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I was a bit concerned about this school based on the rating it received on this site. My son started Kindergarten this year and I was upset that he would be going to a school with such low marks. But after the first few months I realized that the curriculum is wonderful and the scores on this site reflect the population as a whole. And with the majority of the school speaking English as a second language that understandable reduces the overall grades the school gets. My son had a phenomenal teacher whom he adores and I am actually very excited for the fall and how his education will be expanded with an entire day's instruction!
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First year with a child at this school and at first i was worried, but now i'm more aware...my child's teacher is wonderful but could really use help in class with troubled kids its alot of stress for her. very few parents help out and the head pta members are very disorganized at meetings...some administration still seems to be learning but when problems arise they really deal with it i think the best is yet to come from this school, :)
Horizon Elementary has had it's ups and downs and lately it seems more downs. Parent involvement is very low, and part of that is due to the group of PTA parents that run everything. They have done it so long that they seem uncaring and unmotivated. The staff has been changing so much in the last few years that it seems all the wonderful teachers who made Horizon a great school are all gone now and the atmosphere is lacking excitement and encouragement. The school needs a make-over in the PTA most definately and more involvement within the community in general.
I am very disappointed in Horizon Elementary, I am a parent that can not understand why the lack in sports! Yes they handout the fliers for community sports. In which you must then pay for if you want your kids involved! They are not very involved with the kids in the community at all! The teachers are divided, half are friendly and upbeat. The other half are rude and intimidating! I am sure you can only imagine what a child must feel like! My encounter with the principal wasn't much better. I wasn't even meaning on meeting the principal on my drop in at the front office, It wasn't pleasant.
I have children attending Horizon. The teachers, principal and staff are all wonderful and very involved with the kids. Kids get extra help if they need it. Parent involvement seems somewhat low but it is up to parents to get involved. The PTA does a super job of putting on extracurricular activities. Math night had a huge turn out and was super fun and informative. The principal knows many of the kids by their first names. Horizon is a friendly school and it's principal, teachers, office staff and volunteers are very knowledgeable. I'm glad my kids are going to Horizon.
I have two children attending Horizon. Luckily both of my children have GREAT teachers who have made an effort into students who are excelling by providing them with a more challenging curriculum. It is my understanding that resources are available for children who need additional help; however, what about the children who are doing extremely well...what resources are made available for them??? You would think the school would want to also invest in these children especially since it promotes improved WASL scores. We are very active with our children and their academics. I feel the school should also be supporting programs to challenge ALL children as well as help them excel and keep motivated. As for school activities, I don't know if things would be any different if they offered some on evenings other than Thursdays. My children are involved in other activities, so Thursdays aren't good for our family.
My child goes to Horizon and this is the first year I have had a teacher that has kept the parents aware of what the kids were learning in the classroom. Parent involvement is very very low. The school puts on some activities and when they do they don't get a lot of turn out from the families. We go to a a lot and we see the same families involved. I have nieces and nephews in other school districts and they are learning more interesting things and excelling farther. The principal is not that friendly either.
My son has been going to this school for 3 years. There are no challenge courses only courses for those who are behind. The PTA this year is the worst since we have been here. I feel my son is not being challenged. His teacher this year is really good but does not have the resources she needs to provide challenging material.
I found Horizon a very unsatisfying school. The principle was very nice & cordial, the office staff was too - but they had NO energy. My daughter attended kindergarten and LOVED her teacher (who left this year for some of the same reasons I took my daughter out) but the rest of the school was seriously lacking any excitement. I felt that things were only going to get worse as my daughter got older - so I switched her to Madison.The only extracurricular activities were selling things for the school and going to skate deck. The carnival was lame, the kindergartners didn't get to participate in holiday stuff (& they had No K graduation ceremony, other than what the teacher did). We had 1 field trip &, despite the fact that the k's sold more than ANY other classes, they didn't get to participate in ANY events with older classes!
The teachers are great! The music program seems good. They have the reflections program for art, which is awesome! Parent involvement is low, but they're working on making it better.
I think Horizon is an overall good school but there seems to be alott of launguage barriers for the children.
I am new to the state and was very cautious about picking a school. I definitely made the right choice with Horizon. Horizon has a friendly, hardworking, and knowledgeable staff. I feel confident that my child is getting a very good education in a safe and nuturing environment.
Horizon Elementary is a great place for kids and parents to be involved,my children love this school! They have the very best teachers here.I have four children ages 14-9 they all have been at this school and have very good attitudes towards school and homework...I can't say enough great things!
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222 West Casino Rd
Everett, WA 98204
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Genes 2013, 4(3), 375-387; doi:10.3390/genes4030375
Published: 25 July 2013
Abstract: More than fifteen genetic diseases, including Huntington's disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER) are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.
1. Trinucleotide Repeat Instability in Diseases
Trinucleotide repeat (TNR) disorders define a group of more than fifteen neurodegenerative, neurological and neuromuscular diseases [1,2]. These genetic diseases result from the aberrant expansion of TNRs within specific genes. Various types of TNRs can cause diseases, including CAG repeats (Huntington's disease, HD, and several dominant spinocerebellar ataxia), CTG repeats (myotonic dystrophy 1, DM1), CGG repeats (fragile X syndrome, FXS) and GAA repeats (Friedreich ataxia, FRDA). Noticeably, CAG/CTG repeat diseases are the most frequent, accounting for a dozen of disorders. TNRs are polymorphic in the control population; however, above a threshold of 30 to 50 repeat units, the repeats are pathogenic. TNRs associated with diseases are found in various parts of genes, including 3' and 5' UTRs, exons and introns. The location of the repeat expansion within genes influences the pathomechanism, which ranges from loss-of-function (FXS, FRDA) and protein and RNA gain-of-functions (HD and DM1, respectively).
TNR expansions are dynamic mutations, which are ongoing across generations and within tissues, due to germline and somatic instability, respectively [3]. The outcome of repeat instability is contraction or expansion of the repeat. Expansion in the germline can lead to an anticipation effect, corresponding to worsening of the disease in successive generations, i.e., earlier onset and more rapid progression of the symptoms [4]. Depending on the disease, a parent-of-origin effect is observed, resulting in paternal or maternal bias of expansion or contraction. In somatic tissues, expansion events tend to be more frequent than contraction events, leading to the progressive increase of the repeat tract with age. Importantly, somatic instability is tissue-selective. In most TNR diseases, the degree of variation of the repeat tract over time is highly dependent upon tissue or cell-type, and the tissues or cells presenting high TNR instability vary to some extent between diseases [2]. In HD and DM1, somatic instability is most prevalent in the affected tissues and has been proposed to act as a disease modifier, accelerating disease progression [5,6,7,8]. In HD, CAG instability is most elevated in the striatum, the tissue that is most affected [6,9,10,11,12,13]. It is noteworthy that in most CAG/CTG diseases, repeat instability is generally elevated in brain tissues, with the exception of the cerebellum, which presents limited repeat instability [2]. Interestingly, somatic CAG instability is usually great in the central nervous system and, more specifically, in neurons, indicative of the implication of replication-independent mechanisms [6].
2. Trinucleotide Repeat Instability as the Result of Erroneous DNA Repair
Mechanistic models of TNR instability are based upon the assumption that TNRs form stable DNA secondary structures, and error-prone repair of those structures results in repeat size variation [1,3,14]. In vitro experiments have shown that TNR sequences can adopt several structures, and the sequence of the repeat influences both the stability and the nature of the DNA structure [15,16]. For instance, slipped-out CAG and slipped-out CTG repeats adopt predominantly random coil and hairpin conformation, respectively, which explains the increased stability of CTG-associated DNA structures relative to CAG-associated DNA structures [17,18,19,20]. In addition, increasing the length of TNRs augments the stability, as well as the complexity of the secondary structures [15,16,21]. Sequences of more than 10 CAG/CTG repeats can show a pattern involving multiple loops or hairpins [21,22]. An additional level of complexity of DNA structures is suggested by a recent study showing interconverting conformations of slipped-DNA junctions formed by TNRs [23]. Finally, stable DNA:RNA hybrids (R-loops) can also form during transcription across TNRs [24,25].
It remains to be determined whether unusual DNA:DNA structures truly form under physiological conditions, particularly in cells or tissues presenting high levels of repeat instability. However, several pieces of indirect evidence support their in vivo existence. Cellular processes altering DNA or chromatin structure, including DNA repair, replication, transcription and epigenetic-related mechanisms, have been shown to contribute to TNR instability [3]. These processes would either promote the formation of secondary structures at repeats or induce their error-prone repair.
More specifically, studies performed using mice modeling DM1, HD, spinocerebellar ataxia type 7 and spinocerebellar ataxia type 1 indicate that the chromatin, transcription and replication status at repeats modulates repeat instability through gene-specific cis-elements, which include CCCTC-binding factor (CTCF) sites, CpG islands and replication origins [26,27,28,29]. It would remain to be examined whether the level of trans-factors regulating cis-element activity, including CTCF, modulate susceptibility to instability in tissues.
In addition, it has been shown that trans-factors involved in DNA repair are physiological modifiers of TNR instability. Specifically, in HD and/or DM1 mice, TNR instability is reduced upon inactivation of genes involved in mismatch repair (MMR), including Msh2, Msh3 and Pms2 [30,31,32,33,34], base excision repair (BER), including Ogg1 and Neil1 [35,36], and nucleotide excision repair (NER), including Xpa and Csb [37,38]. Thus, abnormal repair at TNR promotes instability. How these different factors and mechanisms interplay in a given tissue is unclear, but it is likely that the contribution of each is dependent upon the tissue considered. Therefore, investigating the mechanisms underlying tissue-selectivity should help in deciphering TNR instability. Our recent data suggest that BER is one mechanism involved in the tissue selectivity of CAG/CTG repeat instability. Below, we discuss, more specifically, the physiological role of BER in the TNR instability associated with disease.
3. In Vivo Mechanism of BER in Trinucleotide Repeat Instability
BER is a DNA repair pathway specialized in the elimination of DNA base damage, of which 8-oxoguanine (8-oxoG) is the most common DNA lesion [39,40]. BER is characterized by a sequence of highly coordinated steps, starting from the removal of the DNA base lesion by a DNA glycosylase. This results in the formation of an abasic site, which is cleaved by an AP endonuclease (Ape1 in mammals) [41,42]. The DNA strand break is then processed by either single-nucleotide base excision repair (SN-BER) or long-patch base excision repair (LP-BER). In SN-BER, DNA polymerase β (Polβ) incorporates a single nucleotide and incises the remaining 5'-sugar phosphate, prior to ligation by DNA ligase III (Lig3). In LP-BER, the flap endonuclease 1 (Fen1) removes the 5'-flap structure generated during the multi-nucleotide synthesis step mediated by Polβ or a replicative DNA polymerase prior to ligation by DNA ligase I (Lig1) [41,42].
3.1. BER in Various Models of Trinucleotide Repeat Instability
Yeast studies demonstrated the first evidence that allowed insight into the involvement of BER proteins in TNR instability. Deficiency or haploinsufficiency of rad27, the homolog of mammalian Fen1 in yeast, led to length-dependent CAG/CTG expansion and instability [43,44]. On the other side, it is the overexpression of Lig1 homolog in yeast (cdc9) that yielded longer repeat tracts [45]. Overexpression of an inactive form of cdc9 possessing a functional binding site for proliferating cell nuclear antigen (PCNA) led to similar results, suggesting that instability is dependent upon PCNA interaction rather than DNA ligase activity [45,46]. Mutations in PCNA and the replicative DNA polymerase Polδ also induced destabilization of the repeat tract [47]. Fen1, PCNA, Lig1 and the replicative DNA polymerases are involved in both replication and LP-BER, and yeast studies did not allow discriminating of whether replication and/or LP-BER contribute most to TNR instability. The effects of Lig1 protein level, activity and capacity to interact with PCNA on replication and repair at CAG/CTG repeats were assessed using human cells and plasmid-based substrates [48]. Consistent with the yeast studies, disruption of Lig1 and PCNA interaction increased instability, due to errors during replication, whereas Lig1 overexpression increased repair-dependent TNR instability. In addition, reduced Lig1 activity did not alter instability.
Mouse genetics was further used to attempt to define the role of BER proteins in TNR instability. DM1 mice were crossed with knock-in mice carrying a mutation in Lig1, resulting in very low residual ligase activity [49,50]. Somatic CTG/CAG instability in DM1 mice expressing the Lig1 mutant was similar to that in DM1 mice. However, DM1 mice mutants for Lig1 showed a maternal instability bias, leading to increased contractions and decreased expansions. Furthermore, HD and DM1 mice were crossed with mice haploinsufficient for Fen1. Somatic CAG/CTG instability was unchanged in HD and DM1 mice heterozygous for Fen1, regardless of the tissues analyzed, though a modest effect on germline instability was observed in HD mice haploinsufficient for Fen1 [51,52]. These results might indicate that the mechanisms underlying CAG/CTG instability in yeast and mammals are different. The involvement of replication in repeat instability might be prominent in proliferative cells, such as yeast, but more limited in mammalian tissues. Alternatively, different compensatory mechanisms might take place in yeast and mammalian tissues that could account for the different effects induced by deficiency of Fen1 or Lig1 in the two model systems. Of note, in contrast to yeast, the complete inactivation of Fen1 could not be achieved in mice, due to the embryonic lethality of full knock-outs [53,54]. In general, assessing the role of BER proteins in CAG/CTG instability using mouse genetics is a difficult task, as inactivation of the main BER genes, including Polβ [55,56], Ape1 [57], Xrcc1 [58], Fen1 or Lig1, is embryonically lethal.
DNA glycosylases represent an exception to this rule. The inactivation of individual DNA glycosylases is compatible with life in mammals, due to functional redundancy. Interestingly, full inactivation of the DNA glycosylase, Ogg1, in HD mice led to reduction of the age-dependent repeat instability in the brain and liver, suggesting the repair of 8-oxoG lesions promotes somatic CAG instability [35]. Inactivation of Ogg1 or Ape1 in a human cell model allowing for detection of repeat contraction events only did not improve repeat stability, possibly due to the low frequency rate of contraction in this model system [59]. In addition, HD mice deficient for the DNA glycosylases, Aag and Nth1, which remove alkylated purines and pyrimidine-derived lesions, respectively, had no effect on CAG instability [35]. In addition, somatic and germline instability was reduced in HD mice deficient for Neil1. Interestingly, somatic instability was decreased in all tissues tested, which included brain and non-brain tissues. Neil1 is a DNA glycosylase that targets pyrimidine-derived lesions, like NTH1 [36]. However, Neil1 can remove DNA lesions in both duplex and single-strand DNA (ssDNA), and can also remove 8-oxoG lesions in both DNA configurations, though removal efficiency for this DNA lesion is poor [60]. Importantly, CAG instability in HD mice was only moderately reduced upon inactivation of Ogg1 and Neil1, and phenotype penetrance (e.g., improved CAG instability) was partial, suggesting that neither Ogg1 nor Neil1 is essential regarding CAG instability, possibly due to overlapping substrate specificities. Whereas these data demonstrate that DNA glycosylases contribute to CAG instability in vivo, the exact nature of mutagenic DNA lesions remains elusive. Assessing the effect of inactivation of additional DNA glycosylases could help in answering this question. Finally, it remains to be determined whether DNA glycosylases contribute to repeat instability in other models of TNR diseases. Interestingly, it was reported that the DNA oxidizing agent, potassium bromate, exacerbates germline repeat expansion in a fragile X premutation model, suggesting that repair of oxidative DNA lesions might be involved in the instability of CGG repeats [61].
3.2. Level and Accessibility of DNA Lesions at Trinucleotide Repeats
Accumulation of oxidative DNA damage with age in specific tissues could explain the age dependency and tissue specificity of somatic instability [35]. However, though the global level of DNA damage increased with age in HD mouse striatum and cerebellum, it was lower in the striatum, which presents high CAG instability levels, when compared to the cerebellum, showing minimal repeat instability [62]. In addition, DNA damage at CAG repeats did not increase with age and was not higher in striatum, though it was abnormally high in HD mouse tissues [62]. These data suggest that the amount of DNA lesions at CAG repeats does not directly contribute to age-dependent and tissue-selective somatic instability, suggesting that other mechanisms explain these features.
The increased level of DNA lesions at CAG repeats found in tissues of HD mice might result from their reduced accessibility to DNA repair proteins. Several studies support this hypothesis. Repair of hairpin-forming substrates with DNA lesions, including 8-oxoG, 5-OHC and the AP site, was impeded, likely due to reduced binding of DNA repair proteins to hairpin structures [36,62,63,64]. Along this line, the degree of stiffness of CAG/CTG substrates with slip-outs negatively influenced repair efficiency [23]. Additionally, hairpin substrates with CAG/CTG repeats contained a hot spot for DNA damage [63]. Thus, both reduced accessibility and increased susceptibility to DNA damage could contribute to lesion accumulation at CAG/CTG expansions.
3.3. Mechanism of BER in Tissue-Selective CAG/CTG Repeat Instability
Several in vitro and cell-based studies have provided insights into the mechanism by which BER proteins might contribute to CAG/CTG instability. It has been reported that processing of CAG/CTG substrates by Polβ, a central component of BER, leads to strand displacement and multi-nucleotide gap filling, due to polymerase slippage at repeats [65,66]. Polymerase slippage would induce the formation of a 5'-flap structure, which would require LP-BER proteins, including Fen1 and Lig1, for completion of repair. Since stable secondary structures forming at TNR repeats prevent efficient excision by Fen1 [67,68], it was hypothesized that expansion of the repeat tract could arise from inefficient excision or alternate cleavage by Fen1 of the 5'-flap structure generated upon multi-nucleotide gap filling by Polβ, followed by ligation of an erroneous number of repeats [14,66]. Alternate cleavage by Fen1 would be required for the generation of a ligatable nick and completion of repair. Studies using partially and fully reconstituted repair assays support these possibilities and further indicate that the level of coordination of BER enzymatic steps is critical in determining the repair outcome at CAG/CTG repeats [69,70,71]. The processing of CAG/CTG substrates preferentially involved LP-BER in contrast to substrates with a random sequence, suggesting that LP-BER is required to repair a lesion at CAG/CTG repeats. Furthermore, repair outcome was influenced by the stoichiometry of BER proteins [62,71]. BER protein levels and activities greatly varied between the striatum and the cerebellum. Although the level of Polβ was similar in the two tissues, LP-BER proteins, including Fen1 and Lig1, were much more abundant in the cerebellum as compared to the striatum. As a result, repair efficiency at CAG/CTG repeats was poor and led to the formation of persistent intermediate products when using the striatal BER protein stoichiometry, as compared to that of the cerebellum. It was hypothesized that the sub-optimal BER activity in the striatum contributes to the increased striatal instability seen in HD, whereas the efficient and well-coordinated BER activity in the cerebellum might limit instability in this tissue, preventing the formation of secondary DNA structures at repeats.
Moreover, the sequence of the repeat (CAG versus CTG) and the position of the lesion within the CAG/CTG substrates also influenced repair outcome, e.g., repair efficiency and LP-BER requirement [71,72]. The results by Lai et al. suggest that the position of the lesion within the repeat substrate determines whether expansion or contraction occurs [72]. It was reported that a lesion located at the 5'-end of CTG repeats results in expansion, whereas a lesion located in the middle or the 3'-end of the repeats results in deletion. In studies using plasmid-based CAG/CTG substrates and mammalian cell extracts, it was also reported that the position of a nick with respect to the repeat tract influences repair outcome [18,20,22,73]. In these assays, repair efficiency was decreased when the slip-out was located on the CTG strand in comparison to the CAG strand. The mechanism of TNR instability includes both stochastic and deterministic components [74]. The occurrence, accessibility and location of a DNA lesion at repeats are stochastic events that might contribute to the stochastic component of instability, whereas damage repair would be involved in the deterministic component. Since BER protein stoichiometry varies between tissues, this BER deterministic component might be tissue-dependent (Figure 1). Interestingly, the level of MMR proteins, including Msh2, Msh3 and Msh6, is also highly variable between mouse tissues [75]. It was suggested that the elevated levels of MMR proteins in embryonic stem cells of DM1 patients might contribute to the high CTG instability level found in these cells [76]. Similar conclusions were drawn using induced pluripotent stem cells derived from fibroblasts of Friedreich ataxia patients [77,78]. However, the relative levels of MMR proteins were higher in the cerebellum, as compared to the striatum and cortex, indicating that high MMR protein amounts do not correlate with high instability levels in somatic tissues. Further studies are required to specify how tissue-specific regulation of trans-factors impacts on tissue selective instability.
4. Conclusions
Many genetic diseases are caused by dynamic mutations, including trinucleotide repeat expansion diseases. Repeat instability can accelerate disease progression. Understanding the etiology of TNR instability is crucial, since instability might represent a therapeutic target. During the last decade, important advances have been made that increase our understanding of the rules governing this particular type of instability. Specifically, it was discovered that oxidative DNA damage and BER play a physiological role in the somatic CAG instability involved in HD and possibly contribute to the tissue selectivity and stochasticity of the instability process. Yet, how broad the involvement of oxidative DNA damage and BER in the TNR instability associated with diseases is would need to be investigated. How BER interacts with other mechanisms modulating TNR instability, including MMR, transcription and replication, is also a question that would deserve interest.
These studies were supported by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Strasbourg and by a grant from the French Agence Nationale de la Recherche (ANR-2011-JSV6-003-01).
Conflict of Interest
The authors declare no conflict of interest.
- Mirkin, S.M. Expandable DNA repeats and human disease. Nature 2007, 447, 932–940, doi:10.1038/nature05977.
- Pearson, C.E.; Nichol Edamura, K.; Cleary, J.D. Repeat instability: Mechanisms of dynamic mutations. Nat. Rev. Genet. 2005, 6, 729–742, doi:10.1038/nrg1689.
- Lopez Castel, A.; Cleary, J.D.; Pearson, C.E. Repeat instability as the basis for human diseases and as a potential target for therapy. Nat. Rev. Mol. Cell Biol. 2010, 11, 165–170, doi:10.1038/nrm2854.
- Pearson, C.E. Slipping while sleeping? Trinucleotide repeat expansions in germ cells. Trends Mol. Med. 2003, 9, 490–495, doi:10.1016/j.molmed.2003.09.006.
- Gonitel, R.; Moffitt, H.; Sathasivam, K.; Woodman, B.; Detloff, P.J.; Faull, R.L.; Bates, G.P. DNA instability in postmitotic neurons. Proc. Natl. Acad. Sci. USA 2008, 105, 3467–3472.
- Shelbourne, P.F.; Keller-McGandy, C.; Bi, W.L.; Yoon, S.R.; Dubeau, L.; Veitch, N.J.; Vonsattel, J.P.; Wexler, N.S.; Arnheim, N.; Augood, S.J. Triplet repeat mutation length gains correlate with cell-type specific vulnerability in huntington disease brain. Hum. Mol. Genet. 2007, 16, 1133–1142, doi:10.1093/hmg/ddm054.
- Swami, M.; Hendricks, A.E.; Gillis, T.; Massood, T.; Mysore, J.; Myers, R.H.; Wheeler, V.C. Somatic expansion of the huntington's disease cag repeat in the brain is associated with an earlier age of disease onset. Hum. Mol. Genet. 2009, 18, 3039–3047, doi:10.1093/hmg/ddp242.
- Morales, F.; Couto, J.M.; Higham, C.F.; Hogg, G.; Cuenca, P.; Braida, C.; Wilson, R.H.; Adam, B.; del Valle, G.; Brian, R.; et al. Somatic instability of the expanded ctg triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity. Hum. Mol. Genet. 2012, 21, 3558–3567, doi:10.1093/hmg/dds185.
- Chong, S.S.; McCall, A.E.; Cota, J.; Subramony, S.H.; Orr, H.T.; Hughes, M.R.; Zoghbi, H.Y. Gametic and somatic tissue-specific heterogeneity of the expanded sca1 cag repeat in spinocerebellar ataxia type 1. Nat. Genet. 1995, 10, 344–350, doi:10.1038/ng0795-344.
- Hashida, H.; Goto, J.; Suzuki, T.; Jeong, S.; Masuda, N.; Ooie, T.; Tachiiri, Y.; Tsuchiya, H.; Kanazawa, I. Single cell analysis of cag repeat in brains of dentatorubral-pallidoluysian atrophy (drpla). J. Neurol. Sci. 2001, 190, 87–93, doi:10.1016/S0022-510X(01)00596-2.
- Kennedy, L.; Shelbourne, P.F. Dramatic mutation instability in hd mouse striatum: Does polyglutamine load contribute to cell-specific vulnerability in huntington's disease? Hum. Mol. Genet. 2000, 9, 2539–2544, doi:10.1093/hmg/9.17.2539.
- Lopes-Cendes, I.; Maciel, P.; Kish, S.; Gaspar, C.; Robitaille, Y.; Clark, H.B.; Koeppen, A.H.; Nance, M.; Schut, L.; Silveira, I.; et al. Somatic mosaicism in the central nervous system in spinocerebellar ataxia type 1 and machado-joseph disease. Ann. Neurol. 1996, 40, 199–206, doi:10.1002/ana.410400211.
- Telenius, H.; Kremer, B.; Goldberg, Y.P.; Theilmann, J.; Andrew, S.E.; Zeisler, J.; Adam, S.; Greenberg, C.; Ives, E.J.; Clarke, L.A.; et al. Somatic and gonadal mosaicism of the huntington disease gene cag repeat in brain and sperm. Nat. Genet. 1994, 6, 409–414, doi:10.1038/ng0494-409.
- McMurray, C.T. Mechanisms of trinucleotide repeat instability during human development. Nat. Rev. Genet. 2010, 11, 786–799, doi:10.1038/nrg2828.
- Gacy, A.M.; Goellner, G.; Juranic, N.; Macura, S.; Mcmurray, C.T. Trinucleotide repeats that expand in human disease form hairpin structures in vitro. Cell 1995, 81, 533–540, doi:10.1016/0092-8674(95)90074-8.
- Pearson, C.E.; Sinden, R.R. Alternative structures in duplex DNA formed within the trinucleotide repeats of the myotonic dystrophy and fragile x loci. Biochemistry 1996, 35, 5041–5053, doi:10.1021/bi9601013.
- Pearson, C.E.; Tam, M.; Wang, Y.H.; Montgomery, S.E.; Dar, A.C.; Cleary, J.D.; Nichol, K. Slipped-strand dnas formed by long (cag)*(ctg) repeats: Slipped-out repeats and slip-out junctions. Nucleic Acids Res. 2002, 30, 4534–4547, doi:10.1093/nar/gkf572.
- Hou, C.; Chan, N.L.; Gu, L.; Li, G.M. Incision-dependent and error-free repair of (cag)(n)/(ctg)(n) hairpins in human cell extracts. Nat. Struct. Mol. Biol. 2009, 16, 869–875, doi:10.1038/nsmb.1638.
- Mitas, M.; Yu, A.; Dill, J.; Kamp, T.J.; Chambers, E.J.; Haworth, I.S. Hairpin properties of single-stranded DNA containing a gc-rich triplet repeat: (ctg)15. Nucleic Acids Res. 1995, 23, 1050–1059, doi:10.1093/nar/23.6.1050.
- Panigrahi, G.B.; Lau, R.; Montgomery, S.E.; Leonard, M.R.; Pearson, C.E. Slipped (ctg)*(cag) repeats can be correctly repaired, escape repair or undergo error-prone repair. Nat. Struct. Mol. Biol. 2005, 12, 654–662, doi:10.1038/nsmb959.
- Pearson, C.E.; Wang, Y.H.; Griffith, J.D.; Sinden, R.R. Structural analysis of slipped-strand DNA (s-DNA) formed in (ctg)n. (cag)n repeats from the myotonic dystrophy locus. Nucleic Acids Res. 1998, 26, 816–823, doi:10.1093/nar/26.3.816.
- Panigrahi, G.B.; Slean, M.M.; Simard, J.P.; Gileadi, O.; Pearson, C.E. Isolated short ctg/cag DNA slip-outs are repaired efficiently by hmutsbeta, but clustered slip-outs are poorly repaired. Proc. Natl. Acad. Sci. USA 2010, 107, 12593–12598.
- Slean, M.M.; Reddy, K.; Wu, B.; Nichol Edamura, K.; Kekis, M.; Nelissen, F.H.; Aspers, R.L.; Tessari, M.; Scharer, O.D.; Wijmenga, S.S.; et al. Interconverting conformations of slipped-DNA junctions formed by trinucleotide repeats affect repair outcome. Biochemistry 2013, 52, 773–785, doi:10.1021/bi301369b.
- Reddy, K.; Tam, M.; Bowater, R.P.; Barber, M.; Tomlinson, M.; Nichol Edamura, K.; Wang, Y.H.; Pearson, C.E. Determinants of r-loop formation at convergent bidirectionally transcribed trinucleotide repeats. Nucleic Acids Res. 2010, 39, 1749–1762.
- Lin, Y.; Dent, S.Y.; Wilson, J.H.; Wells, R.D.; Napierala, M. R loops stimulate genetic instability of ctg.Cag repeats. Proc. Natl. Acad. Sci. USA 2010, 107, 692–697, doi:10.1073/pnas.0909740107.
- Libby, R.T.; Hagerman, K.A.; Pineda, V.V.; Lau, R.; Cho, D.H.; Baccam, S.L.; Axford, M.M.; Cleary, J.D.; Moore, J.M.; Sopher, B.L.; et al. Ctcf cis-regulates trinucleotide repeat instability in an epigenetic manner: A novel basis for mutational hot spot determination. PLoS Genet. 2008, 4, e1000257, doi:10.1371/journal.pgen.1000257.
- Dion, V.; Lin, Y.; Hubert, L., Jr.; Waterland, R.A.; Wilson, J.H. Dnmt1 deficiency promotes cag repeat expansion in the mouse germline. Hum. Mol. Genet. 2008, 17, 1306–1317, doi:10.1093/hmg/ddn019.
- Cleary, J.D.; Tome, S.; Lopez Castel, A.; Panigrahi, G.B.; Foiry, L.; Hagerman, K.A.; Sroka, H.; Chitayat, D.; Gourdon, G.; Pearson, C.E. Tissue- and age-specific DNA replication patterns at the ctg/cag-expanded human myotonic dystrophy type 1 locus. Nat. Struct. Mol. Biol. 2010, 17, 1079–1087.
- Dion, V.; Wilson, J.H. Instability and chromatin structure of expanded trinucleotide repeats. Trends Genet. 2009, 25, 288–297, doi:10.1016/j.tig.2009.04.007.
- Dragileva, E.; Hendricks, A.; Teed, A.; Gillis, T.; Lopez, E.T.; Friedberg, E.C.; Kucherlapati, R.; Edelmann, W.; Lunetta, K.L.; MacDonald, M.E.; et al. Intergenerational and striatal cag repeat instability in huntington's disease knock-in mice involve different DNA repair genes. Neurobiol. Dis. 2009, 33, 37–47, doi:10.1016/j.nbd.2008.09.014.
- Wheeler, V.C.; Lebel, L.A.; Vrbanac, V.; Teed, A.; te Riele, H.; MacDonald, M.E. Mismatch repair gene msh2 modifies the timing of early disease in hdh(q111) striatum. Hum. Mol. Genet. 2003, 12, 273–281.
- Manley, K.; Shirley, T.L.; Flaherty, L.; Messer, A. Msh2 deficiency prevents in vivo somatic instability of the cag repeat in huntington disease transgenic mice. Nat. Genet. 1999, 23, 471–473.
- Savouret, C.; Garcia-Cordier, C.; Megret, J.; te Riele, H.; Junien, C.; Gourdon, G. Msh2-dependent germinal ctg repeat expansions are produced continuously in spermatogonia from dm1 transgenic mice. Mol. Cell. Biol. 2004, 24, 629–637, doi:10.1128/MCB.24.2.629-637.2004.
- Van den Broek, W.J.; Nelen, M.R.; Wansink, D.G.; Coerwinkel, M.M.; te Riele, H.; Groenen, P.J.; Wieringa, B. Somatic expansion behaviour of the (ctg)n repeat in myotonic dystrophy knock-in mice is differentially affected by msh3 and msh6 mismatch-repair proteins. Hum. Mol. Genet. 2002, 11, 191–198, doi:10.1093/hmg/11.2.191.
- Kovtun, I.V.; Liu, Y.; Bjoras, M.; Klungland, A.; Wilson, S.H.; McMurray, C.T. Ogg1 initiates age-dependent cag trinucleotide expansion in somatic cells. Nature 2007, 447, 447–452, doi:10.1038/nature05778.
- Mollersen, L.; Rowe, A.D.; Illuzzi, J.L.; Hildrestrand, G.A.; Gerhold, K.J.; Tveteras, L.; Bjolgerud, A.; Wilson, D.M., 3rd; Bjoras, M.; Klungland, A. Neil1 is a genetic modifier of somatic and germline cag trinucleotide repeat instability in r6/1 mice. Hum. Mol. Genet. 2012, 21, 4939–4947, doi:10.1093/hmg/dds337.
- Hubert, L., Jr.; Lin, Y.; Dion, V.; Wilson, J.H. Xpa deficiency reduces cag trinucleotide repeat instability in neuronal tissues in a mouse model of sca1. Hum. Mol. Genet. 2011, 20, 4822–4830, doi:10.1093/hmg/ddr421.
- Kovtun, I.V.; Johnson, K.O.; McMurray, C.T. Cockayne syndrome b protein antagonizes ogg1 in modulating cag repeat length in vivo. Aging 2011, 3, 509–514.
- Lindahl, T. Instability and decay of the primary structure of DNA. Nature 1993, 362, 709–715, doi:10.1038/362709a0.
- Lindahl, T. Suppression of spontaneous mutagenesis in human cells by DNA base excision-repair. Mutat. Res. 2000, 462, 129–135, doi:10.1016/S1383-5742(00)00024-7.
- Robertson, A.B.; Klungland, A.; Rognes, T.; Leiros, I. DNA repair in mammalian cells: Base excision repair: The long and short of it. Cell Mol. Life Sci. 2009, 66, 981–993, doi:10.1007/s00018-009-8736-z.
- Fortini, P.; Dogliotti, E. Base damage and single-strand break repair: Mechanisms and functional significance of short- and long-patch repair subpathways. DNA Repair 2007, 6, 398–409, doi:10.1016/j.dnarep.2006.10.008.
- Freudenreich, C.H.; Kantrow, S.M.; Zakian, V.A. Expansion and length-dependent fragility of ctg repeats in yeast. Science 1998, 279, 853–856, doi:10.1126/science.279.5352.853.
- Yang, J.; Freudenreich, C.H. Haploinsufficiency of yeast fen1 causes instability of expanded cag/ctg tracts in a length-dependent manner. Gene 2007, 393, 110–115, doi:10.1016/j.gene.2007.01.025.
- Subramanian, J.; Vijayakumar, S.; Tomkinson, A.E.; Arnheim, N. Genetic instability induced by overexpression of DNA ligase i in budding yeast. Genetics 2005, 171, 427–441, doi:10.1534/genetics.105.042861.
- Refsland, E.W.; Livingston, D.M. Interactions among DNA ligase i, the flap endonuclease and proliferating cell nuclear antigen in the expansion and contraction of cag repeat tracts in yeast. Genetics 2005, 171, 923–934, doi:10.1534/genetics.105.043448.
- Schweitzer, J.K.; Livingston, D.M. The effect of DNA replication mutations on cag tract stability in yeast. Genetics 1999, 152, 953–963.
- Lopez Castel, A.; Tomkinson, A.E.; Pearson, C.E. Ctg/cag repeat instability is modulated by the levels of human DNA ligase i and its interaction with proliferating cell nuclear antigen: A distinction between replication and slipped-DNA repair. J. Biol. Chem. 2009, 284, 26631–26645, doi:10.1074/jbc.M109.034405.
- Harrison, C.; Ketchen, A.M.; Redhead, N.J.; O'Sullivan, M.J.; Melton, D.W. Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase i gene. Cancer Res. 2002, 62, 4065–4074.
- Tome, S.; Panigrahi, G.B.; Lopez Castel, A.; Foiry, L.; Melton, D.W.; Gourdon, G.; Pearson, C.E. Maternal germline-specific effect of DNA ligase i on ctg/cag instability. Hum. Mol. Genet. 2011, 20, 2131–2143, doi:10.1093/hmg/ddr099.
- Spiro, C.; McMurray, C.T. Nuclease-deficient fen-1 blocks rad51/brca1-mediated repair and causes trinucleotide repeat instability. Mol. Cell. Biol. 2003, 23, 6063–6074, doi:10.1128/MCB.23.17.6063-6074.2003.
- Van den Broek, W.J.; Nelen, M.R.; van der Heijden, G.W.; Wansink, D.G.; Wieringa, B. Fen1 does not control somatic hypermutability of the (ctg)(n)*(cag)(n) repeat in a knock-in mouse model for dm1. FEBS Lett. 2006, 580, 5208–5214, doi:10.1016/j.febslet.2006.08.059.
- Bentley, D.; Selfridge, J.; Millar, J.K.; Samuel, K.; Hole, N.; Ansell, J.D.; Melton, D.W. DNA ligase i is required for fetal liver erythropoiesis but is not essential for mammalian cell viability. Nat. Genet. 1996, 13, 489–491, doi:10.1038/ng0896-489.
- Kucherlapati, M.; Yang, K.; Kuraguchi, M.; Zhao, J.; Lia, M.; Heyer, J.; Kane, M.F.; Fan, K.; Russell, R.; Brown, A.M.; et al. Haploinsufficiency of flap endonuclease (fen1) leads to rapid tumor progression. Proc. Natl. Acad. Sci. USA 2002, 99, 9924–9929, doi:10.1073/pnas.152321699.
- Cabelof, D.C.; Guo, Z.; Raffoul, J.J.; Sobol, R.W.; Wilson, S.H.; Richardson, A.; Heydari, A.R. Base excision repair deficiency caused by polymerase beta haploinsufficiency: Accelerated DNA damage and increased mutational response to carcinogens. Cancer Res. 2003, 63, 5799–5807.
- Sobol, R.W.; Horton, J.K.; Kuhn, R.; Gu, H.; Singhal, R.K.; Prasad, R.; Rajewsky, K.; Wilson, S.H. Requirement of mammalian DNA polymerase-beta in base-excision repair. Nature 1996, 379, 183–186, doi:10.1038/379183a0.
- Xanthoudakis, S.; Smeyne, R.J.; Wallace, J.D.; Curran, T. The redox/DNA repair protein, ref-1, is essential for early embryonic development in mice. Proc. Natl. Acad. Sci. USA 1996, 93, 8919–8923, doi:10.1073/pnas.93.17.8919.
- Tebbs, R.S.; Flannery, M.L.; Meneses, J.J.; Hartmann, A.; Tucker, J.D.; Thompson, L.H.; Cleaver, J.E.; Pedersen, R.A. Requirement for the xrcc1 DNA base excision repair gene during early mouse development. Dev. Biol. 1999, 208, 513–529, doi:10.1006/dbio.1999.9232.
- Lin, Y.; Wilson, J.H. Transcription-induced cag repeat contraction in human cells is mediated in part by transcription-coupled nucleotide excision repair. Mol. Cell. Biol. 2007, 27, 6209–6217, doi:10.1128/MCB.00739-07.
- Dou, H.; Mitra, S.; Hazra, T.K. Repair of oxidized bases in DNA bubble structures by human DNA glycosylases neil1 and neil2. J. Biol. Chem. 2003, 278, 49679–49684.
- Entezam, A.; Lokanga, A.R.; Le, W.; Hoffman, G.; Usdin, K. Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile x premutation mouse model. Hum. Mutat. 2010, 31, 611–616.
- Goula, A.V.; Berquist, B.R.; Wilson, D.M., 3rd; Wheeler, V.C.; Trottier, Y.; Merienne, K. Stoichiometry of base excision repair proteins correlates with increased somatic cag instability in striatum over cerebellum in huntington's disease transgenic mice. PLoS Genet. 2009, 5, e1000749, doi:10.1371/journal.pgen.1000749.
- Jarem, D.A.; Wilson, N.R.; Delaney, S. Structure-dependent DNA damage and repair in a trinucleotide repeat sequence. Biochemistry 2009, 48, 6655–6663, doi:10.1021/bi9007403.
- Jarem, D.A.; Wilson, N.R.; Schermerhorn, K.M.; Delaney, S. Incidence and persistence of 8-oxo-7,8-dihydroguanine within a hairpin intermediate exacerbates a toxic oxidation cycle associated with trinucleotide repeat expansion. DNA Repair 2011, 10, 887–896, doi:10.1016/j.dnarep.2011.06.003.
- Hartenstine, M.J.; Goodman, M.F.; Petruska, J. Weak strand displacement activity enables human DNA polymerase beta to expand cag/ctg triplet repeats at strand breaks. J. Biol. Chem. 2002, 277, 41379–41389, doi:10.1074/jbc.M207013200.
- Liu, Y.; Wilson, S.H. DNA base excision repair: A mechanism of trinucleotide repeat expansion. Trends Biochem. Sci. 2012, 37, 162–172, doi:10.1016/j.tibs.2011.12.002.
- Spiro, C.; Pelletier, R.; Rolfsmeier, M.L.; Dixon, M.J.; Lahue, R.S.; Gupta, G.; Park, M.S.; Chen, X.; Mariappan, S.V.; McMurray, C.T. Inhibition of fen-1 processing by DNA secondary structure at trinucleotide repeats. Mol. Cell 1999, 4, 1079–1085, doi:10.1016/S1097-2765(00)80236-1.
- Vallur, A.C.; Maizels, N. Complementary roles for exonuclease 1 and flap endonuclease 1 in maintenance of triplet repeats. J. Biol. Chem. 2010, 285, 28514–28519, doi:10.1074/jbc.M110.132738.
- Liu, Y.; Prasad, R.; Beard, W.A.; Hou, E.W.; Horton, J.K.; McMurray, C.T.; Wilson, S.H. Coordination between polymerase beta and fen1 can modulate cag repeat expansion. J. Biol. Chem. 2009, 284, 28352–28366, doi:10.1074/jbc.M109.050286.
- Liu, Y.; Prasad, R.; Wilson, S.H. Hmgb1: Roles in base excision repair and related function. Biochim. Biophys. Acta 2010, 1799, 119–130, doi:10.1016/j.bbagrm.2009.11.008.
- Goula, A.V.; Pearson, C.E.; Della Maria, J.; Trottier, Y.; Tomkinson, A.E.; Wilson, D.M., 3rd; Merienne, K. The nucleotide sequence, DNA damage location, and protein stoichiometry influence the base excision repair outcome at cag/ctg repeats. Biochemistry 2012, 51, 3919–3932, doi:10.1021/bi300410d.
- Lai, Y.; Xu, M.; Zhang, Z.; Liu, Y. Instability of ctg repeats is governed by the position of a DNA base lesion through base excision repair. PLoS One 2013, 8, e56960.
- Hou, C.; Zhang, T.; Tian, L.; Huang, J.; Gu, L.; Li, G.M. The role of xpg in processing (cag)n/(ctg)n DNA hairpins. Cell. Biosci. 2011, 1, 11, doi:10.1186/2045-3701-1-11.
- Higham, C.F.; Morales, F.; Cobbold, C.A.; Haydon, D.T.; Monckton, D.G. High levels of somatic DNA diversity at the myotonic dystrophy type 1 locus are driven by ultra-frequent expansion and contraction mutations. Hum. Mol. Genet. 2012, 21, 2450–2463, doi:10.1093/hmg/dds059.
- Tome, S.; Simard, J.P.; Slean, M.M.; Holt, I.; Morris, G.E.; Wojciechowicz, K.; te Riele, H.; Pearson, C.E. Tissue-specific mismatch repair protein expression: Msh3 is higher than msh6 in multiple mouse tissues. DNA Repair 2013, 12, 46–52, doi:10.1016/j.dnarep.2012.10.006.
- Seriola, A.; Spits, C.; Simard, J.P.; Hilven, P.; Haentjens, P.; Pearson, C.E.; Sermon, K. Huntington's and myotonic dystrophy hescs: Down-regulated trinucleotide repeat instability and mismatch repair machinery expression upon differentiation. Hum. Mol. Genet. 2011, 20, 176–185.
- Hick, A.; Wattenhofer-Donze, M.; Chintawar, S.; Tropel, P.; Simard, J.P.; Vaucamps, N.; Gall, D.; Lambot, L.; Andre, C.; Reutenauer, L.; et al. Induced pluripotent stem cell derived neurons and cardiomyocytes as a model for mitochondrial defects in friedreich's ataxia. Dis. Model. Mech. 2012, 7, doi:10.1242/dmm.010900.
- Du, J.; Campau, E.; Soragni, E.; Ku, S.; Puckett, J.W.; Dervan, P.B.; Gottesfeld, J.M. Role of mismatch repair enzymes in gaa.Ttc triplet-repeat expansion in friedreich ataxia induced pluripotent stem cells. J. Biol. Chem. 2012, 287, 29861–29872.
© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).


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I just bought Nigella Lawson's latest cookbook, 'Nigella Express' which has a recipe for Naan Pizza. The only ingredient I had in was the naan, but I liked the idea and adapted the recipe to fit the ingredients I had in my fridge and larder. The recipe is very versatile and you could play with all kinds of toppings, for example using pizza sauce instead of the pesto, using a different cheese or adding mushrooms. This makes a great snack or even a quick and easy dinner if served with a side salad, it would even make a nice appetizer to share. Oviously you can double, trebble or quadrouple the recipe to meet your needs.
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November 28, 2014
April 5, 2009
The Virginia men's tennis team shut out North Carolina 7-0 in its final home match of the season.
The Cavaliers won the doubles point and went on to sweep the singles matches in front of 502 fans at the Snyder Tennis Center. It was Virginia's 40th consecutive win over an ACC team and 47th consecutive win at home. The Cavaliers have also secured at least a share of the ACC regular season title for the sixth straight year.
Virginia is now 24-0 on the season, 9-0 in the ACC. The Cavaliers will try to stay undefeated on Friday when they head down to Winston-Salem, NC to take on Wake Forest. Following their match with the Demon Deacons, the Cavs will close out the regular season at NC State.
Click the above link for highlights from Sunday's match.
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Italian restaurant near BWI
Need to meet people on Tuesday evening at an Italian restaurant near BWI. Any suggestions?
re: Zevonista
There isn't notable Italian before Columbia/Laurel or Baltimore, but there is a fast mom & pop type place that's OK. On 176 (Dorsey Rd) is Mamma Lucia.
A non-Italian place you could go is G&M - they've been up and down throughout the years and people love or hate the crab cakes, but it is a good experience. W. Nursery & Hammond roads.
re: Zevonista
Carmelo's on Camp Meade Rd
Need to be closer to BWI; people arriving at 5 and at 8 p.m. and want to have dinner in between those arrivals.
Does it have to be Italian? This place has standard dishes, and Snyder's Willow Grove has some pasta dishes. Not sure beyond that but there is good food nearby. Snyder's is an all around crowd pleaser that doubles as a time traveling machine back to the 50's.
Note that I haven't been to Olive Grove.
re: Dennis S
Olive Grove is quite mediocre (although inexplicably popular with the locals).
There's no really good Italian right near the airport; I would just have dinner in downtown Baltimore, which is perhaps 10-15 mins away. Laurel and Columbia, mentioned by the other posters, are at least as far.
Cinghiale or Sotto Sopra at the high end, Cafe Gia or one of the Little Italy haunts lower down the chain.
I'm a big fan of Alberto's. It's not too far from the airport (10 minutes max and no traffic in that direction). Closer and easier to get to and park than Baltimore.


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Book Description:
Okonowo is the greatest warrior alive. His fame has spread like a bushfire in West Africa and he is one of the most powerful men of his clan. But he also has a fiery temper. Determined not to be like his father, he refuses to show weakness to anyone - even if the only way he can master his feelings is with his fists. When outsiders threaten the traditions of his clan, Okonowo takes violent action. Will the great man's dangerous pride eventually destroy him?
Tags: Literature-Fiction, Contemporary,


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Dayan Viciedo fractured his right thumb in the White Sox Cactus League game against the Texas Rangers. | AP
Updated: March 10, 2011 5:04PM
SURPRISE, Ariz. -- White Sox right fielder Dayan Viciedo will miss the next three-to-four weeks after fracturing his right thumb in the Sox' Cactus League game against the Texas Rangers.
Viciedo was hit by a pitch from Rangers right-hander Dave Bush in the eighth inning.
Viciedo, who was converting to right field from third base, was having an exceptional spring. He went into the game batting .476 (10-for-21) and had made three very good plays in right.
When asked Wednesday if any player in particular has impressed him during spring training, manager Ozzie Guillen did not hesitate.
"So far? There's only one guy, that's Viciedo,'' Guillen said. "Everybody else, I expect them to do [well]. I expect [Chris] Sale to be Sale, [Sergio] Santos to be Santos. We've got a lot of guys playing well, but Viciedo is the one that's stood out in my mind.''
Viciedo appeared to be headed to AAA, though, because the Sox would prefer him to play every day in the minors rather than play part-time with the big-league club.


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الانتفاضة الإلكترونية
New security camera footage captures the moment a Palestinian teen was shot by Israeli soldiers during Nakba Day protest.
Churches who helped take aboriginal children away from their parents proved reluctant to cooperate with the Victoria show.
An interview with Radio Islam International about the recent reportage on Israel's killing of two Palestinian teens in the occupied West Bank.
CNN's footage offers further clear proof that Israeli authorities are lying about how boys were killed.
Right-wing extremists "get a free pass" to intimidate Palestinian students.
CCTV shows the two boys being shot down in cold blood on Nakba Day.
This short video featuring women and men in Gaza speaking about their connections to Palestine was published to mark Nakba Day.
An Israeli eyewitness contradicts the dramatic account of an Israeli reporter that he was "seconds away from being beaten to death by a mob of Palestinian masked men" during a demonstration in the West Bank on Friday. Two Palestinian teenagers were killed by Israeli forces at the same spot the day before.
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Dubai rang in the new year last night by shooting flames out of the Burj Khalifa, the world's tallest building. If you ever wondered what a half-mile-tall sparkler looks like, watch the above video.
Ghost Protocol lets Tom Cruise, the Bankable Movie Star, live another day
via Marshall StrabalaFrom our Religious Observances in Skyscrapers department comes an interesting story from the United Arab Emirates. The Washington Post reports that Dubai's top Muslim cleric told residents living above the 80th floor of the 2,717 foot Burj Khalifa to "wait three extra min ... More >>


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3 coupon codes & deals for wedzines.com. A professionally produced magazine especially made for each couple that is designed to remember the future while celebrating the past. A wedding program, personal biography, practical guide and keepsake all rolled into one. A must have magazine for every wedding.
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August 5, 2014
Since May 2011, the CTA has taken a number of steps to improve efforts in tackling crime on the bus and rail systems, including expanding police patrols and rail saturation missions on the CTA system and increasing undercover operations targeting pick-pocket theft rings and other crimes.
July 30, 2014
Chicago Transit Authority's new solicitation for bids will ask manufacturing companies to disclose plans to create American jobs and opportunities for disadvantaged American workers, and evaluates the quality of their responses with a system of price credits.
June 24, 2014
According to transportation officials, it's taking "longer than expected to complete the design" of the project and consult with building owners and stakeholders.
May 27, 2014
The increases are the result of Mayor Rahm Emanuel and CTA President Forrest Claypool's focused efforts to promote and expand the hiring of veterans.
February 26, 2014
Announced in December 2013, Your New Blue includes a number of track and station improvement projects along the 12.5-mile stretch of the O'Hare Branch between the Grand and O'Hare stations.
February 12, 2014
The station work is part of the $492 million "Your New Blue" plan announced in December — the largest comprehensive investment for the Blue Line since 1984.
January 8, 2014
The project includes improving station and platform lighting; installing additional security cameras and CTA Bus and Train Tracker displays and making repairs to the station platform canopy.
December 5, 2013
The $492 million plan, called "Your New Blue," includes several track and station improvement projects along a 12.5-mile stretch of the Blue Line O'Hare Branch between the Grand and Cumberland stations
November 20, 2013
The $240 million reconstruction project, slated to begin in spring 2014, will create a facility that will serve as a community focal point and an anchor for economic opportunity on Chicago's South Side.
October 1, 2013
Mayor Rahm Emanuel was the featured speaker at APTA's 2013 Annual Meeting Opening General Session on Monday.
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WAR: Obama Classmate Flays Obama; He's
A Manchurian Candidate; Lied To Everybody
Non-Birther Wayne Allyn Root lays out exactly what Obama is doing to America how he was trained to do it...
Excerpt via Leftists @ Right Wing Watch (6/24/2014): Chris McDaniel Closes Out Senate Race By Campaigning With Bryan Fischer And Wayne Allyn Root
Republican Senate candidate Chris McDaniel spent this weekend rolling around Mississippi on the Tea Party Express bus, along with a motley assortment of fringe right-wing extremists.
McDaniel's fellow travelers in his last tour before today's runoff election against Sen. Thad Cochran included Wayne Allyn Root, who told audiences that President Obama is a "Manchurian candidate" who lied about his resume; a songwriting duo known for the anti-immigrant song "Press 1 for English"; and notoriously anti-gay, anti-Muslim, anti-many-other-people American Family Association spokesman Bryan Fischer, who granted McDaniel what he said was his very first public endorsement of a candidate for office.
At the group's stop in Biloxi, Root — a one-time Libertarian Party nominee for vice president — regaled the crowd with his theory that President Obama is a "Manchurian candidate" who "cut his Afro" in order to infiltrate the government, collapse the economy and create a permanent Democratic majority.
Strangely, although Root implies that President Obama did not actually attend Columbia University, he also claims that the president learned this "Manchurian" strategy at Columbia.
Root also told the crowd that "we're the makers and Obama's voters are the takers," claiming that conservative radio exists because conservatives are listening to the radio on their way to work, while liberals are "home collecting their checks watching Oprah and Jerry Springer and ads for personal injury attorneys."
[...] Continued @ Right Wing Watch.


text:
Pilot Study to Evaluate The Effectiveness And Safety Of Axiom Worldwide Drx9000™ Spinal Decompression System
This study has been completed.
NEMA Research, Inc.
Information provided by:
NEMA Research, Inc.
ClinicalTrials.gov Identifier:
First received: December 19, 2006
Last updated: February 12, 2009
Last verified: February 2009
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
This pilot study will evaluate the effectiveness and safety of the Axiom Worldwide DRX9000 for active treatment of chronic low back pain.
Low Back Pain
Device: DRX9000™
|Study Type:
|Study Design:
|Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:
|Pilot Study to Evaluate The Effectiveness And Safety Of Axiom Worldwide Drx9000™ Spinal Decompression System For Treatment of Low Back Pain
Resource links provided by NLM:
MedlinePlus related topics: Back PainU.S. FDA Resources
Further study details as provided by NEMA Research, Inc.:
|Ages Eligible for Study:
|18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Male or female, greater than 18 years of age
- Able to understand possible risks and benefits and provide written informed consent (ICF) to the IRB approved clinical multimodal protocol
- LBP with an intensity level of greater than 4 on an eleven point numerical pain rating scale (VRS) of 0-10 (with 0 - no pain and 10 - worst possible pain)
- Completed the necessary diagnostic and medical history evaluations as described in the protocol to confirm the patient's diagnosis and eligibility for the study and DRX9000 treatment protocol.
- Willing and able to complete a six week 20 session of DRX9000 outpatient treatments and a minimum of 6 months follow-up
Exclusion Criteria:
- Pregnancy
- Evidence of neurological motor deficits on clinical examination
- Evidence of spinal cord compression, metastatic cancer, tumor, hematoma, infection or compression fracture
- Evidence of severe central stenosis with neurological deficits or nerve root entrapment
- Litigation for health-related claim (in process or pending), Worker's Compensation, or Personal Injury
- Previous spine fusion surgery, insertion of hardware or artificial disc
- Hemiplegia or paraplegia
- History of severe cardiovascular or metabolic disease, or abdominal aortic aneurysm
- Unwillingness to postpone other types of therapy for LBP during the 6 week treatment sessions
- Known alcohol abuse or drug abuse
- Height less than 4 feet 10 inches (147 cm) or greater than 6 feet 8 inches (203 cm)
- Body weight greater than 300 pounds (136 kg)
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00414596
Please refer to this study by its ClinicalTrials.gov identifier: NCT00414596
|United States, California
|Vibrance Medical Group
|Beverly Hills, California, United States, 90212
|United States, Florida
|Naples Anesthesia and Pain Associates
|Naples, Florida, United States, 34108
|Active Health and Wellness Center
|Tampa, Florida, United States, 33614
Sponsors and Collaborators
NEMA Research, Inc.
|Principal Investigator:
|John Leslie, MD
|Mayo Clinic
|Study Director:
|Charlotte Richmond, PhD
|NEMA Research, Inc.
|Study Chair:
|Joseph V Pergolizzi, MD
|Naples Anesthesia and Pain Associates
More Information
Additional Information:
No publications provided
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on November 25, 2014
Additional Information:
No publications provided
|ClinicalTrials.gov Identifier:
|NCT00414596 History of Changes
|Other Study ID Numbers:
|Study First Received:
|December 19, 2006
|Last Updated:
|February 12, 2009
|Health Authority:
|United States: Institutional Review Board
Additional relevant MeSH terms:
Back Pain
Low Back Pain
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
ClinicalTrials.gov processed this record on November 25, 2014


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How hot does your diesel run?
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Master Mariner
Join Date: Jun 2011
Location: somewhere in the Windward or Leeward Islands
Posts: 1,662
Thanks: 16
Thanked 84 Times in 79 Posts
Rep Power:
Re: How hot does your diesel run?
The important thing to remember with temp gauges is that they may not be an exact reading of the true temp (off even 10 or 15 degrees), but the changes are very significant. For instance, once the thermostat has opened it should come up to a normal operating temp (usually 180ish) and remain there. If the temp fluctuates w/ a change in RPM's, dropping at lower RPM's or rising as you go up, you have a cooling problem. If it begins to creep up (not in a day but over successive trips) from whatever is the normal operating temp, your impeller has probably lost a few vanes.
After a bit of time you will have a good idea of your normal operating temp reading on the gauge and can keep an eye out for changes. Your engine should run at the same temp for half an hour or 20 hours; time should make no difference.
There are odd times, usually in extreme conditions, where the engine is working much harder than usual and the temp can go up a few degrees, but it should never go above 200 (from 180ish), no matter what. I hope you also have an audible alarm, because a plastic bag or something else could cause a blockage in the line and the temp will go up very quickly to damaging levels, unnoticed on the gauge.
"Any idiot can make a boat go; it takes a sailor to stop one." Spike Africa aboard the schooner
in Sausalito, Ca. 1964.
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Education Classes
Online Continuing Education Classes Are Now Available
Currently we have 39 Elective & 6 Designated continuing education credit hours available.
Link to Online Education Classes
Happy St. Patrick's Day! You don't have to be lucky to get this offer you just have to take CE online with us and you'll save 15% on your next order!
Enroll in online Continuing Education today and SAVE 15% on your enrollment fees!
Enter lucky15 at checkout to receive your discount!
Simply Visit: http://alaskarealtors.theceshop.com/
GRI Series Offered in 2014 GRI 200 and 300 will be co-sponsored by the Anchorage and Valley Boards in 2014. Each module is $250.00. Additional information will be posted soon on each course.
GRI 200 – Click HERE for additional information
Thursday – Friday, July 31/August 1, 2014 – Anchorage
Thursday – Friday, August 7 & 8, 2014 – Valley
Thursday – Friday, October 2 & 3, 2014 – Anchorage
Thursday – Friday, October 9 & 10, 2014 – Valley
Expanding Housing Opportunity Classes
Georgia Meacham will be teaching in 5 different areas. This is a four-hour course designed to educate real estate professionals on the range of affordable housing opportunities and clients seeking them. This has been approved for 4 hours of Continuing Education credit.
Wednesday, August 13 – Offered by the Anchorage Board of REALTORS – $25 per person
Thursday, August 14 – Offered by the Valley Board of REALTORS – $20 per person
Friday, August 15 – Offered by the Greater Fairbanks Board of REALTORS – $20 per person
Monday, August 18 – Offered by the Kachemak Board of REALTORS – $25 per person
Tuesday, August 19 – Offered by the Kenai Peninsula Association of REALTORS – $20 per person
View the flyer HERE.
HomeChoice Classes Offered by Alaska Housing Finance Corporation
A FREE 8-Hour Home Buyer Education Class
For more information or to see a schedule of classes, go to www.ahfc.us/classes
Click here for information flyer.


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Subscriber Services
American Airlines
American Airlines
Justice Department
American Airlines Buying Usair?
May 30, 1996
by Scott Flander, Daily News Staff Writer Staff writers Anthony S. Twyman and Kurt Heine contributed to this report
You might go to the airport someday soon and get the impression that American Airlines basically owns the joint. If American Airlines buys USAir Group, more than 70 percent of Philadelphia International Airport's domestic flights would be operated by American. And for Philadelphia travelers, that could mean higher fares and, maybe, fewer flights to choose from, some airline experts say. Right now, it's far from certain that American will buy USAir. But that possibility is reportedly being discussed by American Airlines and British Airways, which appear to be on the verge of a major trans-Atlantic alliance.
American Airlines Opts For Surcharge
August 5, 1990
By Donald D. Groff, Special to The Inquirer
AIRPORT SURCHARGE. American Airlines has begun imposing ticket surcharges of $1 to $4 on each departing passenger at five U.S. airports, in effect passing on to customers charges that the airports have assessed the airline. The airports are New York's La Guardia, Newark International and those in New Orleans and in Fort Myers and West Palm Beach, Fla. The surcharges reflect disagreements over fees between the airline and the airports. At La Guardia, for instance, the airline objects to some airport- improvement costs with which it has been saddled.
American Airlines Plans Layoffs
January 3, 1991
The Inquirer Staff
American Airlines said yesterday that it would lay off an unspecified number of workers because what it termed an illegal sickout by pilots has forced the carrier to cut back its flight schedule. The nation's largest airline said it would reduce the number of flights by 4 percent in mid-January because of what it said was an organized effort by pilots to slow operations to protest a lack of progress in contract talks. The carrier normally operates about 2,300 daily flights worldwide.
Virgin America to end Philadelphia flights
April 30, 2014
By Linda Loyd, Inquirer Staff Writer
Virgin America, California's hip and high-tech airline, is pulling its flights from Philadelphia to Los Angeles and San Francisco, and flying the airplanes instead to more lucrative corporate travel markets - between Dallas and New York City and Washington. The airline began Philadelphia flights two years ago. It said the service will end Oct. 6. The Burlingame, Calif., carrier said Friday that it had been awarded two gates at Dallas' Love Field by the Justice Department and planned to begin flights in October to New York LaGuardia and Reagan Washington National Airports.
American Airlines cancels some flights
March 26, 2008
FORT WORTH, Texas - American Airlines canceled about 200 flights today so its crews can inspect some wire bundles aboard its MD-80 aircraft. The canceled flights represent less than 10 percent of the nation's biggest airline's scheduled service for the day. American canceled most of its flights scheduled for today between Philadelphia International Airport and its hub at Chicago O'Hare Airport, and other flights to its Dallas/Fort Worth and...
110 Jetliners Ordered By American Airlines
March 23, 1989
From Inquirer Wire Services
In a bid to gear up for the next decade, American Airlines said yesterday that it had placed orders for 75 twin-jet aircraft from Dutch manufacturer Fokker and 35 jetliners from Boeing Co. "Taken together, these transactions complete the task of positioning American for the 1990s," chairman Robert Crandall said at a news conference. The airline, owned by AMR Corp. in Fort Worth, Texas, also took options to purchase another 75 aircraft from Fokker. The order is the largest in Fokker's history, it said.
American Airlines pilots reject contract
August 10, 2012
By Linda Loyd, Inquirer Staff Writer
American Airlines' pilots overwhelmingly rejected a tentative agreement with the bankrupt airline Wednesday, putting their fate before a federal bankruptcy judge and potentially delaying US Airways' quest to merge and create the world's biggest airline. The Allied Pilots Association, representing 8,000 pilots, voted 4,600 against and 2,935 in favor of the tentative contract. An approval would have sped American's plan to restructure and emerge from Chapter 11 reorganization as a stand-alone company, or part of a merger, one airline analyst said.
American Airlines attendants approve work changes
August 21, 2012
American Airlines flight attendants have approved cost reductions, including changes to work hours and pensions, sought by the bankrupt carrier, the union said Sunday. Despite the "yes" vote, union leaders said they continue to support a merger with US Airways Group Inc. and have "zero confidence" in American's current management. "We firmly believe that the only way for American Airlines to grow and compete and perhaps even to survive is through a merger" that puts US Airways chief executive Doug Parker and his team in charge, the Association of Professional Flight Attendants said on its website.
American Airlines reduces flight schedule into November
October 12, 2012
American Airlines said Thursday it will reduce its flight schedule by 1 percent through the first half of November because of continuing flight delays and cancellations. While "encouraged" by improvements in some performance metrics, the Fort Worth, Tex.-based carrier said "overall, we are not yet back to the levels our customers deserve and expect. " The change will not affect holiday travel, American said in a memo to employees. American earlier reduced its flying by 1 percent to 2 percent through October.
American Airlines creditors call for replacing board
December 1, 2012
By Linda Loyd, Inquirer Staff Writer
A significant group of financial creditors of bankrupt American Airlines said it would support a stand-alone carrier after bankruptcy only if there were to be a new board of directors - and key stakeholders, including labor, were part of the selection. The group laid out its position in a letter to American pilots' union president Keith Wilson made public to 8,000 members of the Allied Pilots Association (APA) on Wednesday. The 12 creditors, represented by the law firm Milbank, Tweed, Hadley & McCoy, said that as "material" stakeholders "we intend to be one of the primary negotiators of any plan of reorganization.
Next »
New American Airlines will reward miles on distance and not fares
November 6, 2014
By Linda Loyd, Inquirer Staff Writer
US Airways and American Airlines, which are combining their frequent-flier programs, will continue to reward miles for travel based on distance flown, not fares paid. That benefits leisure travelers, who hunt for bargain fares, in contrast to business travelers, who often book expensive last-minute tickets. US Airways Dividend Miles members, who fly occasionally, won't notice much difference - they will get a new American frequent-flier number next year. US Airways' most frequent jet-setters, who log 25,000 miles or more a year, will see changes.
U.S. airlines report healthy 3Q profits, no noticeable Ebola impact
October 25, 2014
By Linda Loyd, Inquirer Staff Writer
U.S. airline stocks rallied Thursday after several carriers reported healthy third-quarter profits, helped by strong bookings and declining jet-fuel prices. Ebola fears have not noticeably discouraged travel, airline executives said. "The demand environment remains solid, and strong revenue trends have continued," Southwest Airlines chief financial officer Tammy Romo said on an investor call. American Airlines, Southwest, and JetBlue Airways posted record profits for the three months ended Sept.
American expands Phila. airport facility for cold freight
August 27, 2014
By Linda Loyd, Inquirer Staff Writer
American Airlines and its merger partner, US Airways, are renovating a warehouse at Philadelphia International Airport to include refrigeration for pharmaceuticals and other health-care products. When it opens this fall, the temperature-controlled plant will be able to handle four to five times the current amount of perishable, time-sensitive, and valuable airfreight, including vaccines and blood products, that arrive and leave in the belly of planes on US Airways and American passenger flights.
George E. Westwood, captain in the Navy
August 7, 2014
By Robert Moran, Inquirer Staff Writer
George E. Westwood III, 60, a Philadelphia native who rose to the rank of captain in the Navy and served during the Gulf war and in Afghanistan, died July 28 after a long struggle with lung cancer. Mr. Westwood, who lived in Jacksonville, Fla., died during a visit to the Mayo Clinic in Jacksonville, said his daughter Mary Lena. He was born in Philadelphia and graduated from William Penn Charter School. He then attended Rollins College in Florida and graduated with a bachelor's degree in psychology.
For many first-class flights, don't come hungry
August 7, 2014
By Linda Loyd, Inquirer Staff Writer
Soon the only thing that might distinguish first class from economy travel on some shorter US Airways and American Airlines flights will be roomier seats, more leg room - and free cocktails. One more accoutrement of air travel is disappearing: the complimentary three-course meal in the "premium" cabin on many domestic flights. Starting Sept. 1, American, which recently merged with US Airways, Philadelphia's dominant airline, will offer snacks instead of a full meal in first class and business class on most flights of less than two hours and 45 minutes in duration.
Airlines report strong quarterly earnings
July 26, 2014
By Linda Loyd, Inquirer Staff Writer
U.S. airlines made money in the second quarter, beating analysts' expectations, as they flew fuller planes and garnered higher passenger revenue. American Airlines, which merged with US Airways in December, announced it would pay its first dividend since 1980, based on a record quarterly profit. The merged US Airways and American, which combined have more than 75 percent of the flights at Philadelphia International Airport, reported net income of $864 million, or $1.17 a share.
Trainer oil refinery helps boost Delta earnings
July 25, 2014
By Linda Loyd, Inquirer Staff Writer
Delta Air Lines said Wednesday that its Trainer oil refinery in Delaware County produced a $13 million profit in the second quarter. Delta, the first U.S. airline to report earnings, posted a second-quarter profit of $889 million, or $1.04 a share, that beat analysts' estimates, driven by strong passenger demand and higher revenue from corporate contracts. Revenue rose 9.4 percent to $10.6 billion. "We will post even better results in the third quarter, with a forecast operating margin of 15 percent to 17 percent," Delta chief executive officer Richard Anderson said on a conference call.
Flights to Tel Aviv canceled
July 24, 2014
BY CINDY STANSBURY, Daily News Staff Writer email@example.com, 215-854-5914
TRAVELERS HOPING to jet off to Tel Aviv yesterday were forced to reschedule plans after airlines suspended service to the Israeli city in the wake of a reported rocket attack. US Airways, the only airline with a direct daily flight between Philadelphia and Tel Aviv, canceled Flight 797 to Philadelphia and Flight 796 to Tel Aviv. The cancellations were brought on by the news that a rocket from Gaza had landed near Tel Aviv's Ben Gurion International Airport. The Federal Aviation Administration issued a 24-hour ban on flights between the U.S. and Tel Aviv beginning at 12:15 p.m. yesterday.
Malaysia Airlines takes another bad blow
July 19, 2014
By Linda Loyd, Inquirer Staff Writer
It couldn't get any worse for Malaysia Airlines, still reeling from the disappearance of Flight 370 in March, when reports came Thursday that Malaysia Airlines Flight 17 crashed in Ukraine as it was flying from Amsterdam to Kuala Lumpur, Malaysia. At the very least, it's a marketing nightmare - two catastrophes for an airline in 41/2 months. What passenger, going forward, will book a flight on the government-run carrier, which until this year had a reputation for high levels of service and safety?
US Airways ground workers reach accord with merged American Airlines
June 18, 2014
By Linda Loyd, Inquirer Staff Writer
The 11,000 mechanics, fleet service, maintenance, and other ground workers at US Airways have reached tentative three-year contract agreements with management of newly-merged US Airways and American Airlines. The International Association of Machinists (IAM) negotiating committees unanimously endorsed the tentative agreements and recommended ratification, paving the way for joint collective bargaining with their American Airlines' counterparts at the Transport Workers Union (TWU)
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Lindsay Lohan Playboy Pictures Hit the Internetby Hilton Hater at . Comments
First, the cover. Now, the entire spread.
A couple days after the Lindsay Lohan Playboy cover leaked online, the same fate has befallen a slew of photos from this magazine's January/February issue. They depict the "actress" doing her best Marilyn Monroe impression... naked, of course.
Dina Lohan has said her daughter's spread will be "tastefully done" and, having seen the photos, we can say this is kind of true, if you consider a lack of full frontal nudity to be "tasteful."
But Lindsay - who reportedly made $1 million for the day of work - is most definitely nude in each shot, often exposing her breasts and a decent amount of crack.
"Someone took photos of Lindsay's pictorial in an advanced copy of the January/February issue," a Playboy rep said. "They posted the photos online without permission. We are not releasing any official images or information until Dec. 15."
We'll publish the Lindsay Lohan photos on THG then. Yes, we love showing you Lindsay's naughty parts - but we love not getting sued even more.
i like theshit out her ii like to eat her pussy
u ar so sexy nd beautiful
i love lindsay alot
I want to Lindsay Lohan Playboy magazine picture
What a derp.
Its tym u fynd sumthng 4 boostng yo popularity Linds!mayb charity wrk than ths!thats lame,yo battries r nw flat i can si!
Gross, she isnt amusing to me at all. Whats weird, is that airbrushing makes things look 10 times better, this was a complete fail for her. I was a fan, she ruined herself. Sad
.....that THAT is not worth a penny. i could go out onto the streets and get someone that looks way better than that and that's not even a lie...
WARNING: ponagaraphy is evil and addictive and it kills and harms marriage, family, children and society. All woman stand up against this evil. Donot support these things that degrade woman into believing that they have to degrade their body to be special or liked. I know that there are many good people out there that are aginst ponagraphy. please speak up against this form of evil.


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Patient with dangerous flu strain isolated
Posted Oct 02nd 2010, 12:00am by Simpson Cheung
... Simpson Cheung A 49-year-old patient admitted to Castle Peak Hospital, Tuen Mun, is infected with influenza A (H3), a strain of the virus that has been known to kill even healthy people ... to be in a stable condition. Three other patients in the same male ward were also confirmed by the hospital on Thursday to have influenza A. ...http://www.scmp.com/article/726309/patient-dangerous-flu-strain-isolated
School suspends classes in flu scare
Posted Mar 18th 2010, 12:00am by Staff Reporter
... Zoe Mak Raimondi College Primary Section in Wan Chai has suspended classes for seven days to stop the spread of a possible influenza in the school. According to the school's website, ... the school to suspend classes for seven days to stop the possible spread of influenza after the outbreak of swine flu and influenza B. According to the investigation, 35 boys and five girls aged ...http://www.scmp.com/article/708881/school-suspends-classes-flu-scare
3 doctors saw man who later died of flu virus
Posted Nov 25th 2010, 12:00am by Patsy Moy
... Patsy Moy PCCW technician Lui Kwan-hang was examined by three doctors when he complained of feeling unwell- they all told him he had minor flu symptoms, prescribed medication and sent him home. But the 20-year-old later collapsed and was two weeks in a co ...http://www.scmp.com/article/731583/3-doctors-saw-man-who-later-died-flu-virus
Chicken abattoir shelved
Posted Jun 10th 2010, 12:00am by Ella Lee
... Ella Lee and Ng Yuk-hang Thirteen years after it was first touted as an essential measure to protect the city from potentially fatal bird flu, the idea of a central slaughterhouse for chickens has been shelved. The Executive Council approved the decision ...http://www.scmp.com/article/716673/chicken-abattoir-shelved
Seasonal peak flu alert issued
Posted Mar 19th 2010, 12:00am by Danny Mok
... Danny Mok The Centre for Health Protection urged the public to take precautionary measures against seasonal flu, which consists mainly of swine flu and influenza B. It said the latest data showed an increasing number of flu samples, which signals that the city has entered the traditional seasonal flu peak. Meanwhile, a 51-year-old man who had been in good health but was admitted ...http://www.scmp.com/article/709032/seasonal-peak-flu-alert-issued
Young enjoy swine flu immunity
Posted Sep 06th 2010, 12:00am by Staff Reporter
... Ng Yuk-hang Almost half of the city's children aged five to 14 were exposed to swine flu during last year's outbreak and have consequently developed immunity against the virus that could protect them in the event of a further outbreak, a study h ...http://www.scmp.com/article/724027/young-enjoy-swine-flu-immunity
Nearly 300 more attend clinics
Posted Mar 05th 2010, 12:00am by Staff Reporter
... Ng Yuk-hang The number of patients attending designated flu clinics rose from 410 two weeks ago to 704 last week. The number of institutional outbreaks between February 28 and March 3 was 23, compared with just three in the two weeks between February 14 a ...http://www.scmp.com/article/707713/nearly-300-more-attend-clinics
Japanese poultry imports banned
Posted Dec 04th 2010, 12:00am by Simpson Cheung
... Simpson Cheung All applications to import poultry and poultry products from Japan are suspended until further notice after the confirmation of an outbreak of the highly virulent H5 bird flu in Yasugi city, Shimane prefecture. The Centre for Food Safety is ...http://www.scmp.com/article/732374/japanese-poultry-imports-banned
Fear of side effects sank swine flu scheme
Posted Aug 28th 2010, 12:00am by Ella Lee
... Ella Lee Most Hongkongers did not have a swine flu vaccination because they feared side effects and felt the chance of infection was low, according to a survey by the Department of Health. Taxpayers spent HK$237 million stockpiling the vaccine and another ...http://www.scmp.com/article/723254/fear-side-effects-sank-swine-flu-scheme
Start of school term brings health warning
Posted Aug 28th 2010, 12:00am by Simpson Cheung
... Simpson Cheung The Centre for Health Protection yesterday reminded schoolchildren and their parents to be on the lookout for cases of hand, foot and mouth disease and flu when classes resume next week. The centre had received reports of 607 outbreaks of h ...http://www.scmp.com/article/723255/start-school-term-brings-health-warning
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Date: 1870
Description: Baraboo was first settled around 1838, and by 1870 it had become the county seat and the thriving village illustrated here. This birds eye drawing depicts...
Date: 1896
Description: View of Black Hawk Bluff, site of the Battle of Wisconsin Heights in the Black Hawk War.
Date: 1852
Description: Devil's Lake from shore flanked by steep tree-covered hillsides. A small solitary rowboat floats near the distant shore.
Date: 1895 ca.
Description: Front view of post office.
Date: 1860 ca.
Description: Exterior view of the Alba House, with individuals standing outside its entrance and on the balcony.
Date: 1898
Description: Students in a chemistry class at Hillside Home School, an early progressive school, operated by Ellen and Jane Lloyd Jones, aunts of Frank Lloyd Wright.
Date: 1874
Description: Bird's-eye map of Reedsburg, on the Baraboo River.
Description: Exterior view of the Kipp residence with a woman in the front yard reclining in a hammock.
Date: 1877 ca.
Description: "The Grand Regatta, at Devil's Lake, June 21st & 22nd, 1877." A stereograph showing spectators gathered behind the starter's cannon on Devil's Lake.
Date: 1895-07 ca.
Description: Two men, W.M. Smith and W.H.D., rest on a large log over Little Bear Creek.
Date: 1880 ca.
Description: View of the Wisconsin River shoreline showing lumber rafts "tied up over Sunday."
Date: 1875 ca.
Description: View of Water Street south of the Highway 12 intersection, looking north.
Description: Elevated view of multiple homes and buildings.
Description: Albert Ludley Tuttle of Baraboo, standing with his grandchildren and grown sons with farm equipment and horses in a field of young trees. In the field in t...
Date: 1886 ca.
Description: Bird's-eye map of Baraboo with inset of Devil's Lake, the south and east sides of the commercial square, the First National Bank, and the Warren House hote...
Date: 1896-04-12
Description: View of a burning Central House engulfed in smoke with a crowd of spectators gathered to watch.
Description: View of people, a pier, a steamboat and row boats on Devil's Lake. An American flag is on the steamboat. The people are elegantly dressed.
Date: 1889 ca.
Description: An original poster advertising the eleventh annual railroad picnic, taking place at Devil's Lake State Park on Saturday, July 27, 1889. In the advertiseme...
Date: 1852-01-01
Description: These manuscript maps, drawn by William H. Canfield in 1852, illustrate mounds primarily in Sauk County, Wisconsin, in the towns of Greenfield, La Valle, M...
Date: 1898 ca.
Description: Man and woman seated on an overgrown hillside. The woman has ferns on her lap and is holding an umbrella. Inscribed on reverse of original mount: "B.D.L. a...
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© 1996-2014 Wisconsin Historical Society, 816 State Street, Madison, WI 53706


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I know, we're all bummed out the Texans lost. But since you've been drinking anyway, you might as well crack open another one and sit through the one awards show even the People's Choice Awards can look down its nose at. I'll be updating this entry throughout the broadcast, so refresh often and try ... More >>
Photo courtesy ABCI've been watching V: The Series, more out of nostalgic fondness for the original than any hope the remake would be worth a damn (and I prefer a long-haired Morena Baccarin anyway). Despite solid efforts by Elizabeth Mitchell (Agent Evans) and Alan Tudyk (whose recent stri ... More >>
Serenity spins a classic tale way out west