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Prep football Week 12: Big plays lead to historic East Beauregard victory
Beauregard Daily News
The Trojans scored five of their six touchdowns on plays longer than 44 yards as the beat No. 10 Logansport 43-26 to advance to the third round of the playoffs for the first time in program history. The last time they won a playoff game was back in 2003 when ...
and more »
AU women win, men lose in home opener
The State
Simpson, who had a game-high 18 points in the Trojans' victory at USC Aiken earlier in the week, had 15 points, six rebounds and four assists in Anderson's league opener. Heather Jankowy came off the bench to lead the winners and all scorers with 16 ...
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GRU Augusta volleyball wins first NCAA Tournament match, advance in ...
The GRU Augusta women's volleyball team made their first NCAA Tournament appearance in the first round of the Division II Southeast Regional Thursday night and won a 3-2 match over the Anderson Trojans in the Cuddy Arena on the campus of Wingate ...
Bears Upend Anderson For First Win
Go Blue Ridge
Anderson's Myson Jones (Aiken, S.C.) finished with a team-high 24 points as the Trojans' rally from an 11-point, second-half deficit with 15:08 remaining. But the comeback fell short. A pair of freshman stepped up big on Saturday afternoon . Freshman guard ...
Lenoir Rhyne College Athletics
Lenoir-Rhyne Men's Basketball Upends Anderson, 71-68, For Its First Win Of ...
Lenoir Rhyne College Athletics
Anderson's Myson Jones (Aiken, S.C.) finished with a team-high 24 points as the Trojans' rally from an 11-point, second-half deficit – 51-40 with 15:08 remaining – came up short. Freshman guard Reed Lucas (Greensboro, N.C.) scored 11 points while ...
and more »
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How much are you earning?
The UAE has seen salary cuts of around 30 percent in the past year, according to a survey. Has your income been affected?
September 7, 2009 12:19 by Aarti Nagraj
Employees in the UAE have seen average salary cuts of between 26 percent and 30 percent over the last year because of global financial crisis, according to a survey conducted by Emirates Business. However, salary cuts differed between sectors and companies.
"Cuts in salaries reflect the drop in rents and overall inflation. It is more important to consider what remains in the pocket than what one takes home," a recruitment expert in the banking sector told the paper.
"It is not possible to generalize for all salaries. Senior executives are paid a package and not just a salary. The package was impacted, mostly including the decrease in accommodation cost. Some of the benefits also decreased. Increased competition led to hiring very qualified individuals at normal remuneration at the market levels. So one would probably say that it is the quality that has been improved, instead of saying that the cost for the company [or the salary] has decreased," said the regional head of an international recruitment company.
According to the GCC Salary Survey released by Bayt.com and YouGov Siraj in January this year, the average salary in the Middle East has risen by more than 15 percent in the last two years. However, the cost of living across the region has increased by an average of 37 percent between December 2007 and December 2008, the report said.
Pages: 1 2
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Oil prices fall to 4-year lows as OPEC production cut looks unlikely
Thought roller coasters and restaurants don't mix?
Deadly diabetes, an increasing threat
3 Comments
I think that professional teaching wages in the UAE are a disgrace. Even though accomodation is provided the total amount received each month as basic salary is totally inappropriate. I believe this is because schools can hire teachers without qualifications and that there is no union or support organisation that helps or supports teachers. There are so many underhanded things go on in teaching here that is why so many teachers leave after 1-2years. The turnover is so high that often the most senior person in a school (private) in Sharjah has less than 5 years teaching experience. This reference refers to teachers not Principals or deputies. What they expect for the pathetic salary they pay is ridiculous.
I agree with Catherine comment. I think that the reason is also because schools are more and more becoming financial institutions which major objective would be the highest possible yearly net profit. Accordingly, wages will be at their lowes and quality of education keeps on deteriorating year after year
30% salary cut is better than out of work.

subset: commoncrawl


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Release: Colmar Brunton
Release: Morrison McDougall
Getting your home repaired as soon as possible so that you can move forward is our priority. We're here to assist you and to ensure that, from here to home, your repair progress moves smoothly.
New: Cathedral Square (southeast quadrant) Closed between Worcester and Hereford for tram works – follow signed detours Fitzgerald Ave - southbound – lane drop between Tuam and St Asaph Streets and no right turn from Fitzgerald into St Asaph Victoria Street - …
The settling of Canterbury earthquake private insurance claims continues apace as pay outs hit the $13 billion mark, advancing at $10 million a day in 2014.
Rebuild Christchurch is partnering with CTV to run a 2-part series that takes us behind the scenes on the residential rebuild in Canterbury. "Covered - restoring our community" looks at how things are progressing post-quake and seeks to get the answers people are wanting on rebuild and insurance matters.
Christchurch City Council has this week been carrying out geotechnical testing on the QEII Park site that will help it to determine whether the land is suitable for a new Eastern Recreation and Sport Centre to be built there.
Compensating flood-risk homeowners for the loss of value to their properties does not fix Christchurch's post-quake flooding woes, the Christchurch High Court has heard.
Initial analysis of the feedback from EVO::SPACE shows a very strong preference for east Christchurch to become the clean green environmental playground of the city.
Ferry Road will be closed to eastbound traffic from Dyers Road roundabout on Saturday 1 November for one day. It will remain open for westbound (city bound) Detours will be signposted for eastbound traffic at Dyers roundabout. Where possible eastbound …
An insurance company warns that any court ruling passing liability for increased flood risk to insurers would cause major delays in the Christchurch rebuild.
Sealing on Carmen/Masham Road may cause delays for road users this weekend, 1st and 2nd November. Lane closures will be in place both north and southbound on Carmen/Masham Road. There will be no right turn on all approaches at …
All clear given following gas leak in Christchurch
Roads have been reopened following a gas main leak which occurred on the corner of Barbadoes Street and Moorhouse Ave earlier today. Thanks to road users for their patience while these closures were in place.
Demolition has been the fate of so many of Christchurch's heritage buildings, it is understandable that a deep sense of loss continues to hang over the city - but it is not the whole story. Here's why the picture may be brighter than some people think.
Hills Road will be northbound only from Acheson Ave/Whitehall Street to Dawe Street for approximately two weeks from Wednesday 29th October. Detours will be in place for southbound drivers from Dawe St to Acheson Ave.
Social Development Minister Anne Tolley says the Government's 3K to Christchurch scheme is a winner with 633 unemployed people taking up the offer.
A lane reduction on Barbadoes Street onto Moorhouse Ave will cause delays for road users, particularly during peak hours. We advise using Fitzgerald Ave or expect some delays through this area.
A lane reduction on Barbadoes Street right onto Moorhouse Ave is causing delays, travellers are advised to use Fitzgerald Ave
Greening the Rubble has opened its largest garden so far.
The Christchurch rebuild will fail without more help for the arts, a survey of artists and art leaders in the city says.
Lance Morrison has a new baby but something is missing.
Broken dreams and unpaid bills pave the road to Motunau Beach, where Joseph Van Roij's Fraemohs cabin sits opposite his grand unfinished home overlooking the Pacific Ocean.
Doubts over the location and economic viability of Christchurch's convention centre could result in the project being a "huge disaster", a designer says.
Hundreds of music students could soon bring new life to the Christchurch Arts Centre, and about half of the historic complex set to reopen by the middle of next year.
To keep up to date with parking changes at Christchurch Hospital click here.
A $7 million revamp of Victoria Square will make the well-known landmark more event-friendly and reflect Christchurch's history, the Christchurch Central Development Unit (CCDU) says.
The plan is a 135km trail. It encircles Christchurch and is split up into eight distinct stages. The details are still to be settled and the project is subject to route approval and access permission.
New: Durham Street – one lane from Conference to Salisbury Street Gloucester Street – now Open from Colombo Street to Oxford Tce Worcester Street - CLOSED east of Manchester Street St Asaph Street – one lane on approach to Madras Street …
For available routes around the Central City please find below the CBD network map. This is updated weekly. Please click here to download the network map - Available Routes Map
Major intersection works will take place at the intersection of Lincoln and Wrights Road this weekend Saturday 24th October and Sunday 25th October. Reduced lanes city bound on Lincoln Road Reduced lanes southbound on Wrights Road on the approach to …
Innes Road between Mahars Rd and Nancy Ave has been closed to eastbound traffic today (23 Oct) for urgent surface treatment.
The following closures will be in place to accommodate the Targa Rally on Monday 27 October from 12.15pm to 4.45pm.
A mini and relocatable grandstand has been designed so people can observe "crowd-worthy" demolitions in comfort.
A mini and relocatable grandstand has been designed so people can among other things observe "crowd-worthy" demolitions in comfort.
Roads in Canterbury and the West Coast will be busy this Labour Day Weekend and the NZ Transport Agency says it will be working with the Police to keep traffic moving and families safe on their travels during the holiday break.
Mayor Lianne Dalziel today officially unveiled the newly-restored Central City landmark, Jubilee Clock Tower, and placed a time capsule on the site for future generations to discover.
Homeowners and contractors are angry over the results of an investigation into asbestos management in Christchurch's residential rebuild.
It seems an odd thought, but Christchurch's rebuild boom is nearly over.
A WorkSafe New Zealand investigation has found deficiencies in the Earthquake Commission (EQC) and Fletcher EQR's management of asbestos but will not lay any charges.
Release: WorkSafe NZ
Canterbury Employers' Chamber of Commerce Chief Executive Peter Townsend talks to Newstalk ZB's Chris Lynch about the report that is saying the rebuild is in full swing.
Works on Linwood Ave on the approaches to the Buckleys/Aldwins intersection will cause delays particularly during peak travel times. Road users should consider alternative travel times or routes where possible or allow extra time for travel through this area.
Christchurch's rebuild is soon to peak.
Christchurch's Waltham Pool will reopen this summer.
Remedial work on one of the city's last remaining industrial stone buildings will begin today.
Release: CHER
Road users are advised that on Saturday 18th October major road works will occur at the Lincoln Road, Barrington Street, and Whiteleigh Ave intersection.
Road users are advised that from Monday 20th October work will start at the Burwood Road intersection roundabout during the hours of for approximately two weeks while wastewater pipe lining work takes place.
This week, week starting Monday 20 October, Victoria Street from Montreal Street will be CLOSED from 7pm – 6am each night for wastewater work. Recommended route northbound to access Bealey Avenue is via Montreal Street. Recommended route southbound is via …
You may have noticed more coloured Journey Time lines on our map across the Central City. Click here to take a look. In addition to this we now have five new virtual variable message signs (VMS) around the CBD. These are …
New: Durham Street – one lane from Conference to Salisbury Street Salisbury Street – down to one lane from Montreal to Colombo Street. Hereford Street - one-way westbound between Manchester and Colombo Street Moorhouse Ave – centre lane drop westbound …
One of Christchurch's few remaining central-city landmarks is to be revamped.
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What: Redskins (3-12) at Giants (6-9)
Where: MetLife Stadium
When: Sunday, 1 p.m.
TV: Fox
Redskins defensive coordinator Jim Haslett spoke to the media on Thursday about the future of his outside linebacker Brian Orakpo.
Brian Orakpo did not practice on Thursday, raising doubts about his availability for Sunday's season finale against the Giants.
With decisions to be made about whether to re-sign certain key defensive players, what will the Redskins do? CSN Insider Tarik El-Bashir discusses.
When Washington's defensive players step onto the field Sunday afternoon at MetLife Stadium, it probably will mark the final time many of them play together as members of the Redskins.


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Are you William A Beard?Claim your profile
Publications (129)704.69 Total impact
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ABSTRACT: DNA polymerases and substrates undergo conformational changes upon forming protein-ligand complexes. These conformational adjustments can hasten or deter DNA synthesis and influence substrate discrimination. From structural comparison of binary DNA and ternary DNA/dNTP complexes of DNA polymerase β, several side-chains have been implicated in facilitating formation of an active ternary complex poised for chemistry. Site-directed mutagenesis of these highly conserved residues (Asp192, Arg258, Phe272, Glu295, and Tyr296) and kinetic characterization provides insight into the role these residues play during correct and incorrect insertion as well as their role in conformational activation. The catalytic efficiencies for correct nucleotide insertion for alanine mutants was wild type ≈ R258A > F272A ≈ Y296A > E295A > D192. Since the efficiencies for incorrect insertion was affected to about the same extent for each mutant, effects on fidelity were modest (<5-fold). The R258A mutant exhibited an increase in the single-turnover rate of correct nucleotide insertion. This suggests that the wild-type Arg258 side-chain generates a population of non-productive ternary complexes. Structures of binary and ternary substrate complexes of the R258A mutant and a mutant associated with gastric carcinomas, E295K, provide molecular insight into intermediate structural conformations not appreciated previously. While the R258A mutant crystal structures were similar to wild-type enzyme, the open ternary complex structure of E295K indicates that Arg258 stabilizes a non-productive conformation of the primer terminus that would decrease catalysis. Significantly, the open E295K ternary complex binds two metal ions indicating that metal binding cannot overcome the modified interactions that have interrupted the closure of the N-subdomain.The Journal of biological chemistry. 09/2014;
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ABSTRACT: Mammalian DNA polymerase (pol) β is the founding member of a large group of DNA polymerases now termed the X-family. DNA polymerase β has been kinetically, structurally, and biologically well characterized and can serve as a phylogenetic reference. Accordingly, we have performed a phylogenetic analysis to understand the relationship between pol β and other members of the X-family of DNA polymerases. The bacterial X-family DNA polymerases, Saccharomyces cerevisiae pol IV, and four mammalian X-family polymerases appear to be directly related. These enzymes originated from an ancient common ancestor characterized in two Bacillus species. Understanding distinct functions for each of the X-family polymerases, evolving from a common bacterial ancestor is of significant interest in light of the specialized roles of these enzymes in DNA metabolism.DNA repair. 08/2014; 22C:77-88.
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ABSTRACT: Cytosine methylation and demethylation in tracks of CpG dinucleotides is an epigenetic mechanism for control of gene expression. The initial step in the demethylation process can be deamination of 5-methylcytosine producing the TpG alteration and T:G mispair, and this step is followed by thymine DNA glycosylase (TDG) initiated base excision repair (BER). A further consideration is that guanine in the CpG dinucleotide may become oxidized to 7,8-dihydro-8-oxoguanine (8-oxoG), and this could affect the demethylation process involving TDG-initiated BER. However, little is known about the enzymology of BER of tandemly altered CpG dinucleotides; e.g., Tp8-oxoG. Here, we investigated interactions between this altered dinucleotide and purified BER enzymes, the DNA glycosylases TDG and 8-oxoG DNA glycosylase 1 (OGG1), apurinic/apyrimidinic (AP) endonuclease 1, DNA polymerase β and DNA ligases. The overall TDG-initiated BER of the Tp8-oxoG dinucleotide is significantly reduced. Specifically, TDG and DNA ligase activities are reduced by a 3[prime]-flanking 8-oxoG. In contrast, OGG1-initiated BER pathway is blocked due to the 5[prime]-flanking T:G mispair; this reduces OGG1, AP endonuclease 1, and DNA polymerase β activities. Further, in TDG-initiated BER, TDG remains bound to its product AP site blocking OGG1 access to the adjacent 8-oxoG. These results reveal BER enzyme specificities enabling suppression of OGG1-initiated BER and coordination of TDG-initiated BER at this tandem alteration in the CpG dinucleotide.Journal of Biological Chemistry 04/2014; · 4.65 Impact Factor
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ABSTRACT: DNA polymerase (pol) β is a multi-domain enzyme with two enzymatic activities that plays a central role in the overlapping base excision repair and single strand break repair pathways. The high frequency of pol β variants identified in tumor-derived tissues suggests a possible role in the progression of cancer, making it of interest to determine the functional consequences of these variants. Pol β containing a proline substitution for leucine 22 in the lyase domain (LD), identified in gastric tumors, has been reported to exhibit severe impairment of both lyase and polymerase activities. NMR spectroscopic evaluations of both pol β and the isolated LD containing the L22P mutation demonstrate destabilization sufficient to result in LD-selective unfolding with minimal structural perturbations to the polymerase domain. Unexpectedly, addition of single-stranded or hairpin DNA resulted in partial refolding of the mutated lyase domain, both in isolation and for the full-length enzyme. Further, formation of an abortive ternary complex using Ca2+ and a complementary dNTP indicates that the fraction of pol β(L22P) containing the folded LD undergoes conformational activation similar to that of the wild-type enzyme. Kinetic characterization of the polymerase activity of L22P pol β indicates that the L22P mutation compromises DNA binding, but nearly wild-type catalytic rates can be observed at elevated substrate concentrations. The organic osmolyte trimethylamine N-oxide (TMAO) is similarly able to induce folding and kinetic activation of both polymerase and lyase activities of the mutant. Kinetic data indicate synergy between the TMAO cosolvent and substrate binding. NMR data indicate that the effect of the DNA results primarily from interaction with the folded LD(L22P), while the effect of the TMAO results primarily from destabilization of the unfolded LD(L22P). These studies illustrate that substrate-induced catalytic activation of pol β provides an optimal enzyme conformation even in the presence of a strongly destabilizing point mutation. Accordingly, it remains to be determined whether this mutation alters the threshold of cellular repair activity needed for routine genome maintenance or whether the 'inactive' variant interferes with DNA repair.Biochemistry 03/2014; · 3.38 Impact Factor
Article: The Transition-State in DNA Polymerase β Catalysis: Rate-limiting Chemistry Altered by Base-Pair Configuration.[Show abstract] [Hide abstract]
ABSTRACT: Kinetics studies of dNTP analogs having pyrophosphate-mimicking β,γ-pCXYp leaving groups with variable X,Y-substitution reveal striking differences in the chemical transition-state energy for DNA polymerase β that depend on all aspects of base pairing configurations, including whether the incoming dNTP is a purine or pyrimidine and if base pairings are right (T•A, G•C) or wrong (T•G, G•T). Brønsted plots of the catalytic rate constant (log(kpol)) vs pKa4 for the leaving group exhibit Linear Free Energy Relationships (LFERs) with negative slopes ranging from -0.6 to -2.0, consistent with chemical rate-determining transition-states in which the active site adjusts to charge stabilization demand during chemistry depending on base-pair configuration. The Brønsted slopes and also intercepts differ dramatically, and provide the first direct evidence that dNTP base recognition by the enzyme-primer-template complex triggers a conformational change in the catalytic region of the active site, that significantly modifies the rate-determining chemical step.Biochemistry 03/2014; · 3.38 Impact Factor
Dataset: ja412701f si 001
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ABSTRACT: To interpret recent structures of the human DNA repair enzyme DNA polymerase β (pol β) differing in the number of Mg(2+) ions, we apply transition path sampling (TPS) to assess the effect of differing ion placement on the transition from the open one-metal to the closed two-metal state. We find that the closing pathway depends on the initial ion position, both in terms of the individual transition states and associated energies. The energy barrier of the conformational pathway varies from 25 to 58 kJ/mol, compared to the conformational energy barrier of 42 kJ/mol for the wild-type pol β reported previously. Moreover, we find a preferred ion route located in the center of the enzyme, parallel to the DNA. Within this route, the conformational pathway is similar to that of the overall open to closed transition of pol β but outside it, especially when ion starts near active site residues Arg258 and Asp190, the conformational pathway diverges significantly. We hypothesize that our findings should apply generally to pol β, since R283 is relatively far from the active site. Our hypothesis suggests further experimental and computational work. Our studies also underscore the common feature that less active mutants have less stable closed states than their open states, in marked contrast to the wild-type enzyme, where the closed state is significantly more stable than the open form.Journal of the American Chemical Society 02/2014; · 10.68 Impact Factor
Article: Watching a DNA polymerase in action.Cell cycle (Georgetown, Tex.) 01/2014; 13(5). · 5.24 Impact Factor
Article: Structural Comparison of DNA Polymerase Architecture Suggests a Nucleotide Gateway to the Polymerase Active Site.Chemical Reviews 12/2013; · 41.30 Impact Factor
Article: Understanding the loss-of-function in a triple missense mutant of DNA polymerase β found in prostate cancer.[Show abstract] [Hide abstract]
ABSTRACT: Human DNA polymerase (pol) β is essential for base excision repair. We previously reported a triple somatic mutant of pol β (p.P261L/T292A/I298T) found in an early onset prostate tumor. This mutation abolishes polymerase activity, and the wild-type allele was not present in the tumor, indicating a complete deficiency in pol β function. The effect on polymerase activity is unexpected because the point mutations that comprise the triple mutant are not part of the active site. Herein, we demonstrate the mechanism of this loss-of-function. In order to understand the effect of the individual point mutations we biochemically analyzed all single and double mutants that comprise the triple mutant. We found that the p.I298T mutation is responsible for a marked instability of the triple mutant protein at 37˚C. At room temperature the triple mutant's low efficiency is also due to a decrease in the apparent binding affinity for the dNTP substrate, which is due to the p.T292A mutation. Furthermore, the triple mutant displays lower fidelity for transversions in vitro, due to the p.T292A mutation. We conclude that distinct mutations of the triple pol β mutant are responsible for the loss of activity, lower fidelity, and instability observed in vitro.International Journal of Oncology 07/2013; · 2.66 Impact Factor
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ABSTRACT: DNA polymerase (pol) β is a model polymerase involved in gap-filling DNA synthesis utilizing two metals to facilitate nucleotidyl transfer. Previous structural studies have trapped catalytic intermediates by utilizing substrate analogs (dideoxy-terminated primer or nonhydrolysable incoming nucleotide). To identify additional intermediates during catalysis, we now employ natural substrates (correct and incorrect nucleotides) and follow product formation in real time with 15 different crystal structures. We are able to observe molecular adjustments at the active site that hasten correct nucleotide insertion and deter incorrect insertion not appreciated previously. A third metal binding site is transiently formed during correct, but not incorrect, nucleotide insertion. Additionally, long incubations indicate that pyrophosphate more easily dissociates after incorrect, compared to correct, nucleotide insertion. This appears to be coupled to subdomain repositioning that is required for catalytic activation/deactivation. The structures provide insights into a fundamental chemical reaction that impacts polymerase fidelity and genome stability.Cell 07/2013; 154(1):157-68. · 31.96 Impact Factor
Article: Amino acid substitution in the active site of DNA polymerase β explains the energy barrier of the nucleotidyl transfer reaction.[Show abstract] [Hide abstract]
ABSTRACT: DNA polymerase β (pol β) is a bifunctional enzyme widely studied for its roles in base excision DNA repair where one key function is gap-filling DNA synthesis. In spite of significant progress in recent years, the atomic level mechanism of the DNA synthesis reaction has remained poorly understood. Based on crystal structures of pol β in complex with its substrates and theoretical considerations of amino acids and metals in the active site, we have proposed that a nearby carboxylate group of Asp256 enables the reaction by accepting a proton from the primer O3´group, thus activating O3´as the nucleophile in the reaction path. Here, we tested this proposal by altering the side chain of Asp256 to Glu and then exploring the impact of this conservative change on the reaction. The D256E enzyme is more than 1,000-fold less active than the wild-type enzyme, and the crystal structures are subtly different in the active sites of the D256E and wild-type enzymes. Theoretical analysis of DNA synthesis by the D256E enzyme shows that the O3´proton still transfers to the nearby carboxylate of residue 256. However, the electrostatic stabilization and location of the O3´ proton transfer during the reaction path are dramatically altered compared with wild-type. Surprisingly, this is due to repositioning of the Arg254 side chain in the Glu256 enzyme active site, such that Arg254 is not in position to stabilize the proton transfer from O3´. The theoretical results with the wild-type enzyme indicate early charge reorganization associated with the O3´ proton transfer, and this does not occur in the D256E enzyme. The charge reorganization is mediated by the catalytic magnesium ion in the active site.Journal of the American Chemical Society 05/2013; · 10.68 Impact Factor
Article: Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts.[Show abstract] [Hide abstract]
ABSTRACT: To aid in the characterization of the relationship of structure and function for human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT), this investigation utilized DNAs containing benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-modified primers and templates as a probe of the architecture of this complex. BPDE lesions that differed in their stereochemistry around the C10 position were covalently linked to N (6)-adenine and positioned in either the primer or template strand of a duplex template-primer. HIV-1 RT exhibited a stereoisomer-specific and strand-specific difference in replication when the BPDE-lesion was placed in the template versus the primer strand. When the C10 R-BPDE adduct was positioned in the primer strand in duplex DNA, 5 nucleotides from the 3΄ end of the primer terminus, HIV-1 RT could not fully replicate the template, producing truncated products; this block to further synthesis did not affect rates of dissociation or DNA binding affinity. Additionally, when the adducts were in the same relative position, but located in the template strand, similar truncated products were observed with both the C10 R and C10 S BPDE adducts. These data suggest that the presence of covalently-linked intercalative DNA adducts distant from the active site can lead to termination of DNA synthesis catalyzed by HIV-1 RT.PLoS ONE 01/2013; 8(9):e72131. · 3.53 Impact Factor
Article: Steady-state, Pre-steady-state, and Single-turnover Kinetic Measurement for DNA Glycosylase Activity.[Show abstract] [Hide abstract]
ABSTRACT: Human 8-oxoguanine DNA glycosylase (OGG1) excises the mutagenic oxidative DNA lesion 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. Kinetic characterization of OGG1 is undertaken to measure the rates of 8-oxoG excision and product release. When the OGG1 concentration is lower than substrate DNA, time courses of product formation are biphasic; a rapid exponential phase (i.e. burst) of product formation is followed by a linear steady-state phase. The initial burst of product formation corresponds to the concentration of enzyme properly engaged on the substrate, and the burst amplitude depends on the concentration of enzyme. The first-order rate constant of the burst corresponds to the intrinsic rate of 8-oxoG excision and the slower steady-state rate measures the rate of product release (product DNA dissociation rate constant, koff). Here, we describe steady-state, pre-steady-state, and single-turnover approaches to isolate and measure specific steps during OGG1 catalytic cycling. A fluorescent labeled lesion-containing oligonucleotide and purified OGG1 are used to facilitate precise kinetic measurements. Since low enzyme concentrations are used to make steady-state measurements, manual mixing of reagents and quenching of the reaction can be performed to ascertain the steady-state rate (koff). Additionally, extrapolation of the steady-state rate to a point on the ordinate at zero time indicates that a burst of product formation occurred during the first turnover (i.e. y-intercept is positive). The first-order rate constant of the exponential burst phase can be measured using a rapid mixing and quenching technique that examines the amount of product formed at short time intervals (<1 sec) before the steady-state phase and corresponds to the rate of 8-oxoG excision (i.e. chemistry). The chemical step can also be measured using a single-turnover approach where catalytic cycling is prevented by saturating substrate DNA with enzyme (E>S). These approaches can measure elementary rate constants that influence the efficiency of removal of a DNA lesion.Journal of Visualized Experiments 01/2013;
Article: DNA polymerase minor groove interactions modulate mutagenic bypass of a templating 8-oxoguanine lesion.[Show abstract] [Hide abstract]
ABSTRACT: A major base lesion resulting from oxidative stress is 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG) that has ambiguous coding potential. Error-free DNA synthesis involves 8-oxoG adopting an anti-conformation to base pair with cytosine whereas mutagenic bypass involves 8-oxoG adopting a syn-conformation to base pair with adenine. Left unrepaired the syn-8-oxoG/dAMP base pair results in a G-C to T-A transversion. During base excision repair of this mispair, DNA polymerase (pol) β is confronted with gap filling opposite 8-oxoG. To determine how pol β discriminates between anti- and syn-8-oxoG, we introduced a point mutation (R283K) to alter insertion specificity. Kinetic studies demonstrate that this substitution results in an increased fidelity opposite 8-oxoG. Structural studies with R283K pol β show that the binary DNA complex has 8-oxoG in equilibrium between anti- and syn-forms. Ternary complexes with incoming dCTP resemble the wild-type enzyme, with templating anti-8-oxoG base pairing with incoming cytosine. In contrast to wild-type pol β, the ternary complex of the R283K mutant with an incoming dATP-analogue and templating 8-oxoG resembles a G-A mismatched structure with 8-oxoG adopting an anti-conformation. These results demonstrate that the incoming nucleotide is unable to induce a syn-8-oxoG conformation without minor groove DNA polymerase interactions that influence templating (anti-/syn-equilibrium) of 8-oxoG while modulating fidelity.Nucleic Acids Research 12/2012; · 8.81 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Although the primary function of DNA polymerase (pol) β is associated with gap-filling DNA synthesis as part of the DNA base excision repair pathway, translesion synthesis activity has also been described. To further understand the potential role of pol β-catalyzed translesion DNA synthesis (TLS) and the structure-function relationships of specific residues in pol β, wild-type and selected mutants of pol β were used in TLS assays with DNA substrates containing bulky polycyclic aromatic hydrocarbon-adducted oligonucleotides. Stereo-specific (+) and (-)-anti-trans-(C10S and C10R) benzo[a]pyrene-7,8- dihydrodiol-9-10-epoxide (BPDE) adducts were covalently attached to both the N(6)-adenine and N(2)-guanine in the major and minor grooves, respectively. For all substrates tested, the presence of the BPDE adducts greatly decreased the efficiency of nucleotide incorporation opposite the lesion and the stereochemistry of the adducts also further modulated the efficiency of the insertion step, such that lesions pointing toward the oncoming polymerase were considerably more blocking than those oriented away from the polymerase. In the absence of a downstream DNA strand, the extension step beyond the adduct was extremely inefficient, relative to a dinucleotide gap-filling reaction, such that in the presence of the downstream DNA, dinucleotide incorporation was strongly favored. In general, analyses of the TLS activities of four pol β mutants revealed similar overall properties but wild-type pol β exhibited more than 50-fold greater extension and bypass of the C10S-dA adducts as compared to a low fidelity mutant R283K expected to interact with the templating base. Replication bypass investigations were further extended to include analyses of HIV-1 reverse transcriptase, and these studies revealed patterns of inhibition very similar to that observed for pol β.Chemical Research in Toxicology 11/2012; · 3.67 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: In recent papers, there has been a lively exchange concerning theories for enzyme catalysis, especially the role of protein dynamics/pre-chemistry conformational changes in the catalytic cycle of enzymes. Of particular interest is the notion that substrate-induced conformational changes that assemble the polymerase active site prior to chemistry are required for DNA synthesis and impact fidelity (i.e., substrate specificity). High-resolution crystal structures of DNA polymerase β representing intermediates of substrate complexes prior to the chemical step are available. These structures indicate that conformational adjustments in both the protein and substrates must occur to achieve the requisite geometry of the reactive participants for catalysis. We discuss computational and kinetic methods to examine possible conformational change pathways that lead from the observed crystal structure intermediates to the final structures poised for chemistry. The results, as well as kinetic data from site-directed mutagenesis studies, are consistent with models requiring pre-chemistry conformational adjustments in order to achieve high fidelity DNA synthesis. Thus, substrate-induced conformational changes that assemble the polymerase active site prior to chemistry contribute to DNA synthesis even when they do not represent actual rate-determining steps for chemistry.Theoretical Chemistry Accounts 11/2012; 131:1287. · 2.14 Impact Factor
Article: Effect of β,γ-CHF- and β,γ-CHCl-dGTP Halogen Atom Stereochemistry on the Transition State of DNA Polymerase β[Show abstract] [Hide abstract]
ABSTRACT: Recently, we synthesized the first individual β,γ-CHX-dGTP diastereomers [(R)- or (S)-CHX, where X is F or Cl] and determined their structures in ternary complexes with DNA polymerase β (pol β). We now report stereospecificity by pol β on the mixed β,γ-CHX diastereomer pairs using nuclear magnetic resonance and on the separate diastereomers using transient kinetics. For both the F and Cl diastereomers, the R isomer is favored over the S isomer for G·C correct incorporation, with stereospecificities [(k(pol)/K(d))(R)/(k(pol)/K(d))(S)] of 3.8 and 6.3, respectively, and also for G·T misincorporation, with stereospecificities of 11 and 7.8, respectively. Stereopreference for the (R)-CHF-dGTP diastereomer was abolished for k(pol) but not K(d) with mutant pol β (R183A). These compounds constitute a new class of stereochemical probes for active site interactions involving halogen atoms. As Arg183 is unique in family X pols, the design of CXY deoxyribonucleotide analogues to enhance interaction is a possible strategy for inhibiting BER selectively in cancer cells.Biochemistry 10/2012; · 3.38 Impact Factor
Article: DNA Sequence Context Effects on the Glycosylase Activity of Human 8-Oxoguanine DNA Glycosylase.[Show abstract] [Hide abstract]
ABSTRACT: Human 8-oxoguanine DNA glycosylase (OGG1) is a key enzyme involved in removing 7,8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic DNA lesion generated by oxidative stress. The removal of 8-oxoG by OGG1 is affected by the local DNA sequence, and this feature most likely contributes to observed mutational hotspots in genomic DNA. To elucidate the influence of local DNA sequence on 8-oxoG excision activity of OGG1, we conducted steady-state, pre-steady-state, and single-turnover kinetic evaluation of OGG1 in alternate DNA sequence contexts. The sequence context effect was studied for a mutational hotspot at a CpG dinucleotide. Altering either the global DNA sequence or the 5(')-flanking unmodified base pair failed to influence the excision of 8-oxoG. Methylation of the cytosine 5(') to 8-oxoG also did not affect 8-oxoG excision. In contrast, a 5(')-neighboring mismatch strongly decreased the rate of 8-oxoG base removal. Substituting the 5(')-C in the CpG dinucleotide with T, A, or tetrahydrofuran (i.e., T:G, A:G and tetrahydrofuran:G mispairs) resulted in a 10-, 13-, and 4-fold decrease in the rate constant for 8-oxoG excision, respectively. A greater loss in activity was observed when T:C or A:C was positioned 5(') of 8-oxoG (59- and 108-fold, respectively). These results indicate that neighboring structural abnormalities 5(') to 8-oxoG deter its repair thereby enhancing its mutagenic potential.Journal of Biological Chemistry 09/2012; · 4.65 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: DNA polymerase and substrate conformational changes are essential for high-fidelity DNA synthesis. Structures of DNA polymerase (pol) β in complex with DNA show the enzyme in an "open" conformation. Subsequent to binding the nucleotide, the polymerase "closes" around the nascent base pair with two metals positioned for chemistry. However, structures of substrate/active site intermediates prior to closure are lacking. By destabilizing the closed complex, we determined unique ternary complex structures of pol β with correct and incorrect incoming nucleotides bound to the open conformation. These structures reveal that Watson-Crick hydrogen bonding is assessed upon initial complex formation. Importantly, nucleotide-bound states representing intermediate metal coordination states occur with active site assembly. The correct, but not incorrect, nucleotide maintains Watson-Crick hydrogen bonds during interconversion of these states. These structures indicate that the triphosphate of the incoming nucleotide undergoes rearrangement prior to closure, providing an opportunity to deter misinsertion and increase fidelity.Structure 09/2012; · 5.99 Impact Factor
Top Journals
- Journal of Biological Chemistry (36)
- Biochemistry (11)
- Structure (7)
- Journal of Biological Chemistry (7)
- Biochemistry (4)
National Institute of Environmental Health Sciences
Durham, North Carolina, United States
- • Laboratory of Structural Biology (LSB)
- • Laboratory of Molecular Genetics (LMG)
National Institutes of Health
Maryland, United States
- • Structural Biophysics Laboratory
- • Chemical Biology Laboratory
CUNY Graduate CenterNew York City, New York, United States
University of Southern California
Los Angeles, CA, United States
- Department of Chemistry
Research Triangle Park Laboratories, Inc.Raleigh, North Carolina, United States
New York University
New York City, NY, United States
- Department of Chemistry
Howard Hughes Medical InstituteAshburn, Virginia, United States
University of Texas Medical Branch at Galveston
Galveston, Texas, United States
- Department of Biochemistry and Molecular Biology
Novosibirsk Institute of Organic ChemistryNovo-Nikolaevsk, Novosibirsk, Russia


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CareFlite will hold open houses at the Mabee EMS Training Center at the Grand Prairie Airport on
Saturdays December 6th and 13th from 11am 'til 3pm. The open houses, which are free and open to all,
will include operation of the Dallas, Fort Worth and North Pole Railroad as well as having an
ambulance and aircraft on display. Refreshments will be served. Please join us and bring the kids...


text:
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November 29, 2014
Two robbery suspects didn't get far after stealing money from an Omaha restaurant Tuesday night.
Police say the men entered the Godfather's Pizza on West Maple Road just west of 150th Street around 8:15 p.m., pulled guns and demanded cash.
Douglas County Sheriff's Department deputies stopped a suspicious vehicle and determined that the men inside were the suspects.
They were identified as 24-year-old Russell Wardlow, booked for robbery, possession of a gun by a prohibited person and use of a weapon to commit a felony, and 19-year-old Jesse Ortiz, booked for robbery.
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Posts tagged Onslaught
Take a look at DC Universe Online's survival mode
DC Universe Online is gearing up to make survivors out of its players. That's kind of the whole focus of the game's upcoming survival mode, which sets players against waves of enemies in a test of endurance and persistence. So what does it look like in action? Well, you can check that out in a fan...
Not So Massively: Elite galaxy lore, D3's Book of Tyrael, and Dota 2 chat bans
Star Citizen introduced new game designer Pete McKay in the latest episode of Wingman's Hangar, and mentioned plans for a planet-side module and an in-game social bar. Elite: Dangerous delved into the fiction of the Elite universe and confirmed that the entire Milky Way galaxy will be available for...
Hands-on with Blacklight: Retribution's biggest update yet
February 27th will mark one year since Blacklight: Retribution threw the doors of its beta wide open. Since then, it's ranked among Steam's 50 most-played shooters. For the game's first anniversary, publisher Perfect World Entertainment is hoping to keep the free-to-play shooter's success story...
Not So Massively: Path of Exile events, Diablo III coming to PS4, and huge MOBA updates
Blizzard revealed this week that Diablo III will be coming to both the PlayStation 3 and Sony's new PlayStation 4 console and will be shown off at PAX. Torchlight II developer Runic Games announced that the game will soon be localised to Japanese and Chinese for its upcoming release in Asia; a...
Featured Stories
The Soapbox: Six reasons MMOs should abandon raiding, part 1
Posted on Nov 24th 2014 12:00PM
The Mog Log: The end of Final Fantasy XIV's 2.0 cycle
Posted on Nov 24th 2014 11:00AM
The Daily Grind: What does your scariest avatar look like?
Posted on Nov 24th 2014 8:00AM


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5 Found Fatally Shot In SoCal Homeless Encampment
Posted: 11/02/2008 - Police say five homeless people were found shot to death in a makeshift camp near some Los Angeles-area freeway ramps.
Posted: 11/02/2008 - Police say five homeless people were found shot to death in a makeshift camp near some Los Angeles-area freeway ramps.
Posted: 11/02/2008 - A state ballot measure that would ban same-sex marriage has put local law enforcement on watch after a handful of incidents were reported over the weekend.
Posted: 11/02/2008 - Rescuers have resumed their search for a 10-month old baby missing after a pickup truck carrying several children plunged into a roadside canal flooded with rainwater.
Posted: 11/02/2008 - Postal officials say residents in the Santa Cruz Mountains will finally receive about 13,000 pieces of mail found stashed in the van of a former mail carrier.
Posted: 11/01/2008 - A University of Southern California sprinter was recovering Saturday after being shot in the leg three times after leaving a Halloween party.
Posted: 11/01/2008 - Scientists have discovered juvenile coho salmon on the North Coast in a number of places where the endangered fish had not been seen for years.
Posted: 11/01/2008 - Authorities are looking for an inmate who was mistakenly released from a San Diego County jail after he switched jail wristbands with an inmate scheduled for release.
Posted: 11/01/2008 - San Francisco Mayor Gavin Newsom and Bay Area religious leaders are calling on voters to reject a ballot measure that would ban same-sex marrige in California.
Posted: 11/01/2008 - Sacramento County authorities are searching for a man suspected of opening fire at a Halloween party, killing one man and wounding four others.
Posted: 11/01/2008 - California voters are almost evenly split on a ballot measure that would require parental notification before most teenagers could get an abortion, according to a new Field Poll.
Posted: 11/01/2008 - A high school band director in Orange County has been accused of having illegal sex with a male student.
Posted: 11/01/2008 - Police confiscated video footage Friday from an Oakland Tribune photographer who was filming students protesting federal immigration policy.
Posted: 10/31/2008 - The fight over the California ballot measure that would ban gay marriage is being closely watched across the nation.
Posted: 10/31/2008 - State drug enforcement officials thought they were on a routine pot bust in Tehama County when whey discovered a cockfighting ring.
Posted: 10/31/2008 - A former Orange County man is facing 125 years to life in prison for molesting children as young as 3 years old.
Posted: 10/31/2008 - A California man suspected of mailing more than 120 hoax anthrax letters to media outlets is due back in court Friday, a day after several more newspapers reported receiving suspicious packages.
Posted: 10/31/2008 - Palo Alto's police chief has instructed officers to question African Americans in the city following a spate of recent street robberies.
Posted: 10/31/2008 - A United Airlines cargo facility at San Diego's Lindbergh Field has gotten the all clear after a suspicious container was determined to be safe.
Posted: 10/30/2008 - Water will be scarce next year for farms and cities that rely on the state for their supplies, a situation that is likely to prompt water rationing and less planting.
Posted: 10/27/2008 - Gov. Arnold Schwarzenegger says California's budget shortfall has surpassed $3 billion and must be dealt with during a special legislative session right after the election.
Posted: 10/26/2008 - A pair of minor-to-moderate offshore earthquakes have struck the northern California coast, but there are no reports of any damage or injury.
Posted: 10/25/2008 - The Sacramento County Sheriff's Office reports that an inmate facing murder and domestic violence charges has died in his jail cell.
Updated: 10/24/2008 - Assembly Democratic leaders sent a letter Friday to Gov. Arnold Schwarzenegger, urging him to address California's high rate of foreclosures as part of an anticipated special legislative session on the budget.
Posted: 10/24/2008 - A jury has found two brothers guilty of murder in the shooting death of a man at an Oakland taco truck stand.
Posted: 10/24/2008 - General Motors is shipping China-bound Buicks and Cadillacs out of Ventura County's Port Hueneme.


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I am currently using forever-monitor to spawn a basic HTTP Node Server, although when I execute the JavaScript that executes the forever-monitor scripts, it isn't sent to the background, when I exit the TTY session, the HTTP server stops.
The code I am using to spawn the server follows.
The question I am asking really is, should I be using Forevers CLI to spawn the script that spawns subsequent servers programatically?
var forever = require('forever-monitor');
var child = new (forever.Monitor)('streams.js', {
max: 3,
silent: true,
options: []
child.on('exit', function () {
console.log('streams.js has exited after 3 restarts');


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Recently I installed Ubuntu 14.04, and I would like to install RabbitVCS on my system. Does RabbitVCS work on the new Ubuntu? Has someone already tried it out?
Take the 2-minute tour ×
Ask Ubuntu is a question and answer site for Ubuntu users and developers. It's 100% free, no registration required.
I personally don't have tried it, but there is a version for trusty (14.04) in the PPA, so I guess it should work.
You can always try if it's working (this will install RabbitVCS for CLI (terminal), gedit and Nautilus 3, if you're using another file manager see the full list of packages here):
And if it doesn't you can remove it:


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Programs & Special Events
Core Clinic Series
Tuesdays 6:00-6:30pm and Wednesdays 7:00-7:30pm, Scifres Functional Fitness
Take your fitness routine to the next level and learn how to maximize our specialized strength equipment. We will focus on how to effectively and efficiently target and challenge your abs, lower back, and gluts by incorporating dynamic, functional movements. No registration required. Space is limited; please arrive early to reserve your spot.
Fundamentals of Olympic Weightlifting
Sundays, 2-4pm, East Fitness, Olympic Lift Platforms
This two hour course will deconstruct the major Olympic lifts, as well as provide tips for basic technique and form. Please register by 12:00pm the Friday before your desired workshop.
November 23
Powerlifting Series
Fridays, 4-4:30pm, East Fitness
Learn the foundations of powerlifting in this three-part series. Each thirty minute session is dedicated to a specific lift in which you will practice and receive constructive feedback. The better your posture and technique, the better you'll be able to execute the movement, and more powerful you'll become! No registration required. Space is limited; please arrive early to reserve your spot.
November 21: The Deadlift
Wellness Workshops
Wednesdays, 7-8pm, Wellness Conference Room
Join us for a variety of workshops designed to enhance your well-being. Please dress in loose, comfortable clothing; socks or bare feet are acceptable. All required equipment will be provided. No registration required.
December 10: A Taste of Relaxation


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Films By Philip Armitage
Across and around the world from oilfields to refineries and from refineries to consumers, oil tankers carry crude oil and its refined ... products. Proud Ships is the story of the tankers and the men who sail in them. It shows the full scale of their world-wide operations, the scope and magnitude ... Read more


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Doug Deming and Dennis Gruenling with the Jewel Tunes recently rocked the Rhythm Room with their high-powered blues and '50s rock 'n' roll. Deming plays a mean guitar, but he also knows how to entertain the crowd in a style that mixes the modern and the vintage. Gruenling gets to share top billing w ... More >>
Travelin' the Dirt Road
(Blue Witch)
Various Artists
House Rockin' and Blues Shoutin'
(Blue Witch)
The rumors are true
The Rhythm Room
Aging finer than wine
Despite the recent passing of some of heritage music's finest, the music continues to flourish thanks to a handful of fine new releases
Local blues crusader Bob Corritore turns his boyhood dreams into reality
May 21 - 27, 1998