Optimal Use of Information in Litigation: Should Regulatory Information Be Withheld to Deter Frivolous Suits?

This is the publisher's version, also available electronically from https://editorialexpress.com/cgi-bin/rje_online.cgi?action=view&year=1997&issue=spr&page=120&&tid=120734&sc=rozmKsTqWe examine the value of incorporating regulatory information into the court liability decision and making it publicly available when the causality of harm is uncertain. Public access to regulatory information, coupled with its use in a liability decision, not only improves the accuracy of court adjudication but also guides victims to more informed decisions about their lawsuits, when victims' private information on causality of harm is verifiable to the court. When victims' information is unverifiable, however, withholding regulatory information until after victims bring lawsuits induces them to utilize their private information better in their litigation decisions

Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo.

BackgroundMany patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma.ResultsTMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6-methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals.ConclusionOur results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC

Exotic magnetism on the quasi-FCC lattices of the d3d^3 double perovskites La2_2NaB′'O6_6 (B′' == Ru, Os)

We find evidence for long-range and short-range ($\zeta$ $=$ 70 \AA~at 4 K) incommensurate magnetic order on the quasi-face-centered-cubic (FCC) lattices of the monoclinic double perovskites La$_2$NaRuO$_6$ and La$_2$NaOsO$_6$ respectively. Incommensurate magnetic order on the FCC lattice has not been predicted by mean field theory, but may arise via a delicate balance of inequivalent nearest neighbour and next nearest neighbour exchange interactions. In the Ru system with long-range order, inelastic neutron scattering also reveals a spin gap $\Delta$ $\sim$ 2.75 meV. Magnetic anisotropy is generally minimized in the more familiar octahedrally-coordinated $3d^3$ systems, so the large gap observed for La$_2$NaRuO$_6$ may result from the significantly enhanced value of spin-orbit coupling in this $4d^3$ material.Comment: 5 pages, 4 figure

Exact quantum states of a general time-dependent quadratic system from classical action

A generalization of driven harmonic oscillator with time-dependent mass and frequency, by adding total time-derivative terms to the Lagrangian, is considered. The generalization which gives a general quadratic Hamiltonian system does not change the classical equation of motion. Based on the observation by Feynman and Hibbs, the propagators (kernels) of the systems are calculated from the classical action, in terms of solutions of the classical equation of motion: two homogeneous and one particular solutions. The kernels are then used to find wave functions which satisfy the Schr\"{o}dinger equation. One of the wave functions is shown to be that of a Gaussian pure state. In every case considered, we prove that the kernel does not depend on the way of choosing the classical solutions, while the wave functions depend on the choice. The generalization which gives a rather complicated quadratic Hamiltonian is simply interpreted as acting an unitary transformation to the driven harmonic oscillator system in the Hamiltonian formulation.Comment: Submitted to Phys. Rev.

Exact Partition Function Zeros of a Polymer on a Simple-Cubic Lattice

We study conformational transitions of a polymer on a simple-cubic lattice by calculating the zeros of the exact partition function, up to chain length 24. In the complex temperature plane, two loci of the partition function zeros are found for longer chains, suggesting the existence of both the coil-globule collapse transition and the melting-freezing transition. The locus corresponding to coil-globule transition clearly approaches the real axis as the chain length increases, and the transition temperature could be estimated by finite-size scaling. The form of the logarithmic correction to the scaling of the partition function zeros could also be obtained. The other locus does not show clear scaling behavior, but a supplementary analysis of the specific heat reveals a first-order-like pseudo-transition.Comment: 21 pages, 4 figure

A_4 flavour symmetry breaking scheme for understanding quark and neutrino mixing angles

We propose a spontaneous A_4 flavour symmetry breaking scheme to understand the observed pattern of quark and neutrino mixing. The fermion mass eigenvalues are arbitrary, but the mixing angles are constrained in such a way that the overall patterns are explained while also leaving sufficient freedom to fit the detailed features of the observed values, including CP violating phases. The scheme realises the proposal of Low and Volkas to generate zero quark mixing and tribimaximal neutrino mixing at tree-level, with deviations from both arising from small corrections after spontaneous A_4 breaking. In the neutrino sector, the breaking is A_4 --> Z_2, while in the quark and charged-lepton sectors it is A_4 --> Z_3 = C_3. The full theory has A_4 completely broken, but the two different unbroken subgroups in the two sectors force the dominant mixing patterns to be as stated above. Radiative effects within each sector are shown to deviate neutrino mixing from tribimaximal, while maintaining zero quark mixing. Interactions between the two sectors -- "cross-talk" -- induce nonzero quark mixing, and additional deviation from tribimaximal neutrino mixing. We discuss the vacuum alignment challenge the scenario faces, and suggest three generic ways to approach the problem. We follow up one of those ways by sketching how an explicit model realising the symmetry breaking structure may be constructed.Comment: 14 pages, no figures; v3: Section 5 rewritten to correct an error; new section added to the appendix; added references; v4: minor change to appendix C, version to be published by JHE

Core-Clickable PEG-Branch-Azide Bivalent-Bottle-Brush Polymers by ROMP: Grafting-Through and Clicking-To

The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic tructures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle. We demonstrate copper-catalyzed azide-alkre cycloaddition (CuAAC) "click-to" coupling of a photocleavable doxorubicin (DOX)-alkyne derivative to the azide core. The CuAAC coupling was quantitative across a wide range of nanoscopic sizes (similar to 6-similar to 50 nrn); UV photolysis of the resulting DOX-loaded materials yielded free DOX that was therapeutically effective against human cancer cells

2,4-Bis(4-fluoro­phen­yl)-3-aza­bicyclo­[3.3.1]nonan-9-one

In the title compound, C20H19F2NO, a crystallographic mirror plane bis­ects the mol­ecule, passing through the N, O and two C atoms of the central ring system. The mol­ecule exists in a twin-chair conformation with equatorial dispositions of the 4-fluoro­phenyl groups on both sides of the secondary amino groups; the dihedral angle between the aromatic ring planes is 28.67 (3)°

The ubiquitin receptor S5a/Rpn10 links centrosomal proteasomes with dendrite development in the mammalian brain

SummaryProteasomes drive the selective degradation of protein substrates with covalently linked ubiquitin chains in eukaryotes. Although proteasomes are distributed throughout the cell, specific biological functions of the proteasome in distinct subcellular locales remain largely unknown. We report that proteasomes localized at the centrosome regulate the degradation of local ubiquitin conjugates in mammalian neurons. We find that the proteasomal subunit S5a/Rpn10, a ubiquitin receptor that selects substrates for degradation, is essential for proteasomal activity at centrosomes in neurons and thereby promotes the elaboration of dendrite arbors in the rodent brain in vivo. We also find that the helix-loop-helix protein Id1 disrupts the interaction of S5a/Rpn10 with the proteasomal lid and thereby inhibits centrosomal proteasome activity and dendrite elaboration in neurons. Together, our findings define a function for a specific pool of proteasomes at the neuronal centrosome and identify a biological function for S5a/Rpn10 in the mammalian brain