Ihlemann, Nikolaj; Franzen, Olaf; Jørgensen, Erik
Mitral valve regurgitation (MR) is the secondmost frequent valve disease in Europe. Untreated MR causes considerable morbidity and mortality. In the elderly, as many as half of these patients are denied surgery because of an estimated high surgical risk. Percutaneous mitral valve repair with the ...... with the MitraClip system resembles the Alfieristitch where a clip is used to connect the tip of the mitral valve leaflets....
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
Xian-bin Kong; Qiu-yan Tang; Xu-yi Chen; Yue Tu; Shi-zhong Sun; Zhong-lei Sun
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.
Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin
Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy
Halvarsson, Britta; Anderson, Harald; Domanska, Katarina
Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...
Halvarsson, Britta; Anderson, Harald; Domanska, Katarina
Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...
Armstead, Theresa L; Rambo, Kirsten; Kearns, Megan; Jones, Kathryn M; Dills, Jenny; Brown, Pamela
According to 2011 data, nearly one in four women and one in seven men in the United States experience severe physical violence by an intimate partner, creating a public health burden requiring population-level solutions. To prevent intimate partner violence (IPV) before it occurs, the CDC developed Domestic Violence Prevention Enhancements and Leadership Through Alliances, Focusing on Outcomes for Communities United with States to identify promising community- and societal-level prevention strategies to prevent IPV. The program funds 10 state domestic violence coalitions for 5 years to implement and evaluate programs and policies to prevent IPV by influencing the environments and conditions in which people live, work, and play. The program evaluation goals are to promote IPV prevention by identifying promising prevention strategies and describing those strategies using case studies, thereby creating a foundation for building practice-based evidence with a health equity approach.
Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold
It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality
Thorell, Lisa B; Eninger, Lilianne; Brocki, Karin C; Bohlin, Gunilla
The present study investigated whether the Childhood Executive Function Inventory (CHEXI) can discriminate between young children fulfilling the diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD) and normally developing children. Unlike other executive function rating instruments, the CHEXI focuses specifically on inhibitory control and working memory, without including items that overlap with the diagnostic criteria of ADHD. The CHEXI was found to discriminate very well between children fulfilling the criteria for ADHD and normally developing children, also when controlling for the effect of IQ and socioeconomic status (SES). Both sensitivity and specificity of the two CHEXI subscales were shown to be high using either parent or teacher ratings. The highest overall classification rate was found for parent ratings on the inhibition subscale, with sensitivity and specificity reaching 93.3. To summarize, the CHEXI should be considered a promising measure for identifying young children with ADHD, although it is for future research to determine whether the CHEXI can be successfully used to also discriminate between different psychopathological groups.
Full Text Available The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF is a heterodimeric endonuclease essential for the nucleotide excision repair (NER DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15 database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.
Ruebe, Claudia E.; Fricke, Andreas; Schneider, Ruth; Simon, Karin; Kuehne, Martin; Fleckenstein, Jochen; Graeber, Stefan; Graf, Norbert; Ruebe, Christian
Purpose: To evaluate, in a pilot study, the phosphorylated H2AX (γH2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting γH2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.
Rocha, Mariella C; Deliza, Rosires; Ares, Gastón; Freitas, Daniela De G C; Silva, Aline L S; Carmo, Margarida G F; Abboud, Antonio C S
An increased production of cherry and gourmet tomato cultivars that are harvested at advanced colour stages and sold at a higher price has been observed in the last 10 years. In this context, producers need information on the sensory characteristics of new cultivars and their perception by potential consumers. The aim of the present work was to obtain a sensory characterisation of nine cherry tomato cultivars produced under Brazilian organic cultivation conditions from a chef and consumer perspective. Nine organic cherry tomato genotypes were evaluated by ten chefs using an open-ended question and by 110 consumers using a check-all-that-apply question. Both methodologies provided similar information on the sensory characteristics of the cherry tomato accessions. The superimposed representation of the samples in a multiple factor analysis was similar for consumers' and chefs' descriptions (RV coefficient 0.728), although they used different methodologies. According to both panels, cherry tomatoes were sorted into five groups of samples with similar sensory characteristics. Results from the present work may provide information to help organic producers in the selection of the most promising cultivars for cultivation, taking into account consumers' and chefs' perceptions, as well as in the design of communication and marketing strategies. © 2012 Society of Chemical Industry.
Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik
Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…
Full Text Available SATB2 (Special AT-rich sequence-binding protein 2 has recently been shown to be a specific biomarker of colorectal cancer (CRC. The aim of this study was to investigate the diagnostic potential of SATB2 as a means of detecting a CRC origin for liver metastases. SATB2 expression was examined in a resection cohort of 101 CRC and 273 non-CRC adenocarcinoma samples using immunohistochemistry (IHC. The diagnostic accuracy of CRC origins of liver metastases based on SATB2 and a three marker panel of SATB2, CK20 and CDX2 was evaluated using an independent cohort of 192 liver biopsies. IHC showed 97 of the 101 (96.0% primary CRC samples were SATB2 positive, compared to only 6 of the 273 (2.1% samples of other cancer types. The sensitivity, specificity and AUC values of SATB2 expression in resection samples were 97%, 97.1% and 0.977, respectively. Meanwhile, for the liver biopsy samples, the sensitivity, specificity and AUC values of a CRC liver metastases was 92.2%, 97.8% and 0.948 for SATB2, 95.1%, 91.0% and 0.959 for CK20, and 100%, 85.4% and 0.976 for CDX2, respectively. Further analysis demonstrated that all three-marker positivity was detected in 92/103 (89.3% CRC and 2/89 (2.2% non-CRC liver metastases sampled by biopsy. Our findings suggest that SATB2, as measured by IHC, could serve as a promising diagnostic biomarker of CRC metastases. Combining evaluation of SATB2 with CK20 and CDX2 to form a three marker panel further improved the detection of metastatic CRCs in liver biopsy tissues.
Full Text Available Despite the growing importance of identifying new business items for small and medium enterprises (SMEs, most previous studies focus on conglomerates. The paucity of empirical studies has also led to limited real-life applications. Hence, this study proposes a systematic approach to find new business items (NBIs that help the prospective SMEs develop, evaluate, and select viable business items to survive the competitive environment. The proposed approach comprises two stages: (1 the classification of diversification of SMEs; and (2 the searching and screening of business items. In the first stage, SMEs are allocated to five groups, based on their internal technological competency and external market conditions. In the second stage, based on the types of SMEs identified in the first stage, a set of alternative business items is derived by combining the results of portfolio analysis and benchmarking analysis. After deriving new business items, a market and technology-driven matrix analysis is utilized to screen suitable business items, and the Bruce Merrifield-Ohe (BMO method is used to categorize and identify prospective items based on market attractiveness and internal capability. To illustrate the applicability of the proposed approach, a case study is presented.
Gupta, Anika; Sun, Min Woo; Paskov, Kelley Marie; Stockham, Nate Tyler; Jung, Jae-Yoon; Wall, Dennis Paul
Despite mounting evidence for the strong role of genetics in the phenotypic manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible for the variable forms of ASD remain undefined. ASD may be best explained by a combinatorial genetic model with varying epistatic interactions across many small effect mutations. Coalitional or cooperative game theory is a technique that studies the combined effects of groups of players, known as coalitions, seeking to identify players who tend to improve the performance--the relationship to a specific disease phenotype--of any coalition they join. This method has been previously shown to boost biologically informative signal in gene expression data but to-date has not been applied to the search for cooperative mutations among putative ASD genes. We describe our approach to highlight genes relevant to ASD using coalitional game theory on alteration data of 1,965 fully sequenced genomes from 756 multiplex families. Alterations were encoded into binary matrices for ASD (case) and unaffected (control) samples, indicating likely gene-disrupting, inherited mutations in altered genes. To determine individual gene contributions given an ASD phenotype, a "player" metric, referred to as the Shapley value, was calculated for each gene in the case and control cohorts. Sixty seven genes were found to have significantly elevated player scores and likely represent significant contributors to the genetic coordination underlying ASD. Using network and cross-study analysis, we found that these genes are involved in biological pathways known to be affected in the autism cases and that a subset directly interact with several genes known to have strong associations to autism. These findings suggest that coalitional game theory can be applied to large-scale genomic data to identify hidden yet influential players in complex polygenic disorders such as autism.
Fracture repair is a complex and multifactorial process, which involves a well-programmed series of cellular and molecular events that result in a combination of intramembranous and endochondral bone formation. The vast majority of fractures is treated successfully. They heal through ‘secondary
Full Text Available Endovascular aneurysm repair (EVAR is perhaps the most widely utilized surgical procedure for patients with large abdominal aortic aneurysms. This procedure is minimally invasive and reduces inpatient hospitalization requirements. The case involves a 72-year-old male who presented to the emergency department with right testicular ischemia two days following EVAR. Given the minimal inpatient hospitalization associated with this procedure, emergency physicians are likely to encounter associated complications. Ischemic and thromboembolic events following EVAR are extremely rare but require prompt vascular surgery intervention to minimize morbidity and mortality.
Ella R Thompson
Full Text Available Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing of thirty-three individuals from 15 breast cancer families to identify potential predisposing genes. Our analysis identified families with heterozygous, deleterious mutations in the DNA repair genes FANCC and BLM, which are responsible for the autosomal recessive disorders Fanconi Anemia and Bloom syndrome. In total, screening of all exons in these genes in 438 breast cancer families identified three with truncating mutations in FANCC and two with truncating mutations in BLM. Additional screening of FANCC mutation hotspot exons identified one pathogenic mutation among an additional 957 breast cancer families. Importantly, none of the deleterious mutations were identified among 464 healthy controls and are not reported in the 1,000 Genomes data. Given the rarity of Fanconi Anemia and Bloom syndrome disorders among Caucasian populations, the finding of multiple deleterious mutations in these critical DNA repair genes among high-risk breast cancer families is intriguing and suggestive of a predisposing role. Our data demonstrate the utility of intra-family exome-sequencing approaches to uncover cancer predisposition genes, but highlight the major challenge of definitively validating candidates where the incidence of sporadic disease is high, germline mutations are not fully penetrant, and individual predisposition genes may only account for a tiny proportion of breast cancer families.
Higgins, Geoff S; Prevo, Remko; Lee, Yin-Fai
The effectiveness of radiotherapy treatment could be significantly improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues. However, many of the key therapeutically exploitable mechanisms that determine intrinsic tumor...... radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B......) and irradiated normal tissue cells (MRC5). Using gammaH2AX foci at 24 hours after IR, we identified several genes, such as BRCA2, Lig IV, and XRCC5, whose knockdown is known to cause increased cell radiosensitivity, thereby validating the primary screening end point. In addition, we identified POLQ (DNA...
Maletzki, Claudia; Huehns, Maja; Bauer, Ingrid; Ripperger, Tim; Mork, Maureen M; Vilar, Eduardo; Klöcking, Sabine; Zettl, Heike; Prall, Friedrich; Linnebacher, Michael
Mismatch-repair deficient (MMR-D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood-form of constitutional mismatch repair-deficiency (CMMR-D); caused by bi-allelic MMR gene mutations. A hallmark of LS-associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR-D patients are thought to display a somatic mutation pattern differing from LS. This study has the main goal to identify cFSM in MSI target genes relevant in CMMR-D and to compare the spectrum of common somatic mutations, including alterations in DNA polymerases POLE and D1 between LS and CMMR-D. CMMR-D-associated tumors harbored more somatic mutations compared to LS cases, especially in the TP53 gene and in POLE and POLD1, where novel mutations were additionally identified. Strikingly, MSI in classical mononucleotide markers BAT40 and CAT25 was frequent in CMMR-D cases. MSI-target gene analysis revealed mutations in CMMR-D-associated tumors, some of them known to be frequently hit in LS, such as RNaseT2, HT001, and TGFβR2. Our results imply a general role for these cFSM as potential new drivers of MMR-D tumorigenesis. © 2017 Wiley Periodicals, Inc.
Full Text Available As one of the most commonly used eukaryotic recombinant protein expression systems, P. pastoris relies heavily on the AOX1 promoter (PAOX1, which is strongly induced by methanol but strictly repressed by glycerol and glucose. However, the complicated signaling pathways involved in PAOX1 regulation when supplemented with different carbon sources are poorly understood. Here we constructed a kinase deletion library in P. pastoris and identified 27 mutants which showed peculiar phenotypes in cell growth or PAOX1 regulation. We analyzed both annotations and possible functions of these 27 targets, and then focused on the MAP kinase Hog1. In order to locate its potential downstream components, we performed the phosphoproteome analysis on glycerol cultured WT and Δhog1 strains and identified 157 differentially phosphorylated proteins. Our results identified important kinases involved in P. pastoris cell growth and PAOX1 regulation, which could serve as valuable targets for further mechanistic studies.
Anurag, Meenakshi; Punturi, Nindo; Hoog, Jeremy; Bainbridge, Matthew N; Ellis, Matthew J; Haricharan, Svasti
This study was undertaken to conduct a comprehensive investigation of the role of DNA damage repair (DDR) defects in poor outcome ER+ disease. Expression and mutational status of DDR genes in ER+ breast tumors were correlated with proliferative response in neoadjuvant aromatase inhibitor therapy trials (discovery data set), with outcomes in METABRIC, TCGA and Loi data sets (validation data sets), and in patient derived xenografts. A causal relationship between candidate DDR genes and endocrine treatment response, and the underlying mechanism, was then tested in ER+ breast cancer cell lines. Correlations between loss of expression of three genes: CETN2 (p<0.001) and ERCC1 (p=0.01) from the nucleotide excision repair (NER) and NEIL2 (p=0.04) from the base excision repair (BER) pathways were associated with endocrine treatment resistance in discovery data sets, and subsequently validated in independent patient cohorts. Complementary mutation analysis supported associations between mutations in NER and BER pathways and reduced endocrine treatment response. A causal role for CETN2, NEIL2 and ERCC1 loss in intrinsic endocrine resistance was experimentally validated in ER+ breast cancer cell lines, and in ER+ patient-derived xenograft models. Loss of CETN2, NEIL2 or ERCC1 induced endocrine treatment response by dysregulating G1/S transition, and therefore, increased sensitivity to CDK4/6 inhibitors. A combined DDR signature score was developed that predicted poor outcome in multiple patient cohorts. This report identifies DDR defects as a new class of endocrine treatment resistance drivers and indicates new avenues for predicting efficacy of CDK4/6 inhibition in the adjuvant treatment setting. Copyright ©2018, American Association for Cancer Research.
Lazarini, Mariana; Bordeaux-Rego, Pedro; Giardini-Rosa, Renata; Duarte, Adriana S S; Baratti, Mariana Ozello; Zorzi, Alessandro Rozim; de Miranda, João Batista; Lenz Cesar, Carlos; Luzo, Ângela; Olalla Saad, Sara Teresinha
Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.
Di Cagno, Massimiliano; Styskala, Jakub; Hlaváč, Jan
Four new 3-hydroxy-quinolinone derivatives with promising anticancer activity could be solubilized using liposomes as vehicle to an extent that allows their in vitro and in vivo testing without use of toxic solvent(s). A screening method to identify the maximum incorporation capacity of hydrophobic......, resulting in a 200-500-fold increase in apparent solubility. Drug-to-lipid ratios in the range of 2-5 Âµg/mg were obtained. Interestingly, the four quinolinone derivatives have shown different association tendencies with liposomes, probably due to the physicochemical properties of the different group bonded...
Schär, Primo; Herrmann, Gernot; Daly, Graham; Lindahl, Tomas
Eukaryotic DNA ligases are ATP-dependent DNA strand-joining enzymes that participate in DNA replication, repair, and recombination. Whereas mammalian cells contain several different DNA ligases, encoded by at least three distinct genes, only one DNA ligase has been detected previously in either budding yeast or fission yeast. Here, we describe a newly identified nonessential Saccharomyces cerevisiae gene that encodes a DNA ligase distinct from the CDC9 gene product. This DNA ligase shares significant amino acid sequence homology with human DNA ligase IV; accordingly, we designate the yeast gene LIG4. Recombinant LIG4 protein forms a covalent enzyme-AMP complex and can join a DNA single-strand break in a DNA/RNA hybrid duplex, the preferred substrate in vitro. Disruption of the LIG4 gene causes only marginally increased cellular sensitivity to several DNA damaging agents, and does not further sensitize cdc9 or rad52 mutant cells. In contrast, lig4 mutant cells have a 1000-fold reduced capacity for correct recircularization of linearized plasmids by illegitimate end-joining after transformation. Moreover, homozygous lig4 mutant diploids sporulate less efficiently than isogenic wild-type cells, and show retarded progression through meiotic prophase I. Spore viability is normal, but lig4 mutants appear to produce a higher proportion of tetrads with only three viable spores. The mutant phenotypes are consistent with functions of LIG4 in an illegitimate DNA end-joining pathway and ensuring efficient meiosis. PMID:9271115
Cowman, Seamus; Gethin, Georgina; Clarke, Eric; Moore, Zena; Craig, Gerardine; Jordan-O'Brien, Julie; McLain, Niamh; Strapp, Helen
To incorporate an international and multidisciplinary consensus in the determination of the research and education priorities for wound healing and tissue repair. A compelling reason for the study is the lack of an agreed list of priorities for wound care research and education. Furthermore, there is a growth in the prevalence of chronic wounds, a growth in wound care products and marketing, and an increase in clinician attendance at conferences and education programmes. The study used a survey method. A four-round eDelphi technique was used to collect responses from an international population of health professionals across 24 countries. Responses were obtained from 360 professionals representing many health care settings. The top education priorities related to the standardisation of all foundation education programmes in wound care, the inclusion of wound care in all professional undergraduate and postgraduate education programmes, selecting dressings and the prevention of pressure ulcers. The top research priorities related to the dressing selection, pressure ulcer prevention and wound infection. conclusion: Professionals from different backgrounds and countries who are engaged in wound management share a common set of priorities for research and education. Most notably, the priorities identified relate to long-established clinical challenges in wound care and underpin the principles of good patient care practices. The priorities are closely allied to an ageing population and identify many challenges ahead for practitioners engaged in wound management services. The provision of wound care is a major investment of health service resources and remains a clinical challenge today. Research is essential to building evidence-based practice and fundamental to development of quality in standards of practice; education is central to achieving competence to deliver effective care. The determination of research and education priorities is therefore an absolute requirement
Aim. To incorporate an international and multidisciplinary consensus in the determination of the research and education priorities for wound healing and tissue repair. Background. A compelling reason for the study is the lack of an agreed list of priorities for wound care research and education. Furthermore, there is a growth in the prevalence of chronic wounds, a growth in wound care products and marketing, and an increase in clinician attendance at conferences and education programmes. Design. The study used a survey method. Methods. A four-round eDelphi technique was used to collect responses from an international population of health professionals across 24 countries. Results. Responses were obtained from 360 professionals representing many health care settings. The top education priorities related to the standardisation of all foundation education programmes in wound care, the inclusion of wound care in all professional undergraduate and postgraduate education programmes, selecting dressings and the prevention of pressure ulcers. The top research priorities related to the dressing selection, pressure ulcer prevention and wound infection. Conclusion. Professionals from different backgrounds and countries who are engaged in wound management share a common set of priorities for research and education. Most notably, the priorities identified relate to long-established clinical challenges in wound care and underpin the principles of good patient care practices. The priorities are closely allied to an ageing population and identify many challenges ahead for practitioners engaged in wound management services. Relevance to clinical practice. The provision of wound care is a major investment of health service resources and remains a clinical challenge today. Research is essential to building evidence-based practice and fundamental to development of quality in standards of practice; education is central to achieving competence to deliver effective care. The
Berquist, Brian R; Singh, Dharmendra Kumar; Fan, Jinshui
XRCC1 operates as a scaffold protein in base excision repair, a pathway that copes with base and sugar damage in DNA. Studies using recombinant XRCC1 proteins revealed that: a C389Y substitution, responsible for the repair defects of the EM-C11 CHO cell line, caused protein instability; a V86R...... mutation abolished the interaction with POLbeta, but did not disrupt the interactions with PARP-1, LIG3alpha and PCNA; and an E98K substitution, identified in EM-C12, reduced protein integrity, marginally destabilized the POLbeta interaction, and slightly enhanced DNA binding. Two rare (P161L and Y576S...
Anker, Thomas Boysen; Kappel, Klemens; Eadie, Douglas
as narrative material to communicate self-identity. Finally, (c) we propose that brands deliver fuzzy experiential promises through effectively motivating consumers to adopt and play a social role implicitly suggested and facilitated by the brand. A promise is an inherently ethical concept and the article...... concludes with an in-depth discussion of fuzzy brand promises as two-way ethical commitments that put requirements on both brands and consumers....
Oliveira, Isabel; Carvalho, Ana L; Radhouani, Hajer; Gonçalves, Cristiana; Oliveira, J Miguel; Reis, Rui L
The osteochondral defect (OD) comprises the articular cartilage and its subchondral bone. The treatment of these lesions remains as one of the most problematic clinical issues, since these defects include different tissues, requiring distinct healing approaches. Among the growing applications of regenerative medicine, clinical articular cartilage repair has been used for two decades, and it is an effective example of translational medicine; one of the most used cell-based repair strategies includes implantation of autologous cells in degradable scaffolds such as alginate, agarose, collagen, chitosan, chondroitin sulfate, cellulose, silk fibroin, hyaluronic acid, and gelatin, among others. Concerning the repair of osteochondral defects, tissue engineering and regenerative medicine started to design single- or bi-phased scaffold constructs, often containing hydroxyapatite-collagen composites, usually used as a bone substitute. Biomolecules such as natural and synthetic have been explored to recreate the cartilage-bone interface through multilayered biomimetic scaffolds. In this chapter, a succinct description about the most relevant natural and synthetic biomolecules used on cartilage and bone repair, describing the procedures to obtain these biomolecules, their chemical structure, common modifications to improve its characteristics, and also their application in the biomedical fields, is given.
Ali, A.; Zahid, M.A.
The present study was aimed to identify the most promising high yielding lentil genotype for a wide range of environments of Pakistan using 8 stability measures. The experiment consisted of 12 lentil genotypes grown at 11 locations falling in different agro-ecological zones of Pakistan for 2 years during 2006/07 and 2007/08 under national uniform yield testing. The General Linear Model (GLM) of MINITAB (version 15) was used for two-way analysis of variance for lentil yield data to examine the total variation into genotypes, environments and genotype x environment interaction. The percent variation of 2 major contributors, environment and GxE interaction, was permissible to perform stability analysis to evaluate stable genotypes across the environments. The genotype x environment interaction means were used for eight stability measures (genotype mean, genotype variance, coefficient of variation, ecovalence, interaction variance, regression slope, deviation mean square, coefficient of determination). The stability measures depicted that the genotype NARC-06-1 with high mean yield (1140 kg/ha -1/), regression slope (1.09) close to unity and less statistics of remaining stability measures except high value of R/sup 2/ for yield proved to be the best within the pool of studied genotypes. The results clearly suggest that the genotype NARC-06-1 may prove to be a widely adapted high yielding stable variety for a broad spectrum of environments of Pakistan. (author)
Fazal, Nadia; Jackson, Suzanne F; Wong, Katy; Yessis, Jennifer; Jetha, Nina
In health promotion and chronic disease prevention, both best and promising practices can provide critical insights into what works for enhancing the healthrelated outcomes of individuals and communities, and how/why these practices work in different situations and contexts. The promising practices criteria were developed using the Public Health Agency of Canada's (PHAC's) existing best practices criteria as the foundation. They were modified and pilot tested (three rounds) using published interventions. Theoretical and methodological issues and challenges were resolved via consultation and in-depth discussions with a working group. The team established a set of promising practices criteria, which differentiated from the best practices criteria via six specific measures. While a number of complex challenges emerged in the development of these criteria, they were thoroughly discussed, debated and resolved. The Canadian Best Practices Portal's screening criteria allow one to screen for both best and promising practices in the fields of public health, health promotion, chronic disease prevention, and potentially beyond.
Leong, Victoria; Schilbach, Leonhard
Social interactions are fundamental for human development, and disordered social interactions are pervasive in many psychiatric disorders. Recent advances in “two-person neuroscience” have provided new tools for characterising social interactions. Accordingly, interaction-based ‘sociometrics’ hold great promise for developmental psychology and psychiatry, particularly in the early identification of social disorders.
Full Text Available Introduction: In health promotion and chronic disease prevention, both best and promising practices can provide critical insights into what works for enhancing the healthrelated outcomes of individuals and communities, and how/why these practices work in different situations and contexts. Methods: The promising practices criteria were developed using the Public Health Agency of Canada’s (PHAC’s existing best practices criteria as the foundation. They were modified and pilot tested (three rounds using published interventions. Theoretical and methodological issues and challenges were resolved via consultation and in-depth discussions with a working group. Results: The team established a set of promising practices criteria, which differentiated from the best practices criteria via six specific measures. Conclusion: While a number of complex challenges emerged in the development of these criteria, they were thoroughly discussed, debated and resolved. The Canadian Best Practices Portal’s screening criteria allow one to screen for both best and promising practices in the fields of public health, health promotion, chronic disease prevention, and potentially beyond.
Yap, Kai Lee; Kiyotani, Kazuma; Tamura, Kenji; Antic, Tatjana; Jang, Miran; Montoya, Magdeline; Campanile, Alexa; Yew, Poh Yin; Ganshert, Cory; Fujioka, Tomoaki; Steinberg, Gary D; O'Donnell, Peter H; Nakamura, Yusuke
Because of suboptimal outcomes in muscle-invasive bladder cancer even with multimodality therapy, determination of potential genetic drivers offers the possibility of improving therapeutic approaches and discovering novel prognostic indicators. Using pTN staging, we case-matched 81 patients with resected ≥pT2 bladder cancers for whom perioperative chemotherapy use and disease recurrence status were known. Whole-exome sequencing was conducted in 43 cases to identify recurrent somatic mutations and targeted sequencing of 10 genes selected from the initial screening in an additional 38 cases was completed. Mutational profiles along with clinicopathologic information were correlated with recurrence-free survival (RFS) in the patients. We identified recurrent novel somatic mutations in the gene UNC5C (9.9%), in addition to TP53 (40.7%), KDM6A (21.0%), and TSC1 (12.3%). Patients who were carriers of somatic mutations in DNA repair genes (one or more of ATM, ERCC2, FANCD2, PALB2, BRCA1, or BRCA2) had a higher overall number of somatic mutations (P = 0.011). Importantly, after a median follow-up of 40.4 months, carriers of somatic mutations (n = 25) in any of these six DNA repair genes had significantly enhanced RFS compared with noncarriers [median, 32.4 vs. 14.8 months; hazard ratio of 0.46, 95% confidence interval (CI), 0.22-0.98; P = 0.0435], after adjustment for pathologic pTN staging and independent of adjuvant chemotherapy usage. Better prognostic outcomes of individuals carrying somatic mutations in DNA repair genes suggest these mutations as favorable prognostic events in muscle-invasive bladder cancer. Additional mechanistic investigation into the previously undiscovered role of UNC5C in bladder cancer is warranted. ©2014 American Association for Cancer Research.
Catherine E Smith
Full Text Available Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.
Smith, Catherine E; Mendillo, Marc L; Bowen, Nikki; Hombauer, Hans; Campbell, Christopher S; Desai, Arshad; Putnam, Christopher D; Kolodner, Richard D
Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.
Sun, Mao-Feng; Chen, Hsin-Yi; Tsai, Fuu-Jen; Lui, Shu-Hui; Chen, Chih-Yi; Chen, Calvin Yu-Chian
Two nuclear plant disasters occurring within a span of 25 years threaten health and genome integrity both in Fukushima and Chernobyl. Search for remedies capable of enhancing DNA repair efficiency and radiation resistance in humans appears to be a urgent problem for now. XRCC4 is an important enhancer in promoting repair pathway triggered by DNA double-strand break (DSB). In the context of radiation therapy, active XRCC4 could reduce DSB-mediated apoptotic effect on cancer cells. Hence, developing XRCC4 inhibitors could possibly enhance radiotherapy outcomes. In this study, we screened traditional Chinese medicine (TCM) database, TCM Database@Taiwan, and have identified three potent inhibitor agents against XRCC4. Through molecular dynamics simulation, we have determined that the protein-ligand interactions were focused at Lys188 on chain A and Lys187 on chain B. Intriguingly, the hydrogen bonds for all three ligands fluctuated frequently but were held at close approximation. The pi-cation interactions and ionic interactions mediated by o-hydroxyphenyl and carboxyl functional groups respectively have been demonstrated to play critical roles in stabilizing binding conformations. Based on these results, we reported the identification of potential radiotherapy enhancers from TCM. We further characterized the key binding elements for inhibiting the XRCC4 activities.
Sabate Rotes, Anna; Bonnichsen, Crystal R; Reece, Chelsea L; Connolly, Heidi M; Burkhart, Harold M; Dearani, Joseph A; Eidem, Benjamin W
Novel echocardiographic techniques based on myocardial deformation have not been extensively evaluated to assess right ventricular (RV) and left ventricular (LV) response after pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot. Between 2003 and 2012, 133 patients undergoing first-time PVR after tetralogy of Fallot repair underwent echocardiographic assessment at Mayo Clinic. The last echocardiogram before PVR and 1 year after surgery were retrospectively analyzed with Velocity Vector Imaging. Mean age at PVR was 35.5 ± 16.2 years (54% women). Longitudinal peak systolic strain and strain rate before PVR were low: for the left ventricle, -14.8 ± 3.5% and -0.8 ± 0.2 sec(-1), and for the right ventricle, -16.2 ± 4.1% and -0.9 ± 0.3 sec(-1), respectively. There was no significant change in either parameter after surgery. A close correlation between LV and RV deformational parameters was found before PVR and was maintained after surgery. In the multivariate analysis, patients with better LV and RV peak systolic strain preoperatively were found to have better LV and RV peak systolic strain after surgery (P = .004 and P = .006, respectively). However, patients with the most improvement in deformation were those with worse RV function preoperatively (P = .002). Mean New York Heart Association class at early follow-up improved from 2.2 ± 0.8 to 1.2 ± 0.6 (P tetralogy of Fallot undergoing PVR, and there was no significant change after surgery. However, preoperative systolic deformational parameters were predictive of postoperative ventricular function and New York Heart Association class after PVR and may be helpful to identify optimal timing for surgical intervention in this cohort. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
McAlpine, J N; El Hallani, S; Lam, S F; Kalloger, S E; Luk, M; Huntsman, D G; MacAulay, C; Gilks, C B; Miller, D M; Lane, P M
Optical imaging systems are robust, portable, relatively inexpensive, and have proven utility in detecting precancerous lesions in the lung, esophagus, colon, oral cavity and cervix. We describe the use of light-induced endogenous fluorescence (autofluorescence) in identifying preinvasive and occult carcinomas in ex vivo samples of human fallopian tube (FT) epithelium. Women undergoing surgery for an i) ovarian mass, ii) a history suggestive of hereditary breast-ovarian cancer, or iii) known serous ovarian cancer following neoadjuvant chemotherapy (NAC) were approached for informed consent. Immediately following surgery, FT's were photographed in reflectance and fluorescence at high resolution. Images included: (1) white-light reflectance of luminal/epithelial surface; (2) narrow-band green reflectance (570 nm) (3) green autofluorescence (405/436 nm excitation); and (4) blue autofluorescence (405 nm excitation). Areas revealing a loss of natural tissue fluorescence or marked increase in tissue microvasculature were recorded and compared to final histopathologic diagnosis (SEE-FIM protocol). Fifty-six cases involving one or both fallopian tubes underwent reflectance and fluorescence visualization. Nine cases were excluded, either secondary to non-ovarian primary pathology (7) or excessive trauma (2) rendering tissue interpretation impossible. Of the 47 cases remaining, there were 11 high grade serous (HGS) and 9 non-serous ovarian carcinomas undergoing primary debulking surgery, 5 serous carcinomas having received NAC, 8 benign ovarian tumors, and 14 women undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). Methodology was feasible, efficient, and reproducible. TIC or carcinoma was identified in 7/11 HGS, 3/5 NAC, and 1/14 RRBSO. Optical images were reviewed to determine test positive or negative based on standardized criteria. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the entire
Wegman, Raymond F
Provides repair methods for adhesive bonded and composite structures; identifies suitable materials and equipment for repairs; describes damage evaluation criteria and techniques, and methods of inspection before and after repair.
Jerome, Mairin A; Gillenwater, Justin; Laub, Donald R; Osler, Turner; Allan, Anna Y; Restrepo, Carolina; Campbell, Alex
To compare anthropometric z-scores with incidence of post-operative complications for patients undergoing primary cleft lip or palate repair. This was a retrospective observational analysis of patients from a surgical center in Assam, India, and includes a cohort from a single surgical mission completed before the opening of the center. Patients included in the study underwent surgery during an Operation Smile mission before the opening of Operation Smile's Guwahati Comprehensive Cleft Care Center in Guwahati, India. The remaining cohort received treatment at the center. All patients received preoperative assessment and screening; surgery; and postoperative care, education, and follow-up. Our sample size included 1941 patients and consisted of all patients with complete information in the database who returned for follow-up after receiving primary cleft lip repair or primary cleft palate repair between January 2011 and April 2013. Preoperative anthropometric measurements. Postoperative complications. Anthropometric z-scores were not a significant predictor of adverse surgical outcomes in the group analyzed. Palate surgery had increased risk of complication versus lip repair, with an overall odds ratio of 5.66 (P < .001) for all patients aged 3 to 228 months. Anthropometric z-scores were not correlated with increased risk of surgical complications, possibly because patients were well screened for malnutrition before surgery at this center. Primary palate repair is associated with an approximate fivefold increased risk of developing postoperative complication(s) compared with primary lip repair.
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
Full Text Available Deciphering the mechanisms regulating the generation of new neurons and new oligodendrocytes, the myelinating cells of the central nervous system, is of paramount importance to address new strategies to replace endogenous damaged cells in the adult brain and foster repair in neurodegenerative diseases. Upon brain injury, the extracellular concentrations of nucleotides and cysteinyl-leukotrienes (cysLTs, two families of endogenous signaling molecules, are markedly increased at the site of damage, suggesting that they may act as "danger signals" to alert responses to tissue damage and start repair. Here we show that, in brain telencephalon, GPR17, a recently deorphanized receptor for both uracil nucleotides and cysLTs (e.g., UDP-glucose and LTD(4, is normally present on neurons and on a subset of parenchymal quiescent oligodendrocyte precursor cells. We also show that induction of brain injury using an established focal ischemia model in the rodent induces profound spatiotemporal-dependent changes of GPR17. In the lesioned area, we observed an early and transient up-regulation of GPR17 in neurons expressing the cellular stress marker heat shock protein 70. Magnetic Resonance Imaging in living mice showed that the in vivo pharmacological or biotechnological knock down of GPR17 markedly prevents brain infarct evolution, suggesting GPR17 as a mediator of neuronal death at this early ischemic stage. At later times after ischemia, GPR17 immuno-labeling appeared on microglia/macrophages infiltrating the lesioned area to indicate that GPR17 may also acts as a player in the remodeling of brain circuitries by microglia. At this later stage, parenchymal GPR17+ oligodendrocyte progenitors started proliferating in the peri-injured area, suggesting initiation of remyelination. To confirm a specific role for GPR17 in oligodendrocyte differentiation, the in vitro exposure of cortical pre-oligodendrocytes to the GPR17 endogenous ligands UDP-glucose and LTD(4
Hengel, Sarah R; Spies, M Ashley; Spies, Maria
To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop resistance to radiation and DNA-damaging chemotherapeutics. Chemical inhibition of the key DNA repair proteins and pharmacologically induced synthetic lethality have become instrumental in both dissecting the complex DNA repair networks and as promising anticancer agents. The difficulty in capitalizing on synthetically lethal interactions in cancer cells is that many potential targets do not possess well-defined small-molecule binding determinates. In this review, we discuss several successful campaigns to identify and leverage small-molecule inhibitors of the DNA repair proteins, from PARP1, a paradigm case for clinically successful small-molecule inhibitors, to coveted new targets, such as RAD51 recombinase, RAD52 DNA repair protein, MRE11 nuclease, and WRN DNA helicase. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ismayilov, H.; Potters, Jan
We set up an experiment with pre-play communication to study the impact of promise elicitation by trustors from trustees on trust and trustworthiness. When given the opportunity a majority of trustors solicits a promise from the trustee. This drives up the promise making rate by trustees to almost
... is surgery to repair birth defects of the spine and spinal membranes. Meningocele and myelomeningocele ... is covered by a sterile dressing. Your child may then be transferred to a neonatal intensive ...
Muth, Thomas R [ORNL; Peter, William H [ORNL
The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.
Van Zeeland, A.A.
In this chapter a series of DNA repair pathways are discussed which are available to the cell to cope with the problem of DNA damaged by chemical or physical agents. In the case of microorganisms our knowledge about the precise mechanism of each DNA repair pathway and the regulation of it has been improved considerably when mutants deficient in these repair mechanisms became available. In the case of mammalian cells in culture, until recently there were very little repair deficient mutants available, because in almost all mammalian cells in culture at least the diploid number of chromosomes is present. Therefore the frequency of repair deficient mutants in such populations is very low. Nevertheless because replica plating techniques are improving some mutants from Chinese hamsters ovary cells and L5178Y mouse lymphoma cells are now available. In the case of human cells, cultures obtained from patients with certain genetic diseases are available. A number of cells appear to be sensitive to some chemical or physical mutagens. These include cells from patients suffering from xeroderma pigmentosum, Ataxia telangiectasia, Fanconi's anemia, Cockayne's syndrome. However, only in the case of xeroderma pigmentosum cells, has the sensitivity to ultraviolet light been clearly correlated with a deficiency in excision repair of pyrimidine dimers. Furthermore the work with strains obtained from biopsies from man is difficult because these cells generally have low cloning efficiencies and also have a limited lifespan in vitro. It is therefore very important that more repair deficient mutants will become available from established cell lines from human or animal origin
Since its launch in September 2015, Heads Up America has collected information on nearly 125 promise programs across the country, many of which were instituted long before President Barack Obama announced the America's College Promise (ACP) plan in 2015. At least 27 new free community college programs have launched in states, communities, and at…
Department of Housing and Urban Development — This tool assists applicants to HUD's Promise Zone initiative prepare data to submit with their application by allowing applicants to draw the exact location of the...
Roberts, III, Herbert Chidsey; Simpson, Stanley F.
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.
Hein, Jim; Bundy, Mike
This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…
Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose
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.
When NASA needed a real-time, online database system capable of tracking documentation changes in its propulsion test facilities, engineers at Stennis Space Center joined with ECT International, of Brookfield, Wisconsin, to create a solution. Through NASA's Dual-Use Program, ECT developed Exdata, a software program that works within the company's existing Promise software. Exdata not only satisfied NASA s requirements, but also expanded ECT s commercial product line. Promise, ECT s primary product, is an intelligent software program with specialized functions for designing and documenting electrical control systems. An addon to AutoCAD software, Promis e generates control system schematics, panel layouts, bills of material, wire lists, and terminal plans. The drawing functions include symbol libraries, macros, and automatic line breaking. Primary Promise customers include manufacturing companies, utilities, and other organizations with complex processes to control.
Rathore, Shakuntla; Joshi, Pankaj Kumar; Gaur, Sudha
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecule that encode it's genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many one million individual molecular lesions per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions include potentially harmful mutation in cell's genome which affect the survival of it's daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. Inherited mutation that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary non polyposis colorectal cancer (HNPCC) is strongly associated with specific mutation in the DNA mismatch repair pathway. BRCA1, BRCA2 two famous mutation conferring a hugely increased risk of breast cancer on carrier, are both associated with a large number of DNA repair pathway, especially NHEJ and homologous recombination. Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing most typically cancer cells are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Modern cancer treatment attempt to localize the DNA damage to cells and tissue only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). (author)
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.
Repairing and Upgrading Your PC delivers start-to-finish instructions, simple enough for even the most inexperienced PC owner, for troubleshooting, repairing, and upgrading your computer. Written by hardware experts Robert Bruce Thompson and Barbara Fritchman Thompson, this book covers it all: how to troubleshoot a troublesome PC, how to identify which components make sense for an upgrade, and how to tear it all down and put it back together. This book shows how to repair and upgrade all of your PC's essential components.
Harichane, Y; Hirata, A; Dimitrova-Nakov, S; Granja, I; Goldberg, A; Kellermann, O; Poliard, A
Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-based therapies.
Dos Vultos, Tiago; Mestre, Olga; Tonjum, Tone; Gicquel, Brigitte
Our understanding of Mycobacterium tuberculosis DNA repair mechanisms is still poor compared with that of other bacterial organisms. However, the publication of the first complete M. tuberculosis genome sequence 10 years ago boosted the study of DNA repair systems in this organism. A first step in the elucidation of M. tuberculosis DNA repair mechanisms was taken by Mizrahi and Andersen, who identified homologs of genes involved in the reversal or repair of DNA damage in Escherichia coli and related organisms. Genes required for nucleotide excision repair, base excision repair, recombination, and SOS repair and mutagenesis were identified. Notably, no homologs of genes involved in mismatch repair were identified. Novel characteristics of the M. tuberculosis DNA repair machinery have been found over the last decade, such as nonhomologous end joining, the presence of Mpg, ERCC3 and Hlr - proteins previously presumed to be produced exclusively in mammalian cells - and the recently discovered bifunctional dCTP deaminase:dUTPase. The study of these systems is important to develop therapeutic agents that can counteract M. tuberculosis evolutionary changes and to prevent adaptive events resulting in antibiotic resistance. This review summarizes our current understanding of the M. tuberculosis DNA repair system.
... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...
Full Text Available Alterations of the subchondral bone are pathological features associated with spontaneous osteochondral repair following an acute injury and with articular cartilage repair procedures. The aim of this review is to discuss their incidence, extent and relevance, focusing on recent knowledge gained from both translational models and clinical studies of articular cartilage repair. Efforts to unravel the complexity of subchondral bone alterations have identified (1 the upward migration of the subchondral bone plate, (2 the formation of intralesional osteophytes, (3 the appearance of subchondral bone cysts, and (4 the impairment of the osseous microarchitecture as potential problems. Their incidence and extent varies among the different small and large animal models of cartilage repair, operative principles, and over time. When placed in the context of recent clinical investigations, these deteriorations of the subchondral bone likely are an additional, previously underestimated, factor that influences the long-term outcome of cartilage repair strategies. Understanding the role of the subchondral bone in both experimental and clinical articular cartilage repair thus holds great promise of being translated into further improved cell- or biomaterial-based techniques to preserve and restore the entire osteochondral unit.
Jungmann, Pia M.; Baum, Thomas; Bauer, Jan S.; Karampinos, Dimitrios C.; Link, Thomas M.; Li, Xiaojuan; Trattnig, Siegfried; Rummeny, Ernst J.; Woertler, Klaus; Welsch, Goetz H.
Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair. PMID:24877139
Pia M. Jungmann
Full Text Available Background. New quantitative magnetic resonance imaging (MRI techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, and diffusion weighted imaging (DWI are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.
Atkinson, Mark J; Lohs, Jan; Kuhagen, Ilka; Kaufman, Julie; Bhaidani, Shamsu
This proof of concept (POC) study was designed to evaluate the use of an Internet-based bulletin board technology to aid parallel cross-cultural development of thematic content for a new set of patient-reported outcome measures (PROs). The POC study, conducted in Germany and the United States, utilized Internet Focus Groups (IFGs) to assure the validity of new PRO items across the two cultures--all items were designed to assess the impact of excess facial oil on individuals' lives. The on-line IFG activities were modeled after traditional face-to-face focus groups and organized by a common 'Topic' Guide designed with input from thought leaders in dermatology and health outcomes research. The two sets of IFGs were professionally moderated in the native language of each country. IFG moderators coded the thematic content of transcripts, and a frequency analysis of code endorsement was used to identify areas of content similarity and difference between the two countries. Based on this information, draft PRO items were designed and a majority (80%) of the original participants returned to rate the relative importance of the newly designed questions. The use of parallel cross-cultural content analysis of IFG transcripts permitted identification of the major content themes in each country as well as exploration of the possible reasons for any observed differences between the countries. Results from coded frequency counts and transcript reviews informed the design and wording of the test questions for the future PRO instrument(s). Subsequent ratings of item importance also deepened our understanding of potential areas of cross-cultural difference, differences that would be explored over the course of future validation studies involving these PROs. The use of IFGs for cross-cultural content development received positive reviews from participants and was found to be both cost and time effective. The novel thematic coding methodology provided an empirical platform on which to
Chaoqi, Fu; Ying, Wang; Kun, Zhao; Yangjun, Gao
Invulnerability is not the only factor of importance when considering complex networks' security. It is also critical to have an effective and reasonable repair strategy. Existing research on network repair is confined to the static model. The dynamic model makes better use of the redundant capacity of repaired nodes and repairs the damaged network more efficiently than the static model; however, the dynamic repair model is complex and polytropic. In this paper, we construct a dynamic repair model and systematically describe the energy-transfer relationships between nodes in the repair process of the failure network. Nodes are divided into three types, corresponding to three structures. We find that the strong coupling structure is responsible for secondary failure of the repaired nodes and propose an algorithm that can select the most suitable targets (nodes or links) to repair the failure network with minimal cost. Two types of repair strategies are identified, with different effects under the two energy-transfer rules. The research results enable a more flexible approach to network repair.
Lund, Jens Friis; Sungusia, Eliezeri; Mabele, Mathew Bukhi
REDD+ is an ambition to reduce carbon emissions from deforestation and forest degradation in the Global South. This ambition has generated unprecedented commitment of political support and financial funds for the forest-development sector. Many academics and people-centered advocacy organizations...... have conceptualized REDD+ as an example of ‘‘green grabbing” and have voiced fears of a potential global rush for land and trees. In this paper we argue that, in practice and up until now, REDD+ resembles longstanding dynamics of the development and conservation industry, where the promise of change...... becomes a discursive commodity that is constantly reproduced and used to generate value and appropriate financial resources. We thus argue for a re-conceptualization of REDD+ as a conservation fad within the broader political economy of development and conservation. We derive this argument from a study...
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
Street, Matthew; Thambyah, Ashvin; Dray, Michael; Amirapu, Satya; Tuari, Donna; Callon, Karen E; McIntosh, Julie D; Burkert, Kristina; Dunbar, P Rod; Coleman, Brendan; Cornish, Jillian; Musson, David S
Rotator cuff tears can cause significant pain and functional impairment. Without surgical repair, the rotator cuff has little healing potential, and following surgical repair, they are highly prone to re-rupture. Augmenting such repairs with a biomaterial scaffold has been suggested as a potential solution. Extracellular matrix (ECM)-based scaffolds are the most commonly used rotator cuff augments, although to date, reports on their success are variable. Here, we utilize pre-clinical in vitro and in vivo assays to assess the efficacy of a novel biomaterial scaffold, ovine forestomach extracellular matrix (OFM), in augmenting rotator cuff repair. OFM was assessed in vitro for primary tenocyte growth and adherence, and for immunogenicity using an assay of primary human dendritic cell activation. In vivo, using a murine model, supraspinatus tendon repairs were carried out in 34 animals. Augmentation with OFM was compared to sham surgery and unaugmented control. At 6- and 12-week time points, the repairs were analysed biomechanically for strength of repair and histologically for quality of healing. OFM supported tenocyte growth in vitro and did not cause an immunogenic response. Augmentation with OFM improved the quality of healing of the repaired tendon, with no evidence of excessive inflammatory response. However, there was no biomechanical advantage of augmentation. The ideal rotator cuff tendon augment has not yet been identified or clinically implemented. ECM scaffolds offer a promising solution to a difficult clinical problem. Here, we have shown improved histological healing with OFM augmentation. Identifying materials that offset the poorer mechanical properties of the rotator cuff post-injury/repair and enhance organised tendon healing will be paramount to incorporating augmentation into surgical treatment of the rotator cuff.
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.
Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan
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
This supplement of the Revista Médica del Instituto Mexicano del Seguro Social includes 10 original contributions, and also six current themes, all of them related to childhood obesity. It is the result of an institutional program that it has been identified as Redes de Investigación Institucional, and it has been promoted and developed by the Coordinación de Investigación of the Instituto Mexicano del Seguro Social.
Coppens, C.H.; Engel-Hoek, L. van den; Scharbatke, H.E.; Groot, S.A. de; Draaisma, J.M.T.
Dysphagia is a common problem in children with repaired oesophageal atresia (OA). Abnormalities in the oropharyngeal and oesophageal phase have hardly been studied. The aims of this study were to assess the prevalence of dysphagia in children with repaired OA and to identify and differentiate oral
Mara, Leo M.
Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.
commitments with differently imagined futures. I argue that promises are constitutive of the stem cell biology, rather than being derivative of it. Since the biological concept of stem cells is predicated on the future that they promise, the biological life of stem cells is inextricably intertwined...... patients’ bodies in anticipation of materializing the promises of stem cell biology, they are produced as a new form of biovaluable. The promises of biology move beyond the closed circuit of scientific knowledge production, and proliferate in the speculative marketplaces of promises. Part II looks at how...... of technologized biology and biological time can appear promising with the backdrop of the imagined intransigence of social, political, and economic order in the Korean society....
Randall D. McKinnon
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.
Desai, Amar; Webb, Bryan; Gerson, Stanton L.
Background: Radioresistance in human tumors has been linked in part to a subset of cells termed cancer stem cells (CSCs). The prominin 1 (CD133) cell surface protein is proposed to be a marker enriching for CSCs. We explore the importance of DNA repair in contributing to radioresistance in CD133+ lung cancer cells. Materials and methods: A549 and H1299 lung cancer cell lines were used. Sorted CD133+ cells were exposed to either single 4 Gy or 8 Gy doses and clonogenic survival measured. ϒ-H2AX immunofluorescence and quantitative real time PCR was performed on sorted CD133+ cells both in the absence of IR and after two single 4 Gy doses. Lentiviral shRNA was used to silence repair genes. Results: A549 but not H1299 cells expand their CD133+ population after single 4 Gy exposure, and isolated A549 CD133+ cells demonstrate IR resistance. This resistance corresponded with enhanced repair of DNA double strand breaks (DSBs) and upregulated expression of DSB repair genes in A549 cells. Prior IR exposure of two single 4 Gy doses resulted in acquired DNA repair upregulation and improved repair proficiency in both A549 and H1299. Finally Exo1 and Rad51 silencing in A549 cells abrogated the CD133+ IR expansion phenotype and induced IR sensitivity in sorted CD133+ cells. Conclusions: CD133 identifies a population of cells within specific tumor types containing altered expression of DNA repair genes that are inducible upon exposure to chemotherapy. This altered gene expression contributes to enhanced DSB resolution and the radioresistance phenotype of these cells. We also identify DNA repair genes which may serve as promising therapeutic targets to confer radiosensitivity to CSCs
The Collision Repair Campaign targets meaningful risk reduction in the Collision Repair source category to reduce air toxic emissions in their communities. The Campaign also helps shops to work towards early compliance with the Auto Body Rule.
... medicines Problems breathing You may not recover full vision. ... detachments can be repaired. Failure to repair the retina always results in loss of vision to some degree. After surgery, the quality of ...
Thompson, L.H.; Weber, C.A.; Jones, N.J.
Several genes involved in mammalian DNA repair pathways were identified by complementation analysis and chromosomal mapping based on hybrid cells. Eight complementation groups of rodent mutants defective in the repair of uv radiation damage are now identified. At least seven of these genes are probably essential for repair and at least six of them control the incision step. The many genes required for repair of DNA cross-linking damage show overlap with those involved in the repair of uv damage, but some of these genes appear to be unique for cross-link repair. Two genes residing on human chromosome 19 were cloned from genomic transformants using a cosmid vector, and near full-length cDNA clones of each gene were isolated and sequenced. Gene ERCC2 efficiently corrects the defect in CHO UV5, a nucleotide excision repair mutant. Gene XRCC1 normalizes repair of strand breaks and the excessive sister chromatid exchange in CHO mutant EM9. ERCC2 shows a remarkable /approximately/52% overall homology at both the amino acid and nucleotide levels with the yeast RAD3 gene. Evidence based on mutation induction frequencies suggests that ERCC2, like RAD3, might also be an essential gene for viability. 100 refs., 4 tabs
Daley, George Q.
Stem cells are the seeds of tissue repair and regeneration and a promising source for novel therapies. However, apart from hematopoietic stem cell (HSC) transplantation for hematologic disease, essentially all other stem cell treatments remain experimental. High hopes have inspired numerous clinical trials, but it has been difficult to obtain unequivocal evidence for robust clinical benefit, likely owing to our primitive state of knowledge about therapeutic mechanisms. Outside the standard cl...
Cormac W. Joyce, MB BCh
Conclusions: We demonstrated that a 4-strand knotless, barbed method attained comparable strength to that of the traditional Adelaide repair technique. The barbed method had a significantly reduced cross-sectional area at the repair site compared with the Adelaide group. The 2-mm gap formation force was less in the barbed group than the Adelaide group. Barbed repairs show promise for tendon repairs; this simple method warrants further study in an animal model.
O'Donnell, Thomas F X; Li, Chun; Swerdlow, Nicholas J; Liang, Patric; Pothof, Alexander B; Patel, Virendra I; Giles, Kristina A; Malas, Mahmoud B; Schermerhorn, Marc L
Conflicting reports exist regarding whether patients undergoing surgery on the weekend or later in the week experience worse outcomes. We identified patients undergoing abdominal aortic aneurysm (AAA) repair in the Vascular Quality Initiative between 2009 and 2017 [n = 38,498; 30,537 endovascular aneurysm repair (EVAR) and 7961 open repair]. We utilized mixed effects logistic regression to compare adjusted rates of perioperative mortality based on the day of repair. Tuesday was the most common day for elective repair (22%), Friday for symptomatic repairs (20%), and ruptured aneurysms were evenly distributed. Patients with ruptured aneurysms experienced similar adjusted mortality whether they underwent repair during the week or on weekends. Transfers of ruptured AAA were more common over the weekend. However, patients transferred on the weekend experienced higher adjusted mortality than those transferred during the week (28% vs 21%, P = 0.02), despite the fact that during the week, transferred patients actually experienced lower adjusted mortality than patients treated at the index hospital (21% vs 31%, P AAA repair. However, patients with ruptured AAA transferred on the weekend experienced higher mortality than those transferred during the week, suggesting a need for improvement in weekend transfer processes.
Full Text Available Abstract Background The Host Cell Reactivation Assay (HCRA is widely used to identify circumstances and substances affecting the repair capacity of cells, however, it is restricted by the transfection procedure used and the sensitivity of the detection method. Primary skin cells are particularly difficult to transfect, and therefore sensitive methods are needed to detect any variations due to the cell-type or inter-individual differences or changes induced by diverse substances. A sensitive and repeatable method to detect the repair capacity of skin cells would be useful in two different aspects: On the one hand, to identify substances influencing the repair capacity in a positive manner (these substances could be promising ingredients for cosmetic products and on the other hand, to exclude the negative effects of substances on the repair capacity (this could serve as one step further towards replacing or at least reducing animal testing. Results In this paper, we present a rapid and sensitive assay to determine the repair capacity of primary keratinocytes, melanocytes and fibroblasts based on two wave-length Green Fluorescent Protein (GFP and DsRed reporter technology in order to test different substances and their potential to influence the DNA repair capacity. For the detection of plasmid restoration, we used FACS technology, which, in comparison to luminometer technology, is highly sensitive and allows single cell based analysis. The usefulness of this assay and studying the repair capacity is demonstrated by the evidence that DNA repair is repressed by Cyclosporin A in fibroblasts. Conclusions The methodology described in this paper determines the DNA repair capacity in different types of human skin cells. The described transfection protocol is suitable for the transfection of melanocytes, keratinocytes and fibroblasts, reaching efficacies suitable for the detection of the restored plasmids by FACS technology. Therefore the repair capacity
Aragones, Enriqueta; Palfrey, Thomas R.; Postlewaite, Andrew
We analyze conditions under which candidates' reputations may affect voters' beliefs over what policy will be implemented by the winning candidate of an election. We develop a model of repeated elections with complete information in which candidates are purely ideological. We analyze an equilibrium in which voters' strategies involve a credible threat to punish candidates who renege on their campaign promises and in which all campaign promises are believed by voters and honored by candidates....
Schuh, Joseph; Mitchell, Brent; Locklear, Louis; Belson, Martin A.; Al-Shihabi, Mary Jo Y.; King, Nadean; Norena, Elkin; Hardin, Derek
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.
Experiments on the combined action of radiation and a DNA inhibitor using Crepis roots and on split-dose irradiation of human lymphocytes lead to the conclusion that there are two types of repair. The 'regular' repair takes place twice in each mitotic cycle and ensures the maintenance of genetic stability. The 'emergency' repair is induced at all stages of the mitotic cycle by high levels of injury. (author)
Coppens, C.H.; Engel-Hoek, L. van den; Scharbatke, H.E.; Groot, S.A. de; Draaisma, J.M.T.
Dysphagia is a common problem in children with repaired oesophageal atresia (OA). Abnormalities in the oropharyngeal and oesophageal phase have hardly been studied. The aims of this study were to assess the prevalence of dysphagia in children with repaired OA and to identify and differentiate oral and pharyngeal dysphagia based on videofluoroscopic swallow study (VFSS) findings in a limited number of children in this cohort. Medical records of 111 patients, born between January 1996 and July ...
Andresen, Kristoffer; Rosenberg, Jacob
Background For the repair of inguinal hernias, several surgical methods have been presented where the purpose is to place a mesh in the preperitoneal plane through an open access. The aim of this systematic review was to describe preperitoneal repairs with emphasis on the technique. Data sources...... A systematic review was conducted and reported according to the PRISMA statement. PubMed, Cochrane library and Embase were searched systematically. Studies were included if they provided clinical data with more than 30 days follow up following repair of an inguinal hernia with an open preperitoneal mesh......-analysis. Open preperitoneal techniques with placement of a mesh through an open approach seem promising compared with the standard anterior techniques. This systematic review provides an overview of these techniques together with a description of surgical methods and clinical outcomes....
Andresen, Kristoffer; Rosenberg, Jacob
BACKGROUND: For the repair of inguinal hernias, several surgical methods have been presented where the purpose is to place a mesh in the preperitoneal plane through an open access. The aim of this systematic review was to describe preperitoneal repairs with emphasis on the technique. DATA SOURCES......: A systematic review was conducted and reported according to the PRISMA statement. PubMed, Cochrane library and Embase were searched systematically. Studies were included if they provided clinical data with more than 30 days follow up following repair of an inguinal hernia with an open preperitoneal mesh......-analysis. Open preperitoneal techniques with placement of a mesh through an open approach seem promising compared with the standard anterior techniques. This systematic review provides an overview of these techniques together with a description of surgical methods and clinical outcomes....
Monoexponential repair kinetics is based on the assumption of a single, dose-independent rate of repair of sublethal injury in the target cells for tissue injury after exposure to ionizing radiation. Descriptions of the available data based on this assumption have proved fairly successful for both acutely responding (skin, lip mucosa, gut) and late-responding (lung, spinal cord) normal tissues. There are indications of biphasic exponential repair in both categories, however. Unfortunately, the data usually lack sufficient resolution to permit unambiguous determination of the repair rates. There are also indications that repair kinetics may depend on the size of the dose. The data are conflicting on this account, however, with suggestions of both faster and slower repair after larger doses. Indeed, experiments that have been explicitly designed to test this hypothesis show either no effect (gut, spinal cord), faster repair after higher doses (lung, kidney), or slower repair after higher doses (skin). Monoexponential repair appears to be a fairly accurate description that provides an approximation to a more complicated picture, the elucidation of whose details will, however, require very careful and extensive experimental study. (author). 30 refs.; 1 fig
Kubosch, Eva Johanna; Lang, Gernot Michael; Fürst, David
for the treatment of large, isolated, full thickness cartilage defects. Several disadvantages such as the need for two surgical procedures or hypertrophic regenerative cartilage, underline the need for alternative cell sources. OBJECTIVE: Mesenchymal stem cells, particularly synovium-derived mesenchymal stem cells......, represent a promising cell source. Synovium-derived mesenchymal stem cells have attracted considerable attention since they display great chondrogenic potential and less hypertrophic differentiation than mesenchymal stem cells derived from bone marrow. The aim of this review was to summarize the current...... knowledge on the chondrogenic potential for synovial stem cells in regard to cartilage repair purposes. RESULTS: A literature search was carried out identifying 260 articles in the databases up to January 2017. Several in vitro and initial animal in vivo studies of cartilage repair using synovia stem cell...
Joost, Patrick; Veurink, Nynke; Holck, Susanne
BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...
Hennessy, Stephen S.; Conrad, Rex
This teacher's guide contains 14 units on snowmobile repair: (1) introduction to snowmobile repair; (2) skis, front suspension, and steering; (3) drive clutch; (4) drive belts; (5) driven clutch; (6) chain drives; (7) jackshafts and axles; (8) rear suspension; (9) tracks; (10) shock absorbers; (11) brakes; (12) engines; (13) ignition and…
Fission yeast S. pombe is assumed to be a good model for cloning of human DNA repair genes, because human gene is normally expressed in S. pombe and has a very similar protein sequence to yeast protein. We have tried to elucidate the DNA repair mechanisms of S. pombe as a model system for those of mammals. (J.P.N.)
In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...
Ratcliffe, Anthony; Butler, David L; Dyment, Nathaniel A; Cagle, Paul J; Proctor, Christopher S; Ratcliffe, Seena S; Flatow, Evan L
Enhanced tendon and ligament repair would have a major impact on orthopaedic surgery outcomes, resulting in reduced repair failures and repeat surgeries, more rapid return to function, and reduced health care costs. Scaffolds have been used for mechanical and biologic reinforcement of repair and regeneration with mixed results. This review summarizes efforts made using biologic and synthetic scaffolds using rotator cuff and ACL as examples of clinical applications, discusses recent advances that have shown promising clinical outcomes, and provides insight into future therapy. PMID:25650098
Marais, Karen B.
One class of maintenance optimization problems considers the notion of general repair maintenance policies where systems are repaired or replaced on failure. In each case the optimality is based on minimizing the total maintenance cost of the system. These cost-centric optimizations ignore the value dimension of maintenance and can lead to maintenance strategies that do not maximize system value. This paper applies these ideas to the general repair optimization problem using a semi-Markov decision process, discounted cash flow techniques, and dynamic programming to identify the value-optimal actions for any given time and system condition. The impact of several parameters on maintenance strategy, such as operating cost and revenue, system failure characteristics, repair and replacement costs, and the planning time horizon, is explored. This approach provides a quantitative basis on which to base maintenance strategy decisions that contribute to system value. These decisions are different from those suggested by traditional cost-based approaches. The results show (1) how the optimal action for a given time and condition changes as replacement and repair costs change, and identifies the point at which these costs become too high for profitable system operation; (2) that for shorter planning horizons it is better to repair, since there is no time to reap the benefits of increased operating profit and reliability; (3) how the value-optimal maintenance policy is affected by the system's failure characteristics, and hence whether it is worthwhile to invest in higher reliability; and (4) the impact of the repair level on the optimal maintenance policy. -- Highlights: •Provides a quantitative basis for maintenance strategy decisions that contribute to system value. •Shows how the optimal action for a given condition changes as replacement and repair costs change. •Shows how the optimal policy is affected by the system's failure characteristics. •Shows when it is
Legters, Nettie; Balfanz, Robert; McPartland, James
Promising solutions to the failings of traditional comprehensive high schools were reviewed to identify basic principles and strategies for improving high schools nationwide. Selected research studies, policy documents, and promising high school programs were reviewed. The review revealed the following principles for helping high schools better…
Nuclear energy has distinctive merits (sustainable resources, low costs, no greenhouse gases) but its development must overcome serious hurdles (fear of accidents, radio-phobia, waste management). The large unit size of present-day reactors is compatible only with large electrical grids, and involves a high capital cost. Taking into account these different factors, the paper outlines how nuclear energy may contribute to the reduction of greenhouse gases, and which are the most promising developments. (author)
Brown, Michael F; Brown, Alexander A
Yu et al. (2016) demonstrated that algorithms designed to find efficient routes in standard mazes can be integrated with the natural processes controlling rat navigation and spatial choices, and they pointed out the promise of such "cyborg intelligence" for biorobotic applications. Here, we briefly describe Yu et al.'s work, explore its relevance to the study of comparative cognition, and indicate how work involving cyborg intelligence would benefit from interdisciplinary collaboration between behavioral scientists and engineers.
Bunkers, Sandra Schmidt
The idea of freedom as a promise of possibility is explored in this column. The core concepts from a research study on considering tomorrow (Bunkers, 1998) coupled with humanbecoming community change processes (Parse, 2003) are used to illuminate this notion. The importance of intentionality in human freedom is discussed from both a human science and a natural science perspective. © The Author(s) 2015.
Field, S.B.; Hornsey, S.
Between each fraction in radiotherapy, there is repair and recovery of both normal and neoplastic tissues. Several different types of repair have been identified. Some relate specifically to the effect of changing the number of fractions and others to the overall treatment time. Each will be discussed and particular attention will be paid to slow repair phenomena which have recently been the subject of much interest. (orig.) [de
.... Recent work, however, has identified improved equations to account for load attraction into the stiffened repaired area, and evaluate the thermally induced stresses in the repaired structure and the patch...
Eqiupment for nuclear reactor fuel assembly repairing produced by Westinghouse and Brawn Bovery companies is described. Repair of failed fuel assemblies replacement of defect fuel elements gives a noticeable economical effect. Thus if the cost of a new fuel assembly is 450-500 thousand dollars, the replacement of one fuel element in it costs approximately 40-60 thousand dollars. In simple cases repairing includes either removal of failed fuel elements from a fuel assembly and its reinsertion with the rest of fuel elements into the reactor core (reactor refueling), or replacement of unfailed fuel elements from one fuel assembly to a new one (fuel assembly overhaul and reconditioning)
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.
... incarcerated) in the hernia and become impossible to push back in. This is usually painful. The blood supply ... you are lying down or that you cannot push back in. Risks The risks of ventral hernia repair ...
... this page: //medlineplus.gov/ency/presentations/100033.htm Omphalocele repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Omphalocele is an abdominal wall defect at the base ...
Chawla, Tanveer Singh
While in service, wind turbine blades experience various modes of loading. An example is impact loading in the form of hail or bird strikes, which might lead to localized damage or formation of cracks a few plies deep on the blade surface. One of the methods to conduct repairs on wind turbine blades that are damaged while in service is hand lay-up of the repair part after grinding out the damaged portion and some of its surrounding area. The resin used for such repairs usually differs from the parent plate resin in composition and properties such as gel time, viscosity, etc. As a result the properties of the repaired parts are not the same as that of the undamaged blades. Subsequent repetitive loading can be detrimental to weak repairs to such an extent so as to cause delamination at the parent-repair bondline causing the repairs to eventually fall off the blade. Thus the strength and toughness of the repair are of critical importance. Initial part of this work consists of an effort to increase repair strength by identifying an optimum hand layup repair resin for fiberglass wind turbine blades currently being manufactured by a global company. As delamination of the repair from the parent blade is a major concern and unidirectional glass fibers along with a polymer resin are used to manufacture blades under consideration, testing method detailed in ASTM D 5528 (Test Method for Mode I Interlaminar Fracture Toughness of Unidirectional Fiber-Reinforced Polymer Matrix Composites) was followed to determine propagation fracture toughness values of the prospective vinyl ester repair resin candidates. These values were compared to those for a base polyester repair resin used by the company. Experimental procedure and results obtained from the above mentioned testing using double cantilever beam (DCB) specimens are detailed. Three new repair resins were shortlisted through mode I testing. It was also found that variation in the depth of the ground top ply of the parent part
The second edition of Chitin underscores the important factors for standardizing chitin processing and characterization. It captures the essential interplay between chitin's assets and limitations as a biomaterial, placing the past promises of chitin in perspective, addressing its present realities and offering insight into what is required to realize chitin's destiny (including its derivative, chitosan) as a biomaterial of the twenty-first century. This book is an ideal guide for both industrialists and researchers with a vested interest in commercializing chitin.An upd
Kunkel, Thomas A
This year, the Nobel Prize in Chemistry has been awarded to Tomas Lindahl, Aziz Sancar, and Paul Modrich for their seminal studies of the mechanisms by which cells from bacteria to man repair DNA damage that is generated by normal cellular metabolism and stress from the environment. These studies beautifully illustrate the remarkable power of DNA repair to influence life from evolution through disease susceptibility. Copyright © 2015 Elsevier Inc. All rights reserved.
Active integrity constraints (AICs) are a form of integrity constraints for databases that not only identify inconsistencies, but also suggest how these can be overcome. The semantics for AICs defines different types of repairs, but deciding whether an inconsistent database can be repaired...... and finding possible repairs is a NP- or Σ2p-complete problem, depending on the type of repairs one has in mind. In this paper, we introduce two different relations on AICs: an equivalence relation of independence, allowing the search to be parallelized among the equivalence classes, and a precedence relation...
Current methods of patching pavement must evolve to meet increasing mobility demands. : To address this need, MDOT has been testing a new generation of rapid set full-depth : pavement repair materials. Initial results are promising. The new materials...
Thompson, L.H.; Weber, C.A.; Brookman, K.W.; Salazar, E.P.; Stewart, S.A.; Mitchell, D.L.
The DNA repair systems of rodent and human cells appear to be at least as complex genetically as those in lower eukaryotes and bacteria. The use of mutant lines of rodent cells as a means of identifying human repair genes by functional complementation offers a new approach toward studying the role of repair in mutagenesis and carcinogenesis. In each of six cases examined using hybrid cells, specific human chromosomes have been identified that correct CHO cell mutations affecting repair of damage from uv or ionizing radiations. This finding suggests that both the repair genes and proteins may be virtually interchangeable between rodent and human cells. Using cosmid vectors, human repair genes that map to chromosome 19 have cloned as functional sequences: ERCC2 and XRCC1. ERCC1 was found to have homology with the yeast excision repair gene RAD10. Transformants of repair-deficient cell lines carrying the corresponding human gene show efficient correction of repair capacity by all criteria examined. 39 refs., 1 fig., 1 tab
Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno
Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.
Wall, Lindley B; Keener, Jay D; Brophy, Robert H
A review of the current literature will show a difference between the biomechanical properties of double-row and single-row rotator cuff repairs. Rotator cuff tears commonly necessitate surgical repair; however, the optimal technique for repair continues to be investigated. Recently, double-row repairs have been considered an alternative to single-row repair, allowing a greater coverage area for healing and a possibly stronger repair. We reviewed the literature of all biomechanical studies comparing double-row vs single-row repair techniques. Inclusion criteria included studies using cadaveric, animal, or human models that directly compared double-row vs single-row repair techniques, written in the English language, and published in peer reviewed journals. Identified articles were reviewed to provide a comprehensive conclusion of the biomechanical strength and integrity of the repair techniques. Fifteen studies were identified and reviewed. Nine studies showed a statistically significant advantage to a double-row repair with regards to biomechanical strength, failure, and gap formation. Three studies produced results that did not show any statistical advantage. Five studies that directly compared footprint reconstruction all demonstrated that the double-row repair was superior to a single-row repair in restoring anatomy. The current literature reveals that the biomechanical properties of a double-row rotator cuff repair are superior to a single-row repair. Basic Science Study, SRH = Single vs. Double Row RCR.
The Mirror Fusion Test Facility (MFTF) has been in construction at Lawrence Livermore National Laboratory (LLNL) for 3 years, and most of the major subsystems are nearing completion. Recently, the scope of this project was expanded to meet new objectives, principally to reach plasma conditions corresponding to energy break-even. To fulfill this promise, the single-cell minimum-B mirror configuration will be replaced with a tandem mirror configuration (MFTF-B). The facility must accordingly be expanded to accomodate the new geometry. This paper briefly discusses the status of the major MFTF subsystems and describes how most of the technological objectives of MFTF will be demonstrated before we install the additional systems necessary to make the tandem. It also summarizes the major features of the expanded facility
Civil engineering, mechanics and waste conditioning companies are thriving around the market of nuclear facilities dismantlement which is promised to a huge development in the coming decade. This paper presents a map of the opportunities of the dismantlement market throughout Europe (research and power reactors, fuel fabrication plants, spent fuel reprocessing plants) and a cost estimation of a given dismantling work with respect to the different steps of the work. In France a small core of about twenty companies is involved in nuclear dismantlement but the French market is also looking towards foreign specialists of this activity. The British market is also targeted by the French companies but for all the actors the technological or commercial advance gained today will be determining for the future markets. (J.S.)
Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A.
Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting
Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: email@example.com [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)
Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.
Joyce, Cormac W; Sugrue, Conor; Chan, Jeffrey C; Delgado, Luis; Zeugolis, Dimitrios; Carroll, Seam M; Kelly, Jack L
Barbed suture technology has shown promise in flexor tendon repairs, as there is an even distribution of load and the need for a knot is eliminated. We propose that a quick and simple, novel, barbed technique without any exposed barbs on the tendon surface has comparable strength and a smaller cross-sectional area at the repair site than traditional methods of repair. Forty porcine flexor tendons were randomized to polybutester 4-strand barbed repair or to 4-strand Adelaide monofilament repair. The cross-sectional area was measured before and after repair. Biomechanical testing was carried out and 2-mm gap formation force, ultimate strength of repair, and method of failure were recorded. The mean ultimate strength of the barbed repairs was 54.51 ± 17.9 while that of the Adelaide repairs was 53.17 ± 16.35. The mean 2-mm gap formation force for the barbed group was 44.71 ± 17.86 whereas that of the Adelaide group was 20.25 ± 4.99. The postrepair percentage change in cross-sectional area at the repair site for the Adelaide group and barbed group was 12.0 ± 2.3 and 4.6 ± 2.8, respectively. We demonstrated that a 4-strand knotless, barbed method attained comparable strength to that of the traditional Adelaide repair technique. The barbed method had a significantly reduced cross-sectional area at the repair site compared with the Adelaide group. The 2-mm gap formation force was less in the barbed group than the Adelaide group. Barbed repairs show promise for tendon repairs; this simple method warrants further study in an animal model.
Barber, F Alan
Arthroscopic rotator cuff repair is a commonly performed repair. Technical developments provide surgeons the tools to create biomechanically robust repairs. How can the biological response mirror the strong and stable surgery? Platelet-rich plasma (PRP) is a supraphysiological platelet concentration which may positively augment rotator cuff healing. Not all PRPs are the same. High leukocyte levels and thrombin activation may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors and may actually inhibit some parts of the healing response. Clear differences exist between liquid PRP (products released within hours after activation) and solid fibrin PRP which slowly releases factors over days. The heterogenicity data and grouping liquid and solid PRP together make systematic reviews confusing. Solid PRP fibrin constructs are often associated with increased tendon healing. PRP fibrin matrix offers the greatest promise for improving clinical success after rotator cuff tendon repair.
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
Recombinational repair may or may not be synonymous with postreplication repair. Considerable progress has been made in the study of the relevant enzymes, particularly those from bacteria. In this workshop we focus on the recombination enzyme RecA protein. What structural changes take place in the protein and in DNA during repair. How does homologous pairing take place. How is ATP hydrolysis coupled to the stand exchange reaction and the formation of heteroduplx DNA. Turning to another enzyme needed for certain kinds of bacterial recombination, we will ask whether the purified recB protein and recC protein complement each other and are sufficient for exonuclease V activity. In higher cells, we would like to know whether sister exchanges, which occur in bacteria after uv irradiation, are also seen in animal cells
Maddox, Grady E; Ludwig, Jonathan; Craig, Eric R; Woods, David; Joiner, Aaron; Chaudhari, Nilesh; Killingsworth, Cheryl; Siegal, Gene P; Eberhardt, Alan; Ponce, Brent
To compare and analyze biomechanical properties and histological characteristics of flexor tendons either repaired by a 4-strand modified Kessler technique or using barbed suture with a knotless repair technique in an in vivo model. A total of 25 chickens underwent surgical transection of the flexor digitorum profundus tendon followed by either a 4-strand Kessler repair or a knotless repair with barbed suture. Chickens were randomly assigned to 1 of 3 groups with various postoperative times to death. Harvested tendons were subjected to biomechanical testing or histologic analysis. Harvested tendons revealed failures in 25% of knotless repairs (8 of 32) and 8% of 4-strand Kessler repairs (2 of 24). Biomechanical testing revealed no significant difference in tensile strength between 4-strand Kessler and barbed repairs; however, this lack of difference may be attributed to lower statistical power. We noted a trend toward a gradual decrease in strength over time for barbed repairs, whereas we noticed the opposite for the 4-strand Kessler repairs. Mode of failure during testing differed between repair types. The barbed repairs tended toward suture breakage as opposed to 4-strand Kessler repairs, which demonstrated suture pullout. Histological analysis identified no difference in the degree of inflammation or fibrosis; however, there was a vigorous foreign body reaction around the 4-strand Kessler repair and no such response around the barbed repairs. In this model, knotless barbed repairs trended toward higher in vivo failure rates and biomechanical inferiority under physiologic conditions, with each repair technique differing in mode of failure and respective histologic reaction. We are unable to recommend the use of knotless barbed repair over the 4-strand modified Kessler technique. For the repair techniques tested, surgeons should prefer standard Kessler repairs over the described knotless technique with barbed suture. Copyright © 2015 American Society for Surgery
Jonghun Park; Laszlo Horvath; Robert J. Bush
This study documented the current status of wood pallet repair in the United States by identifying the types of processing and equipment usage in repair operations from an automation prespective. The wood pallet repair firms included in the sudy received an average of approximately 1.28 million cores (i.e., used pallets) for recovery in 2012. A majority of the cores...
Barber, F A; Herbert, M A
Meniscal repair devices not requiring accessory incisions are attractive. Many factors contribute to their clinical effectiveness including their biomechanical characteristics. This study compared several new meniscal repair devices with standard meniscal suture techniques. Using a porcine model, axis-of-insertion loads were applied to various meniscal sutures and repair devices. A single device or stitch was placed in a created meniscal tear and a load applied. Both loads and modes of failure were recorded. The load-to-failure data show stratification into 4 distinct statistical groups. Group A, 113 N for a double vertical stitch; group B, 80 N for a single vertical stitch; group C, 57 N for the BioStinger, 56 N for a horizontal mattress stitch, and 50 N for the T-Fix stitch; and group D, 33 N for the Meniscus Arrow (inserted by hand or gun), 32 N for the Clearfix screw, 31 N for the SDsorb staple, 30 N for the Mitek meniscal repair system, and 27 N for the Biomet staple. The failure mechanism varied. Sutures broke away from the knot. The Meniscus Arrow and BioStinger pulled through the inner rim with the crossbar intact. The Clearfix screw failed by multiple mechanisms, whereas 1 leg of the SDsorb staple always pulled out of the outer rim. The Mitek device usually failed by pullout from the inner rim. The Biomet staple always broke at the crosshead or just below it. Although the surgeon should be aware of the material properties of the repair technique chosen for a meniscal repair, this information is only an indication of device performance and may not correlate with clinical healing results.
Barnes, L A Fink; Kim, H M; Caldwell, J-M; Buza, J; Ahmad, C S; Bigliani, L U; Levine, W N
Advances in arthroscopic techniques for rotator cuff repair have made the mini-open approach less popular. However, the mini-open approach remains an important technique for repair for many surgeons. The aims of this study were to compare the integrity of the repair, the function of the shoulder and satisfaction post-operatively using these two techniques in patients aged > 50 years. We identified 22 patients treated with mini-open and 128 patients treated with arthroscopic rotator cuff repair of July 2007 and June 2011. The mean follow-up was two years (1 to 5). Outcome was assessed using the American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) scores, and satisfaction. The integrity of the repair was assessed using ultrasonography. A power analysis ensured sufficient enrolment. There was no statistically significant difference between the age, function, satisfaction, or pain scores (p > 0.05) of the two groups. The integrity of the repair and the mean SST scores were significantly better in the mini-open group (91% of mini-open repairs were intact versus 60% of arthroscopic repairs, p = 0.023; mean SST score 10.9 (standard deviation (sd) 1.3) in the mini-open group; 8.9 (sd 3.5) in arthroscopic group; p = 0.003). The ASES scores were also higher in the mini-open group (mean ASES score 91.0 (sd 10.5) in mini-open group; mean 82.70 (sd 19.8) in the arthroscopic group; p = 0.048). The integrity of the repair and function of the shoulder were better after a mini-open repair than after arthroscopic repair of a rotator cuff tear in these patients. The functional difference did not translate into a difference in satisfaction. Mini-open rotator cuff repair remains a useful technique despite advances in arthroscopy. Cite this article: Bone Joint J 2017;99-B:245-9. ©2017 The British Editorial Society of Bone & Joint Surgery.
In 7 chapters, the book answers the following questions: 1) What reactions are induced in biological matter by absorption of radiation energy. 2) In what parts of the cell do the radiation-induced reactions with detectable biological effects occur. 3) In which way are these cell components changed by different qualities of radiation. 4) What are the cell mechanisms by which radiation-induced changes can be repaired. 5) What is the importance of these repair processes for man, his life and evolution. At the end of each chapter, there is a bibliography of relevant publications in this field. (orig./MG) [de
It has been shown previously by others that at least two independent repair mechanisms are present in Bacillus subtilis for removing ''spore photoproduct'' from DNA of ultraviolet (254 nm)-irradiated spores after germination. One of these, designated as ''spore repair,'' is shown in this study to restore ''spore photoproduct'' to two thymine residues, leaving the DNA backbone intact at the end of the process in vivo. The circumstances under which this repair can occur and some characteristics of its energy requirements have been clarified. The second repair process is identified as excision repair, which can excise both ''spore photoproduct'' from DNA of irradiated spores and cyclobutane-type pyrimidine dimers from DNA of irradiated vegetative cells. In this study it is shown that the gene hcr 1 affects an enzyme activity for the incision step initiating this repair, while the gene hcr 42 affects a step subsequent to incision in the mechanism. In addition a third, independent repair system, termed ''germinative excision repair,'' is discovered and shown to be specific for excising only cyclobutane-type pyrimidine dimers but not ''spore photoproduct.'' This repair system is responsible for the observed high ultraviolet-resistance and temporary capacity for host cell reactivation on recently germinated spores of Bacillus subtilis HCR - strains
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.
Santos, Emanuel; Faria, Daniel; Pesquita, Catia; Couto, Francisco M
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.
National Aeronautics and Space Administration — GTL has developed an innovative composite repair methodology known as the Composite Repair System (CRS). In this phase I effort, CRS is being developed for the...
EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.
Vesicovaginal Fistula Repair During Pregnancy: A Case Report ... Abstract. We report a repair of Vesicovaginal fistula during pregnancy that was aimed at preventing another spontaneous ... practices that encourage teenage marriage and girl.
The effects of intermittent work patterns and funding on the costs of ship repair and maintenance were modeled for the San Diego region in 2002 for Supervisor of Shipbuilding and Repair (SUPSHIP) San Diego...
Ejstrup, Rasmus; Wiencke, Anne K; Toft, Peter B
PURPOSE: To investigate the functional and cosmetic results after primary surgical repair of bicanalicular lacerations. METHODS: We identified patients diagnosed with bicanalicular lacerations at the Eye Clinic of Rigshospitalet, Copenhagen from 2000 through 2009. Patient charts were reviewed and...
Ratan, Zubair Ahmed; Son, Young-Jin; Uddin, Bhuiyan Mohammad Mahtab; Yusuf, Md. Abdullah; Zaman, Sojib Bin; Kim, Jong-Hoon; Banu, Laila Anjuman
Bacteria and archaea possess adaptive immunity against foreign genetic materials through clustered regularly interspaced short palindromic repeat (CRISPR) systems. The discovery of this intriguing bacterial system heralded a revolutionary change in the field of medical science. The CRISPR and CRISPR-associated protein 9 (Cas9) based molecular mechanism has been applied to genome editing. This CRISPR-Cas9 technique is now able to mediate precise genetic corrections or disruptions in in vitro and in vivo environments. The accuracy and versatility of CRISPR-Cas have been capitalized upon in biological and medical research and bring new hope to cancer research. Cancer involves complex alterations and multiple mutations, translocations and chromosomal losses and gains. The ability to identify and correct such mutations is an important goal in cancer treatment. In the context of this complex cancer genomic landscape, there is a need for a simple and flexible genetic tool that can easily identify functional cancer driver genes within a comparatively short time. The CRISPR-Cas system shows promising potential for modeling, repairing and correcting genetic events in different types of cancer. This article reviews the concept of CRISPR-Cas, its application and related advantages in oncology. PMID:29434679
Stefano Geuna; Pierluigi Tos; Bruno Battiston
It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that,to further improve clinical outcome,the involvement of different scientific disciplines is required.This evolving reconstructive/regenerative approach is based on the interdisciplinary and integrated pillars of tissue engineering such as reconstructive microsurgery,transplantation and biomaterials.In this paper,some of the most promising innovations for the tissue engineering of nerves,emerging from basic science investigation,are critically overviewed with special focus on those approaches that appear today to be more suitable for clinical translation.
Fahnøe, Kristian Relsted
organisations, friends and family, and communities. These social relations are viewed as the foundation of citizenship as experienced and practised. Focusing on how two dimensions of lived citizenship, namely rights-responsibilities and belonging, are affected by the social repairs, the chapter shows how...
Hires, Bill; And Others
This curriculum guide contains the basic information needed to repair all two- and four-stroke cycle engines. The curriculum covers four areas, each consisting of one or more units of instruction that include performance objectives, suggested activities for teacher and students, information sheets, assignment sheets, job sheets, visual aids,…
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Thanks to the pioneering research work of Lindahl, Sancar, Modrich and their colleagues, we now have an holistic awareness of how DNA damage occurs and how the damage is rectified in bacteria as well as in higher organisms including human beings. A comprehensive understanding of DNA repair has proven crucial ...
Zaichkina, S.I.; Rozanova, O.M.; Aptikaev, G.F.; Ganassi, E.Eh.
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
... this page: //medlineplus.gov/ency/article/002979.htm Cleft lip and palate repair To use the sharing features on this ... Cheiloplasty; Cleft rhinoplasty; Palatoplasty; Tip rhinoplasty Patient Instructions Cleft lip and palate repair - discharge Images Cleft lip repair - series References ...
Regan, J.D.; Carrier, W.L.; Kusano, I.; Furuno-Fukushi, I.; Dunn, W.C. Jr.; Francis, A.A.; Lee, W.H.
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)
21 years ago, the DNA Repair Enzyme was declared "Molecule of the Year". Today, we are celebrating another "year of repair", with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.
Stormont, John [Univ. of New Mexico, Albuquerque, NM (United States)
Nanocomposite wellbore repair materials have been developed, tested, and modeled through an integrated program of laboratory testing and numerical modeling. Numerous polymer-cement nanocomposites were synthesized as candidate wellbore repair materials using various combinations of base polymers and nanoparticles. Based on tests of bond strength to steel and cement, ductility, stability, flowability, and penetrability in opening of 50 microns and less, we identified Novolac epoxy reinforced with multi-walled carbon nanotubes and/or alumina nanoparticles to be a superior wellbore seal material compared to conventional microfine cements. A system was developed for testing damaged and repaired wellbore specimens comprised of a cement sheath cast on a steel casing. The system allows independent application of confining pressures and casing pressures while gas flow is measured through the specimens along the wellbore axis. Repair with the nanocomposite epoxy base material was successful in dramatically reducing the flow through flaws of various sizes and types, and restoring the specimen comparable to an intact condition. In contrast, repair of damaged specimens with microfine cement was less effective, and the repair degraded with application of stress. Post-test observations confirm the complete penetration and sealing of flaws using the nanocomposite epoxy base material. A number of modeling efforts have supported the material development and testing efforts. We have modeled the steel-repair material interface behavior in detail during slant shear tests, which we used to characterize bond strength of candidate repair materials. A numerical model of the laboratory testing of damaged wellbore specimens was developed. This investigation found that microannulus permeability can satisfactorily be described by a joint model. Finally, a wellbore model has been developed that can be used to evaluate the response of the wellbore system (casing, cement, and microannulus
Rafael A. Maioli
Full Text Available ABSTRACT Objective: The purpose of this video is to present the laparoscopic repair of a VUF in a 42-year-old woman, with gross hematuria, in the immediate postoperative phase following a cesarean delivery. The obstetric team implemented conservative management, including Foley catheter insertion, for 2 weeks. She subsequently developed intermittent hematuria and cystitis. The urology team was consulted 15 days after cesarean delivery. Cystoscopy indicated an ulcerated lesion in the bladder dome of approximately 1.0cm in size. Hysterosalpingography and a pelvic computed tomography scan indicated a fistula. Materials and Methods: Laparoscopic repair was performed 30 days after the cesarean delivery. The patient was placed in the lithotomy position while also in an extreme Trendelenburg position. Pneumoperitoneum was established using a Veress needle in the midline infra-umbilical region, and a primary 11-mm port was inserted. Another 11-mm port was inserted exactly between the left superior iliac spine and the umbilicus. Two other 5-mm ports were established under laparoscopic guidance in the iliac fossa on both sides. The omental adhesions in the pelvis were carefully released and the peritoneum between the bladder and uterus was incised via cautery. Limited cystotomy was performed, and the specific sites of the fistula and the ureteral meatus were identified; thereafter, the posterior bladder wall was adequately mobilized away from the uterus. The uterine rent was then closed using single 3/0Vicryl sutures and two-layer watertight closure of the urinary bladder was achieved by using 3/0Vicryl sutures. An omental flap was mobilized and inserted between the uterus and the urinary bladder, and was fixed using two 3/0Vicryl sutures, followed by tube drain insertion. Results: The operative time was 140 min, whereas the blood loss was 100ml. The patient was discharged 3 days after surgery, and the catheter was removed 12 days after surgery
Tailored treatment is not new in radiotherapy; it has been the major subject for the last 20-30 years. Radiation responses and RBE (relative biological effectiveness) depend on assay systems, endpoints, type of tissues and tumors, radiation quality, dose rate, dose fractionation, physiological and environmental factors etc, Latent times to develop damages also differ among tissues and endpoints depending on doses and radiation quality. Recent progress in clarification of radiation induced cell death, especially of apoptotic cell death, is quite important for understanding radiosensitivity of tumor cure process as well as of tumorigenesis. Apoptotic cell death as well as dormant cells had been unaccounted and missed into a part of reproductive cell death. Another area of major progress has been made in clarifying repair mechanisms of radiation damage, i.e., non-homologous end joining (NHEJ) and homologous recombinational repair (HRR). New approaches and developments such as cDNA or protein micro arrays and so called informatics in addition to basic molecular biological analysis are expected to aid identifying molecules and their roles in signal transduction pathways, which are multi-factorial and interactive each other being involved in radiation responses. (authors)
Moeller, Benjamin J.; Sidman, Richard L.; Pasqualini, Renata; Arap, Wadih
Small molecule inhibitors of DNA repair are emerging as potent and selective anti-cancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. To address this challenge, we used a subtractive combinatorial selection approach to identify a panel of peptide ligands that bind DNA repair complexes. Supporting the concept that these ligands have therapeutic potential, we show that one selected peptide specifically binds and non-competitively inactivates DNA-PKcs, a protein kinase critical in double-strand DNA break repair. In doing so, this ligand sensitizes BRCA-deficient tumor cells to genotoxic therapy. Our findings establish a platform for large-scale parallel screening for ligand-directed DNA repair inhibitors, with immediate applicability to cancer therapy. PMID:21343400
The following topics are discussed; public policy for setting radiation standards; use of linear, nonthreshold theory in setting radiation standards; dose-rate dependence; occupational exposure to radiation; radon inhalation from radium in the soil in the vicinity of the phosphate industry; relation of repair mechanisms for cell survival to cancer induction; application of information on genetic repair to humans and to cancer induction; importance of repair processes in radiation protection standards; corrective factors for repair processes; relation of repair processes to age, sex, and other factors; and population distribution in radiosensitivity
Williams, Timothy K; Clouse, W Darrin
Extremity venous injury management remains controversial. The purpose of this communication is to offer perspective as well as experiential and technical insight into extremity venous injury repair. Available literature is reviewed and discussed. Historical context is provided. Indication, the decision process for repair, including technical conduct, is delineated. In particular, the authors' experiences in both civilian and wartime injury are used for perspective. Extremity venous injury repair was championed within data from the Vietnam Vascular Registry. However, patterns of extremity venous injury differ between combat and civilian settings. Since Vietnam, civilian descriptive series opine the benefits and potential complications associated with both venous injury repair and ligation. These surround extremity edema, chronic venous insufficiency, thromboembolism, and limb loss. Whereas no clear superiority in either approach has been identified to date, there appears to be no increased risk of pulmonary embolism or chronic venous changes with repair. Newer data from the wars in Iraq and Afghanistan and meta-analysis have reinforced this and also have suggested limb salvage benefit for extremity venous repair in combined arterial and venous injuries in modern settings. The patient's physiologic state and associated injury drive five triage categories suggesting vein injury management. Vein repair thrombosis occurs in a significant proportion, yet many recanalize and possibly have a positive impact on limb venous return. Further, early decompression favors reduced blood loss, acute edema, and inflammation, supporting collateral development. Large soft tissue injury minimizing collateral capacity increases the importance of repair. Constructs of repair are varied with modest differences in patency. Venous shunting is feasible, but specific roles remain nebulous. An aggressive posture toward extremity venous injury repair seems justified today because of the likely
Guenther, Paul L; Lesko, Jon M; Stedman, Donald H
In return for a temporary waiver from converting five vehicles to operate on compressed natural gas (CNG) for the Denver Clean Fuels program, the University of Denver identified, tested, repaired, and retested nine employee commuter vehicles. The results of the study validated the concept that employer-based identification and repair programs can be carried out in a cost-effective way. On average, each repaired vehicle removed fifty times more carbon monoxide (CO) emissions from Denver air than each CNG conversion. The average cost of each repair was eight times less than the average cost of each conversion. The average fuel economy benefit from the repairs was enough to pay for the average cost of repairs in less than three years of normal driving. When the expected lifetimes of repairs and conversions are included, the targeted repair program appears to be over sixty times more cost-effective as a CO emissions reduction strategy than CNG conversion.
Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.
Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...... base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby...
Mollon, Brent; Mahure, Siddharth A; Ensor, Kelsey L; Zuckerman, Joseph D; Kwon, Young W; Rokito, Andrew S
To quantify the incidence of and identify the risk factors for subsequent shoulder procedures after isolated SLAP repair. New York's Statewide Planning and Research Cooperative System database was searched between 2003 and 2014 to identify individuals with the sole diagnosis of a SLAP lesion who underwent isolated arthroscopic SLAP repair. Patients were longitudinally followed up for a minimum of 3 years to analyze for subsequent ipsilateral shoulder procedures. Between 2003 and 2014, 2,524 patients met our inclusion criteria. After 3 to 11 years of follow-up, 10.1% of patients (254 of 2,524) underwent repeat surgical intervention on the same shoulder as the initial SLAP repair. The mean time to repeat shoulder surgery was 2.3 ± 2.1 years. Subsequent procedures included subacromial decompression (35%), debridement (26.7%). repeat SLAP repair (19.7%), and biceps tenodesis or tenotomy (13.0%). After isolated SLAP repair, patients aged 20 years or younger were more likely to undergo arthroscopic Bankart repair (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.36-6.21; P = .005), whereas age older than 30 years was an independent risk factor for subsequent acromioplasty (OR, 2.3; 95% CI, 1.4-3.7; P surgery after isolated SLAP repair, often related to an additional diagnosis, suggesting that clinicians should consider other potential causes of shoulder pain when considering surgery for patients with SLAP lesions. In addition, the number of isolated SLAP repairs performed has decreased over time, and management of failed SLAP repair has shifted toward biceps tenodesis or tenotomy over revision SLAP repair in more recent years. Level III, case-control study. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Blackwell, Ryan; Schmitt, Laura C; Flanigan, David C; Magnussen, Robert A
The goal of this study is to determine whether patients who smoke cigarettes at the time of surgery are at significantly increased risk of early meniscus repair failure relative to non-smokers. Retrospective chart review identified 64 current smokers within a series of 444 consecutive patients who underwent meniscus repair during a 7 years period. Fifty-two of these 64 smokers were available for follow-up and were matched by age, sex, and ACL status with non-smokers from the same cohort. Records of these 104 patients with a total of 120 meniscus repairs were reviewed to identify meniscus repair failure (defined as repeat surgery on the index meniscus) during the median 13-month (range: 3-79 months) follow-up period. The smoking and non-smoking groups were similar in age, sex, ACL status, BMI, meniscus repair technique, and meniscus involved. Meniscus repair failure occurred in 19 of the 112 menisci in 104 patients, for an overall failure risk of 17 %. Of the 19 failures, 14 occurred in 79 repaired medial menisci (18 % failure risk) and 5 occurred in 33 repaired lateral menisci (15 % failure risk). Meniscus repair failure occurred in significantly more smokers (15 failures in 56 menisci in 52 patients -27 % failure risk) than non-smokers (4 failures in 56 menisci in 52 patients -7 % failure risk) (p = 0.0076). Smoking is associated with significantly increased risk of early meniscus repair failure as defined by the incidence of repeat surgery on the index meniscus. III.
Conway, L.; Carelli, M.D.; Dzodzo, M. [Westinghouse Science and Technology, Pittsburgh, PA (United States); Hossain, Q.; Brown, N.W. [Lawrence Livermore National Lab., CA (United States); Wade, D.C.; Sienick, J.J. [Argonne National Lab., IL (United States); Greenspan, E.; Kastenberg, W.E.; Saphier, D. [University of California Dept of Nuclear Engineering, Berkeley, CA (United States)
Promising design options for the Encapsulated Nuclear Heat Source (ENHS) liquid-metal cooled fast reactor were identified during the first year of the DOE NERI program sponsored feasibility study. Many opportunities for incorporation of innovations in design and fabrication were identified. Three of the innovations are hereby described: a novel IHX (intermediate heat exchanger) made of a relatively small number of rectangular channels, an ENHS module design featuring 100% natural circulation, and a novel conceptual design of core support and fuelling. As a result of the first year study the ENHS concept appears more practical and more promising than perceived at the outset of this study. (authors)
Conway, L.; Carelli, M.D.; Dzodzo, M.; Hossain, Q.; Brown, N.W.; Wade, D.C.; Sienick, J.J.; Greenspan, E.; Kastenberg, W.E.; Saphier, D.
Promising design options for the Encapsulated Nuclear Heat Source (ENHS) liquid-metal cooled fast reactor were identified during the first year of the DOE NERI program sponsored feasibility study. Many opportunities for incorporation of innovations in design and fabrication were identified. Three of the innovations are hereby described: a novel IHX (intermediate heat exchanger) made of a relatively small number of rectangular channels, an ENHS module design featuring 100% natural circulation, and a novel conceptual design of core support and fuelling. As a result of the first year study the ENHS concept appears more practical and more promising than perceived at the outset of this study. (authors)
Chin, Christopher J; Kus, Lukas; Rotenberg, Brian W
The purpose of our article is to review the use of the DuraSeal Sealant System (Confluent Surgical Inc., Waltham, MA) in the repair of complex cerebrospinal fluid (CSF) leaks in endoscopic skull-base surgery. Retrospective chart review. London Health Sciences Centre. A database of endoscopic skull-base cases between 2007 and 2009 that involved CSF leakage repaired with DuraSeal was created. Demographic data and operative reports were collected and analyzed qualitatively. Recurrence of CSF leak after repair. Five cases were identified that met study criteria. In four of the five cases, the repair was successful. There were no complications related to DuraSeal use. Comparison to a subset of patients using Tisseel Fibrin Sealant (Baxter, Toronto, ON) for repair did not show a significant difference in failure rate (χ2 = 0.029, p = .858). There are a variety of techniques described to repair CSF rhinorrhea, with various studies demonstrating the advantages of using tissue glues in CSF leak repairs. We used DuraSeal in five patients to enhance graft strength and form a watertight seal. The system was effective in the majority of patients. Our study is the first to report on endoscopic endonasal repair of CSF leaks using DuraSeal.
Hallén, Magnus; Westerdahl, Johan; Nordin, Pär; Gunnarsson, Ulf; Sandblom, Gabriel
Previous studies have suggested that the use of mesh in groin hernia repair may be associated with an increased risk for male infertility as a result of inflammatory obliteration of structures in the spermatic cord. In a recent study, we could not find an increased incidence of involuntary childlessness. The aim of this study was to evaluate this issue further. Men born between 1950 and 1989, with a hernia repair registered in the Swedish Hernia Register between 1992 and 2007 were cross-linked with all men in the same age group with the diagnosis of male infertility according to the Swedish National Patient Register. The cumulative and expected incidences of infertility were analyzed. Separate multivariate logistic analyses, adjusted for age and years elapsed since the first repair, were performed for men with unilateral and bilateral repair, respectively. Overall, 34,267 men were identified with a history of at least 1 inguinal hernia repair. A total of 233 (0.7%) of these had been given the diagnosis of male infertility after their first operation. We did not find any differences between expected and observed cumulative incidences of infertility in men operated with hernia repair. Men with bilateral hernia repair had a slightly increased risk for infertility when mesh was used on either side. However, the cumulative incidence was less than 1%. Inguinal hernia repair with mesh is not associated with an increased incidence of, or clinically important risk for, male infertility. Copyright © 2012 Mosby, Inc. All rights reserved.
Abtahi, Amir M; Granger, Erin K; Tashjian, Robert Z
Rotator cuff repair has been shown to have good long-term results. Unfortunately, a significant proportion of repairs still fail to heal. Many factors, both patient and surgeon related, can influence healing after repair. Older age, larger tear size, worse muscle quality, greater muscle-tendon unit retraction, smoking, osteoporosis, diabetes and hypercholesterolemia have all shown to negatively influence tendon healing. Surgeon related factors that can influence healing include repair construct-single vs double row, rehabilitation, and biologics including platelet rich plasma and mesenchymal stem cells. Double-row repairs are biomechanically stronger and have better healing rates compared with single-row repairs although clinical outcomes are equivalent between both constructs. Slower, less aggressive rehabilitation programs have demonstrated improved healing with no negative effect on final range of motion and are therefore recommended after repair of most full thickness tears. Additionally no definitive evidence supports the use of platelet rich plasma or mesenchymal stem cells regarding improvement of healing rates and clinical outcomes. Further research is needed to identify effective biologically directed augmentations that will improve healing rates and clinical outcomes after rotator cuff repair. PMID:25793161
Photolyase is a flavin photoenzyme that repairs two DNA base damage products induced by ultraviolet (UV) light: cyclobutane pyrimidine dimers and 6-4 photoproducts. With femtosecond spectroscopy and site-directed mutagenesis, investigators have recently made significant advances in our understanding of UV-damaged DNA repair, and the entire enzymatic dynamics can now be mapped out in real time. For dimer repair, six elementary steps have been characterized, including three electron transfer reactions and two bond-breaking processes, and their reaction times have been determined. A unique electron-tunneling pathway was identified, and the critical residues in modulating the repair function at the active site were determined. The dynamic synergy between the elementary reactions for maintaining high repair efficiency was elucidated, and the biological nature of the flavin active state was uncovered. For 6-4 photoproduct repair, a proton-coupled electron transfer repair mechanism has been revealed. The elucidation of electron transfer mechanisms and two repair photocycles is significant and provides a molecular basis for future practical applications, such as in rational drug design for curing skin cancer.
Soni, Shelly; Moldenhauer, Julie S; Spinner, Susan S; Rendon, Norma; Khalek, Nahla; Martinez-Poyer, Juan; Johnson, Mark P; Adzick, N Scott
Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure. The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes. This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined. A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were
state of leapin- fn’rw.rd. Tn recent years, many mechanical repair workers often write and ask us to reprint the book. In our consideration, however...ast 4iron 1. .-eat _--OSIS-RTS 5.5 . . 4-5 t4- cast -3.01 -6 ~.0 ’ ɘ. 5,,:e j?24 2 * 10- 5 aron C l 50 S lcon : Ielt rSSIS-RQTS-s;.4 u a 2.47 5at- .0
McNickle, Allison G; Provencher, Matthew T; Cole, Brian J
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.
Dietz, Volker; Schwab, Martin E
Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.
Mahapatra, Piyush; Horriat, Saman; Anand, Bobby S
review the current literature with regards to bio-enhancement in the form platelet rich plasma, bio-scaffolds and stem cells. On the basis of current evidence, there appears to be a role for bio-enhancement, however, this is not yet translated into clinical practice. Several promising avenues of further research now exist in the form of mechanical and biological augmentation techniques. Further work is clearly needed but there is renewed interest and focus for primary ACL repair that may yet prove the new frontier in ligament repair.
Azzam, Michael G; Dugas, Jeffrey R; Andrews, James R; Goldstein, Samuel R; Emblom, Benton A; Cain, E Lyle
Rotator cuff tears are rare injuries in adolescents but cause significant morbidity if unrecognized. Previous literature on rotator cuff repairs in adolescents is limited to small case series, with few data to guide treatment. Adolescent patients would have excellent functional outcome scores and return to the same level of sports participation after rotator cuff repair but would have some difficulty with returning to overhead sports. Case series; Level of evidence 4. A retrospective search of the practice's billing records identified all patients participating in at least 1 sport who underwent rotator cuff repair between 2006 and 2014 with an age Rotator Cuff Index. Thirty-two consecutive adolescent athletes (28 boys and 4 girls) with a mean age of 16.1 years (range, 13.2-17.9 years) met inclusion criteria. Twenty-nine patients (91%) had a traumatic event, and 27 of these patients (93%) had no symptoms before the trauma. The most common single tendon injury was to the supraspinatus (21 patients, 66%), of which 2 were complete tendon tears, 1 was a bony avulsion of the tendon, and 18 were high-grade partial tears. Fourteen patients (56%) underwent single-row repair of their rotator cuff tear, and 11 (44%) underwent double-row repair. All subscapularis injuries were repaired in open fashion, while all other tears were repaired arthroscopically. Twenty-seven patients (84%) completed the outcome questionnaires at a mean 6.2 years after surgery (range, 2-10 years). The mean ASES score was 93 (range, 65-100; SD = 9); mean Western Ontario Rotator Cuff Index, 89% (range, 60%-100%; SD = 13%); and mean numeric pain rating, 0.3 (range, 0-3; SD = 0.8). Overall, 25 patients (93%) returned to the same level of play or higher. Among overhead athletes, 13 (93%) were able to return to the same level of play, but 8 (57%) were forced to change positions. There were no surgical complications, but 2 patients did undergo a subsequent operation. Surgical repair of high-grade partial
Tao, Xu; Liu, Junpeng; Chen, Lei; Zhou, You; Tang, Kanglai
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.
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.
Mathematical models are the only way of examining the return of radioactivity from nuclear waste to the environment over long periods of time. Work in Britain has helped identify areas where more basic data is required, but initial results look very promising for final disposal of high level waste in hard rock repositories. A report by the National Radiological Protection Board of a recent study, is examined.
Tolver, Mette Astrup; Rosenberg, Jacob; Bisgaard, Thue
. Furthermore, snowball search was performed in reference lists of identified articles. Randomized controlled trials and prospective comparative or non-comparative trials of high quality were included. Trials with ≥100 patients, >18 years of age and manuscripts in English were included. Scoring systems were...... used for assessment of quality. RESULTS: The literature search identified 1039 papers. Thirty-four trials were included in the final review including 14,273 patients. There was overall a large variation in duration of convalescence. Trials using non-restrictive recommendations of 1-2 days or "as soon...... factors for prolonged convalescence extending more than a few days after laparoscopic inguinal hernia repair. CONCLUSIONS: Patients should be recommended a duration of 1-2 days of convalescence after laparoscopic inguinal hernia repair. Short and non-restrictive recommendations may reduce duration...
Whitelock, R.G.; Dyce, J.; Houlton, J.E.F.
The records and radiographs of 24 dogs that underwent femoral trochanteric osteotomy repair were reviewed. Osteotomy repair was performed with either a pin and tension band wire or a lag screw technique. Significant clinical complications associated with the osteotomy were identified in one dog (4 per cent) six weeks after surgery, although abnormal radiographic changes were evident in 15 dogs (62 per cent). The method of repair did not influence healing and there were comparable radiographic complication rates. It is concluded that femoral trochanteric osteotomy is not associated with significant clinical problems, despite a high incidence of abnormal radiographic findings
.... Additionally, research was conducted to document the management process for determining repair requirements at the Naval Inventory Control Point Philadelphia and how those requirements are accepted...
Klarskov, Louise Laurberg; Ladelund, Steen; Holck, Susanne
Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliabi......Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data...... on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein...... variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance...
Raudner, M.; Roehrich, S.; Zalaudek, M.; Trattnig, S.; Schreiner, M.M.
Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account. (orig.) [de
One of the 21st century’s most promising technologies is nanotechnology. Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve. Nanotechnology is a collective term referring to technological developments on the nanometer scale, usually 0.1-100 nm. A nanometer is one-billionth of a meter, too small to be seen with a conventional laboratory microscope. It ...
Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda
In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…
Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao
Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.
Lambert, J.A.; Gilston, P.F.
A preliminary assessment has been carried out to determine the suitability of the hot wire tungsten inert gas (TIG) welding process for the repair of thick section, ferritic steel nuclear pressure vessels. The objective has been to identify a hot wire TIG temper bead procedure, suitable for repairs without post weld heat treatment. This procedure involves depositing two weld layers with carefully selected welding parameters such that overlapping thermal cycles produce a refined and tempered heat affected zone, HAZ, microstructure. (author)
Seung Taek Ji
Full Text Available The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration.
Hashimoto, Daniel A; Rosman, Guy; Rus, Daniela; Meireles, Ozanan R
The aim of this review was to summarize major topics in artificial intelligence (AI), including their applications and limitations in surgery. This paper reviews the key capabilities of AI to help surgeons understand and critically evaluate new AI applications and to contribute to new developments. AI is composed of various subfields that each provide potential solutions to clinical problems. Each of the core subfields of AI reviewed in this piece has also been used in other industries such as the autonomous car, social networks, and deep learning computers. A review of AI papers across computer science, statistics, and medical sources was conducted to identify key concepts and techniques within AI that are driving innovation across industries, including surgery. Limitations and challenges of working with AI were also reviewed. Four main subfields of AI were defined: (1) machine learning, (2) artificial neural networks, (3) natural language processing, and (4) computer vision. Their current and future applications to surgical practice were introduced, including big data analytics and clinical decision support systems. The implications of AI for surgeons and the role of surgeons in advancing the technology to optimize clinical effectiveness were discussed. Surgeons are well positioned to help integrate AI into modern practice. Surgeons should partner with data scientists to capture data across phases of care and to provide clinical context, for AI has the potential to revolutionize the way surgery is taught and practiced with the promise of a future optimized for the highest quality patient care.
Fujita, B; Zimmermann, W-H
There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM). © 2017 American Society for Clinical Pharmacology and Therapeutics.
Luiten, EEM; Akkerman, [No Value; Koulman, A; Kamermans, P; Reith, H; Barbosa, MJ; Sipkema, D; Wijffels, RH
High-quality research in the field of marine biotechnology is one of the key-factors for successful innovation in exploiting the vast diversity of marine life. However, fascinating scientific research with promising results and claims on promising potential applications (e.g. for pharmaceuticals,
Luiten, E.E.M.; Akkerman, I.; Koulman, A.; Kamermans, P.; Reith, H.; Barbosa, M.J.; Sipkema, D.; Wijffels, R.H.
High-quality research in the field of marine biotechnology is one of the key-factors for successful innovation in exploiting the vast diversity of marine life. However, fascinating scientific research with promising results and claims on promising potential applications (e.g. for pharmaceuticals,
Littlepage, Ben; Clark, Teresa; Wilson, Randal; Stout, Logan
Community colleges in Tennessee, either directly or indirectly, experienced unprecedented change as a result of Tennessee Promise. The present study explored how student support service administrators at three community colleges responded to organizational change as a result of the Tennessee Promise legislation. Investigators selected community…
Brittberg, Mats; Gomoll, Andreas H; Canseco, José A; Far, Jack; Lind, Martin; Hui, James
Background and purpose Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints. PMID:27910738
Sauvaigo, S.; Sarrazy, F.; Breton, J.; Caillat, S.; Chapuis, V.
Radiation therapy is an essential part of cancer treatment as about 50% of patients will receive radiations at least once. Significant broad variation in radiosensitivity has been demonstrated in patients. About 5-10% of patients develop acute toxicity after radiotherapy. Therefore there is a need for the identification of markers able to predict the occurrence of adverse effects and thus adapt the radiotherapy regimen for radiosensitive patients. As a first step toward this goal, and considering the DNA repair defects associated with hypersensitivity radiation syndromes, we investigated the DNA repair phenotype of patients receiving radiotherapy. More precisely, we used a functional repair assay on support to follow the evolution of the glycosylases/AP endonuclease activities of PBMCs extracts of a series of patients during the time course of radiotherapy. For each patient, we collected one PBMCs sample before the first radiotherapy application (S1) and three samples after (S2 to S4) (one day and one week after application 1, and one at the end of the radiotherapy protocol). These four samples have been analysed for 11 donors. Clustering analyses of the results demonstrated a great heterogeneity of responses among the patients. Interestingly, this heterogeneity decreased between S1 and S4 where only 2 classes of patients remained if we except one patient that exhibited an atypical DNA repair phenotype. Furthermore, we showed that repair of several oxidized bases significantly increased between S1 and S3 or S4 (8oxoG, thymine glycol, A paired with 8oxoG), suggesting an adaptation of patients repair systems to the oxidative stress generated by the ionising radiations. Our preliminary results provided evidence that the DNA repair phenotype was impacted by the radiotherapy regimen. Further characterization of patients with known repair defects are needed to determine if atypical repair phenotypes could be associated with radiotherapy complications. Finally
Embree, Mildred C.; Chen, Mo; Pylawka, Serhiy; Kong, Danielle; Iwaoka, George M.; Kalajzic, Ivo; Yao, Hai; Shi, Chancheng; Sun, Dongming; Sheu, Tzong-Jen; Koslovsky, David A.; Koch, Alia; Mao, Jeremy J.
Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues. PMID:27721375
Zhou, Ye; Notterpek, Lucia
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.
Chromosome mapping of repair genes involved in U.V. sensitivity is reported. Twenty-three of 25 hybrid cells were resistant to U.V. light. Survival curves of 2 U.V.-resistant cell strains, which possessed mouse chromosomes and human chromosome No.7 - 16, were similar to those of wild strain (L5178Y). On the other hand, survival curves of U.V.-sensitive hybrid cells was analogous to those of Q31. There was a definitive difference in the frequency of inducible chromosome aberrations between U.V. resistant and sensitive mouse-human hybrid cells. U.V.-resistant cell strains possessed the ability of excision repair. Analysis of karyotype in hybrid cells showed that the difference in U.V. sensitivity is dependent upon whether or not human chromosome No.13 is present. Synteny test on esterase D-determining locus confirmed that there is an agreement between the presence of chromosome No.13 and the presence of human esterase D activity. These results led to a conclusion that human genes which compensate recessive character of U.V.-sensitive mutant strain, Q31, with mouse-human hybrid cells are located on the locus of chromosome No.13. (Namekawa, K.)
Kanzow, Philipp; Wiegand, Annette; Göstemeyer, Gerd; Schwendicke, Falk
Repair instead of complete replacement is recommended to manage partially defective restorations. It is unclear if and why such treatment is taught at dental schools or practiced by dentists. We aimed to identify barriers and facilitators for repairs using a systematic review and meta- and qualitative analysis. Electronic databases (PubMed, CENTRAL, Embase, PsycINFO) were searched. Quantitative studies reporting on the proportion of (1) dentists stating to perform repairs, (2) dental schools teaching repairs, (3) failed restorations having been repaired were included. We also included qualitative studies on barriers/facilitators for repairs. Random-effects meta-analyses, meta-regression and a thematic analysis using the theoretical domains framework were conducted. 401 articles were assessed and 29, mainly quantitative, studies included. 7228 dentists and 276 dental schools had been surveyed, and treatment data of 30,172 restorations evaluated. The mean (95% CI) proportion of dentists stating to perform repairs was 71.5% (49.7-86.4%). 83.3% (73.6-90.0%) of dental schools taught repairs. 31.3% (26.3-36.7%) of failed restorations had been repaired. More recent studies reported significantly more dentists to repair restorations (p=0.004). Employment in public health practices and being the dentist who placed the original restoration were facilitators for repairs. Amalgam restorations were repaired less often, and financial aspects and regulations came as barriers. While most dentists state to perform repairs and the vast majority of dental schools teach repairs, the proportion of truly repaired restorations was low. A number of interventions to implement repair in dental practice can be deduced from our findings. Partially defective restorations are common in dental practice. While repairs are taught and dentists are aware of the recommendation towards repairs, the actually performed proportion of repairs seems low. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available The article focuses on the approaches to the process and methods of expenditure audit on repair and modernization of fixed assets and the author considers that there is no single approach to understanding the issue. The author improves the organizational and methodological support of internal audit of expenditures on the fixed assets repair and modernization that forms the accurate information for management repair and modernization of fixed assets. The paper specifies the goals and objectives of internal expenditures on repair and modernization of fixed assets, depending on the sources of such facilities to the company, allowing the author to determine the documentary control methods to be applied by an auditor to perform each task. The article determines the areas of risk components of internal control that can lead to ineffective implementation of authority by officials of an enterprise in the process of fixed assets repair, which can cause inefficient use of resources and, consequently, decrease in the efficiency of the work of fixed assets repair and modernization. The author proposes the list of auditor’s questions to assess the internal control system in the repair of fixed assets and these questions will help identify the significant drawbacks of control means.
Data repairing aims at discovering and correcting erroneous data in databases. In this paper, we develop Web-ADARE, an end-to-end web-aided data repairing system, to provide a feasible way to involve the vast data sources on the Web in data repairing. Our main attention in developing Web-ADARE is paid on the interaction problem between web-aided repairing and rule-based repairing, in order to minimize the Web consultation cost while reaching predefined quality requirements. The same interaction problem also exists in crowd-based methods but this is not yet formally defined and addressed. We first prove in theory that the optimal interaction scheme is not feasible to be achieved, and then propose an algorithm to identify a scheme for efficient interaction by investigating the inconsistencies and the dependencies between values in the repairing process. Extensive experiments on three data collections demonstrate the high repairing precision and recall of Web-ADARE, and the efficiency of the generated interaction scheme over several baseline ones.
Gu, Binbin; Li, Zhixu; Yang, Qiang; Xie, Qing; Liu, An; Liu, Guanfeng; Zheng, Kai; Zhang, Xiangliang
Data repairing aims at discovering and correcting erroneous data in databases. In this paper, we develop Web-ADARE, an end-to-end web-aided data repairing system, to provide a feasible way to involve the vast data sources on the Web in data repairing. Our main attention in developing Web-ADARE is paid on the interaction problem between web-aided repairing and rule-based repairing, in order to minimize the Web consultation cost while reaching predefined quality requirements. The same interaction problem also exists in crowd-based methods but this is not yet formally defined and addressed. We first prove in theory that the optimal interaction scheme is not feasible to be achieved, and then propose an algorithm to identify a scheme for efficient interaction by investigating the inconsistencies and the dependencies between values in the repairing process. Extensive experiments on three data collections demonstrate the high repairing precision and recall of Web-ADARE, and the efficiency of the generated interaction scheme over several baseline ones.
Paterson, M.C.; Smith, P.J.; Bech-Hansen, N.T.; Smith, B.P.; Sell, B.M.
The most significant danger to irradiated individuals is the induction of cancer. Ataxia telangiectasia (AT) is known as a disorder linking radiosensitivity with cancer proneness, and AT is a rare inherited disorder. This is the degenerative multisystem affliction that is transmitted as a simple autosomal recessive trait. Cell culture studies disclosed the relationship between the cellular hypersensitivity to γ-ray inactivation in vitro and the propensity to develop cancer in vivo. The molecular evidence for the defects in the repair of radiogenic DNA damage has as yet been obtained only for AT, and it seems likely that anomalous DNA repair may not be the key causal factor in the development of some of the clinical abnormalities associated with the disease, including the tendency to develop lymphoproliferative cancer. Nevertheless, AT, Rothmund-Thomson syndrome (RTS), and acute myelogenous leukemia (AML) family show promise as the models for elucidating the importance of cellular radiosensitivity and imperfect DNA repair in the induction of cancer by radiation and radiomimetic carcinogens in the biosphere. Expanded efforts are required to identify heterozygosity for the AT genes in general population and to assess the role of the interaction between this genetic make-up and environmental carcinogens in the occurrence of common cancers. (Yamashita, S.)
Nayeemuddin, M.; Pherwani, A.D.; Asquith, J.R.
Open repair is still considered the reference standard for long-term repair of abdominal aortic aneurysms (AAA). In contrast to endovascular aneurysm repair (EVAR), patients with open surgical repair of AAA are not routinely followed up with imaging. Although complications following EVAR are widely recognized and routinely identified on follow-up imaging, complications also do occur following open surgical repair. With frequent use of multi-slice computed tomography (CT) angiography (CTA) in vascular patients, there is now improved recognition of the potential complications following open surgical repair. Many of these complications are increasingly being managed using endovascular techniques. The aim of this review is to illustrate a variety of potential complications that may occur following open surgical repair and to demonstrate their management using both surgical and endovascular techniques.
a suitable level of anesthesia , a semi-lunar incision was made in the midline from the superior sagittal crest to the middle of the nasal bone. The...internal fixation of Fractures, and as intraosseous bone repair materials. A promising use for these polymers has been as carriers for osteogenic...acids. Oral Surg. 37:142, 1974. 7. Getter, L., Cutright, D.E., Bhaskar, S.N., and Augsburg, J.K. A biodegradable intraosseous apliance in the
Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.
BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old
This paper describes the permanent pipeline repair system, developed by Tekmar, which is powered by seawater hydraulics and is easily installed and tested by any workclass remotely operated vehicle (rov). Details are given of the two main components of the system, namely, the diverless high pressure split repair clamp and the rov-operated tool to install it.
Eijk, Patrick van
Nucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP). The yeast Saccharomyces cerevisiae is an excellent model organism to study the mechanism of NER. The
21 years ago, the DNA Repair Enzyme was declared “Molecule of the Year”. Today, we are celebrating another “year of repair”, with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.
Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo
Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain...
O'Connor, K M
BACKGROUND: This is a review of our experience with the Snodgrass technique for distal hypospadias repair and we point to lessons learned in improving results. METHODS: We reviewed all patients who underwent Snodgrass hypospadias repair for distal hypospadias over a four-year period by a single surgeon. Chart review followed by parental telephone interview was used to determine voiding function, cosmesis and complication rate. RESULTS: Thirty children and three adults were identified. Age at surgery ranged from seven months to 39 years. The urinary stream was straight in 94%, and 97% reported a good or satisfactory final cosmetic outcome. One patient (3.3%) developed a urethral fistula and 21% developed meatal stenosis which required general anaesthetic. CONCLUSION: The Snodgrass urethroplasty provides satisfactory cosmetic and functional results. High rates of meatal stenosis initially encountered have improved with modifications to technique which include modified meatoplasty and routine meatal dilatation by the parents.
Ashvin K. Dewan
Full Text Available Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells and associated scaffolds (natural or synthetic, hydrogels or membranes. ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient’s knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.
After a general review of the operation experience in the history of more than 12 operating years, the organization in the plant will be shown with special aspect to quality assurance, capacity of the workshops and connected groups as radiation protection, chemical laboratories etc. The number, time intervals and manpower effort for the repeating tests will be discussed. Reasons and examples for back-fitting activities in the plant are given. Besides special repair and maintenance procedures as repair of the steam generators, in-service inspection of the reactor pressure vessel, repair of a feed-water pipe and repair of the core structure in the pressure vessel, the general system to handle maintenance and repair-work in the KWO-plant will be shown. This includes also the detailed planning of the annual refueling and revision of the plant. (orig./RW)
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)
Hallén, Magnus; Sandblom, Gabriel; Nordin, Pär; Gunnarsson, Ulf; Kvist, Ulrik; Westerdahl, Johan
Several animal studies have raised concern about the risk for obstructive azoospermia owing to vasal fibrosis caused by the use of alloplastic mesh prosthesis in inguinal hernia repair. The aim of this study was to determine the prevalence of male infertility after bilateral mesh repair. In a prospective study, a questionnaire inquiring about involuntary childlessness, investigation for infertility and number of children was sent by mail to a group of 376 men aged 18-55 years, who had undergone bilateral mesh repair, identified in the Swedish Hernia Register (SHR). Questionnaires were also sent to 2 control groups, 1 consisting of 186 men from the SHR who had undergone bilateral repair without mesh, and 1 consisting of 383 men identified in the general population. The control group from the SHR was matched 2:1 for age and years elapsed since operation. The control group from the general population was matched 1:1 for age and marital status. The overall response rate was 525 of 945 (56%). Method of approach (anterior or posterior), type of mesh, and testicular status at the time of the repair had no significant impact on the answers to the questions. Nor did subgroup analysis of the men ≤40 years old reveal any significant differences. The results of this prospective study in men do not support the hypothesis that bilateral inguinal hernia repair with alloplastic mesh prosthesis causes male infertility at a significantly greater rate than those operated without mesh. Copyright Â© 2011 Mosby, Inc. All rights reserved.
Rodríguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguileraa, Luis Eduardo
Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40 days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40 d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.
Marino, Emanuele; Kodger, Thomas E; Crisp, Ryan W; Timmerman, Dolf; MacArthur, Katherine E; Heggen, Marc; Schall, Peter
Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We utilized atomically thin semiconductor nanoplatelets as a convenient platform for studying, both microscopically and spectroscopically, the development of defects during ligand exchange with the conductive ligands Na 4 SnS 4 and (NH 4 ) 4 Sn 2 S 6 . These defects can be repaired via mild chemical or thermal routes, through the addition of L-type ligands or wet annealing, respectively. This results in a higher-quality, conductive, colloidally stable nanomaterial that may be used as the active film in optoelectronic devices. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Castro, I.T. [Departamento de Matematicas, Facultad de Veterinaria, Universidad de Extremadura, Avenida de la Universidad, s/n. 10071 Caceres (Spain)]. E-mail: firstname.lastname@example.org; Perez-Ocon, R. [Departamento de Estadistica e Investigacion Operativa, Facultad de Ciencias, Universidad de Granada, Avenida de Severo Ochoa, s/n. 18071 Granada (Spain)]. E-mail: email@example.com
This paper analyzes a system subject to repairable and non-repairable failures. Non-repairable failures lead to replacement of the system. Repairable failures, first lead to repair but they lead to replacement after a fixed number of repairs. Operating and repair times follow phase type distributions (PH-distributions) and the pattern of the operating times is modelled by a geometric process. In this context, the problem is to find the optimal number of repairs, which maximizes the long-run average reward per unit time. To this end, the optimal number is determined and it is obtained by efficient numerical procedures.
Castro, I.T.; Perez-Ocon, R.
This paper analyzes a system subject to repairable and non-repairable failures. Non-repairable failures lead to replacement of the system. Repairable failures, first lead to repair but they lead to replacement after a fixed number of repairs. Operating and repair times follow phase type distributions (PH-distributions) and the pattern of the operating times is modelled by a geometric process. In this context, the problem is to find the optimal number of repairs, which maximizes the long-run average reward per unit time. To this end, the optimal number is determined and it is obtained by efficient numerical procedures
Cassier-Chauvat, Corinne; Veaudor, Théo; Chauvat, Franck
Cyanobacteria are fascinating photosynthetic prokaryotes that are regarded as the ancestors of the plant chloroplast; the purveyors of oxygen and biomass for the food chain; and promising cell factories for an environmentally friendly production of chemicals. In colonizing most waters and soils of our planet, cyanobacteria are inevitably challenged by environmental stresses that generate DNA damages. Furthermore, many strains engineered for biotechnological purposes can use DNA recombination to stop synthesizing the biotechnological product. Hence, it is important to study DNA recombination and repair in cyanobacteria for both basic and applied research. This review reports what is known in a few widely studied model cyanobacteria and what can be inferred by mining the sequenced genomes of morphologically and physiologically diverse strains. We show that cyanobacteria possess many E. coli-like DNA recombination and repair genes, and possibly other genes not yet identified. E. coli-homolog genes are unevenly distributed in cyanobacteria, in agreement with their wide genome diversity. Many genes are extremely well conserved in cyanobacteria (mutMS, radA, recA, recFO, recG, recN, ruvABC, ssb, and uvrABCD), even in small genomes, suggesting that they encode the core DNA repair process. In addition to these core genes, the marine Prochlorococcus and Synechococcus strains harbor recBCD (DNA recombination), umuCD (mutational DNA replication), as well as the key SOS genes lexA (regulation of the SOS system) and sulA (postponing of cell division until completion of DNA reparation). Hence, these strains could possess an E. coli-type SOS system. In contrast, several cyanobacteria endowed with larger genomes lack typical SOS genes. For examples, the two studied Gloeobacter strains lack alkB, lexA, and sulA; and Synechococcus PCC7942 has neither lexA nor recCD. Furthermore, the Synechocystis PCC6803 lexA product does not regulate DNA repair genes. Collectively, these findings
Demary, Markus; Demary, Vera
Digitization affects all sectors of the economy. A new and possibly disruptive digital technology is the blockchain, a decentralized ledger, which seems to offer great promise for many financial and business applications.
Thames, H.D. Jr.; Peters, L.J.
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.)
Evans, Jemma; Yap, Joanne; Gamage, Thillini; Salamonsen, Lois; Dimitriadis, Evdokia; Menkhorst, Ellen
Menstruation involves the shedding of the functional layer of the endometrium in the absence of pregnancy. At sites where tissue shedding is complete, re-epithelialization of the tissue is essential for repair and termination of bleeding. The complement of growth factors that mediate post-menstrual endometrial repair are yet to be completely elucidated. Galectins regulate many cell functions important for post-menstrual repair, such as cell adhesion and migration. Galectin-7 has a well characterized role in re-epithelialization and wound healing. We hypothesized that galectin-7 would be important in re-epithelialization during post-menstrual repair. We aimed to identify endometrial expression of galectin-7 in women undergoing normal endometrial repair and in women with amenorrhoea who do not experience endometrial breakdown and repair, and to determine whether galectin-7 enhances endometrial re-epithelialization in vitro. Galectin-7 immunolocalized to the endometrial luminal and glandular epithelium during the late secretory and menstrual phases, and to decidualized stroma in regions exhibiting tissue breakdown. Immunostaining intensity was significantly reduced in the endometrium of women with amenorrhoea compared with normally cycling woman. ELISA identified galectin-7 in menstrual fluid at significantly elevated levels compared with matched peripheral plasma. Exogenous galectin-7 (2.5 µg/ml) significantly enhanced endometrial epithelial wound repair in vitro; this was abrogated by inhibition of integrin binding. Galectin-7 elevated epithelial expression of extracellular matrix-related molecules likely involved in repair including β-catenin, contactin and TGF-β1. In conclusion, galectin-7 is produced by the premenstrual and menstrual endometrium, where it accumulates in menstrual fluid and likely acts as a paracrine factor to facilitate post-menstrual endometrial re-epithelialization. © The Author 2014. Published by Oxford University Press on behalf of the
Randell Scott H
Full Text Available Abstract Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung.
Mochizuki, Masahito; Toyoda, Masao
Residual stress by repair welds is computed using the thermal elastic-plastic analysis with phase-transformation effect. Coupling phenomena of temperature, microstructure, and stress-strain fields are simulated in the finite-element analysis. Weld bond of a plate butt-welded joint is gouged and then deposited by weld metal in repair process. Heat source is synchronously moved with the deposition of the finite-element as the weld deposition. Microstructure is considered by using CCT diagram and the transformation behavior in the repair weld is also simulated. The effects of initial stress, heat input, and weld length on residual stress distribution are studied from the organic results of numerical analysis. Initial residual stress before repair weld has no influence on the residual stress after repair treatment near weld metal, because the initial stress near weld metal releases due to high temperature of repair weld and then stress by repair weld regenerates. Heat input has an effect for residual stress distribution, for not its magnitude but distribution zone. Weld length should be considered reducing the magnitude of residual stress in the edge of weld bead; short bead induces high tensile residual stress. (author)
Full Text Available Shaohua Ge,1 Ning Zhao,1 Lu Wang,1 Meijiao Yu,1 Hong Liu,2 Aimei Song,1 Jing Huang,1 Guancong Wang,2 Pishan Yang11Key Laboratory of Oral Biomedicine of Shandong Province, Department of Periodontology, School of Stomatology, 2Center of Bio and Micro/Nano Functional Materials, State Key Laboratory of Crystal Materials, Shandong University, Jinan, ChinaBackground: A nanohydroxyapatite-coated chitosan scaffold has been developed in recent years, but the effect of this composite scaffold on the viability and differentiation of periodontal ligament stem cells (PDLSCs and bone repair is still unknown. This study explored the behavior of PDLSCs on a new nanohydroxyapatite-coated genipin-chitosan conjunction scaffold (HGCCS in vitro as compared with an uncoated genipin-chitosan framework, and evaluated the effect of PDLSC-seeded HGCCS on bone repair in vivo.Methods: Human PDLSCs were cultured and identified, seeded on a HGCCS and on a genipin-chitosan framework, and assessed by scanning electron microscopy, confocal laser scanning microscopy, MTT, alkaline phosphatase activity, and quantitative real-time polymerase chain reaction at different time intervals. Moreover, PDLSC-seeded scaffolds were used in a rat calvarial defect model, and new bone formation was assessed by hematoxylin and eosin staining at 12 weeks postoperatively.Results: PDLSCs were clonogenic and positive for STRO-1. They had the capacity to undergo osteogenic and adipogenic differentiation in vitro. When seeded on HGCCS, PDLSCs exhibited significantly greater viability, alkaline phosphatase activity, and upregulated the bone-related markers, bone sialoprotein, osteopontin, and osteocalcin to a greater extent compared with PDLSCs seeded on the genipin-chitosan framework. The use of PDLSC-seeded HGCCS promoted calvarial bone repair.Conclusion: This study demonstrates the potential of HGCCS combined with PDLSCs as a promising tool for bone regeneration.Keywords: periodontal ligament, stem
Muiños-López, Emma; Hermida-Gómez, Tamara; Fuentes-Boquete, Isaac; de Toro-Santos, Javier; Blanco, Francisco Javier; Díaz-Prado, Silvia María
Localized trauma-derived breakdown of the hyaline articular cartilage may progress toward osteoarthritis, a degenerative condition characterized by total loss of articular cartilage and joint function. Tissue engineering technologies encompass several promising approaches with high therapeutic potential for the treatment of these focal defects. However, most of the research in tissue engineering is focused on potential materials and structural cues, while little attention is directed to the most appropriate source of cells endowing these materials. In this study, using human amniotic membrane (HAM) as scaffold, we defined a novel static in vitro model for cartilage repair. In combination with HAM, four different cell types, human chondrocytes, human bone marrow-derived mesenchymal stromal cells (hBMSCs), human amniotic epithelial cells, and human amniotic mesenchymal stromal cells (hAMSCs) were assessed determining their therapeutic potential. A chondral lesion was drilled in human cartilage biopsies simulating a focal defect. A pellet of different cell types was implanted inside the lesion and covered with HAM. The biopsies were maintained for 8 weeks in culture. Chondrogenic differentiation in the defect was analyzed by histology and immunohistochemistry. HAM scaffold showed good integration and adhesion to the native cartilage in all groups. Although all cell types showed the capacity of filling the focal defect, hBMSCs and hAMSCs demonstrated higher levels of new matrix synthesis. However, only the hAMSCs-containing group presented a significant cytoplasmic content of type II collagen when compared with chondrocytes. More collagen type I was identified in the new synthesized tissue of hBMSCs. In accordance, hBMSCs and hAMSCs showed better International Cartilage Research Society scoring although without statistical significance. HAM is a useful material for articular cartilage repair in vitro when used as scaffold. In combination with hAMSCs, HAM showed better
Keijzers, Guido; Bakula, Daniela; Scheibye-Knudsen, Morten
Maintaining the stability of the genome is essential for all organisms, and it is not surprising that damage to DNA has been proposed as an explanation for multiple chronic diseases.1-5 Conserving a pristine genome is therefore of central importance to our health. To overcome the genotoxic stress...... of a growing number of human diseases. Notably, many of these monogenic DNA-repair disorders display features of accelerated aging, supporting the notion that genome maintenance is a key factor for organismal longevity. This review focuses on the physiological consequences of loss of DNA repair, particularly...... in the context of monogenic DNA-repair diseases....
... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a... killing or growth inhibition of repair deficient bacteria in a set of repair proficient and deficient...
Govoni, K E
Equine bone fractures are often catastrophic, potentially fatal, and costly to repair. Traditional methods of healing fractures have limited success, long recovery periods, and a high rate of reinjury. Current research in the equine industry has demonstrated that stem cell therapy is a promising novel therapy to improve fracture healing and reduce the incidence of reinjury; however, reports of success in horses have been variable and limited. Stem cells can be derived from embryonic, fetal, and adult tissue. Based on the ease of collection, opportunity for autologous cells, and proven success in other models, adipose- or bone marrow-derived mesenchymal stem cells (MSC) are often used in equine therapies. Methods for isolation, proliferation, and differentiation of MSC are well established in rodent and human models but are not well characterized in horses. There is recent evidence that equine bone marrow MSC are able to proliferate in culture for several passages in the presence of autologous and fetal bovine serum, which is important for expansion of cells. Mesenchymal stem cells have the capacity to differentiate into osteoblasts, the bone forming cells, and this complex process is regulated by a number of transcription factors including runt-related transcription factor 2 (Runx2) and osterix (Osx). However, it has not been well established if equine MSC are regulated in a similar manner. The data presented in this review support the view that equine bone marrow MSC are regulated by the same transcription factors that control the differentiation of rodent and human MSC into osteoblasts. Although stem cell therapy is promising in equine bone repair, additional research is needed to identify optimal methods for reintroduction and potential manipulations to improve their ability to form new bone.
Montes, Samantha D; Zweig, David
Promises are positioned centrally in the study of psychological contract breach and are argued to distinguish psychological contracts from related constructs, such as employee expectations. However, because the effects of promises and delivered inducements are confounded in most research, the role of promises in perceptions of, and reactions to, breach remains unclear. If promises are not an important determinant of employee perceptions, emotions, and behavioral intentions, this would suggest that the psychological contract breach construct might lack utility. To assess the unique role of promises, the authors manipulated promises and delivered inducements separately in hypothetical scenarios in Studies 1 (558 undergraduates) and 2 (441 employees), and they measured them separately (longitudinally) in Study 3 (383 employees). The authors' results indicate that breach perceptions do not represent a discrepancy between what employees believe they were promised and were given. In fact, breach perceptions can exist in the absence of promises. Further, promises play a negligible role in predicting feelings of violation and behavioral intentions. Contrary to the extant literature, the authors' findings suggest that promises may matter little; employees are concerned primarily with what the organization delivers.
Cleaver, J.E.; Bootsma, D.; Friedberg, E.
DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)
Cleaver, J.E.; Bootsma, D.; Friedberg, E.
DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed
Barrett, J. [Canadian Nuclear Association, Ottawa, ON (Canada)
'Full text:'Countries work together to develop effective governance and regulation. Canada has made big investments in these areas and it carries a premium for us. The rapid build-out of nuclear technology around the Pacific Rim holds vast promise for our populations in better climate, better air, affordable and reliable electricity, and longer lives. The biggest risk is not another accident: rather, it is the risk of failing to fulfill that promise to our people. Every country that wants the benefits of nuclear must also want to be sure that those benefits are realized and sustained by good governance and regulation. Canada has the people, laws, organizations, public institutions, and relationships that can help our partners fulfill the whole and lasting promise of nuclear technology. (author)
This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair
This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.
In order to improve handling of subsidence damages the Illinois Mine Subsidence Insurance Fund supported the development of novel cost-effective methods of repair. The research in developing the repairs was directed towards the most common and costly damages that had been observed. As a result repair techniques were designed for structurally cracked foundations in the tension zone; structurally cracked foundations in the compression zone; and damaged or undamaged tilted foundations. When appropriate the postulated methods would result in: 1. significant cost savings (over conventional procedures); 2. a structural capacity greater than when the foundation was uncracked; and 3. an aesthetic appeal. All the postulated repair methodologies were laboratory and/or field tested. This paper will summarize the essentials of each technique developed and the test results
... treatment. The indications for umbilical hernia repair include: incarcerated (strangulated) umbilical hernia defects not spontaneously closed by 4 to 5 years of age children under 2 with very large defects unacceptable to ...
Wood, Richard D.
The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.
Successful repair without any downtime, of the Sabana Yegua power and irrigation structure in the western Dominican Republic by Aquatic Sciences Ltd., a St. Catherine, Ontario-based underwater specialist company, is discussed. The structure was damaged by Hurricane George last when when rising water levels damaged a major valve in the control gate chamber. The repair strategy designed by Aquatic Sciences used a remotely operated vehicle with a mechanical arm for minor tasks which placed a specially-made plug into the inlet pipe. The work was completed in one week, saving the utility company a great deal of money by making it possible to make the repairs remotely in the gate chamber without having to drain the tunnel, as would have been necessary had the repair been completed manually. The remotely operated vehicles use a scanning sonar as well as light to find their way. They are particularly well adapted to work underwater under low-visibility conditions
Brimnes, Eydbjørn; Dali, Bogi í; Larsen, Erik Stoklund
Concrete repairs on 11 pillars on bridges built in the sixties and repaired 8 to 9 years ago have been examined. Especially the chloride penetration in the repair concrete have been measured. Chloride penetration in the repair concrete is much lower than in the original concrete....
... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1005 Section 63.1005... Standards for Equipment Leaks-Control Level 1 § 63.1005 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected no later than 15 calendar days after it is detected, except as...
... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical, but not later than 15 calendar...
... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Leak repair. 65.105 Section 65.105... FEDERAL AIR RULE Equipment Leaks § 65.105 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical but not later than 15 calendar days after it is...
Zhang, Yi-Jun; Zhang, Chi; Wang, Quan; Lin, Xiang-Jin
Although simple end-to-end repair of the Achilles tendon is common, many augmented repair protocols have been implemented for acute Achilles tendon rupture. However, whether augmented repair is better than nonaugmented repair of an acute Achilles tendon rupture is still unknown. To conduct a meta-analysis to determine whether augmented surgical repair of an acute Achilles tendon rupture improved subjective patient satisfaction without an increase in rerupture rates. Secondary outcomes assessed included infections, ankle range of motion, calf muscle strength, and minor complications. Meta-analysis. A systematic literature search of peer-reviewed articles was conducted to identify all randomized controlled trials (RCTs) comparing augmented repair and nonaugmented repair for acute Achilles tendon rupture from January 1980 to August 2016 in the electronic databases of PubMed, Web of Science (SCI-E/SSCI/A&HCI), and EMBASE. The keywords (Achilles tendon rupture) AND (surg* OR operat* OR repair* OR augment* OR non-augment* OR end-to-end OR sutur*) were combined, and results were limited to human RCTs and controlled clinical trials published in the English language. Four RCTs involving 169 participants were eligible for inclusion; 83 participants were treated with augmented repair and 86 were treated with nonaugmented repair. Augmented repair led to similar responses when compared with nonaugmented repair for acute Achilles tendon rupture (93% vs 90%, respectively; P = .53). The rerupture rates showed no significant difference for augmented versus nonaugmented repair (7.2% vs 9.3%, respectively; P = .69). No differences in superficial and deep infections occurred in augmented (7 infections) and nonaugmented (8 infections) repair groups during postoperative follow-up ( P = .89). The average incisional infection rate was 8.4% with augmented repair and 9.3% with nonaugmented repair. No significant differences in other complications were found between augmented (7.2%) and
Podkopaev, Anton; Lahav, Ori; Vafeiadis, Viktor
We prove the correctness of compilation of relaxed memory accesses and release-acquire fences from the "promising" semantics of [Kang et al. POPL'17] to the ARMv8 POP machine of [Flur et al. POPL'16]. The proof is highly non-trivial because both the ARMv8 POP and the promising semantics provide some extremely weak consistency guarantees for normal memory accesses; however, they do so in rather different ways. Our proof of compilation correctness to ARMv8 POP strengthens the results of the Kan...
Carter, Jonathan; Duh, Quan-Yang
For patients with recurrent inguinal hernia, or bilateral inguinal hernia, or for women, laparoscopic repair offers significant advantages over open techniques with regard to recurrence risk, pain, and recovery. For unilateral first-time hernias, either laparoscopic or open repair with mesh can offer excellent results. The major drawback of laparoscopy is that the technique requires a significant number of cases to master. For surgeons in group practice, it makes sense to have one surgeon in ...
Affordable Combat Aircraft, AGARD - CP -600, 1997.  Helbling J, Grover R and Ratwani M. M “Analysis and Structural Test of Composite Reinforcement to...considered suitable for the composite patch repair of aluminum structure. Ductile adhesives such as FM- 73 are preferred over brittle adhesives Repair Types...zone. A proper cure cycle is followed as prescribed by the adhesive manufacturer. For FM- 73 adhesive cure at 2500F (1210C) for 120 minutes is
Bai, Yichun; Liu, Yang; Su, Zhenlei; Ma, Yana; Ren, Chonghua; Zhao, Runzhen; Ji, Hong-Long
Respiratory diseases, which are leading causes of mortality and morbidity in the world, are dysfunctions of the nasopharynx, the trachea, the bronchus, the lung and the pleural cavity. Symptoms of chronic respiratory diseases, such as cough, sneezing and difficulty breathing, may seriously affect the productivity, sleep quality and physical and mental well-being of patients, and patients with acute respiratory diseases may have difficulty breathing, anoxia and even life-threatening respiratory failure. Respiratory diseases are generally heterogeneous, with multifaceted causes including smoking, ageing, air pollution, infection and gene mutations. Clinically, a single pulmonary disease can exhibit more than one phenotype or coexist with multiple organ disorders. To correct abnormal function or repair injured respiratory tissues, one of the most promising techniques is to correct mutated genes by gene editing, as some gene mutations have been clearly demonstrated to be associated with genetic or heterogeneous respiratory diseases. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) systems are three innovative gene editing technologies developed recently. In this short review, we have summarised the structure and operating principles of the ZFNs, TALENs and CRISPR/Cas9 systems and their preclinical and clinical applications in respiratory diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Full Text Available Philippe TaupinNational Neuroscience Institute, National University of SingaporeAbstract: Stem cells are self-renewing undifferentiated cells that give rise to multiple types of specialized cells of the body. In the adult, stem cells are multipotents and contribute to homeostasis of the tissues and regeneration after injury. Until recently, it was believed that the adult brain was devoid of stem cells, hence unable to make new neurons and regenerate. With the recent evidences that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS, the adult brain has the potential to regenerate and may be amenable to repair. The function(s of NSCs in the adult CNS remains the source of intense research and debates. The promise of the future of adult NSCs is to redefine the functioning and physiopathology of the CNS, as well as to treat a broad range of CNS diseases and injuries.Keywords: neurogenesis, transdifferentiation, plasticity, cellular therapy
Tan, Xi; Gong, Yong-Zhen; Wu, Ping; Liao, Duan-Fang; Zheng, Xi-Long
Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.
Perineal hernias are infrequent complications following abdominoperineal operations. Various approaches have been described for repair of perineal hernias including open transabdominal, transperineal or combined abdominoperineal repairs. The use of laparoscopic transabdominal repair of perineal hernias is not well-described. We present a case report demonstrating the benefits of laparoscopic repair of perineal hernia following previous laparoscopic abdominoperineal resection (APR) using a nonabsorbable mesh to repair the defect. We have demonstrated that the use of laparoscopy with repair of the pelvic floor defect using a non absorbable synthetic mesh offers an excellent alternative with many potential advantages over open transabdominal and transperineal repairs.
Cohen, Daniel L; Lipton, Jeffrey I; Bonassar, Lawrence J; Lipson, Hod
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.
Crane, Andrea K; Myers, Erinn M; Lippmann, Quinn K; Matthews, Catherine A
Knowledge of how to anatomically reconstruct extensive posterior-compartment defects is variable among gynecologists. The objective of this video is to demonstrate an effective technique of overlapping sphincteroplasty and posterior repair. In this video, a scripted storyboard was constructed that outlines the key surgical steps of a comprehensive posterior compartment repair: (1) surgical incision that permits access to posterior compartment and perineal body, (2) dissection of the rectovaginal space up to the level of the cervix, (3) plication of the rectovaginal muscularis, (4) repair of internal and external anal sphincters, and (5) reconstruction of the perineal body. Using a combination of graphic illustrations and live video footage, tips on repair are highlighted. The goals at the end of repair are to: (1) have improved vaginal caliber, (2) increase rectal tone along the entire posterior vaginal wall, (3) have the posterior vaginal wall at a perpendicular plane to the perineal body, (4) reform the hymenal ring, and (5) not have an overly elongated perineal body. This video provides a step-by-step guide on how to perform an overlapping sphincteroplasty and posterior repair.
Full Text Available The use of composite materials, such as carbon-fiber reinforced plastic (CFRP composites, aero-structures has led to an increased need of advanced assembly joining and repair technologies. Adhesive bonded repairs as an alternative to recover full or part of initial strength were investigated. Tests were conducted with the objective of evaluating the effectiveness of techniques used for repairing damage fiber reinforced laminated composites. Failure loads and failure modes were generated and compared with the following parameters: scarf angles, roughness of grind tool and number of external plies. Results showed that scarf angle was the critical parameter and the largest tensile strength was observed with the smallest scarf angle. Besides, the use of external plies at the outer surface could not increase the repairs efficiency for large scarf angle. Preparing the repair surfaces by sanding them with a sander ranging from 60 to 100 grit number had significant effect on the failure load. These results allowed the proposal of design principles for repairing CFRP structures.
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.
Fox, Sarah S; Janczyk, Randy; Warren, Jeremy A; Carbonell, Alfredo M; Poulose, Benjamin K; Rosen, Michael J; Hope, William W
The purpose of this review was to evaluate outcomes relating to parastomal hernia repair. Data from the Americas Hernia Society Quality Collaborative were used to identify patients undergoing parastomal hernia repair from 2013 to 2016. Parastomal hernia repairs were compared with other repairs using Pearson's test and Wilcoxon test with a P value Ostomy disposition included ostomy left in situ (47%), moved to a new site (18%), taken down (22%), and rematured in same location in (13%). Outcomes related to parastomal hernia repair included 10 per cent surgical site infection, 24 per cent surgical site occurrence, and 12 per cent surgical site occurrences requiring procedural interventions with a 13 per cent readmission rate and 6 per cent reoperation rate. When comparing parastomal hernias with other ventral hernia repairs, parastomal hernias had a significantly higher surgical site infection, surgical site occurrence, surgical site occurrences requiring procedural intervention, readmission, reoperation rate, and length of stay, and were less commonly performed laparoscopically (P < 0.05). Most parastomal hernias are being repaired open with synthetic mesh in the sublay position. Less favorable outcomes of parastomal hernia repair when compared with other ventral hernia repairs are likely related to the complexity of parastomal hernia repair.
Full Text Available Background Rotator cuff defects are frequently occurring shoulder pathologies associated with pain and movement impairment. Aims The aim of the study was to analyse the pathologies that lead to operative revisions after primary open rotator cuff repair. Methods In 216 patients who underwent primary rotator cuff repair and later required operative revision between 1996 to 2005, pathologies found intraoperatively during the primary operation and during revision surgery were collected, analysed and compared. Results The average age at the time of revision surgery was 54.3 years. The right shoulder (61.6 per cent was more often affected than the left, males (63.4 per cent more often than females. At primary operation – apart from rotator cuff repair – there were the following surgical procedures performed: 190 acromioplasty, 86 Acromiclavicular joint resections, 68 tenodesis, 40 adhesiolysis and 1 tenotomy. If an ACJ-resection had been performed in the primary operation, ACJ-problems were rare in revision surgery (p<0.01. Primary gleno-humeral adhesions were associated with a significant rise in re-tearing rate (p=0.049. Primary absence of adhesions went along with a significant lower rate of adhesions found at revision (p=0.018. Primary performed acromioplasty had no influence on re-tearing rate (p=0.408 or on the rate of subacromial impingement at revision surgery (p=0.709. Conclusion To avoid operative revision after rotator cuff repair relevant copathologies of the shoulder have to be identified before or during operation and treated accordingly. Therefore, even during open rotator cuff repair, the surgeon should initially start with arthroscopy of the shoulder joint and subacromial space to recognise co-pathologies.
Lukas, Jiri; Altmeyer, Matthias
Long non-coding RNAs (lncRNAs) have emerged as regulators of various biological processes, but to which extent lncRNAs play a role in genome integrity maintenance is not well understood. In this issue of EMBO Reports, Sharma et al  identify the DNA damage-induced lncRNA DDSR1 as an integral...... player of the DNA damage response (DDR). DDSR1 has both an early role by modulating repair pathway choices, and a later function when it regulates gene expression. Sharma et al  thus uncover a dual role for a hitherto uncharacterized lncRNA during the cellular response to DNA damage....
Hoeijmakers, J.H.J.; van Duin, M.; Westerveld, A.; Yasui, A.; Bootsma, D.
To identify human DNA repair genes we have transfected human genomic DNA ligated to a dominant marker to excision repair deficient xeroderma pigmentosum (XP) and CHO cells. This resulted in the cloning of a human gene, ERCC-1, that complements the defect of a UV- and mitomycin-C sensitive CHO mutant 43-3B. The ERCC-1 gene has a size of 15 kb, consists of 10 exons and is located in the region 19q13.2-q13.3. Its primary transcript is processed into two mRNAs by alternative splicing of an internal coding exon. One of these transcripts encodes a polypeptide of 297 aminoacids. A putative DNA binding protein domain and nuclear location signal could be identified. Significant AA-homology is found between ERCC-1 and the yeast excision repair gene RAD10. 58 references, 6 figures, 1 table
Tice, R R
A review of the literature on DNA repair processes in relation to aging is presented under the following headings: DNA repair processes; age-related occurrence of unrepaired DNA lesions; DNA repair capability as a function of age; tissue-specific DNA repair capability; acceleration of the aging process by exposure to DNA damaging agents; human genetic syndromes; and longevity and DNA repair processes. (HLW)
Full Text Available Interest in osteochondral repair has been increasing with the growing number of sports-related injuries, accident traumas, and congenital diseases and disorders. Although therapeutic interventions are entering an advanced stage, current surgical procedures are still in their infancy. Unlike other tissues, the osteochondral zone shows a high level of gradient and interfacial tissue organization between bone and cartilage, and thus has unique characteristics related to the ability to resist mechanical compression and restoration. Among the possible therapies, tissue engineering of osteochondral tissues has shown considerable promise where multiple approaches of utilizing cells, scaffolds, and signaling molecules have been pursued. This review focuses particularly on the importance of scaffold design and its role in the success of osteochondral tissue engineering. Biphasic and gradient composition with proper pore configurations are the basic design consideration for scaffolds. Surface modification is an essential technique to improve the scaffold function associated with cell regulation or delivery of signaling molecules. The use of functional scaffolds with a controllable delivery strategy of multiple signaling molecules is also considered a promising therapeutic approach. In this review, we updated the recent advances in scaffolding approaches for osteochondral tissue engineering.
Bederson, Benjamin B.
Zoomable user interfaces (ZUIs) have received a significant amount of attention in the 18 years since they were introduced. They have enjoyed some success, and elements of ZUIs are widely used in computers today, although the grand vision of a zoomable desktop has not materialised. This paper describes the premise and promise of ZUIs along with…
Zhu, Hui; Wang, Xiaolei; Yang, Fan; Yang, Xiurong [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 (China)
Activated carbons with promising performance in capacitors are produced from fungi via a hydrothermal assistant pyrolysis approach. This study introduces a facile strategy to discover carbonaceous materials and triggers interest in exploring fungi for material science applications. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)
Dhargalkar, V.K.; Pereira, N.
Seaweeds, one of the important marine living resources could be termed as the futuristically promising plants. These plants have been a source of food, feed and medicine in the orient as well as in the west, since ancient times. Although, seaweeds...
Dershowitz, N.; Tzameret, Iddo
Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/ citation .cfm?doid=1740582.1740586
Dershowitz, N.; Tzameret, Iddo
Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/citation.cfm?doid=1740582.1740586
... comprehensive education reforms that are linked to improved educational outcomes for children and youth in... parents or family members who report talking with their child about the importance of college and career... DEPARTMENT OF EDUCATION RIN 1855-ZA07 Promise Neighborhoods Program Catalog of Federal Domestic...
Zhang, Yi; Tang, Jun; Tian, Zhiqiang; van Velkinburgh, Jennifer C; Song, Jianxun; Wu, Yuzhang; Ni, Bing
Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.
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.
Rauner, Felix; And Others
Trends in training for employment in the motor vehicle repair and sales sectors in the 12 European Community (EC) countries were identified through a review of 12 national reports that were prepared by 16 research teams involved in an EC study on continuing training in the motor vehicle sales and repair sector. Special attention was paid to the…
de Windt, T.S.; Welsch, G.H.; Brittberg, M.; Vonk, L.A.; Marlovits, S.; Trattnig, S.; Saris, Daniël B.F.
Background: While MRI can provide a detailed morphological evaluation after articular cartilage repair, its additional value in determining clinical outcome has yet to be determined. Purpose: To evaluate the correlation between MRI and clinical outcome after cartilage repair and to identify
G. Giglia-Mari (Giuseppina); C. Miquel (Catherine); A.F. Theil (Arjan); P.O. Mari (Pierre-Olivier); D. Hoogstraten (Deborah); J.M.Y. Ng (Jessica); C. Dinant (Christoffel); J.H.J. Hoeijmakers (Jan); W. Vermeulen (Wim)
textabstractTranscription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein.
Vanclooster, P; Smet, B; de Gheldere, C; Segers, K
Since 6 years, the totally extraperitoneal laparoscopic hernia repair has become our procedure of choice to manage inguinal hernia in adult patients, especially for bilateral hernias and recurrences after classical anterior repair. Between March 1993 and March 1999, 976 patients underwent 1259 hernia repairs by an endoscopic total extraperitoneal approach. A large polypropylene prosthesis (15 x 15 cm) is placed and covers all potential defects. Follow-up on patients ranged from 6 to 79 months (mean, 39 months). Per- and postoperative morbidity and complications were acceptable (8.4%) and included conversion to open surgery (0.4%), bleedings (0.3%), urinary retention (4.2%), seromas (2.7%), neuralgias (0.2%), vague persistent groin discomfort (0.4%), orchitis (0.08%) and sigmoido-cutaneous fistula (0.08%). Recurrence rate so far is 0.1%. This retrospective study shows that the totally extraperitoneal repair for inguinal hernia should have a promising future because of low morbidity and low recurrence rate.
Fortier, Lisa A; Cole, Brian J; McIlwraith, C Wayne
Microfracture of subchondral bone to enhance cartilage repair is a popular surgical technique used in human and animal patients. Clinical results with resolution or improvement in pain are promising and last on average for 2 to 3 years. Animal studies aimed at understanding microfracture indicate that the repair tissue continues to remodel toward chondrogenesis for at least a year, but longer term results are not available to gain insight into the mechanism of microfracture function or failure over time. Subchondral bone sclerosis and central lesional osteophyte formation following subchondral bone microfracture have been observed in animal models of microfracture, but studies do not provide any insight into the etiology of these pathologies. The continued maturation of microfracture repair tissue over time supports further investigation of microfracture or microfracture-augmented cartilage repair procedures with caution for the investigator and clinician to be observant for conditions that lead to subchondral bone sclerosis or central osteophyte formation, and what affect these boney reactions have on clinical outcome.
De Felice F
Full Text Available Francesca De Felice,1 Vincenzo Tombolini,1 Francesco Marampon,2 Angela Musella,3 Claudia Marchetti3 1Department of Radiotherapy, Policlinico Umberto I, “Sapienza” University of Rome, Rome, 2Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L’Aquila, L’Aquila, 3Department of Gynecological and Obstetrical Sciences and Urological Sciences, “Sapienza” University of Rome, Rome, Italy Abstract: The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1 and breast cancer 2 gene (BRCA2 mutations are implicated in the highest risk of prostate cancer (PC predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC. Keywords: prostate cancer, metastatic disease, castration resistant, BRCA, DNA-repair, PARP, olaparib
Lee, Y.C.; Byfield, J.E.; Bennett, L.R.; Chan, P.Y.M.
Repair replication has been studied in detail in mouse L1210 leukemia cells. A method of identifying and quantitating repair replication using a pre- and postradiation block of normal replication with cytosine arabinoside is illustrated. The method derived does not require isolation of DNA per se and appears to be satisfactory for screening for inhibitors of repair replication. Repair replication can be demonstrated at doses in the 1000-rad range in bromouridine deoxyriboside-substituted cells and at slightly higher doses in nonsubstituted cells. Drugs that are known to bind to DNA inhibit this x-ray-induced repair replication. Drugs with these properties may be identified by the methods described and compared quantitatively in their ability to inhibit this type of x-ray damage. Since these phenomena can be demonstrated for low radiation doses and at drug concentrations attainable in vivo during human cancer chemotherapy this class of anticancer agent may be worthy of closer study. Application to the L1210 leukemia system should permit comparison of in vitro and in vivo drug effects in the context of the extensive in vivo pharmacological data already available for L1210 cells. (U.S.)
Full Text Available This paper presents results from a field study of asphaltic pavement patching operations performed by three different contractors working in a total of ten sites. It forms part of an ongoing research programme towards improving the performance of pothole repairs. Thermal imaging technology was used to record temperatures of the patching material throughout the entire exercise, from the stage of material collection, through transportation to repair site, patch forming, and compaction. Practical complications occurring during patch repairs were also identified. It was found that depending on the weather conditions, duration of the travel and poor insulation of the transported hot asphalt mix, its temperature can drop as high as 116.6 °C over the period that the reinstatement team travel to the site and prepare the patch. This impacting is on the durability and performance of the executed repairs. Cold spots on the asphalt mat and temperature differentials between the new hot-fill asphalt mix and existing pavement were also identified as poorly compacted areas that were prone to premature failure. For example, over the five-minute period, the temperature at one point reduced by 33% whereas the temperatures of nearby areas decreased by 65% and 71%. A return visit to the repair sites, three months later, revealed that locations where thermal segregation was noted, during the patching operation, had failed prematurely.
Sadler, Philip M.; Sonnert, Gerhard; Coyle, Harold P.; Miller, Kelly A.
The psychometrically sound development of assessment instruments requires pilot testing of candidate items as a first step in gauging their quality, typically a time-consuming and costly effort. Crowdsourcing offers the opportunity for gathering data much more quickly and inexpensively than from most targeted populations. In a simulation of a…
Clark, D. H.
Lakes fed by glacier outwash should have a clastic particle-size record distinct from non-glacial lakes in the same area, but do they? The unique turquoise color of alpine glacial lakes reflects the flux of suspended clastic glacial rock flour to those lakes; conversely, lakes not fed by outwash are generally clear with sediments dominated by organics or slope-wash from nearby hillslopes. This contrast in sediment types and sources should produce a distinct and measureable different in grain sizes between the two settings. Results from a variety of lakes suggest the actual situation is often more subtle and complex. I compare grain size results to other proxies to assess the value of grain size analysis for paleoglacier studies. Over the past 10 years, my colleagues and I have collected and analyzed sediment cores from a wide variety of lakes below small alpine glaciers in an attempt to constrain the timing and magnitude of alpine glaciation in those basins. The basic concept is that these lakes act as continuous catchments for any rock flour produced upstream by glacier abrasion; as a glacier grows, the flux of rock flour to the lake will also increase. If the glacier disappears entirely, rock flour deposition will also cease in short order. We have focused our research in basins with simple sedimentologic settings: mostly small, high-altitude, stripped granitic or metamorphic cirques in which the cirque glaciers are the primary source of clastic sediments. In most cases, the lakes are fed by meltwater from a modern glacier, but were ice free during the earlier Holocene. In such cases, the lake cores should record formation of and changes in activity of the glacier upstream. We used a Malvern Mastersizer 2000 laser particle size analyzer for our grain size analyses, as well as recording magnetic susceptibility, color, and organics for the same cores. The results indicate that although lakes often experience increases in silt and clay-size (<0.63 mm) clastic particles when a glacier is present upstream, the signal can be highly variable and complex, most likely the result of stochastic processes in the basin. Our analyses indicate that although particle size reflects glacier activity upstream, it is rarely the best record of glacier change and is most useful in combination with other proxies, most notably MS, color, and organic content.
Johnson, Kathleen H.; Bergren, Martha Dewey; Westbrook, Linda Oakes
A gap in data prevents measurement of the needs of school-age children and the influence of school nursing interventions on student health and education outcomes. Its remedy is in the data collected in school health rooms. A national clinical database describing school health will allow education and health leaders to build evidence-based programs…
David M. Sawyer
Full Text Available Inflammatory processes are implicated in many diseases of the vasculature and have been shown to play a key role in the formation of intracranial aneurysms (IAs. Although the specific mechanisms underlying these processes have been thoroughly investigated in related pathologies, such as atherosclerosis, there remains a paucity of information regarding the immunopathology of IA. Cells such as macrophages and lymphocytes and their effector molecules have been suggested to be players in IA, but their specific interactions and the role of other components of the inflammatory response have yet to be determined. Drawing parallels between the pathogenesis of IA and other vascular disorders could provide a roadmap for developing a mechanistic understanding of the immunopathology of IA and uncovering useful targets for therapeutic intervention. Future research should address the presence and function of leukocyte subsets, mechanisms of leukocyte recruitment and activation, and the role of damage-associated molecular patterns in IA.
... repair, equipment damaged, dismantling retired property, fringe benefits, other casualties and insurance, lease rentals, joint facility rents, other rents, depreciation, joint facility, repairs billed to others... maintenance, machinery repair, equipment damaged, dismantling retired property, fringe benefits, other...
Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.
Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of
Since its inception in 2013, PROMISE (PROactive Management of Integrated Services and Environments) has been supporting service users and staff at the Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) on a journey to reduce reliance on force. The author's own personal experiences led to the founding of PROMISE and illustrates how individual experiences can influence a patient to lead change. Coproduction is actively embedded in PROMISE. Patients have been meaningfully involved because they are innovators and problem solvers who bring an alternative viewpoint by the very nature of their condition. A patient is more than just a person who needs to be 'fixed' they are individuals with untapped skills and added insight. There have been 2 separate Patient Advisory Groups (PAGs) since the project was first established. The first Patient Advisory Group was recruited to work with the PROMISE researchers on a study which used a participatory qualitative approach. Drawing on their lived experience and different perspectives the PAG was instrumental in shaping the qualitative study, including the research questions. Their active involvement helped to ensure that that the study was sensitively designed, methodologically robust and ethically sound. The 2 nd PAG was formed in 2016 to give the project an overall steer. Patients in this group contributed to the work on the 'No' Audit and reviewed several CPFT policies such as the Seclusion and Segregation policy which has impacted on frontline practice. They also made a significant contribution to the study design for a funding application that was submitted by the PROMISE team to the National Institute for Health Research (NIHR). Both PAGs were supported by funding from East of England Collaboration for Leadership in Applied Health Research and Care (CLAHRC EoE) and were influential in different ways. An evaluation of the 2 nd PAG which was conducted in June 2017 showed very high satisfaction levels. The free text
Wocial, Lucia D; Sego, Kelly; Rager, Carrie; Laubersheimer, Shellee; Everett, Linda Q
The purpose of this qualitative study was to explore the meaning of the phrase "image of the nurse" in the context of the desired brand experience of assurance. A brand is a promise that lives in the minds of consumers. Nurses play a key role in delivering on the brand promise of a hospital. Using focus groups, the authors applied a deductive approach to generate data. Discussion transcripts were analyzed by establishing codes and identifying themes. The most frequent comment from participants was that for nurses to communicate assurance, they must 1st be clean, well groomed, and understated in overall appearance. Nurse behaviors that reassure patients include being present with patients, helping patients know what to expect, and demonstrating a consistent team approach. Overall appearance and behaviors define the image of nurses and contribute significantly to the brand of assurance.
Sholtis, J.A. Jr.
Decisions involving the use of hazardous technologies are often made based on risk-benefit considerations. This is the case for U.S. space mission use of nuclear power and propulsion systems, where launch decisions are made within the office of the President. A great deal of time and effort is spent characterizing the risk for each nuclear-powered space mission. However, this is not so for benefits, even though they are no less important. To correct this situation, a new technical term--promise--is defined, and a new methodology--promise assessment--is proposed. This paper introduces and advances this concept, addresses its future application, as a tool, can be developed sufficiently and applied to methodically identify and characterized benefits. Further, it can introduce a degree of balance when judgments concerning the use of hazardous technologies are involved
Wood, Roger; Sonobe, Yoshiaki; Jin Zhen; Wilson, Bruce
Perpendicular recording has long been advocated as a means of achieving the highest areal densities. In particular, in the context of the 'superparamagnetic limit', perpendicular recording with a soft underlayer promises several key advantages. These advantages include a higher coercivity, thicker media that should permit smaller diameter grains and higher signal-to-noise ratio. Also, the sharper edge-writing will facilitate recording at very high track densities (lower bit aspect ratio). Recent demonstrations of the technology have shown densities comparable with the highest densities reported for longitudinal recording. This paper further examines the promise that perpendicular recording will deliver an increase in areal density two to eight times higher than that achievable with longitudinal recording. There are a number of outstanding issues but the key challenge is to create a low-noise medium with a coercivity that is high and is much larger than the remanent magnetization
A summary review of deepwater Gulf of Mexico (GOM) oil production was presented for the years 1989 to 1998. Trends and prospects in deepwater GOM production and leasing were assessed. Promises and forecasts made in the early 1990s were compared with what actually happened since then. Forecasts in the early 1990s promised deeper, faster and cheaper developments in the deepwater Gulf. Results of the comparison showed that the prognosticators were correct on all three counts. Regarding the future of the Gulf, one can be justified in being optimistic in so far as more experience, robust economics, more and cheaper rigs can be taken as reliable indicators of optimism. In contrast, there are certain negatives to consider, such as low commodity prices, budget constraints, lease expirations, technical challenges and increased competition. . 12 figs
Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw
The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts
Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte
Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose...
Full Text Available The article surveys printing and publishing market and its strong and weak aspects. The concept of a new product is described as well as its lifetime and the necessity of its introduction to the market. The enterprise X operating on the market is analyzed, its strong and weak characteristics are presented. The segmentation of the company consumers is performed. On the basis of the performed analysis the potential promising company products are defined.Article in Lithuanian
Ozao-Choy, Junko; Lee, Delphine J.; Faries, Mark B.
Synopsis Cancer vaccines were one of the earliest forms of immunotherapy to be investigated. Past attempts to vaccinate against cancer, including melanoma, have mixed results, revealing the complexity of what was thought to be a simple concept. However, several recent successes and the combination of improved knowledge of tumor immunology and the advent of new immunomodulators make vaccination a promising strategy for the future. PMID:25245965
Korpershoek, Jasmijn V.; de Windt, Tommy S.; Hagmeijer, Michella H.; Vonk, Lucienne A.; Saris, Daniel B. F.
Background: Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult. Purpose: To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies. Study Design: Systematic review. Methods: A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based. Results: After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold
Mouser, Vivian H M; Dautzenberg, Noël M M; Levato, Riccardo; van Rijen, Mattie H P; Dhert, Wouter J A; Malda, Jos; Gawlitta, Debby
The implantation of chondrocyte-laden hydrogels is a promising cartilage repair strategy. Chondrocytes can be spatially positioned in hydrogels and thus in defects, while current clinical cell-therapies introduce chondrocytes in the defect depth. The main aim of this study was to evaluate the effect
Bochynska, A. I.; Van Tienen, T. G.; Hannink, G.; Buma, P.; Grijpma, D. W.
Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study,
Sangadji, S.; Schlangen, H.E.J.G.
To repair concrete cracks in difficult or dangerous conditions such as underground structures or hazardous liquid containers, self healing mechanism is a promising alternative method. This research aims to imitate the bone self healing process by putting porous concrete internally in the concrete
Catena, C.; Mattoni, A.
Damage an repair of radiation induced DNA strand breaks were measured by alkaline lysis and hydroxyapatite chromatography. PHA stimulated human lymphocytes show that the rejoining process is complete within the first 50 min., afterwords secondary DNA damage and chromatid aberration. DNA repair, in synchronized culture, allows to evaluate individual repair capacity and this in turn can contribute to the discovery of individual who, although they do not demonstrate apparent clinical signs, are carriers of DNA repair deficiency. Being evident that a correlation exists between DNA repair capacity and carcinogenesis, the possibility of evaluating the existent relationship between DNA repair and survival in tumor cells comes therefore into discussion
Rozanova, O.M.; Zaichkina, S.I.; Aptikaev, G.F.; Ganassi, E.Eh.
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
Ito, Arata; Kimura, Motohiko
The present invention provides a device for inspecting and repairing the inside of a reactor container even if it is narrow, with no trouble by using a swimming-type operation robot. Namely, the device of the present invention conducts inspection and repairing operations for the inside of the reactor by introducing a swimming type operation robot into the reactor container. The swimming-type operation robot comprises a robot main body having a propeller, a balancer operably disposed to the robot main body and an inspection and repairing unit attached detachable to the balancer. In the device of the present invention, since the inspection and preparing unit is attached detachably to the swimming robot, a robot which transports tools is formed as a standard product. As a result, the production cost can be reduced, and the reliability of products can be improved. Appropriate operations can be conducted by using best tools. (I.S.)
Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett
The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis
Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett
The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis.
Daniels, B.D.; Green, D.; Henderson, J.D.C.
The prototype fast reactor at Dounreay has experienced a number of unscheduled shutdowns due to leaking reheater and superheater shell welds. There was a need to determine the cracking mechanism and to design a general repair technique simultaneously. Detailed investigations revealed that the crack locations correlated with the positions of rectification welds made at the time of vessel manufacture. A creep crack growth mechanism was identified; this requires through wall residual stress for through cracks to develop. A repair technique has been devised and successfully applied to the sites of a number of leaks. (author)
Pilous, V.; Kovarik, R.
Specific welding conditions are described in repair of the pressure vessels of nuclear reactors in operation and the effect is pointed out to of neutrons on changes in steel properties. Some of the special regulations are discussed to be observed in welding jobs. The welding methods are briefly described; the half-bead method is most frequently used. It is stressed that the defect must first be identified using a nondestructive method and the stages must be defined of the welding repair of the pressure vessel. (J.B.). 4 figs., 1 tab., 16 refs
Jensen, Andrew R; Cha, Peter S; Devana, Sai K; Ishmael, Chad; Di Pauli von Treuheim, Theo; D'Oro, Anthony; Wang, Jeffrey C; McAllister, David R; Petrigliano, Frank A
Medicare insures the largest population of patients at risk for rotator cuff tears in the United States. To evaluate the trends in incidence, concomitant procedures, and complications with open and arthroscopic rotator cuff repairs in Medicare patients. Cohort study; Level of evidence, 3. All Medicare patients who had undergone open or arthroscopic rotator cuff repair from 2005 through 2011 were identified with a claims database. Annual incidence, concomitant procedures, and postoperative complications were compared between these 2 groups. In total, 372,109 rotator cuff repairs were analyzed. The incidence of open repairs decreased (from 6.0 to 4.3 per 10,000 patients, P rotator cuff repairs have increased in incidence and now represent the majority of rotator cuff repair surgery. Among concomitant procedures, subacromial decompression was most commonly performed despite evidence suggesting a lack of efficacy. Infections and stiffness were rare complications that were slightly but significantly more frequent in open rotator cuff repairs.
Adenwalla, H. S.; Narayanan, P. V.
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...
Kyle R Cron
Full Text Available Despite optimal radiation therapy (RT, chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and proteasome inhibition showed synergistic effects. Proteasome inhibition resulted in an 80-90% decrease in homologous recombination (HR, a 50% decrease in expression of NF-κB-inducible HR genes BRCA1 and FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced foci. IκBα RNAi knockdown rescued NSCLC radioresistance. Irradiation of mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly increased murine survival compared to either treatment alone. Proteasome inhibition is a promising strategy for NSCLC radiosensitization via inhibition of NF-κB-mediated expression of Fanconi Anemia/HR DNA repair genes.
Gorna, Alina E; Bowater, Richard P; Dziadek, Jaroslaw
Mycobacteria, including most of all MTB (Mycobacterium tuberculosis), cause pathogenic infections in humans and, during the infectious process, are exposed to a range of environmental insults, including the host's immune response. From the moment MTB is exhaled by infected individuals, through an active and latent phase in the body of the new host, until the time they reach the reactivation stage, MTB is exposed to many types of DNA-damaging agents. Like all cellular organisms, MTB has efficient DNA repair systems, and these are believed to play essential roles in mycobacterial pathogenesis. As different stages of infection have great variation in the conditions in which mycobacteria reside, it is possible that different repair systems are essential for progression to specific phases of infection. MTB possesses homologues of DNA repair systems that are found widely in other species of bacteria, such as nucleotide excision repair, base excision repair and repair by homologous recombination. MTB also possesses a system for non-homologous end-joining of DNA breaks, which appears to be widespread in prokaryotes, although its presence is sporadic within different species within a genus. However, MTB does not possess homologues of the typical mismatch repair system that is found in most bacteria. Recent studies have demonstrated that DNA repair genes are expressed differentially at each stage of infection. In the present review, we focus on different DNA repair systems from mycobacteria and identify questions that remain in our understanding of how these systems have an impact upon the infection processes of these important pathogens.
Boyd, J.B.; Setlow, R.B.
Mutants of Drosophila melanogaster, with suspected repair deficiencies, were analyzed for their capacity to repair damage induced by x-rays, and uv radiation. Analysis was performed on cell cultures derived from embryos of homozygous mutant stocks. Postreplication repair following uv radiation has been analyzed in mutant stocks derived from a total of ten complementation groups. Cultures were irradiated, pulse-labeled, and incubated in the dark prior to analysis by alkaline sucrose gradient centrifugation. Kinetics of the molecular weight increase in newly synthesized DNA were assayed after cells had been incubated in the presence or absence of caffeine. Two separate pathways of postreplication repair have been tentatively identified by mutants derived from four complementation groups. The proposed caffeine sensitive pathway (CAS) is defined by mutants which also disrupt meiosis. The second pathway (CIS) is caffeine insensitive and is not yet associated with meiotic functions. All mutants deficient in postreplication repair are also sensitive to nitrogen mustard. The mutants investigated display a normal capacity to repair single-strand breaks induced in DNA by x-rays, although two may possess a reduced capacity to repair damage caused by localized incorporation of high specific activity thymidine- 3 H. The data have been employed to construct a model for repair of uv-induced damage in Drosophila DNA. Implications of the model for DNA repair in mammals are discussed
Boodhwani, Munir; de Kerchove, Laurent; Glineur, David; Poncelet, Alain; Rubay, Jean; Astarci, Parla; Verhelst, Robert; Noirhomme, Philippe; El Khoury, Gébrine
Valve repair for aortic insufficiency requires a tailored surgical approach determined by the leaflet and aortic disease. Over the past decade, we have developed a functional classification of AI, which guides repair strategy and can predict outcome. In this study, we analyze our experience with a systematic approach to aortic valve repair. From 1996 to 2007, 264 patients underwent elective aortic valve repair for aortic insufficiency (mean age - 54 +/- 16 years; 79% male). AV was tricuspid in 171 patients bicuspid in 90 and quadricuspid in 3. One hundred fifty three patients had type I dysfunction (aortic dilatation), 134 had type II (cusp prolapse), and 40 had type III (restrictive). Thirty six percent (96/264) of the patients had more than one identified mechanism. In-hospital mortality was 1.1% (3/264). Six patients experienced early repair failure; 3 underwent re-repair. Functional classification predicted the necessary repair techniques in 82-100% of patients, with adjunctive techniques being employed in up to 35% of patients. Mid-term follow up (median [interquartile range]: 47 [29-73] months) revealed a late mortality rate of 4.2% (11/261, 10 cardiac). Five year overall survival was 95 +/- 3%. Ten patients underwent aortic valve reoperation (1 re-repair). Freedoms from recurrent Al (>2+) and from AV reoperation at 5 years was 88 +/- 3% and 92 +/- 4% respectively and patients with type I (82 +/- 9%; 93 +/- 5%) or II (95 +/- 5%; 94 +/- 6%) had better outcomes compared to type III (76 +/- 17%; 84 +/- 13%). Aortic valve repair is an acceptable therapeutic option for patients with aortic insufficiency. This functional classification allows a systematic approach to the repair of Al and can help to predict the surgical techniques required as well as the durability of repair. Restrictive cusp motion (type III), due to fibrosis or calcification, is an important predictor for recurrent Al following AV repair.
Longerich, Simonne; Li, Jian; Xiong, Yong; Sung, Patrick
Fanconi anemia (FA) represents a paradigm of rare genetic diseases, where the quest for cause and cure has led to seminal discoveries in cancer biology. Although a total of 16 FA genes have been identified thus far, the biochemical function of many of the FA proteins remains to be elucidated. FA is rare, yet the fact that 5 FA genes are in fact familial breast cancer genes and FA gene mutations are found frequently in sporadic cancers suggest wider applicability in hematopoiesis and oncology. Establishing the interaction network involving the FA proteins and their associated partners has revealed an intersection of FA with several DNA repair pathways, including homologous recombination, DNA mismatch repair, nucleotide excision repair, and translesion DNA synthesis. Importantly, recent studies have shown a major involvement of the FA pathway in the tolerance of reactive aldehydes. Moreover, despite improved outcomes in stem cell transplantation in the treatment of FA, many challenges remain in patient care. PMID:25237197
Burcharth, J; Pedersen, M S; Pommergaard, H-C
in Denmark on December 31st, 2010 was performed. Within this population all umbilical and epigastric hernia repairs from January 1st, 2006 to December 31st, 2010 were identified using data from the Danish National Hospital Register, and 5-year prevalence estimates were calculated. RESULTS: The study...... hernia repairs was seen in males aged 60-70 years with a 5-year prevalence of 0.53 % (95 % CI 0.51-0.56 %) and the highest age-specific 5-year prevalence of epigastric hernia repair was seen in 40-50 year females with a 5-year prevalence of 0.086 % (95 % CI 0.077-0.095 %). CONCLUSION: The gender and age...
Lee, Stella Juhyun; Brennan, Emily; Gibson, Laura Anne; Tan, Andy S. L.; Kybert-Momjian, Ani; Liu, Jiaying; Hornik, Robert
Several message topic selection approaches propose that messages based on beliefs pretested and found to be more strongly associated with intentions will be more effective in changing population intentions and behaviors when used in a campaign. This study aimed to validate the underlying causal assumption of these approaches which rely on cross-sectional belief–intention associations. We experimentally tested whether messages addressing promising themes as identified by the above criterion were more persuasive than messages addressing less promising themes. Contrary to expectations, all messages increased intentions. Interestingly, mediation analyses showed that while messages deemed promising affected intentions through changes in targeted promising beliefs, messages deemed less promising also achieved persuasion by influencing nontargeted promising beliefs. Implications for message topic selection are discussed. PMID:27867218
Tsang, Julian S
The purpose of this study is to evaluate the use of endovascular stent grafts in the treatment of para-anastomotic aneurysms (PAAs) as an alternative to high-risk open surgical repair. We identified all patients with previous open aortic aneurysm repair who underwent infrarenal endovascular aneurysm repair (EVAR) at our institution from June 1998 to April 2007. Patient demographics, previous surgery, and operative complications were recorded. One hundred forty-eight patients underwent EVAR during the study period and 11 patients had previous aortic surgery. Of these 11 redo patients, the mean age was 62 years at initial surgery and 71 years at EVAR. All patients were male. Initial open repair was for rupture in five (45%) patients. The average time between initial and subsequent reintervention was 9 years. All patients were ASA Grade III or IV. Fifty-five percent of the PAAs involved the iliac arteries, 36% the abdominal aorta, and 9% were aortoiliac. Ten patients had endovascular stent-grafts inserted electively, and one patient presented with a contained leak. Aorto-uni-iliac stent-grafts were deployed in seven patients, and bifurcated stent-grafts in four patients. A 100% successful deployment rate was achieved. Perioperative mortality was not seen and one patient needed surgical reintervention to correct an endoleak. Endovascular repair of PAAs is safe and feasible. It is a suitable alternative and has probably now become the treatment of choice in the management of PAAs.
Comparative long-term results of mitral valve repair in adults with chronic rheumatic disease and degenerative disease: is repair for "burnt-out" rheumatic disease still inferior to repair for degenerative disease in the current era?
Dillon, Jeswant; Yakub, Mohd Azhari; Kong, Pau Kiew; Ramli, Mohd Faizal; Jaffar, Norfazlina; Gaffar, Intan Fariza
Mitral valve repair is perceived to be of limited durability for advanced rheumatic disease in adults. We aim to examine the long-term outcomes of repair for rheumatic disease, identify predictors of durability, and compare with repair for degenerative disease. Rheumatic and degenerative mitral valve repairs in patients aged 40 years or more were prospectively analyzed. The primary outcomes investigated were mortality, freedom from reoperation, and valve failure. Logistic regression analysis was performed to define predictors of poor outcome. Between 1997 and 2011, 253 rheumatic and 148 degenerative mitral valves were repaired. The age of patients in both groups was similar, with a mean of 54.1 ± 8.4 years versus 55.6 ± 7.3 years (P = .49). Freedom from reoperation for rheumatic valves at 5 and 10 years was 98.4%, comparable to 95.3% (P = .12) for degenerative valves. Freedom from valve failure at 5 and 10 years was 91.4% and 81.5% for rheumatic repairs and 82.5% and 75.4% for degenerative repairs, respectively (P = .15). The presence of residual mitral regurgitation greater than 2+ before discharge was the only significant independent predictor of reoperation, whereas residual mitral regurgitation greater than 2+ and leaflet procedures were significant risk factors for valve failure. The durability of rheumatic mitral valve repair in the current era has improved and is comparable to the outstanding durability of repairs for degenerative disease, even in the adult rheumatic population. Modifications of standard repair techniques, adherence to the importance of good leaflet coaptation, and strict quality control with stringent use of intraoperative transesophageal echocardiography have all contributed to the improved long-term results. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Bertrand, P.; Tishkoff, D.X.; Filosi, N.; Dasgupta, R.; Kolodner, R.D.
Nucleotide excision repair (NER) and DNA mismatch repair are required for some common processes although the biochemical basis for this requirement is unknown. Saccharomyces cerevisiae RAD14 was identified in a two-hybrid screen using MSH2 as 'bait,' and pairwise interactions between MSH2 and RAD1, RAD2, RAD3, RAD10, RAD14, and RAD25 subsequently were demonstrated by two-hybrid analysis. MSH2 coimmunoprecipitated specifically with epitope-tagged versions of RAD2, RAD10, RAD14, and RAD25. MSH2 and RAD10 were found to interact in msh3 msh6 and mlh1 pms1 double mutants, suggesting a direct interaction with MSH2. Mutations in MSH2 increased the UV sensitivity of NER-deficient yeast strains, and msh2 mutations were epistatic to the mutator phenotype observed in NER-deficient strains. These data suggest that MSH2 and possibly other components of DNA mismatch repair exist in a complex with NER proteins, providing a biochemical and genetical basis for these proteins to function in common processes
Riede, Felix; Andersen, Per; Price, Neil
formalized ethical codes or promises that not only guide the dissemination of data but oblige scientists to relate to fundamentally political issues. This article couples a survey of the recent environmental ethics literature with two case studies of how past natural hazards have affected vulnerable...... societies in Europe?s prehistory. We ask whether cases of past calamities and their societal effects should play a greater role in public debates and whether archaeologists working with past environmental hazards should be more outspoken in their ethical considerations. We offer no firm answers, but suggest...... that archaeologists engage with debates in human?environment relations at this interface between politics, public affairs and science....
The Collision Repair Campaign offers outreach materials to help collision repair shops reduce toxic air exposure. Materials include a DVD, poster, training video, and materials in Spanish (materiales del outreach en español).
repair is inadequately done, it may leave the woman suffering from perineal pain and other long term conditions with serious impact on the .... The maternity section had an average of ... with the job of performing episiotomy repair necessitating.
N.G.J. Jaspers (Nicolaas); J.H.J. Hoeijmakers (Jan)
textabstractThe eukaryotic nucleotide excision-repair pathway has been reconstituted in vitro, an achievement that should hasten the full enzymological characterization of this highly complex DNA-repair pathway.
Conclusion: For women with identified preoperative risk factors, including MCC 60 months, preoperative counseling should consist of a discussion about persistent UUI symptoms following TVM repair and the development of de novo stress urinary incontinence.
Tan, Shanjun; Wu, Guohao; Zhuang, Qiulin; Xi, Qiulei; Meng, Qingyang; Jiang, Yi; Han, Yusong; Yu, Chao; Yu, Zhen; Li, Ning
The role of laparoscopic surgery in the repair for peptic ulcer disease is unclear. The present study aimed to compare the safety and efficacy of laparoscopic versus open repair for peptic ulcer disease. Randomized controlled trials (RCTs) comparing laparoscopic versus open repair for peptic ulcer disease were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and references of identified articles and relevant reviews. Primary outcomes were postoperative complications, mortality, and reoperation. Secondary outcomes were operative time, postoperative pain, postoperative hospital stay, nasogastric tube duration, and time to resume diet. Statistical analysis was carried out by Review Manage software. Five RCTs investigating a total of 549 patients, of whom, 279 received laparoscopic repair and 270 received open repair, were included in the final analysis. There were no significant differences between these two procedures in some primary outcomes including overal postoperative complication rate, mortality, and reoperation rate. Subcategory analysis of postoperative complications showed that laparoscopic repair had also similar rates of repair site leakage, intra-abdominal abscess, postoperative ileus, pneumonia, and urinary tract infection as open surgery, except of the lower surgical site infection rate (P peptic ulcer. The obvious advantages of laparoscopic surgery are the lower surgical site infection rate, shorter nasogastric tube duration and less postoperative pain. However, more higher quality studies should be undertaken to further assess the safety and efficacy of laparoscopic repair for peptic ulcer disease. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Williams, M.C. [National Energy Technology Lab., Pittsburgh, PA (United States). Dept. of Energy
The niche or early entry market penetration by ONSI and its phosphoric acid fuel cell technology has proven that fuel cells are reliable and suitable for premium power and other opportunity fuel niche market applications. Now, new fuel cell technologies - solid oxide fuel cells, molten carbonate fuel cells, and polymer electrolyte fuel cells - are being developed for near-term distributed generation shortly after 2003. Some of the evolving fuel cell systems are incorporating gas turbines in hybrid configurations. The combination of the gas turbine with the fuel cell promises to lower system costs and increase efficiency to enhance market penetration. Market estimates indicate that significant early entry markets exist to sustain the initially high cost of some distributed generation technologies. However, distributed generation technologies must have low introductory first cost, low installation cost, and high system reliability to be viable options in competitive commercial and industrial markets. In the long-term, solid state fuel cell technology with stack costs under $100/kilowatt (kW) promises deeper and wider market penetration in a range of applications including a residential, auxillary power, and the mature distributed generation markets. The solid state energy conversion alliance (SECA) with its vision for fuel cells in 2010 was recently formed to commercialize solid state fuel cells and realize the full potential of the fuel cell technology. Ultimately, the SECA concept could lead to megawatt-size fuel-cell systems for commercial and industrial applications and Vision 21 fuel cell turbine hybrid energy plants in 2015. (orig.)
The control system is the brain of a power plant. The traditional goal of control systems has been productivity. However, in nuclear power plants the potential for disaster requires safety to be the dominant concern, and the worldwide political climate demands trustworthiness for nuclear power plants. To keep nuclear generation as a viable option for power in the future, trust is the essential critical goal which encompasses all others. In most of today's nuclear plants the control system is a hybrid of analog, digital, and human components that focuses on productivity and operates under the protective umbrella of an independent engineered safety system. Operation of the plant is complex, and frequent challenges to the safety system occur which impact on their trustworthiness. Advances in nuclear reactor design, computer sciences, and control theory, and in related technological areas such as electronics and communications as well as in data storage, retrieval, display, and analysis have opened a promise for control systems with more acceptable human brain-like capabilities to pursue the required goals. This paper elaborates on the promise of futuristic nuclear power plants with intelligent control systems and addresses design requirements and implementation approaches
Roč. 17, č. 4 (2015), s. 963-972 ISSN 1387-5841 Institutional support: RVO:67985556 Keywords : Reliability analysis * Repair models * Regression Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.782, year: 2015 http://library.utia.cas.cz/separaty/2015/SI/novak-0450902.pdf
This competency-based curriculum guide for teachers addresses the skills a technician will need to service microwave ovens and to provide customer relations to help retain the customer's confidence in the product and trust in the service company that performs the repair. The guide begins with a task analysis, listing 20 cognitive tasks and 5…
Jeggo, P.A.; Carr, A.M.; Lehmann, A.R.
Many human genes involved in the repair of UV damage have been cloned using different procedures and they have been of great value in assisting the understanding of the mechanism of nucleotide excision-repair. Genes involved in repair of ionizing radiation damage have proved more difficult to isolate. Positional cloning has localized the XRCC5 gene to a small region of chromosome 2q33-35, and a series of yeast artificial chromosomes covering this region have been isolated. Very recent work has shown that the XRCC5 gene encodes the 80 kDa subunit of the Ku DNA-binding protein. The Ku80 gene also maps to this region. Studies with fission yeast have shown that radiation sensitivity can result not only from defective DNA repair but also from abnormal cell cycle control following DNA damage. Several genes involved in this 'check-point' control in fission yeast have been isolated and characterized in detail. It is likely that a similar checkpoint control mechanism exists in human cells. (author)
Ashok k. Hemal
Full Text Available PURPOSE: To demonstrate the feasibility of pure robotic retrocaval ureter repair. MATERIALS AND METHODS: A 33 year old female presented with right loin pain and obstruction on intravenous urography with the classical "fish-hook" appearance. She was counseled on the various methods of repair and elected to have a robot assisted repair. The following steps are performed during a pure robotic retrocaval ureter repair. The patient is placed in a modified flank position, pneumoperitoneum created and ports inserted. The colon is mobilized to expose the retroperitoneal structures: inferior vena cava, right gonadal vein, right ureter, and duodenum. The renal pelvis and ureter are mobilized and the renal pelvis transected. The ureter is transposed anterior to the inferior vena cava and a pyelopyelostomy is performed over a JJ stent. RESULTS: This patient was discharged on postoperative day 3. The catheter and drain tube were removed on day 1. Her JJ stent was removed at 6 weeks postoperatively. The postoperative intravenous urography at 3 months confirmed normal drainage of contrast medium. CONCLUSION: Pure robotic retrocaval ureter is a feasible procedure; however, there does not appear to be any great advantage over pure laparoscopy, apart from the ergonomic ease for the surgeon as well the simpler intracorporeal suturing.
Alfa, Attahiru Sule; Castro, I. T.
We consider, in discrete time, a single machine system that operates for a period of time represented by a general distribution. This machine is subject to failures during operations and the occurrence of these failures depends on how many times the machine has previously failed. Some failures are repairable and the repair times may or may not depend on the number of times the machine was previously repaired. Repair times also have a general distribution. The operating times...
Cells of all living systems possess a variety of mechanisms that allow to repair spontaneous and exogeneously induced DNA damage. DNA repair deficiencies may invoke enhanced sensitivity towards DNA-damaging agents such as ionizing radiation. They may also enhance the risk of cancer development, both spontaneously or after induction. This article reviews several DNA repair mechanisms, especially those dealing with DNA double-strand breaks, and describes hereditary diseases associated with DNA repair defects. (orig.) [de
Bohnstedt, H.J.; Loebert, P.
In some cases, turbine parts can be repaired by welding, even rotating parts such as the shaft or the blades. Practical examples of successful repair work are explained, as for instance: welding of the last web of the turbine wheel of two MD-rotors, repair of erosion damage on turbine blades, of solid-matter erosion on a medium-pressure blading, or welding repair of a high-pressure turbine casing. (DG) [de
Iwanejko, L A; Jones, N J
The subjects of the talks at this 1-day DNA Repair Network meeting, held at City University, London on December 15, 1997, encompassed a range of topics and reflected some of the current areas of research in the United Kingdom. Topics included DNA double-strand break repair, V(D)J recombination, DNA ligases, the RecQ family of helicases and Bloom's syndrome, UVB and immunosuppression, the repair of oxidative damage and mismatch repair mechanisms.
Thompson, L.H.; Salazar, E.P.; Brookman, K.W.; Collins, C.C.; Stewart, S.A.; Busch, D.B.; Weber, C.A.
Repair deficient mutants of Chinese hamster ovary (CHO) cells are being used to identify human genes that correct the repair defects and to study mechanisms of DNA repair and mutagenesis. Five independent tertiary DNA transformants were obtained from the EM9 mutant. In these clones a human DNA sequence was identified that correlated with the resistance of the cells to CldUrd. After Eco RI digestion, Southern transfer, and hybridization of transformant DNAs with the BLUR-8 Alu family sequence, a common fragment of 25 to 30 kb was present. 37 refs., 4 figs., 3 tabs
Boyd, J.B.; Harris, P.V.; Sakaguchi, K.
This paper discusses Drosophila, the premier metazoan organism for analyzing many fundamental features of eukaryotic gene regulation. The authors present adaptations of several approaches for studying DNA repair to an analysis of repair-defective mutants in Drosophila. A current understanding of Drosophila DNA repair is described
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicle repair. 56.6801 Section 56.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Vehicle repair. Vehicles containing explosive material and oxidizers shall not be taken into a repair...
Van der Krogt, R.P.J.; De Weerdt, M.M.
Plan repair has two faces. Alternately, a plan repair method looks like a planning method, or looks like a method that does exactly the opposite, i.e., removing actions from a plan. We propose a general framework for plan repair that shows the relation between these two alternating steps. Any plan
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Tire repairs. 57.14104 Section 57.14104 Mineral... Devices and Maintenance Requirements § 57.14104 Tire repairs. (a) Before a tire is removed from a vehicle for tire repair, the valve core shall be partially removed to allow for gradual deflation and then...
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Tire repairs. 56.14104 Section 56.14104 Mineral... Devices and Maintenance Requirements § 56.14104 Tire repairs. (a) Before a tire is removed from a vehicle for tire repair, the valve core shall be partially removed to allow for gradual deflation and then...
M. V. Demesсhenko
Full Text Available Purpose: to identify anatomical landmarks on tibial articular surface to serve as reference in preparing tibial canal with respect to the center of ACL footprint during single bundle arthroscopic repair.Materials and methods. Twelve frozen knee joint specimens and 68 unpaired macerated human tibia were studied using anatomical, morphometric, statistical methods as well as graphic simulation.Results. Center of the tibial ACL footprint was located 13,1±1,7 mm anteriorly from posterior border of intercondylar eminence, at 1/3 of the distance along the line connecting apexes of internal and external tubercles and 6,1±0,5 mm anteriorly along the perpendicular raised to this point.Conclusion. Internal and external tubercles, as well as posterior border of intercondylar eminence can be considered as anatomical references to determine the center of the tibial ACL footprint and to prepare bone canals for anatomic ligament repair.
Pincheira, J.; Rodriguez, M.; Bravo, M.; Navarrete, M.H.; Lopez-Saez, J.F.
Lymphocytes from both Down syndrome (DS) patients and age-matched control donors have been investigated to identify a possible disturbance in chromosomal G2 repair. Analyses of caffeine treatments during G2 have shown that the frequency of chromosomal aberrations is higher in DS lymphocytes than in normal lymphocytes. Likewise, G2 duration is longer in DS cells than in normal cells. In both control and DS lymphocytes, caffeine treatments increase the frequencies of chromatid breakages and decrease the average of G2 duration. The reversal of the caffeine potentiation effect by adenosine and niacinamide is higher in DS cells than in normal cells. Furthermore, ATP content per cell in DS lymphocytes is one third of that estimated in normal lymphocytes. The increase of ATP level produced by adenosine or niacinamide generally correlates with the reversal of the caffeine effect on chromosome aberrations. Under the experimental conditions tested, a good negative exponential correlation between ATP level and chromosome aberrations has been detected in both normal and DS lymphocytes which were or were not X-irradiated. Finally, we postulate a decrease in G2 repair capability of DS lymphocytes caused by a low availability of ATP and/or some other factor correlating with it. (au)
Jayakumar, Sundarraj; Pal, Debojyoti; Sandur, Santosh K., E-mail: firstname.lastname@example.org
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
Knoot, Cory J; Ungerer, Justin; Wangikar, Pramod P; Pakrasi, Himadri B
Cyanobacteria are photosynthetic prokaryotes showing great promise as biocatalysts for the direct conversion of CO 2 into fuels, chemicals, and other value-added products. Introduction of just a few heterologous genes can endow cyanobacteria with the ability to transform specific central metabolites into many end products. Recent engineering efforts have centered around harnessing the potential of these microbial biofactories for sustainable production of chemicals conventionally produced from fossil fuels. Here, we present an overview of the unique chemistry that cyanobacteria have been co-opted to perform. We highlight key lessons learned from these engineering efforts and discuss advantages and disadvantages of various approaches. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
Vanhoutteghem, Lies; Tommerup, Henrik M.; Svendsen, Svend
This report focuses on analyses of the most promising existing sustainable renovation concepts, i.e. full-service concepts and technical concepts, for single-family houses. As a basis for the analyses a detailed building stock analysis was carried out. Furthermore, as a basis a general working...... method for proposals on package solutions for sustainable renovation was described. The method consists of four steps, going from investigation of the house to proposal for sustainable renovation, detailed planning and commissioning after renovation. It could be used by teams of consultants...... of the building envelope and the electricity required to run the system. Positive impact on the indoor environment can be expected. Thermal comfort will be improved by insulation and air-tightness measures that will increase surface temperatures and reduce draught from e.g. badly insulated windows. A ventilation...
Agarwal, Pratul K; Alam, Sadaf R
Proteins work as highly efficient machines at the molecular level and are responsible for a variety of processes in all living cells. There is wide interest in understanding these machines for implications in biochemical/biotechnology industries as well as in health related fields. Over the last century, investigations of proteins based on a variety of experimental techniques have provided a wealth of information. More recently, theoretical and computational modeling using large scale simulations is providing novel insights into the functioning of these machines. The next generation supercomputers with petascale computing power, hold great promises as well as challenges for the biomolecular simulation scientists. We briefly discuss the progress being made in this area
Gong-He, Du; Zhao-Yu, Ren; Ji-Ming, Zheng; Ping, Guo
We introduce polar substituents such as F, Cl, Br into pentacene to enhance the dissolubility in common organic solvents while retaining the high charge-carrier mobilities of pentacene. Geometric structures, dipole moments, frontier molecule orbits, ionization potentials and electron affinities, as well as reorganization energies of those molecules, and of pentacene for comparison, are successively calculated by density functional theory. The results indicate that halopentacenes have rather small reorganization energies (< 0.2 eV), and when the substituents are in position 2 or positions 2 and 9, they are polarity molecules. Thus we conjecture that they can easily be dissolved in common organic solvents, and are promising candidates for organic semiconductors. (condensed matter: electronicstructure, electrical, magnetic, and opticalproperties)
The apparent advantages of staple plants over the minor tropical plants often result only from the disproportionate research attention they have been given. A world-wide inquiry resulted in a list of 400 promising but neglected species. The 36 most important species are described in compact monographs and concern cereals (Echinochloa turnerana, grain amaranths, quinua and Zosterea mazina), roots and tubers (Arrachacha, cocoyams and taro), vegetables (chaya, hearts of palms, wax gourd, winged bean), fruits (durian, mangosteen, naranjilla, pejibaye, pummelo, soursop, uvilla), oilseeds (babassu palm, buffalo gourd, Caryocar species, Hessenia polycarpa and jojoba), forage (Acacia albida, Brosimum alicastrum Cassia sturtii, saltbushes and tamarugo) and other crops (buriti palm, Calathea lutea, candelilla, guar, guayule, Paspalum vaginatum, ramie and Spirulina).
Prasad, Leena Kumari; O'Mary, Hannah; Cui, Zhengrong
An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease.
Alkurt, Murat; Yeşil Duymuş, Zeynep; Gundogdu, Mustafa
Acrylic resin denture fracture is common in prosthodontic practice. When fractured denture bases are repaired, recurrent fractures frequently occur at the repair surface interface or adjacent areas. The purpose of this study was to evaluate the effect of different surface treatments on the flexural strength of the acrylic resin denture base repaired with heat-polymerized acrylic resin, autopolymerizing resin, and light-polymerized acrylic resin. Ninety-six specimens of heat-polymerized acrylic resin were prepared according to the American Dental Association Specification No. 12 (65.0 × 10.0 × 2.5 mm) and sectioned into halves to create a repair gap (3.0 × 10 × 2.5 mm). The sectioned specimens were divided into 3 groups according to their repair materials. The specimens from each group were divided into 4 subgroups according to their surface treatments: a control group without any surface treatment; an experimental group treated with methyl methacrylate monomer (MMA group); an experimental group treated with airborne-particle abrasion with aluminum oxide particles of 250-μm particle size (abrasion group); and an experimental group treated with erbium:yttrium-aluminum-garnet laser (laser group). After the surface treatments, the 3 materials were placed into the repair gaps and then polymerized. After all of the specimens had been ground and polished, they were stored in distilled water at 37°C for 1 week and subjected to a 3-point bend test. Data were analyzed with a 2-way analysis of variance, and the Tukey honestly significant difference test was performed to identify significant differences (α=.05). The effects of the surface treatments and repair resins on the surface of the denture base resin were examined with scanning electron microscopy. Significant differences were found among the groups in terms of repair resin type (P<.001). All surface-treated specimens had higher flexural strength than controls, except the surface treated with the methyl
Full Text Available Farm machinery managers often need to make complex economic decisions on machinery replacement. Repair and maintenance costs can have significant impacts on this economic decision. The farm manager must be able to predict farm machinery repair and maintenance costs. This study aimed to identify a regression model that can adequately represent the repair and maintenance costs in terms of machine age in cumulative hours of use. The regression model has the ability to predict the repair and maintenance costs for longer time periods. Therefore, it can be used for the estimation of the economic life. The study was conducted using field data collected from 11 John-Deer 955 combine harvesters used in several western provinces of Iran. It was found that power model has a better performance for the prediction of combine repair and maintenance costs. The results showed that the optimum replacement age of John-Deer 955 combine was 54300 cumulative hours.
Ciarrocchi, G.; Linn, S.
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
Aly, O.; Green, A.; Joy, M.; Wong, C.H.; Malik, M
To systematically review randomized controlled trials, (RCT) evidence comparing Lichtenstein to total extraperitoneal (TEP) hernia repair in terms of clinical and cost effectiveness. Study Design: Case series. Place and Duration of Study: The study was conducted at University of Abderdeen, U.K. Methodology: A comprehensive online literature search was undertaken using databases such as MEDLINE, PubMed, EMBASE and Springerlink. Studies were then short listed according to the selection criteria (RCT with over 100 subject and English language publications from 1995 onwards) and appraised using the SIGN Methodology Checklist. A meta analysis of the data was also performed using RevMan software. Results: Analysis of reported data shows that TEP has less postoperative pain and return to work than Lichtenstein method. Operation time is shown to be longer in the TEP but this difference is shortened with increasing surgeon experience. The meta-analysis of the data on complications shows that there are no significant differences between the two types of procedures. TEP causes more short-term recurrences which are attributed to the learning curve effect. Long term recurrence rates on the other hand show no significant differences. At present TEP is slightly more expensive than Lichtenstein repair. Conclusion: Both TEP and Lichtenstein repair are clinically effective procedures. The choice between them should be made on a case-by-case basis; which depends on the patient's preference and characteristics such as age, work and health status. (author)
Thangarajah, Tanujan; Pendegrass, Catherine J.; Shahbazi, Shirin; Lambert, Simon; Alexander, Susan; Blunn, Gordon W.
Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon. PMID:26665095
First, ultraviolet light (UVL)- and dimethylsulfate (DMS)-induced excision repair was examined in quiescent and lectin-stimulated bovine lymphocytes. Upon mitogenic stimulation, UVL-induced repair increased by a factor of 2 to 3, and reached this maximum 2 days before the onset of DNA replication. However, DMS-induced repair increased sevenfold in parallel with DNA replication. Repair patch sizes were smaller for DMS-induced damage reflecting patches of 7 nucleotides in quiescent lymphocytes compared to 20 nucleotides induced by UVL. The patch size increased during lymphocyte stimulation until one day prior to the peak of DNA replication when patch sizes of 45 and 35 nucleotides were produced in response to UVL- and DMS-induced damage, respectively. At the peak of DNA replication, the patch sizes were equal for both damaging agents at 34 nucleotides. In the second study, a small amount of repair replication was observed in undamaged quiescent and concanavalin A-stimulated bovine lymphocytes as well as in human T98G glioblastoma cells. Repair incorporation doubled in the presence of hydroxyurea. Thirdly, the enhanced repair replication induced by the poly (ADP-ribose) polymerase inhibitor, 3-aminobenzamide, (3-AB), could not be correlated either with an increased rate of repair in the presence of 3-AB or with the use of hydroxyurea in the repair protocol. Finally, treatment of unstimulated lymphocytes with hyperthermia was accompanied by decreased repair replication while the repair patches remained constant at 20 nucleotides.
For the past few decades, the repair of rotator cuff tears has evolved significantly with advances in arthroscopy techniques, suture anchors and instrumentation. From the biomechanical perspective, the focus in arthroscopic repair has been on increasing fixation strength and restoration of the footprint contact characteristics to provide early rehabilitation and improve healing. To accomplish these objectives, various repair strategies and construct configurations have been developed for rotator cuff repair with the understanding that many factors contribute to the structural integrity of the repaired construct. These include repaired rotator cuff tendon-footprint motion, increased tendon-footprint contact area and pressure, and tissue quality of tendon and bone. In addition, the healing response may be compromised by intrinsic factors such as decreased vascularity, hypoxia, and fibrocartilaginous changes or aforementioned extrinsic compression factors. Furthermore, it is well documented that torn rotator cuff muscles have a tendency to atrophy and become subject to fatty infiltration which may affect the longevity of the repair. Despite all the aforementioned factors, initial fixation strength is an essential consideration in optimizing rotator cuff repair. Therefore, numerous biomechanical studies have focused on elucidating the strongest devices, knots, and repair configurations to improve contact characteristics for rotator cuff repair. In this review, the biomechanical concepts behind current rotator cuff repair techniques will be reviewed and discussed. PMID:23730471
Kurthkoti, Krishna; Varshney, Umesh
About a third of the human population is estimated to be infected with Mycobacterium tuberculosis. Emergence of drug resistant strains and the protracted treatment strategies have compelled the scientific community to identify newer drug targets, and to develop newer vaccines. In the host macrophages, the bacterium survives within an environment rich in reactive nitrogen and oxygen species capable of damaging its genome. Therefore, for its successful persistence in the host, the pathogen must need robust DNA repair mechanisms. Analysis of M. tuberculosis genome sequence revealed that it lacks mismatch repair pathway suggesting a greater role for other DNA repair pathways such as the nucleotide excision repair, and base excision repair pathways. In this article, we summarize the outcome of research involving these two repair pathways in mycobacteria focusing primarily on our own efforts. Our findings, using Mycobacterium smegmatis model, suggest that deficiency of various DNA repair functions in single or in combinations severely compromises their DNA repair capacity and attenuates their growth under conditions typically encountered in macrophages. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Chen, Xiang-Yuan; Wang, Zhen [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Bei [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zhang, Ying-Jian, E-mail: email@example.com [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Ying-Yi, E-mail: firstname.lastname@example.org [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)
Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer. - Highlights: • This is first study to demonstrate that Pim-3 is endogenously induced by ionizing radiation in pancreatic cancer cells, and Pim-3 overexpression enhanced radioresistance of pancreatic cancer cells both in vitro and in vivo. • This is first study to provide evidence that radioresistance induced by Pim-3 is mainly attributed to Pim-3 induces activation of ATM, which subsequently activates checkpoint 1, leading to amplification of DNA repair through cell cycle arrest and DNA repair pathways. • This is first study to indicate that targeting Pim-3 may be a promising strategy to provide better treatment efficacy in combination with radiotherapy in human pancreatic
Chen, Xiang-Yuan; Wang, Zhen; Li, Bei; Zhang, Ying-Jian; Li, Ying-Yi
Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer. - Highlights: • This is first study to demonstrate that Pim-3 is endogenously induced by ionizing radiation in pancreatic cancer cells, and Pim-3 overexpression enhanced radioresistance of pancreatic cancer cells both in vitro and in vivo. • This is first study to provide evidence that radioresistance induced by Pim-3 is mainly attributed to Pim-3 induces activation of ATM, which subsequently activates checkpoint 1, leading to amplification of DNA repair through cell cycle arrest and DNA repair pathways. • This is first study to indicate that targeting Pim-3 may be a promising strategy to provide better treatment efficacy in combination with radiotherapy in human pancreatic
Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline
Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.
Maynard, Scott; de Souza-Pinto, Nadja C; Scheibye-Knudsen, Morten
The main source of mitochondrial DNA (mtDNA) damage is reactive oxygen species (ROS) generated during normal cellular metabolism. The main mtDNA lesions generated by ROS are base modifications, such as the ubiquitous 8-oxoguanine (8-oxoG) lesion; however, base loss and strand breaks may also occur....... Many human diseases are associated with mtDNA mutations and thus maintaining mtDNA integrity is critical. All of these lesions are repaired primarily by the base excision repair (BER) pathway. It is now known that mammalian mitochondria have BER, which, similarly to nuclear BER, is catalyzed by DNA...... glycosylases, AP endonuclease, DNA polymerase (POLgamma in mitochondria) and DNA ligase. This article outlines procedures for measuring oxidative damage formation and BER in mitochondria, including isolation of mitochondria from tissues and cells, protocols for measuring BER enzyme activities, gene...
Nuding, W.; Grimm, R.; Link, R.; Schroeder, P.; Schroeder, G.
The status of a joint project is reported, which is to develop a computerized testing and welding system for repair work in turbine blades. An X-ray radiographic testing device consisting of microfocus tube, manipulator and image processing system, is modified for this purpose so as to offer a greater number of image points scanned for image processing, and to thus achieve a better resolution for reliable detection of even very small defects. The consistency of the X-ray tube performance, which is a pre-requisite for automation, is to be achieved by a wa tercooled, high-duty tube head. The recording of defect coordinates in the repair zone is done for input into a welding robot to be developed by other partners in the project, so as to allow automated welding work. (orig.) [de
Adenwalla, H S; Narayanan, P V
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.
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.
Inoue, Tadashi; Kada, Tsuneo
An enzyme which enhances the priming activity of γ-irradiated DNA for type I DNA polymerase (EC 188.8.131.52) was identified and partially purified from extracts of Bacillus subtilis cells. The enzyme preferentially degraded γ-irradiated DNA into acid-soluble materials. DNA preparations treated with heat, ultraviolet light, pancreatic DNAase (EC 184.108.40.206) or micrococcal DNAase (EC 220.127.116.11) were not susceptible to the enzyme. However, sonication rendered DNA susceptible to the enzyme to some extent. From these results, it is supposed that this enzyme may function by 'cleaning' damaged terminals produced by γ-irradiation to serve as effective primer of sites for repair synthesis by the type I DNA polymerase
These antimicrobial peptides are implicated in the resistance of epithelial surfaces to microbial colonisation and have been shown to be upregulated...be equivalent to standard autograft repair in rodent models. Outcomes have now been validated in a large animal (swine) model with 5 cm ulnar nerve...Goals of the Project Task 1– Determine mechanical properties, seal strength and resistance to biodegradation of candidate photochemical nerve wrap
The reactor shutdown was decided on the 15th of November 1984, because the evolution of the carbon dioxide quantity in the helium blanket of the heavy water. Leaks have been localized on three different channels. Repairs have been made in hard conditions taking into account the reactor state (materials strongly irradiated). The restart has been authorized on the 24th of January 1985 [fr
Ionescu, Lara C.; Lee, Gregory C.; Huang, Kevin L.; Mauck, Robert L.
Few therapeutic options exist for meniscus repair after injury. Local delivery of growth factors may stimulate repair and create a favorable environment for engineered replacement materials. In this study, we assessed the effect of basic fibroblast growth factor (bFGF) (a pro-mitotic agent) and transforming growth factor beta 3 (TGF-β3) (a pro-matrix formation agent) on meniscus repair and the integration/maturation of electrospun poly(ε-caprolactone) (PCL) scaffolds for meniscus tissue engineering. Circular meniscus repair constructs were formed and refilled with either native tissue or scaffolds. Repair constructs were cultured in serum-containing media for 4 and 8 weeks with various growth factor formulations, and assessed for mechanical strength, biochemical content, and histological appearance. Results showed that either short-term delivery of bFGF or sustained delivery of TGF-β3 increased integration strength for both juvenile and adult bovine tissue, with similar findings for engineered materials. While TGF-β3 increased proteoglycan content in the explants, bFGF did not increase DNA content after 8 weeks. This work suggests that in vivo delivery of bFGF or TGF-β3 may stimulate meniscus repair, but that the time course of delivery will strongly influence success. Further, this study demonstrates that electrospun scaffolds are a promising material for meniscus tissue engineering, achieving comparable or superior integration compared to native tissue. PMID:22698946
Sedgwick, S.G.; Chao Ho; Woodgate, R.
Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium u mu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umuDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention
Toussaint, John S; Berry, Leonard L
An urgent need in American health care is improving quality and efficiency while controlling costs. One promising management approach implemented by some leading health care institutions is Lean, a quality improvement philosophy and set of principles originated by the Toyota Motor Company. Health care cases reveal that Lean is as applicable in complex knowledge work as it is in assembly-line manufacturing. When well executed, Lean transforms how an organization works and creates an insatiable quest for improvement. In this article, we define Lean and present 6 principles that constitute the essential dynamic of Lean management: attitude of continuous improvement, value creation, unity of purpose, respect for front-line workers, visual tracking, and flexible regimentation. Health care case studies illustrate each principle. The goal of this article is to provide a template for health care leaders to use in considering the implementation of the Lean management system or in assessing the current state of implementation in their organizations. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Local-regional hyperthermia (HT) when used in conjunction with radiation therapy (XRT), has been shown in numerous clinical trials to result in considerable improvement in response rates and local tumor control rates when compared with treatment by XRT alone. Although considerable progress has been made in understanding the biological basis for hyperthermia induced cytotoxicity and radiosensitization, additional research remains in establishing the optimal treatment schedules for the clinical utilization of HT-XRT. The number of HT treatments; the sequencing of HT and XRT; the frequency of administration of HT; and the ideal temperature-time parameters all remain to be better defined for the clinical setting. The role of tumor blood flow on the thermal distributions also warrants further investigation. In addition, considerable effort is needed to improve hyperthermia equipment in order to provide more uniform therapeutic temperature distributions (temperatures ≥42.5%C). Better heating equipment is particularly needed for the treatment of deep seeted tumors. Pertinent clinical literature will be presented summarizing the clinical promise of hyperthermia and the above mentioned clinical challenges
Grynberg, Michael; Ayoubi, Jean-Marc; Bulletti, Carlo; Frydman, Rene; Fanchin, Renato
Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. © 2011 New York Academy of Sciences.
Choong Ho Lee
Full Text Available The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.
Cavalheiro, Mafalda; Teixeira, Miguel Cacho
Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed. PMID:29487851
Cavalheiro, Mafalda; Teixeira, Miguel Cacho
Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis , and Candida parapsilosis , highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.
Lee, Choong Ho; Yoon, Hyung-Jin
The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.
Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B
Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.
Zuke, William A; Leroux, Timothy S; Gregory, Bonnie P; Black, Austin; Forsythe, Brian; Romeo, Anthony A; Verma, Nikhil N
As health care transitions from a pay-for-service to a pay-for-performance infrastructure, the value of orthopaedic care must be defined accurately. Significant efforts have been made in defining quality and cost in arthroplasty; however, there remains a lag in ambulatory orthopaedic care. Two-year follow-up has been a general requirement for reporting outcomes after rotator cuff repair. However, this time requirement has not been established scientifically and is of increasing importance in the era of value-based health care. Given that arthroscopic rotator cuff repair is a common ambulatory orthopaedic procedure, the purpose of this study was to establish a time frame for maximal medical improvement (the state when improvement has stabilized) after arthroscopic rotator cuff repair. Systematic review. A systematic review of the literature was conducted, identifying studies reporting sequential patient-reported outcomes up to a minimum of 2 years after arthroscopic rotator cuff repair. The primary clinical outcome was patient-reported outcomes at 3-month, 6-month, 1-year, and 2-year follow-up. Secondary clinical outcomes included range of motion, strength, retears, and complications. Clinically significant improvement was determined between various time intervals by use of the minimal clinically important difference. The review included 19 studies including 1370 patients who underwent rotator cuff repair. Clinically significant improvement in patient-reported outcomes was seen up to 1 year after rotator cuff repair, but no clinical significance was noted from 1 year to 2 years. The majority of improvement in strength and range of motion was seen up to 6 months, but no clinically meaningful improvement was seen thereafter. All reported complications and the majority of retears occurred within 6 months after rotator cuff repair. After rotator cuff repair, a clinically significant improvement in patient-reported outcomes, range of motion, and strength was seen up to 1
Chauhan, Aakash; Schimoler, Patrick; Miller, Mark C; Kharlamov, Alexander; Merrell, Gregory A; Palmer, Bradley A
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.
Yuan, Fenghua; Lai, Fangfang; Gu, Liya; Zhou, Wen; El Hokayem, Jimmy; Zhang, Yanbin
Mismatch repair corrects biosynthetic errors generated during DNA replication, whose deficiency causes a mutator phenotype and directly underlies hereditary non-polyposis colorectal cancer and sporadic cancers. Because of remarkably high conservation of the mismatch repair machinery between the budding yeast (Saccharomyces cerevisiae) and humans, the study of mismatch repair in yeast has provided tremendous insights into the mechanisms of this repair pathway in humans. In addition, yeast cells possess an unbeatable advantage over human cells in terms of the easy genetic manipulation, the availability of whole genome deletion strains, and the relatively low cost for setting up the system. Although many components of eukaryotic mismatch repair have been identified, it remains unclear if additional factors, such as DNA helicase(s) and redundant nuclease(s) besides EXO1, participate in eukaryotic mismatch repair. To facilitate the discovery of novel mismatch repair factors, we developed a straightforward in vitro cell-free repair system. Here, we describe the practical protocols for preparation of yeast cell-free nuclear extracts and DNA mismatch substrates, and the in vitro mismatch repair assay. The validity of the cell-free system was confirmed by the mismatch repair deficient yeast strain (Deltamsh2) and the complementation assay with purified yeast MSH2-MSH6.
Full Text Available The Fanconi Anemia (FA pathway consists of proteins involved in repairing DNA damage, including interstrand cross-links (ICLs. The pathway contains an upstream multiprotein core complex that mediates the monoubiquitylation of the FANCD2 and FANCI heterodimer, and a downstream pathway that converges with a larger network of proteins with roles in homologous recombination and other DNA repair pathways. Selective killing of cancer cells with an intact FA pathway but deficient in certain other DNA repair pathways is an emerging approach to tailored cancer therapy. Inhibiting the FA pathway becomes selectively lethal when certain repair genes are defective, such as the checkpoint kinase ATM. Inhibiting the FA pathway in ATM deficient cells can be achieved with small molecule inhibitors, suggesting that new cancer therapeutics could be developed by identifying FA pathway inhibitors to treat cancers that contain defects that are synthetic lethal with FA.
P. Marco eFisichella
Full Text Available Background: Historically all paraesophageal hernias were repaired surgically, today intervention is reserved for symptomatic paraesophageal hernias. In this review, we describe the indications for repair and explore the controversies in paraesophageal hernia repair, which include a comparison of open to laparoscopic paraesophageal hernia repair, the necessity of complete sac excision, the routine performance of fundoplication, and the use of mesh for hernia repair.Methods: We searched Pubmed for papers published between 1980 and 2015 using the following keywords: hiatal hernias, paraesophageal hernias, regurgitation, dysphagia, gastroesophageal reflux disease, aspiration, GERD, endoscopy, manometry, pH monitoring, proton pump inhibitors, anemia, iron deficiency anemia, Nissen fundoplication, sac excision, mesh, mesh repair. Results: Indications for paraesophageal hernia repair have changed, and currently symptomatic paraesophageal hernias are recommended for repair. In addition, it is important not to overlook iron-deficiency anemia and pulmonary complaints, which tend to improve with repair. Current practice favors a laparoscopic approach, complete sac excision, primary crural repair with or without use of mesh, and a routine fundoplication.
Tse, Andrew K; Lam, Patrick H; Walton, Judie R; Hackett, Lisa
Background Rotator cuff repair aims to reattach the torn tendon to the greater tuberosity footprint with suture anchors. The present study aimed to assess the diagnostic accuracy of ultrasound in predicting rotator cuff tear repairability and to assess which sonographic and pre-operative features are strongest in predicting repairability. Methods The study was a retrospective analysis of measurements made prospectively in a cohort of 373 patients who had ultrasounds of their shoulder and underwent rotator cuff repair. Measurements of rotator cuff tear size and muscle atrophy were made pre-operatively by ultrasound to enable prediction of rotator cuff repairability. Tears were classified following ultrasound as repairable or irreparable, and were correlated with intra-operative repairability. Results Ultrasound assessment of rotator cuff tear repairability has a sensitivity of 86% (p tear size (p tear size ≥4 cm2 or anteroposterior tear length ≥25 mm indicated an irreparable rotator cuff tear. Conclusions Ultrasound assessment is accurate in predicting rotator cuff tear repairability. Tear size or anteroposterior tear length and age were the best predictors of repairability. PMID:27582996
The 21st century promises the most open, competitive, and globalized markets in human history, as well as the most rapid pace of technological change ever. For nuclear energy, as any other, that presents challenges. Though the atom now supplies a good share of world electricity, its share of total energy is relatively small, anywhere from four to six per cent depending on how it is calculated. And, while energy is most needed in the developing world, four of every five nuclear plants are in industrialized countries. Critical problems that need to be overcome are well known - high capital costs for new plants, and concerns over proliferation risks and safety, (including safety of waste disposal) stand high among them. The IAEA and other programmes are confronting these problems through ambitious initiatives involving both industrialized and developing countries. They include the collaborative efforts known as the Generation-IV International Forum (GIF) and the IAEA International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). They use ideas, results and the best experiences from today's research and development tools and advanced types of nuclear energy systems to meet tomorrow's challenges. Though the market often decides the fate of new initiatives, the market is not always right for the common good. Governments, and the people that influence them, play an indispensable role in shaping progress in energy fields for rich and poor countries alike. They shoulder the main responsibilities for fundamental science, basic research, and long-term investments. For energy in particular, government investment and support will prove instrumental in the pace of innovation toward long-term options that are ready to replace limited fossil fuel supplies, and respond to the growing premium put on clean energy alternatives. Yet governments cannot go it alone. The challenges are too diverse and complex, and public concerns - about proliferation or safety - go beyond
Van Neste, Leander; Herman, James G; Otto, Gaëtan; Bigley, Joseph W; Epstein, Jonathan I; Van Criekinge, Wim
Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology. One gene in particular, GSTP1, has been widely studied in prostate cancer. Therefore a meta-analysis has been conducted to examine the role of this and other genes and the potential contribution to prostate cancer management and screening refinement. More than 30 independent, peer reviewed studies have reported a consistently high sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy tissue. The meta-analysis combined and compared these results. GSTP1 methylation detection can serve an important role in prostate cancer managment. The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of this and other genes and prostate cancer. Detection of DNA methylation in genes, including GSTP1, could serve an important role in clinical practice. Copyright © 2011 Wiley Periodicals, Inc.
Full Text Available Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.
Awad, Hanan; El-Aneed, Anas
With the fast growing market of pure enantiomer drugs and bioactive molecules, new chiral-selective analytical tools have been instigated including the use of mass spectrometry (MS). Even though MS is one of the best analytical tools that has efficiently been used in several pharmaceutical and biological applications, traditionally MS is considered as a "chiral-blind" technique. This limitation is due to the MS inability to differentiate between two enantiomers of a chiral molecule based merely on their masses. Several approaches have been explored to assess the potential role of MS in chiral analysis. The first approach depends on the use of MS-hyphenated techniques utilizing fast and sensitive chiral separation tools such as liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled to MS detector. More recently, several alternative separation techniques have been evaluated such as supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC); the latter being a hybrid technique that combines the efficiency of CE with the selectivity of LC. The second approach is based on using the MS instrument solely for the chiral recognition. This method depends on the behavioral differences between enantiomers towards a foreign molecule and the ability of MS to monitor such differences. These behavioral differences can be divided into three types: (i) differences in the enantiomeric affinity for association with the chiral selector, (ii) differences of the enantiomeric exchange rate with a foreign reagent, and (iii) differences in the complex MS dissociation behaviors of the enantiomers. Most recently, ion mobility spectrometry was introduced to qualitatively and quantitatively evaluate chiral compounds. This article provides an overview of MS role in chiral analysis by discussing MS based methodologies and presenting the challenges and promises associated with each approach. © 2013 Wiley Periodicals, Inc.
Alisky, J; Iczkowski, K; Rapoport, A; Troitsky, N
The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed
Maestri, Leah Adriana
Repair is typically seen in design as the restoration of broken objects to their original state. Repair by non-experts, or everyday repair, can often lead to novel forms of repair resulting in the creative repurposing of objects that are often unforeseen by designers. Using a grounded theory approach, this study describes key aspects of repair including: the techniques non-experts employ for repairing their objects; the motivations that prompt acts of repair; and the outcomes that result fr...
Kottemann, Molly C; Smogorzewska, Agata
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.
Colon, Modesto J; Telem, Dana A; Chin, Edward; Weber, Kaare; Divino, Celia M; Nguyen, Scott Q
Both polyester composite (POC) and polytetrafluoroethylene (PTFE) mesh are commonly used for laparoscopic ventral hernia repair. However, sparse information exists comparing perioperative and long-term outcome by mesh repair. A prospective database was utilized to identify 116 consecutive patients who underwent laparoscopic ventral hernia repair at The Mount Sinai Hospital from 2004-2009. Patients were grouped by type of mesh used, PTFE versus POC, and retrospectively compared. Follow-up at a mean of 12 months was achieved by telephone interview and office visit. Of the 116 patients, 66 underwent ventral hernia repair with PTFE and 50 with POC mesh. Patients were well matched by patient demographics. No difference in mean body mass index (BMI) was demonstrated between the PTFE and POC group (31.8 vs. 32.5, respectively; P=NS). Operative time was significantly longer in the PTFE group (136 vs.106 minutes, PPTFE group and none in the POC group (P NS). No other major complications occurred in the immediate postoperative period (30 days). At a mean follow-up of 12 months, no significant difference was demonstrated between the PTFE and POC groups in hernia recurrence (3% vs. 2%), wound complications (1% vs. 0%), mesh infection, requiring removal (3% vs. 0%), bowel obstruction (3% vs. 2%), or persistent pain or discomfort (28% vs. 32%), respectively (P=NS). Our study demonstrated no significant association between types of mesh used and postoperative complications. In the 12-month follow-up, no differences were noted in hernia recurrence.
Carlsen, C G; Lindorff-Larsen, K; Funch-Jensen, P; Lund, L; Charles, P; Konge, L
Lichtenstein hernia repair is a common surgical procedure and one of the first procedures performed by a surgical trainee. However, formal assessment tools developed for this procedure are few and sparsely validated. The aim of this study was to determine the reliability and validity of an assessment tool designed to measure surgical skills in Lichtenstein hernia repair. Key issues were identified through a focus group interview. On this basis, an assessment tool with eight items was designed. Ten surgeons and surgical trainees were video recorded while performing Lichtenstein hernia repair, (four experts, three intermediates, and three novices). The videos were blindly and individually assessed by three raters (surgical consultants) using the assessment tool. Based on these assessments, validity and reliability were explored. The internal consistency of the items was high (Cronbach's alpha = 0.97). The inter-rater reliability was very good with an intra-class correlation coefficient (ICC) = 0.93. Generalizability analysis showed a coefficient above 0.8 even with one rater. The coefficient improved to 0.92 if three raters were used. One-way analysis of variance found a significant difference between the three groups which indicates construct validity, p fashion with the new procedure-specific assessment tool. We recommend this tool for future assessment of trainees performing Lichtenstein hernia repair to ensure that the objectives of competency-based surgical training are met.
Taiwo, T.; Kim, T.K.; Feng, B.; Stauff, N.; Hoffman, E.; Ganda, F.; Todosow, M.; Brown, N.; Raitses, G.; Gehin, J.; Powers, J.; Youinou, G.; Hiruta, H.; Wigeland, R.
A recent Evaluation and Screening (E/S) study of nuclear fuel cycle options was conducted by grouping all potential options into 40 Evaluation Groups (EGs) based on similarities in fundamental physics characteristics and fuel cycle performance. Through a rigorous evaluation process considering benefit and challenge metrics, 4 of these EGs were identified by the E/S study as 'most promising'. All 4 involve continuous recycle of U/Pu or U/TRU with natural uranium feed in fast critical reactors. However, these most promising EGs also include fuel cycle groups with variations on feed materials, neutron spectra, and reactor criticality. Therefore, the impacts of the addition of natural thorium fuel feed to a system that originally only used natural uranium fuel feed, using an intermediate spectrum instead of a fast spectrum, and using externally-driven systems versus critical reactors were evaluated. It was found that adding thorium to the natural uranium feed mixture leads to lower burnup, higher mass flows, and degrades fuel cycle benefit metrics (waste management, resource utilization, etc.) for fuel cycles that continuously recycle U/Pu or U/TRU. Adding thorium results in fissions of 233 U instead of just 239 Pu and in turn results in a lower average number of neutrons produced per absorption (η) for the fast reactor system. For continuous recycling systems, the lower η results in lower excess reactivity and subsequently lower achievable fuel burnup. This in turn leads to higher mass flows (fabrication, reprocessing, disposal, etc.) to produce a given amount of energy and subsequent lower metrics performance. The investigated fuel cycle options with intermediate spectrum reactors also exhibited degraded performance in the benefit metrics compared to fast spectrum reactors. Similarly, this is due to lower η values as the spectrum softens. The best externally-driven systems exhibited similar performance as fast critical reactors in terms of mass flows
Goldberg, Andy; Mitchell, Katrina; Soans, Julian; Kim, Louise; Zaidi, Razi
The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre
Jiang Wenchun; Xu, X.P.; Gong, J.M.; Tu, S.T.
Highlights: ► Residual stress in the repair weld of a stainless steel clad plate is investigated. ► The effect of repair length on residual stress has been studied. ► Large tensile residual stress is generated in the repair weld and heat affected zone. ► With the increase of repair length, transverse stress is decreased. ► Repair length has little effect on longitudinal stress. - Abstract: A 3-D sequential coupling finite element simulation is performed to investigate the temperature field and residual stress in the repair weld of a stainless steel clad plate. The effect of repair length on residual stress has been studied, aiming to provide a reference for repairing the cracked clad plate. The results show that large tensile residual stresses are generated in the repair weld and heat affected zone (HAZ), and then decrease gradually away from the weld and HAZ. The residual stresses through thickness in the clad layer are relative uniform, while they are non-uniform in the base metal. A discontinuous stress distribution is generated across the interface between weld metal and base metal. The repair length has a great effect on transverse stress. With the increase of repair length, the transverse stress is decreased. When the repair length is increased to 14 cm, the peak of transverse stress has been decreased below yield strength, and the transverse stress in the weld and HAZ has also been greatly decreased. But the repair length has little effect on longitudinal stress.
WANG, MIN-CONG; LI, CHUN-LI; CUI, JIE; JIAO, MIN; WU, TAO; JING, LI; NAN, KE-JUN
BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types. PMID:26622537
Full Text Available Parkinson’s Disease is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.
Löckenhoff, Corinna E
The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.
Klein, William M P; Shepperd, James A; Suls, Jerry; Rothman, Alexander J; Croyle, Robert T
The theories, phenomena, empirical findings, and methodological approaches that characterize contemporary social psychology hold much promise for addressing enduring problems in public health. Indeed, social psychologists played a major role in the development of the discipline of health psychology during the 1970s and 1980s. The health domain allows for the testing, refinement, and application of many interesting and important research questions in social psychology, and offers the discipline a chance to enhance its reach and visibility. Nevertheless, in a review of recent articles in two major social-psychological journals (Personality and Social Psychology Bulletin and Journal of Personality and Social Psychology), we found that only 3.2% of 467 studies explored health-related topics. In this article, we identify opportunities for research at the interface of social psychology and health, delineate barriers, and offer strategies that can address these barriers as the discipline continues to evolve. © 2014 by the Society for Personality and Social Psychology, Inc.
Robert J. Torphy
Full Text Available Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3, B and T lymphocyte attenuator (BTLA, programmed death-1 homolog (PD-1H, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1, and the poliovirus receptor (PVR-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy.
Blanc, Dominique; Barochez, Aurelie de; Cozic, Aela
Issues of green bonds, socially responsible bonds and climate bonds are on the rise. Novethic estimates that some Euro 5 billion in such bonds has been issued since the start of 2013 by development banks, the main issuers of this type of debt. The figure is equal to over half of their total issues since 2007. Including local authorities, corporations and banks, a total Euro 8 billion of these bonds has been issued thus far in 2013. Given the size of the bond market, which the OECD estimated at Euro 95,000 billion in 2011, green and social bonds are still something of a niche but have strong growth potential. A number of large issues, from Euro 500 million to Euro 1 billion, were announced at the end of the year. Unlike conventional bonds, green and social bonds are not intended to finance all the activities of the issuer or refinance its debt. They serve instead to finance specific projects, such as producing renewable energy or adapting to climate change, the risk of which is shouldered by the issuer. This makes them an innovative instrument, used to earmark investments in projects with a direct environmental or social benefit rather than simply on the basis of the issuer's sustainable development policy. With financing being sought for the ecological transition, green and social bonds are promising instruments, sketching out at global level the shape of tools adapted to the financing of a green economy. On the strength of these advantages, the interest of responsible investors - the main target of green and social bond issuers - is growing fast. Judging by issuer press releases and the most commonly used currencies, the main subscribers today are US investors, among them CalSTRS and fund managers like Calvert Investment Management and Trillium Asset Management. European asset owners are also starting to focus on green and social bonds. A Novethic survey shows that 13% of them have already subscribed to such an issue or plan to do so. The present study
Full Text Available Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1 significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features.
This article discusses the cleaning and recoating/repair of condensate tanks or other vessels in a nuclear power plant. The topics of the article include the safety and regulatory need for this system of repair, a description of the work done on the Brown's Ferry MK-1 suppression chamber, coating failure mechanisms, qualitative inspection, quantitative inspection, quantitative inspection results, spot repairs, and economic considerations
Full Text Available MV repair in the rheumatic population is feasible with acceptable long-term results.1 Incidence of mitral stenosis (MS following mitral valve (MV repair for severe rheumatic mitral regurgitation (MR and usefulness of percutaneous transluminal mitral valvuloplasty (PTMC in these patients is not described in literature. We report a case of successful PTMC in severe MS following MV repair for severe rheumatic MR.
Rosenberg, J; Kehlet, H
PURPOSE: The aim of this study was to describe an accelerated-stay program for repair of the external anal sphincter. METHODS: Twenty consecutive patients undergoing overlapping repair of the external anal sphincter were included in the study. Effect parameters were length of hospitalization....... CONCLUSION: We have described a safe accelerated-stay program (24 to 48 hours) for overlapping repair of external anal sphincter....
Full Text Available Tomas Lindahl completed his medical studies at Karolinska Institute in 1970. Yet, his work has always been dedicated to unraveling fundamental mechanisms of DNA decay and DNA repair. His research is characterized with groundbreaking discoveries on the instability of our genome, the identification of novel DNA repair activities, the characterization of DNA repair pathways, and the association to diseases, throughout his 40 years of scientific career.
Wu, Darrell; Coselli, Joseph S.; Johnson, Michael L.; LeMaire, Scott A.
Background: After thoracoabdominal aortic aneurysm (TAAA) repair, blood tests assessing hepatopancreaticobiliary (HPB) organs commonly have abnormal results. The clinical significance of such abnormalities is difficult to determine because the expected postoperative levels have not been characterized. Therefore, we sought to establish expected trends in HPB laboratory values after TAAA repair. Methods: This 5-year study comprised 155 patients undergoing elective Crawford extent II TAAA repair...
Elliott, Christopher G.; Kim, Shawna S.; Hamilton, Douglas W.
In the past year, three papers have been published exploring the role of the matricellular protein periostin in excisional skin repair. These papers all show a delay in wound closure and the kinetics of this delay are strikingly similar across the three reports. The similarities between these papers end, however, when each investigates the mechanism through which periostin influences skin repair. Three proposed mechanisms have been identified: (1) myofibroblast differentiation, (2) keratinocy...
Paskin, Matthew A.; Trevino, Alice W.; Ferrer, Geraldo; Dillard, John T.
Today’s environment of increased operations tempo is stressing the KC- 135 Stratotanker fleet. With an 80-year life span expectancy, effectively maintaining these aircraft is challenging. This research modeled the KC- 135 programmed depot maintenance (PDM) flight controls repair cell to identify improvement opportunities within the repair process. Computational organizational modeling (COM) incorporates the human element along with organizational design theory. By employing ...
DeFroda, Steven F; Mehta, Nabil; Owens, Brett D
Outcomes after arthroscopic Bankart repair can be highly dependent on compliance and participation in physical therapy. Additionally, there are many variations in physician-recommended physical therapy protocols. The rehabilitation protocols of academic orthopaedic surgery departments vary widely despite the presence of consensus protocols. Descriptive epidemiology study. Level 3. Web-based arthroscopic Bankart rehabilitation protocols available online from Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery programs were included for review. Individual protocols were reviewed to evaluate for the presence or absence of recommended therapies, goals for completion of ranges of motion, functional milestones, exercise start times, and recommended time to return to sport. Thirty protocols from 27 (16.4%) total institutions were identified out of 164 eligible for review. Overall, 9 (30%) protocols recommended an initial period of strict immobilization. Variability existed between the recommended time periods for sling immobilization (mean, 4.8 ± 1.8 weeks). The types of exercises and their start dates were also inconsistent. Goals to full passive range of motion (mean, 9.2 ± 2.8 weeks) and full active range of motion (mean, 12.2 ± 2.8 weeks) were consistent with other published protocols; however, wide ranges existed within the reviewed protocols as a whole. Only 10 protocols (33.3%) included a timeline for return to sport, and only 3 (10%) gave an estimate for return to game competition. Variation also existed when compared with the American Society of Shoulder and Elbow Therapists' (ASSET) consensus protocol. Rehabilitation protocols after arthroscopic Bankart repair were found to be highly variable. They also varied with regard to published consensus protocols. This discrepancy may lead to confusion among therapists and patients. This study highlights the importance of attending surgeons being very clear and specific with
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.
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.
Falk, Martin; Lukášová, Emilie; Gabrielová, Barbora; Ondřej, Vladan; Kozubek, Stanislav
Roč. 1773, č. 10 (2007), s. 1534-1545 ISSN 0167-4889 R&D Projects: GA ČR(CZ) GP204/06/P349; GA ČR(CZ) 1QS500040508; GA AV ČR(CZ) IAA1065203; GA MŠk(CZ) 1P05OC084 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : chromatin structure * double- strand breaks (DSB) * DNA repair Subject RIV: BO - Biophysics Impact factor: 4.374, year: 2007
Full Text Available stream_source_info Moodley_2011.pdf.txt stream_content_type text/plain stream_size 32328 Content-Encoding ISO-8859-1 stream_name Moodley_2011.pdf.txt Content-Type text/plain; charset=ISO-8859-1 Root Justi cations... the ontology, based on the no- tion of root justi cations [8, 9]. In Section 5, we discuss the implementation of a Prot eg e3 plugin which demonstrates our approach to ontology repair. In this section we also discuss some experimental results comparing...
Woodson, R Dodge
The success of a repair or rehabilitation project depends on the specific plans designed for it. Concrete Structures: Protection, Repair and Rehabilitation provides guidance on evaluating the condition of the concrete in a structure, relating the condition of the concrete to the underlying cause or causes of that condition, selecting an appropriate repair material and method for any deficiency found, and using the selected materials and methods to repair or rehabilitate the structure. Guidance is also provided for engineers focused on maintaining concrete and preparing concrete investigation r
Induced repair and mutagenesis of animal cells against UV were studied in contrast with SOS repair of E. coli primarily by the use of viruses. Since UV-enhanced reactivation is a phenomenon similar to UV-reactivation (mutagenesis) and the presence of lesion bypass synthsis has been suggested, UV-enhanced reactivation has several common aspects with SOS reactivation of E. coli. However, correlation is not necessarily noted between increase in the viral survival rate and mutagenesis, nor do protease blockers exert any effect. Therefore, SOS repair of E. coli may have different mechansms from induced repair and mutagenesis in animal cells. (Ueda, J.)
The biological impact of any DNA damaging agent is a combined function of the chemical nature of the induced lesions and the efficiency and accuracy of their repair. Although much has been learned frommicrobes and mammals about both the repair of DNA damage and the biological effects of the persistence of these lesions, much remains to be learned about the mechanism and tissue-specificity of repair in plants. This review focuses on recent work on the induction and repair of DNA damage in higher plants, with special emphasis on UV-induced DNA damage products. (author)
Studies on DNA repair have been performed using microorganisms such as Escherichia coli and cultured human and mammalian cells. However, it is well known that cultured organic cells differ from each other in many respects, although DNA repair is an extremely fundamental function of organisms to protect genetic information from environmental mutagens such as radiation and 0 radicals developing in the living body. To answer the question of how DNA repair is different between the animal species, current studies on DNA repair of cultured vertebrate cells using the methods similar to those in mammalian experiments are reviewed. (Namekawa, K.)
Jenkins, Gareth J.S.; Zair, Zoulikha; Johnson, George E.; Doak, Shareen H.
It has been long assumed that DNA damage is induced in a linear manner with respect to the dose of a direct acting genotoxin. Thus, it is implied that direct acting genotoxic agents induce DNA damage at even the lowest of concentrations and that no 'safe' dose range exists. The linear (non-threshold) paradigm has led to the one-hit model being developed. This 'one hit' scenario can be interpreted such that a single DNA damaging event in a cell has the capability to induce a single point mutation in that cell which could (if positioned in a key growth controlling gene) lead to increased proliferation, leading ultimately to the formation of a tumour. There are many groups (including our own) who, for a decade or more, have argued, that low dose exposures to direct acting genotoxins may be tolerated by cells through homeostatic mechanisms such as DNA repair. This argument stems from the existence of evolutionary adaptive mechanisms that allow organisms to adapt to low levels of exogenous sources of genotoxins. We have been particularly interested in the genotoxic effects of known mutagens at low dose exposures in human cells and have identified for the first time, in vitro genotoxic thresholds for several mutagenic alkylating agents (Doak et al., 2007). Our working hypothesis is that DNA repair is primarily responsible for these thresholded effects at low doses by removing low levels of DNA damage but becoming saturated at higher doses. We are currently assessing the roles of base excision repair (BER) and methylguanine-DNA methyltransferase (MGMT) for roles in the identified thresholds (Doak et al., 2008). This research area is currently important as it assesses whether 'safe' exposure levels to mutagenic chemicals can exist and allows risk assessment using appropriate safety factors to define such exposure levels. Given human variation, the mechanistic basis for genotoxic thresholds (e.g. DNA repair) has to be well defined in order that susceptible individuals are
Full text: Thesis. The 'NPT regime' has arrived at a fateful crossroads. Though extended indefinitely in 1995, its future is my no means secure. The future 'progress' of this treaty will depend upon whether the 'promises' of its States parties are fully implemented and, eventually, upon the treaty's success in achieving fully universal membership. Challenges The treaty faces many short-term and longer-term challenges: Short term - The first Preparatory Committee meeting for the 2005 Review Conference will meet next year. NNWS will want to see some evidence of progress on nuclear disarmament (Art. VI), along the lines prescribed in the 13 'practical steps' agreed at the last Review Conference. Yet progress has been set back by: uncertainties over the future of the ABM Treaty; the failure of START II and the CTBT to enter into force; the lack of a FISMAT treaty and a treaty establishing a NWFZ in Central Asia; continued qualitative improvements in nuclear weapons; hints that nuclear testing may one day resume; the persistence of doctrines of first-use, pre-emptive use, and use against states that use CBW. Other compliance-related questions will arise over safeguards (e.g. the inability of the IAEA to conduct inspections in the DPRK; signs of a breakdown of the norm of full-scope IAEA safeguards, e.g. in South Asia). There are also concerns over the implementation of non-proliferation commitments (e.g. persisting allegations about nuclear weapon programmes in existing NNWS). The terrorist attacks in New York and Washington, D.C. on 11 September should also serve as a reminder of the new terrorist dangers relating to the possible use of weapons of mass destruction and unorthodox delivery systems. Longer term - Selectivity in the enforcement of NPT norms; unilateralism; IAEA funding uncertainties and shortfalls; difficulties in reaching universal membership (India, Pakistan, and Israel); continuing compliance problems with respect to both non-proliferation and
Erbel, Raimund; Böse, Dirk; Haude, Michael; Kordish, Igor; Churzidze, Sofia; Malyar, Nasser; Konorza, Thomas; Sack, Stefan
Coronary stent implantation started in Germany 20 years ago. In the beginning, the progress was very slow and accelerated 10 years later. Meanwhile, coronary stent implantation is a standard procedure in interventional cardiology. From the beginning of permanent stent implantation, research started to provide temporary stenting of coronary arteries, first with catheter-based systems, later with stent-alone technology. Stents were produced from polymers or metal. The first polymer stent implantation failed except the Igaki-Tamai stent in Japan. Newly developed absorbable polymer stents seem to be very promising, as intravascular ultrasound (IVUS) and optical coherence tomography have demonstrated. Temporary metal stents were developed based on iron and magnesium. Currently, the iron stent is tested in peripheral arteries. The absorbable magnesium stent (Biotronik, Berlin, Germany) was tested in peripheral arteries below the knee and meanwhile in the multicenter international PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting with Absorbable Metal Stents) study. The first magnesium stent implantation was performed on July 30, 2004 after extended experimental testing in Essen. The magnesium stent behaved like a bare-metal stent with low recoil of 5-7%. The stent struts were absorbed when tested with IVUS. Stent struts were not visible by fluoroscopy or computed tomography (CT) as well as magnetic resonance imaging (MRI). That means, that the magnesium stent is invisible and therefore CT and MRI can be used for imaging of interventions. Only using micro-CT the stent struts were visible. The absorption process could be demonstrated in a patient 18 days after implantation due to suspected acute coronary syndrome, which was excluded. IVUS showed a nice open lumen. Stent struts were no longer visible, but replaced by tissue indicating the previous stent location. Coronary angiography after 4 months showed an ischemia-driven target lesion
Full Text Available Given recent developments in relation to the prosecution of international crimes, it might be thought that one of the last bastions of sovereignty has been breached, and international criminal law has not only entrenched itself in international law. Indeed further to this, it has assumed a supranational position that stands entirely above States, promising justice for all and as a trump card over depredations committed in the name of State sovereignty. After all, Charles Taylor from Liberia is standing trial before the Special Court for Sierra Leone, Slobodan Milošević only escaped judgment by the International Criminal Tribunal for the former
Ritter, Gary W.; Ash, Jennifer
Promise programs are place-based scholarships, generally tied to a city or school district, offering near-universal access to all living in the "place." While Promise programs share some characteristics with other scholarship programs, they're unique because they seek to change communities and schools. Underlying such promise programs is…
Charland, Patrick J; Robbins, Tom; Rodriguez, Evilio; Nifong, Wiley L; Chitwood, Randolph W
To determine if the time required to perform mitral valve repairs using telemanipulation technology decreases with experience and how that decrease is influenced by patient and procedure variables. A single-center retrospective review was conducted using perioperative and outcomes data collected contemporaneously on 458 mitral valve repair surgeries using telemanipulative technology. A regression model was constructed to assess learning with this technology and predict total robot time using multiple predictive variables. Statistical analysis was used to determine if models were significantly useful, to rule out correlation between predictor variables, and to identify terms that did not contribute to the prediction of total robot time. We found a statistically significant learning curve (P learning percentage∗ derived from total robot times† for the first 458 recorded cases of mitral valve repair using telemanipulative technology is 95% (R(2) = .40). More than one third of the variability in total robot time can be explained through our model using the following variables: type of repair (chordal procedures, ablations, and leaflet resections), band size, use of clips alone in band implantation, and the presence of a fellow at bedside (P Learning in mitral valve repair surgery using telemanipulative technology occurs at the East Carolina Heart Institute according to a logarithmic curve, with a learning percentage of 95%. From our regression output, we can make an approximate prediction of total robot time using an additive model. These metrics can be used by programs for benchmarking to manage the implementation of this new technology, as well as for capacity planning, scheduling, and capital budget analysis. Copyright © 2011 The American Association for Thoracic Surgery. All rights reserved.
Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour
X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...
BARTLETT, R.S.; GUILLE, J.T.; CHEN, X.; CHRISTENSEN, M.B.; WANG, S.F.; THIBEAULT, S.L.
Background Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. Methods Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. Results and discussion Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]β1, alpha smooth muscle actin, interleukin-1β, interleukin-17β and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC–treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair. PMID:27637759
Hammond, Barry D; Cooper, Jeril R; Lazarchik, David A
The importance of provisional restorations is often downplayed, as they are thought of by some as only "temporaries." As a result, a less-than-ideal provisional is sometimes fabricated, in part because of the additional chair time required to make provisional modifications when using traditional techniques. Additionally, in many dental practices, these provisional restorations are often fabricated by auxillary personnel who may not be as well trained in the fabrication process. Because provisionals play an important role in achieving the desired final functional and esthetic result, a high-quality provisional restoration is essential to fabricating a successful definitive restoration. This article describes a method for efficiently and predictably repairing both methacrylate and bis-acryl provisional restorations using flowable composite resin. By use of this relatively simple technique, provisional restorations can now be modified or repaired in a timely and productive manner to yield an exceptional result. Successful execution of esthetic and restorative dentistry requires attention to detail in every aspect of the case. Fabrication of high-quality provisional restorations can, at times, be challenging and time consuming. The techniques for optimizing resin provisional restorations as described in this paper are pragmatic and will enhance the delivery of dental treatment.
Aguilar H, F.
Due to the corrosion problems of the aluminum coating of the reactor pool, a periodic inspections program by ultrasound to evaluate the advance grade and the corrosion speed was settled down. This inspections have shown the necessity to repair some areas, in those that the slimming is significant, of not making it can arrive to the water escape of the reactor pool. The objective of the repair is to place patches of plates of 1/4 inch aluminum thickness in the areas of the reactor 'liner', in those that it has been detected by ultrasound a smaller thickness or similar to 3 mm. To carry out this the fuels are move (of the core and those that are decaying) to a temporary storage, the structure of the core is confined in a tank that this placed inside the pool of the reactor, a shield is placed in the thermal column and it is completely extracted the water for to leave uncover the 'liner' of the reactor. (Author)
Brytsko A. A.
Full Text Available Background. It is well known that meniscectomy leads to osteoarthritis of the knee and proprioception impairment. Objective. The aim of this study was to assess retrospectively the joint position sense after meniscal suture and partial medial meniscal resection and to estimate the patients’ satisfaction with knee function. Material and Methods. We evaluated the outcomes of 27 patients after meniscal repair and compared them to those of 24 patients after partial meniscal resection. We estimated the joint position sense at 30°, 45° and 60° of flexion using the Biodex system 4 Pro. All patients were assessed with the IKDC 2000 subjective knee score. Results. A statistically significant worsening in reproducing the injured joint position in comparison to the healthy limb in both groups was observed. These impairments were mostly expressed at 45° and 60° of knee flexion, and were worsening over time in the group of patients who had undergone medial meniscal resection. An average value by the IKDC 2000 scale after 24 months in the meniscorrhaphy group was 76.73 ± 11.17% and 68.93 ± 14.76% after partial medial meniscal resection. Сonclusion. The control over position of the knee is not impaired after meniscal repair. An overall satisfaction with joint function is higher in patients who undergo meniscal suture in comparison to the partial medial meniscal resection group.
A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model.
Fu, Wei-Li; Zhou, Chun-Yan; Yu, Jia-Kuo
Bone marrow (BM) has been considered as a major source of mesenchymal stem cells (MSCs), but it has many disadvantages in clinical application. However, MSCs from peripheral blood (PB) could be obtained by a less invasive method and be more beneficial for autologous transplantation than BM MSCs, which makes PB a promising source for articular cartilage repair in clinical use. To assess whether MSCs from mobilized PB of New Zealand White rabbits have similar biological characteristics in vitro and chondrogenesis in vivo as BM MSCs. Controlled laboratory study. A combined method of drug administration containing granulocyte colony stimulating factor (G-CSF) plus CXCR4 antagonist AMD3100 was adopted to mobilize the PB stem cells of adult New Zealand White rabbits in vitro. The isolated cells were identified as MSCs by morphological characteristics, surface markers, and differentiation potentials. A comparison between PB MSCs and BM MSCs was made in terms of biological characteristics in vitro and chondrogenesis in vivo. This issue was investigated from the aspects of morphology, immune phenotype, multiple differentiation capacity, expansion potential, antiapoptotic capacity, and ability to repair cartilage defects in vivo of PB MSCs compared with BM MSCs. Peripheral blood MSCs were successfully mobilized by the method of combined drug administration, then isolated, expanded, and identified in vitro. No significant difference was found concerning the morphology, immune phenotype, and antiapoptotic capacity between PB MSCs and BM MSCs. Significantly, MSCs from both sources compounded with decalcified bone matrix showed the same ability to repair cartilage defects in vivo. For multipluripotency, BM MSCs exhibited a more osteogenic potential and higher proliferation capacity than PB MSCs, whereas PB MSCs possessed a stronger adipogenic and chondrogenic differentiation potential than BM MSCs in vitro. Although there are some differences in the proliferation and
Zhang, Rui; Rosen, Joseph M
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.
Zhovmer, Alexander; Oksenych, Valentyn; Coin, Frédéric
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.
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.
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
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.
Yussra, Y; Sutton, P A; Kosai, N R; Razman, J; Mishra, R K; Harunarashid, H; Das, S
Inguinal hernia remains the most commonly encountered surgical problem. Various methods of repair have been described, and the most suitable one debated. Single port access (SPA) surgery is a rapidly evolving field, and has the advantage of affording 'scarless' surgery. Single incision laparoscopic surgery (SILS) for inguinal hernia repair is seen to be feasible in both total extraperitoneal (TEP) and transabdominal pre-peritoneal (TAPP) approaches. Data and peri-operative information on both of these however are limited. We aimed to review the clinical experience, feasibility and short term complications related to laparoscopic inguinal hernia repair via single port access. A literature search was performed using Google Scholar, Springerlink Library, Highwire Press, Surgical Endoscopy Journal, World Journal of Surgery and Medscape. The following search terms were used: laparoscopic hernia repair, TAPP, TEP, single incision laparoscopic surgery (SILS). Fourteen articles in English language related to SILS inguinal hernia repair were identified. Nine articles were related to TEP repair and the remaining 5 to TAPP. A total of 340 patients were reported within these studies: 294 patients having a TEP repair and 46 a TAPP. Only two cases of recurrence were reported. Various ports have been utilized, including the SILS port, Tri-Port and a custom- made port using conventional laparoscopic instruments. The duration of surgery was 40-100 minutes and the average length of hospital stay was one day. Early outcomes of this novel technique show it to be feasible, safe and with potentially better cosmetic outcome.
Zhang Yuanlin; Wang Guanjun
In this paper, a deteriorating cold standby repairable system consisting of two dissimilar components and one repairman is studied. For each component, assume that the successive working times form a decreasing geometric process while the consecutive repair times constitute an increasing geometric process, and component 1 has priority in use and repair. Under these assumptions, we consider a replacement policy N based on the number of repairs of component 1 under which the system is replaced when the number of repairs of component 1 reaches N. Our problem is to determine an optimal policy N* such that the average cost rate (i.e. the long-run average cost per unit time) of the system is minimized. The explicit equation of the average cost rate of the system is derived and the corresponding optimal replacement policy N* can be determined analytically or numerically. Finally, a numerical example with Weibull distribution is given to illustrate some theoretical results in this paper.
Full Text Available In recent times, infertility among both man and woman has become a major concern affecting about 20 per cent of the population worldwide and has been attributed in part to several aetiological factors such as changes in lifestyle, which includes sedentary life, dietary habits, sleep anomalies, environmental pollution, etc. Assisted reproductive technologies (ART have come to the rescue of many such couples, but presence of metabolic disorders such as obesity, diabetes with insulin resistance (IR and its secondary complications (micro- and macro-vascular complications, become confounders to the outcome of ART. Cell therapies are arising as a new hope in the management of reproductive disorders and currently, the efficacy of mesenchymal stem cells (MSCs harvested from the adult sources finds wide application in the management of diseases like stroke, neuropathy, nephropathy, myopathy, wounds in diabetes, etc. Given the capacity of MSCs to preferentially home to damaged tissue and modulate the cellular niche/microenvironment to augment tissue repairs and regeneration, the present review outlines the applications of MSCs in the management of infertility/reproductive disorders.
Wang, Jianyun; Ersan, Yusuf Cagatay; Boon, Nico; De Belie, Nele
The beneficial effect of microbially induced carbonate precipitation on building materials has been gradually disclosed in the last decade. After the first applications of on historical stones, promising results were obtained with the respect of improved durability. An extensive study then followed on the application of this environmentally friendly and compatible material on a currently widely used construction material, concrete. This review is focused on the discussion of the impact of the two main applications, bacterial surface treatment and bacteria based crack repair, on concrete durability. Special attention was paid to the choice of suitable bacteria and the metabolic pathway aiming at their functionality in concrete environment. Interactions between bacterial cells and cementitious matrix were also elaborated. Furthermore, recommendations to improve the effectiveness of bacterial treatment are provided. Limitations of current studies, updated applications and future application perspectives are shortly outlined.
Kenneth H. Green; Willie E. Rochefort; Nick Wannenmacher; John A. Clark; Kevin Harris
Current procedures for repairing polyethylene (PE) gas pipe require excavation, isolation, and removal of the damaged section of pipe followed by fusing a new section of pipe into place. These techniques are costly and very disruptive. An alternative repair method was developed at Timberline Tool with support from Oregon State University (OSU) and funding by the U. S. Department of Energy National Energy Technology Laboratory (DOE/NETL). This project was undertaken to design, develop and test a tool and method for repairing damaged PE pipe remotely and externally in situ without squeezing off the flow of gas, eliminating the need for large-scale excavations. Through an iterative design and development approach, a final engineered prototype was developed that utilizes a unique thermo-chemical and mechanical process to apply a permanent external patch to repair small nicks, gouges and punctures under line pressure. The project identified several technical challenges during the design and development process. The repair tool must be capable of being installed under live conditions and operate in an 18-inch keyhole. This would eliminate the need for extensive excavations thus reducing the cost of the repair. Initially, the tool must be able to control the leak by encapsulating the pipe and apply slight pressure at the site of damage. Finally, the repair method must be permanent at typical operating pressures. The overall results of the project have established a permanent external repair method for use on damaged PE gas pipe in a safe and cost-effective manner. The engineered prototype was subjected to comprehensive testing and evaluation to validate the performance. Using the new repair tool, samples of 4-inch PE pipe with simulated damage were successfully repaired under line pressure to the satisfaction of DOE/NETL and the following natural gas companies: Northwest Natural; Sempra Energy, Southwest Gas Corporation, Questar, and Nicor. However, initial results of
Uraki, Keiichi; Okamura, Hisanobu; Matsumoto, Toshimi
In structures or equipment made of stainless steel, Ni-based alloy or a low alloy steel and undergoing neutron irradiation and causing a crack-like defect in a reactor pressure vessel, a plate is applied to a region where the crack-like detect is caused, and pressure is applied locally to bond the plate by generated resistance. Namely, electric current is supplied to the portion to be bonded while pressurizing to bond it by generated resistance heat. Then the propagation of cracks can be prevented and occurrence of cracks upon repairing can be prevented relative to a structural member undergoing neutron irradiation in the reactor pressure vessel and causing a crack-like defect thereby enabling to provide effects of preventing occurrence of an accident due to stress corrosion cracking of a nuclear power plant and prolonging the integrity of the plant. (N.H.)
Plewczynski, Dariusz; Hoffmann, Marcin; Grotthuss, Marcin von; Knizewski, Lukasz; Rychewski, Leszek; Eitner, Krystian; Ginalski, Krzysztof
In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation
Radnor, Zoe J; Holweg, Matthias; Waring, Justin
In an effort to improve operational efficiency, healthcare services around the world have adopted process improvement methodologies from the manufacturing sector, such as Lean Production. In this paper we report on four multi-level case studies of the implementation of Lean in the English NHS. Our results show that this generally involves the application of specific Lean 'tools', such as 'kaizen blitz' and 'rapid improvement events', which tend to produce small-scale and localised productivity gains. Although this suggests that Lean might not currently deliver the efficiency improvements desired in policy, the evolution of Lean in the manufacturing sector also reveals this initial focus on the 'tool level'. In moving to a more system-wide approach, however, we identify significant contextual differences between healthcare and manufacturing that result in two critical breaches of the assumptions behind Lean. First, the customer and commissioner in the private sector are the one and the same, which is essential in determining 'customer value' that drives process improvement activities. Second, healthcare is predominantly designed to be capacity-led, and hence there is limited ability to influence demand or make full use of freed-up resources. What is different about this research is that these breaches can be regarded as not being primarily 'professional' in origin but actually more 'organisational' and 'managerial' and, if not addressed could severely constrain Lean's impact on healthcare productivity at the systems level. Copyright © 2011 Elsevier Ltd. All rights reserved.
Case, Andrew D; Todd, Nathan R; Kral, Michael J
Community psychology recognizes the need for research methods that illuminate context, culture, diversity, and process. One such method, ethnography, has crossed into multiple disciplines from anthropology, and indeed, community psychologists are becoming community ethnographers. Ethnographic work stands at the intersection of bridging universal questions with the particularities of people and groups bounded in time, geographic location, and social location. Ethnography is thus historical and deeply contextual, enabling a rich, in-depth understanding of communities that is aligned with the values and goals of community psychology. The purpose of this paper is to elucidate the potential of ethnography for community psychology and to encourage its use within the field as a method to capture culture and context, to document process, and to reveal how social change and action occur within and through communities. We discuss the method of ethnography, draw connections to community psychology values and goals, and identify tensions from our experiences doing ethnography. Overall, we assert that ethnography is a method that resonates with community psychology and present this paper as a resource for those interested in using this method in their research or community activism.
Birt, Diane F; Boylston, Terri; Hendrich, Suzanne; Jane, Jay-Lin; Hollis, James; Li, Li; McClelland, John; Moore, Samuel; Phillips, Gregory J; Rowling, Matthew; Schalinske, Kevin; Scott, M Paul; Whitley, Elizabeth M
Ongoing research to develop digestion-resistant starch for human health promotion integrates the disciplines of starch chemistry, agronomy, analytical chemistry, food science, nutrition, pathology, and microbiology. The objectives of this research include identifying components of starch structure that confer digestion resistance, developing novel plants and starches, and modifying foods to incorporate these starches. Furthermore, recent and ongoing studies address the impact of digestion-resistant starches on the prevention and control of chronic human diseases, including diabetes, colon cancer, and obesity. This review provides a transdisciplinary overview of this field, including a description of types of resistant starches; factors in plants that affect digestion resistance; methods for starch analysis; challenges in developing food products with resistant starches; mammalian intestinal and gut bacterial metabolism; potential effects on gut microbiota; and impacts and mechanisms for the prevention and control of colon cancer, diabetes, and obesity. Although this has been an active area of research and considerable progress has been made, many questions regarding how to best use digestion-resistant starches in human diets for disease prevention must be answered before the full potential of resistant starches can be realized.
Published three months before the Copenhagen Conference, this analysis aims at identifying the postures of the different negotiators, at deciphering what is at stake as far as the future regime of struggle against climate change is concerned, and at giving the keys of a possible positive outcome for these negotiations. First, the authors comment the challenges of the definition of mitigation objectives for greenhouse gas emissions which requires an agreement between developed countries, emerging countries, developing countries, and less advanced developing countries which, until now, are not submitted to the same regime. Developed countries already have some obligations and will have to define these objectives, and the challenge is to obtain a commitment of emerging countries (notably China), and maybe of some developing countries, to adopt some constraints. On another hand, these negotiations could be the occasion of a revision of North-South and South-South relationships because of diverging interests between emerging countries and developing countries on technological issues. Other issues are at stake: intellectual property rights, the CDM (Clean development mechanism) reform, the deforestation. Finally, the authors highlight the difficult issues of financial transfers
Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)
In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.
Full Text Available PURPOSE: In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. METHODS AND MATERIALS: In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. RESULTS: Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. CONCLUSIONS: Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.
Full Text Available Spinal cord injury (SCI remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.
da Silva, Jucélia Barbosa; Temponi, Vanessa dos Santos; Gasparetto, Carolina Miranda; Fabri, Rodrigo Luiz; Aragão, Danielle Maria de Oliveira; Pinto, Nícolas de Castro Campos; Ribeiro, Antônia; Scio, Elita; Del-Vechio-Vieira, Glauciemar; de Sousa, Orlando Vieira
The present study evaluated the antioxidant potential of Vernonia condensata Baker (Asteraceae). Dried and powdered leaves were exhaustively extracted with ethanol by static maceration followed by partition to obtain the hexane, dichloromethane, ethyl acetate, and butanol fractions. Total phenols and flavonoids contents were determined through spectrophotometry and flavonoids were identified by HPLC-DAD system. The antioxidant activity was assessed by DPPH radical scavenging activity, TLC-bioautography, reducing power of Fe+3, phosphomolybdenum, and TBA assays. The total phenolic content and total flavonoids ranged from 0.19 to 23.11 g/100 g and from 0.13 to 4.10 g/100 g, respectively. The flavonoids apigenin and luteolin were identified in the ethyl acetate fraction. The IC50 of DPPH assay varied from 4.28 to 75.10 µg/mL and TLC-bioautography detected the antioxidant compounds. The reducing power of Fe+3 was 19.98 to 336.48 μg/mL, while the reaction with phosphomolybdenum ranged from 13.54% to 32.63% and 56.02% to 135.00% considering ascorbic acid and rutin as reference, respectively. At 30 mg/mL, the ethanolic extract and fractions revealed significant effect against lipid peroxidation. All these data sustain that V. condensata is an important and promising source of bioactive substances with antioxidant activity. PMID:24489987
Full Text Available The most important performance for repair materials is adhesion to the substrate. The authors experimentally find out that high modulus fine aggregates in repair material enhance strength of it as well as the strength of the interface repaired with it, compared to the ordinary repair without fine aggregates. This paper elaborates the mechanisms for that with fractographic observation and FEM analysis based on the results of experiment. Also the authors discuss the ways for enhancing the strength and ductility of the repaired mortar
Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana
The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).
Lädermann, Alexandre; Denard, Patrick J; Burkhart, Stephen S
Importance Recurrent tear after rotator cuff repair (RCR) is common. Conservative, and open and arthroscopic revisions, have been advocated to treat these failures. Aim or objective The purpose of this systematic review was to evaluate the different options for managing recurrent rotator cuff tears. Evidence review A search was conducted of level I through 4 studies from January 2000 to October 2015, to identify studies reporting on failed RCR. 10 articles were identified. The overall quality of evidence was very low. Findings Mid-term to long-term follow-up of patients treated conservatively revealed acceptable results; a persistent defect is a well-tolerated condition that only occasionally requires subsequent surgery. Conservative treatment might be indicated in most patients, particularly in case of posterosuperior involvement and poor preoperative range of motion. Revision surgery might be indicated in a young patient with a repairable lesion, a 3 tendon tear, and in those with involvement of the subscapularis. Conclusions and relevance The current review indicates that arthroscopic revision RCR can lead to improvement in functional outcome despite a high retear rate. Further studies are needed to develop specific rehabilitation in the case of primary rotator cuff failure, to better understand the place of each treatment option, and, in case of repair, to optimise tendon healing. PMID:27134759
This document contains the abstracts of 105 papers presented at the Congress. Topics covered include the Escherichia coli nucleotide excision repair system, DNA repair in malignant transformations, defective DNA repair, and gene regulation. (TEM)
This document contains the abstracts of 105 papers presented at the Congress. Topics covered include the Escherichia coli nucleotide excision repair system, DNA repair in malignant transformations, defective DNA repair, and gene regulation
bilateral hernias, and recurrent hernias), there are data demonstrating an ... no reports of laparoscopic inguinal hernia repair from the. Anglophone ... MATERIALS AND METHODS .... inguinal hernia repair has advantages over open repair for.
.... To evaluate this hypothesis we quantify DNA repair capacity in blood cells using comet assay and evaluate how this repair capacity is related to genetic variants in OGG1 and XRCC1 DNA repair genes...
.... To evaluate this hypothesis we quantify DNA repair capacity in blood cells using comet assay and evaluate how this repair capacity is related to genetic variants in OGG1 and XRCC1 DNA repair genes...
.... To evaluate this hypothesis, we quantify DNA repair capacity in blood cells using comet assay and evaluate how this repair capacity is related to genetic variants in OGG1 and XRCC1 DNA repair genes...
The DNA excision repair capacity of peripheral human lymphocytes after radiation therapy has been analyzed. Different forms of application of the radiation during the therapy have been taken into account. No inhibition of repair was found if cells were allowed a certain amount of accomodation to radiation, either by using lower doses or longer application times. (G.G.)
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
A standard model was established for the prediction of repair and maintenance costs of vehicles in a non-profit making government parastatal. The model was derived based on data collected over a ten year period from a non-profit making government parastatal, and it predicts repair and maintenance costs as a linear ...
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicle repair. 57.6801 Section 57.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... and Underground § 57.6801 Vehicle repair. Vehicles containing explosive material and oxidizers shall...
Galvez Chavez, Julio Cesar; Sanchez Wals, Lenia; Monzon Fernandez, Abel Nicolas; Morales Tirado, Roxana
Tumor relapse is one of the more fearsome complications of the oncologic course and also to obscure the life prognosis, causing the loss of many reconstructions and of exhausting the repairing surgical possibilities. The aim of this study was to determine the relapse frequency, the repercussion on the repair and the subsequent medical course of patients operated on malign nasal tumors
The objective of this effort was to demonstrate the feasibility of impact-initiated delivery of repair chemicals through hollow fiber architectures embedded within graphite fiber reinforced polymer matrix composites, representative of advanced drone aircraft component material systems. Self-repairing structures through coupon and elements were demonstrated, and evaluated.
... the cost of acquisition or production or the gain or loss basis of the taxpayer's plant, equipment, or other property, as the case may be, is not increased by the amount of such expenditures. Repairs in the... incidental repairs which neither materially add to the value of the property nor appreciably prolong its life...
Turgeon, Marc-Olivier; Perry, Nicholas J. S.; Poulogiannis, George
Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part of accurate double strand break repair. (2) Glutamine, aspartate, and other nutrients are essential for de novo nucleotide synthesis, which dictates the availability of the nucleotide pool, and thereby influences DNA repair and replication. (3) Reactive oxygen species, which can increase oxidative DNA damage and hence the load of the DNA-repair machinery, are regulated through different metabolic pathways. Interestingly, while metabolism affects DNA repair, DNA damage can also induce metabolic rewiring. Activation of the DNA damage response (DDR) triggers an increase in nucleotide synthesis and anabolic glucose metabolism, while also reducing glutamine anaplerosis. Furthermore, mutations in genes involved in the DDR and DNA repair also lead to metabolic rewiring. Links between cancer metabolism and DNA damage/DNA repair are increasingly apparent, yielding opportunities to investigate the mechanistic basis behind potential metabolic vulnerabilities of a substantial fraction of tumors. PMID:29459886
Method of Repair. Cases. AGE, SEX ... method is at fault and not the dexterity of the operator or his technique. .... Physio- therapy seldom makes stiff fingers work, but it prevents .... or repaired later by direct suture, graft or transplant. No. of.
Van der Krogt, R.P.J.; De Weerdt, M.M.
In dynamic environments, agents have to deal with changing situations. In these cases, repairing a plan is often more efficient than planning from scratch, but existing planning techniques are more advanced than existing plan repair techniques. Therefore, we propose a straightforward method to
Sleptchenko, A.V.; Adan, I.J.B.F.; Van Houtum, G.-J.
In this paper, we present and analyze a mathematical model for the computation of the system availability for a system of parallel machines with redundancies and repair priorities. Using the presented models, we show that the repair priorities have a strong effect on the performance of the system.
Melissa Lo Monaco
Full Text Available Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs or induced pluripotent stem cells (iPSCs have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.
Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo
Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.
Carlsen, C G; Lindorff Larsen, Karen; Funch-Jensen, P
PURPOSE: Lichtenstein hernia repair is a common surgical procedure and one of the first procedures performed by a surgical trainee. However, formal assessment tools developed for this procedure are few and sparsely validated. The aim of this study was to determine the reliability and validity...... of an assessment tool designed to measure surgical skills in Lichtenstein hernia repair. METHODS: Key issues were identified through a focus group interview. On this basis, an assessment tool with eight items was designed. Ten surgeons and surgical trainees were video recorded while performing Lichtenstein hernia...... a significant difference between the three groups which indicates construct validity, p skills can be assessed blindly by a single rater in a reliable and valid fashion with the new procedure-specific assessment tool. We recommend this tool for future assessment...
Janion, C.; Grzesiuk, E.; Fabisiewicz, A.; Tudek, B.; Ciesla, J.; Graziewicz, M.; Wojcik, A.; Speina, E.
Full text. The discovery that the mfd gene codes for a transcription-coupling repair factor (TRCF) prompted us to re-investigate the MFD (mutation frequency decline) phenomenon in E.coli K-12 strain when mutations were induced by ultraviolet light, halogen light or MMS-treatment. These studies revealed that: (i) the process of MFD involves the proofreading activity of DNA pol III and the mismatch repair system, as well as, TRCF and the UvrABC-excinuclease (ii) a semi-rich plate test may be replaced by a rich liquid medium, (iii) the T-T pyrimidine dimers are the lesions excised with the highest activity, and (iv) overproduction of UmuD(D'C) proteins leads to a great increase in mutant frequency in irradiated and MMS-treated cells. The role of mismatch repair (MR) in MMS-induced mutagenesis is obscured by the fact that the spectra of mutational specificity are different in bacteria proficient and deficient in MR. It has been found that transposons Tn10 (and Tn5) when inserted into chromosomal DNA of E. coli influence the phenotype lowering the survival and frequency of mutations induced by UV or halogen light irradiation. This is connected with a deficiency of UmuD(D') and UmuC proteins. Transformation of bacteria with plasmids bearing the umuD(D')C genes, suppresses the effects of the transposon insertion, a phenomenon which has not been described before. Single-stranded DNA of M13mp18 phage was oxidized in vitro by a hydroxyl radical generating system including hypoxanthine/xanthine oxidase/Fe3+/EDTA, and it was found that Fapy-Ade, Fapy-Gua, 8-oxyAde and thymine glycol were the main products formed. Replication of the oxidized template by T7 phage DNA polymerase, Klenow fragment of polymerase I, or polymerase beta from bovine thymus has revealed that oxidized pyrimidines are stronger blockers than oxidized purines for T7 phage and Klenow fragment polymerases and the blocking potency depends on the neighboring bases and on the type of polymerase. Studies of
Ahmed, F E; Setlow, R B
Excision repair seems to reach a plateau in normal human cells at a 254 nm dose near 20 J/m/sup 2/. We measured excision repair in normal human fibroblasts up to 80 J/m/sup 2/. The four techniques used (unscheduled DNA synthesis, photolysis of BrdUrd incorporated during repair, loss of sites sensitive to a UV endonuclease from Micrococcus luteus, and loss of pyrimidine dimers from DNA) showed little difference between the two doses. Moreover, the loss of endonuclease sites in 24h following two 20 J/m/sup 2/ doses separated by 24h was similar to the loss observed following one dose. Hence, we concluded that the observed plateau in excision repair is real and does not represent some inhibitory process at high doses but a true saturation of one of the rate limiting steps in repair.
A simple cost-wise comparison between the minimal and perfect repair of a system is discussed first using a relevant example. The main focus of this note, however, is on imperfect (general) repair. The best repair for our system in this case is defined as the one that corresponds to the optimal level (extent) of repair actions that minimize the long-run expected cost per unit of time. This complex optimization problem is considered for a specific imperfect repair model (Kijima II), using the developed earlier asymptotic approach to the corresponding virtual age modelling. It is shown that the optimal solution exists when the failure rate of a system tends to infinity as t tends to infinity and the corresponding cost function decreases sufficiently fast. An example illustrating the optimization procedure is considered
Joshi M P
Full Text Available Automobile repair workers are at risk of developing skin morbidity including occupational dermatoses because of their exposure to mineral oils, petroleum products and its derivatives and lubricating oil. This cross- sectional study was carried out at Maharashtra State Road Transport Corporation workshops in Nagpur city to investigate prevalence of skin morbidity including contact dermatitis in automobile repair workers. The study included 288 (49.9% automobile repair workers 180 (31.3% workshop office staff and 109 (18.8% divisional office employees. Dermatitis was the commonest skin morbidity in all the study subjects and it was significantly more prevalent in automobile repair workers. Folliculitis was detected in 13.2% of auto â€" repair workers and was not seen in the other two groups. Increasing trend of skin morbidity was correlated with the length of service of employees. Proper protective measures along with suitable washing facilities should be provided
Finkelstein, Maxim [Department of Mathematical Statistics, University of the Free State, PO Box 339, 9300 Bloemfontein (South Africa) and Max Planck Institute for Demographic Research, Rostock (Germany)]. E-mail: FinkelM.SCl@mail.uovs.ac.za
In this theoretical paper we generalize the notion of minimal repair to the heterogeneous case, when the lifetime distribution function can be modeled by continuous or a discrete mixture of distributions. The statistical (black box) minimal repair and the minimal repair based on information just before the failure of an object are considered. The corresponding failure (intensity) rate processes are defined and analyzed. Demographic lifesaving model is also considered: each life is saved (cured) with some probability (or equivalently a proportion of individuals who would have died are now resuscitated and given another chance). Those who are saved experience the statistical minimal repair. Both of these models are based on the Poisson or non-homogeneous Poisson processes of underlying events, which allow for considering heterogeneity. We also consider the new model of imperfect repair in the homogeneous case and present generalizations to the heterogeneous setting.
Full Text Available All reliability models consisting of random time factors form stochastic processes. In this paper we recall the definitions of the most common point processes which are used for modelling of repairable systems. Particularly this paper presents stochastic processes as examples of reliability systems for the support of the maintenance related decisions. We consider the simplest one-unit system with a negligible repair or replacement time, i.e., the unit is operating and is repaired or replaced at failure, where the time required for repair and replacement is negligible. When the repair or replacement is completed, the unit becomes as good as new and resumes operation. The stochastic modelling of recoverable systems constitutes an excellent method of supporting maintenance related decision-making processes and enables their more rational use.
Kohl, Andreas Pagh; Andresen, Kristoffer; Rosenberg, Jacob
OBJECTIVE:: To determine whether patients who receive an inguinal hernia repair father the same number of children as the background population. BACKGROUND:: Although the effect of inguinal hernia repair on male fertility has previously been investigated through indirect measures, no previous...... studies have evaluated the final measure of male fertility, which is the number of children fathered by patients. METHODS:: Prospectively collected data on 32,621 male patients between the ages of 18 and 55 years who received 1 or more inguinal hernia repairs during the years 1998 to 2012 were found in 5...... hernia repair using Lichtenstein technique or laparoscopic approach did not father fewer children than expected. Thus, inguinal hernia repair using Lichtenstein or laparoscopic approach did not impair male fertility....
Cadet, Jean; Davies, Kelvin J A
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.
Newsome, D.A.; Kraemer, K.H.; Robbins, J.H.
Xeroderma pigmentosum (XP) is an autosomal recessive disease with tumor formation on sun-exposed areas of the skin and eyes. Cells from most XP patients are deficient in repairing DNA damaged by ultraviolet (uv) light as shown by a reduced rate of tritiated thymidine (3HTdR) incorporation during their DNA repair synthesis. We have studied such repair synthesis in conjunctival cells from an XP patient with a conjunctival epithelioma and from normal cadaver conjunctiva. Cultured conjunctival cells were irradiated with uv light and then incubated with 3HTdR. Autoradiograms were prepared and showed that uv radiation induced a considerably slower rate of DNA repair synthesis in the XP cells than in normal cells. Many of the ocular abnormalities of XP, including tumor formation, may be the result of this defective DNA repair process
Mithoefer, Kai; Saris, Daniel B.F.; Farr, Jack; Kon, Elizaveta; Zaslav, Kenneth; Cole, Brian J.; Ranstam, Jonas; Yao, Jian; Shive, Matthew; Levine, David; Dalemans, Wilfried; Brittberg, Mats
Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Results: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. Conclusions: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project
Sikar, Hasan Ediz; Çetin, Kenan; Eyvaz, Kemal; Kaptanoglu, Levent; Küçük, Hasan Fehmi
Suprapubic hernia is the term to describe ventral hernias located less than 4 cm above the pubic arch in the midline. Hernias with an upper margin above the arcuate line encounter technical difficulties, and the differences in repair methods forced us to define them as large suprapubic hernias. To present our experience with laparoscopic repair of large suprapubic hernias that allows adequate mesh overlap. Nineteen patients with suprapubic incisional hernias who underwent laparoscopic repair between May 2013 and January 2015 were included in the study. Patients with laparoscopic extraperitoneal repair who had a suprapubic hernia with an upper margin below the arcuate line were excluded. Two men and 17 women, with a mean age of 58.2, underwent laparoscopic repair. Most of the incisions were midline vertical (13/68.4%). Twelve (63.1%) of the patients had previous incisional hernia repair (PIHR group); the mean number of previous incisional hernia repair was 1.4. Mean defect size of the PIHR group was higher than in patients without previous repair - 107.3 cm 2 vs. 50.9 cm 2 (p < 0.05). Mean operating time of the PIHR group was higher than in patients without repair - 126 min vs. 77.9 min (p < 0.05). Although all complications occurred in the PIHR group, there was no statistically significant difference. Laparoscopic repair of large suprapubic hernias can be considered as the first option in treatment. The low recurrence rates reported in the literature and the lack of recurrence, as observed in our study, support this view.
Drabløs, Finn; Feyzi, Emadoldin; Aas, Per Arne
Alkylation lesions in DNA and RNA result from endogenous compounds, environmental agents and alkylating drugs. Simple methylating agents, e.g. methylnitrosourea, tobacco-specific nitrosamines and drugs like temozolomide or streptozotocin, form adducts at N- and O-atoms in DNA bases. These lesions...... are mainly repaired by direct base repair, base excision repair, and to some extent by nucleotide excision repair (NER). The identified carcinogenicity of O(6)-methylguanine (O(6)-meG) is largely caused by its miscoding properties. Mutations from this lesion are prevented by O(6)-alkylG-DNA alkyltransferase......, inactivation of the MMR system in an AGT-defective background causes resistance to the killing effects of O(6)-alkylating agents, but not to the mutagenic effect. Bifunctional alkylating agents, such as chlorambucil or carmustine (BCNU), are commonly used anti-cancer drugs. DNA lesions caused by these agents...
Stilling, Nicolaj M; Fristrup, Claus; Wettergren, André
BACKGROUND: The aim of this retrospective study was to evaluate the peri-operative and long-term outcome after early repair with a hepaticojejunostomy (HJ). METHODS: Between 1995 and 2010, a nationwide, retrospective multi-centre study was conducted. All iatrogenic bile duct injury (BDI) sustained...... during a cholecystectomy and repaired with HJ in the five Hepato-Pancreatico-Biliary centres in Denmark were included. RESULTS: In total, 139 patients had an HJ repair. The median time from the BDI to reconstruction was 5 days. A concomitant vascular injury was identified in 26 cases (19%). Post...... with BDI repaired by early HJ we found a considerable risk of long-term complications (e.g. 30% stricture rate) and mortality in both the short- and the long-term perspective....
Dubey, Shailendra Kumar Damodar; Kute, Sunil
Due to earthquake, buildings are damaged partially or completely. Particularly structures with soft storey are mostly affected. In general, such damaged structures are repaired and reused. In this regard, an experimental investigation was planned and conducted on models of single-bay, single-storey of partial concrete infilled reinforced concrete (RC) frames up to collapse with corner, central and diagonal steel bracings. Such collapsed frames were repaired with epoxy resin and retested. The initiative was to identify the behaviour, extent of restored ultimate strength and deflection of epoxy-retrofitted frames in comparison to the braced RC frames. The performance of such frames has been considered only for lateral loads. In comparison to bare RC frames, epoxy repaired partial infilled frames have significant increase in the lateral load capacity. Central bracing is more effective than corner and diagonal bracing. For the same load, epoxy repaired frames have comparable deflection than similar braced frames.
Roach, David W.; Rackow, Kirk A.
An unavoidable by-product of a metallic structure's use is the appearance of crack and corrosion flaws. Economic barriers to the replacement of these structures have created an aging infrastructure and placed even greater demands on efficient and safe repair methods. In the past decade, an advanced composite repair technology has made great strides in commercial aviation use. Extensive testing and analysis, through joint programs between the Sandia Labs FAA Airworthiness Assurance Center and the aviation industry, have proven that composite materials can be used to repair damaged aluminum structure. Successful pilot programs have produced flight performance history to establish the durability of bonded composite patches as a permanent repair on commercial aircraft structures. With this foundation in place, this effort is adapting bonded composite repair technology to civil structures. The use of bonded composite doublers has the potential to correct the difficulties associated with current repair techniques and the ability to be applied where there are no rehabilitation options. It promises to be cost-effective with minimal disruption to the users of the structure. This report concludes a study into the application of composite patches on thick steel structures typically used in mining operations. Extreme fatigue, temperature, erosive, and corrosive environments induce an array of equipment damage. The current weld repair techniques for these structures provide a fatigue life that is inferior to that of the original plate. Subsequent cracking must be revisited on a regular basis. The use of composite doublers, which do not have brittle fracture problems such as those inherent in welds, can help extend the structure's fatigue life and reduce the equipment downtime. Two of the main issues for adapting aircraft composite repairs to civil applications are developing an installation technique for carbon steel and accommodating large repairs on extremely thick
Zavil'gel'skiĭ, G B
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.
Full Text Available A vesicovaginal fistula is one of the complications that a gynaecologist is bound to face after oncological operations, especially in postmenopausal women. Over the years there have been introduced many techniques of surgical treatment of this entity, including transabdominal and transvaginal approaches.We present a case of a 46-year-old patient who suffered from urinary leakage via the vagina due to the presence of a vesicovaginal fistula that developed after radical abdominal hysterectomy and subsequent radiotherapy. The decision was made to repair it laparoscopically due to retracted, fibrous and scarred tissue in the vaginal apex that precluded a transvaginal approach. A small cystotomy followed by an excision of fistula borders was performed. After six-month follow-up no recurrence of the disease has been noted.We conclude that laparoscopy is an interesting alternative to traditional approaches that provides comparable results.
Hansson, J E; Eklund, L; Kihlberg, S; Ostergren, C E
The main objective of the study was to find efficient hand tools which caused only minor vibration loading. Vibration measurements were carried out under standardised working conditions. The time during which car body repairers in seven companies were exposed to vibration was determined. Chisel hammers, impact wrenches, sanders and saws were the types of tools which generated the highest vibration accelerations. The average daily exposure at the different garages ranged from 22 to 70 min. The risk of vibration injury is currently rated as high. The difference between the highest and lowest levels of vibration was considerable in most tool categories. Therefore the choice of tool has a major impact on the magnitude of vibration exposure. The importance of choosing the right tools and working methods is discussed and a counselling service on vibration is proposed.
Ferrante, K; Winograd, B; Canetta, R
The positive impact on survival of traditional chemotherapeutic agents has renewed interest in developing newer cytotoxic agents and orally active compounds with improved therapeutic indices. In addition, new insights into the pathways of human tumorigenesis have led to novel approaches aimed at specific mechanism-based targets. The taxane class, of which paclitaxel was the first member, has the unique ability to promote and stabilize microtubule function directly, thereby inhibiting mitotic progression and inducing apoptotic cell death. Paclitaxel provides treatment benefit in a broad range of solid tumors including breast, ovarian, and lung cancer. The success with paclitaxel stimulated interest in the microtubule as a new therapeutic target. Taxane analogues with improved preclinical efficacy have been identified and are entering clinical trials. The enthusiasm for oral anticancer agents and the therapeutic importance of platinum compounds has led to the development of JM216 (satraplatin), a novel platinum IV coordination complex with oral activity in cisplatin-resistant cell lines, which is now in phase III trials in prostate cancer. Another compound in late development is DPPE, a chemopotentiator that enhances the in vivo antitumor effects of cytotoxic agents such as doxorubicin, cyclophosphamide, and cisplatin. Agents that inhibit topoisomerase I and II have also been of interest. TAS-103 is a dual topoisomerase I and II inhibitor with preclinical efficacy in a broad spectrum of tumors and in multidrug-resistant tumor cell lines. Vaccination strategies represent a rational therapeutic approach in the minimal residual disease or high-risk adjuvant therapy setting. The GMK and MGV vaccines utilizing ganglioside antigens overexpressed on human tumors such as melanoma and small cell lung cancer appear to induce antibody production reliably at tolerable doses and are under further clinical investigation. Inhibition of matrix metalloproteinases (MMPs) is another
Scarbrough, Peter M; Weber, Rachel Palmieri; Iversen, Edwin S; Brhane, Yonathan; Amos, Christopher I; Kraft, Peter; Hung, Rayjean J; Sellers, Thomas A; Witte, John S; Pharoah, Paul; Henderson, Brian E; Gruber, Stephen B; Hunter, David J; Garber, Judy E; Joshi, Amit D; McDonnell, Kevin; Easton, Doug F; Eeles, Ros; Kote-Jarai, Zsofia; Muir, Kenneth; Doherty, Jennifer A; Schildkraut, Joellen M
DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. We identified three susceptibility DNA repair genes, RAD51B (P cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. ©2015 American Association for Cancer Research.
Benito, Cristina; Davis, Catherine M; Gomez-Sanchez, Jose A; Turmaine, Mark; Meijer, Dies; Poli, Valeria; Mirsky, Rhona; Jessen, Kristjan R
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
Successfully building, flying, and maintaining the space shuttles was an immensely complex job that required a high level of detailed, precise engineering. After each shuttle landed, it entered a maintenance, repair, and overhaul (MRO) phase. Each system was thoroughly checked and tested, and worn or damaged parts replaced, before the shuttle was rolled out for its next mission. During the MRO period, workers needed to record exactly what needed replacing and why, as well as follow precise guidelines and procedures in making their repairs. That meant traceability, and with it lots of paperwork. In 2007, the number of reports generated during electrical system repairs was getting out of hand-placing among the top three systems in terms of paperwork volume. Repair specialists at Kennedy Space Center were unhappy spending so much time at a desk and so little time actually working on the shuttle. "Engineers weren't spending their time doing technical work," says Joseph Schuh, an electrical engineer at Kennedy. "Instead, they were busy with repetitive, time-consuming processes that, while important in their own right, provided a low return on time invested." The strain of such inefficiency was bad enough that slow electrical repairs jeopardized rollout on several occasions. Knowing there had to be a way to streamline operations, Kennedy asked Martin Belson, a project manager with 30 years experience as an aerospace contractor, to co-lead a team in developing software that would reduce the effort required to document shuttle repairs. The result was System Maintenance Automated Repair Tasks (SMART) software. SMART is a tool for aggregating and applying information on every aspect of repairs, from procedures and instructions to a vehicle s troubleshooting history. Drawing on that data, SMART largely automates the processes of generating repair instructions and post-repair paperwork. In the case of the space shuttle, this meant that SMART had 30 years worth of operations
Kothari, Anai N.; Halandras, Pegge M.; Drescher, Max; Blackwell, Robert H.; Graunke, Dawn M.; Kliethermes, Stephanie; Kuo, Paul C.; Cho, Jae S.
Objective The purpose of this study was to determine whether new-onset transient postoperative atrial fibrillation (TPAF) affects mortality rates after abdominal aortic aneurysm (AAA) repair and to identify predictors for the development of TPAF. Methods Patients who underwent open aortic repair or endovascular aortic repair for a principal diagnosis AAA were retrospectively identified using the Healthcare Cost and Utilization Project-State Inpatient Database (Florida) for 2007 to 2011 and monitored longitudinally for 1 year. Inpatient and 1-year mortality rates were compared between those with and without TPAF. TPAF was defined as new-onset atrial fibrillation that developed in the postoperative period and subsequently resolved in patients without a history of atrial fibrillation. Cox proportional hazards models, adjusted for age, gender, comorbidities, rupture status, and repair method, were used to assess 1-year survival. Predictive models were built with preoperative patient factors using Chi-squared Automatic Interaction Detector decision trees and externally validated on patients from California. Results A 3.7% incidence of TPAF was identified among 15,148 patients who underwent AAA repair. The overall mortality rate was 4.3%. The inpatient mortality rate was 12.3% in patients with TPAF vs 4.0% in those without TPAF. In the ruptured setting, the difference in mortality was similar between groups (33.7% vs 39.9%, P = .3). After controlling for age, gender, comorbid disease severity, urgency (ruptured vs nonruptured), and repair method, TPAF was associated with increased 1-year postoperative mortality (hazard ratio, 1.48; P predict an individual's probability of developing TPAF at the point of care. Conclusions The development of TPAF is associated with an increased risk of mortality in patients undergoing repair of nonruptured AAA. Predictive modeling can be used to identify those patients at highest risk for developing TPAF and guide interventions to improve
Full Text Available Electrospun fiber has highly structural similarity with natural bone extracelluar matrix (ECM. Many researches about fabricating organic–inorganic composite materials have been carried out in order to mimic the natural composition of bone and enhance the biocompatibility of materials. In this work, pearl powder was added to the poly (3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV and the composite nanofiber scaffold was prepared by electrospinning. Mineralization ability of the composite scaffolds can be evaluated by analyzing hydroxyapatite (HA formation on the surface of nanofiber scaffolds. The obtained composite nanofiber scaffolds showed an enhanced mineralization capacity due to incorporation of pearl powder. The HA formed amount of the composite scaffolds was raised as the increase of pearl powder in composite scaffolds. Therefore, the prepared PHBV/pearl composite nanofiber scaffolds would be a promising candidate as an osteoconductive composite material for bone repairing.
Chicha, L; Smith, T; Guzman, R
Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.
Bricker, E.M.; Johnston, W.D.; Patwardhan, R.V.
The results of 21 operations for repair of rectovaginal fistula and/or stricture secondary to irradiation for pelvic cancer are presented. The operations rely on the use of proximal nonirradiated colon with normal blood supply for effecting the repair. In patients having had a previous colostomy, it is possible to use the proximal end of the bypassed colon for this purpose. There is minimal dissection of the rectal ampulla and the presacral space is never entered. Continuity is established by anastomosis to the anterior rectal wall via an abdominal approach alone, or by a combined abdominovaginal or abdominoperineal approach. It has been found that nonirradiated colon of normal vascularity can be expected to heal to irradiated colon or rectum, thus making the extensive resections associated with correction of these abnormalities unnecessary. The functional result in 18 of 19 patients who underwent this procedure was satisfactory to excellent. One patient had a poor result because of partial rectal incontinence. Two operations out of the 21 were total failures and one of these patients died of complications secondary to irradiation damage to the small intestine. One patient has not yet had final colostomy closure. The results are considered promising enough to warrant continued trial
Prakash Hande, M.
Telomerase reactivation is essential for telomere maintenance in human cancer cells ensuring indefinite proliferation. Targeting telomere homeostasis has become one of the promising strategies in the therapeutic management of tumours. One major potential drawback, however, is the time lag between telomerase inhibition and critically shortened telomeres triggering cell death, allowing cancer cells to acquire drug resistance. Numerous studies over the last decade have highlighted the role of DNA repair proteins such as Poly (ADP-Ribose) Polymerase-1 (PARP-1), and DNA-dependent protein kinase (DNA-PKcs) in the maintenance of telomere homoeostasis. Dysfunctional telomeres, resulting from the loss of telomeric DNA repeats or the loss of function of telomere-associated proteins trigger DNA damage responses similar to that observed for double strand breaks. We have been working on unravelling such synthetic lethality in cancer cells and this talk would be on one such recently concluded study that demonstrates that inhibition of DNA repair pathways, i.e., NHEJ pathway and that of telomerase could be an alternative strategy to enhance anti-tumour effects and circumvent the possibility of drug resistance. (author)
Leung, Kit Nam Francis; Zhang Yuanlin; Lai, Kin Keung
In this paper, a cold standby repairable system consisting of two dissimilar components and one repairman is studied. Assume that working time distributions and repair time distributions of the two components are both exponential, and Component 1 has repair priority when both components are broken down. After repair, Component 1 follows a geometric process repair while Component 2 obeys a perfect repair. Under these assumptions, using the perfect repair model, the geometric process repair model and the supplementary variable technique, we not only study some important reliability indices, but also consider a replacement policy T, under which the system is replaced when the working age of Component 1 reaches T. Our problem is to determine an optimal policy T* such that the long-run average loss per unit time (i.e. average loss rate) of the system is minimized. The explicit expression for the average loss rate of the system is derived, and the corresponding optimal replacement policy T* can be found numerically. Finally, a numerical example for replacement policy T is given to illustrate some theoretical results and the model's applicability. - Highlights: → A two-dissimilar-component cold standby system with repair priority is formulated. → The successive up/repair times of Component 1 form a decreasing/increasing geometric process. → Not only some reliability indices but also a replacement policy are studied.
A hypothesis is proposed according to which E. coli possesses an inducible DNA repair system. This hypothetical repair, which we call SOS repair, is manifested only following damage to DNA, and requires de novo protein synthesis. SOS repair in E. coli requires some known genetic elements: recA + , lex + and probably zab + . Mutagenesis by ultraviolet light is observed only under conditions of functional SOS repair: we therefore suspect that this is a mutation-prone repair. A number of phenomena and experiments is reviewed which at this point can best be interpreted in terms of an inducible mutagenic DNA repair system. Two recently discovered phenomena support the proposed hypothesis: existence of a mutant (tif) which, after a shift to elevated temperature, mimicks the effect of uv irradiation in regard to repair of phage lambda and uv mutagenesis, apparent activation of SOS repair by introduction into the recipient cell of damaged plasmid or Hfr DNA. Several specific predictions based on SOS repair hypothesis are presented in order to stimulate further experimental tests. (U.S.)
Razman, J; Shaharin, S; Lukman, M R; Sukumar, N; Jasmi, A Y
Laparoscopic repair of ventral and incisional hernia has become increasingly popular as compared to open repair. The procedure has the advantages of minimal access surgery, reduction of post operative pain and the recurrence rate. A prospective study of laparoscopic incisional hernia repair was performed in our center from August 2002 to April 2004. Eighteen cases (n: 18) were performed during the study period. Fifteen cases (n: 15) had open hernia repair previously. Sixteen patients (n: 16) had successful repair of the hernia with the laparoscopic approach and two cases were converted to open repair. The mean hernia defect size was 156cm2. There was no intraoperative or immediate postoperative complication. The mean operating time was 100 +/- 34 minutes (75 - 180 minutes). The postoperative pain was graded as mild to moderate according to visual analogue score. The mean day of discharge after surgery was two days (1 - 3 days). During follow up, three patients (16.7%) developed seroma at the hernia sac which was resolved with conservative management after three weeks. One (5.6%) patient developed recurrence six months after surgery. In conclusion, laparoscopic repair of incisional hernia particularly recurrent hernia has been shown to be safe and effective in our centre. However, careful patient selection and acquiring the necessary advanced laparoscopic surgical skills coupled with the proper use of equipment are mandatory before embarking on this procedure.
The repair of DNA lesions in Deinococcus radiodurans was examined with particular reference to DNA excision repair of ultraviolet light (UV) induced pyrimidine dimers. The characteristics of excision repair via UV endonucleases α and β in vivo varied with respect to (a) the substrate range of the enzymes, (b) the rate of repair of DNA damage (c) the requirement for a protein synthesised in response to DNA damage to attenuate exonuclease action at repairing regions. UV endonuclease α is postulated to incise DNA in a different manner from UV endonuclease β thus defining the method of subsequent repair. Several DNA damage specific endonuclease activities independent of α and β are described. Mutations of the uvsA, uvsF and uvsG genes resulted in an increase in single-strand breaks in response to DNA damage producing uncontrolled DNA degradation. Evidence is presented that these genes have a role in limiting the access of UV endonuclease β to DNA lesions. uvsF and uvsG are also shown to be linked to the mtoA gene. Mutation of uvsH and reo-1 produces further distinct phenotypes which are discussed. An overall model of excision repair of DNA damage in Deinococcus radiodurans is presented. (author)
Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.
Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565
Iskhakov, I.; Ribakov, Y.; Holschemacher, K.; Mueller, T.
Highlights: ► Steel fibered high strength concrete is effective for repairing concrete elements. ► Changing fibers’ content, required ductility of the repaired element is achieved. ► Experiments prove previously developed design concepts for two layer beams. -- Abstract: Steel fibered high strength concrete (SFHSC) is an effective material that can be used for repairing concrete elements. Design of normal strength concrete (NSC) elements that should be repaired using SFHSC can be based on general concepts for design of two-layer beams, consisting of SFHSC in the compressed zone and NSC without fibers in the tensile zone. It was previously reported that such elements are effective when their section carries rather large bending moments. Steel fibers, added to high strength concrete, increase its ultimate deformations due to the additional energy dissipation potential contributed by fibers. When changing the fibers’ content, a required ductility level of the repaired element can be achieved. Providing proper ductility is important for design of structures to dynamic loadings. The current study discusses experimental results that form a basis for finding optimal fiber content, yielding the highest Poisson coefficient and ductility of the repaired elements’ sections. Some technological issues as well as distribution of fibers in the cross section of two-layer bending elements are investigated. The experimental results, obtained in the frame of this study, form a basis for general technological provisions, related to repairing of NSC beams and slabs, using SFHSC.