Antitrust - Merger - Divestiture Action

The Supreme Court of the United States has held that the failing company doctrine cannot successfully be invoked as a defense to an anti-merger action unless defendant establishes both that the acquiring company is the only available purchaser and that there is dim or non-existent hope for reorganization of the failing company through bankruptcy procedures. Citizen Publishing Company v. United States, 89 S. Ct. 927 (1969)

Quantum criticality and emergent symmetry in coupled quantum dots

We consider strongly correlated regimes which emerge at low temperature in coupled quantum dot (or magnetic impurity) systems. In strongly correlated systems a single particle description fails to explain the observed behaviour, so we resort to many body methods. We describe our system using a 2-impurity Anderson model and develop a numerical renormalisation group procedure which provides non-perturbative insight into the low energy behaviour, through calculation of dynamic quantities. We combine this approach with renormalised perturbation theory, thus acquiring a picture of how the Hamiltonian and interactions change at low energies. These approaches are first used to study the emergence of a Kondo effect with an SU(4) symmetry in capacitively-coupled double quantum dot systems. We classify the 'types' of SU(4) symmetry which can emerge and show how an experimentalist might achieve such emergence through tuning their system. We provide a way of distinguishing between the SU(2) and SU(4) Kondo regimes by considering the conductance. We also study a quantum critical point which occurs in the Heisenberg coupled quantum dot/impurity model. There is an anomalous entropy contributed by the impurities in this regime which is indicative of an uncoupled Majorana Fermion. We calculate dynamic quantities in regimes with different symmetries and establish correspondence with the 2-channel Kondo model. We formulate possible pictures of the underlying mechanisms of the critical point and construct a Majorana fermion model for the case with particle-hole symmetry, which explains the non-Fermi liquid energy levels and degeneracies obtained. We conjecture that a Majorana zero mode is present, and that this is responsible for the anomalous entropy.Open Acces

Arthroplasty for Proximal Femur Fracture

With an increasing global incidence of hip fractures, designing appropriate treatment strategies for hip fractures is fundamentally important to healthcare professionals, policymakers, and payers of healthcare services. We will evaluate the role of total hip replacement (THR) in the setting of trauma for the acute treatment of hip fractures. In this chapter, we will compare hemiarthroplasty and total hip replacement in the acute setting while also examining the role of arthroplasty in the setting of failed internal fixation, as well as in pathologic fractures. We will describe the pearls and pitfalls of surgical technique in these scenarios, highlighted with case examples

First Principles Derivation of Effective Ginzburg-Landau Free Energy models for Crystalline Systems

The expression of the free energy density of a classical crystalline system as a gradient expansion in terms of a set of order parameters is developed using classical density functional theory. The goal here is to extend and complete an earlier derivation by L{\"o}wen et al (Europhys. Lett.9, 791, 1989). The limitations of the resulting expressions are also discussed including the boundary conditions needed for finite systems and the fact that the results cannot, at present, be used to take into account elastic relaxation.Comment: 12 pages, no figures, sumitted to Physica

In silico and in vitro screening for potential anticancer candidates targeting GPR120

The G-protein coupled receptor - GPR120 has recently been implicated as a novel target for colorectal cancer (CRC) and other cancer managements. In this study, a homology model of GPR120S (short isoform) was generated to identify potential anti-cancer compounds targeting the GPR120 receptor using a combined in silico docking-based virtual screening (DBVS), structure-activity relationships (SAR) and in vitro screening approach. SPECS database of synthetic chemical compounds (~350,000) was screened using the developed GPR120S model to identify molecules binding to the orthosteric binding pocket followed by an AutoDock SMINA rigid-flexible docking protocol. The best 13 hit molecules were then tested in vitro to evaluate their cytotoxic activity against SW480 - human CRC cell line expressing GPR120. The test compound 1 (3-(4-methylphenyl)-2-[(2-oxo-2-phenylethyl)sulfanyl]-5,6-dihydrospiro(benzo[h]quinazoline-5,1\u27-cyclopentane)-4(3H)-one) showed ~ 90% inhibitory effects on cell growth with micromolar affinities (IC50 = 23.21-26.69 µM). Finally, SAR analysis of compound 1 led to the identification of a more active compound from the SPECS database showing better efficacy during cell-based cytotoxicity assay -5 (IC50 = 5.89-6.715 µM), while a significant reduction in cytotoxic effects of 5 was observed in GPR120-siRNA pre-treated SW480 cells. The GPR120S homology model generated, and SAR analysis conducted by this work discovered a potential chemical scaffold, dihydrospiro(benzo[h]quinazoline-5,1\u27-cyclopentane)-4(3H)-one, which will aid future research on anti-cancer drug development for CRC management

JNK regulates Fas receptor mediated apoptosis in prostate cancer cell lines

Prostate Cancer is a disease that primarily affects elderly men. The incidence of prostate cancer has been progressively increasing in the western world over the last two decades. Life expectancy and diet are believed to be the main factors contributing to this increase in prevalence. Prostate cancer is a slowly progressing disorder and patients often live for over 10 years after initially being diagnosed with prostate cancer. However, patients with hormone refractory prostate cancer have a poor prognosis and generally do not survive for longer than 2 or 3 years. Hormone refractory prostate cancer is responsible for over 200,000 deaths each year and current chemotherapeutic regimens are only useful as palliative agents. The long-term survival rate is poor and chemotherapy does not significantly increase this. Cell lines derived from hormone refractory tumours usually display elevated resistance to many cytotoxic drugs. The Fas receptor is a membrane bound protein capable of binding to a ligand called Fas ligand. Engagement of Fas receptor with Fas ligand results in clustering of Fas receptor on the plasma membrane of cells. A number of proteins responsible for initiating apoptosis are recruited to the plasma membrane and are activated in response to elevated local concentrations. This series of events initiates a proteolysis cascade and that culminates in the degradation of structural and enzymatic processes and the repackaging of cellular constituents within membrane bound vesicles that can be endocytosed and recycled by surrounding phagocytic cells. The Fas receptor is believed to be a key mechanism by which immune cells can destroy damaged cells. Consequently, resistance to Fas receptor mediated apoptosis often correlates with tumour progression. It has been reported that prostate cancer cell lines display elevated resistance to Fas receptor mediated apoptosis and this correlates with the stage of tumour from which the cell lines were isolated. JNK, a stress-activated protein kinase, has been implicated both with increased survival and increased apoptosis in prostate cancer. Elevated endogenous JNK activity has been demonstrated to correlate with prostate cancer progression. It has been shown that endogenous JNK activity increases the expression of anti-apoptotic proteins and can increase the resistance of prostate cancer cell lines to chemotherapy. In addition, elevated endogenous JNK activity is required for improved proliferation and transformation of a number of epithelial tumours. However, prolonged JNK activation in response to cytotoxic stimuli can increase the sensitivity of cells to apoptosis. Prolonged JNK activity appears to induce the expression of a separate set of genes responsible for promoting apoptosis. Our group has recently shown that activation of JNK by chemotherapeutic drugs can sensitise DU 145 prostate carcinoma cells to Fas receptor mediated apoptosis. In order toidentify novel targets for treating hormone refractory prostate cancer we have investigated the role of JNK in Fas receptor mediated apoptosis. We have demonstrated that prolonged JNK activation is defective in DU 145 cells in response to Fas receptor activation alone. Co-administering anisomycin, a JNK agonist, greatly enhances the ability of DU 145 cells to undergo apoptosis by increasing the rate of Caspase 8 cleavage. We also investigated the role of endogenous JNK activity in Fas receptor mediated

3D mammalian cell culture models in toxicology testing

3D cell culture can be successfully used as an alternative to laboratory animals, and as a cost effective and time-saving tissue culture technique, which also reduces the trial period for drug testing