The pharmacologic basis of high dose chemotherapy with haematopoietic stem cell support for solid tumours

The theoretical basis of high dose chemotherapy with haematopoietic stem cell support (HDT) for solid tumours is the presumption of a linear, steep dose-response relationship for chemotherapy conditioning agents. We review preclinical pharmacologic studies evaluating steep dose-response relationships for different chemotherapeutic agents, identified through a MED-LINE and CANCER-LIT search of the English medical literature from January 1966 to December 1999. Only BCNU, melphalan, nitrogen mustard, and the combination of thiotepa and cyclophosphamide demonstrated steep dose-response relationships over a wide dose-range. The pharmacologic evidence for the use of other antineoplastic agents for HDT in solid tumours is non-existent. More preclinical studies are needed for a rational development of this therapeutic approach for solid tumours. © 2001 Cancer Research Campaign http://www.bjcancer.co

Apolipoprotein E Allelic Frequency Altered in Women with Early-onset Breast Cancer

Among women, the most prevalent type of cancer is breast cancer, affecting 1 out of every 8 women in the United States; in Puerto Rico, 70 out of every 100,000 will develop some type of breast cancer. Therefore, a better understand of the potential risk factors for breast cancer could lead to the development of early detection tools. A gene that has been proposed as a risk factor in several populations around the world is Apolipoprotein E (apoE). ApoE functions as a mechanism of transport for lipoproteins and cholesterol throughout the body, with 3 main isoforms present in humans (apoE2, apoE3, and apoE4). Whether or not apoE4 is a risk factor for breast cancer remains controversial. Previous studies have either included test subjects of all ages (20–80) or have focused on late-onset (after age 50) breast cancer; none has concentrated specifically on early-onset (aged 50 and younger) breast cancer. The objectives of this study was to examine (in a Puerto Rican population) the differences in the relative frequency of occurrence of apoE4 in non-breast cancer versus breast cancer patients and to examine, as well, the potential differences of same in early- versus late-onset patients. We found an increased frequency of apoE4 (odds ratio 2.15) only in early-onset breast cancer survivors, which is similar to the findings of those studies that combined or adjusted for age as well as for an association between apoE4 and decreased tumor size. ApoE is also a potential risk factor for long-term cognitive effects after chemotherapy and affects response to hormone replacement. Our data supports the theory that knowing the apoE genotype of women who are at risk of developing breast cancer may be beneficial, as such knowledge would aid in the prediction of tumor size and the development of treatment regimens

LOTIS Upper Limits and the Prompt OT from GRB 990123

GRB 990123 established the existence of prompt optical emission from gamma-ray bursts (GRBs). The Livermore Optical Transient Imaging System (LOTIS) has been conducting a fully automated search for this kind of simultaneous low energy emission from GRBs since October 1996. Although LOTIS has obtained simultaneous, or near simultaneous, coverage of the error boxes obtained with BATSE, IPN, XTE, and BeppoSAX for several GRBs, image analysis resulted in only upper limits. The unique gamma-ray properties of GRB 990123, such as very large fluence (top 0.4%) and hard spectrum, complicate comparisons with more typical bursts. We scale and compare gamma-ray properties, and in some cases afterglow properties, from the best LOTIS events to those of GRB 990123 in an attempt to determine whether the prompt optical emission of this event is representative of all GRBs. Furthermore, using LOTIS upper limits in conjunction with the relativistic blast wave model, we weakly constrain the GRB and afterglow parameters such as density of the circumburster medium and bulk Lorentz factor of the ejecta.Comment: 5 pages, 2 figures, To appear in Proceedings of the 5th Huntsville Gamma-Ray Burst Symposiu

LOTIS Search for Early Time Optical Afterglows: GRB 971227

We report on the very early time search for an optical afterglow from GRB 971227 with the Livermore Optical Transient Imaging System (LOTIS). LOTIS began imaging the `Original' BATSE error box of GRB 971227 approximately 14 s after the onset of gamma-ray emission. Continuous monitoring of the position throughout the evening yielded a total of 499 images (10 s integration). Analysis of these images revealed no steady optical afterglow brighter than R=12.3 +- 0.2 in any single image. Coaddition of different combinations of the LOTIS images also failed to uncover transient optical emission. In particular, assuming a constant early time flux, no optical afterglow brighter than R=14.2 +- 0.2 was present within the first 1200 s and no optical afterglow brighter than R=15.0 +- 0.2 was present in the first 6.0 h. Follow up observations by other groups revealed a likely X-ray afterglow and a possible optical afterglow. Although subsequent deeper observations could not confirm a fading source, we show that these transients are not inconsistent with our present knowledge of the characteristics of GRB afterglows. We also demonstrate that with the upgraded thermoelectrically cooled CCDs, LOTIS is capable of either detecting very early time optical afterglow or placing stringent constraints on the relationship between the gamma-ray emission and the longer wavelength afterglow in relativistic blast wave models.Comment: 17 pages, 3 eps figures, revisions based on reviewers comment

The Taiwanese-American Occultation Survey: The Multi-Telescope Robotic Observatory

The Taiwanese-American Occultation Survey (TAOS) operates four fully automatic telescopes to search for occultations of stars by Kuiper Belt Objects. It is a versatile facility that is also useful for the study of initial optical GRB afterglows. This paper provides a detailed description of the TAOS multi-telescope system, control software, and high-speed imaging.Comment: 11 pages, 11 figure

The TAOS Project Stellar Variability I. Detection of Low-Amplitude delta Scuti Stars

We analyzed data accumulated during 2005 and 2006 by the Taiwan-American Occultation Survey (TAOS) in order to detect short-period variable stars (periods of <~ 1 hour) such as delta Scuti. TAOS is designed for the detection of stellar occultation by small-size Kuiper Belt Objects (KBOs) and is operating four 50cm telescopes at an effective cadence of 5Hz. The four telescopes simultaneously monitor the same patch of the sky in order to reduce false positives. To detect short-period variables, we used the Fast Fourier Transform algorithm (FFT) inasmuch as the data points in TAOS light-curves are evenly spaced. Using FFT, we found 41 short-period variables with amplitudes smaller than a few hundredths of a magnitude and periods of about an hour, which suggest that they are low-amplitude delta Scuti stars (LADS). The light-curves of TAOS delta Scuti stars are accessible online at the Time Series Center website (http://timemachine.iic.harvard.edu)Comment: Accepted for publication in A

Optical Properties of Deep Ice at the South Pole - Absorption

We discuss recent measurements of the wavelength-dependent absorption coefficients in deep South Pole ice. The method uses transit time distributions of pulses from a variable-frequency laser sent between emitters and receivers embedded in the ice. At depths of 800 to 1000 m scattering is dominated by residual air bubbles, whereas absorption occurs both in ice itself and in insoluble impurities. The absorption coefficient increases approximately exponentially with wavelength in the measured interval 410 to 610 nm. At the shortest wavelength our value is about a factor 20 below previous values obtained for laboratory ice and lake ice; with increasing wavelength the discrepancy with previous measurements decreases. At around 415 to 500 nm the experimental uncertainties are small enough for us to resolve an extrinsic contribution to absorption in ice: submicron dust particles contribute by an amount that increases with depth and corresponds well with the expected increase seen near the Last Glacial Maximum in Vostok and Dome C ice cores. The laser pulse method allows remote mapping of gross structure in dust concentration as a function of depth in glacial ice.Comment: 26 pages, LaTex, Accepted for publication in Applied Optics. 9 figures, not included, available on request from [email protected]

A Close Binary Star Resolved from Occultation by 87 Sylvia

The star BD+29 1748 was resolved to be a close binary from its occultation by the asteroid 87 Sylvia on 2006 December 18 UT. Four telescopes were used to observe this event at two sites separated by some 80 km apart. Two flux drops were observed at one site, whereas only one flux drop was detected at the other. From the long-term variation of Sylvia, we inferred the probable shape of the shadow during the occultation, and this in turn constrains the binary parameters: the two components of BD+29 1748 have a projected separation of 0.097" to 0.110" on the sky with a position angle 104 deg to 107 deg. The asteroid was clearly resolved with a size scale ranging from 130 to 290 km, as projected onto the occultation direction. No occultation was detected for either of the two known moonlets of 87 Sylvia.Comment: 12 pages, 4 figures, 2 tables; submitted to the PAS

First Results From The Taiwanese-American Occultation Survey (TAOS)

Results from the first two years of data from the Taiwanese-American Occultation Survey (TAOS) are presented. Stars have been monitored photometrically at 4 Hz or 5 Hz to search for occultations by small (~3 km) Kuiper Belt Objects (KBOs). No statistically significant events were found, allowing us to present an upper bound to the size distribution of KBOs with diameters 0.5 km < D < 28 km.Comment: 5 pages, 5 figure, accepted in Ap

The AMANDA Neutrino Telescope: Principle of Operation and First Results

AMANDA is a high-energy neutrino telescope presently under construction at the geographical South Pole. In the Antarctic summer 1995/96, an array of 80 optical modules (OMs) arranged on 4 strings (AMANDA-B4) was deployed at depths between 1.5 and 2 km. In this paper we describe the design and performance of the AMANDA-B4 prototype, based on data collected between February and November 1996. Monte Carlo simulations of the detector response to down-going atmospheric muon tracks show that the global behavior of the detector is understood. We describe the data analysis method and present first results on atmospheric muon reconstruction and separation of neutrino candidates. The AMANDA array was upgraded with 216 OMs on 6 new strings in 1996/97 (AMANDA-B10), and 122 additional OMs on 3 strings in 1997/98.Comment: 36 pages, 23 figures, submitted to Astroparticle Physic