On Certiorari to the Ninth Circuit Court of Appeals : The Supreme Court\u27s Review of Ninth Circuit Cases During the October 2006 Term

Whether reversed, affirmed, vacated, or remanded, a review of the interaction between the two courts over twenty-two cases reveals several fundamental differences between the two courts on key issues. This Comment examines these differences by exploring twenty of those decisions and how they illustrate the relationship between the Ninth Circuit and Supreme Court. Part I examines the decisions that arose from the Supreme Court\u27s review of Ninth Circuit decisions. Part II ties these decisions and conclusions into a larger motif emerging between the Ninth Circuit and Supreme Court, and Part III ultimately concludes that the future is likely to continue to see disagreements between the two courts

Current-voltage Relation For A Field Ionizing He Beam Detector

Emerging interest in utilizing the transverse coherence properties of thermal energy atomic and molecular beams motivates the development of ionization detectors with near unit detection efficiency and adequate spatial resolution to resolve interference fringes of submicron dimension. We demonstrate that a field ionization tip coupled to a charged particle detector meets these requirements. We have systematically studied the current-voltage relationship for field ionization of helium using tungsten tips in diffuse gas and in a supersonic helium beam. For all 16 tips used in this study, the dependence of ion current on voltage for tips of fixed radius was found to differ from that for tips held at constant surface electric field. A scaling analysis is presented to explain this difference. Ion current increased on average to the 2.8 power of voltage for a tip at fixed field and approximately fifth power of voltage for fixed radius for a liquid nitrogen cooled tip in room temperature helium gas. For the helium beam, ion current increased as 2.2 power of voltage with constant surface field. The capture region of the tips was found to be up to 0.1 mu m(2) for diffuse gas and 0.02 mu m(2) in the beam. Velocity dependence and orientation of tip to beam were also studied

Response of the Shockley surface state to an external electrical field: A density-functional theory study of Cu(111)

The response of the Cu(111) Shockley surface state to an external electrical field is characterized by combining a density-functional theory calculation for a slab geometry with an analysis of the Kohn-Sham wavefunctions. Our analysis is facilitated by a decoupling of the Kohn-Sham states via a rotation in Hilbert space. We find that the surface state displays isotropic dispersion, quadratic until the Fermi wave vector but with a significant quartic contribution beyond. We calculate the shift in energetic position and effective mass of the surface state for an electrical field perpendicular to the Cu(111) surface; the response is linear over a broad range of field strengths. We find that charge transfer occurs beyond the outermost copper atoms and that accumulation of electrons is responsible for a quarter of the screening of the electrical field. This allows us to provide well-converged determinations of the field-induced changes in the surface state for a moderate number of layers in the slab geometry.Comment: 11 pages, 6 figures, 4 tables; accepted for publication by Phys. Rev. B; changes from v1 in response to referee comments, esp. to Sections I and V.B (inc. Table 4), with many added references, but no change in results or conclusion

Anderson Transition in Disordered Graphene

We use the regularized kernel polynomial method (RKPM) to numerically study the effect disorder on a single layer of graphene. This accurate numerical method enables us to study very large lattices with millions of sites, and hence is almost free of finite size errors. Within this approach, both weak and strong disorder regimes are handled on the same footing. We study the tight-binding model with on-site disorder, on the honeycomb lattice. We find that in the weak disorder regime, the Dirac fermions remain extended and their velocities decrease as the disorder strength is increased. However, if the disorder is strong enough, there will be a {\em mobility edge} separating {\em localized states around the Fermi point}, from the remaining extended states. This is in contrast to the scaling theory of localization which predicts that all states are localized in two-dimensions (2D).Comment: 4 page

Pollen dimorphism and dioecy in Vitis aestivalis

Problems of low production and sterile pollen in varieties of Vitis vinifera may be tracable to their ancestral relations with dioecious wild grapes.Like V. riparia, the wild summer grape V. aestivalis has dimorphic male and female flowers; but unlike V. riparia it also has dimorphic pollen grains with the pollen from the female flower being significantly smaller.It seems fairly certain that V. aestivalis is truly dioecious

Speckle Patterns With Atomic And Molecular De Broglie Waves

We have developed a nozzle source that delivers a continuous beam of atomic helium or molecular hydrogen having a high degree of transverse coherence and with adequate optical brightness to enable new kinds of experiments. Using this source we have measured single slit diffraction patterns and the first ever speckle-diffraction patterns using atomic and molecular de Broglie waves. Our results suggest fruitful application of coherent matter beams in dynamic scattering and diffractive imaging at short wavelength and with extreme surface sensitivity

Comprehensive analysis of T cell leukemia signals reveals heterogeneity in the PI3 kinase-Akt pathway and limitations of PI3 kinase inhibitors as monotherapy.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer. Poly-chemotherapy with cytotoxic and genotoxic drugs causes substantial toxicity and more specific therapies targeting the underlying molecular lesions are highly desired. Perturbed Ras signaling is prevalent in T-ALL and occurs via oncogenic RAS mutations or through overexpression of the Ras activator RasGRP1 in ~65% of T-ALL patients. Effective small molecule inhibitors for either target do not currently exist. Genetic and biochemical evidence link phosphoinositide 3-kinase (PI3K) signals to T-ALL, PI3Ks are activated by Ras-dependent and Ras-independent mechanisms, and potent PI3K inhibitors exist. Here we performed comprehensive analyses of PI3K-Akt signaling in T-ALL with a focus on class I PI3K. We developed a multiplex, multiparameter flow cytometry platform with pan- and isoform-specific PI3K inhibitors. We find that pan-PI3K and PI3K γ-specific inhibitors effectively block basal and cytokine-induced PI3K-Akt signals. Despite such inhibition, GDC0941 (pan-PI3K) or AS-605240 (PI3Kγ-specific) as single agents did not efficiently induce death in T-ALL cell lines. Combination of GDC0941 with AS-605240, maximally targeting all p110 isoforms, exhibited potent synergistic activity for clonal T-ALL lines in vitro, which motivated us to perform preclinical trials in mice. In contrast to clonal T-ALL lines, we used a T-ALL cancer model that recapitulates the multi-step pathogenesis and inter- and intra-tumoral genetic heterogeneity, a hallmark of advanced human cancers. We found that the combination of GDC0941 with AS-605240 fails in such trials. Our results reveal that PI3K inhibitors are a promising avenue for molecular therapy in T-ALL, but predict the requirement for methods that can resolve biochemical signals in heterogeneous cell populations so that combination therapy can be designed in a rational manner

Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy.

Activating mutations in FLT3 confer poor prognosis for individuals with acute myeloid leukemia (AML). Clinically active investigational FLT3 inhibitors can achieve complete remissions but their utility has been hampered by acquired resistance and myelosuppression attributed to a 'synthetic lethal toxicity' arising from simultaneous inhibition of FLT3 and KIT. We report a novel chemical strategy for selective FLT3 inhibition while avoiding KIT inhibition with the staurosporine analog, Star 27. Star 27 maintains potency against FLT3 in proliferation assays of FLT3-transformed cells compared with KIT-transformed cells, shows no toxicity towards normal human hematopoiesis at concentrations that inhibit primary FLT3-mutant AML blast growth, and is active against mutations that confer resistance to clinical inhibitors. As a more complete understanding of kinase networks emerges, it may be possible to define anti-targets such as KIT in the case of AML to allow improved kinase inhibitor design of clinical agents with enhanced efficacy and reduced toxicity

Chemical Genetic Inhibition of Mps1 in Stable Human Cell Lines Reveals Novel Aspects of Mps1 Function in Mitosis

Proper execution of chromosome segregation relies on tight control of attachment of chromosomes to spindle microtubules. This is monitored by the mitotic checkpoint that allows chromosome segregation only when all chromosomes are stably attached. Proper functioning of the attachment and checkpoint processes is thus important to prevent chromosomal instability. Both processes rely on the mitotic kinase Mps1.We present here two cell lines in which endogenous Mps1 has been stably replaced with a mutant kinase (Mps1-as) that is specifically inhibited by bulky PP1 analogs. Mps1 inhibition in these cell lines is highly penetrant and reversible. Timed inhibition during bipolar spindle assembly shows that Mps1 is critical for attachment error-correction and confirms its role in Aurora B regulation. We furthermore show that Mps1 has multiple controls over mitotic checkpoint activity. Mps1 inhibition precludes Mad1 localization to unattached kinetochores but also accelerates mitosis. This acceleration correlates with absence of detectable mitotic checkpoint complex after Mps1 inhibition. Finally, we show that short-term inhibition of Mps1 catalytic activity is sufficient to kill cells.Mps1 is involved in the regulation of multiple key processes that ensure correct chromosome segregation and is a promising target for inhibition in anti-cancer strategies. We report here two cell lines that allow specific and highly penetrant inhibition of Mps1 in a reproducible manner through the use of chemical genetics. Using these cell lines we confirm previously suggested roles for Mps1 activity in mitosis, present evidence for novel functions and examine cell viability after short and prolonged Mps1 inhibition. These cell lines present the best cellular model system to date for investigations into Mps1 biology and the effects of penetrance and duration of Mps1 inhibition on cell viability