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In this paper, we expand the double price elasticity theory developed by Greenhut, Hwang, and Ohta (1974) by including a general cost condition for a profit-maximizing monopolist, cartel, or price leader. Our model generalizes the conventional second-order condition as it incorporates the non-converging price elasticity. Contrary to the textbook prediction, a structural changes or an income effect in tobacco, crude oil and other demand inelastic markets can render the price elasticity of demand to oscillate for a long time but never reach its theoretical limit even in a very long time.

The aqueous solution of poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers (>15. wt. %) undergoing “clear sol−gel−turbid sol” transition as the temperature increases from 20 to 60 °C has been developed. Light scattering and ¹³C NMR study suggested that the transition mechanisms are the micellar aggregation for the clear sol to gel transition (lower transition), whereas the increase in PCL molecular motion for gel to turbid sol transition (upper transition). In contrast to the previous thermogelling biodegradable polymers with a sticky paste morphology, the powder form of the PEG-PCL-PEG triblock copolymers makes it easy to handle and allows fast dissolution in water. Therefore, the lyophilization into a powder form followed by facile reconstitution was possible. This system is believed to be promising for drug delivery, cell therapy, and tissue engineering.

Abrus agglutinin (AAG), a low-toxicity protein from the plant Abrus precatorius, is less lethal than abrina (ABRa) in mice (LD(50) = 5 mg/kg versus 20 microg/kg of body weight). Nucleotide sequence analysis of a cDNA clone encoding full-length AAG showed an open reading frame with 1641 base pairs, corresponding to a 547-amino acid residue preproprotein containing a signal peptide and a linker region (two amino acid residues) between the AAG-A and AAG-B subunits. AAG had high homology to ABRa (77.8%). The 13 amino acid residues involved in catalytic function, which are highly conserved among abrins and ricins, were also conserved within AAG-A. The protein synthesis inhibitory activity of AAG-A (IC(50) = 3.5 nM) was weaker than that of ABRa-A (0.05 nM). Molecular modeling followed by site-directed mutagenesis showed that Pro(199) of AAG-A, located in amphiphilic helix H and corresponding to Asn(200) of ABRa-A, can induce bending of helix H. This bending would presumably affect the binding of AAG-A to its target sequence, GpApGpAp, in the tetraloop structure of the 28 S rRNA subunit and could be one of the major factors contributing to the relatively weak protein synthesis inhibitory activity and toxicity of AAG.

The effect of poly(ethylenimine) (PEI) dissolved in water on the surface pressure−area (π−A) isotherm of stearic acid (STA) at the air/water interface was investigated. When the concentration of PEI was quite low, for example, 2.2 × 10^-4 g/L (5.1 × 10^-6 M in monomeric unit concentration), the isotherm of the STA monolayer was little affected by PEI. On a concentrated PEI solution, for example, at 2.2 × 10^-2 g/L, the isotherm of the STA monolayer exhibited a noticeable variation as a function of subphase pH, particularly in basic conditions. The isotherm of STA could be obtained very reproducibly even at pH 10.4. At basic pHs, PEI induced the occurrence of a wide plateau region in an isotherm that could be attributed to the coexistence of liquid-condensed (LC) and liquid-expanded (LE) phases of STA on a water subphase. In addition, the collapse pressure of the STA monolayer was raised to 68 mN/m, indicating that the stability of the monolayer could be increased dramatically by virtue of an acid−base-type interaction between the amine group of PEI and the carboxyl group of STA. In situ reflection−absorption infrared (RAIR) spectroscopy revealed that at acidic pHs STA molecules should form two-dimensional crystalline domains even at high “per molecular” area. In contrast, at basic pHs RAIR spectral data dictated that STA molecules were strongly disordered at high per molecular area, and a near-crystalline structure seemed to form only when the per molecular area was lowered to a value corresponding to a pure LC phase in the π−A isotherm of STA on the PEI-containing subphase.

Territrem B (TRB) is a fungal metabolite isolated from Aspergillus terreus shown previously to be a potent and irreversible inhibitor of acetylcholinesterase (AChE). In the present study, a number of binding and inhibition assays were carried out to further characterize the inhibitory effect of TRB. The results indicate that the binding of TRB (a) is much more selective than a well characterized selective inhibitor of AChE, BW284C51, (b) adopts a one-to-one stoichiometry with the enzyme, (c) cannot be undone by an AChE-regenerating oxime agent, which contrasts the ability of 8 M urea to release AChE-bound TRB, (d) is enhanced by high concentration NaCl but prevented, unless preincubated, by Triton X-100, and (e) exhibits quasi-first order kinetics with an overall inhibition constant of 0.01 nM(-1) min(-1). Together these results suggest a very different irreversible binding (a noncovalent type) from that of the covalent type, which involves typical irreversible AChE inhibitors such as diisopropylfluorophosphate and neostigmine. According to the prediction of a molecular modeling study, the distinct AChE inhibitory characteristics of TRB may arise from the inhibitor being noncovalently trapped within a unique active-site gorge structure of the enzyme. It was predicted that an optimal TRB. AChE binding would position a narrowing connection of the TRB structure at a constricted area near the entrance of the gorge, thereby providing a structural basis for the observed irreversible binding.

As the field of biomolecular structure advances, there is an ever‐growing need for accurate modeling of molecular energy surfaces to simulate and predict the properties of these important systems. To address this need, a second generation amide force field for use in simulations of small organics as well as proteins and peptides has been derived. The critical question of what accuracy can be expected from calculations in general, and with this class II force field in particular, is addressed for structural, dynamic, and energetic properties. The force field is derived from a recent methodology we have developed that involves the systematic use of quantum mechanical observables. Systematic ab initiocalculations were carried out for numerous configurations of 17 amide and related compounds. Relative energies and first and second derivatives of the energy of 638 structures of these compounds resulted in 140,970 ab initioquantum mechanical observables. The class II peptide quantum mechanical force field (QMFF), containing 732 force constants and reference values, was parameterized against these observables. A major objective of this work is to help establish the role of anharmonicity and coupling in improving the accuracy of molecular force fields, as these terms have not yet become an agreed upon standard in the ever more extensive simulations being used to probe biomolecular properties. This has been addressed by deriving a class I harmonic diagonal force field (HDFF), which was fit to the same energy surface as the QMFF, thus providing an opportunity to quantify the effects of these coupling and anharmonic contributions. Both force field representations are assessed in terms of their ability to fit the observables. They have also been tested by calculating the properties of 11 stationary states of these amide molecules. Optimized structures, vibrational frequencies, and conformational energies obtained from the quantum calculations and from both the QMFF and the HDFF are compared. Several strained and derivatized compounds including urea, formylformamide, and butyrolactam are included in these tests to assess the range of applicability (transferability) of the force fields. It was found that the class II coupled anharmonic force field reproduced the structures, energies, and vibrational frequencies significantly more faithfully than the class I harmonic diagonal force field. An important measure, rms energy deviation, was found to be 1.06 kcal/mol with the class II force field, and 2.30 kcal/mol with the harmonic diagonal force field. These deviations represent the error in relative configurational energy differences for strained and distorted structures calculated with the force fields compared with quantum mechanics. This provides a measure of the accuracy that might be expected in applications where strain may be important such as calculating the energy of a system as it approaches a (rotational) barrier, in ligand binding to a protein, or effects of introducing substituents into a molecule that may induce strain. Similar results were found for structural properties. Protein dynamics is becoming of ever‐increasing interest, and, to simulate dynamic properties accurately, the dynamic behavior of model compounds needs to be well accounted for. To this end, the ability of the class I and class II force fields to reproduce the vibrational frequencies obtained from the quantum energy surface was assessed. An rms deviation of 43 cm−1was achieved with the coupled anharmonic force field, as compared to 105 cm−1with the harmonic diagonal force field. Thus, the analysis presented here of the class II force field for the amide functional group demonstrates that the incorporation of anharmonicity and coupling terms in the force field significantly improves the accuracy and transferability with regard to the simulation of structural, energetic, and dynamic properties of amides.  © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 430–458, 1998

The methodology for deriving class II force fields has been applied to acetal, hemiacetal, and carbohydrate compounds. A set of eighteen model compounds containing one or more anomeric centers was selected for generating the quantum mechanical energy surface, from which the force field was derived and the functional form assessed. The quality of the fit was tested by comparing the energy surface predicted by the force field with ab initio results. Structural, energetic, and dynamic properties (vibrational frequencies) were analyzed. In addition, α and β anomeric equilibrium structures and energies of 2-methoxytetrahydropyran, 2-deoxyribose, and glucose were computed at the HF/6-31G* and higher ab initio levels. These calculations provide test data from molecules outside the training set used to derive the force field. The quantum calculations were used to assess the ability of the class II force field and two quadratic diagonal (class I) force fields, CVFF, and Homans' extension of the AMBER force field, to account for the anomeric effects on the structural and energetic properties of carbohydrate systems. These class I force fields are unable to account for observed structural and energetic trends, exhibiting deviations as large as 5 kcal/mol in relative energies. The class II force field, on the other hand, is shown to reproduce anomeric structural as well as energetic differences. An energy component analysis of this force field shows that the anomeric differences are dominated by torsional energies, although coupling terms, especially angle/torsion, also make significant contributions (roughly 1 kcal/mol in glucose). In addition, the force field accurately accounts for both anomeric and exo-anomeric energy differences in 2-methoxytetrahydropyran, and anomeric energy differences in 2-deoxyribose and glucose. © 1998 John Wiley & Sons, Inc. Biopoly 45: 435–468, 1998

This paper extends Löschian theory towards the end of claiming its applicability to heterogeneous space economies as well as to the homogeneous space economy. It then tests the theory by examining the relationships between fixed costs and market-area sizes. The result is an empirical demonstration that the level of fixed costs in the United States is so low that market areas too large to be approximated by the optimal hexagonal market-area shape are not likely to be associated with competition in free-enterprise countries. It is in fact indicated that competitive firms sell over comparatively small market areas. The related conclusion follows that there is nothing in market-area studies (empirical or theoretical) that would imply inefficiency or failure to maximize consumer wants.

Recently, a quantum mechanical Class II force field (QMFF) was derived from a fit of HF/6–31G* ab initio energy and energy derivative data for alkanes, and a comparison of this quantum force field and the ab initio energy and energy derivatives was presented. In this work, the quantum force field is further evaluated with regard to its accuracy, and, more importantly, transferability. A detailed comparison between structures, frequencies, and energies calculated from quantum mechanics and from the classical analytical form is given for a set of molecules selected from both those used in the original training set and molecules selected from outside the training set. None of these properties were used directly in the original derivation of the force field. In order to assess the importance of anharmonic and coupling interactions that occur in and contribute to molecular energy surfaces, the results are compared to a diagonal quadratic force field. It is demonstrated that the QMFF functional form is capable of calculating the ab initio bond lengths, bond angles, torsion angles, and conformational energy differences to an rms accuracy of 0.003 Å, 0.4°, 1.2°, and 1.0 kcal/mol, respectively. This compares quite well to corresponding deviations of 0.006 Å, 0.8 Å, 2.3°, and 3.3 kcal/mol for a harmonic diagonal force field. Excluding three‐ or four‐membered rings, the QMFF rms frequency deviations were 24 cm−1, which again is much better than the ˜100 cm−1deviations for the harmonic diagonal force field. Larger average rms frequency deviations of 36 and 71 cm−1were found with QMFF for molecules with three‐ and four‐membered rings. An in‐depth analysis of C‐H and C‐C bond length, H‐C‐H, H‐C‐C, and C‐C‐C bond angle, and C‐C‐C‐C torsion angle deviations is also presented, along with a similar characterization of frequency deviations in C‐H stretching, C‐C stretching, C‐C‐C bending, and torsion modes. It is concluded from these results that the use of quantum energy surfaces allows us to derive a (Class II) functional form which is not only more accurate, but also more transferable than previous generation force fields.

An experiment with well defined gas-water interfacial surface area was developed to study the crystallization and crystal growth of methane hydrates. Measurable formation rates were observed only when melting ice was involved. No hydrates nucleated from liquid water or from non-melting ice. It is concluded that melting ice, which like hydrate water is hydrogen-bonded, provides a template for hydrate nucleation as well as providing a heat sink for absorbing the heat of formation during hydrate growth. The experiment was conducted in the absence of mixing so that hydrate crystals grew under quiescent conditions.

A critical survey of previously reported van der Waals parameters for alkali metal cations and halide anions is presented. A new set of force field parameters is proposed, derived by fitting the experimental lattice constants and lattice energies of 20 ionic alkali halide crystals. These parameters are constrained to satisfy two relationships connecting the ions with the isoelectronic noble gases&sbd;the relative van der Waals radii R* and the coefficients of the London dispersion energies C6&sbd;using the experimentally determined noble gas van der Waals parameters. In addition to reproducing physical trends in common with atoms of isoelectronic species, the present parameters predict more accurate crystal structures and energies and, when combined with a molecular force field for water, also quite accurate gas-phase ion−water interaction energies and aqueous solution structures compared to the computed results previously reported by other authors.

Lacking structures resolved at atomic resolution, the great majority of membrane proteins have typically been depicted in a schematic two-dimensional (2D) topology consisting of putative transmembrane domains predicted from hydropathy plots. As more and more sequences of membrane proteins become available from genome projects, there is a need to automate the process of generating the schematic topology while allowing important information, such as the individual amino acid and the extent to which it is conserved in evolution, to be conveniently inspected. We addressed this need by developing a program called VHMPT.

Background & Aim: After Vapotherm HHFNC was discontinued, the other type of HHFNC (RT329 Infant Oxygen Delivery System) was introduced but there are few studies using this system. The aim of this study is to evaluate the effectiveness and safety of HHFNC as a mode of respiratory support after extubation for preterm infants compared with nCPAP.Methods: This was a retrospective study of preterm infants supplied by HHFNC or nCPAP after extubation at Korea University Ansan Hospital. For short term effects, the change of heart rate, respiration rate and FiO2 needed for respiratory stabilization were monitored. The rates of re-intubation/weaning within 72 hours after extubation were measured. The complication (localized nasal necrosis, localized nasal infection and air leak syndrome) after use were recorded.Results: HHFNC group (n=23) and nCPAP group (n=23) had similar gestational age and birth weight. There were no significant differences of short term effects in both groups. The rate of re-intubation was 26% (6/23) in HHFNC group and 17% (4/23) in nCPAP group (P=0.78). The rate of weaning from the device was 39% (9/23) in HHFNC group and 48% (11/23) in nCPAP group (P=0.52). There were no statistically significant differences of complications in both groups.Conclusions: Comparing HHFNC with nCPAP, there were the similar rates of re-intubation/weaning and no differences in adverse outcomes. HHFNC may be an effective and safe as a mode of respiratory support after extubation in preterm infants. However, well-designed random trial control studies are needed for clinical application.