Although the overall dynamics of globular clusters involves many complexities, much of their dynamics can be understood on the basis of some simple and straightforward physical arguments. Those ...arguments are presented here, in an effort to lead the reader through the basic stages of cluster dynamics in a quick and easy way.
We present the first results of a large Advanced Camera for Surveys (ACS) survey of Galactic globular clusters. This Hubble Space Telescope (HST) Treasury project is designed to obtain photometry ...with S/N (signal-to-noise ratio) 10 for main-sequence stars with masses 0.2 M in a sample of globulars using the ACS Wide Field Channel. Here we focus on clusters without previous HST imaging data. These include NGC 5466, NGC 6779, NGC 5053, NGC 6144, Palomar 2, E3, Lynga 7, Palomar 1, and NGC 6366. Our color-magnitude diagrams (CMDs) extend reliably from the horizontal branch to as much as 7 mag fainter than the main-sequence turnoff and represent the deepest CMDs published to date for these clusters. Using fiducial sequences for three standard clusters (M92, NGC 6752, and 47 Tuc) with well-known metallicities and distances, we perform main-sequence fitting on the target clusters in order to obtain estimates of their distances and reddenings. These comparisons, along with fitting the cluster main sequences to theoretical isochrones, yield ages for the target clusters. We find that the majority of the clusters have ages that are consistent with the standard clusters at their metallicities. The exceptions are E3, which appears ~2 Gyr younger than 47 Tuc, and Pal 1, which could be as much as 8 Gyr younger than 47 Tuc.
VNP20009, a genetically modified strain of Salmonella typhimurium with deletions in the msbB and purI loci, exhibited antitumor activities when given systemically to tumor-bearing mice. VNP20009 ...inhibited the growth of subcutaneously implanted B16F10 murine melanoma, and the human tumor xenografts Lox, DLD-1, A549, WiDr, HTB177, and MDA-MB-231. A single intravenous injection of VNP20009, at doses ranging from 1 x 10(4) to 3 x 10(6) cfu/mouse, produced tumor growth inhibitions of 57-95%. Tumor volume doubling time, another indicator for tumor growth inhibition, also significantly increased in mice treated with VNP20009. Using mice with immune system deficiencies, we also demonstrated that the antitumor effects of VNP20009 did not depend on the presence of T and B cells. In addition, VNP20009, given intravenously, inhibited the growth of lung metastases in mice. Only live bacteria showed the antitumor effect.
1. Laromustine (VNP40101M, also known as Cloretazine) is a novel sulfonylhydrazine alkylating (anticancer) agent. This article describes the use of quantitative whole-body autoradiography (QWBA) and ...mass balance to study the tissue distribution, the excretion mass balance and pharmacokinetics after intravenous administration of
14
CVNP40101M to rats. A single 10 mg/kg IV bolus dose of
14
CVNP40101M was given to rats.
2. The recovery of radioactivity from the Group 1 animals over a 7-day period was an average of 92.1% of the administered dose, which was accounted for in the excreta and carcass. Most of the radioactivity was eliminated within 48 h via urine (48%), with less excreted in feces (5%) and expired air accounted for (11%). The plasma half-life of
14
Claromustine was approximately 62 min and the peak plasma concentration (C
max
) averaged 8.3 μg/mL.
3. The QWBA study indicated that the drug-derived radioactivity was widely distributed to tissues through 7 days post-dose after a single 10 mg/kg IV bolus dose of
14
CVNP40101M to male pigmented Long-Evans rats. The maximum concentrations were observed at 0.5 or 1 h post-dose for majority tissues (28 of 42). The highest concentrations of radioactivity were found in the small intestine contents at 0.5 h (112.137 µg equiv/g), urinary bladder contents at 3 h (89.636 µg equiv/g) and probably reflect excretion of drug and metabolites. The highest concentrations in specific organs were found in the renal cortex at 1 h (28.582 µg equiv/g), small intestine at 3 h (16.946 µg equiv/g), Harderian gland at 3 h (12.332 µg equiv/g) and pancreas at 3 h (12.635 µg equiv/g). Concentrations in the cerebrum (1.978 µg equiv/g), cerebellum (2.109 µg equiv/g), medulla (1.797 µg equiv/g) and spinal cord (1.510 µg equiv/g) were maximal at 0.5 h post-dose and persisted for 7 days.
4. The predicted total body and target organ exposures for humans given a single 100 µCi IV dose of
14
CVNP40101M were well within the medical guidelines for maximum radioactivity exposures in human subjects.
<!CDATA
The Handbook of Economic Sociology, Second Edition is the most comprehensive and up-to-date treatment of economic sociology available. The first edition, copublished in 1994 by Princeton ...University Press and the Russell Sage Foundation as a synthesis of the burgeoning field of economic sociology, soon established itself as the definitive presentation of the field, and has been widely read, reviewed, and adopted. Since then, the field of economic sociology has continued to grow by leaps and bounds and to move into new theoretical and empirical territory.
The second edition, while being as all-embracing in its coverage as the first edition, represents a wholesale revamping. Neil Smelser and Richard Swedberg have kept the main overall framework intact, but nearly two-thirds of the chapters are new or have new authors. As in the first edition, they bring together leading sociologists as well as representatives of other social sciences. But the thirty chapters of this volume incorporate many substantial thematic changes and new lines of research--for example, more focus on international and global concerns, chapters on institutional analysis, the transition from socialist economies, organization and networks, and the economic sociology of the ancient world. The Handbook of Economic Sociology, Second Edition is the definitive resource on what continues to be one of the leading edges of sociology and one of its most important interdisciplinary adventures. It is a must read for all faculty, graduate students, and undergraduates doing work in the field.
A thoroughly revised and updated version of the most comprehensive treatment of economic sociology available
Almost two-thirds of the chapters are new or have new authors
Authors include leading sociologists as well as representatives of other social sciences
Substantial thematic changes and new lines of research, including more focus on international and global concerns, institutional analysis, the transition from socialist economies, and organization and networks
The definitive resource on what continues to be one of the leading edges of sociology and one of its most important interdisciplinary adventures
A must read for faculty, graduate students, and undergraduates doing work in the field
>
1. Alkylating agents are capable of introducing an alkyl group into nucleophilic sites on DNA or RNA through covalent bond. Laromustine is an active member of a relatively new class of ...sulfonylhydrazine prodrugs under development as antineoplastic alkylating agents, and displays significant single-agent activity.
2. This is the first report of the population pharmacokinetic analysis of laromustine, 106 patients, 66 with hematologic malignancies and 40 with solid tumors, participated in five clinical trials worldwide. Of these, 104 patients were included in the final NONMEM analysis.
3. The population estimates for total clearance (CL) and volume of distribution of the central compartment (V
1
) were 96.3 L/h and 45.9 L, associated with high inter-patient variability of 52.9% and 79.8% and inter-occasion variability of 26.7% and 49.3%, respectively. The population estimates for Q and V
2
were 73.2 L/h and 29.9 L, and inter-patient variability in V
2
was 63.1%, respectively.
4. The estimate of V
ss
(75.8 L) exceeds total body water, indicating that laromustine is distributed to tissues. The half-life is short, less than 1 h, reflecting rapid clearance. Population PK analysis showed laromustine pharmacokinetics to be independent of dose and organ function with no effect on subsequent dosing cycles.
The ideal anticancer regimen is one that is specific for cancer cells with limited toxicity to normal tissues. Genetically modified, nonpathogenic Salmonella offer a potential way to induce direct ...tumoricidal activity or to deliver tumoricidal agents to tumors. An attenuated strain of Salmonella typhimurium, called VNP20009, and its derivative TAPET-CD (which expresses Escherichia coli cytosine deaminase) are highly selective for tumor tissue and can deliver therapeutic proteins preferentially to tumors in preclinical models. Both VNP20009 and TAPET-CD have been investigated successfully in Phase 1 clinical trials in cancer patients.
PDF
