6%; Table 2) that did not differ significantly from dMMR tumors o

6%; Table 2) that did not differ significantly from dMMR tumors of the sporadic subtype or pMMR tumors lacking BRAFV600E and KRAS mutations ( Table 4). Of note, DFS for dMMR tumors of the familial subtype was poorer among distal vs proximal tumors ( Figure 2A and B). Among distal pMMR cancers, statistically significant differences in DFS were found only for KRAS-mutated tumors (vs those without KRAS and BRAF mutations), yet statistical

power was limited ( Table 4). A trend toward better DFS was found in distal vs proximal tumors with BRAFV600E mutations and tumors without BRAFV600E or KRAS mutations ( Table 2). Among patients with N1 tumors, the association of tumor subtypes with DFS did not differ significantly from the overall Talazoparib cohort (Figures 1B and 2C). Among patients with N2 tumors, however, poor DFS was observed for dMMR tumors of the sporadic subtype ( Table 2, Figure 2D) that did not differ significantly from DFS of pMMR subtypes with mutated KRAS (Padjusted = .9195) or mutated

BRAFV600E (Padjusted = .8231) ( Table 4). In contrast, N1 tumors of the dMMR sporadic subtype had DFS rates that were significantly improved find more compared with DFS of patients with pMMR mutated KRAS tumors (HR = 0.51; 95% CI: 0.31–0.82; Padjusted = .0054), or showed a strong trend vs the mutated BRAFV600E (HR = 0.50; 95% CI: 0.28–0.91; Padjusted = .0238) subtype ( Figure 2C). We attempted to validate the prognostic Dapagliflozin utility of our classifier in an independent

cohort of stage III colon cancer patients treated with 5-FU–based adjuvant chemotherapy. Patients from this external cohort were categorized into the same molecular subtypes as in our dataset, with the exception that dMMR tumors were divided based on BRAF status alone (see Materials and Methods). In this independent cohort, a statistically significant difference was seen among the 5 molecular subtypes (P = .014) as was demonstrated in the primary N0147 cohort ( Figure 3). A similarly favorable outcome for pMMR tumors lacking BRAFV600E or KRAS mutations and dMMR tumors was observed. In addition, poorer DFS among patients with BRAFV600E mutant or KRAS mutant pMMR cancers was observed as reflected in their 5-year DFS rates ( Figure 3, Table 2). Accordingly, the key prognostic findings of our biomarker classifier were validated. In patients undergoing surgical resection of CRC, prognosis and management are based entirely on the TNM staging system,24 despite considerable stage-independent variability in outcomes. Accordingly, prognostic classifiers that can be readily implemented into clinical practice are needed to enhance clinical decision making. In stage III colon cancers from a recent adjuvant chemotherapy trial,26 we classified tumors into 5 prespecified subtypes using a biomarker combination of BRAFV600E and KRAS mutations, MLH1 methylation, and MMR status.

This information was complemented through the study of Clemente (

This information was complemented through the study of Clemente (2009), from which it was obtained Epacadostat that each wholesaler had one or more trucks,

and that each truck employed 4 people for the sale. This employment was added to a total pool of people in cleaning, surveillance, administration, transportation (stevedores), and quality controls, among others. For each site visit, the number of people working was counted, and that number was used as denominator to the total volume of fish (tons) that was marketed on the given day based on official PRODUCE data. From this the total employment per ton was obtained. People employed to export products from fishing plants were included in the staff of the plants (for instance for fishmeal and fish oil plants). In the case of reduction fisheries, only a very small amount of the overall production was exported using brokers. In this case, a broker only employed a secretary. The same was true for guano Proteasome purification exporters. The export by such brokers was estimated,

and from this the employment per t of product as well as their fees per t of product. Similar calculations were made for the distribution of seafood products such as artisanally cured products, cured products, frozen products, and cans. Further, official PRODUCE data was used for local consumption of marine fish and invertebrates for 2009. Using ‘typical truck’ units based on capacity (tonnage), the products they transport, and the distance traveled, the total number of trips per year per truck (based on interviews with truck drivers and company owners) and the volume of fish transported by the trucks per productive process, gave the number of trucks required to move the products per productive process to their destination. It was assumed that each truck employed one driver and that in 20% of the cases they had a helper or copilot. When transporting cans and cured products, trucks are rarely filled only with one product, (e.g., also with other cans, milk, juices, eggs, or beans), but for the calculation of the total employment per ton

transported it was assumed that only fish were transported. In Thymidine kinase the calculations, the office and administrative staff for the companies that distribute cured, canned, and frozen products across Peru was also considered. These were estimated from interviews. For the frozen seafood wholesalers, the total amount of frozen seafood that was not distributed to local markets throughout Peru, (which mainly is to the highlands) was estimated. People who buy products from freezing plants and domestic distributer’s storage facilities and transport them to frozen wholesaler markets were also considered, as were people who sell products at the frozen wholesaler markets, including administrative and surveillance staff.

The complex inheritance pattern ultimately results in reduced exp

The complex inheritance pattern ultimately results in reduced expression of Y14, the protein encoded by RBM8A and a core member of the exon-junction H 89 nmr complex (EJC), in platelets. Further research is needed to explain how Y14 insufficiency, and presumably subsequent defect of the EJC, explains the unique skeletal, hematological and additional features of TAR syndrome. Papers of particular interest, published within the period of review, have been highlighted

as: • of special interest The authors would like to thank the patient support groups for children with upper limb defects (REACH), and for TAR syndrome (the TAR Association). The study was supported by grants from the National Institute for Health Research (NIHR) (RP-PG-0310-1002, to CG and WHO) and the British Heart Foundation (FS/09/039 to CG, RG/09/12/28096 to CAA). “
“Current Opinion in Genetics & Development 2013, 23:345–351 This review comes from a themed issue on Molecular and genetic bases of disease Edited by buy Alectinib Jim Lupski and Nancy Maizels For a complete overview see the Issue and the Editorial Available online 19th March 2013 0959-437X/$ – see front matter, © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.gde.2013.02.012 Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterised

by long incubation periods, accumulation of abnormal prion protein

(PrPSc), spongiosis, gliosis and neuronal loss [1]. They include scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt–Jakob disease (CJD) in human. Sporadic CJD typically presents in late middle-old age as a rapidly progressive multifocal cortical dementia with additional neurological features including cerebellar ataxia, pyramidal and extrapyramidal motor dysfunction, myoclonus and dysfunction DNA ligase of the visuoperceptual system. Despite increasing ascertainment, these remain rare conditions, with typical incidences in the developed world of 1–2 cases/million/year. Variant CJD (vCJD), resulting from the human transmission of BSE mainly through dietary exposure, has steadily declined in incidence in the UK since 2000, with a total 176 cases [1 and 2]. Although the decline in vCJD is most welcome, the prevalence of subclinical infection indicated by anonymous surveys of appendiceal tissue, remains a significant concern at around 1:2000 in the UK (http://www.hpa.org.uk/hpr/archives/2012/news3212.htm#bnrmlprn). Subclinically infected individuals may never convert to clinical cases, however they pose risks for iatrogenic transmission by blood or blood product transfusion, by dentistry and surgery. PrP is central to the disease process with its misfolded form thought to be the principal component of the infectious particle.

T C ) and checked by a second (M R , R A , or R W ) In an amendm

T.C.) and checked by a second (M.R., R.A., or R.W.). In an amendment to the published protocol, all articles were appraised using the Effective Public Health Practice selleckchem Project tool17 to enable assessment of all study designs with the same rubric. Appraisal considered the method of sample selection, potential for bias connected with study design, differences between groups at baseline and how these were dealt with in the analysis, assessment of outcome measures, description of the flow of patients through the study, and use of a valid and reliable primary outcome measure. Changes in medication use were reported in all included studies. However, the multitude of different formats in

which the data were provided

and the range of included study designs precluded formal pooling of the data. For example, among the randomized studies, medication use was variously reported as psychoactive drug use score, proportion of residents who had antipsychotic selleck chemicals llc medications discontinued, number of days of antipsychotic therapy per patient per month, proportion of residents taking antipsychotic medications, and dose of antipsychotic medication. Data were therefore tabulated, grouped according to study design and outcome, and discussed narratively. The electronic searches retrieved a total of 5071 unique citations. Screening of title and abstracts against the inclusion and exclusion criteria resulted Ponatinib ic50 in the retrieval of the full text of 80 articles. Fifty-nine articles were excluded because the following aspects of the article did not meet the inclusion criteria: population (n = 3), intervention (n = 14), reported outcomes (n = 1), and study design (n = 32). Six articles were published as conference abstracts only with insufficient information provided and we were unable to locate a full-text publication despite contact with authors, and 3 were duplicate publications. One additional article was located through hand searching of the bibliographies

of identified systematic review articles. The update search identified an additional 985 articles, of which 7 were retrieved in full text and 1 article met the inclusion criteria. A total of 23 articles were included, describing 22 studies. Figure 1 shows the flow of studies through the review. Table 2 shows the study characteristics of all included articles. All the included studies provided quantitative data. We did not identify any articles reporting the views and experiences of prescribers with specific interventions. Our search identified a number of qualitative articles exploring factors that influence prescribing practice in care homes; these are considered further in the discussion. Six of the studies are randomized,14, 18, 19, 20, 21 and 22 5 have a controlled design,23, 24, 25, 26, 27 and 28 and 11 are uncontrolled before and after studies.

These associations are described below in order of chromosome, wi

These associations are described below in order of chromosome, with the numbering of Fonsêca et al. [32]. On linkage group B01, the alignment of the anthracnose resistance genes Co-1, Co-w, and Co-x and the rust R-gene Ur-9 is evident at the top of the short

arm of the equivalent chromosome Regorafenib mouse near the RGH-SSR markers BMr205, BMr285, BMr291, BMr300, BMr305, and BMr328. A large number of QTL for resistance to anthracnose, common bacterial blight, and white mold are known to map to the long arm of this chromosome [9] and probably are associated with the ten RGH-SSR markers located in the interval between BMr201 and BMr250. All of these markers provide tools for marker-assisted selection for this linkage group and would assist in the dissection of the cluster of Andean anthracnose R-genes or alleles of Co-1 at the top of the short arm of this chromosome [51]. On linkage

group B02, alignment of four BMr markers (BMr227, BMr265, BMr268, and BMr292) can be postulated with QTL for anthracnose, common bacterial blight, Fusarium root rot, halo blight, and white mold. However, it appears that no RGH-SSR was found for genes I, Pse-3, and Co-u [51]. The dominant I gene against bean common mosaic virus has been shown to lie within a cluster of NBS-LRR genes [52], Natural Product Library datasheet but perhaps its sequence was not picked up by our library screening. Linkage group B03 had only one RGH-SSR in the region of QTL for common bacterial blight and Fusarium root rot resistance. Generally, this chromosome seems not to contain many RGH genes, although recessive virus R-genes such as bc-12, bgm-1 and perhaps bc-u have been mapped subtelomerically to the chromosome. Dimethyl sulfoxide The map of linkage group B04 was among the most interesting, as this chromosome has been well characterized for many major R-genes and RGH sequences [53] and [54]. These include the anthracnose resistance genes Co-3, Co-9, Co-10, Co-x, and Co-y and rust resistance genes Ur-5, Ur-Ouro negro, Ur-Dorado, as well as many QTL against angular leaf spot, anthracnose, common bacterial blight, Fusarium root rot, and bean golden yellow mosaic virus [9]. This region has eight RGH-SSR and two RGH-RFLP (2a and 14) on the full chromosome,

except at the end of the long arm, which contains the APA locus [55]. This is an example of a linkage group with well-characterized disease resistance factors coincident with panoply of potential R-gene markers. Fine mapping of R-genes, QTL and new markers are needed to determine the utility of the new RGH-SSR for marker assisted selection. Linkage group B05 is an example of a chromosome that has been under-studied for resistance factors and yet had six RGH-SSR markers. So far, only QTL have been described for B05 with possible association between BMr329 a common bacterial blight QTL near the end of the short arm, as well as a cluster of five BMr markers in the middle of the linkage group associated with a QTL for Fusarium root rot resistance [9].

Via PubMed 5 reviews and 159 RCTs, via Embase 21 reviews and 202

Via PubMed 5 reviews and 159 RCTs, via Embase 21 reviews and 202 RCTs, via Cinahl 344 reviews/RCTs, and via Pedro 7 reviews and 28 RCTs were found. Finally, no (Cochrane) reviews and 17 additional RCTs (14 via PubMed, 3 via Embase, 0 via Cinahl or Pedro) were included: 16 studied ESWT (10 for calcific and 6 for non-calcific tendinosis) and one studied Radial ShockWave Therapy (RSWT) for calicific tendinosis. RSWT is pneumatically generated with low- or medium-energy shockwaves (Cacchio et al., 2006) www.selleckchem.com/products/PD-0332991.html and therefore should have a lower peak-pressure and longer rise-time than ESWT. Further, the focal

point is centred on the tip of the applicator instead of on the target zone, as is done in ESWT. Therefore, it is supposed to be less painful, of less risk and should target the calcification more effectively (Haake et al., 2002). The characteristics of the studies are described in Appendix II. Of the 17 RCTs, 10 were classified as high-quality GSK1120212 purchase and 7 as low-quality (Table 2) by using the list of Furlan et al. (2009) The most prevalent methodological flaws were ‘care giver’ (i.e. the one who provides the intervention) not blinded’ (65%), and ‘no intention-to-treat analysis’ (35%). Table 3 and Table 4 show the evidence for effectiveness we found in this study. A high-quality study (Gerdesmeyer

et al., 2003) (n = 96) compared high-ESWT (EFD: 0.32 mJ/mm2) to placebo for calcific supraspinatus tendinosis. At 3, 6, and 12 months follow-up, there were significant between-group differences in favour of the treatment group on pain, the total Constant Score, and on calcific deposit size (mm2). See Appendix II for the exact data. A low-quality study (Hsu et al., 2008) (n = 46) compared high-ESWT Tideglusib (EFD: 0.55 mJ/mm2) to placebo for calcifying shoulder tendinosis. The treatment group showed significant decrease on pain and the Constant score compared to the sham group at 3, 6 and 12 months follow-up. The calcium deposit width

reduction was bigger in the treatment group at 12 months, although no statistical comparisons were made between the groups. In conclusion, there is moderate evidence for effectiveness of ESWT compared with placebo in the short-, mid- and long-term. A low-quality RCT (Loew et al., 1999) (n = 80) studied high-ESWT-1-session versus high-ESWT-2-sessions versus no treatment for calcific shoulder tendinosis. There were no baseline differences on the Constant score; at 3 months follow-up significant higher Constant scores for the ESWT groups (63.7 (14.6) (mean (SD)) (high-ESWT-1-session), 68.5 (13.1) (high-ESWT-2-sessions), 47.8 (11.4) (no treatment)) was found. There is limited evidence for the effectiveness of high-ESWT (1 session and 2 sessions) compared to no treatment in the short-term. One low-quality RCT (Loew et al., 1999) studied effectiveness of high-ESWT-1-session versus high-ESWT-2-sessions.

0 m and a slope gradient of 4° (Figure 14 – Profiles 03 and 04)

0 m and a slope gradient of 4° (Figure 14 – Profiles 03 and 04). All the furrows formed by trailer suction dredging had disappeared completely after 11 months (Figure 14 – Profiles 05, 06, 07) except for one depression 70–80 m in diameter and with a maximum depth of 0.5 m left by the deepest pair of furrows, initially

1.9 m deep. The increasing scale of offshore dredging is raising questions not only HSP inhibition about the impact of these activities on the marine environment, but also about the availability of sand and gravel resources. There is a scarcity of sediments in many regions of the Baltic Sea owing to the low input of material. Therefore, information on the age and origin of the sand and gravel deposits as well as about their BIBW2992 ic50 stability and potential for regeneration are of great importance. Considering the age of the layer of marine sand under

discussion and taking into account the rsl curve for the southern Baltic (UŚCINOWICZ 2003, 2006), we can state that the transgressing sea reached the area of investigation ca 8500 years ago. The radiocarbon age of marine shells (3275–3145 and 4775–4590 cal. y. BP) and the significant admixtures of gravel in the lowermost part of the bed of sand indicate that erosion and redeposition predominated during ca 5000–4000 years, and that when transgression ceased and the sea level approached the contemporary one, the accumulation of sand started. During the following ca 3500–4500 years, a 2–4 m layer of marine sand accumulated; it would seem that at that time

redeposition during storms probably did not reach the floor of the layer. The thickness of the contemporarily mobile layer of sand, as determined by measurements of the 137Cs content in the cores, is between ca 0.40 m in core COST-8 and ca 0.8 m in core COST-3 (Figure 7). A similar thickness of sands containing radiocaesium (0.4–0.6 m) was shown by investigations carried out 15–20 km to south-east of the test area at 15–20 m depth (Łęczyński 2009). The depth of radiocaesium penetration depends not only on near-bottom hydrodynamics but also on the grain size distribution of sediments. The water depth at the sites where cores COST-3 and COST-8 were taken is nearly the same: 15.1 m and 15.6 m respectively. Farnesyltransferase This halfmetre difference in water depth does not justify the difference in the depth of 137Cs penetration into the deposits. This is most probably due to the dissimilarity in grain sizes. Coarse sand with an admixture of gravel is present in the area from which core COST-8 was taken, whereas medium sand overlies the area where core COST-3 was obtained. Medium sand needs a lower critical current velocity to initiate its movement than coarse sand, and storms can rework a thicker layer of the deposit. Other basic questions concern the rate of regeneration, i.e. the rate of disappearance of morphological changes and changes in sediment distribution.

3) GUA treatment suppressed this CLP effect on memory CLP impai

3). GUA treatment suppressed this CLP effect on memory. CLP impaired the novel object recognition memory, i.e., rats

from this group did not spend a significant higher percentage of time exploring the novel object during short and long-term retention test sessions in comparison to the training trial (Fig. 4). GUA treatment suppressed this CLP effect on memory. CLP caused an increase p53 inhibitor in the immobility time, compared to the sham group (Fig. 5) in the test session (5 min) of the forced swimming task, suggesting a depressive-like behavioral effect. GUA treatment suppressed this CLP effect. In the present study, we showed that GUA was effective in reversing oxidative brain damage and cognitive impairment in an animal model of sepsis, a model that is characterized by presenting cognitive impairment in survivors associated with deleterious effects caused, at least in part, by reactive oxygen species in brain tissue. Normal glutamatergic neurotransmission is essential for synaptic development Navitoclax ic50 and plasticity as well as learning and memory. In contrast, excessive glutamate excitation

plays a role in a variety of neurological disorders. Survival pathways appear to be mediated via NMDA receptor synaptic activity, whereas neuronal damage may be mediated by excessive extrasynaptic activity (Okamoto et al., Guanylate cyclase 2C 2009). Severe overstimulation of excitatory receptors can cause necrotic cell death, while less fulminant or chronic overstimulation

can cause apoptotic or other forms of cell death (Budd et al., 2000). These events are associated with overactivation of NMDA receptors that causes an excessive influx of Ca2+ ions, which trigger a series of toxic events ultimately leading to cell death by generating ROS and activating neuronal NO synthase (nNOS) (Garthwaite et al., 1988). Since GUA is thought to serve as an important local regulator of glutamatergic neurotransmission (Schmidt et al., 2007), the therapeutic value of GUA, other guanine-based purines and their analogs are under active investigation for disorders whose pathophysiology is thought to include abnormalities of NMDA receptor mediated neurotransmission (Hardingham, 2009). An extensive body of evidence from experimental and clinical studies indicates that sepsis is associated with excess glutamate release, activation of glutamate receptors that results in several metabolic alterations in the brain, such as decreased energy supplies, ATP depletion, increased ROS production, depletion of antioxidants, and accumulation of markers of oxidative stress (Dal-Pizzol et al., 2010). In an animal model, oxidative damage occurred early in the course of sepsis development in several brain regions (Barichello et al.

, 2006) These accidents frequently result in severe and fatal en

, 2006). These accidents frequently result in severe and fatal envenomation. As the antilonomic serum produced by Instituto Butantan in Brazil is the only clinical recourse to revert the dramatic hemorrhagic syndrome in poisoned patients, the limitations in effective treatments, has motivated the increase of knowledge on the biological effects of the whole venom in

experimental models, and also on the molecular mechanisms enrolled in the particular effects of its numerous toxic active principles (for reviews: Berger et al., 2010; Alvarez Flores et al., 2010). The accidents with the caterpillar L. obliqua occurs when the whole animal is crushed by the victim, and the insect’s chitinous bristles are broken and the venomous

hemolymph penetrate in the human skin, reaching blood vessels ( Veiga et al., 2001). The most charactheristic and severe symptoms described for of L. obliqua envenomation are related to hemostatic disturbances, characterized by consumptive DAPT clinical trial coagulopathy, a Lumacaftor in vivo secondary fibrinolysis ( Kelen et al., 1995), and depending on severity, a compromised renal function ( Burdmann et al., 1996; Fan et al., 1998), which can lead to a poor outcome ( Kowacs et al., 2006; Garcia and Danni-Oliveira, 2007). In vivo and in vitro studies have shown that the L. obliqua venom contains several toxins with pro-coagulant, anticoagulant and antithrombotic activities. Toxic components isolated from L. obliqua’s venom have shown to be responsible for many features of the hemorrhagic syndrome, contributing for the apparently paradoxical actions of the venom on the coagulation system, expressed as simultaneous pro- and anti-clotting effects ( Pinto et al., 2010). In addition to hemorrhagic syndrome, L. obliqua envenomation is characterized by many local effects at mafosfamide the contact site, such as burning sensation, pain and erythematic signs, which start immediately after contact. Edema formation and leukocyte migration to the site of injury was also described in animal models, characterizing the inflammatory response ( Fan et al., 1998; Correa et al., 2004; Ramos et al.,

2004). Most of inflammatory effects during envenomation rely on the production or release of humoral factors (bradykinin, prostaglandins, histamine), but L. obliqua venomous proteins have been also proposed to induce activation of cellular responses through the up-regulation of several genes that could be involved in the generation and/or amplification of clinical manifestations ( Pinto et al., 2008 and Pinto et al., 2010). Lopap, a prothrombin activator ( Reis et al., 2006) and Losac, a factor X activator ( Chudzinski-Tavassi and Alvarez Flores, 2006), two active proteins isolated from L. obliqua venom, besides their effects on coagulation system, were shown to stimulate endothelial cells, affecting expression of mediators involved in coagulation, fibrinolysis and inflammation ( Carrijo-Carvalho and Chudzinski-Tavassi, 2007).

However, when PARP is impaired, cells are noted to become exquisi

However, when PARP is impaired, cells are noted to become exquisitely sensitive to DNA damaging agents such as radiotherapy [14] and [15]. As a result, the clinical development of PARP inhibitors has followed two approaches: 1) combining PARP1/2 inhibition with DNA-damaging agents, such as radiation, to derive additional therapeutic benefit; and 2) targeting tumor

cells with pre-existing defects in double-strand DNA break repair, such as Brease Cancer (BRCA)-deficient cells, which are genetically predisposed to die when PARP activity is lost [16]. ABT-888 is an orally available, small molecule inhibitor of PARP which has been shown to potentiate the effects of alkylators and radiotherapy in xenograft tumor models [17]. Recognizing the therapeutic potential of PARP-1/2 inhibition in PDAC, we have investigated the addition

of veliparib to focused radiation in vitro and in vivo using a novel preclinical pancreatic cancer buy GSI-IX radiation research model [18] and [19]. The PDAC cell line, MiaPaCa-2, stably transfected with the luciferase-aminoglycoside phosphotransferase Dapagliflozin concentration fusion gene under the control of the elongation factor-1α promoter, was kindly provided by Dr. Ralph Graeser, ProQinase GMBH, Freiburg, Germany. Cells were grown in Dulbecco’s modified Eagle’s medium (DMEM; Invitrogen, Carlsbad, CA) supplemented with 10% fetal bovine serum, and 100 units/mL penicillin/streptomycin. Subconfluent cell monolayers were removed using Immune system 0.25% trypsin containing 1 mmol/L EDTA (Invitrogen) and passaged at a ratio of 1:3 or utilized for study. Cells were seeded in triplicate monolayer and treated with varying doses of ionizing radiation using a 137Cs irradiator (5 Gy/min; Mark I, Shepherd and Associates), ABT-888 (Selleck Chemicals, Houston, TX), or a combination of the two. All in

vitro studies were performed in triplicate. When cells were co-treated, ABT-888 was added to the cell suspension 30 minutes prior to irradiation and left until routine media change at 48 hours. Cell viability was determined by the ability to convert a redox dye (resazurin) into a fluorescent end product (resorufin) using the Cell Titer-Blue® Assay (Promega Corporation, Madison, WI) at varying time points after treatment. Treatment doses resulting in 10% (IC10), 20% (IC20) and 50% (IC50) cell death were calculated for ABT-888 and irradiation, respectively. ABT-888 dose enhancement factors were determined after co-treatment with varying irradiation doses. Levels of apoptosis were determined using a chemiluminescent caspase 3/7 assay (G8091, Promega Corporation, Madison, WI) 48 hours after treatment with ABT-888, radiation, or a combination thereof. PARP-1/2 inhibition was quantitated using an enzyme-linked immunosorbent assay for PAR protein (Trevigen, Gaithersburg, MD) after treatment with ABT-888, radiation, ABT-888 plus radiation, or no treatment. Total protein extracts were harvested 6 hours after treatment and PAR levels were determined by chemiluminescence.