cssi/SciSciGPT-SciSciNet huggingface dataset:
'Not a Box of Nuts and Bolts': Distribution Channels for Specialty Drugs

One of the most important trends in the pharmaceutical industry is the rapid growth of specialty drugs. Specialty drugs, mostly bio-based, tend to be high-risk, high-priced, and more regulated than traditional drugs, resulting in unprecedented challenges in distribution. Such challenges lead to the emergence of specialty distributors (SDs), which, compared with traditional wholesalers (WSs), manage more controlled networks and carry a smaller variety of drugs. Using a unique dataset assembled from multiple proprietary and public data sources on transactions, inventory, and chargebacks for 419 specialty drugs across 11 manufacturers (including 8 of the top 15 pharmaceutical manufacturers),161 distributors, and129,911 POCs (point-of-care) in 2012-2015, we investigate unique factors associated with manufacturers’ SD usage (vs. WSs). We also develop a nested logit model to examine factors that drive manufacturers’ choice of specific SDs if they were to use an SD channel. We find that the restrictive access element of regulations (instead of regulations in general), downstream POC’s required drug variety, and distributors’ experience in providing critical value-added services for manufacturers (i.e., managing chargebacks) are associated with higher SD usage. Moreover, if a manufacturer were to use an SD channel, it is more likely to choose one if it has used this SD or the SD-affiliated WS before, or if this SD has better performance. WSs and SDs represent distinct approaches to balance channel accessibility and channel control. Our results provide important insights and guidance to manufacturers, regulators, and downstream POCs, while contributing to the limited empirical research on B2B distribution decisions.
Moving-Image Astrometry with the Multi-Anode Microchannel Array (MAMA) Detector

Consider the possible astrometric use of the following concept: If the image of a field of stars is moved past a high-speed detector array at a precisely known velocity, relative positions can be determined by measuring time intervals. Attractive features of this approach are: times can be measured very accurately with photoelectric detectors; a relatively large area of the sky may be swept for reference stars; the images are measured essentially on-axis; and seeing effects can be partially frozen out. The only available detector with spatial and temporal resolution and stability adequate for this technique is the MAMA. A rudimentary observational test with this detector has yielded promising results. Further observations are planned to determine whether milliarcsecond accuracy can be obtained.
Evaluation and Enhancement of Bayesian Rule-Sets in a Genetic Algorithm Learning Environment for Classification Tasks

The paper describes a learning environment named DEL-VAUX for classification tasks that learns Bayesian rule-sets from sets of examples. A genetic algorithm approach is used for this purpose, in which a population consists of sets of rule-sets that generate offspring through the exchange of rules, permitting fitter rule-sets to produce offspring with a higher probability. A bucket brigade algorithm for Bayesian rule-sets called reward punishment mechanism is introduced, which evaluates the performance of a Bayesian rule within a rule-set. It employs fuzzy techniques to measure the ”goodness” of a rule within a rule-set.
New flavoenzymes: Current Opinion in Structural Biology 1991, 1:954–967

Abstract Ten new flavoenzyme structures have been determined during the period of this review. Five new members of the flavoenzyme family represented by glutathione reductase have been identified; these work on a diverse range of substrates and show features of both divergent and convergent evolution. The number of structural classes or families has been expanded from four to six. The two new classes of flavoenzyme are both electron transferase. One of these, ferredoxin reductase, appears to be prototypical for a large family of flavoenzymes.
Design for a lithographically patterned bioartificial endocrine pancreas.

Cell encapsulation provides a means to transplant therapeutic cells for a variety of diseases including diabetes. However, due to the large numbers of cells, approximately on the order of a billion, that need to be transplanted for human diabetes therapy, adequate mass transport of nutrients such as oxygen presents a major challenge. Proof-of-concept for the design of a bioartificial endocrine pancreas (BAEP) that is optimized to minimize hypoxia in a scalable and precise architecture is demonstrated using a combination of simulations and experiments. The BAEP is composed of an array of porous, lithographically patterned polyhedral capsules arrayed on a rolled-up alginate sheet. All the important structural variables such as the capsule dimensions, pore characteristics, and spacing can be precisely engineered and tuned. Further, all cells are encapsulated within a single device with a volume not much greater than the total volume of the encapsulated cells, and no cell within the device is located more than 200 μm from the surrounding medium that facilitates efficient mass transport with the surroundings. Compared with gel-based encapsulation methods, our approach offers unprecedented precision and tunability of structural parameters as well as the volume of the encapsulated cells and consequently the amount of secreted insulin. Our work highlights the utility of lithography and self-assembly in the fabrication of micro- and nanostructured three-dimensional structures that simulate the function of natural endocrine organs.
Mechanical testing of metallic and polymeric intrafascicular electrodes

The authors are exploring alternatives to Pt/Ir wire for constructing ultra-flexible neural intrafascicular electrodes suitable for chronic implantation. In this study the authors measured the flexural properties of several kinds of fine metal wires and conducting polymer fibers. The fibers were made either of intrinsically conductive polymers (polyaniline, polythiophene) or good mechanical polymers (nylon, Kevlar). The latter were made conductive through sputter coating with a thin layer of platinum. While the fiber flexibility (moment required for a 7.5/spl deg/ deflection) of the nylon and Kevlar fibers ranged from 10-35 /spl mu/g-cm, some 50 to 150 times less stiff than Pt/Ir wire, their tensile strengths were approximately equal to that of Pt/Ir wire. Polymer fibers represent promising materials for ultra-flexible nerve electrodes. >
Protamine-induced Aggregation of Unilamellar Liposomes

Separation of non-encapsulated drug from unilamellar liposomes is critical for accurate estimation of encapsulation as well as to recover the non-encapsulated drug. The most commonly used methods for this purpose are either tedious or expensive. In this study we investigated the separation of free drug by aggregation of unilamellar liposomes by the addition of protamine. Several phospholipids and cholesterol were used in the preparation of liposomes. Stearylamine was added to provide positive charge and phosphatidylserine or dicetylphosphate for negative charge. Multilamellar liposomes (MLVs) were prepared by thin-film hydration and were converted to large unilamellar liposomes (LUVs) by passing through a 0.2 μm polycarbonate membrane using an extruder. Particle size of liposome preparations was characterized. Protamine solution in phosphate-buffered saline (PBS) was added to LUV preparations, vortex mixed and equilibrated overnight at room temperature. Aggregates of protamine-liposome were separated by centrifugation. The negatively charged liposomes aggregated immediately after the addition of protamine, whereas neutral and positively charged liposomes required overnight incubation. Also, the amount of protamine required for aggregation was significantly higher for neutral and positively charged liposomes (40 mg mL−1) compared with negatively charged liposomes (5 mg mL-1). The results indicated no leakage of encapsulated drug due to aggregation. It can be concluded that neutral as well as charged liposomes can be separated by protamine aggregation to estimate encapsulation efficiency as well as to separate non-encapsulated drug from liposomes.
Effect of thermal pretreatment on equilibrium moisture content of lignocellulosic biomass

The equilibrium moisture content (EMC) of raw lignocellulosic biomass, along with four samples subjected to thermal pretreatment, was measured at relative humidities ranging from 11% to 97% at a constant temperature of 30 °C. Three samples were prepared by treatment in hot compressed water by a process known as wet torrefaction, at temperatures of 200, 230, and 260 °C. An additional sample was prepared by dry torrefaction at 300 °C. Pretreated biomass shows EMC below that of raw biomass. This indicates that pretreated biomass, both dry and wet torrefied, is more hydrophobic than raw biomass. The EMC results were correlated with a recent model that takes into account additional non-adsorption interactions of water, such as mixing and swelling. The model offers physical insight into the water activity in lignocellulosic biomass.
Corporate governance under proportional electoral systems

This paper provides a political explanation for the form of corporate governance captured by the degree of minority shareholder protection (MSP). Using a multi-stage game model of three-party competition under proportional electoral systems, I demonstrate that the electoral threshold—the minimum percentage of votes a party must receive to get at least one seat in parliamentary PR systems—is inversely related to the degree of MSP. This finding represents an important modification to formal models in the political economic literature that tends to omit the political process.
Measurement of the Incremental Friction Coefficient of Several Homologous Series of Straight‐Chain Hydrocarbon Compounds

Summary The incremental friction coefficient fΔ was measured as a function of speed for a number of straight-chain polar hydrocarbon compounds. These compounds included alcohols, acids, amines, and two esters. In most cases, it was found to be independent of speed at slow speeds and decreased with speed at higher speeds. The amines were the only exception, in that the value of fΔ rose slightly with speed. The constant slow speed value of fΔ was found to decrease generally with increasing chain length in any single homologous series. There seems to be more correlation of the shape of this curve offΔ vs. chain length with the surface metal than with the lubricant type. The friction of mixtures of two acids of rather different chain lengths showed no evidence of any strongly preferential adsorption of either component. This agrees with the relatively small difference in their adsorption energies. The friction of a dibasic acid was high and the damage to the surfaces was great. This agrees with what is known about the orientation of adsorbed molecules of compounds of this type.
Digitally Savvy Citizenship: The Role of Internet Skills and Engagement in Young Adults' Political Participation around the 2008 Presidential Election

Popular narratives assume that digital media play a central role mobilizing voters and especially young adults. Based on unique survey data of a diverse group or young adults from Spring, 2009, we ...
PROPERTIES OF A PROTEIN ANTIGENICALLY RELATED TO TRYPTOPHAN SYNTHETASE IN NEUROSPORA CRASSA

Sufficient evidence has accumulated in recent years, in part through gene enzyme studies in microorganisms (Bonner, 1951; Yanofsky, 1956), to implicate the gene as a regulator of certain qualitative and quantitative aspects of protein formation (Horowitz, 1956). Although examples of alterations in protein structure arising through gene mutation are limited in number, there are many cases in which gene change has resulted in the loss of a specific enzymatic activity. Since the basis for detecting an enzyme deficiency primarily rests on an inability to demonstrate enzymatic activity under various experimental conditions (Mitchell and Lein, 1948; Yanofsky, 1952) several fundamental problems arise. It is of the greatest interest to know whether enzyme deficiencies represent a complete loss of the capacity to synthesize the enzyme, or whether molecules structurally similar to the enzyme, but devoid of enzymatic activity, continue to be formed. This aspect of the problem becomes particularly significant in those cases where numerous mutations at a particular locus have been observed to cause the same enzyme deficiency (Yanofsky and Bonner, 1955a, 1955b). One wonders whether in such instances each of the mutations has actually affected the synthesis of the protein in exactly the same manner, or whether such enzyme deficiencies really reflect a damage to different sensitive areas within the gene, each of which is essential for the formation of the fully active enzyme molecule (Yanofsky, 1956; Suskind, 1956a; Bonner, 1956). Answers to some of these questions have recently been sought by employing immunochemical methods to study certain allelic tryptophan requiring mutants (td) of Neurospora crassa unable to form the enzyme tryptophan synthetase (Suskind et al., 1955). Evidence has been obtained
LIMITATIONS OF RHEOLOGY IN FOOD TEXTURE MEASUREMENTS1

Rheological measurements constitute an important part of food texture measurements but they d o not cover all the factors that make up the “texture” of a food. Mastication is a process in which lumps of food are ground into a fine state, mixed with saliva and converted into a liquid slurry at approximately body temperature ready. for swallowing. The processes of size reduction, wetting with saliva, melting, release of moisture or fat are not rheological processes. The perception of moistness, size, shape and roughness of food particles are important factors in texture sensations that are not rheological and yet these oral sensations are an important aspect of the acceptability of a food. This leads to the conclusion that food texture measurement lies partly with-in and partly outside the field of conventional rheology.
Localization of ultrastructural alterations induced in rat liver by dietary polybromobiphenyls (FireMaster BP-6).

In 1973 and 1974, widespread environmental pollution and animal losses in Michigan were caused by the accidental incorporation of polybrominated biphenyls (PBBs, FireMaster FF-1) in livestock feed. This study documents the deleterious changes in the liver during an early state of polybrominated biphenyl-induced toxicosis. Male weanling Fischer rats were fed diets containing either 0 or 100 ppm of polybromobiphenyls (Fire-Master BP-6) (PBBs) for 10 days. Dietary PBBs did not affect body weight or food consumption. At necropsy, the liver was removed and processed for light and electron microscopy. The livers of PBB-treated rats were enlarged and friable. Light microscopic changes included moderate enlargement of centrilobular and midzonal hepatocytes which exhibited a foamy cytoplasm. Periportal hepatocytes appeared normal except that most bile canaliculi were dilated. Ultrastructural alterations within centrilobular hepatocytes consisted of small and dense mitochondria, abundant smooth endoplasmic reticulum, deep stacks of rough endoplasmic reticulum which appeared disorganized with fewer attached ribosomes, numerous lipid droplets, and dilated bile canaliculi which often contained myelin-like figures. The ultrastructural changes within mid-zonal hepatocytes were similar to centrilobular hepatocytes except there was less proliferation of smooth and rough endoplasmic reticulum, larger and less dense mitochondria, and more numerous lipid droplets which varied greatly in size. Glycogen depletion was apparent in both centrilobular and midzonal hepatocytes as was numerous multi-vesicular bodies associated with the Golgi apparatus.
Determination of the molecular structures of tungstates by Raman spectroscopy

An empirical correlation is developed for relating the wavenumbers of (WO) stretching modes to WO bond lengths and bond strengths for tungsten oxide reference compounds. A least-squares exponential fit of crystallographically determined WO bond lengths to the wavenumbers of their Raman stretching modes is presented along with a relation between WO bond strengths, in valence units, and wavenumbers of Raman stretching modes. The empirical bond length/stretching mode wavenumber/bond strength relationships lead to a unique and effective method of interpreting Raman spectra of tungstate species. This method leads to the WO bond lengths and coordination of the tungstate species. The utility of the method is illustrated by estimating the wavenumbers of the Raman stretching modes for the ideal WO4 tetrahedron and WO6 octahedron, and the bonds lengths and coordinations of the tungstate species in the reference compounds Na2WO4, PbWO4, CaWO4 and Bi2WO6. In addition, the WO bond lengths of the WO6 octahedra in crystalline Ba2MgWO6 are reported for the first time. This new approach for evaluating the Raman spectra of tungstate species is expected to be generally applicable to all tungstates, regardless of environment, physical state, or oxidation state.
Optimizing restriction fragment fingerprinting methods for ordering large genomic libraries.

We present a statistical analysis of the problem of ordering large genomic cloned libraries through overlap detection based on restriction fingerprinting. Such ordering projects involve a large investment of effort involving many repetitious experiments. Our primary purpose here is to provide methods of maximizing the efficiency of such efforts. To this end, we adopt a statistical approach that uses the likelihood ratio as a statistic to detect overlap. The main advantages of this approach are that (1) it allows the relatively straightforward incorporation of the observed statistical properties of the data; (2) it permits the efficiency of a particular experimental method for detecting overlap to be quantitatively defined so that alternative experimental designs may be compared and optimized; and (3) it yields a direct estimate of the probability that any two library members overlap. This estimate is a critical tool for the accurate, automatic assembly of overlapping sets of fragments into islands called “contigs.” These contigs must subsequently be connected by other methods to provide an ordered set of overlapping fragments covering the entire genome. Q 1990 Academic press, Inc.
Clypeola is United with Alyssum (Brassicaceae)

Abstract. Several molecular phylogenetic studies have consistently demonstrated that the smaller Clypeola is nested within the larger and more widespread Alyssum (Brassicaceae). Therefore, as in many other similar cases in the family, these two genera are united herein. A new name (A. boissieri) and six new combinations (A. asperum, A. cyclodonteum, A. dichotomum, A. elegans, A. lappaceum, and A. raddeanum) are proposed. The characters often used to distinguish the two genera are discussed in light of other molecular phylogenetic and comparative morphological studies.
Optimal Design Using Chaotic Descent Method

This paper describes a method for searching of global minima in design optimization problems. The method is applicable to any general nonlinear function. It is based on utilizing sensitive fractal areas to locate all of the solutions along one direction in a variable space. The search begins from an arbitrary chosen point in the variable space and descends towards a better design along a randomly chosen direction. Descent depends on finding points that belong to a fractal set which can be used to locate all of the solutions along that direction. The process is repeated until optimal design is obtained. To examine the behavior of the algorithm appropriate examples were selected and results discussed.
Competitive intramolecular nucleophilic aromaticsubstitution: a new route to coumarins

4-Hydroxy-3-(2′-pyridyl)coumarins (4) (R = 6-Cl, H, 6-NO2, 8-NO2) were prepared in moderate to good yields by the intramolecular nucleophilic aromatic substitution reaction of β-ketoesters (I) in refluxing xylenes; evidence for the reversible formation of benzo[c]quinolizinium III from I (X = 4-Cl), with eventual formation of 4 (R = 6-Cl), is also presented.
Expression of wild-type and mutant forms of influenza hemagglutinin: The role of folding in intracellular transport

The hemagglutinin of influenza virus is synthesized as a monomeric subunit that is cotranslationally translocated across the membrane of the rough endoplasmic reticulum. We show that folding and assembly of hemagglutinin monomers into trimeric structures takes approximately 7-10 min and is completed before the protein leaves the endoplasmic reticulum. Mutants of hemagglutinin that fail to be transported from the endoplasmic reticulum are blocked at different stages of the folding pathway. Unfolded molecules of hemagglutinin are associated with a cellular protein of 77 kd that has been shown previously to bind to IgG heavy chain in the endoplasmic reticulum of certain myelomas. We discuss why assembly of native structures is required for transport of proteins through the exocytotic pathway.
Parallel interpretations for level matching enhancements in inner-shell vacancy production in ion-atom collisions

Abstract The qualitative features of observed enhancements in X-ray production, usually interpreted using the molecular orbital model, may also be understood in terms of direct charge exchange.
Improved Switchgrass Gasification Using Molten Carbonate Salts

The use of concentrated solar energy for gasification of biomass is an efficient means for production of hydrogen rich synthesis gas. Utilizing molten alkali-carbonate salts as a reaction and heat transfer medium offers enhanced heat transfer, faster kinetics, and stability for solar transients. The effect of the molten salts on gasification of switchgrass is examined in terms of the reaction rates and product composition. Experiments were carried out in an electrically heated molten salt reactor. Switchgrass was gasified with steam at 1200 K in an inert gas and with salt. Reactivity indexes were calculated from measured gas production rates. Product composition was established via mass spectrometry. In salt, the total useful syngas production increased by 30% while reducing net carbon dioxide production. Reactivity increased 81%. Secondary products, in the form of condensable tar and unreacted char, were reduced by 77%.Copyright © 2011 by ASME
Some psychological correlates of population density in east Africa.

Among the Logoli of Kenya high population density has been found to correlate with some highly positive adaptive outcomes. This study compares such findings among the Logoli and similarly high-density population with low-density groups in order to tap psychological correlates of population density. 1084 rural students from 8 secondary schools in western Kenya representing communities of varying density levels were asked to fill in landmarks on maps that contained a road boundary and three circles representing home. Overall findings revealed that participants from high-density areas did not use more of the overall map than those from low-density areas. With respect to crowding participants from the low-density areas drew more boundaries between houses compared to participants from high-density areas but the high-density participants displayed higher variance in the number of houses they drew. However both groups did not differ on the depiction of subsistence with respect to resources concerns. In this perspective it is indicated that high-density group made more unrestricted use of the space available than the low-density participants.
An application of the coalescence theory to branching random walks.

In a discrete-time single-type Galton--Watson branching random walk {Zn, ?n}n=0, where Zn is the population of the nth generation and ?n is a collection of the positions on of the Zn individuals in the nth generation, let Yn be the position of a randomly chosen individual from the nth generation and Zn (x) be the number of points in ?n that are less than or equal to x for x ? R. In this paper we show in the explosive case (i.e. m = ? (Z1 | Z0 = 1) = 8 when the offspring distribution is in the domain of attraction of a stable law of order or, 0 < a < 1, that the sequence of random functions {Zn(x)/Zn : - 8 < x < 8} converges in the finite-dimensional sense to {dx: - 8 < x < 8}, where dx = 1{N=x} and N is an N(0, 1) random variable.
Live Standing Crop and Metabolism of the Marsh Grass Spartina patens as Related to Edaphic Factors in a Brackish, Mixed Marsh Community in Louisiana

Effects of soil factors on physiological indicators ofSpartina patens and live standing crop of the macrophyte community were investigated in a brackish marsh. Three distinct physiognomic zones were studied along a transect perpendicular to a tidal creek: the marsh edge, which was directly adjacent to the creek; the levee berm, 6 to 8 m from the creek; and the inland zone, which extended through the marsh interior. Soil physicochemical factors (soil moisture, redox potential, interstitial pH, salinity, and ammonium and sulfide concentrations) were compared to physiological indicators ofSpartina patens (leaf adenine nucleotides, root alcohol dehydrogenase (ADH) activity, and levels of ethanol, lactate, alanine and malate in the roots). In correlation matrices of soil and plant factors, increases in soil moisture and decreases in redox potential were associated with depressed leaf adenylate energy charge ratios (AEC, an integrative measure of plant stress) and elevated ADH activities and metabolite levels in the roots. ADH activity was greatest in roots from the inland zone where soil waterlogging was greatest and exhibited seasonal increases that followed seasonal declines in soil redox potential. Leaf AEC was greatest in the berm and generally lowest in the inland plants. End of season live standing crop was also greatest on the berm, but did not closely follow any edaphic trends across the three zones. This suggests that several factors, (i.e., soil aeration, and sulfide and nitrogen levels) may be of greater importance to standing crop than any single factor, as is thought for salt marshes dominated byS. alterniflora.
A support vector data description scheme for hyperspectral target detection using first-order Markov modeling

Spectral variability remains a challenging problem for target detection in hyperspectral (HS) imagery. In this paper, we have applied the kernel-based support vector data description (SVDD) to perform full-pixel target detection. In target detection scenarios, we do not have a collection of samples characterizing the target class; we are typically given a pure target signature that is obtained from a spectral library. In our work, we use the pure target signature and first-order Markov theory to generate N samples to model the spectral variability of the target class. We vary the value of N and observe its effect to determine a value of N that provides acceptable detection performance. We have inserted target signatures into an urban HS scene with varying levels of spectral variability to explore the performance of the proposed SVDD target detection scheme in these scenarios. The proposed approach makes no assumptions regarding the underlying distribution of the scene data as do traditional stochastic detectors such as the adaptive matched filter (AMF). Detection results in the form of confusion matrices and receiver-operating-characteristic (ROC) curves demonstrate that the proposed SVDD-based scheme is highly accurate and yields higher true positive rates (TPR) and lower false positive rates (FPR) than the AMF.
Multiple sclerosis and Hodgkin's disease in Denmark.

There has been a hypothesis that Hodgkin's disease in young adults and multiple sclerosis may have related causes because the age of clinical onset and the geographic distribution of both are similar. This hypothesis was tested for data in Denmark. Between 1943–62, the average annual incidence rate for Hodgkin's disease in Denmark was 2.25 per 100,000 population (2.68 male and 1.83 female). Between 1951–69, the average annual death rate for Hodgkin's disease was 2.15 per 100,000 (2.66 male and 1.64 female). the average annual incidence rate for multiple sclerosis in Denmark was calculated from age at onset for 2,481 prevalent cases of 1949, the 1940 population, and an average annual incidence of 128,86 cases for 1939-45: the average annual incidence rate per 100,000 was then 3.35 (3.00 male and 3.69 female). Age specific incidence and death rates for Hodgkin's disease in Denmark each showed a bimodal curve, with one peak at age 25–29 and the other at age 70–74; this was found for each sex, with male rates consistently higher than female. the age specific incidence rates for multiple sclerosis were clearly unimodal with a peak at age 25–29 more definite in females than males. Rates for MS were notably higher for young females than males but about equal by sex for those over the age of 30. the geographic distribution of multiple sclerosis within the counties (amter) of Denmark was markedly non-random, with the major concentration of high prevalence areas across middle Jutland and on to Fyn. Geographic distribution of Hodgkin's disease, whether for the young or the old, and whether from incident or death cases, showed no significant variation from a homogeneous distribution. In formal testing there was no correlation of any Hodgkin's distribution with that of MS. A review of the Hodgkin's data for distribution in the United States, on which the original hypothesis was based, suggests the variation there may be little more than reporting artifact. Accordingly, we conclude that there is no relation between distributions of these two disorders, and the factors they do appear to have in common are either quite non-specific or of questionable validity. Thus there is no reason to believe that multiple sclerosis and Hodgkin's disease, even in the young, share a common etiology.
Discussion of “Forward Versus Trailing Earnings in Equity Valuation”

The focus of this discussion is on the empirical implications of Yee (2004, this issue). Yee's key contribution is the introduction of belief dependency into the model developed in Ohlson (1995), Feltham and Ohlson (1995, 1996), and Ohlson and Zhang (1998). Yee's primary conclusion is that accruals that do not incorporate beliefs about unobservable information lead to contemporaneous accounting data that are not sufficient for valuation but often belief-free accruals can lead to forward earnings that may be valuation sufficient. Yee (2004) provides an alternative theoretical model of the relation between firm value, trailing earnings, and forward earnings. This model may be used (1) to re-interpret the results of numerous empirical studies of the relation between market metrics, trailing earnings, and forward earnings, and (2) as the basis for framing further hypotheses and empirical studies.
Using E-Z reader to model the effects of higher level language processing on eye movements during reading

Although computational models of eye-movement control during reading have been used to explain how saccadic programming, visual constraints, attention allocation, and lexical processing jointly affect eye movements during reading, these models have largely ignored the issue of how higher level, postlexical language processing affects eye movements. The present article shows how one of these models, E-Z Reader (Pollatsek, Reichle, & Rayner, 2006c), can be augmented to redress this limitation. Simulations show that with a few simple assumptions, the model can account for the fact that effects of higher level language processing are not observed on eye movements when such processing is occurring without difficulty, but can capture the patterns of eye movements that are observed when such processing is slowed or disrupted.
Curve Number Derivation for Watersheds Draining Two Headwater Streams in Lower Coastal Plain South Carolina, USA

The objective of this study was to assess curve number (CN) values derived for two forested headwater catchments in the Lower Coastal Plain (LCP) of South Carolina using a three-year period of storm event rainfall and runoff data in comparison with results obtained from CN method calculations. Derived CNs from rainfall/runoff pairs ranged from 46 to 90 for the Upper Debidue Creek (UDC) watershed and from 42 to 89 for the Watershed 80 (WS80). However, runoff generation from storm events was strongly related to water table elevation, where seasonally variable evapotranspirative wet and dry moisture conditions persist. Seasonal water table fluctuation is independent of, but can be compounded by, wet conditions that occur as a result of prior storm events, further complicating flow prediction. Runoff predictions for LCP first-order watersheds do not compare closely to measured flow under the average moisture condition normally associated with the CN method. In this study, however, results show improvement in flow predictions using CNs adjusted for antecedent runoff conditions and based on water table position. These results indicate that adaptations of CN model parameters are required for reliable flow predictions for these LCP catchments with shallow water tables. Low gradient topography and shallow water table characteristics of LCP watersheds allow for unique hydrologic conditions that must be assessed and managed differently than higher gradient watersheds.
Lynx1, a Cholinergic Brake, Limits Plasticity in Adult Visual Cortex

Experience-dependent brain plasticity typically declines after an early critical period during which circuits are established. Loss of plasticity with closure of the critical period limits improvement of function in adulthood, but the mechanisms that change the brain’s plasticity remain poorly understood. Here, we identified an increase in expression of Lynx1 protein in mice that prevented plasticity in the primary visual cortex late in life. Removal of this molecular brake enhanced nicotinic acetylcholine receptor signaling. Lynx1 expression thus maintains stability of mature cortical networks in the presence of cholinergic innervation. The results suggest that modulating the balance between excitatory and inhibitory circuits reactivates visual plasticity and may present a therapeutic target.
p53-dependent radiation-induced crypt intestinal epithelial cells apoptosis is mediated in part through TNF-TNFR1 system

Radiation induces apoptosis of crypt intestinal epithelial cells (IEC) through a pathway that is largely dependent on p53. However, exactly how p53 mediates IEC apoptosis is unclear. Studies in vitro suggest that one mechanism by which p53 mediates apoptosis is through its ability to transactivate members of the TNF receptor family of 'Death Receptors'. Here, we examined the role of one of its member, TNF receptor type 1 (TNFR1), in an in vivo model of p53-dependent radiation-induced IEC apoptosis. We demonstrate that mice genetically engineered to be deficient in TNF receptor type 1 (TNFR1(-/-)) and mice injected with TNFR1-fusion chimeric protein (TNFR1-Fc; a competitive inhibitor of TNFR1) were partially protected (30-40%) from p53-dependent radiation-induced IEC apoptosis. However, we found no evidence to support the possibility p53 transcriptionally regulates the expression of TNFR1 nor increases the susceptibility of IEC to TNF-mediated apoptosis. Interestingly, we found that injection of TNF readily induced IEC apoptosis and that radiation induced a p53-dependent increase in the intestinal level of TNF. Furthermore, injection of a neutralizing anti-TNF mAb reduced p53-dependent radiation-induced IEC apoptosis by approximately 60%. Overall, these results suggest that p53-dependent radiation-induced IEC apoptosis is mediated in part through ability of p53 to regulate TNF, which subsequently induces IEC apoptosis through TNFR1.
Evaluating metal ion salts as acid hydrolase mimics: metal-assisted hydrolysis of phospholipids at lysosomal pH

Niemann-Pick disease and drug-induced phospholipidosis are lysosomal storage disorders in which there is an excessive accumulation of sphingomyelin in cellular lysosomes. Here we have explored the possibility of developing metal-based therapeutic agents to reverse phospholipid build-up through phosphate ester bond hydrolysis at lysosomal pH (~4.8). Towards this end, we have utilized a malachite green/molybdate-based colorimetric assay to quantitate the inorganic phosphate released upon the hydrolysis of sphingomyelin by twelve d- and f-block metal ion salts. In reactions conducted at 60 °C, the yields produced by the cerium(IV) complex Ce(NH4)2(NO3)6 were superior. An Amplex® Red-based colorimetric assay and mass spectrometry were then employed to detect choline. The data consistently showed that Ce(IV) hydrolyzed sphingomyelin more efficiently at lysosomal pH: i.e., yields of choline and phosphate were 54 ± 4 and 22 ± 5 % at pH ~ 4.8, compared to 8 ± 1 and 5 ± 2 % at pH ~ 7.2. Hydrolysis at 60 °C could be significantly increased by converting sphingomyelin vesicles to mixed lipid vesicles and mixed micelles of Triton X-100. We then utilized cerium(IV) to cleave sphingomyelin at 37 °C (no Triton X-100). Although choline and phosphate levels were relatively low, hydrolysis continued to be considerably more efficient at lysosomal pH. A side by side comparison to phosphatidylcholine was then made. While the yields of choline and phosphate produced by phosphatylcholine were higher, the ratio of pH ~ 4.8 hydrolysis to pH ~ 7.2 hydrolysis was usually more favorable for sphingomyelin (37 and 60 °C).
Temperature dependence of the kinetics of the acylase hydrolysis reaction by differential stopped flow microcalorimetry

The rates of the hydrolysis of N-acetylglycine, N-acetyl-L-methionine, and N-acetyl-L-phenylalanine by porcine acylase I in 0.1M phosphate buffer, which is inhibited by acetate product formation, were monitored calorimetrically at temperatures between 15.2 and 45.3 degrees C by a differential stopped-flow microcalorimeter. Since the acylase is thermally stable and the pH of the phosphate buffer changes by less than 0.01 pH units over this temperature range, any temperature effect on the hydrolysis reaction can be attributed to the effect of temperature on the kinetics of the reaction. Analysis of the integrated heat released by the reaction as a function of time with regard to the integrated Michaelis-Menten equation yields apparent values for k(cat) and apparent values for Km that depend on the product inhibition constant. The apparent values for Km also exhibited a dependence on the initial substrate concentration because of the acetate product inhibition at each temperature. By assuming that the inhibition constant is independent of temperature over this temperature range and from extrapolation of Km to its value at zero substrate concentration, intrinsic values of Km and k(cat) were determined over the temperature range from 15.2 to 45.3 degrees C. The intrinsic values of Km exhibited very little variation over this temperature range while the intrinsic values of k(cat) exhibited an increase over the same temperature range. The heats of reaction also exhibited an increase with temperature over this range with an average heat capacity change of -94 Jmol(-1)K(-1) for the three substrates.
Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches

Osteoporosis is a skeletal disorder characterized by bone loss, which results in architectural deterioration of the skeleton, compromised bone strength and an increased risk of fragility fractures. Most current therapies for osteoporosis stabilize the skeleton by inhibiting bone resorption (antiresorptive agents), but the development of anabolic therapies that can increase bone formation and bone mass is of great interest. Wnt signalling induces differentiation of bone-forming cells (osteoblasts) and suppresses the development of bone-resorbing cells (osteoclasts). The Wnt pathway is controlled by antagonists that interact either directly with Wnt proteins or with Wnt co-receptors. The importance of Wnt signalling in bone formation is indicated by skeletal disorders such as sclerosteosis and van Buchem syndrome, which are caused by mutations in the gene encoding the Wnt antagonist sclerostin (SOST). Experiments in mice have shown that downregulation or neutralization of Wnt antagonists enhances bone formation. Phase II clinical trials show that 1-year treatment with antisclerostin antibodies increases bone formation, decreases bone resorption and leads to a substantial increase in BMD. Consequently, Wnt signalling can be targeted by the neutralization of its extracellular antagonists to obtain a skeletal anabolic response.
A normative explanation of antisocial punishment

Abstract While much research shows that people punish free-riders, recent studies find evidence that people also engage in antisocial punishment. That is, they sometimes punish those who contribute generously to collective actions. Such sanctioning is puzzling because generous individuals increase the welfare of all group members. When and why are such individuals punished? In this paper, we propose that descriptive norms are part of the explanation. People may sanction those whose behavior is atypical – even when that behavior benefits the group. We test our theory with a laboratory experiment. We examine the effect of descriptive norms on sanctioning of generous and stingy deviants and find that descriptive norms encourage antisocial punishment, but not punishment of free-riders.
Nanodispersing thymol in whey protein isolate-maltodextrin conjugate capsules produced using the emulsion–evaporation technique

Abstract This work presents simple processes to prepare transparent aqueous dispersions of thymol, a lipophilic antimicrobial compound. The emulsion–evaporation technique involved the preparation of capsules by spray-drying oil-in-water emulsions containing thymol dissolved in hexane emulsified using conjugates of whey protein isolate and maltodextrin. Hydration of spray-dried capsules resulted in transparent and heat stable nanodispersions containing thymol at concentrations well above its solubility limit, even at pH around the isoelectric points of whey proteins. The efficiency of encapsulation and the heat-stability of nanodispersions were affected by the emulsion composition. An encapsulation efficiency of 51.4% was obtained for one sample that corresponded to dispersions, adjusted to pH 3.0–7.0, with mean diameters of
Aspirin and the Transmucosal Potential Difference

Excerpt Although the gastric potential difference has been known since 1834, Swyngedauw in 1928 was probably the first to record it in man. Since then it has been studied by many investigators. Mea...
A field simulation of the effect of acidic rain on ion balance in a woodland salamander

The natural density of red-backed salamanders, Plethodon cinereus, is 4–5 times greater at the New York study site in hardwood than in hemlock forests. The hypothesis that physico-chemical differences between forest types differentially affect the physiology of P. cinereus was tested. Salamanders were confined in individual enclosures in either a beech or a hemlock forest for 22 d. At the end of the enclosure period, they were analyzed for total body content of sodium, potassium, calcium, and magnesium, and for wet mass, dry mass, and body water concentration. Salamanders from the two forest types did not differ in any body parameter after the 22 d enclosure period. Also, the hypothesis that artificially acidified “rain” would inhibit the ability of salamanders to maintain ion balance was tested. Salamanders were confined for 34 d in individual enclosures in the two forests and exposed periodically to artificial rain of either pH 3 or pH 5. Soil pHs in the enclosures changed during the enclosure period, and artificial rain of both pHs caused soil pHs in the hemlock forest to increase even though pHs outside enclosures decreased. Enclosures that received artificial rain of pH 3 had lower soil pHs than enclosures that received artificial rain of pH 5. Salamanders in enclosures at pH 3 had reduced body sodium levels and tended to have lower body water concentration than salamanders in enclosures at pH 5 or controls. Thus, these terrestrial salamanders in a field setting demonstrated a physiological response to simulated acidic deposition consistent with the effects of exposure to acidic substrate previously observed in the laboratory. Since P. cinereus is frequently an abundant member of forest floor communities, and since it is sensitive to altered chemical inputs, it may be a useful indicator for assessing anthropogenic changes in ecosystems.
Connection between dynamics and thermodynamics of liquids on the melting line

Abstract : The dynamics of a large number of liquids and polymers exhibit scaling properties characteristic of a simple repulsive inverse power-law potential, most notably the superpositioning of relaxation data as a function of the variable TV gamma , where T is temperature, V the specific volume, and gamma a material constant. A related scaling law Tm Vm Gamma , with the same exponent Gamma = gamma, links the melting temperature Tm and volume Vm of the model IPL liquid; liquid dynamics is then invariant at the melting point. Motivated by a similar invariance of dynamics experimentally observed at transitions of liquid crystals, we determine dynamic and melting-point scaling exponents and Gamma for a large number of nonassociating liquids. Rigid, spherical molecules containing no polar bonds have Gamma = gramma; consequently, the reduced relaxation time, viscosity, and diffusion coefficient are each constant along the melting line. For other liquids gamma Gamma always; that is, the dynamics is more sensitive to volume than is the melting point, and for these liquids the dynamics at the melting point slows down with increasing Tm (that is, increasing pressure).
Mothers' union histories and the mental and physical health of adolescents born to unmarried mothers

As nonmarital childbearing becomes a dominant pathway to family formation, understanding its long-term consequences for children’s well-being is increasingly important. Analysis of linked mother-child data from the 1979 National Longitudinal Survey of Youth indicates a negative association of having been born to a never-married mother with adolescent self-assessed health but not with depressive symptoms. We also consider the role of mothers’ subsequent union histories in shaping the adolescent health outcomes of youth born to unmarried mothers. With two exceptions, unmarried mothers’ subsequent unions appear to have little consequence for the health of their offspring during adolescence. Adolescents whose mothers subsequently married and remained with their biological fathers reported better health, yet adolescents whose mothers continuously cohabited with their biological fathers without subsequent marriage reported worse adolescent mental health compared with adolescents whose mothers remained continual...