Search

Presents a kinetic study that utilizes a method for varying the concentrations of the possible Ce(IV) species and computing the concentration distribution of the sulfato and hydroxo species of Ce(IV). (MLH)

The present work search the protective capacity of Fusarium oxysporum phosphate buffer extract (FO) against gamma radiation (ɣ-IR) based on evaluating the changes in some blood components in rat model. The variations in haematological and pairs of biochemical parameters were determined for 40 albino male rats which divided into five groups : negative control , positive control, i.e. irradiated only , and three treated groups administrated increasing dose of (FO) after single four Gray (Gy) gamma irradiation dose. Three doses of FO extract (0.15, 0.3 and 0.6 mg/g body mass) were chosen, as protective doses, for subsequent evaluating of its antioxidant activity and ameliorating capacity toward radiation-induced oxidative stress. The changes in the chosen parameters, due to 4 Gy irradiation and then administrating the FO, were computed after 1, 2, 3 and 7 days. Total serum protein, albumin, total globulin, besides some parameters of complete blood count (CPC) were determined and the data reached were analysed to evaluate the capacity of FO to compensate the gamma irradiation injures. The present work is assuming that: biocomponents extracted from FO fungi have a protective role against gamma radiation which can establish protocols for medical management of radiation injuries based on natural medication.

Radioactive sulfate wastes are generated from boiling water reactors (BWRs) and should be immobilized before their disposing to avoid the back release of their hazardous components under the impact of water flooding incident in the disposal site, which gives rise of secondary contamination at the surrounding area. A cement-polymer composite formulated from recycled post-consumer polystyrene foam waste and Portland cement was proposed as an incorporating matrix for solidification/stabilization (S/S) of sulfate waste simulate in laboratory scale experiments. To imitate a water-flooding incident, the reached solidified waste form was completely immersed in three types of water, namely, tap-, ground-, and seawater for increasing periods up to 420 days. Compressive strength, porosity and mass change of the solidified waste samples were evaluated at the end of various immersion periods. Besides, FT-IR, XRD, SEM with EDX analyses were performed to follow the internal changes of the product post the immersion. Based on the data obtained, it could be concluded that the comparative stability of the nominated composite under the impact of water flooding incident candidates it as an acceptable matrix for immobilizing the radioactive sulfate wastes. In addition to its stability, the formulated composite have the advantage of upgrading post-consumer non-biodegradable polystyrene foam waste, therefore, thus introducing a sustainable technique and saving landfill area by using significant amounts of one of the major municipal solid wastes.

Oxidative stress in plants is attributed to the exposure to overbearing amounts of heavy metal pollutants in their ecosystem in parallel, unbalanced cellular redox state, and, moreover, a disturbance in mitochondrial electron transport, which elevates the reactive oxygen species (ROS) generation and accumulation at both cellular and molecular levels. Heavy metal pollution is a consequence of the release of the pollutants into the soil, water, and air, from natural sources, as well as the increase in anthropogenic activities. Phytotoxicity is a factor of bioavailability of the heavy metal ions in the plant’s environment, and moreover their interactions with other metal ions, in addition to nutritional status, age, and mycorrhizal infection of the plant. Many proposed mechanisms have been put forward to assume the entry and the transport of the toxic heavy metal ions, after their accumulation, into the biological cells. Oxidative stress is a condition where oxidation, due to reactive oxygen species, exceeds the antioxidant tools in the living systems. Definitely, sometimes the oxidative stress is beneficial; yet, the disturbance in the balance between its generation and detoxification leads to serious problems to plant. Under that environmental stress conditions, plant has its defense mechanisms; moreover, mitochondria are assumed to be elaborated in redox signaling and the mitochondrial ROS can start a signaling cascade balancing the overall stress response, i.e., harm against adaptation.

Hard wood–polymer composite (HWC) was prepared, based on hot press technique, by mixing air-dried rice straw waste as a filler into a molten of chemically recycled extended polystyrene foam waste (PS) and its maleated form (PS-g-MA) as a matrix. Two fire retardants (FRs), namely zinc borate (ZB) and/or anhydrous magnesium hydroxide (MH), were dispersed into the composite to compensate for the poor thermal stability and flammability of the composite. Thermal properties of the reached HWC were evaluated by different techniques including thermogravimetric analysis, differential scanning calorimetric, in addition to, flammability analyses. Mechanical characterization was, also, rated based on tensile strength and elongation at break measurements. It was found that incorporation of the nominated fire retardants improved the thermal stability of the final products. Besides, flammability resistance was enhanced as ZB and/or MH was added to the hard wood–polymer composite formulation. The onset temperature of degradation and mass loss rates were significantly reduced in the presence of the FRs. The tensile strength of HWC was reinforced by marked additions of the FRs. The obtained data can fulfill the required optimal performance of the HWC to fire and mechanical characterizations which are necessary for many applications in the residential construction, transportation and furniture industries.

Cement-polymer composites were developed to enhance the mechanical durability and reduce the porosity of cement, and to acquire a value-added end product useful for many applications in the construction sector. The novel product should be stable during exposure to various challenging environments, e.g., water of different quality, origin, and dissolved ions. The present work evaluated the impact of immersing the new cement-polymer composites (CPs), containing different fractions of recycled waste polystyrene foam, in plain, ground and sea water on the composites’ properties. After 420 days of immersion in all studied types of water, the obtained CPs showed acceptable compressive strength values (more than 30 MPa); in addition, corrosion resistance coefficients (K) were increased more than unity in comparison to non-immersed samples. Moreover, this study also determined alterations of internal architecture of composite specimens cured for 28 days after immersion for up to 420 days in water of different composition. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used for these studies.

This work was funded by the King Abdullah University of Science and Technology through the baseline funding (BAS/1/1396-01-01).

Assay of cell-free DNA in blood offers an approach to assessment of tumor DNA. We sought to determine whether Epstein-Barr virus (EBV) DNA in cell-free blood is also a good surrogate for the presence of tumor DNA in children with Hodgkin lymphoma, as it is in adults, and whether it correlates with pediatric outcomes. Pediatric patients enrolled in a Children's Oncology Group trial (AHOD0031) were studied at baseline and at 8 days after the initiation of treatment. At baseline, EBV DNA in cell-free blood correlated with the presence of EBV in tumor, and EBV DNA 8 days after the initiation of therapy predicted inferior event-free survival. EBV DNA in cell-free blood warrants further investigation as a marker of inadequate tumor response in Hodgkin lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00025259.

The productive performance of cachama and nile tilapia reared in biofloc and fed diets of vegetal origin was evaluated. In 1000L tanks with permanent aeration, were placed80 fish/m3, in a ratio 1:1 (cachama : tilapia); fish were fed with three levels of crude protein (CP): 16% (T16), 24% (T24) and 32% (T32) for 120 days. Parameters of growth, yield, water quality, production costs and proximal analysis of the flocs were estimated. Dissolved oxygen showed saturation above 100% and nitrogen compounds (NO2 = 0.4-0.5 mg/l, NO3 = 0.4-0.5 mg/l, NH3 = 0.2-0.3 mg/l, TAN = 2.2-2.4 mg/l)showed no statistical difference between treatments (P > 0.05). The final weight of the cachama (173.5-196.2 g) were between two and four times those obtained by tilapia(43.0-87.9 g). The tilapia recorded a better daily gain of weight in T24 (0.7 g/day); while the cachama ranged between 1.2-1.3 g/day, with no significant difference between these values (P > 0.05). The best bi-culture yield was obtained in T24 diet (11.4 ± 1.3 kg/m3), which also recorded the lowest FCA (0.9 ± 0.3). To produce one kilogram of fish cost between COP$3.148 (T24) and COP$4.445 (T32); of which the food represented between 49.2% (T16) and 63.3% (T32) and energy between 10.3% (T32) and 14.2%(T16) of total costs. Proximal analysis of the flocs recorded crude protein levels suitable(29-36% PB) for cachama and tilapia; but with low lipid levels (< 1.0%). The productive performance and the production costs allow to suggest the viability of the biofloc system for the production of fish meat with 24% CP diet of vegetal origin.

Unlike chronic myeloid leukemia, patients with acute lymphoblastic leukemia (ALL) with Philadelphia chromosome (Ph+) do not respond well to Imatinib or tyrosine kinase inhibitors (TKI). In addition, TKI might induce resistant mutations in kinase domain (KD) of ABL in patients with relapsed diseases. Of the histone deacetylase (HDAC) inhibitors, suberoylanilide hydroxamic acid (SAHA) has shown to induce potent cytotoxicity on acute myeloid leukemia cell lines but Givinostat effect on acute lymphoblastic leukemia (ALL) has not been reported. We investigated if Givinostat could exert similar inhibitory effect on SUP-B15, an established B-cell ALL with Philadelphia chromosome (Ph+). Two Ph+ leukemia cell lines, SUP-B15 and an AML cell line K562 were studied in parallel for their responses to Givinostat. Mutation status of TP53 genes was also examined to correlate cellular proliferation and apoptosis. Givinostat significantly inhibited cell proliferation of SUP-B15 (IC50:0.18±0.03μM) and simultaneously inhibited BCR-ABL signal pathway. A remarkable apoptosis was induced by 0.25μM Givinostat in SUP-B15 along with the activation of caspase cascades and increased expression of p21. These inhibitory and proapoptotic effects were not observed in K562 simultaneously treated with Givinostat. Finally our studies showed that TP53 mutation status might determine responder or non-responder to Givinostat in these two Ph+ leukemia cell lines.

The present study focused on synthesizing a series of novel derivatives of 4-aryl-1-[2-(3-benzyl-4-oxo(3H)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-2-ylsulphanyl) acetyl] thiosemicarbazide 5a-d and evaluating their antitumor activity. The structure of the synthesized compounds has been elucidated on the basis of elemental analyses and spectroscopic methods (IR, 1H-NMR, 13C-NMR and MS). The in vitro cytotoxic activity of the synthesized derivatives was evaluated against two human cell lines: prostate cancer (PC-3) and colon cancer (HCT-116).

The altitude relight of a gas turbine combustor is an FAA and EASA regulation which dictates the successful re-ignition of an engine and its proper spool-up after an in-flight shutdown. Combustor pressure loss, ambient pressure, ambient temperature, and equivalence ratio were all studied on a full-scale, 3-cup, single-annular aviation combustor sector to create an ignition map. The flame development process was studied through the implementation of high-speed video. Testing was conducted by placing the sector horizontally upstream of an air jet ejector in a high altitude relight testing facility. Air was maintained at room temperature for varying pressure, and then the cryogenic heat exchanger was fed with liquid nitrogen to chill the air down to a limit of −50 deg F, corresponding with an altitude of 30,000 feet. Fuel was injected at constant equivalence ratios across multiple operating conditions, giving insight into the ignition map of the combustor sector. Results of testing indicated difficulty in achieving ignition at high altitudes for pressure drops greater than 2%, while low pressure drops show adequate performance. Introducing low temperatures to simulate the ambient conditions yielded a worse outcome, with all conditions having poor results except for 1%. High-speed video of the flame development process during the relight conditions across all altitudes yielded a substantial effect of the pressure drop on ignitability of the combustor. An increase in pressure drop was associated with a decrease in the likelihood of ignition success, especially at increasing altitudes. The introduction of the reduced temperature effect exacerbated this effect, further hurting ignition. High velocity regions in the combustor were detrimental to the ignition, and high area, low velocity regions aided greatly. The flame tended to settle into the corner recirculation zone and recirculate back into the center-toroidal recirculation zone (CTRZ), spreading downstream and likewise into adjacent swirl cups. These tests demonstrate the need for new combustor designs to consider adding large recirculation zones for combustor flame stability that will aid in relight requirements.

Cementation of hazardous organic liquid wastes such as radioactive liquid scintillator is receiving increasing importance. Using clay as natural adsorbent to improve the incorporation process of these organic wastes into cement paste was performed. The waste form composed of water/cement at the ratio 0.3 with 3 % solid natural clay by the weight of cement and incorporating up to 15 % real spent organic liquid scintillator waste by the weight of cement-based paste was prepared. The temperature changes accompanying with the cementation process were followed. The nominated solidified cement–clay composite was also subjected to free falling test at different heights to evaluate its structural stability during unexpected transportation events or disposal site impacts. Scanning electron microscopy and X-ray investigations were used to evaluate the microstructure of the composite. The results revealed that the proposed cement–clay composite could be nominated structurally as a durable matrix for incorporating up to 15 % of liquid scintillator safely. .

An advanced composite of cement and water extended polyester based on the recycled Poly(ethylene terephthalate) waste was developed to incorporate the borate waste. Previous studies have reported the characterizations of the waste form (cement–polymer composite immobilizing borate waste simulates) after 28 days of curing time. The current work studied the performance of waste form aged for 7 years and subjected to flooding scenario during 260 days using three types of water. The state of waste form was assessed at the end of each definite interval of the water infiltration through visual examination and mechanical measurement. Scanning electron microscopy, infrared spectroscopy, X-ray diffraction and thermal analyses were used to investigate the changes that may occur in the microstructure of the waste form under aging and flooding effects. The actual experimental results indicated reasonable evidence for the durable waste form. Acceptable consistency was confirmed for the waste form even after aging 7 years and exposure to flooding scenario for 260 days.

Objectives: To compare between the qualitative estimation of biochemical markers Point-of-Care testing) with the quantitative estimation of the same markers in the diagnosis of acute coronary syndrome (ACS). Design: Case-series study. Setting: This study was carried out in coronary care unit in Ibn- Sena Teaching Hospital in Mosul city from January to November, 2008. Participant: Sixty five patients with acute coronary syndrome (ACS) presented with chest pain. Main outcome measures: Three cardiac markers (Creatine kinase (CK-MB) activities (marker of necrosis), myoglobin (marker of muscle injury), and troponin I (marker of necrosis), were estimated qualitatively (near the patient= Point-of-Care testing), and quantitatively, and the results were compared. Kappa test was used for the association between the quantitative and qualitative test results. Results: The case-series study showed correlation of attributes between qualitative estimation results of troponin I, myoglobin and CK-MB and quantitative estimation results of the same parameters in (88.9%) tests. Conclusion: The early diagnosis of ACS might be facilitated by the use of qualitative point-of-care testing based on CK-MB, troponin I and myoglobin tests.

There is a growing keen interest aimed at recycling post-consumer poly(ethylene terephthalate), PET, wastes for both environmental and economic reasons. In this study ethanolamine (EA) has been investigated for aminolytic degradation of PET waste in the presence of dibutyl tin oxide (DBTO) as a catalyst. The process proceeds at 190 °C and under atmospheric pressure. The yield of white precipitate was subject to spectroscopic measurements (FT-IR, NMR, XRD and MS), to thermal analyses (DSC, DTA and TG) and to chemical testing (elemental analysis and solubility characterization). Based on the data reached from various examinations, the product formed is identified as bis(2-hydroxyethylene) terephthalamide (BHETA) which could be consider a source for differing polyurethanes. These kinds of materials have potential for many applications such as adhesives and coatings.

The determination of local convection heat transfer coefficients of pipe flow using pulsed laser heating (PLH) from a combination of experimental and numerical study is presented in this paper. The method is advantageous because it is fluid-independent, contact-free and high in spatial and temporal resolution. For simplicity, the experiment used water at different temperatures and flow rates inside two long circular tubes which were subject to radiation heating using a finite size (20 mm in diameter) pulsed laser beam. An infrared camera was used to image and measure its surface temperatures. Two correlations for convection heat transfer coefficient in the thermal/combined entry length region were used in this paper for comparison with the experimental results. The experimental results using the thermal circuit method processed by MATLAB® agree well with both correlations. To gain better insight and quantify the uncertainty, a 3-D conjugated heat transfer simulation was carried out using Fluent CFD. The implication of the accuracy and limitation of the PLH method on the determination of local heat transfer coefficients are also discussed in the analysis.Copyright © 2015 by ASME

This paper discusses the suitability of Ordinary Portland Cement (OPC), water-extended polyester (WEP), based on recycled polyethylene terephthalate (PET), composite for stabilization/solidification (S/S) of borate waste solution originating from the primary coolant circuit of pressurized water reactors (PWRs). This treatment is a new and attractive economical process that aims at keeping man and his environment healthy through controlling the dispersion of radioactive wastes (i.e., borate waste solution) and the solid plastic waste materials (i.e., PET). Mechanical integrity of the WEP as well as its polymer composite (PC) with OPC was studied under different experimental conditions. Compressive strength measurements for the final waste forms of PC containing borate waste simulate were also evaluated using various compositions of the PC (e.g., water of hydration, polymer:cement ratio, borate content, etc.) Based on the data obtained so far, it could be concluded that the candidate PC with the fo...

Paclitaxel (PTX) is used as first line treatment for metastatic breast cancer but the relief comes at a heavy cost in terms of accompanying adverse effects. The pharmaceutical credentials of PTX are further dampened by the intrinsically low aqueous solubility. In order to sideline such insidious tendencies, PTX was incorporated in a vitamin E nanoemulsion using high pressure homogenization. The encapsulation efficiency of PTX in nanoemulsion was 97.81±2.7% and a sustained drug release profile was obtained. PTX loaded nanoemulsion exhibited higher cytotoxicity in breast cancer cell line (MCF-7) when compared to free PTX and marketed formulation (Taxol). Cell cycle arrest study depicted that MCF-7 cells treated with PTX loaded nanoemulsion showed high arrest in G2-M phase. Moreover blank nanoemulsion induced additional apoptosis in breast cancer cells through G1-S arrest by disrupting mitochondrial membrane potential. Cytokine estimation study in macrophages showed that both PTX loaded nanoemulsion and blank nanoemulsion enhanced secretion of IL-12 and downregulated secretion of IL-4 and IL-10. Results suggest that inclusion of vitamin E in nanoemulsion opened multiple complementary molecular effects which not only magnified the principle antiproliferative activity of PTX but also independently showcased potential in restoring the proactive nature of the breast cancer slackened chronic immune response. In-vivo anticancer activity showed significantly improved efficacy of PTX loaded nanoemlsion compare to Taxol and free PTX. The list of plausible advantages of PTX nanoemulsification was further substantiated by acceptable haemolytic potential, reduced in-vivo toxicity and conveniently modified pharmacokinetic profile in which the AUC and MRT were extended considerably. Overall, there were strong evidences that developed formulation can serve as a viable alternative to currently available PTX options.

Objectives: Hypotestosteronemia has been reported in approximately half of type 2 diabetic men in general. This study aims to assess serum total testosterone levels in type 2 diabetics with erectile dysfunction and to correlate the degree of improvement between sildenafil citrate and testosterone levels. Methods: A cross sectional and prospective comparative interventional study was conducted at the Diabetic Clinic of Assalam Teaching Hospital in Mosul, during the period from January 1, 2009 through to December 31, 2011. The study enrolled 120 type 2 diabetic males with erectile dysfunction who were analyzed with regard to age, duration of diabetes, duration and severity of erectile dysfunction, serum total testosteron levels and the degree of response to sildenafil citrate in terms of testosterone levels. The data were statistically analyzed using the independent two-sample Student t test, χ 2 χ 2 χ test and Pearson correlation test. A p- value of

1. Dark urine and fever; markedly reduced RBC count, hemoglobin level, and hematocrit; reticulocytosis on hospital day 1 that resolved by hospital day 3 following transfusion of 5 doses of packed RBCs on day 1 (3 doses) and days 2 (1 dose) and 4 (1 dose); markedly elevated ESR, LD, and bilirubin (total, direct, and indirect) levels; a reduced haptoglobin level; a red and hazy urine containing detectable amounts of protein, ketones, urobilinogen, and a large amount of occult blood, along with microscopic findings of a large number of RBCs/hpf; positive antibody findings for Epstein-Barr virus viral capsid antigen IgG antibody (EBV VCA IgG Ab) and EBV nuclear antigen (NA) IgG antibodies; and positive direct antiglobulin test (DAT), using anti-C3 antiserum only, and strongly positive 3cell antibody screen findings at 4°C (Table 1).

Seven activated esters of indole-3-acetic acid (IAA) [4-oxo-1,2,3-benzotriazin-3-yl indole-3-acetate (IAA-3HBO), succinimido indole-3-acetate (IAA-NHS), 5-norbornene-1,3-dicarboximido indole-3-acetate (IAA-NHND), phthalimido indole-3-acetate (IAA-NHP), naphthalimido indole-3-acetate (IAA-NHN), 4-nitrophenyl indole-3-acetate (IAA-4NP), 8-quinolyl indole-3-acetate (IAA-8HQ)] were prepared and characterized. Their kinetics of aminolysis with butylamine, piperidine, and pyrrolidine in acetonitrile were investigated

Seven activated esters of indole-3-acetic acid (IAA) [4-oxo-1,2,3-benzotriazin-3-yl indole-3-acetate (IAA-3HBO), succinimido indole-3-acetate (IAA-NHS), 5-norbornene-1,3-dicarboximido indole-3-acetate (IAA-NHND), phthalimido indole-3-acetate (IAA-NHP), naphthalimido indole-3-acetate (IAA-NHN), 4-nitrophenyl indole-3-acetate (IAA-4NP), 8-quinolyl indole-3-acetate (IAA-8HQ)] were prepared and characterized. Their kinetics of aminolysis with butylamine, piperidine, and pyrrolidine in acetonitrile were investigated

This paper investigates the combustion dynamics of a single cup gas turbine combustor sector, a swirl-stabilized burner with dilution and cooling air holes. The burner was fueled by natural gas and was operated at one atmospheric pressure with various air inlet temperatures, air pressure drops, and air–fuel ratios. Acoustic emissions as functions of operating conditions were measured. Chemiluminescence imaging with a high-speed CCD camera and simultaneous dynamic pressure measurements has been used to characterize the combustor’s behavior. Imaging of the combustion energy release rate has provided an insight on the flame structure and its interaction with the dilution air jets. The combustion dynamics were correlated well with the heat release rate in the primary zone or in the dilution air jet region. Two low-frequency combustion dynamics modes (fuel-rich combustor domes with frequency around 420Hz, and fuel-lean combustor domes with frequency around 280 Hz) were identified by a dynamic microphone, dynamic pressure transducers, and a high-speed CCD camera. A two-dimensional distribution of the heat release rate dynamics (amplitude and phase angle) reveals different combustion dynamics driving mechanisms for fuel-lean and fuel rich modes. The acoustic emissions for the fuel-lean combustion mode correlated well with the energy release rate dynamics of the swirling jet inside the combustor dome. The acoustic emissions for the fuel-rich mode were associated with the unsteady chemical energy release rate from interactions between the dilution air jets and the fuel-rich mixture convected from the combustor dome.

An experimental study has been conducted to study the behavior of liquid jets injected into a crossflow containing a shear layer. The shea r layer was generated by merging two codirectional air streams of differing velocities. Th e injection liquid was water, and an injection diameter of 0.5 mm was used. An initial p art of this study used PIV and MieScattering to investigate the jet penetration and v elocity distribution. The current work furthers the investigation using PDPA to study the droplet size and volume flux distributions in the jet flow field. The parameters of interest w ere the ratio of the velocity of the two crossflowing streams creating the shear layer (R), and the liquid-air momentum flux ratio (q). The jet penetration increased for R > 1 an dde creased for R 1, higher SMD values were observed, but were uniformly distributed throughout the jet plume. For R < 1, SMD values were smaller, indicating better atomization. An increase in q increases the jet penetration and creates high SMD regions near the top of the jet periphery.

** † An experimental study has been conducted to study the behavior of liquid jets injected into a crossflow containing a shear layer, generated by merging two co-directional air streams of differing velocities. The injection liquid was water, and a nozzle diameter of 0.5 mm was used. Two streamwise locations were available for jet injection, 6.35 cm and 15.24 cm from the location of the merging of the two airstreams. Mie-scattering and Particle Image Velocimetry (PIV) were used to investigate the jet behavior. The structure of the flow containing the shear layer, and the jet penetration and the droplet velocity distribution were studied. The parameters of interest were the ratio of velocity of the two air streams (R), the aerodynamic Weber number (We), the liquid-air momentum ratio (q) and the streamwise location of jet injection (Xi). For R > 1, the jets penetrate further into the crossflow, but spray coverage gets confined to the upper portion of the jet trajectory. For R < 1, the penetration is lesser, but uniform spray coverage was obtained. As the injection location moves further downstream, more mixing occurs between the two airstreams, weakening the shear layer. As a result, the effects of the shear layer on the jet also get dampened.

Abstract 1809 Poster Board I-835 Bone marrow infiltration by myeloma cells and osteolytic bone lesions are the major features of Multiple Myeloma. Magnetic Resonance Imaging (MRI) has been used in MM not only to image bone marrow (BM) and to identify lytic bone disease but to also evaluate therapeutic response and prognosis. Gadolinium (Gd)-based contrast agents are frequently used to enhance MRI resolution. We evaluated effect of the most common Gd-containing agent, Omniscan, on myeloma cells. We observed that Omniscan induced both time and dose dependent MM cell growth in vitro (8-20 fold increase relative to control). Importantly, the presence of BMSC enhanced the effect of Omniscan on growth of both MM cell lines and primary MM cells. However, Omniscan was not able to overcome cytotoxic effects of conventional and novel agents in MM. This growth promoting effects were not observed on normal BM stromal cells. Evaluating the molecular mechanism of action of Omniscan on MM cells, we observed time dependent ERK1/2 phosphorylation as well as reversal of growth promoting effects of Omniscan by specific inhibition of ERK signaling; however, Omniscan had no effect on STAT3 and AKT signaling pathways. Next, we investigated in vivo effect of Omniscan in a murine xenograft model of MM. Following detection of tumor, mice were treated with either iv Omniscan or PBS. Treatment with Omniscan significantly induced MM tumor growth compared to control mice (1042 ±243 mm3 vs 502 ±137 mm3 respectively; p=0.0001). Finally in autopsies in 8 MM patients with repeated exposure to Omniscan, we quantified gadolinium in various tissues using Inductively-coupled mass spectrometry. We observed massive quantities of gadolinium accumulation in tissues of these MM patients regardless of their renal function. These results, confirming both in vitro and in vivo growth promoting effects of Gd-containing contrast agent on MM, suggest the need for further analysis of the mechanism of its action on myeloma cells and careful analysis of its clinical impact in MM patients undergoing MRI evaluation. Disclosures No relevant conflicts of interest to declare.

Abstract 1105 Poster Board I-127 Genetic recombination plays a critical role in telomere maintenance, chromosomal translocation, and gene amplification, and may therefore underlie the chromosomal aberrations observed with high frequency in number of malignancies. The molecular mechanism/s inducing genomic instability remains ill-defined and their elucidation may provide methods to prevent tumor progression and development of drug resistance. Our earlier work has demonstrated that homologous recombination (HR) activity is elevated in multiple myeloma (MM) cells and leads to increased rate of mutation and progressive accumulation of genetic variation over time. We have further demonstrated that the inhibition of HR activity in MM cells by siRNAs targeting recombinase leads to significant reduction in the acquisition of new genetic changes in the genome; and conversely, induction of HR activity leads to significant elevation in the number of new mutations over time, and development of drug resistance in MM cells. Here we have evaluated a PI3K inhibitor Wortmaninin which has significant inhibitory activity against both HR and non-HR (nHR) pathways. Exposure of MM cells (OPM1, ARP and RPMI 8226) to wortmannin (WM) led to reduced expression of recombinase (hsRAD51) and nearly complete inhibition of HR activity, within 24 hrs as determined by a plasmid based assay in which generation of active gene product by recombination is measured. Similarly nHR was evaluated by measuring generation of intact gene product from a linearized plasmid. We evaluated effect of WM on nHR by 3 hours preincubation before transfecting the plasmid followed by cell culture for 72 hrs at 37° C. Cells were harvested and analyzed for nHR as previously described. Treatment with WM led to >40% reduction in nHR, indicating that WM affects both HR and NHR pathways. Downregulation of these pathways by wortmannin was also associated with a reduced growth rate of myeloma cells in culture by 20-25% at 48 hours. Importantly, WM treatment markedly decreased the acquisition of new genomic changes in MM as measured by genome-wide loss of heterozygosity assay as an indicator of genomic stability. To evaluate the impact of WM on in vivo tumor growth, OPM1 cells were injected subcutaneously in SCID mice and following appearance of palpable tumors, mice were treated with WM at 0.75 mg/kg, injecting daily intraperitoneally. Treatment with WM was associated with almost complete inhibition of tumor growth in vivo. Long term exposure of myeloma cells to WM was consistently associated with reduced telomere length, probably by blocking HR dependent ALT pathway. These data identifies dysregulated recombination activity as a key mediator of DNA instability and progression of MM, and WM as a potential therapeutic agent for prevention of myeloma progression and possibly drug resistance. Disclosures Anderson: Millenium: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Munshi:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis : Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

While it is well known that chair forms of cyclohexane can interconvert without passing through the boat conformation, the same statement frequently comprises a source of confusion regarding the location of the boat conformation on the energy surface of the conformational inversion of cyclohexane. To alleviate this problem, a novel three-dimensional energy diagram has been introduced showing explicitly how the chair forms of cyclohexane interconvert through twist conformations along a first reaction coordinate that coincides with the x direction of a Cartesian system of coordinates, while simultaneously the twist conformations have the potential to interconvert through boat conformation transition states (pseudorotation) along a second reaction coordinate that coincides with the y direction of the same system of coordinates.