INSTABILITY STUDIES WITH EBR-I, MARK III

The results of instability studies suggest that the operational characteristics of the fully ribbed and rigid Mark III loading are governed by feedback processes that guarantee safe and stable operation under normal operating condiiions. No evidence of positive reactivity effects was noted for the fully-ribbed rigid core. Logical extrapolations of full-power full-flow test data indicate that the reactor could be brought into a resonant condition for power levels exceeding 1000 Mw. Strong nonlinearities were observed in power coefficients and were considered to pose no serious operational problems above 200 kw in the power range associated with the tests. An application of the Nyquist stability criterion to the extrapolated fully sheared data results in the conclusion that the reactor would attain resonance instability at full flow at - 11 Mw. Logical extrapolations of test data for one-third flow results in resonance instability at -10 Mw, a power level -20 times that designed for onethird flow. Rib shearing was shown to result in an unexpected and unexplained increase in the magnitude of the delayed structural power coefficient component. An empirical fit of feedback data to a model describing the dynamic and static behavior of the partially sheared core resulted in ihe values for the respective prompt negative, rod-bowing, and delayed structural power coefficient components of -2.21 x 10/sup -6/ +0.543 x 10/sup -6/ and -0.873 x 10/sup -6/4 delta /k/kw. The over all behavior of the Mark III core, whether fully ribbed and rigid, fully ribbed and loose, or even partially or fully sheared, is one of extreme stability. The inclusion of stabilizing ribs and a system of tightening rods in the Mark lII design elimuinated, or at least reduced to a point beyond detection, the prompt positive rod-bowing component that existed in the Mark II. (B.O.G.

Categorical versus continuous circulating tumor cell enumeration as early surrogate marker for therapy response and prognosis during docetaxel therapy in metastatic prostate cancer patients

Background: Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel. Methods: CTC-counts were assessed in 122 serial samples, as continuous or categorical (= 5 CTCs) variables, at baseline (q0) and after 1 (q1),4 (q4) and 10 (q10) cycles of docetaxel (3-weekly, 75 mg/m2) in 33 mCRPC patients. Treatment response (TR) was defined as non-progressive (non-PD) and progressive disease (PD),by morphologic RECIST or clinical criteria at q4 and q10. Binary logistic and Cox proportional hazards regression analyses were used as statistical methods. Results: Categorical CTC-count status predicted PD at q4 already after one cycle (q1) and after 4 cycles (q4) of chemotherapy with an odds ratio (OR) of 14.9 (p = 0.02) and 18.0 (p = 0.01). Continuous CTC-values predicted PD only at q4 (OR 1.04, p = 0.048). Regarding PFS, categorical CTC-counts at q1 were independent prognostic markers with a hazard ratio (HR) of 3.85 (95 % CI 1.1-13.8, p = 0.04) whereas early continuous CTC-values at q1 failed significance (HR 1.02, 95 % CI 0.99-1.05, p = 0.14). For OS early categorical and continuous CTC-counts were independent prognostic markers at q1 with a HR of 3.0 (95 % CI 1.6-15.7, p = 0.007) and 1.02 (95 % CI 1.0-1.040, p = 0.04). Conclusions: Categorical CTC-count status is an early independent predictor for TR, PFS and OS only 3 weeks following treatment initiation with docetaxel whereas continuous CTC-counts were an inconsistent surrogate marker in mCRPC patients. For clinical practice, categorical CTC-counts may provide complementary information towards individualized treatment strategies with early prediction of treatment efficacy and optimized sequential treatment

Argonne National Laboratory Report ANL-6408

Report documenting the fast zero power reactor experiment (ZPRG-III). This includes a description of the experiment and the reactor, hazards, and accidents

A Mechanism Explaining the Instability of EBR-I, Mark III

Presented at the International Atomic Energy Agencysponsored Seminar on the Physics of Fast and Intermediate Reactors. Vienna, August 3-11, 196l. A feedback model, was developed to account for resonant instabilities in the Mark II core. In this model, the prompt positive power coefficient effect is ascribed to fuel rod bowing and the delayed negative power coefficient effect to thermally lnduced motions in the lower shield plate. Since this model is supported by observations, it is concluded that the instability of Mark II is chiefly due to lack of radial coupling between fuel rods. (D.L.C.

Liposomal Hsp90 cDNA induces neovascularization via nitric oxide in chronic ischemia

Objective: Induction of angiogenesis has been reported subsequent to eNOS overexpression or activation, the latter involving Hsp90 as a chaperone protein. Here, we investigated the potential of regional Hsp90 overexpression to induce therapeutic neovascularization in vivo in a chronic rabbit hindlimb ischemia model. Methods: In rabbits (n=7 per group), the external femoral artery was excised at day 0 (0). At d7, liposomes containing eGFP (control group) or Hsp90 were retroinfused into the anterior tibial vein. At day 7 and day 35, angiographies were obtained and analyzed for collateral formation and perfusion velocity (frame count score) (% of d7 values). Capillary/muscle fiber (C/MF) ratio was calculated from five muscle areas of the ischemic limb. L-NAME and Geldanamycin were co-applied, where indicated. Results: Compared to mock-treated controls, Hsp90 transfected increased C/MF ratio at day 35 (1.78 +/- 0.15 vs. 1.19 +/- 0.13, p<0.05), an effect blunted by L-NAME (1.39 +/- 0.11). Hsp90 transfection increased collateral formation (157 +/- 11% vs. 110 +/- 13%) and frame count score (174 +/- 18% vs. 117 +/- 10%), both sensitive to inhibition by L-NAME coapplication (135 +/- 17% and 134 +/- 14%, respectively). Of note, C/MF ratio was found elevated 3 days after Hsp90 transfection (1.61 +/- 0.16 at d10), at a time point when collateral formation was unchanged (106 6%), and tended to remain elevated in the presence of L-NAME applied thereafter (1.64 +/- 0.35 at d35), though L-NAME blocked subsequent changes in collateral growth or increase in perfusion at d35. Conclusions: We conclude that Hsp90 is capable of inducing angiogenesis and arteriogenesis via nitric oxide (NO) in a rabbit model of chronic ischemia. Our findings describe the capillary level as an initial site of Hsp90-cDNA-induced neovascularization, followed by growth of larger conductance vessels, resulting in an improved hindlimb perfusion. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reseved

HAZARD EVALUATION REPORT ON THE FAST REACTOR ZERO POWER EXPERIMENT (ZPR- III)

An evaluation was made of the hazards associated with studies of the use of U/sup 235/ as fuel in the Fast Reactor Zero Power Experiment (ZPR-III) in the design of EBR-II. The systems are blanketed cores having a range of compositions in which the volume fractions of U/sup 235/, U/sup 238/ Fe, and Na are varied. Methods used for protection against accident or damage are described. Excursions resulting if the safety mechanisms did not operate are discussed. (M.C.G.