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The Preparation of Carbon-Metal Replicas for the Study of Carboniferous Coal Ball Fossils: Replication and Cleaning Procedures

In the early stages of a previous study of fossil spores of Botryopteris globosa and B. americana from the Carboniferous (Phillips & Rosso, 1970), considerable difficulty was encountered in replicating and cleaning spore materials and associ- ated debris from the carbon-platinum spore replicas. After numerous attempts to clean these carbon films, the techniques presented in this paper proved ef- ficient and reliable for transmission electron microscope examination of Botry- opteris spores found in calcified coal ball fossils

Repurposing cancer drugs, batimastat and marimastat, to inhibit the activity of a group I metalloprotease from the venom of the Western Diamondback rattlesnake, Crotalus atrox

Snakebite envenomation causes over 140,000 deaths every year predominantly in developing countries. As a result, it is one of the most lethal neglected tropical diseases. It is associated with an incredibly complex pathophysiology due to the vast number of unique toxins/proteins found in the venoms of diverse snake species found worldwide. Here, we report the purification and functional characteristics of a group I metalloprotease (CAMP-2) from the venom of the western diamondback rattlesnake, Crotalus atrox. Its sensitivity to matrix metalloprotease inhibitors (batimastat and marimastat) was established using specific in vitro experiments and in silico molecular docking analysis. CAMP-2 shows high sequence homology to atroxase from the venom of Crotalus atrox and exhibits collagenolytic, fibrinogenolytic and mild haemolytic activities. It exerts a mild inhibitory effect on agonist-induced platelet aggregation in the absence of plasma proteins. Its collagenolytic activity was completely inhibited by batimastat and marimastat. Zinc chloride also inhibits the collagenolytic activity of CAMP-2 by around 75% at 50 M, while it is partially potentiated by calcium chloride. Molecular docking studies demonstrate that batimastat and marimastat are able to bind strongly to the active site residues of CAMP-2. This study demonstrates the impact of matrix metalloprotease inhibitors in the modulation of a purified, group I metalloprotease activities in comparison to the whole venom. By improving our understanding of snake venom metalloproteases and their sensitivity to small molecule inhibitors, we can begin to develop novel and improved treatment strategies for snakebites

Spitzer Observations of the z=2.73 Lensed Lyman Break Galaxy, MS1512-cB58

We present Spitzer infrared (IR) photometry and spectroscopy of the lensed Lyman break galaxy (LBG), MS1512-cB58 at z=2.73. The large (factor ~30) magnification allows for the most detailed infrared study of an L*_UV(z=3) LBG to date. Broadband photometry with IRAC (3-10 micron), IRS (16 micron), and MIPS (24, 70 & 160 micron) was obtained as well as IRS spectroscopy spanning 5.5-35 microns. A fit of stellar population models to the optical/near-IR/IRAC photometry gives a young age (~9 Myr), forming stars at ~98 M_sun/yr, with a total stellar mass of ~10^9 M_sun formed thus far. The existence of an old stellar population with twice the stellar mass can not be ruled out. IR spectral energy distribution fits to the 24 and 70 micron photometry, as well as previously obtained submm/mm, data give an intrinsic IR luminosity L_IR = 1-2 x10^11 L_sun and a star formation rate, SFR ~20-40 M_sun/yr. The UV derived star formation rate (SFR) is ~3-5 times higher than the SFR determined using L_IR or L_Halpha because the red UV spectral slope is significantly over predicting the level of dust extinction. This suggests that the assumed Calzetti starburst obscuration law may not be valid for young LBGs. We detect strong line emission from Polycyclic Aromatic Hydrocarbons (PAHs) at 6.2, 7.7, and 8.6 microns. The line ratios are consistent with ratios observed in both local and high redshift starbursts. Both the PAH and rest-frame 8 micron luminosities predict the total L_IR based on previously measured relations in starbursts. Finally, we do not detect the 3.3 micron PAH feature. This is marginally inconsistent with some PAH emission models, but still consistent with PAH ratios measured in many local star-forming galaxies.Comment: Accepted for publication in ApJ. aastex format, 18 pages, 7 figure

EXAFS Characterization of Dendrimer-Derived Pt/γ-Al2O3

The various steps involved in the preparation of a Pt/-Al2O3 material using hydroxyl-terminated generation four (G4OH) PAMAM dendrimers as templates were monitored by EXAFS. The results indicate that Cl ligands in the Pt precursors (H2PtCl6 and K2PtCl4) were partially replaced by aquo ligands upon hydrolysis to form [PtCl3(H2O)3]+ and [PtCl2(H2O)2] species. After interaction of such species with G4OH, Cl ligands from the first coordination shell of Pt were further replaced by nitrogen atoms from the dendrimer interior, indicating the complexation of Pt with the dendrimer. This process was accompanied by a transfer of the electron density from the dendrimer to Pt, indicating that the former plays the role of a ligand. Following treatment of the H2PtCl6/G4OH and K2PtCl4/G4OH composites with NaBH4, no substantial changes were detected in the electronic or coordination environment of Pt, and no formation of metal nanoparticles was observed. However, when the reduction treatment was performed with H2, the formation of extremely small Pt clusters incorporating no more than 4 Pt atoms was observed. These Pt species remained strongly bonded to the dendrimer and their nuclearity depends on the length of the H2 treatment. Formation of Pt nanoparticles with an average diameter of approximately 10 Å was finally observed after the deposition of H2PtCl6/G4OH on -Al2O3 and drying, suggesting that their formation may be related to the collapse of the dendrimer structure. The Pt nanoparticles formed appear to have high mobility, since subsequent thermal treatment in O2/H2 led to further sintering

Time and Space Bounds for Reversible Simulation

We prove a general upper bound on the tradeoff between time and space that suffices for the reversible simulation of irreversible computation. Previously, only simulations using exponential time or quadratic space were known. The tradeoff shows for the first time that we can simultaneously achieve subexponential time and subquadratic space. The boundary values are the exponential time with hardly any extra space required by the Lange-McKenzie-Tapp method and the ($\log 3$)th power time with square space required by the Bennett method. We also give the first general lower bound on the extra storage space required by general reversible simulation. This lower bound is optimal in that it is achieved by some reversible simulations.Comment: 11 pages LaTeX, Proc ICALP 2001, Lecture Notes in Computer Science, Vol xxx Springer-Verlag, Berlin, 200

Challenges in diagnosing and treating snakebites in a rural population of Tamil Nadu, India: the views of clinicians

Snakebites cause death, disability and economic devastation to their victims, people who live almost exclusively in rural areas. Annually an estimated two million venomous bites cause as many as 100,000 deaths worldwide as well as hundreds of thousands of deformities and amputations. Recent studies suggest that India has the highest incidence of snakebite and associated deaths worldwide. In this study, we interviewed 25 hospital-based clinicians who regularly treat snakebites in Tamil Nadu, India, in order to gauge their opinions and views on the diagnostic tools and treatment methods available at that time, the difficulties encountered in treating snakebites and improvements to snakebite management protocols they deem necessary. Clinicians identified the improvement of community education, training of medical personnel, development of standard treatment protocols and improved medication as priorities for the immediate future

The Rest-Frame Optical Spectrum of MS 1512-cB58

Moderate resolution, near-IR spectroscopy of MS1512-cB58 is presented, obtained during commissioning of the the Near IR Spectrometer (NIRSPEC) on the Keck II telescope. The strong lensing of this z=2.72 galaxy by the foreground cluster MS1512+36 makes it the best candidate for detailed study of the rest-frame optical properties of Lyman Break Galaxies. A redshift of z=2.7290+/-0.0007 is inferred from the emission lines, in contrast to the z=2.7233 calculated from UV observations of interstellar absorption lines. Using the Balmer line ratios, we find an extinction of E(B-V)=0.27. Using the line strengths, we infer an SFR=620+/-18 Msun/yr (H_0=75, q_0=0.1, Lambda =0), a factor of 2 higher than that measured from narrow-band imaging observations of the galaxy, but a factor of almost 4 lower than the SFR inferred from the UV continuum luminosity. The width of the Balmer lines yields a mass of M_vir=1.2x10^10 Msun. We find that the oxygen abundance is 1/3 solar, in good agreement with other estimates of the metallicity. However, we infer a high nitrogen abundance, which may argue for the presence of an older stellar population.Comment: 14 pages, including 3 figures. Accepted for publication in ApJ Letter

Current Understanding of Circulating Tumor Cells - Potential Value in Malignancies of the Central Nervous System

Detection of circulating tumor cells (CTCs) in the blood via so-called 'liquid biopsies' carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems such as the widely used Cell Search system are reliant on markers such as the epithelial cell adhesion molecule (EpCAM) which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors

The failures of ethnobotany and phytomedicine in delivering novel treatments for snakebite envenomation

Snakebite envenomation (SBE) is a high priority, neglected tropical disease. This devastating occupational health hazard disproportionately affects rural farming communities in tropical countries. This is exacerbated by the distribution and densities of venomous snakes, incidence of encounters and limited access to advanced healthcare, including antivenom. Before the development of antivenom, desperation and spiritual beliefs led patients to experiment with a wide range of traditional treatments. Many of these treatments still survive today, particularly in regions where access to healthcare is limited. Plants are a major source of bioactive molecules, including several lifesaving medications that are widely used to this day. However, much of the research into the use of traditional plant treatments for SBE are limited to preliminary analysis, or have focused on techniques used to confirm antibody efficacy that are not suitable for non-antibody containing treatments. Modern drugs are developed through a robust pharmaceutical drug discovery and development process, which applies as much to SBE as it does to any other disease. This review discusses specifically why research into ethnobotanical practices has failed to identify or develop a novel treatment for SBE, and proposes specific approaches that should be considered in this area of research in the future