when the oxygen shot was given 1 ms after the irradiation pulse. A detailed analysis of the chemical repair kinetics showed that depletion of GSH led to a reduction in the first-order rate constant for dsb precursors from 385 s -1 to 144 s -1 , and for lethal lesion precursors from 533 s -1 to 165 s -1 . (Author)

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

Directory of Open Access Journals (Sweden)

Ewelina A Wojcik

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

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

Science.gov (United States)

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

2012-01-01

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

[Patient safety and errors in medicine: development, prevention and analyses of incidents].

Science.gov (United States)

Rall, M; Manser, T; Guggenberger, H; Gaba, D M; Unertl, K

2001-06-01

"Patient safety" and "errors in medicine" are issues gaining more and more prominence in the eyes of the public. According to newer studies, errors in medicine are among the ten major causes of death in association with the whole area of health care. A new era has begun incorporating attention to a "systems" approach to deal with errors and their causes in the health system. In other high-risk domains with a high demand for safety (such as the nuclear power industry and aviation) many strategies to enhance safety have been established. It is time to study these strategies, to adapt them if necessary and apply them to the field of medicine. These strategies include: to teach people how errors evolve in complex working domains and how types of errors are classified; the introduction of critical incident reporting systems that are free of negative consequences for the reporters; the promotion of continuous medical education; and the development of generic problem-solving skills incorporating the extensive use of realistic simulators wherever possible. Interestingly, the field of anesthesiology--within which realistic simulators were developed--is referred to as a model for the new patient safety movement. Despite this proud track record in recent times though, there is still much to be done even in the field of anesthesiology. Overall though, the most important strategy towards a long-term improvement in patient safety will be a change of "culture" throughout the entire health care system. The "culture of blame" focused on individuals should be replaced by a "safety culture", that sees errors and critical incidents as a problem of the whole organization. The acceptance of human fallability and an open-minded non-punitive analysis of errors in the sense of a "preventive and proactive safety culture" should lead to solutions at the systemic level. This change in culture can only be achieved with a strong commitment from the highest levels of an organization. Patient

Comparison of hybrid endovascular and open surgical repair for proximal aortic arch diseases.

Science.gov (United States)

Kang, Woong Chol; Ko, Young-Guk; Shin, Eak Kyun; Park, Chul-Hyun; Choi, Donghoon; Youn, Young Nam; Lee, Do Yun

2016-01-15

To compare the outcomes of hybrid endovascular and open surgical repair for proximal aortic arch diseases. A total of 55 consecutive patients with aortic arch aneurysm or aortic dissection involving any of zone 0 to 1 (39 male, age 63.4 ± 14.3 years) underwent a hybrid endovascular repair (n=35) or open surgical repair (n=20) from 2006 to 2014 were analyzed retrospectively. Perioperative and late outcomes were compared. Baseline characteristics were similar between the two groups, except age and EuroSCORE II, which were higher in the hybrid group. Perioperative mortality or stroke was not significantly different between the two groups, however, tended to be lower in the hybrid repair group than in the open repair group (11.4% vs. 30.0%, p=0.144). Incidences of other morbidities did not differ. During follow-up, over-all survival was similar between the hybrid and the open repair was similar (87.3% vs. 79.7% at 1 year and 83.8% vs. 72.4% at 3 years; p=0.319). However, reintervention-free survival was significantly lower for hybrid repair compared with open repair (83.8% vs. 100% at 1 year and 65.7% vs. 100% at 3 years; p=0.022). Hybrid repair of proximal aortic disease showed comparable perioperative and late outcomes compared with open surgical repair despite a higher reintervention rate during follow-up. Therefore, hybrid repair may be considered as an acceptable treatment alternative to surgery especially in patients at high surgical risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The application of viral vectors to enhance regeneration after peripheral nerve repair

NARCIS (Netherlands)

Tannemaat, Martijn R; Verhaagen, J.; Malessy, Martijn J A

2008-01-01

OBJECTIVE: Despite great advancements in surgical repair techniques, a considerable degree of functional impairment remains in the majority of patients after peripheral nerve reconstruction. New concepts to promote regeneration of the peripheral nerve are needed since it is generally held that

Modeling for prediction of restrained shrinkage effect in concrete repair

International Nuclear Information System (INIS)

Yuan Yingshu; Li Guo; Cai Yue

2003-01-01

A general model of autogenous shrinkage caused by chemical reaction (chemical shrinkage) is developed by means of Arrhenius' law and a degree of chemical reaction. Models of tensile creep and relaxation modulus are built based on a viscoelastic, three-element model. Tests of free shrinkage and tensile creep were carried out to determine some coefficients in the models. Two-dimensional FEM analysis based on the models and other constitutions can predict the development of tensile strength and cracking. Three groups of patch-repaired beams were designed for analysis and testing. The prediction from the analysis shows agreement with the test results. The cracking mechanism after repair is discussed

Errors in drug administration by anaesthetists in public hospitals in ...

African Journals Online (AJOL)

Objective. To investigate errors in administering drugs by anaesthetists working in public hospitals in the Free State province. Methods. Anonymous questionnaires were distributed to doctors performing anaesthesia in public hospitals in the Free State, i.e. 188 doctors at 22 public sector hospitals. Outcomes included ...

Human error theory: relevance to nurse management.

Science.gov (United States)

Armitage, Gerry

2009-03-01

Describe, discuss and critically appraise human error theory and consider its relevance for nurse managers. Healthcare errors are a persistent threat to patient safety. Effective risk management and clinical governance depends on understanding the nature of error. This paper draws upon a wide literature from published works, largely from the field of cognitive psychology and human factors. Although the content of this paper is pertinent to any healthcare professional; it is written primarily for nurse managers. Error is inevitable. Causation is often attributed to individuals, yet causation in complex environments such as healthcare is predominantly multi-factorial. Individual performance is affected by the tendency to develop prepacked solutions and attention deficits, which can in turn be related to local conditions and systems or latent failures. Blame is often inappropriate. Defences should be constructed in the light of these considerations and to promote error wisdom and organizational resilience. Managing and learning from error is seen as a priority in the British National Health Service (NHS), this can be better achieved with an understanding of the roots, nature and consequences of error. Such an understanding can provide a helpful framework for a range of risk management activities.

Overview of existing cartilage repair technology.

Science.gov (United States)

McNickle, Allison G; Provencher, Matthew T; Cole, Brian J

2008-12-01

Currently, autologous chondrocyte implantation and osteochondral grafting bridge the gap between palliation of cartilage injury and resurfacing via arthroplasty. Emerging technologies seek to advance first generation techniques and accomplish several goals including predictable outcomes, cost-effective technology, single-stage procedures, and creation of durable repair tissue. The biologic pipeline represents a variety of technologies including synthetics, scaffolds, cell therapy, and cell-infused matrices. Synthetic constructs, an alternative to biologic repair, resurface a focal chondral defect rather than the entire joint surface. Scaffolds are cell-free constructs designed as a biologic "net" to augment marrow stimulation techniques. Minced cartilage technology uses stabilized autologous or allogeneic fragments in 1-stage transplantation. Second and third generation cell-based methods include alternative membranes, chondrocyte seeding, and culturing onto scaffolds. Despite the promising early results of these products, significant technical obstacles remain along with unknown long-term durability. The vast array of developing technologies has exceptional promise and the potential to revolutionize the cartilage treatment algorithm within the next decade.

Durability of Aortic Valve Cusp Repair With and Without Annular Support.

Science.gov (United States)

Zeeshan, Ahmad; Idrees, Jay J; Johnston, Douglas R; Rajeswaran, Jeevanantham; Roselli, Eric E; Soltesz, Edward G; Gillinov, A Marc; Griffin, Brian; Grimm, Richard; Hammer, Donald F; Pettersson, Gösta B; Blackstone, Eugene H; Sabik, Joseph F; Svensson, Lars G

2018-03-01

To determine the value of aortic valve repair rather than replacement for valve dysfunction, we assessed late outcomes of various repair techniques in the contemporary era. From January 2001 to January 2011, aortic valve repair was planned in 1,124 patients. Techniques involved commissural figure-of-8 suspension sutures (n = 63 [6.2%]), cusp repair with commissuroplasty (n = 481 [48%]), debridement (n = 174 [17%]), free-margin plication (n = 271 [27%]) or resection (n = 75) or both, or annulus repair with resuspension (n = 230 [23%]), root reimplantation (n = 252 [25%]), or remodeling (n = 35 [3.5%]). Planned repair was aborted for replacement in 115 patients (10%); risk factors included greater severity of aortic regurgitation (AR; p = 0.0002) and valve calcification (p < 0.0001). In-hospital outcomes for the remaining 1,009 patients included death (12 [1.2%]), stroke (13 [1.3%]), and reoperation for valve dysfunction (14 [1.4%]). Freedom from aortic valve reoperation at 1, 5, and 10 years was 97%, 93%, and 90%, respectively. Figure-of-8 suspension sutures, valve resuspension, and root repair and replacement were least likely to require reoperation; cusp repair with commissural sutures, plication, and commissuroplasty was most likely (p < 0.05). Survival at 1, 5, and 10 years was 96%, 92%, and 83%. Immediate postoperative AR grade was none-mild (94%), moderate (5%), and severe (1%). At 10 years after repair, AR grade was none (20%), mild (33%), moderate (26%), and severe (21%). Patients undergoing root procedures were less likely to have higher-grade postoperative AR (p < 0.0001). Valve repair is effective and durable for treating aortic valve dysfunction. Greater severity of AR preoperatively is associated with higher likelihood of repair failure. Commissural figure-of-8 suspension sutures and repair with annular support have the best long-term durability. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights

Low intensity infrared laser affects expression of oxidative DNA repair genes in mitochondria and nucleus

International Nuclear Information System (INIS)

Fonseca, A S; Magalhães, L A G; Mencalha, A L; Geller, M; Paoli, F

2014-01-01

Practical properties and physical characteristics of low intensity lasers have made possible their application to treat soft tissue diseases. Excitation of intracellular chromophores by red and infrared radiation at low energy fluences with increase of mitochondrial metabolism is the basis of the biostimulation effect but free radicals can be produced. DNA lesions induced by free radicals are repaired by the base excision repair pathway. In this work, we evaluate the expression of POLγ and APEX2 genes related to repair of mitochondrial and nuclear DNA, respectively. Skin and muscle tissue of Wistar rats were exposed to low intensity infrared laser at different fluences. One hour and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis, and evaluation of POLγ and APEX2 mRNA expression by real time quantitative polymerase chain reaction. Skin and muscle tissue of Wistar rats exposed to laser radiation show different expression of POLγ and APEX2 mRNA depending of the fluence and time after exposure. Our study suggests that a low intensity infrared laser affects expression of genes involved in repair of oxidative lesions in mitochondrial and nuclear DNA. (paper)

Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells

DEFF Research Database (Denmark)

Garm, Christian; Moreno-Villanueva, Maria; Bürkle, Alexander

2013-01-01

Exogenous and endogenous damage to DNA is constantly challenging the stability of our genome. This DNA damage increase the frequency of errors in DNA replication, thus causing point mutations or chromosomal rearrangements and has been implicated in aging, cancer, and neurodegenerative diseases...... in a study population consisting of 216 individuals from a population-based sample of twins aged 40-77 years. Age in this range did not seem to have any effect on the SSB parameters. However, γ-H2AX response and DSB repair capacity decreased with increasing age, although the associations did not reach...... statistical significance after adjustment for batch effect across multiple experiments. No gender differences were observed for any of the parameters analyzed. Our findings suggest that in PBMCs, the repair of SSBs is maintained until old age, whereas the response to and the repair of DSBs decrease....

The Acid-Secreting Parietal Cell as an Endocrine Source of Sonic Hedgehog During Gastric Repair

Science.gov (United States)

Engevik, Amy C.; Feng, Rui; Yang, Li

2013-01-01

Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues. Despite its known function in tissue regeneration, the role of Shh secreted from the gastric epithelium during tissue repair in the stomach remains unknown. Here we tested the hypothesis that Shh secreted from the acid-secreting parietal cell is a fundamental circulating factor that drives gastric repair. A mouse model expressing a parietal cell-specific deletion of Shh (PC-ShhKO) was generated using animals bearing loxP sites flanking exon 2 of the Shh gene (Shhflx/flx) and mice expressing a Cre transgene under the control of the H+,K+-ATPase β-subunit promoter. Shhflx/flx, the H+,K+-ATPase β-subunit promoter, and C57BL/6 mice served as controls. Ulcers were induced via acetic acid injury. At 1, 2, 3, 4, 5, and 7 days after the ulcer induction, gastric tissue and blood samples were collected. Parabiosis experiments were used to establish the effect of circulating Shh on ulcer repair. Control mice exhibited an increased expression of Shh in the gastric tissue and plasma that correlated with the repair of injury within 7 days after surgery. PC-ShhKO mice showed a loss of ulcer repair and reduced Shh tissue and plasma concentrations. In a parabiosis experiment whereby a control mouse was paired with a PC-ShhKO littermate and both animals subjected to gastric injury, a significant increase in the circulating Shh was measured in both parabionts. Elevated circulating Shh concentrations correlated with the repair of gastric ulcers in the PC-ShhKO parabionts. Therefore, the acid-secreting parietal cell within the stomach acts as an endocrine source of Shh during repair. PMID:24092639

Repair of 3-methyladenine and abasic sites by base excision repair mediates glioblastoma resistance to temozolomide

Energy Technology Data Exchange (ETDEWEB)

Bobola, Michael S.; Kolstoe, Douglas D.; Blank, A. [Department of Neurological Surgery, University of Washington Medical Center, Seattle, WA (United States); Chamberlain, Marc C. [Department of Neurological Surgery, University of Washington Medical Center, Seattle, WA (United States); Department of Neurology, University of Washington Medical Center, Seattle, WA (United States); Silber, John R., E-mail: jrsilber@u.washington.edu [Department of Neurological Surgery, University of Washington Medical Center, Seattle, WA (United States)

2012-11-30

Alkylating agents have long played a central role in the adjuvant therapy of glioblastoma (GBM). More recently, inclusion of temozolomide (TMZ), an orally administered methylating agent with low systemic toxicity, during and after radiotherapy has markedly improved survival. Extensive in vitro and in vivo evidence has shown that TMZ-induced O{sup 6}-methylguanine (O{sup 6}-meG) mediates GBM cell killing. Moreover, low or absent expression of O{sup 6}-methylguanine-DNA methyltransferase (MGMT), the sole human repair protein that removes O{sup 6}-meG from DNA, is frequently associated with longer survival in GBMs treated with TMZ, promoting interest in developing inhibitors of MGMT to counter resistance. However, the clinical efficacy of TMZ is unlikely to be due solely to O{sup 6}-meG, as the agent produces approximately a dozen additional DNA adducts, including cytotoxic N3-methyladenine (3-meA) and abasic sites. Repair of 3-meA and abasic sites, both of which are produced in greater abundance than O{sup 6}-meG, is mediated by the base excision repair (BER) pathway, and occurs independently of removal of O{sup 6}-meG. These observations indicate that BER activities are also potential targets for strategies to potentiate TMZ cytotoxicity. Here we review the evidence that 3-meA and abasic sites mediate killing of GBM cells. We also present in vitro and in vivo evidence that alkyladenine-DNA glycosylase, the sole repair activity that excises 3-meA from DNA, and Ape1, the major human abasic site endonuclease, mediate TMZ resistance in GBMs and represent potential anti-resistance targets.

[Aesthetic effect of wound repair with flaps].

Science.gov (United States)

Tan, Qian; Zhou, Hong-Reng; Wang, Shu-Qin; Zheng, Dong-Feng; Xu, Peng; Wu, Jie; Ge, Hua-Qiang; Lin, Yue; Yan, Xin

2012-08-01

To investigate the aesthetic effect of wound repair with flaps. One thousand nine hundred and ninety-six patients with 2082 wounds hospitalized from January 2004 to December 2011. These wounds included 503 deep burn wounds, 268 pressure sores, 392 soft tissue defects caused by trauma, 479 soft tissue defects due to resection of skin cancer and mole removal, 314 soft tissue defects caused by scar excision, and 126 other wounds. Wound area ranged from 1.5 cm x 1.0 cm to 30.0 cm x 22.0 cm. Sliding flaps, expanded flaps, pedicle flaps, and free flaps were used to repair the wounds in accordance with the principle and timing of wound repair with flaps. Five flaps showed venous congestion within 48 hours post-operation, 2 flaps of them improved after local massage. One flap survived after local heparin wet packing and venous bloodletting. One flap survived after emergency surgical embolectomy and bridging with saphenous vein graft. One flap showed partial necrosis and healed after skin grafting. The other flaps survived well. One thousand three hundred and twenty-one patients were followed up for 3 months to 2 years, and flaps of them were satisfactory in shape, color, and elasticity, similar to that of normal skin. Some patients underwent scar revision later with good results. Application of suitable flaps in wound repair will result in quick wound healing, good function recovery, and satisfactory aesthetic effect.

* Comparison of Autologous, Allogeneic, and Cell-Free Scaffold Approaches for Engineered Tendon Repair in a Rabbit Model-A Pilot Study.

Science.gov (United States)

Wang, Wenbo; Deng, Dan; Wang, Bin; Zhou, Guangdong; Zhang, WenJie; Cao, Yilin; Zhang, Peihua; Liu, Wei

2017-08-01

Tendons are subjected to high strength dynamic mechanical forces in vivo. Mechanical strength is an essential requirement for tendon scaffold materials. A composite scaffold was used in this study to provide mechanical strength, which was composed of an inter part of nonwoven polyglycolic acid (PGA) fibers and an outer part of the net knitted with PGA and polylactic acid (PLA) fibers in a ratio of 4:2. This study compared three different approaches for in vivo tendon engineering, that is, cell-free scaffold and allogeneic and autologous cell seeded scaffolds, using a rabbit Achilles tendon repair model. Dermal fibroblasts were, respectively, isolated from the dermis of regular rabbits or green fluorescence protein transgenic rabbits as the autologous and the allogeneic cell sources, respectively. The cell scaffolds and cell-free scaffolds were implanted to bridge a partial segmental defect of rabbit Achilles tendon. The engineered tendons were harvested at 7 and 13 months postsurgery for various examinations. The results showed that all three groups could achieve in vivo tendon regeneration similarly with slightly better tissue formation in autologous group than in other two groups, including better scaffold degradation and relatively thicker collagen fibrils. There were no statistically significant differences in mechanical parameters among three groups. This work demonstrated that allogeneic fibroblasts and scaffold alone are likely to be used for tendon tissue engineering.

Repairable-conditionally repairable damage model based on dual Poisson processes.

Science.gov (United States)

Lind, B K; Persson, L M; Edgren, M R; Hedlöf, I; Brahme, A

2003-09-01

The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

Fuzzy Context- Free Languages. Part 2: Recognition and Parsing Algorithms

NARCIS (Netherlands)

Asveld, P.R.J.

2000-01-01

In a companion paper \\cite{Asv:FCF1} we used fuzzy context-free grammars in order to model grammatical errors resulting in erroneous inputs for robust recognizing and parsing algorithms for fuzzy context-free languages. In particular, this approach enables us to distinguish between small errors

Total Defense + Repair: A Novel Concept in Solar Protection and Skin Rejuvenation.

Science.gov (United States)

McDaniel, David H; Hamzavi, Iltefat H; Zeichner, Joshua A; Fabi, Sabrina G; Bucay, Vivian W; Harper, Julie C; Comstock, Jody A; Makino, Elizabeth T; Mehta, Rahul C; Vega, Virginia L

2015-07-01

elastin fibers and expression of MMP-1. Initial clinical studies indicate that TDR+R SPF34 reduces the increase in surface temperature seen with IR radiation. A significant improvement in the appearance of lines and wrinkles was reported as early as week 2 in patients using TDR+R SPF34. In summary, we observed that the unique blend of antioxidants present in TD+R acts in harmony with SPF active ingredients, expanding solar protection beyond UV radiation and counterbalancing the deleterious effects of free radicals on skin cells by promoting endogenous repair.

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate

International Nuclear Information System (INIS)

Borek, C.; Troll, W.

1983-01-01

Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and the enzyme catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase, EC 1.11.1.6) on x-ray-and bleomycin-induced transformation and on the enhancement of radiogenic transformation by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). We find that superoxide dismutase inhibits (i) transformation induced by x-ray and bleomycin and (ii) promotional action of TPA in vitro. The results suggest that the oncogenic action of x-rays and bleomycin and the enhancement of oncogenic transformation by TPA are mediated in part by free radicals. The findings also suggest that superoxide dismutase can serve as an inhibitor of oncogenesis and that its actions, as seen in this in vitro system, are most predominantly on inhibiting late events in the progression of cellular transformation--those associated with promotion

Concurrent Mesh Repair of a Morgagni and Umbilical Hernia during a Laparoscopic Sleeve Gastrectomy in a Morbidly Obese Individual

Directory of Open Access Journals (Sweden)

N.R Kosai

2016-10-01

Full Text Available Morgagni Hernia is a rare form of diaphragmatic hernia. It is mainly asymptomatic and often identified incidentally during surgery. Tension-free synthetic mesh repair is the preferred treatment modality. However, the use of synthetic mesh concurrently during a clean-contaminated surgery such as sleeve gastrectomy remains controversial due to the remote possibility of mesh infection. A middle-aged female 2 with BMI of 47 Kg/m was admitted electively for laparoscopic sleeve gastrectomy with concurrent umbilical hernia repair. Intra-operatively, a left Morgagni Hernia containing omentum and a segment of transverse colon was noted. She underwent a laparoscopic sleeve gastrectomy and simultaneous laparoscopic tension-free composite mesh repair of both Morgagni and umbilical hernia. Outpatient review three months later revealed excess weight loss of almost 30% with no recurrence of either hernia. In conclusion, the advantages of concurrent hernia repair during bariatric surgery outweigh the risk of mesh infection and should be performed to prevent future risk of visceral herniation and strangulation. Laparoscopic mesh repair of a Morgagni Hernia and umbilical hernia in the setting of an electively planned sleeve gastrectomy is feasible, effective and safe in the hands of a trained laparoscopic surgeon.

Human Postmeiotic Segregation 2 Exhibits Biased Repair at Tetranucleotide Microsatellite Sequences

OpenAIRE

Shah, Sandeep N.; Eckert, Kristin A.

2009-01-01

The mismatch repair (MMR) system plays a major role in removing DNA polymerization errors, and loss of this pathway results in hereditary cancers characterized by microsatellite instability. We investigated microsatellite stability during DNA replication within human postmeiotic segregation 2 (hPMS2)–deficient and proficient human lymphoblastoid cell lines. Using a shuttle vector assay, we measured mutation rates at reporter cassettes containing defined mononucleotide, dinucleotide, and tetra...

Tissue repair capacity and repair kinetics deduced from multifractionated or continuous irradiation regimens with incomplete repair

International Nuclear Information System (INIS)

Thames, H.D. Jr.; Peters, L.J.

1984-01-01

A model is proposed for cell survival after multiple doses, when the interfraction interval is insufficient for complete Elkind repair. In the limit of ever-increasing number of ever-smaller fractional doses, the model transforms into the accumulation model of survival after continuous irradiation. When adapted to describe tissue responses to isoeffective multifractionated regimens, wherein repair is incomplete, a generalization of the usually linear plot of reciprocal total dose versus dose per fraction is obtained, in which downward curvature is evident. There is an advantage in studying tissue responses to multifractionated regimens with incomplete repair in the interfraction intervals, or continuous exposures at various dose rates since, in addition to determination of repair capacity, there is an estimate of repair kinetics. Results of analyses of previously published data are presented as illustration. Estimated from the response of three acutely responding normal tissues in the mouse (jejunum, colon and bone marrow), repair halftimes ranged from 0.3-0.9 h and values of β/delta were approximately 0.1 Gy -1 . From the response of mouse lung (LD50 for pneumonitis) to multifractionated regimens with incomplete repair, the repair halftime was estimated at 1.5 h and β/delta was 0.27 Gy -1 . In the rat spinal cord β/delta was 0.7 Gy -1 and Tsub(1/2) was 1.5 h. (U.K.)

Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC).

Science.gov (United States)

Newton, K; Jorgensen, N M; Wallace, A J; Buchanan, D D; Lalloo, F; McMahon, R F T; Hill, J; Evans, D G

2014-12-01

Lynch syndrome (LS) patients have DNA mismatch repair deficiency and up to 80% lifetime risk of colorectal cancer (CRC). Screening of mutation carriers reduces CRC incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour-derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from LS (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of constitutional mutations. Tumour DNA was extracted (formalin fixed, paraffin embedded, FFPE tissue) and pyrosequencing used to test for MLH1 promoter methylation and presence of the BRAF c.1799T>A, p.(Val600Glu) mutation 71 CRCs from individuals with pathogenic MLH1 mutations and 73 CRCs with sporadic MLH1 loss. Specificity and sensitivity was compared. Unmethylated MLH1 promoter: sensitivity 94.4% (95% CI 86.2% to 98.4%), specificity 87.7% (95% CI 77.9% to 94.2%), Wild-type BRAF (codon 600): sensitivity 65.8% (95% CI 53.7% to 76.5%), specificity 98.6% (95% CI 92.4% to 100.0%) for the identification of those with pathogenic MLH1 mutations. Quantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparing Biomechanical Properties, Repair Times, and Value of Common Core Flexor Tendon Repairs.

Science.gov (United States)

Chauhan, Aakash; Schimoler, Patrick; Miller, Mark C; Kharlamov, Alexander; Merrell, Gregory A; Palmer, Bradley A

2018-05-01

The aim of the study was to compare biomechanical strength, repair times, and repair values for zone II core flexor tendon repairs. A total of 75 fresh-frozen human cadaveric flexor tendons were harvested from the index through small finger and randomized into one of 5 repair groups: 4-stranded cross-stitch cruciate (4-0 polyester and 4-0 braided suture), 4-stranded double Pennington (2-0 knotless barbed suture), 4-stranded Pennington (4-0 double-stranded braided suture), and 6-stranded modified Lim-Tsai (4-0 looped braided suture). Repairs were measured in situ and their repair times were measured. Tendons were linearly loaded to failure and multiple biomechanical values were measured. The repair value was calculated based on operating room costs, repair times, and suture costs. Analysis of variance (ANOVA) and Tukey post hoc statistical analysis were used to compare repair data. The braided cruciate was the strongest repair ( P > .05) but the slowest ( P > .05), and the 4-stranded Pennington using double-stranded suture was the fastest ( P > .05) to perform. The total repair value was the highest for braided cruciate ( P > .05) compared with all other repairs. Barbed suture did not outperform any repairs in any categories. The braided cruciate was the strongest of the tested flexor tendon repairs. The 2-mm gapping and maximum load to failure for this repair approached similar historical strength of other 6- and 8-stranded repairs. In this study, suture cost was negligible in the overall repair cost and should be not a determining factor in choosing a repair.

Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

Science.gov (United States)

Bailis, Julie M; Weidmann, Alyson G; Mariano, Natalie F; Barton, Jacqueline K

2017-07-03

The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)] 2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells.

Science.gov (United States)

King, Harry O; Brend, Tim; Payne, Helen L; Wright, Alexander; Ward, Thomas A; Patel, Karan; Egnuni, Teklu; Stead, Lucy F; Patel, Anjana; Wurdak, Heiko; Short, Susan C

2017-01-10

Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation. In GSCs, the small-molecule RAD51 inhibitors RI-1 and B02 prevent RAD51 focus formation, reduce DNA DSB repair, and cause significant radiosensitization. We further demonstrate that treatment with these agents combined with radiation promotes loss of stem cells defined by SOX2 expression. This indicates that RAD51-dependent repair represents an effective and specific target in GSCs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Botulinum toxin is detrimental to repair of a chronic rotator cuff tear in a rabbit model.

Science.gov (United States)

Gilotra, Mohit; Nguyen, Thao; Christian, Matthew; Davis, Derik; Henn, R Frank; Hasan, Syed Ashfaq

2015-08-01

Re-tear continues to be a problem after rotator cuff repair. Intramuscular botulinum toxin (Botox) injection can help optimize tension at the repair site to promote healing but could have an adverse effect on the degenerated muscle in a chronic tear. We hypothesized that Botox injection would improve repair characteristics without adverse effect on the muscle in a chronic rotator cuff tear model. The supraspinatus tendon of both shoulders in 14 rabbits underwent delayed repair 12 weeks after transection. One shoulder was treated with intramuscular Botox injection and the other with a saline control injection. Six weeks after repair, outcomes were based on biomechanics, histology, and magnetic resonance imaging. Botox-treated repairs were significantly weaker (2.64 N) than control repairs (5.51 N, p = 0.03). Eighty percent of Botox-treated repairs and 40% of control repairs healed with some partial defect. Fatty infiltration of the supraspinatus was present in all shoulders (Goutallier Grade 3 or 4) but was increased in the setting of Botox. This study provides additional support for the rabbit supraspinatus model of chronic cuff tear, showing consistent fatty infiltration. Contrary to our hypothesis, Botox had a negative effect on repair strength and might increase fatty infiltration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.

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Ian R Kelsall

Full Text Available The many proteins that function in the Fanconi anaemia (FA monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments indicate that both of these FA genes collaborate to promote nucleotide excision repair rather than translesion bypass to protect cells form UV genotoxicity. Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the FA pathway shares two components with nucleotide excision repair, intimating not only crosstalk between the two major repair pathways, but also potentially identifying a UBE2T-mediated ubiquitin-signalling response pathway that contributes to nucleotide excision repair.

Transformation mechanism of benzophenone-4 in free chlorine promoted chlorination disinfection.

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Xiao, Ming; Wei, Dongbin; Yin, Junxia; Wei, Guohua; Du, Yuguo

2013-10-15

The UV-filter BP-4 (2-hydroxy-4-methoxybenzophenone-5-sulfonic acid) has been frequently observed in the environment, showing high potentials to invade drinking water, swimming water, or wastewater reclamation treatment systems. With the help of high performance liquid chromatography-high resolution mass spectrometry and nuclear magnetic resonance spectroscopy, 10 new products from free chlorine-promoted BP-4 disinfection have been disclosed and their possible transformation routes have been investigated. The first route is chlorine substitution of BP-4 and its transformation products, forming mono-, di-, and tri-chlorinated BP-4 analogs. The second is Baeyer-Villiger-Type oxidation, converting diphenyl ketone to phenyl ester derivatives. The third is ester hydrolysis, generating corresponding phenolic and benzoic products. The fourth is decarboxylation, replacing the carboxyl group by chloride in the benzoic-type intermediate. The fifth is desulfonation, degrading the sulfonic group through an alternative chlorine substitution on the benzene ring. Orthogonal experiments have been established to investigate the species transformed from BP-4 at different pH values and free available chlorine (FAC) dosages. The reaction pathways are strongly dependent on pH conditions, while an excessive amount of FAC eliminates BP-4 to the smaller molecules. The initial transformation of BP-4 in chlorination system follows pseudo-first-order kinetics, and its half-lives ranged from 7.48 s to 1.26 × 10(2) s. More importantly, we have observed that the FAC-treated BP-4 aqueous solution might increase the genotoxic potentials due to the generation of chlorinated disinfection by-products. Copyright © 2013 Elsevier Ltd. All rights reserved.

High Throughput and Mechano-Active Platforms to Promote Cartilage Regeneration and Repair

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Mohanraj, Bhavana

Traumatic joint injuries initiate acute degenerative changes in articular cartilage that can lead to progressive loss of load-bearing function. As a result, patients often develop post-traumatic osteoarthritis (PTOA), a condition for which there currently exists no biologic interventions. To address this need, tissue engineering aims to mimic the structure and function of healthy, native counterparts. These constructs can be used to not only replace degenerated tissue, but also build in vitro, pre-clinical models of disease. Towards this latter goal, this thesis focuses on the design of a high throughput system to screen new therapeutics in a micro-engineered model of PTOA, and the development of a mechanically-responsive drug delivery system to augment tissue-engineered approaches for cartilage repair. High throughput screening is a powerful tool for drug discovery that can be adapted to include 3D tissue constructs. To facilitate this process for cartilage repair, we built a high throughput mechanical injury platform to create an engineered cartilage model of PTOA. Compressive injury of functionally mature constructs increased cell death and proteoglycan loss, two hallmarks of injury observed in vivo. Comparison of this response to that of native cartilage explants, and evaluation of putative therapeutics, validated this model for subsequent use in small molecule screens. A primary screen of 118 compounds identified a number of 'hits' and relevant pathways that may modulate pathologic signaling post-injury. To complement this process of therapeutic discovery, a stimuli-responsive delivery system was designed that used mechanical inputs as the 'trigger' mechanism for controlled release. The failure thresholds of these mechanically-activated microcapsules (MAMCs) were influenced by physical properties and composition, as well as matrix mechanical properties in 3D environments. TGF-beta released from the system upon mechano-activation stimulated stem cell

Peripheral nerve repair: a hot spot analysis on treatment methods from 2010 to 2014

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Guang-yao Liu

2015-01-01

Full Text Available Therapeutic strategies for neurological deficits and for promoting nerve regeneration after peripheral nerve injuries have received much focus in clinical research. Advances in basic research in recent years have increased our understanding of the anatomy of peripheral nerves and the importance of the microenvironment. Various new intervention methods have been developed, but with varying effectiveness. In the present study, we selected 911 papers on different repair methods for peripheral nerve injury from the Web of Science and indexed in the Science Citation Index from 2010 to 2014. We quantitatively examine new repair methods and strategies using bibliometrics, and we discuss the present state of knowledge and the problems and prospects of various repair methods, including nerve transfer, neural transplantation, tissue engineering and genetic engineering. Our findings should help in the study and development of repair methods for peripheral nerve injury.

Reduction of errors during practice facilitates fundamental movement skill learning in children with intellectual disabilities.

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Capio, C M; Poolton, J M; Sit, C H P; Eguia, K F; Masters, R S W

2013-04-01

Children with intellectual disabilities (ID) have been found to have inferior motor proficiencies in fundamental movement skills (FMS). This study examined the effects of training the FMS of overhand throwing by manipulating the amount of practice errors. Participants included 39 children with ID aged 4-11 years who were allocated into either an error-reduced (ER) training programme or a more typical programme in which errors were frequent (error-strewn, ES). Throwing movement form, throwing accuracy, and throwing frequency during free play were evaluated. The ER programme improved movement form, and increased throwing activity during free play to a greater extent than the ES programme. Furthermore, ER learners were found to be capable of engaging in a secondary cognitive task while manifesting robust throwing accuracy performance. The findings support the use of movement skills training programmes that constrain practice errors in children with ID, suggesting that such approach results in improved performance and heightened movement engagement in free play. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

[Medication error management climate and perception for system use according to construction of medication error prevention system].

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Kim, Myoung Soo

2012-08-01

The purpose of this cross-sectional study was to examine current status of IT-based medication error prevention system construction and the relationships among system construction, medication error management climate and perception for system use. The participants were 124 patient safety chief managers working for 124 hospitals with over 300 beds in Korea. The characteristics of the participants, construction status and perception of systems (electric pharmacopoeia, electric drug dosage calculation system, computer-based patient safety reporting and bar-code system) and medication error management climate were measured in this study. The data were collected between June and August 2011. Descriptive statistics, partial Pearson correlation and MANCOVA were used for data analysis. Electric pharmacopoeia were constructed in 67.7% of participating hospitals, computer-based patient safety reporting systems were constructed in 50.8%, electric drug dosage calculation systems were in use in 32.3%. Bar-code systems showed up the lowest construction rate at 16.1% of Korean hospitals. Higher rates of construction of IT-based medication error prevention systems resulted in greater safety and a more positive error management climate prevailed. The supportive strategies for improving perception for use of IT-based systems would add to system construction, and positive error management climate would be more easily promoted.

HYDROGEL-BASED NANOCOMPOSITES OF THERAPEUTIC PROTEINS FOR TISSUE REPAIR.

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Zhu, Suwei; Segura, Tatiana

2014-05-01

The ability to design artificial extracellular matrices as cell instructive scaffolds has opened the door to technologies capable of studying cell fates in vitro and to guide tissue repair in vivo . One main component of the design of artificial extracellular matrices is the incorporation of protein-based biochemical cues to guide cell phenotypes and multicellular organizations. However, promoting the long-term bioactivity, controlling the bioavailability and understanding how the physical presentations of these proteins impacts cellular fates are among the challenges of the field. Nanotechnolgy has advanced to meet the challenges of protein therapeutics. For example, the approaches to incorporating proteins into tissue repairing scaffolds have ranged from bulk encapsulations to smart nanodepots that protect proteins from degradations and allow opportunities for controlled release.

Recognition of medical errors' reporting system dimensions in educational hospitals.

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Yarmohammadian, Mohammad H; Mohammadinia, Leila; Tavakoli, Nahid; Ghalriz, Parvin; Haghshenas, Abbas

2014-01-01

Nowadays medical errors are one of the serious issues in the health-care system and carry to account of the patient's safety threat. The most important step for achieving safety promotion is identifying errors and their causes in order to recognize, correct and omit them. Concerning about repeating medical errors and harms, which were received via theses errors concluded to designing and establishing medical error reporting systems for hospitals and centers that are presenting therapeutic services. The aim of this study is the recognition of medical errors' reporting system dimensions in educational hospitals. This research is a descriptive-analytical and qualities' study, which has been carried out in Shahid Beheshti educational therapeutic center in Isfahan during 2012. In this study, relevant information was collected through 15 face to face interviews. That each of interviews take place in about 1hr and creation of five focused discussion groups through 45 min for each section, they were composed of Metron, educational supervisor, health officer, health education, and all of the head nurses. Concluded data interviews and discussion sessions were coded, then achieved results were extracted in the presence of clear-sighted persons and after their feedback perception, they were categorized. In order to make sure of information correctness, tables were presented to the research's interviewers and final the corrections were confirmed based on their view. The extracted information from interviews and discussion groups have been divided into nine main categories after content analyzing and subject coding and their subsets have been completely expressed. Achieved dimensions are composed of nine domains of medical error concept, error cases according to nurses' prospection, medical error reporting barriers, employees' motivational factors for error reporting, purposes of medical error reporting system, error reporting's challenges and opportunities, a desired system

A first population-based long-term outcome study in adults with repaired tetralogy of Fallot in Malta.

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Caruana, Maryanne; Grech, Victor

2017-05-01

To determine overall and reintervention-free survival for repaired Maltese tetralogy of Fallot patients and to investigate the potential impact of gender, age at repair, genetic syndromes, previous palliation, and type of repair on these outcomes. All 130 tetralogy of Fallot patients born before the end of 1997 included in the local database were extracted. Surgical repair type, age at repair and operative survival were analyzed among the 103/130 repaired patients. Kaplan-Meier survival analyses were performed on the 75 repair survivors with complete follow-up data (mean follow-up 26.37 ± 9.27 (range 9.95-51.21) years). Patients born after 1985 were operated at a younger age (median 1.28 years) compared with patients born before 1985 (median 9.64 years) (P tetralogy of Fallot repair in contemporary patients is very good, cardiac death can occur at any stage and structural reintervention is common. Regular follow-up with imaging and rhythm monitoring remains of utmost importance in all patients. © 2016 Wiley Periodicals, Inc.

DNA Polymerases λ and β: The Double-Edged Swords of DNA Repair

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Elisa Mentegari

2016-08-01

Full Text Available DNA is constantly exposed to both endogenous and exogenous damages. More than 10,000 DNA modifications are induced every day in each cell’s genome. Maintenance of the integrity of the genome is accomplished by several DNA repair systems. The core enzymes for these pathways are the DNA polymerases. Out of 17 DNA polymerases present in a mammalian cell, at least 13 are specifically devoted to DNA repair and are often acting in different pathways. DNA polymerases β and λ are involved in base excision repair of modified DNA bases and translesion synthesis past DNA lesions. Polymerase λ also participates in non-homologous end joining of DNA double-strand breaks. However, recent data have revealed that, depending on their relative levels, the cell cycle phase, the ratio between deoxy- and ribo-nucleotide pools and the interaction with particular auxiliary proteins, the repair reactions carried out by these enzymes can be an important source of genetic instability, owing to repair mistakes. This review summarizes the most recent results on the ambivalent properties of these enzymes in limiting or promoting genetic instability in mammalian cells, as well as their potential use as targets for anticancer chemotherapy.

DNA Polymerases λ and β: The Double-Edged Swords of DNA Repair.

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Mentegari, Elisa; Kissova, Miroslava; Bavagnoli, Laura; Maga, Giovanni; Crespan, Emmanuele

2016-08-31

DNA is constantly exposed to both endogenous and exogenous damages. More than 10,000 DNA modifications are induced every day in each cell's genome. Maintenance of the integrity of the genome is accomplished by several DNA repair systems. The core enzymes for these pathways are the DNA polymerases. Out of 17 DNA polymerases present in a mammalian cell, at least 13 are specifically devoted to DNA repair and are often acting in different pathways. DNA polymerases β and λ are involved in base excision repair of modified DNA bases and translesion synthesis past DNA lesions. Polymerase λ also participates in non-homologous end joining of DNA double-strand breaks. However, recent data have revealed that, depending on their relative levels, the cell cycle phase, the ratio between deoxy- and ribo-nucleotide pools and the interaction with particular auxiliary proteins, the repair reactions carried out by these enzymes can be an important source of genetic instability, owing to repair mistakes. This review summarizes the most recent results on the ambivalent properties of these enzymes in limiting or promoting genetic instability in mammalian cells, as well as their potential use as targets for anticancer chemotherapy.

Generation IV SFR Nuclear Reactors: Under-Sodium Repair for ASTRID

International Nuclear Information System (INIS)

Baque, F.; Chagnot, C.; Bruguiere, L.; Augem, J.M.; Delalande, V.; Sibilo, J.

2013-06-01

For non-removable components of the future ASTRID prototype, repair operations will be performed in a gas environment. If the faulty area is located under the sodium free level, the gas-tight system will have to contain the inspection and repair tools and to protect them from the surrounding liquid sodium. Concerning repair tools, the unique laser tool has been selected for future SFRs: the repair scenario for in-sodium structures will first involve removing the sodium (after bulk draining), then machining and finally welding. Concerning conventional tools (brush or gas blower for sodium removal, milling machine for machining and TIG for welding for which its feasibility was demonstrated in the 1990's) are still considered as a back-up solution. In-pile examination or repair requires robotic carriers. These carriers have to be compatible with the sodium environment: either in the cover-gas plenum or in gas after sodium draining, or even under liquid sodium. This R and D programme has been divided into nine parts in order to provide an overall design of the required robotic carriers and to develop technological solutions for their components: detailed definition for SFR carrier needs (access to internal structures, possible defects to be detected/repaired), definition and specifications of carrier architecture (depending on inspection and repair scenarios), in-sodium leak-tightness of carrier components, carrier material compatibility with sodium, temperature resistance (200 deg. C), irradiation resistance (depending on the location of the main vessel), gas-tight bell for operations under liquid sodium, carrier positioning control in liquid sodium, development, validation and qualification of technological solutions, for future SFRs, and worldwide benchmark regarding the previous areas of investigation. (authors)

Conversational Repair in School-Aged Children with High-Functioning Autism

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Pei-Mei Lu

2015-12-01

Full Text Available The main purpose of this study was to investigate the conversational repair skills of Mandarin Chinese-speaking children with high-functioning autism (HFA as compared with those of typically developing children (TD. Ten school-aged children (age 9 to 12 with HFA were recruited and matched against ten TD children in the control group based on age, gender, and verbal intelligence level. During three different conversation situations (free talk, story picture description, play, an examiner engineered 9 episodes of communicative breakdowns. Each consisted of a stacked series of three prompts for responding to requests for clarification (RQCLs (i.e.‘What?’, ‘I don’t understand’, ‘I still don’t know’. Verbal responses to each RQCL were then coded for further analyses. The results showed that (1 In response to the stacked series RQCLs, children with HFA were similar to the control group children in evidencing repetition, revision, and addition types of repair. Furthermore, children with HFA showed fewer cue type of repair and more inappropriate type of repair than TD group. (2For both groups, the pattern of responding over the series of RQCLs was similar in varying the repetition and revision types of repair strategies. However, the pattern in the addition, cue, and inappropriate types of repair strategies were different. Children with HFA were significantly more likely to respond to an RQCL with an inappropriate response than the language and age-matched controls. It is suggested that teachers and parents could facilitate the conversational repair skills of children with high-functioning autism by offering them opportunities to manage different types of communicative breakdowns.

Understanding DNA Repair in Hyperthermophilic Archaea: Persistent Gaps and Other Reasons to Focus on the Fork

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Dennis W. Grogan

2015-01-01

Full Text Available Although hyperthermophilic archaea arguably have a great need for efficient DNA repair, they lack members of several DNA repair protein families broadly conserved among bacteria and eukaryotes. Conversely, the putative DNA repair genes that do occur in these archaea often do not generate the expected phenotype when deleted. The prospect that hyperthermophilic archaea have some unique strategies for coping with DNA damage and replication errors has intellectual and technological appeal, but resolving this question will require alternative coping mechanisms to be proposed and tested experimentally. This review evaluates a combination of four enigmatic properties that distinguishes the hyperthermophilic archaea from all other organisms: DNA polymerase stalling at dU, apparent lack of conventional NER, lack of MutSL homologs, and apparent essentiality of homologous recombination proteins. Hypothetical damage-coping strategies that could explain this set of properties may provide new starting points for efforts to define how archaea differ from conventional models of DNA repair and replication fidelity.

Enhanced capacity of DNA repair in human cytomegalovirus-infected cells

International Nuclear Information System (INIS)

Nishiyama, Y.; Rapp, F.

1981-01-01

Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate. Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone. A similar enhancement by HCMV was observed in human embryonic fibroblasts, but not in xeroderma pigmentosum (XP12BE) cells. It was also found that HCMV infection enhanced hydroxyurea-resistant DNA synthesis induced by UV light or methylmethanesulfonate. Alkaline sucrose gradient sedimentation analysis revealed an enhanced rate of synthesis of all size classes of DNA in UV-irradiated HCMV-infected Vero cells. However, HCMV infection did not induce repairable lesions in cellular DNA and did not significantly inhibit host cell DNA synthesis, unlike UV or methylmethanesulfonate. These results indicate that HCMV enhanced DNA repair capacity in the host cells without producing detectable lesions in cellular DNA and without inhibiting DNA synthesis. This repair appeared to be error proof for UV-damaged herpes simplex virus DNA when tested with herpes simplex virus thymidine kinase-negative mutants

CARTILAGE CONSTRUCTS ENGINEERED FROM CHONDROCYTES OVEREXPRESSING IGF-I IMPROVE THE REPAIR OF OSTEOCHONDRAL DEFECTS IN A RABBIT MODEL

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Madry, Henning; Kaul, Gunter; Zurakowski, David; Vunjak-Novakovic, Gordana; Cucchiarini, Magali

2015-01-01

Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects. PMID:23588785

Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model

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H Madry

2013-04-01

Full Text Available Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

Hybrid aortic repair with antegrade supra-aortic and renovisceral debranching from ascending aorta.

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Del Castro-Madrazo, José Antonio; Rivas-Domínguez, Margarita; Fernández-Prendes, Carlota; Zanabili Al-Sibbai, Amer; Llaneza-Coto, José Manuel; Alonso-Pérez, Manuel

2017-05-01

Aortic dissection is a life threatening condition. Hybrid repair has been described for the treatment of complex aortic pathology such as thoracoabdominal aortic aneurysms (TAAA) and type A and B dissections, although open and total endovascular repair are also possible. Open surgery is still associated with substantial perioperative morbi-mortality rates, thus less invasive techniques such as endovascular repair and hybrid procedures can achieve good results in centers with experience. We present the case of a patient with a chronic type B dissection and TAAA degeneration that was treated in a single stage hybrid procedure with antegrade supra-aortic and renovisceral debranching from the ascending aorta and TEVAR. At three-year follow up, the patient is free of intervention-related complications.

Tunable error-free optical frequency conversion of a 4ps optical short pulse over 25 nm by four-wave mixing in a polarisation-maintaining optical fibre

Science.gov (United States)

Morioka, T.; Kawanishi, S.; Saruwatari, M.

1994-05-01

Error-free, tunable optical frequency conversion of a transform-limited 4.0 ps optical pulse signalis demonstrated at 6.3 Gbit/s using four-wave mixing in a polarization-maintaining optical fibre. The process generates 4.0-4.6 ps pulses over a 25nm range with time-bandwidth products of 0.31-0.43 and conversion power penalties of less than 1.5 dB.

Medication errors reported to the National Medication Error Reporting System in Malaysia: a 4-year retrospective review (2009 to 2012).

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Samsiah, A; Othman, Noordin; Jamshed, Shazia; Hassali, Mohamed Azmi; Wan-Mohaina, W M

2016-12-01

Reporting and analysing the data on medication errors (MEs) is important and contributes to a better understanding of the error-prone environment. This study aims to examine the characteristics of errors submitted to the National Medication Error Reporting System (MERS) in Malaysia. A retrospective review of reports received from 1 January 2009 to 31 December 2012 was undertaken. Descriptive statistics method was applied. A total of 17,357 MEs reported were reviewed. The majority of errors were from public-funded hospitals. Near misses were classified in 86.3 % of the errors. The majority of errors (98.1 %) had no harmful effects on the patients. Prescribing contributed to more than three-quarters of the overall errors (76.1 %). Pharmacists detected and reported the majority of errors (92.1 %). Cases of erroneous dosage or strength of medicine (30.75 %) were the leading type of error, whilst cardiovascular (25.4 %) was the most common category of drug found. MERS provides rich information on the characteristics of reported MEs. Low contribution to reporting from healthcare facilities other than government hospitals and non-pharmacists requires further investigation. Thus, a feasible approach to promote MERS among healthcare providers in both public and private sectors needs to be formulated and strengthened. Preventive measures to minimise MEs should be directed to improve prescribing competency among the fallible prescribers identified.