Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling

In this report, inhibitors of the gamma-secretase enzyme have been exploited to characterize the antiproliferative relationship between target inhibition and cellular responses in Notch-dependent human T cell acute lymphoblastic leukemia (T-ALL) cell lines. Inhibition of gamma-secretase led to decreased Notch signaling, measured by endogenous NOTCH intracellular domain (NICD) formation, and was associated with decreased cell viability. Flow cytometry revealed that decreased cell viability resulted from a G(0)/G(1) cell cycle block, which correlated strongly to the induction of apoptosis. These effects associated with inhibitor treatment were rescued by exogenous expression of NICD and were not mirrored when a markedly less active enantiomer was used, demonstrating the gamma-secretase dependency and specificity of these responses. Together, these data strengthen the rationale for using gamma-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic.     

UTILIZATION OF TOOLS FOR SUCCESSFUL. TROUBLESHOOTING OF STRUCTURAL PROBLEMS

A structural failure problem was solved using an integrated and iterative program of testing and analysis. The steps taken in solving the problem were: analytical calculations; operational testing; qualifications of analytical results; problem identification; design of corrective action; and confirmatory testing.     

Vortex lattice transitions in YNi2B2C

We have performed extensive small-angle neutron scattering (SANS) diffraction studies of the vortex lattice in single crystal YNi₂B₂C for B‖c. High-resolution SANS, combined with a field-oscillation vortex lattice preparation technique, allows us to separate Bragg scattered intensities from two orthogonal domains and accurately determine the unit cell angle, β. The data suggest that upon increasing field there is a finite transition width where both low- and high-field distorted hexagonal vortex lattice phases, mutually rotated by 45°, coexist. The smooth variation of diffracted intensity from each phase through the transition corresponds to a redistribution of populations between the two types of domains.     

Transitions in glasses at low temperatures

Length-temperature measurements from ?180°C to the glass transition temperature have been made on a poly(vinyl alkyl ether) series, poly(ethylene terephthalate), and a tetrafluoroethylene-trifluoropropylene copolymer series.

Consistent with low frequency dynamic measurements, the poly(vinyl alkyl ethers) exhibit a glass-glass transition? Tgg [1] between Tg and Tg ?70°C with evidence of another at about ?160 to ?180°C. With increasing side-chain length, the expansion coefficient below Tg- and the magnitude of the g-g transition increase, and the value of the Simha-Boyer free-volume product decreases, suggesting retention of excess free volume by the flexible pendant group. This behavior is analogous to that observed for poly(alkyl methacrylates) except that the latter system exhibited two g-g transitions, the lower of which coincided with Tgg [1] observed here.

Poly(ethylene terephthalate) samples, both amorphous and crystalline, exhibit two T > Tg transitions at about ?85 and ?40°C. Dynamic results resolve only one relaxation in this temperature range.

The glass temperatures of the tetrafluoroethylene-trifluoropropylene copolymer series, as determined by both dilatometry and differential scanning calorimetry, extrapolate to a Tg, for 100% amorphous PTFE of 11-16°C. Two g-g transitions, present in each homo-polymer, persist in the copolymers, indicating that only a small number of molecular units are involved. The magnitude of these relaxations, however, as measured by the change in expansion coefficient, is dependent on copolymer composition.     

Flow phenomena in floppy tubes

Collapsible tubes, which occur all over the body, have unique properties from the point of view of both physics and physiology. A brief review is attempted of first the basic observable properties, followed by simple theory to explain the steady-flow aspects and an overview of the somewhat more complex theories for unsteady flow, in particular the flow-induced oscillations. The experimental evidence from laboratory studies is reviewed with particular emphasis on the dynamical system aspects. A final section looks at the current position and prospects.     

Modelling medieval military logistics: an agent-based simulation of a Byzantine army on the march

Although historical studies are frequently perceived as clear narratives defined by a series of fixed events; in reality, even where critical historical events may be identified, historic documentation frequently lacks corroborative detail to support verifiable interpretation. Consequently, interpretation rarely rises above the level of unproven assertion and is rarely tested against a range of evidence. Agent-based simulation can provide an opportunity to break these cycles of academic claim and counter-claim. This paper discusses the development of an agent-based simulation designed to investigate medieval military logistics so that new evidence may be generated to supplement existing historical analysis. It uses as a use-case the Byzantine army’s march to the battle of Manzikert (AD 1071), a key event in medieval history. The paper focuses primarily on the design of the agents and the environment they interact with, as well as how the agent-based simulation as a whole can be used to generate new parameters with which historical evidence can be situated.     

Magnetism and superconductivity in ErNi2B2C

We have performed a series of neutron diffraction experiments from the magnetic order and the vortex lattice in single crystal ErNi₂B₂C. The incommensurate magnetic structure develops additional even harmonics below the ‘ferromagnetic’ ordering temperature, T _F of 2.3 K. This feature and the existence of rods of diffuse scattering suggest the development of ferromagnetic microdomain walls. The magnetic structure is very sensitive to the application of a magnetic field with changes in modulation vector and harmonic content. Studies of the vortex lattice show the presence of a 45° reorientation transition and a distorted hexagonal to square transition as a function of applied field. Further distortions of the vortex lattice occur at T _N, but no changes are seen at T _F.