cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancement of the intestinal absorption of peptides and nonpeptides

Abstract It is not uncommon for peptides and structurally-similar non-peptides to have poor intestinal permeability and low oral bioavailability. One possible way to solve a permeability problem is to formulate the compound with membrane permeation-enhancing excipients. Important criteria for success of this approach are: (1) achieving reproducible intestinal permeation, (2) doing so without causing toxicity, and (3) understanding the mechanisms of permeation enhancement. Some effective and potentially safe permeation enhancers are fatty acids, glycerides, surfactants, acyl carnitines, and bile salts. The literature on permeation enhancement with these agents is briefly reviewed. We evaluated permeation enhancement approaches to increase the oral bioavailability of a non-metabolized, cyclic peptide fibrinogen antagonist, DMP 728. Sodium caprate (15 mM) increased the in vitro intestinal permeation rate 3-fold. Oral absorption in dogs was also increased approximately 3-fold using a formulation containing 150 mg sodium caprate. Inter-animal variability in absorption was considerable, though. A diacidic, non-peptide angiotensin II antagonist, DuP 532, presented another case of a poorly membrane permeable lead compound. Sodium caprate did not affect DuP 532 oral bioavailability in rats. However, oral bioavailability of DuP 532 in rats and dogs was increased approximately 3-fold using glyceride vehicles. These excipients have the advantage of already being used in marketed products. As with DMP 728, there was substantial inter-animal variability of DuP 532 oral bioavailability, and optimization of the formulation would be required to improve reproducibility. These examples demonstrate the possibilities of significantly improving oral bioavailability of poorly permeable drugs using seemingly acceptable excipients.
The Drazin inverse and a spectral inequality of marcus, minc, and moyls

Some properties of the Drazin inverse of a square matrix are derived which, together with elementary divisor theory, are used to investigate a spectral inequality which relates the maximal eigenvalues of two nonnegative indecomposable matrices.
Rarity for Semimeasures

The notion of Kolmogorov-Martin-Lof Random sequences is extended from computable to enumerable distributions. This allows definitions of various other properties, such as mutual information in infinite sequences. Enumerable distributions (as well as distributions faced in some finite multi-party settings) are semi measures, handling those requires care.
Understanding Conduction System Development: A Hop, Skip and Jump Away?

See related article, pages 898–903 In the late 1800s, W.H. Gaskell demonstrated that impulse propagation from the atrium to the ventricle of the tortoise heart reflected conduction along myocardial tissue rather than nerve tissue.1 A decade later, Stanley Kent proposed, incorrectly as it turns out, that multiple muscular connections normally link the atria and ventricles of mammals,2 but it was not until the remarkably detailed report almost 100 years ago by Sunao Tawara, working in the laboratory of Ludwig Aschoff in Germany, that the histological identification and characterization of the atrioventricular node, the penetrating bundle of His, the left and right bundle branches and Purkinje fiber network was established.3 The notion that aberrant conduction between atria and ventricles might account for rhythm disturbances was first proposed in 1930, when the renowned American cardiologist Paul Dudley White and the English physicians John Parkinson and Louis Wolff reported on a series of patients with a short PR interval and apparent bundle branch block who were prone to paroxysmal tachycardia.4 During the past decade, there has been growing realization of the importance of diseases involving the cardiac conduction system (CCS), maladies that are now known to reflect diverse pathologic mechanisms including not only post-operative complications following surgical repair of congenital heart defects, but also immunological and metabolic disorders, degenerative processes and most recently - transcriptional dysregulation.5–9 Classically, the adult …
Modeling a Two-Phase Control-Oriented Transient Model of a Single PEM Fuel Cell

This paper proposed a 1D non-isothermal control-oriented transient model of PEM fuel cell unit considering the two-phase water dynamics in gas flow channel, gas diffusion layer, catalyst layer and membrane. It is known that the accumulated liquid water in the gas flow channels can block the transport path in the gas diffusion layer for the reactant gases and degrade the performance of the fuel cell, while the proper water amount in the gas flow channels and other layers can help to maintain high proton conductivity in the membrane. The I-V curve and the change of gas concentrations, liquid water amount and temperature at specific operating conditions are obtained by sweeping the current of fuel cell. The voltage, gas concentration, temperature and water dynamic changes are investigated by applying the step change of the load current. The fuel cell performance affected by temperature and water dynamics is studied by the analysis of the simulation result.Copyright © 2010 by ASME
System dynamics modeling of childhood obesity

Effective strategies for prevention of obesity, particularly in youths, have been elusive since the recognition of obesity as a major public health issue two decades ago. In general, obesity is a result of chronic, quantitative imbalance between energy intake and energy expenditure, which is influenced by a combination of genetic, environmental, psychological and social factors. Therefore, a systems perspective is needed to examine effective obesity prevention strategies. In this study, a systems dynamics model was developed using the data from the Girls health Enrichment Multi-site Studies (GEMS). GEMS tested the efficacy of a 2-year family-based intervention to reduce excessive increase in body mass index (BMI) in 8–10 year old African- American girls. First, an optimum model was built by systematically adding variables to fit the observed data by regression analysis for 50 randomly selected individuals from the cohort. The final model included nutrition, physical activity, and several environmental factors. Next, the model was used to compare two intervention strategies used in the GEMS study. Consistent with previous reports, we found that the two strategies did not affect the BMI increases observed in this cohort. Interestingly however, the model predicted that a 10 min increase in exercise would decrease BMI in the group receiving behavioral counseling. Our work suggests that system dynamics modeling may be useful for testing potential intervention strategies in complex disorders such as obesity.
Identifying Risk Factors for the Development of Diabetic Ketoacidosis in New Onset Type 1 Diabetes Mellitus

To identify risk factors associated with the development of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes mellitus, a retrospective chart review of 139 new onset type 1 diabetes patients from 1995 to 1998 was conducted. Categorical data were examined with contingency table analysis. Age range was 0.5 to 18 years. Overall, 38% of the patients presented in DKA. Sixty-two percent of the patients with either Medicaid or no insurance presented in DKA compared to 34% of the patients with private insurance, odds ratio 3.17 (92% CI 1.2-8.3) p = 0.03. Sixty-eight percent of patients in whom the diagnosis was missed (n = 25) presented in DKA (mean age, 5.4 +/- 4.4 years) compared to 32% in whom the diagnosis was not missed (mean age, 8.8 +/- 4.0 years) odds ratio 4.6 (95% CI 1.9-11.7), p = 0.0012; age p = 0.00019. Lack of private insurance, although a risk factor for the development of DKA, did not increase the likelihood of a missed diagnosis. Lack of private insurance (a proxy for socioeconomic status) and young age are apparent risk factors for the development of ketoacidosis. Misdiagnosis by the physician at initial patient encounter is especially prevalent in the young child but not related to insurance. Both increased public awareness and greater medical alertness are necessary to reduce the high rates of DKA in new-onset type 1 diabetic children.
Improved calorimetric procedure for monitoring the approach to thermodynamic equilibrium in glassy polymers

Techniques for measuring the enthalpy change during isothermal aging of polymer glasses are discussed. Critical analysis of conventional scanning calorimetry reveals that its accuracy may be suspect under certain circumstances due to the thermal lag inherent in a temperature scanning experiment. An additional problem is that the conventional technique is restricted to certain kinds of paths for reaching the aging temperature. It is proposed that both problems can be overcome by analyzing the output of a scanning calorimeter not only during steady heating but also during the transients at the beginning and end of a heating scan. This data analysis method represents an extension of a method used previously by others in accurate measurements of the much larger heat of fusion of crystalline polymers. Practical feasibility of the improved technique is demonstrated by preliminary measurements of enthalpy relaxation during aging of well-characterized polystyrene at 80°C. In particular, the initial departure from equilibrium of a glass prepared by 5°C/min cooling from the liquid state is found to be 6.9 ± 0.6 J/g. This measured value agrees with a value calculated on the basis of the glass transition temperature corresponding to 5°C/min cooling and heat-capacity data from the literature.
Mesh deformation-based multi-tissue mesh generation for brain images

Multi-tissue meshing is necessary for the realistic building of a biomechanical model of the brain, which has been widely used in brain surgery simulation, brain shift, and non-rigid registration. A two step multi-tissue mesher is developed. First, a coarse multi-tissue mesh is generated by redistributing labels of a body-centered cubic (BCC) mesh. Second, all the surfaces of the submeshes are deformed to their corresponding tissue boundaries. To deform the mesh, two strategies are developed. One is based on a point-based registration (PBR) and the other is based on a robust point matching (RPM). The PBR method explicitly calculates the correspondence, which takes both smoothing and quality into account, then resolves the displacement vector by minimizing an energy function. Unlike PBR method, RPM does not require the correspondence between the source points and the target points to be known in advance. To simultaneously resolve the displacement vector and the correspondence, the Expectation and Maximization optimization is employed to alternately estimate the correspondence and the displacement vector. To effectively cope with outliers, least trimmed square, a robust regression technique, is employed to correct the regression bias induced by outliers. Both methods are effective in deforming the multi-tissue mesh. However, the PBR method favors quality and smoothing, and the RPM method favors fidelity. The resulting mesh is characterized by its flexible control of four mesh properties: (1) tissue-dependent resolution, (2) fidelity to tissue boundaries, (3) smoothness of mesh surfaces, and (4) element quality. Each mesh property can be controlled on a tissue level. Our experiments conducted on synthetic data, clinic MRI, visible human data, and brain atlas effectively demonstrate these features of this multi-tissue mesher.
Tropomyosin Dephosphorylation Results in Compensated Cardiac Hypertrophy

Phosphorylation of tropomyosin (Tm) has been shown to vary in mouse models of cardiac hypertrophy. Little is known about the in vivo role of Tm phosphorylation. This study examines the consequences of Tm dephosphorylation in the murine heart. Transgenic (TG) mice were generated with cardiac specific expression of α-Tm with serine 283, the phosphorylation site of Tm, mutated to alanine. Echocardiographic analysis and cardiomyocyte cross-sectional area measurements show that α-Tm S283A TG mice exhibit a hypertrophic phenotype at basal levels. Interestingly, there are no alterations in cardiac function, myofilament calcium (Ca2+) sensitivity, cooperativity, or response to β-adrenergic stimulus. Studies of Ca2+ handling proteins show significant increases in sarcoplasmic reticulum ATPase (SERCA2a) protein expression and an increase in phospholamban phosphorylation at serine 16, similar to hearts under exercise training. Compared with controls, the decrease in phosphorylation of α-Tm results in greater functional defects in TG animals stressed by transaortic constriction to induce pressure overload-hypertrophy. This is the first study to investigate the in vivo role of Tm dephosphorylation under both normal and cardiac stress conditions, documenting a role for Tm dephosphorylation in the maintenance of a compensated or physiological phenotype. Collectively, these results suggest that modification of the Tm phosphorylation status in the heart, depending upon the cardiac state/condition, may modulate the development of cardiac hypertrophy.
Improving the quality of electron backscatter diffraction (EBSD) patterns from nanoparticles.

Summary In this study, we investigated the relative contributions of atomic number (Z) and density (ρ) to the degradation of the electron backscatter diffraction (EBSD) pattern quality for nanoparticles < 500 nm in diameter. This was accomplished by minimizing the diffuse scattering from the conventional thick mounting substrate through the design of a sample holder that can accommodate particles mounted on thin-film TEM substrates. With this design, the contributions of incoherently scattered electrons that result in the diffuse background are minimized. Qualitative and quantitative comparisons were made of the EBSD pattern quality obtained from Al2O3 particles approximately 200 nm in diameter mounted on both thick- and thin-film C substrates. For the quantitative comparison we developed a ‘quality’ factor for EBSD patterns that is based on the ratio of two Hough transforms derived from a given EBSD pattern image. The calculated quality factor is directly proportional to the signal-to-noise ratio for the EBSD pattern. In addition to the comparison of the thick and thin mounting substrates, we also estimated the effects of Z and ρ by comparing the EBSD pattern quality from the Al2O3 particles mounted on thin-film substrates with the quality of patterns obtained from Fe–Co nanoparticles approximately 120 nm in diameter. The results indicate that the increased background generated in EBSD patterns by the electrons escaping through the bottom of the small particles is the dominant reason for the poor EBSD pattern quality from nanoparticles < 500 nm in size. This was supported by the fact that we were able to obtain usable EBSD patterns from Al2O3 particles as small as 130 nm using the thin-film mounting method.
Thermal performance and limitations of silicon–substrate packaged GaAs laser arrays

Thermal resistance and crosstalk have been investigated for a source package consisting of a monolithic, multilaser heterojunction array mounted on a single crystalline silicon substrate, which is in turn laminated to a copper heatsink. Models for 2-D and 3-D heat spreading are used to calculate the heat flow distribution and to obtain upper and lower bounds for both resistance of single devices and crosstalk in arrays. Results for experimental five-laser arrays are shown to fall within these limits. Active cooling is required to maintain junctions at safe operating temperatures prerequisite to stable, long-lived operation.
Faecal microbiota transplantation in 2013: Developing human gut microbiota as a class of therapeutics

Although the idea of faecal transplantation dates back many decades, only with advances in scientific technologies can we begin systematic development of this new class of therapeutics. The primary focus remains on treatment of Clostridium difficile infection—new applications are beginning to emerge, but a long journey remains ahead.
A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

Germline mutations of the Brcal gene are responsible for most cases of familial breast and ovarian cancers, but somatic mutations are rarely detected in sporadic events. Moreover, mouse embryos deficient for Brca1 have been shown to die during early embryogenesis due to a proliferation defect. These findings seem incompatible with the tumor suppress function assigned to this gene and raise questions about the mechanism by which Brca1 mutations cause tumorigenesis. We now directly demonstrate that BRCA1 is responsible for the integrity of the genome. Murine embryos carrying a Brca1 null mutation are developmentally retarded and hypersensitive to gamma-irradiation, suggesting a failure in DNA damage repair. This notion is supported by spectral karyotyping (SKY) of metaphase chromosomes, which display numerical and structural aberrations. However, massive chromosomal abnormalities are only observed when a p53-/- background is introduced. Thus, a p53 dependent cell cycle checkpoint arrests the mutant embryos and prevents the accumulation of damaged DNA. Brca1-/- fibroblasts are not viable, nor are Brca1-/-:p53-/- fibroblasts. However, proliferative foci arise from Brca1-/-: p53-/- cells, probably due to additional mutations that are a consequence of the accumulating DNA damage. We believe that the increased incidence of such additional mutations accounts for the mechanism of tumorigenesis associated with Brca1 mutations in humans.
Poly(ADP-ribose) synthetase activation mediates increased permeability induced by peroxynitrite in Caco-2BBe cells

Abstract Background & Aims: Peroxynitrite induces cytotoxicity by generating DNA single-strand breaks and activating poly(ADP-ribose) synthetase (PARS), a nuclear enzyme that consumes oxidized nicotinamide adenine dinucleotide (NAD + ) and depletes cellular adenosine triphosphate (ATP). The aim of this study was to examine this mechanism of injury in an intestinal epithelial cell model after exposure to exogenous peroxynitrite (ONOO − ) and nitric oxide (NO). Methods: Caco-2BBe cell monolayers exposed to donors of peroxynitrite (3-morpholino-sydnonimine [SIN-1], 3 mmol/L) or NO ( S -nitroso- N -acetyl penicillamine [SNAP]; 3 mmol/L) were analyzed for DNA strand breaks, [NAD + ], [ATP], and transepithelial flux of fluorescein sulfonic acid. Results: SIN-1 but not SNAP induced DNA single-strand breakage. Both SIN-1 and SNAP reduced [ATP], but only SIN-1 reduced [NAD + ]. Inhibition of PARS activity by the PARS inhibitors 5-iodo-6-amino 1,2- benzopyrone or 3-aminobenzamide prevented the SIN-1–induced reduction in [NAD + ] and [ATP] but had no effect on the SNAP-induced reduction in [ATP]. PARS inhibition reduced SIN-1–but not SNAP-induced hyperpermeability. Conclusions: Peroxynitrite but not NO increases transepithelial permeability by inducing DNA strand breaks that activate the PARS pathway and cause the depletion of intracellular energy stores. Inhibition of PARS activity may represent a novel strategy in ameliorating peroxynitrite-mediated epithelial injury during intestinal inflammation. GASTROENTEROLOGY 1998;114:510-518
Predicting toddler anxiety/depressive symptoms: Effects of caregiver sensitivity on temperamentally vulnerable children

Ces recherches examinent si la sensibilite maternelle dans la petite enfance reduit l'anxiete et les symptomes depressifs plus tard pour les enfants avec une plus de vulnerabilite du temperament, et si ces effets sont differents pour les garcons et les filles. Des donnees de l'etude du soin precoce de l'enfant, avec 1226 sujets (631 garcons, 595 filles), faite par l'Institut National de la Sante de l'Enfant et du Developpement Humain ont ete analysees. Les meres et d'autres modes de soin ont evalue le temperament difficile des enfants a un et six mois. Des observateurs qualifies ont evalue la sensibilite maternelle quand les enfants avaient six et quinze mois. Les symptomes d'anxiete/depressifs ont ete evalues par les meres et d'autres modes de soin lorsque les enfants avaient deux et trois ans. La sensibilite maternelle durant la petite enfance a fortement predit des symptomes d'anxiete/depressifs diminues chez les enfants de 2 et 3 ans. Les enfants avec le temperament le plus difficile etaient bien plus a meme de faire preuve de symptomes d'anxiete/depressifs diminues a 2 ans si leur mere avait ete plus sensible. La sensibilite maternelle etait aussi un facteur de prediction important de symptomes d'anxiete/depressifs diminues pour les garcons au temperaments les plus difficiles, et on a trouve que les garcons au temperament difficile avec des meres plus sensibles etaient beaucoup plus a meme que les filles a faire preuve de symptomes d'anxiete/depressifs diminues a l'âge de trois ans. Les resultats de ces recherches pilotes suggerent que le fait de faciliter et de soutenir une plus grand sensibilite pour les meres avec des enfants au temperament plus difficile pourrait etre benefique.
Discrete and continuous deformation during nanoindentation of thin films

Abstract This paper describes nanoindentation experiments on thin films of polycrystalline Al of known texture and different thicknesses, and of single crystal Al of different crystallographic orientations. Both single-crystalline and polycrystalline films, 400–1000 nm in thickness, are found to exhibit multiple bursts of indenter penetration displacement, h, at approximately constant indentation loads, P. Recent results from the nanoindentation studies of Suresh et al. (Suresh, S., Nieh T.-G. and Choi, B.W., Scripta mater., 1999, 41, 951) along with new microscopy observations of thin films of polycrystalline Cu on Si substrates are also examined in an attempt to extract some general trends on the discrete and continuous deformation processes. The onset of the first displacement burst, which is essentially independent of film thickness, appears to occur when the computed maximum shear stress at the indenter tip approaches the theoretical shear strength of the metal films for all the cases examined. It is reasoned that these displacement bursts are triggered by the nucleation of dislocations in the thin films. A simple model to estimate the size of the prismatic dislocation loops is presented along with observations of deformation using transmission electron microscopy and atomic force microscopy. It is demonstrated that the response of the nanoindented film is composed of purely elastic behavior with intermittent microplasticity. The overall plastic response of the metal films, as determined from nanoindentation, is shown to scale with film thickness, in qualitative agreement with the trends seen in wafer curvature or X-ray diffraction measurements.
There's a time and a place for MYCN.

Brain tumors display extensive diversity. In this issue of Cancer Cell , Swartling et al. provide evidence that the temporal and spatial transcriptional programs in neural stem cells underlie a diverse response to the MYCN oncogene, potentially contributing to cancer diversity.
Repeat Times of Large Earthquakes: Implications for Earthquake Mechanics and Long-Term Prediction

Information on the time intervals between large earthquakes is now available for several fault segments along plate boundaries in Japan, Alaska, California, Cascadia, and Turkey. When dates in a sequence are known historically, as along much of the Nankai trough, they provide information on the natural (intrinsic) variability of the rupture process. Most sets of repeat times, however, are dominated by paleoseismic determinations of dates of older large earthquakes, which contain measurement uncertainties in addition to intrinsic variability. A Bayesian technique along with prior information on measurement uncertainties is used to make maximum-likelihood estimates of intrinsic repeat time and its normalized standard deviation, the coefficient of variation (cv). It is these intrinsic parameters and their uncertainties that are most useful for understanding the mechanics of earthquakes and for prediction for timescales of a few decades. Our estimates of intrinsic cv are small, 0 to 0.25, for several very active fault segments where deformation is relatively simple, large events do not appear to be missing in historic and paleoseismic records, and data are available at or near major asperities and away from the ends of rupture zones. cv is larger for regions of multibranched faulting, overlapping slip near the ends of rupture zones and for data from uplifted terraces at subduction zones. A Poisson process is an inferior characterization of all of the 11 segments we examined. Scenarios used by recent working groups that assume either Poissonian behavior or renewal processes with cv of 0.5 ± 0.2 for the most active fault segments in the San Francisco Bay area likely lead to incorrect 30-year probability estimates. The Hayward fault and perhaps the Peninsular segment of the San Andreas fault in the San Francisco Bay area appear to be advanced in their buildup of stress that will be released in future large earthquakes. Multibranched faulting may account for why the predicted Tokai earthquake in Japan has not occurred as of 2006. Parkfield earthquakes from 1857 to 2004 were characterized by the largest uncertainty of the sequences we studied, cv = 0.37, which may account for the failure of past predictions. The large cv for Parkfield fits our hypothesis that relatively weak fault segments are characterized by more irregular earthquake recurrence. Paleoseismic data from coastal sites along the Cascadia subduction zone are characterized by cvs of about 0.3.
Building a robust software-based router using network processors

Recent efforts to add new services to the Internet have increased interest in software-based routers that are easy to extend and evolve. This paper describes our experiences using emerging network processors---in particular, the Intel IXP1200---to implement a router. We show it is possible to combine an IXP1200 development board and a PC to build an inexpensive router that forwards minimum-sized packets at a rate of 3.47Mpps. This is nearly an order of magnitude faster than existing pure PC-based routers, and sufficient to support 1.77Gbps of aggregate link bandwidth. At lesser aggregate line speeds, our design also allows the excess resources available on the IXP1200 to be used robustly for extra packet processing. For example, with 8 × 100Mbps links, 240 register operations and 96 bytes of state storage are available for each 64-byte packet. Using a hierarchical architecture we can guarantee line-speed forwarding rates for simple packets with the IXP1200, and still have extra capacity to process exceptional packets with the Pentium. Up to 310Kpps of the traffic can be routed through the Pentium to receive 1510 cycles of extra per-packet processing.
CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance

Intravenous treatment with Ag (peptide)-coupled, ethylene carbodiimide-fixed syngeneic splenocytes (Ag-SP) is a powerful method to induce anergy in vitro and peripheral T cell tolerance in vivo. In this study, we examined the effects of Ag-SP administration on T cell activity ex vivo and in vivo using OVA-specific DO11.10 TCR transgenic T cells. Although treatment with OVA323-339-SP resulted in a strong inhibition of peptide-specific T cell recall responses in vitro, examination of the immediate effects of Ag-SP treatment on T cells in vivo demonstrated that tolerogen injection resulted in rapid T cell activation and proliferation. Although there was an increase in the number of OVA-specific DO11.10 T cells detected in the lymphoid organs, these previously tolerized T cells were strongly inhibited in mounting proliferative or inflammatory responses upon rechallenge in vivo with peptide in CFA. This unresponsiveness was reversible by treatment with anti-CTLA-4 mAb. These results are consistent with the hypothesis that Ag-SP injection induces a state of T cell anergy that is maintained by CTLA-4 engagement.
Optical wireless: a prognosis

This paper sets out to review the applications for optical free space links in future broadband networks, covering both long (0.5 to 5 km) and short (< 500 m) external as well as internal systems. The fundamental properties of optical systems -- high bandwidth, minimal regulation and potential low cost, together with the challenges of a relatively low power margin and extreme attenuation in heavy fog -- are evaluated in the light of 5 year's research by the authors.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Managing a Retailer's Shelf Space, Inventory, and Transportation

Retailers must constantly strive for excellence in operations; extremely narrow profit margins leave little room for waste and inefficiency. This article reports a retailer's challenge to balance transportation, shelf space, and inventory costs. A retailer sells multiple products with stochastic demand. Trucks are dispatched from a warehouse and arrive at a store with a constant lead time. Each truck has a finite capacity and incurs a fixed shipping cost, no matter the number of units shipped. There is a per unit shelf-space cost as well as holding and backorder penalty costs. Three policies are considered for dispatching trucks: a minimum quantity continuous review policy, a full service periodic review policy, and a minimum quantity periodic review policy. The first policy ships a truck when demand since the previous shipment equals a fixed fraction of a truck's capacity, i.e., a minimum truck utilization. The exact analysis of that policy is the same as the analysis of reorder point policies for the multiechelon problem with one-warehouse, multiple retailers, and stochastic demand. That analysis is not computationally prohibitive, but the minimum quantity level can be chosen with a simple economic order quantity (EOQ) heuristic. An extensive numerical study finds the following: Either of the two periodic review policies may have substantially higher costs than the continuous review policy, in particular when the warehouse to store lead time is short; the EOQ heuristic performs quite well; the minimum quantity policy's total cost is relatively insensitive to the chosen transportation utilization, and its total cost is close to a lower bound developed for this problem.
Guaranteeing Pfair supertasks by reweighting

We reconsider the "supertask" approach, in which a set of Pfair tasks is scheduled as a single task. We define a "safe" weight threshold for a given supertask in a multiprocessor system with either hard or soft deadlines and either strict or relaxed rate constraints.
Quantitative mapping of protein structure by hydroxyl radical footprinting-mediated structural mass spectrometry: a protection factor analysis.

Measurements from hydroxyl radical footprinting (HRF) provide rich information about the solvent accessibility of amino acid side chains of a protein. Traditional HRF data analyses focus on comparing the difference in the modification/footprinting rate of a specific site to infer structural changes across two protein states, e.g., between a free and ligand-bound state. However, the rate information itself is not fully used for the purpose of comparing different protein sites within a protein on an absolute scale. To provide such a cross-site comparison, we present a new, to our knowledge, data analysis algorithm to convert the measured footprinting rate constant to a protection factor (PF) by taking into account the known intrinsic reactivity of amino acid side chain. To examine the extent to which PFs can be used for structural interpretation, this PF analysis is applied to three model systems where radiolytic footprinting data are reported in the literature. By visualizing structures colored with the PF values for individual peptides, a rational view of the structural features of various protein sites regarding their solvent accessibility is revealed, where high-PF regions are buried and low-PF regions are more exposed to the solvent. Furthermore, a detailed analysis correlating solvent accessibility and local structural contacts for gelsolin shows a statistically significant agreement between PF values and various structure measures, demonstrating that the PFs derived from this PF analysis readily explain fundamental HRF rate measurements. We also tested this PF analysis on alternative, chemical-based HRF data, showing improved correlations of structural properties of a model protein barstar compared to examining HRF rate data alone. Together, this PF analysis not only permits a novel, to our knowledge, approach of mapping protein structures by using footprinting data, but also elevates the use of HRF measurements from a qualitative, cross-state comparison to a quantitative, cross-site assessment of protein structures in the context of individual conformational states of interest.
Impact modification of poly(vinyl chloride) with chlorinated polyethylene II. Irreversible deformation

Etude de la nature des deformations irreversibles dues a l'absorption d'energie mecanique par microscopies optiques et electroniques
Personal Care Aide Turnover in Residential Care Settings: An Assessment of Ownership, Economic, and Environmental Factors

Turnover among personal care aides is a chronic problem facing long-term-care industries. High turnover leads to high recruitment and training costs and to the potential for substandard care. Studi...
Computational experience with a branch-and-cut algorithm for flowshop scheduling with setups

This paper presents a branch-and-cut (B&C) algorithm for the problem of minimizing the makespan associated with scheduling n jobs in an m-machine flowshop with setup times (SDST flowshop). Two different mathematical formulations are considered. Model A is based on a traveling salesman problem-like formulation. Model B uses fewer binary variables and constraints, but is less structured than model A. A number of valid inequalities, including facet-inducing inequalities, for these two different formulations are evaluated. It was found that the B&C approach outperforms conventional branch and bound. With respect to computational effort, model B proved superior.
Improvements in iron status and cognitive function in young women consuming beef or non-beef lunches.

Iron status is associated with cognitive performance and intervention trials show that iron supplementation improves mental function in iron-deficient adults. However, no studies have tested the efficacy of naturally iron-rich food in this context. This investigation measured the hematologic and cognitive responses to moderate beef consumption in young women. Participants (n = 43; age 21.1 ± 0.4 years) were randomly assigned to a beef or non-beef protein lunch group [3-oz (85 g), 3 times weekly] for 16 weeks. Blood was sampled at baseline, and weeks 8 and 16, and cognitive performance was measured at baseline and week 16. Body iron increased in both lunch groups (p < 0.0001), with greater improvement demonstrated in women with lower baseline body iron (p < 0.0001). Body iron had significant beneficial effects on spatial working memory and planning speed (p < 0.05), and ferritin responders (n = 17) vs. non-responders (n = 26) showed significantly greater improvements in planning speed, spatial working memory strategy, and attention (p < 0.05). Lunch group had neither significant interactions with iron status nor consistent main effects on test performance. These findings support a relationship between iron status and cognition, but do not show a particular benefit of beef over non-beef protein consumption on either measure in young women.
On the Performance of High- $Q$ Multiring Optical Filters

We study the performance of multiring-based optical filters in the presence of resonant frequency mismatch among the microrings induced by fabrication error, optical absorption, and nonlinear optical effects, as well as in the context of silicon-on-insulator technology. A general framework is developed to evaluate the worst-case impact of fabrication error and input power on the performance of a bandpass multiring optical filter with Butterworth response.
Delay performance of different MAC schemes for multihop wireless networks

This paper studies the end-to-end (e2e) delay performance of a multihop wireless network fed with a single constant bit rate (CBR) source. Two MAC schemes are investigated, m-phase TDMA and probabilistic slotted ALOHA. A delay model is used to analyze the resulting tandem queueing system and derive tight upper bounds on the delay mean. The e2e delay linearly increases with the route length and its distribution converges to a Gaussian distribution. For channels with reception probability greater than 0.5, TDMA significantly outperforms ALOHA. For unreliable channels, the situation is less clear
The Ethics of Offering Dialysis for AKI to the Older Patient: Time to Re-Evaluate?

Older patients are more susceptible to AKI. In the elderly, AKI has been associated with increased morbidity and mortality, and it is a significant risk factor for CKD and dialysis-dependent ESRD. There are now accumulating data that the start of dialysis for some older patients is associated with poor outcomes, such as high treatment intensity, suffering, and limited life prolongation, which occur at the expense of dignity and quality of life. The biomedicalization of aging is a relatively recent field of ethical inquiry with two directly relevant features to decisions about starting dialysis for older patients with AKI: (1) the routinization of geriatric clinical interventions, such as dialysis, which results in the overshadowing of patient choice, and (2) the transformation of the technological imperative into the moral imperative. A major consequence of the biomedicalization of aging is that societal expectations about standard medical care have resulted in the relatively unquestioned provision of dialysis for AKI to older patients. This paper calls for nephrologists to re-examine the data and their attitudes to offering dialysis to older patients with AKI, especially those patients with underlying CKD and significant comorbidities. Shared decision-making and the reinforcement of the right of the patient to make a choice need to slow down the otherwise ineluctable routinization of starting old and very sick patients on dialysis. In the process of shared decision-making, nephrologists should not automatically recommend dialysis for older patients; in those patients who can be predicted to do poorly, recommending against dialysis upholds the Hippocratic maxim to be of benefit and do no harm. This paper challenges the automatic transformation of the technological imperative into the moral imperative for older patients with AKI and points to the need for a re-evaluation of dialysis ethics in this population.
Sapir's Poetic Experience

In a review (AA 85:345-355, 1983) of Stanley Diamond's poetry, Dan Rose notes that Edward Sapir and Ruth Benedict were, like Diamond and other present-day practitioners, both anthropologists and poets. Though Rose pays tribute to the poetic adventurousness of these anthropological ancestors, he sees them as a "warning" rather than as an example for those concerned to combine the two endeavors. Ac-
Can modifications to the bedroom environment improve the sleep of new parents? Two randomized controlled trials

Postpartum sleep disruption is common among new parents. In this randomized controlled trial we evaluated a modified sleep hygiene intervention for new parents (infant proximity, noise masking, and dim lighting) in anticipation of night-time infant care. Two samples of new mothers (n = 118 and 122) were randomized to the experimental intervention or attention control, and sleep was assessed in late pregnancy and first 3 months postpartum using actigraphy and the General Sleep Disturbance Scale. The sleep hygiene strategies evaluated did not benefit the more socioeconomically advantaged women or their partners in Sample 1, but did improve postpartum sleep among the less advantaged women of Sample 2. Simple changes to the bedroom environment can improve sleep for new mothers with few resources.
The latent resources of the child's mind

Dr. Hess was Asked to prepare this paper for presentation at several of the conferences in connection with the NASDTEC-AAAS Study of Guidelines for Science and Mathematics in the Preparation Program of Elementary School Teachers in the winter and spring of 1961–62. His task was to stimulate thought by the conference participants on various issues related to the education of elementary school science and mathematics teachers. His thoughts may also stimulate science educators to consider research in the area of early experience in the learning of science.
Kinesin carries the signal

Abstract Conventional kinesin has long been known to be a molecular motor that transports vesicular cargo, but only recently have we begun to understand how it functions in cells. Regulation of kinesin involves self-inhibition in which a head-to-tail interaction prevents microtubule binding. Although the mechanism of motor activation remains to be clarified, recent progress with respect to cargo binding might provide a clue. Kinesin binds directly to the JIPs (JNK-interacting proteins), identified previously as scaffolding proteins in the JNK (c-Jun NH 2 -terminal kinase) signaling pathway. The JIPs can allow kinesin to transport many different cargoes and to concentrate and respond to signaling pathways at certain sites within the cell. The use of scaffolding proteins could be a general mechanism by which molecular motors link to their cargoes.
Utilization of diets containing graded levels of ethanol production co-products by Nile tilapia

Summary A feeding trial was performed to investigate inclusion levels of distillers dried grains with solubles (DDGS) as a fishmeal replacement for juvenile Nile tilapia (Oreochromis niloticus). On a dry matter basis, five isocaloric [19.3 ± 0.4 kJ/g (mean ± SE)], isonitrogenous (39.1 ± 0.5% crude protein) diets were formulated to contain 17.5%, 20%, 22.5%, 25%, and 27.5% DDGS and compared against a 0% DDGS, reference diet (gross energy = 14.5 kJ/g; crude protein = 39.8%). The reference diet resulted in significantly higher body weight gain (BWG), food conversion ratio (FCR), and protein efficiency ratio (PER) than experimental diets except that 17.5% DDGS provided similar FCR and PER. The diet containing 27.5% DDGS had significantly lower FCR and PER values than all other diets even though apparent digestibility did not significantly differ among experimental diets. Although DDGS can be incorporated at higher levels, 20% DDGS provided the highest apparent BWG among experimental diets, while 17.5% promoted the best FCR and PER. Fishmeal may be replaced with low levels of fuel-based DDGS to reduce feeding cost; however, additional supplements should be considered to enhance fish performance.
Organizational assimilation of complex technologies: an empirical study of component-based software development

The rapid rate at which new information technologies are emerging and their increasing complexity pose significant challenges for information systems departments in understanding and assimilating them. This has lead to a need for studies focused on the barriers to the adoption and assimilation of complex technologies. This research synthesizes the economic and organizational learning perspectives of technology adoption and identifies key adoption barriers, mechanism to reduce these barriers, and proposes a research model that interrelate these factors to the assimilation of complex technologies. The research context for this paper is the assimilation of one complex technology, namely, component-based software development (CBD) by information systems (IS) departments. Data collected from IS units in the United States is used to test the model using partial least square analysis. The results provide evidence that organizations better positioned to overcome knowledge barriers because of their knowledge stocks are likely to be further along in the assimilation process than others and that knowledge sharing by technology vendors positively influences technology assimilation by reducing the learning burden of the adopters. It was also found that exposure to signals from technology vendors reduced the technology uncertainty perceived by the adopters.
Patterns and Implications of MR Contrast Enhancement in Perinatal Asphyxia: A Preliminary Report

PURPOSE To determine the presence and location of MR contrast enhancement in infants with perinatal asphyxia and to evaluate the utility of enhancement in assessing extent of brain damage. METHODS Precontrast and postcontrast MR examinations within the first 10 days of life were evaluated in 10 infants with suspected hypoxic-ischemic birth injury. Findings were correlated with clinical birth history and short-term neurologic follow-up. RESULTS All four infants with MR signal abnormalities and contrast enhancement in the basal ganglia and brain stem had early seizures and profound neurologic deficits at early follow-up. Two infants had abnormal scans but no contrast enhancement; one with MR signal abnormality within the basal ganglia is neurologically healthy at 10-month follow-up, whereas the other, in status epilepticus at the time of imaging at age 2 days, died. Two infants with minimal parasagittal subcortical white matter enhancement had no early seizure activity and only mild developmental delay at early follow-up. Two infants with normal precontrast and postcontrast MR had no early seizures and remain healthy at early follow-up, despite initial clinical parameters similar to more severely injured infants. CONCLUSION Although the number of patients is small, our results indicate that the presence of contrast enhancement in asphyxiated neonates may indicate more severe brain damage and, hence, a poorer prognosis.
Use of the Direct-Current Electric Potential Method to Monitor Large Amounts of Crack Growth in Highly Ductile Metals

The direct-current electric potential method is receiving increasing attention for monitoring crack extension in J-resistance curve testing. Among its advantages over the unloading-compliance method are: (1) no time-consuming unloadings are required, (2) a continuous record of crack extension versus displacement can be obtained, and (3) the method can be used at higher strain rates where unloading compliance cannot be used. Despite the advantages of the direct-current electric potential method, questions persist regarding its ability to monitor large amounts of crack growth in highly ductile materials where large displacements and large amounts of plastic strain occur. This paper presents details of an experiment conducted on a 3T planform-size compact specimen of 25.4 mm thickness to assess the ability of the direct-current electric potential method to accurately measure crack extension in a highly ductile material. The material selected was Type 304 austenitic stainless steel. It was found that the Johnson expression, often used to calculate crack extension from direct-current electric potential data, significantly underestimated the actual amount of crack extension. However, a simple modification of the Johnson expression resulted in excellent agreement between calculated and measured crack extensions.
Is high altitude pulmonary edema relevant to Hawai'i?

High altitude clinical syndromes have been described in the medical literature but may be under recognized in the state of Hawai‘i. As tourism increases, high altitude injuries may follow given the easy access to high altitude attractions. Visitors and clinicians should be aware of the dangers associated with the rapid ascent to high altitudes in the perceived comfort of a vehicle. This paper will review the basic pathophysiology, prevention, and treatment of the most serious of the high altitude clinical syndromes, high altitude pulmonary edema.