20 research outputs found
To what extent are investment bank-differentiating factors relevant for firms floating moderate-sized IPOs?
One explanation provided for the relatively high and increasingly stable spreads for moderate-sized IPOs (80 million) documented in Chen and Ritter (2000) is that issuing firms focus less on price and more on a combination of investment bank-differentiating factors (such as underwriter prestige, analyst coverage, industry expertise, under-pricing, price stabilization activities, liquidity provision, and so on,) and banks use industry-based differentiation as a source of market power. Using a new approach developed in a model of firm location choice due to Ellison and Glaeser (1997), this paper presents some evidence on the combined relevance of such bank-differentiating factors, over and above bank size, for firms choosing investment banks for floating IPOs. For moderate-sized IPOs, there is a little, but not much evidence that such factors are a good explanation for high and increasingly stable spreads. Other than in a few of the largest industries, bank-differentiating factors are not significantly relevant for a large proportion of industries. Moreover, one aggregate measure of differentiation is declining over time.Investment Banking, Initial Public Offering, Differentiating Factors, Concentration, 7 percent puzzle
Inverse Heat Conduction Problem in a Semi-Infinite Circular Plate and its Thermal Deflection by Quasi-Static Approach
This paper concerns the inverse heat conduction problem in a semi-infinite thin circular plate subjected to an arbitrary known temperature under unsteady condition and the behavior of thermal deflection has been discussed on the outer curved surface with the help of mathematical modeling. The solutions are obtained in an analytical form by using the integral transform technique
Inverse Heat Conduction Problem in a Semi-Infinite Cylinder and its Thermal Stresses by Quasi-Static Approach
The present paper deals with the determination of unknown temperature and thermal stresses on the curved surface of a semi-infinite circular cylinder defined as 0 ≤ r ≤ a , 0 ≤ z ≤ ∞. The circular cylinder is subjected to an arbitrary known temperature under unsteady state condition. Initially, the cylinder is at zero temperature and temperature at the lower surface is held fixed at zero. The governing heat conduction equation has been solved by using the integral transform method. The results are obtained in series form in terms of Bessel’s functions. A mathematical model has been constructed for aluminum material and illustrates the results graphically
A study of SSPE: early clinical features
Thirty two patients with subacute sclerosing panencephalitis (SSPE) admitted under the care of Department of Neurology at JJ Hospital and Grant Medical College, Mumbai during the period 1998-2003 were analyzed. All patients were evaluated clinically, with relevant investigations and neuroimaging wherever possible. Particular attention was given to early clinical features. Diagnosis was confirmed by cerebrospinal fluid study for measles antibody and by electroencephalography. The mean age of our patients was 13.4 years and the vaccinated patients tended to be older. Nine patients had received measles vaccination. Twelve percent of patients were older than the age of 20 years at the onset of symptoms. Approximately 40.6% of patients presented with symptoms of loss of vision, seizures and behavioral change. At this stage myoclonus and cognitive decline were conspicuous by their absence. Eventually typical features like myoclonus and cognitive decline evolved after a mean period of 8 months. Even in the present era, SSPE continues to remain the most important cause of progressive myoclonic epilepsy. With progressive increase in age of presentation, in patients with features like loss of vision, seizures and behavioral changes, SSPE should be carefully considered. (J Pediatr Neurol 2004; 2(2): 73-77)
BACE-1 inhibition by protriptyline.
<p><b>A</b>. Determination of IC50 of BACE-1 by using various concentrations of protriptyline. The sigmoidal curve indicates the best fit for the percentage inhibition data obtained <b>B</b>. Lineweaver-Burk analysis to estimate the kinetic constants. It showed competitive inhibition. <b>C</b>. Snapshot of drug binding with active site of BACE-1. Active site residues in BACE-1 are in line representation. <b>D</b>. Active site of BACE-1. The structures from unbound (green) and ligand bound (orange) simulations are shown after all - atom superimposition. Snapshots are generated using PyMol.</p
Molecular Investigations of Protriptyline as a Multi-Target Directed Ligand in Alzheimer's Disease
<div><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non-toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE), β-secretase (BACE-1), and amyloid β (Aβ) aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment.</p></div
Destabilization of amyloid dimer by protriptyline.
<p><b>A</b>. Evolution of monomer-monomer interaction strength over time for free dimer (broken line) and Protriptylline-bound dimer (solid line). <i>Inset</i>. Distributions of the interactions from multiple trajectories, and the dimer interactions with Protriptylline (in brown) <b>B</b>. Distributions of the asphericity for free (in broken line) and Protriptylline-bound (solid line) dimer <b>C</b>. Representative snapshot of most populated cluster of free, and <b>D</b>. Protriptylline-bound dimer [16–20 region in blue colour with 19–20 showed in line representation; protriptyline in red colour and two Aβ peptides are in cyan and limon colour respectively] <b>E</b>. Residue-residue contact probabilities for free dimer, and <b>F</b>. Protriptylline-bound dimer <b>G</b>. Residue-wise Beta sheet percentages for free dimer (in red) and Protriptylline-bound dimer (in blue) <b>H</b>. Residue-wise helical percentages for free dimer (in red) and Pro-bound dimer (in blue).</p
Protriptyline as MTDL.
<p>The scheme represents that protriptyline (at the center) is able to inhibit key targets of AD pathogenesis such as AChE, BACE-1, Amyloid aggregation and glycation induced amyloid aggregation.</p
Virtual screening by docking.
<p><b>A</b>. Heat map analysis of binding constants of 140 FDA approved nervous system drugs screened against Aβ, AChE and β-secretase by Autodock tool 4.2. In the gradient ruler, red colour indicated strong binding (ΔG<−6 kcal/mol), while green colour indicate weak binding (ΔG>−3 kcal/mol) and the five drugs showing higher affinity to all the above mentioned targets were zoomed. <b>B</b>. Chemical structures of the five drugs. All are tricyclic anti-depressant drugs.</p
Cell viability in neuro2a cells.
<p>Effect of various concentrations of protriptyline (25–500 µM) on cell viability was assessed by MTT assay. Cells were 90% viable up to 150 µM protriptyline concentration.</p