Adventures in radioisotope research; the collected papers of George Hevesy.

2

Sedimentation rates calculated on surface sediment samples from different site of the Atlantic and Pacific Oceans (Table 1)

Radiocarbon ages on CaCO3 from deep-sea cores offer constraints on the nature of the CaCO3 dissolution process. The idea is that the toll taken by dissolution on grains within the core top bioturbation zone should be in proportion to their time of residence in this zone. If so, dissolution would shift the mass distribution in favor of younger grains, thereby reducing the mean radiocarbon age for the grain ensemble. We have searched in vain for evidence supporting the existence of such an age reduction. Instead, we find that for water depths of more than 4 km in the tropical Pacific the radiocarbon age increases with the extent of dissolution. We can find no satisfactory steady state explanation and are forced to conclude that this increase must be the result of chemical erosion. The idea is that during the Holocene the rate of dissolution of CaCO3 has exceeded the rain rate of CaCO3. In this circumstance, bioturbation exhumes CaCO3 from the underlying glacial sediment and mixes it with CaCO3 raining from the sea surface.

Applications of iodine-123 in nuclear medicine : proceedings of a conference held in Rockville, Maryland, May 19-20, 1975.

Mode of access: Internet.

Use of the Radioisotopic Sand Tracer (RIST) system /

"June 1975."

Retention efficiencies of charcoal traps for fission gases : technical report /

"August 23, 1957."

Retention efficiencies of selected adsorbents for krypton : technical report /

"April 15, 1958."

A conference on the use of isotopes in plant and animal research,

Includes bibliographical references.

Determination of sediment density by gamma attenuation /

Mode of access: Internet.

Report: Course on "principles and practice of radioisotope usage in biological research"; Spring semester--1959.

Mode of access: Internet.

Proceedings of the second Japan Conference on Radioisotopes, 1958.

Sponsored by the Japan Atomic Industrial Forum and Japan Radioisotopes Association.

Tagged atom method of studying the biosynthesis of chlorophyll (Metod mechenych atomov v izuchenii biosinteza chlorofilla)

Translated from a publication of the Academy of Sciences, of Belorussiya, S.S.R., Minsk, 1956.

Radioisotope renography: a kidney function test performed with radioisotope-labeled agents.

Includes bibliography.

The contribution of atomic energy to agriculture.

Mode of access: Internet.

Discovery and Characterization of a Novel Fatty Acid Synthase Inhibitor with Antineoplastic Activity against Breast Cancer

During oncogenesis, cancer cells go through metabolic reprogramming to maintain their high growth rates and adapt to changes in the microenvironment and the lack of essential nutrients. Several types of cancer are dependent on de novo fatty acid synthesis to sustain their growth rates by providing precursors to construct membranes and produce vital signaling lipids. Fatty acid synthase (FASN) catalyze the terminal step of de novo fatty acid synthesis and it is highly expressed in many types of cancers where it’s up-regulation is correlated with cancer aggressiveness and low therapeutic outcome. Many FASN inhibitors were developed and showed potent anticancer activity however, only one inhibitor advanced to early stage clinical trials with some dose limiting toxicities. Using a modified fluorescence-linked enzyme chemoproteomic strategy (FLECS) screen, we identified HS-106, a thiophenopyrimiden FASN inhibitor that has anti-neoplastic activity against breast cancer in vitro and in vivo. HS-106 was able to inhibit both; purified human FASN activity and cellular fatty acid synthesis activity as evaluated by radioactive tracers incorporation into lipids experiments. In proliferation and apoptosis assays, HS-106 was able to block proliferation and induce apoptosis in several breast cancer cell lines. Several rescue experiment and global lipidome analysis were performed to probe the mechanism by which HS-106 induces apoptosis. HS-106 was found to induce several changes in lipids metabolism: (i) inhibit fatty acids synthesis. (ii) Inhibit fatty acids oxidation as indicated by the ability of inhibiting Malonyl CoA accumulation to block HS-106 induced apoptosis and the increase in the abundance of ceramides. (iii) Increase fatty acids uptake and neutral lipids formation as confirmed 14C Palmitate uptake assay and neutral lipids staining. (iv)Inhibit the formation of phospholipids by inhibiting de novo fatty acid synthesis and diverting exogenous fatty acids to neutral lipids. All of these events would lead to disruption in membranes structure and function. HS-106 was also tested in Lapatinib resistant cell lines and it was able to induce apoptosis and synergizes Lapatinib activity in these cell lines. This may be due the disruption of lipid rafts based on the observation that HS-106 reduces the expression of both HER2 and HER3. HS-106 was found to be well tolerated and bioavailable in mice with high elimination rate. HS-106 efficacy was tested in MMTV neu mouse model. Although did not significantly reduced tumor size (alone), HS-106 was able to double the median survival of the mice and showed potent antitumor activity when combined with Carboplatin. Similar results were obtained when same combinations and dosing schedule was used in C3Tag mouse model except for the inability of HS-106 affect mice survival.

From the above, HS-106 represent a novel FASN inhibitor that has anticancer activity both in vivo and in vitro. Being a chemically tractable molecule, the synthetic route to HS-106 is readily adaptable for the preparation of analogs that are similar in structure, suggesting that, the pharmacological properties of HS-106 can be improved.

Evaluation of Cross Correlation Technique to Measure Flow in Pipes of the Oil Industry

The present work is concerned with the use of the cross correlation technique to measure delay time between two simulated signals displaced with respect to time, in order to develop a cross correlator system that will be used to measure the water and oil pipes flowrate in which the detection system is composed by two external low intensity radiation sources located along the tube and two NaI(Tl) gamma-ray detectors. The final purpose of the correlator system is to use the natural disturbances, as the turbulence in the own flow rather than to inject radioactive tracers to the fluid flow as usually is carried out. In the design of this correlator is evaluated the point-by-point calculation method for the cross correlation function in order to produce a system accurate and fast. This method is divided at the same time in three modes of operation: direct, relay and polarity.