bluuebunny/crossref_metadata_2025 huggingface dataset:
Me thamphe tarnine‐Induced Dopaminergic Toxicity in Mice
Authors: ALI SYED F. , NEWPORT GLENN D. , SLIKKER WILLIAM
Published: December 2006

SUMMARY AND CONCLUSIONS

1. Multiple injections of METH (4 × 10 mg/kg, ip) at room temperature (23°C) produced a significant depletion of dopamine (DA) and its metabolites DOPAC and HVA in striatum at 24 and 72 hr, and 1 and 2 wk.

2. Three days post 4 × 10 mg/kg METH at 23°C, an 80% decrease in striatal dopamine (DA) occurred, while the same dose at 4°C produced only a 20% DA decrease, and 4 × 20 mg/kg METH at 4°C produced a 54% DA decrease. A similar pattern in the decreases of the DA metabolites DOPAC and HVA was observed after METH administration.

3. At 23°C (+)MK‐801 completely blocked while phenobarbital (40% decrease) and diazepam (65% decrease) partially blocked decreases in striatal DA produced by 4 × 10 mg/kg METH. Decreases in DOPAC and HVA were similar to the decreases in DA after METH and antagonists.

4. Multiple injections of METH (4 × 10 mg/kg, ip) at room temperature also produced a significant depletion of serotonin (5‐HT) in striatum at 24 and 72 hr, and 1 and 2 wk. The depletion of 5‐HT metabolite 5‐HIAA was found only at 72 hr post‐dosing.

5. This depletion of 5‐FIT and its metabolite 5‐HIAA at room temperature was blocked either by changing the environmental temperature to 4°C, or by pretreatment with MK‐801, diazepam and phenobarbital after METH treatment.

6. Therefore, these data suggest that drugs that block METH toxicity, such as haloperidol (D2 receptors), pentobarbital and phenobarbital (chloride channels) and MK‐801 (NMDA/glutamate receptors), do not necessarily have the same mechanism of action but may either induce hypothermia or block induction of hyperthermia.

7. In summary, these studies show that in the mouse, environmental temperature greatly influences METH neurotoxicity, and that the protective effects of compounds such as diazepam, phenobarbital and MK‐801 may be mediated by blockade of METH‐induced hyperthermia.
Alexandroff and Scott Topologies for Generalized Metric Spaces
Authors: BONSANGUE M.M. , VAN BREUGEL F. , RUTTEN J.J.M.M.
Published: December 2006

Generalized metric spaces are a common generalization of preorders and ordinary metric spaces. Every generalized metric space can be isometrically embedded in a complete function space by means of a metric version of the categoricalYoneda embedding. This simple fact gives naturally rise to: 1. a topology for generalized metric spaces which for arbitrary preorders corresponds to the Alexandroff topology and for ordinary metric spaces reduces to the ε‐ball topology; 2. a topology for algebraic generalized metric spaces generalizing both the Scott topology for algebraic complete partial orders and the ε‐ball topology for metric spaces.
Axiomatic Characterizations of Hyperuniverses and Applicationsa
Authors: FORTI MARCO , HONSELL FURIO , LENISA MARINA
Published: December 2006

Hyperuniverses are topological structures exhibiting strong closure properties under formation of subsets. They have been used both in computer science, for giving denotational semantics à la Scott‐de Bakker, and in mathematical logic, in order to show the consistency of set theories that do not abid***e by the “limitation‐of‐size” principle. We present correspondence between set‐theoretic properties and topological properties of hyperuniverses. We give existence theorems and discuss applications and generalizations to the non‐κ‐compact case.
On Volterra Spaces II
Authors: GAULD DAVID , GREENWOOD SINA , PIOTROWSKI ZBIGNIEW
Published: December 2006

We say that a topological space X is Volterra if for each pair f, g: X→ℝ for which the sets of points at which f, respectively g, are continuous are dense, there is a common point of continuity; and X is strongly Volterra if in the same circumstances the set of common points of continuity is dense in X. For both of these concepts equivalent conditions are given and the situation involving more than two functions is explored.
Partial Metrics, Valuations, and Domain Theory
Authors: O'NEILL S. J.
Published: December 2006

In this paper we develop some connections between the partial metrics of Matthews and the topological aspects of domain theory. We do this by introducing the valuation spaces, which are a special class of partial metric spaces. We develop the natural duality of partial metrics and propose that a natural context in which to view a partial metric space is as a bitopological space. We then see that successive conditions on a valuation can ensure that the pmetric topology is first of all order consistent (with the underlying poset), then equivalent to the Scott topology, and finally that the induced metric topology is equivalent to the patch topology.
Examples of Recurrence
Authors: PELANT JAN , WILLIAMS SCOTT W.
Published: December 2006

We present five examples illustrating that results well known for discrete dynamical systems on (locally) compact metric spaces and continuous functions can fail if either (local) compactness or metrizable is removed. Some samples are: A homeomorphism h from the space ℙ of irrationals to itself such that [ℙ; h] has each point recurrent, but [ℙ; h] has no minimal sets. Commuting homeomorphisms f and g from a compact space X to itself such that [X; f] and [X; g] have no common recurrent points.
Convergence Axioms for Topology
Authors: WYLER OSWALD
Published: December 2006

We obtain axioms for a topology using filter convergence as the basic construct, and two very simple axioms for a topology in terms of ultrafilter convergence.
Long‐period Comets and the Oort Cloud
Authors: WEISSMAN PAUL R.
Published: December 2006

ABSTRACT: The long‐period comets pose a unique problem for the impact hazard problem. Because of their very long orbital periods and generally large distances from the Sun, they cannot be surveyed and catalogued in the same manner as the near‐Earth asteroids and short‐period comets. They appear at random, uniformly distributed on the celestial sphere. Current technologies can detect long‐period comets at distances of ∼5 AU, giving somewhat less than a one year warning time for potential Earth impactors. The mean impact probability for a long‐period comet crossing the Earth's orbit is 2.2 to 2.5 × 10−9 per perihelion passage. The mean impact velocity is ∼52 km sec−1, but the most probable impact energy is characterized by a velocity of 56 to 58 km sec−1. The estimated current impact rate for cometary nuclei large enough to create 10 km diameter (or larger) craters on the Earth is between 5 × 10−7 and 2.8 × 10−6 per year, with a best estimated value of 1.0 × 10−6 per year. Nuclei large enough to initiate global climatic disturbances strike the Earth, on average, every 16 Myr. The impact frequency may be increased substantially for brief periods of time during cometary showers, initiated by major perturbations of the Oort cloud. Improved technologies are needed to detect approaching long‐period comets at large heliocentric distances so as to increase the warning time for potential impactors.
Historical Detection of Atmospheric Impacts by Large Bolides Using Acoustic‐Gravity Wavesa
Authors: REVELLE DOUGLAS O.
Published: December 2006

ABSTRACT: During the period from about 1960 to the early 1980's a number of large bolides (meteor‐fireballs) entered the atmosphere which were sufficiently large to generate blast waves during their drag interaction with the air. For example, the remnant of the blast wave from a single kiloton class event was subsequently detected by up to six ground arrays of microbarographs which were operated by the U.S. Air Force during this presatellite period. Data have also been obtained from other sources during this period as well and are also discussed in this summary of the historical data. The Air Force data have been analyzed in terms of their observable properties in order to infer the influx rate of NEOs (near‐Earth objects) in the energy range from 0.2 to 1100 kt. The determined influx is in reasonable agreement with that determined by other methods currently available such as Rabinowitz [21], Ceplecha[4], [5] and by Chapman and Morrison [8] despite the fact that due to sampling deficiencies only a portion of the “true” flux of large bodies has been obtained by this method, i.e., only sources at relatively low elevations have been detected. Thus the weak, fragile cometary bodies which do not penetrate the atmosphere as deeply are less likely to have been sampled by this type of detection system. Future work using the proposed CTBT (Comprehensive Test Ban Treaty) global scale infrasonic network will be likely to improve upon this early estimate of the global influx of NEOs considerably.
A Unified Theory of Impact Crises and Mass Extinctions: Quantitative Tests
Authors: RAMPINO MICHAEL R. , HAGGERTY BRUCE M. , PAGANO THOMAS C.
Published: December 2006

ABSTRACT: Several quantitative tests of a general hypothesis linking impacts of large asteroids and comets with mass extinctions of life are possible based on astronomical data, impact dynamics, and geological information. The waiting times of large‐body impacts on the Earth derived from the flux of Earth‐crossing asteroids and comets, and the estimated size of impacts capable of causing large‐scale environmental disasters, predict that impacts of objects ≥ 5 km in diameter (≥ 107 Mt TNT equivalent) could be sufficient to explain the record of ∼ 25 extinction pulses in the last 540 Myr, with the 5 recorded major mass extinctions related to impacts of the largest objects of ≥ 10 km in diameter (≥ 108 Mt events). Smaller impacts (∼ 106 Mt), with significant regional environmental effects, could be responsible for the lesser boundaries in the geologic record.

Tests of the “kill curve” relationship for impact‐induced extinctions based on new data on extinction intensities, and several well‐dated large impact craters, also suggest that major mass extinctions require large impacts, and that a step in the kill curve may exist at impacts that produce craters of ∼100 km diameter, smaller impacts being capable of only relatively weak extinction pulses. Single impact craters less than ∼60 km in diameter should not be associated with detectable global extinction pulses (although they may explain stage and zone boundaries marked by lesser faunal turnover), but multiple impacts in that size range may produce significant stepped extinction pulses.

Statistical tests of the last occurrences of species at mass‐extinction boundaries are generally consistent with predictions for abrupt or stepped extinctions, and several boundaries are known to show “catastrophic” signatures of environmental disasters and biomass crash, impoverished postextinction fauna and flora dominated by stress‐tolerant and opportunistic species, and gradual ecological recovery and radiation of new taxa. Isotopic and other geochemical signatures are also generally consistent with the expected after‐effects of catastrophic impacts. Seven of the recognized extinction pulses seem to be associated with concurrent (in some cases multiple) stratigraphic impact markers (e.g., layers with high iridium, shocked minerals, microtektites), and/or large, dated impact craters. Other less well‐studied crisis intervals show evated iridium, but well below that of the K/T spike, which might be explained by low‐Ir impactors, ejecta blowoff, or sedimentary reworking and dilution of impact signatures.

The best explanation for a possible periodic component of ∼30 Myr in mass extinctions and clusters of impacts is the pulselike modulation of the comet flux associated with the solar system's periodic passage through the plane of the Milky Way Galaxy. The quantitative agreement between paleontologic and astronomical data suggests an important underlying unification of the processes involved.
Mining Near‐Earth Resources
Authors: GERTSCH RICHARD , GERTSCH LESLIE SOUR , REMO JOHN L.
Published: December 2006

ABSTRACT: Mining the potentially vast storehouse of natural resources contained within near‐Earth objects (NEOs) could assist mitigation of the danger that a threatening object presents to life on Earth. Properly planned, NEO mining could provide a substantial basis for the exploration and development of space, in addition to providing important tools and opportunities for mitigating impact hazards.

The key to successful NEO mining is the appropriate modification of tried‐and‐true terrestrial mining techniques for the very unfamiliar and dangerous environment of space. Mining engineering is unlike traditional engineering disciplines in that, as a whole, it is less easily quantified; the practitioner must retain flexibility and resilience in the face of wide and unknown variations in material properties. This unique element of mining engineering will be an asset in space operations. Understanding of the basics of mining and processing will improve the planning and designing of NEO mitigation missions.

Space possesses many properties that are unique in human experience. Some of these can provide efficient new means of accomplishing old tasks. Others will prove to be obstacles that must be overcome. Mining and processing techniques that are inefficient curiosities on Earth may form the basis of powerful new methodologies in space. On the other hand, some vital processes will demand innovative engineering for success. This paper discusses the effects of the space environment on the application to NEO resources of mining methodologies developed over more than a thousand years on Earth. It will focus on the four mechanical classifications of NEOs described in Gertsch et al. (this volume).
Electron Microscopy of Amyloid Fibrils and Microvessels
Authors: MIYAKAWA TAIHEI
Published: December 2006

ABSTRACT: Senile plaques and microvessels in the cortices of brains with Alzheimer's disease were examined using serial sections under light and electorn microscopes. In addition, observations were carried out by using an immunostaining method. The results obtained were as follows: (1) Every senile plaque contains some amyloid fibrils, and many senile plaques have degenerated capillaries with amyloid fibrils. (2) Amyloid fibrils without senile plaques continue directly to the capillaries. (3) A considerable number of preamyloids are observed surrounding the capillaries when a methenamine silver stain is used. (4) α1‐antichymotrypsin is found in amyloid fibrils, endothelial cells, and vascular feet or astrocytic processes. Our findings strongly suggest that amyloid fibrils forming senile plaques have a close relationship to the capillaries. Moreover, a protease inhibitor, such as α1‐antichymotrypsin, could possibly play an important role in producing the amyloid fibrils.
The Vasoactivity of Aβ Peptides
Authors: CRAWFORD FIONA , SUO ZHIMING , FANG CHUNHONG , SAWAR ASAD , SU GEORGE , ARENDASH GARY , MULLAN MIKE
Published: December 2006

ABSTRACT: We have demonstrated that freshly solubilized Aβ peptides can enhance vasoconstriction by phenylephrine or endothelin of isolated rat aorta. Concentrations of peptide producing these effects (100 nM—1 μM) are much lower than those requiring toxicity to endothelial cells in culture, and effects are immediate, not requiring the prolonged time periods for aggregation necessary in Aβ cell culture toxicity experiments. Pre‐treatment with SOD diminishes the enhancement of vasoconstriction by Aβ peptides, suggesting that the effects are partly mediated via a decrease in the nitric oxide/superoxide ratio. Enhancement of endothelin vasoconstriction is observed with Aβ1‐40 and Aβ1‐42, but not with Aβ25‐35 even at 5 μM, again suggesting the mechanism of Aβ vasoactivity is distinct from that of Aβ cytotoxicity. These observations raise the possibility that Aβ peptides in contact with the cerebrovasculature could result in vasoconstriction, hypoperfusion and oxygen free radical imbalance contributing to the neurodegeneration of AD.
Production of Neurotoxic Factors by Brain Endothelium in Alzheimer's Diseasea
Authors: GRAMMAS PAULA , BOTCHLET TOYA R. , MOORE PETE , WEIGEL PAUL H.
Published: December 2006

ABSTRACT: The cerebral vasculature is central to the maintenance of the neuronal microenvironment. We have previously demonstrated that brain microvessels in Alzheimer's disease produce high, potentially toxic, levels of nitric oxide. It is our hypothesis that neuronal injury in Alzheimer's disease occurs because an abnormal endothelium secretes factors that are toxic to neurons. In this study, we report that inhibition of protein kinase C in endothelial cells causes release of a factor that is toxic to neurons in vitro. Our results demonstrate that this endothelium‐derived toxic factor is soluble, heat‐labile, susceptible to proteolysis, and loses activity with repeated freeze—thawing. The molecular weight of this putative protein is between 10 and 50 kDa, and 8 hours are required after protein kinase C inhibition to detect the endothelium‐derived toxic factor in the media. Finally, the endothelium‐derived toxic factor kills neurons within 2 hours, suggesting that cell death occurs via necrosis, not apoptosis. These data support the notion that endothelial cells can create an injurious microenvironment for neurons by producing molecules with noxious properties. Altered/dysfunctional endothelial cells in the cerebral microcirculation could be a novel, unexplored source of neurotoxic factors in Alzheimer's disease.
Vascular Basement Membrane Pathology and Alzheimer's Disease
Authors: ZAROW CHRIS , BARRON ERNESTO , CHUI HELENA CHANG , PERLMUTTER LYNN S.
Published: December 2006

ABSTRACT: We have previously demonstrated that the capillary vascular basement membrane (VBM) is pathologically altered in Alzheimer's disease (AD). This microangiopathy is highlighted by the immunocytochemical localization of the three principal intrinsic VBM components: heparan sulfate proteoglycan, collagen type IV, and laminin. These three VBM components also immunolabel amyloid deposits and senile plaque‐associated glial processes. The present study examines the ultrastructure of the VBM in one brain region severely affected (temporal gyrus) and one relatively spared (cerebellum) from the lesions of AD in both AD and neurological control cases. The cross‐sectional area as well as the width of the VBM were found to be greater in AD cortical capillaries. In addition, we found ultrastructural evidence for the activation of microglial‐related perivascular cells, and their apparent extravasation through the VBM, findings consistent with the hypothesis that these cells are being recruited as part of a disease‐related immune response. The recruitment of these “resting” microglial‐like cells from their intra‐VBM location to plaques and tangles in AD may explain (1) the thickening and vacuolization of the VBM; (2) the specificity of this VBM alteration to brain regions where there are plaques and tangles; and (3) the source of some of the large number of activated microglia in these affected areas. Thus, while VBM alterations may not be specific to AD, these changes appear to be specifically related to the disease process.
Magnetic Resonance Spectroscopic Changes in Alzheimer's Diseasea
Authors: PETTEGREW J. W. , KLUNK W. E. , PANCHALINGAM K. , McCLURE R. J. , STANLEY J. A.
Published: December 2006

ABSTRACT: In vitro and in vivo31P magnetic resonance (MR) spectroscopy studies of Alzheimer's disease (AD) brain have revealed alterations in membrane phospholipid metabolism and high‐energy phosphate metabolism. Mildly demented AD patients compared with control subjects have increased levels of phosphomonoesters, decreased levels of phosphocreatine and probably adenosine diphosphate and an increased oxidative metabolic rate. As the dementia worsens, levels of phosphomonoesters decrease and levels of phosphocreatine and adenosine diphosphate increase. The changes in oxidative metabolic rate suggest that the AD brain is under energetic stress. The phosphomonoester findings support our in vitro findings and implicate basic defects in membrane metabolism in AD brain. MR spectroscopy provides new diagnostic insights and a noninvasive method to follow the progression of the disease and the metabolic response to therapeutic interventions.
Omental Transposition to the Brain for Alzheimer's Disease
Authors: GOLDSMITH HARRY S.
Published: December 2006

ABSTRACT: Omental transposition (OT) to revascularize the brain was first performed in animals in the late 1960s, where it was shown that blood vessels originating from the omentum crossed through the omental‐cerebral interface prior to developing into large‐sized vessels that penetrated directly and deeply into the underlying brain. The additional cerebral blood flow coming from the omentum was of sufficient volume to protect an animal's brain from cerebral infarction even in the presence of middle cerebral artery ligation. It was also learned that the omentum was a rich source for neurotransmitters and omentum‐derived nerve growth substance. OT to the brain is now being done for a variety of conditions which include strokes, TIAs, epilepsy, and Parkinson's disease. Of recent interest is the published information that OT may play some role in Alzheimer's disease (AD). The placement of the omentum on an AD brain has led to a profound decrease in senile plaque formation. The omentum may ultimately prove to be beneficial in reversing or at least stabilizing the dementia associated with the devastation of AD.
Tobacco and Cancer: Approaches Using Carcinogen Biomarkers and Chemoprevention
Authors: HECHT STEPHEN S.
Published: December 2006

ABSTRACT: Tobacco products are the leading cause of avoidable cancer death in the U.S., accounting for approximately 30% of all cancer deaths. While avoidance of tobacco and smoking cessation are clearly the best way to decrease tobacco‐related cancer, these approaches have not been uniformly successful. Approximately 25% of the U.S. population over 18 years of age smokes cigarettes, while 6% use smokeless tobacco products; these figures have not changed markedly in recent years. Our approach toward the tobacco and cancer problem is based on an understanding of the carcinogens in tobacco smoke. These carcinogens form the link between nicotine addiction and cancer. In this paper, two strategies for cancer prevention—the development of carcinogen‐derived biomarkers and chemopre‐ventive agents—are discussed. Carcinogen‐derived biomarkers can provide specific information on individual metabolic activation and detoxification of tobacco carcinogens. This information can be used to assess individual risk for cancer development upon exposure to tobacco products. Chemopreventive agents can be targeted against the important carcinogens in tobacco smoke. Isothiocyanates, strong inhibitors of lung cancer development by the tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone, are discussed as an example of this approach.
The Behavioral Neurobiology of Self‐injurious Behavior in Rhesus Monkeys
Authors: KRAEMER GARY W. , SCHMIDT DENNIS E. , EBERT MICHAEL H.
Published: December 2006

ABSTRACT: The objective of this report is to critically review past reports and present new data on the psychobiology of self‐injurious behavior (SIB) and/or “risky” or “impulsive” behavior in primates (human and nonhuman). One aim was to reexamine how early social deprivation and neurobiological changes caused by deprivation might contribute to SIB in monkeys, and how the causes of SIB in monkeys might inform us about the psychobiology of suicide in humans. A second aim was to examine the evidence that social deprivation in monkeys produces reductions in brain 5‐HT system function that are causal or coincident factors associated with self‐injurious or impulsive behavior. Prior studies and new data indicate that the environmental causes of SIB and unusual aggression in rhesus monkeys do not produce reductions in brain 5‐HT system activity and that experimental production of low levels of brain 5‐HT system activity does not reliably promote either SIB or unusual other‐directed aggression in monkeys. A third and final aim was to suggest that in severe cases of environmentally induced SIB and/or aggression in monkeys, having relatively high or low levels of 5‐HT system activity may not be related to ongoing behavior because the 5‐HT system may not interact with other neurotransmitter systems in the usual way. Overall, the contention is that primates exhibiting SIB and unusual aggression may have altered 5‐HT system function, but this may be but one aspect of a more profound disorganization of brain function involving many neurohormonal and transmitter systems. Contemporary theorizing and experimentation tends to be restricted to the idea that altered function in one key system might be the cause of a specific form of psychopathology. In the future, research examining the probable change interactions of neurotransmitter and neuroendocrine systems as underlying causes of behavioral disorders should have a high priority.
Low Central Nervous System Serotonergic Activity Is Traitlike and Correlates with Impulsive Behavior
Authors: HIGLEY J. D. , LINNOILA M.
Published: December 2006

ABSTRACT:We have used nonhuman primates to examine developmental and behavioral correlates of CNS serotonergic activity, as measured by concentrations of the serotonin metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) in the cerebrospinal fluid (CSF). These studies show that interindividual differences in CNS serotonin turnover rate exhibit traitlike qualities and are stable across time and settings, with interindividual differences in CSF 5‐HIAA concentrations showing positive correlations across repeated sampling. Primates with low CNS serotonergic activity exhibit behaviors indicative of impaired impulse control, unrestrained aggression, social isolation, and low social dominance. Maternal and paternal genetic influences play major roles in producing low CNS serotonin functioning, beginning early in life. These genetic influences on serotonin functioning are further influenced by early rearing experiences, particularly parental deprivation.
Postmortem Findings in Suicide Victims. Implications for in Vivo Imaging Studiesa
Authors: ARANGO VICTORIA , UNDERWOOD MARK D. , MANN J. JOHN
Published: December 2006

Abstract Alterations in serotonergic and noradrenergic receptor binding in membrane homogenates from the brain of suicide victims suggest a biological substrate for the vulnerability to commit suicide. We and others have employed high‐resolution quantitative autoradiography of full coronal sections of the prefrontal cortex to map the locus of maximal change in receptor binding. We found alternations in binding to the serotonin transporter, the 5‐HT1A', and the 5‐HT2A receptors primarily in the ventral and ventrolateral prefrontal cortex of suicide victims. Importantly, these changes are often modest in magnitude and anatomically restricted to one or two Brodmann areas. Furthermore, we have found that care in case selection is essential, because sex, age, drugs, and comorbid diagnoses contribute to receptor binding. The implications for in vivo imaging are considerable, directing the focus of such studies toward the ventrolateral prefrontal cortex. However, because ligands are limited, as is the resolution of current methods, including PET, automated analyses that produce statistical images, rather than manual selection of individual slices, will likely lack the ability to detect the discrete receptor changes found postmortem. Alternatively, the advantages of examining large numbers of subjects, imaging the entire brain, obtaining detailed clinical information in the living patient, and magnifying the changes with neuropharmacological challenges present a promising outlook for making major advances into the identification of brain abnormalities associated with suicide risk.
Retargeted Oncolytic Measles Strains Entering via the EGFRvIII Receptor Maintain Significant Antitumor Activity against Gliomas with Increased Tumor Specificity
Authors: Allen Cory , Vongpunsawad Sompong , Nakamura Takafumi , James C. David , Schroeder Mark , Cattaneo Roberto , Giannini Caterina , Krempski James , Peng Kah-Whye , Goble Jenny M. , Uhm Joon H. , Russell Stephen J. , Galanis Evanthia
Published: December 2006

Among the best-characterized genetic alterations in gliomas is the amplification of the epidermal growth factor receptor (EGFR) gene, present in ∼40% of glioblastoma multiforme, and frequently associated with the EGFRvIII gene rearrangement. We have previously shown that attenuated vaccine strains of measles virus have potent antitumor activity against gliomas, and identified H protein mutations, which ablate recognition of the natural measles virus receptors CD46 and SLAM. Retargeted recombinant viruses were generated from the measles Edmonston-NSe vaccine strain displaying a single-chain antibody against EGFRvIII at the COOH terminus of H and containing the marker green fluorescent protein (GFP) gene in position 1. Two different H mutants were employed: HSNS (V451S, Y481N, and A527S)-CD46 blind, and HAA (Y481A and R533A)-CD46 and SLAM blind. MV-GFP virus was used as a positive control. Both EGFRvIII-retargeted viruses had significant antitumor activity against EGFRvIII-expressing glioblastoma multiforme but no cytopathic effect against normal cells. In an orthotopic model of EGFRvIII-expressing GBM39 xenografts, there was comparable therapeutic efficacy between retargeted strains and unmodified MV-GFP and statistically significant prolongation of survival in treated animals compared with the control group (P = 0.001). Formation of syncytia was observed in tumors treated with retargeted viruses, with a surrounding infiltrate consisting of macrophages and natural killer cells. In summary, EGFRvIII-retargeted oncolytic measles virus strains have comparable therapeutic efficacy with the unmodified MV-GFP strain against EGFRvIII-expressing glioma lines and xenografts with improved therapeutic index, a finding with potential translational implications in glioma virotherapy. (Cancer Res 2006; 66(24): 11840-50)
Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells
Authors: Santra Manoranjan , Zhang Xuepeng , Santra Sutapa , Jiang Feng , Chopp Michael
Published: December 2006

Doublecortin (DCX) is one of the three genes found from Affymetrix gene chip analysis related to glioma patient survival. Two other genes (e.g., osteonectin and semaphorin 3B) are well characterized as antioncogenic and tumor suppressor genes. However, there is no report about the involvement of DCX in cancer. Here, we show that gene transfer technology into DCX-deficient glioblastoma cell lines, such as A172, U87, U251N, RG2, and 9L, with DCX cDNA significantly suppressed growth of these glioma cells. U87 cells with ectopic expression of DCX exhibit a marked suppression of the transformed phenotype as growth arrested in the G2 phase of the cell cycle progression, small colony formation in soft agar, and no tumor formation in nude rats. This transformed phenotype can be restored by knocking down DCX expression with DCX small interfering RNA. DCX was highly phosphorylated in glioma cells. Phosphorylation in the glioma cells was greater than in noncancer cells such as mouse NIH 3T3 and human embryonic kidney 293T cells. Coimmunoprecipitation of the phosphorylated DCX and spinophilin/neurabin II from DCX-synthesizing glioma cells indicated their interaction. This interaction would lead to a block of anchorage-independent growth as neurabin II is a synergistic inhibitor of anchorage-independent growth with p14ARF (ARF). Interaction between phosphorylated DCX and neurabin II may induce the association of the protein phosphatase 1 catalytic subunit (PP1) with neurabin II and inactivate PP1 and block mitosis during G2 and M phases of the cell cycle progression. Thus, DCX seems to be a tumor suppressor of glioma. (Cancer Res 2006; 66(24): 11726-35)
Activation of p53 in Cervical Cancer Cells by Human Papillomavirus E6 RNA Interference Is Transient, but Can Be Sustained by Inhibiting Endogenous Nuclear Export–Dependent p53 Antagonists
Authors: Koivusalo Riku , Mialon Antoine , Pitkänen Hanna , Westermarck Jukka , Hietanen Sakari
Published: December 2006

p53 is degraded in cervical cancer cells by the human papillomavirus E6 and can be stabilized with short interfering RNA (siRNA) molecules targeting E6 mRNA. In this in vitro study, we show that E6 siRNA–induced p53 activation is transient in HeLa cervical cancer cells despite continuous suppression of E6 mRNA; activation can be sustained if the endogenous p53 antagonists COP1, MDM2, Pirh2, and c-Jun-NH2-kinase are also targeted by siRNAs or by inhibiting the nuclear export of p53 with leptomycin B. The direct targeting of any one of these four cellular p53 antagonists had no effect on p53 activity when E6 was intact, but inhibited the fading off of E6 siRNA–induced p53 activation in nonstress conditions. The effect was additive when multiple cellular antagonists were concomitantly inhibited, indicating that all these proteins degrade p53 when E6 is inactivated. The antiproliferative effect induced by E6 silencing was enhanced when the endogenous p53 antagonists were additionally targeted. In conclusion, if human papillomavirus E6 is inhibited under nonstress conditions, the subsequent p53 activation is quickly reversed by the endogenous p53 degenerative machinery. The present results indicate that several cellular p53 antagonists must be inhibited for sustained p53 activity if E6 siRNA therapy is attempted and if no combined genotoxic therapy is applied. (Cancer Res 2006; 66(24): 11817-24)
Reduced Repair of the Oxidative 8-Oxoguanine DNA Damage and Risk of Head and Neck Cancer
Authors: Paz-Elizur Tamar , Ben-Yosef Rami , Elinger Dalia , Vexler Akiva , Krupsky Meir , Berrebi Alain , Shani Adi , Schechtman Edna , Freedman Laurence , Livneh Zvi
Published: December 2006

An increasing number of studies indicate that reduced DNA-repair capacity is associated with increased cancer risk. Using a functional assay for the removal of the oxidative DNA lesion 8-oxoguanine by the DNA-repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), we have previously shown that reduced OGG activity is a risk factor in lung cancer. Here, we report that OGG activity in peripheral blood mononuclear cells from 37 cases with squamous cell carcinoma of the head and neck (SCCHN) was significantly lower than in 93 control subjects, frequency matched for age and gender. Retesting of OGG activity 3 to 4 years after diagnosis and successful treatment of 18 individuals who recovered from the disease showed that OGG activity values were similar to those determined at diagnosis, suggesting that reduced OGG activity in case patients was not caused by the disease. Logistic regression analysis indicated that the adjusted odds ratio (OR) associated with a unit decrease in OGG activity was statistically significantly increased [OR, 2.3; 95% confidence interval (95% CI), 1.5–3.4]. Individuals in the lowest tertile of OGG activity exhibited an increased risk of SCCHN with an OR of 7.0 (95% CI, 2.0–24.5). The combination of smoking and low OGG was associated with a highly increased estimated relative risk for SCCHN. These results suggest that low OGG is associated with the risk of SCCHN, and if confirmed by additional epidemiologic studies, screening of smokers for low OGG activity might be used as a strategy for the prevention of lung cancer and SCCHN. (Cancer Res 2006; 66(24): 11683-9)
Simulation of the 1976/77 Climate Transition over the North Pacific: Sensitivity to Tropical Forcing
Authors: Deser Clara , Phillips Adam S.
Published: December 2006

This study examines the contribution of tropical sea surface temperature (SST) forcing to the 1976/77 climate transition of the winter atmospheric circulation over the North Pacific using a combined observational and modeling approach. The National Center for Atmospheric Research (NCAR) Community Atmospheric Model version 3 (CAM3) simulates approximately 75% of the observed 4-hPa deepening of the wintertime Aleutian low from 1950–76 to 1977–2000 when forced with the observed evolution of tropical SSTs in a 10-member ensemble average. This response is driven by precipitation increases over the western half of the equatorial Pacific Ocean. In contrast, the NCAR Community Climate Model version 3 (CCM3), the predecessor to CAM3, simulates no significant change in the strength of the Aleutian low when forced with the same tropical SSTs in a 12-member ensemble average. The lack of response in CCM3 is traced to an erroneously large precipitation increase over the tropical Indian Ocean whose dynamical impact is to weaken the Aleutian low; this, when combined with the response to rainfall increases over the western and central equatorial Pacific, results in near-zero net change in the strength of the Aleutian low. The observed distribution of tropical precipitation anomalies associated with the 1976/77 transition, estimated from a combination of direct measurements at land stations and indirect information from surface marine cloudiness and wind divergence fields, supports the models’ simulated rainfall increases over the western half of the Pacific but not the magnitude of CCM3’s rainfall increase over the Indian Ocean.
Simulated Arctic Ocean Freshwater Budgets in the Twentieth and Twenty-First Centuries
Authors: Holland Marika M. , Finnis Joel , Serreze Mark C.
Published: December 2006

The Arctic Ocean freshwater budgets in climate model integrations of the twentieth and twenty-first century are examined. An ensemble of six members of the Community Climate System Model version 3 (CCSM3) is used for the analysis, allowing the anthropogenically forced trends over the integration length to be assessed. Mechanisms driving trends in the budgets are diagnosed, and the implications of changes in the Arctic–North Atlantic exchange on the Labrador Sea and Greenland–Iceland–Norwegian (GIN) Seas properties are discussed. Over the twentieth and the twenty-first centuries, the Arctic freshens as a result of increased river runoff, net precipitation, and decreased ice growth. For many of the budget terms, the maximum 50-yr trends in the time series occur from approximately 1975 to 2025, suggesting that we are currently in the midst of large Arctic change. The total freshwater exchange between the Arctic and North Atlantic increases over the twentieth and twenty-first centuries with decreases in ice export more than compensated for by an increase in the liquid freshwater export. Changes in both the liquid and solid (ice) Fram Strait freshwater fluxes are transported southward by the East Greenland Current and partially removed from the GIN Seas. Nevertheless, reductions in GIN sea ice melt do result from the reduced Fram Strait transport and account for the largest term in the changing ocean surface freshwater fluxes in this region. This counteracts the increased ocean stability due to the warming climate and helps to maintain GIN sea deep-water formation.
Systematic and Heuristic Processing of Majority and Minority-Endorsed Messages: The Effects of Varying Outcome Relevance and Levels of Orientation on Attitude and Message Processing
Authors: Martin Robin , Hewstone Miles , Martin Pearl Y.
Published: December 2006

Two experiments investigated the conditions under which majority and minority sources instigate systematic processing of their messages. Both experiments crossed source status (majority vs. minority) with message quality (strong vs. weak arguments). In each experiment, message elaboration was manipulated by varying either motivational (outcome relevance, Experiment 1) or cognitive (orientating tasks, Experiment 2) factors. The results showed that when either motivational or cognitive factors encouraged low message elaboration, there was heuristic acceptance of the majority position without detailed message processing. When the level of message elaboration was intermediate, there was message processing only for the minority source. Finally, when message elaboration was high, there was message processing for both source conditions. These results show that majority and minority influence is sensitive to motivational and cognitive factors that constrain or enhance message elaboration and that both sources can lead to systematic processing under specific circumstances.
On Hopeite and other zinc phosphates and associated minerals from the Broken Hill mines, North-Western Rhodesia
Authors: Spencer L. J.
Published: December 2006

The new and remarkable mineral locality known as Rhodesia Broken Hill is situated in North-Western Rhodesia, at a distance of about 300 miles to tile north-east of tile Victoria Falls, and at the present terminus of the Cape to Cairo Railway. The outcrop of lead and zinc ore which occurs here was accidentally discovered in January, 1902, by Mr. T. G. Davey, while he was prospecting the country for copper, Rising out of the flat surrounding country is a series of low hills or kopjes, the largest of them being about 90 feet in height ; and these consist almost entirely of oxidized ore. The surrounding rocks are mainly crystalline limestones with some beds of sandstone, conglomerate, and phyllite.
Kaolinization and other changes in West of England rocks
Authors: Butler Francis H.
Published: December 2006

The behaviour of a mass of molten but cooling igneous rock under moderate pressure may be compared to that of liquid cupelled silver, which at a certain temperature can no longer retain the oxygen, many times its volume, that it has occluded. Thus, during the submarine eruption off the island of Pantelleria in 1891, blocks of lava that swam for a while on the surface of the sea exploded with violence. Chilling by contact with sea-water had occasioned exactly what Lowthian Bell observed to happen on the sudden cooling of masses of slag by contact with water. There was a discharge within the set outer envelope, at something near a red heat, of previously dissolved water and gases, converting the floating ejectamenta into a species of bombs.
Contributions to the study of parallel growths of different substances
Authors: Kreutz Stefan
Published: December 2006

Mr. T. V. Barker has lately shown that the parallel growth of isostructural substances upon one another is conditioned by similarity of molecular volume. This very important conclusion invites further investigation from this new point of view, and Professor H. A. Miers suggested to me, while working in his laboratory last summer, that I should make experiments on the parallel growth of sodium nitrate on the pseudo-rhombohedral mineral barytocalcite.

The first experiments, which were made on crystals of barytocalcite in the Oxford collection, were unsuccessful, the crystals employed being small and somewhat impure. Later, I received, from the Museum of Practical Geology in London, some very good and perfectly pure crystals of barytocalcite from Blagilt, near Alston, in Cumberland.
The meteorite craters at Henbury, Central Australia
Authors: Alderman Arthur Richard
Published: December 2006

In the early part of 1931 public interest in South Australia was stimulated by the fall of the Karoonda meteorite on November 25, 1930, and its subsequent discovery by an Adelaide University party led by Prof. Kerr Grant. In consequence of this Prof. Grant was informed separately by Mr. B. Bowman of Tempe Downs and Mr. J. M. Mitchell of Oodnadatta that fragments of meteoric iron were to be found surrounding several crater-like depressions near Henbury Cattle Station in Central Australia. The number of craters was variously described as three and five.
A new pallasite from Alice Springs, Central Australia
Authors: Spencer L. J.
Published: December 2006

Dr. Herbert Basedow of Adelaide generously presented in November 1931 for the British Museum collection of meteorites a pallasite which he had collected in Central Australia in 1924 while leading the Vice-Regal Expedition. During his extensive explorations in Central and Northern Australia it had remained unpacked for some years. He gives the locality as on the Burr Plains, NNE. of Bond Springs in the Alice Springs district ; lat. 23° 33′ S., long. 133° 52′ E. This is immediately north of the MacDonnell Ranges and about ten miles north of Alice Springs. The fragment was found lying on the surface and only partly buried in loose ferruginous sand. No doubt other pieces of this material remain to be found in the district.
Studies on the zeolites. Part II. Thomsonite (including faroelite) and gonnardite
Authors: Hey Max H.
Published: December 2006

Thomsonite was first recognized by H. J. Brooke (1820) in a JL study of the mesotypes or 'needlestones'. The 'needlestone' of Lochwinnoch and Old Kilpatrick, Dumbartonshire, was found to be an independent species, in addition to the natrolite, mesolite, and scolecite into which k. F. Gehlen and J. N. Fachs, and J. N. Fuchs, had divided the mesotype of R. J. Haüy. The new species was named thomsonite, in honour of Dr. T. Thomson, who analysed the material a few months later.
Crystals of brookite tabular parallel to the basal plane
Authors: Coles Phillips F.
Published: December 2006

During the last year, Dr. R. H. Rastall has been engaged on an investigation of the mineral content of certain sandstones of Middle Jurassic age in north-east Yorkshire. These sandstones proved to be unusually rich in the titanium minerals rutile and anatase. In some samples the proportion of the last-named is greater than in any other specimen previously recorded, so far as can be ascertained. Some of the heavy-mineral separations also contained a number of crystals of quite unmistakable brookite, with normal crystallographic development and normal optical properties, namely Bx perpendicular to (100) and intense dispersion ρ > v. Associated with these, however, there were often observed a number of smaller crystals of very similar appearance, whose optical orientation seemed to be entirely different. In particular, no optic picture could be obtained, and the extinction between crossed nicols in parallel light was perfectly sharp, with no suggestion of strong dispersion. Dr. Rastall therefore asked me to carry out some further investigations into the nature of these crystals, which were unlike anything he had previously seen in sedimentary rocks.
Legrandite, a new zinc arsenate
Authors: Drugman Julien , Hey Max H.
Published: December 2006

Among a number of specimens which the senior author (J. l)rugman) obtained some years ago from the widow of a mine manager, Mr. Legrand, of Belgian nationality, was one of massive blendc from the Flor de Peña mine, Lampazos, Nuevo Leon, Mexico, which carried a small quantity of a bright yellow, transparent substance that could not be identified with any known mineral. Goniometric and optical examination showed it to be monoclinic, but the material was mainly massive radiating-prismatic, and the few freely developed crystals gave only very approximate measurements (see table II). A chemical analysis by the iunior author showed it to be indeed a new mineral, a basic zinc arsenate, and the name ‘legrandite’ is proposed for it in recognition of the collector. The larger part of what remains after investigation of the small specimen has been presented to the British Museum for preservation in the mineral collection.
Note on the occurrence of piedmontite in quartz-muscovite-schist from Shotover valley, western Otago, New Zealand
Authors: Turner F. J.
Published: December 2006

Specimens of quartz-muscovite-schist obtained fro: boulders in the Shotover river, western Otago, New Zealand, ere recently examined by the writer and found to contain abundant piedmontite, a mineral not previously recorded from New Zealand. The specimens had been collected twenty years before and were labelled ' micaceous quartz schist coloured with haematite' in the geological collections of the Otago University. The following description is submitted pending further field investigations.