cssi/SciSciGPT-SciSciNet huggingface dataset:
Studies on the properties of peptide hydrolases in the brush-border and soluble fractions of small intestinal mucosa of rat and man

Abstract The properties of intestinal peptide hydrolases from two main subcellular loci, the brush-border and the cytosol fractions from man and rat, were studied. Peptide hydrolases were partially purified from the brush-border and cytosol fractions of small intestinal mucosa and the properties of these enzymes were examined using the following peptide substrates: l -alanylglycine, l -alanyldiglycine, l -alanyltriglycine, l -alanyltetraglycine, glycyl- l -alanine, diglycyl- l -alanine, di-, tri- and tetraglycine and a heterohexapeptide. Analysis of the reaction products after incubation of these peptides with intestinal peptide hydrolases indicated that in man and rat, both the brush-border and the cytosol enzymes are amino-oligopeptidases. When these peptides were used as substrates, the cytosol enzymes of both rat and human small intestinal mucosa were capable of hydrolyzing di- and tripeptides but could not hydrolyze peptides of greater chain length. In contrast, the brush-border enzymes prepared from both rat and man hydrolyzed all the peptide substrates including a heterohexapeptide. Data obtained from studies of heat stability and competition with various peptide substrates suggest that two enzymes probably are involved in the hydrolysis of l -alanylglycine and l -alanyldiglycine by the cytosol fraction. A similar study obtained with a brush-border preparation suggests that a single binding site may be involved in the hydrolysis of peptides of varying chain length. The data presented herein indicate that the peptide hydrolases of the brush-border and the cytosol fraction are distinct and further suggest that these enzymes from two subcellular loci play important roles in different stages of digestion and absorption of dietary proteins.
Peptide map analyses of murine Ia antigens of the I-E subregion using HPLC.

THE I REGION of the major histocompatibility complex (H–2) of the mouse1 controls various immunologically related functions including immune responsiveness and T-cell, B-cell and macrophage interactions2,3. The only gene products of the I region which have been identified by immunochemical techniques are the Ia antigens which are encoded by loci mapping to the I–A and I–E subregions of the I region4. Previously there has been ambiguity over whether the I–E and/or I–C subregion(s) control molecules detected by immunoprecipitation. Recent evidence suggests that the former, not the latter, controls these molecules5,6. The Ia antigens are highly polymorphic by serological analysis and are expressed predominantly on B lymphocytes and epidermal cells7. Ia molecules are integral cell-surface glycoproteins and consist of two subunits of approximate molecular weights 35,000 (α) and 28,000 (β) which are noncovalently associated7. A general nomenclature has been agreed upon for the Ia polypeptides8. For example, the α polypeptide from the I–E subregion of a mouse of the H–2d haplotype is denoted Eαd. Partial N-terminal amino acid sequence analyses of Ia polypeptides from the I–E and I–A subregions of mice8–14, humans14,15 and guinea pigs16 have led to several important observations. (1) The Eα polypeptides of mice show striking homology with human α chains (p34) at least at their N-termini. The Eβ polypeptides of mice also demonstrate some homology with their guinea pig and human counterparts. (2) The Ia polypeptides from the I–A subregion of mouse show little apparent homology with their human, guinea pig and I–E-subregion counterparts. (3) The Aα, Aβ and Eβ polypeptides of various haplotypes differ by one or more residues at their N-termini. However, for the Eαd and Eαk polypeptides no amino acid differences have been unequivocally demonstrated. To determine whether the N-terminal differences in the Eβ polypeptides extend throughout other regions of these polypeptides and whether the Eα polypeptides are identical, we have undertaken tryptic peptide analyses of two Ia molecules from the I–E subregion. We report here the application of high-pressure liquid chromatography (HPLC) to the separation of tryptic peptides and present comparative tryptic peptide maps for I–E subregion products from the H–2d and H–2k haplotypes.
Nonconvex Splitting for Regularized Low-Rank + Sparse Decomposition

We develop new nonconvex approaches for matrix optimization problems involving sparsity. The heart of the methods is a new, nonconvex penalty function that is designed for efficient minimization by means of a generalized shrinkage operation. We apply this approach to the decomposition of video into low rank and sparse components, which is able to separate moving objects from the stationary background better than in the convex case. In the case of noisy data, we add a nonconvex regularization, and apply a splitting approach to decompose the optimization problem into simple, parallelizable components. The nonconvex regularization ameliorates contrast loss, thereby allowing stronger denoising without losing more signal to the residual.
Electronic and magnetic structure of the mixed-valence cobaltite CaBaCo 4 O 7

Using first-principles density functional calculations we study the electronic and magnetic structure of mixed-valent cobaltite, CaBaCo${}_{4}$O${}_{7}$, consisting of alternate stacking of kagome and triangular layers. The compound belongs to the ``114'' series with the general formula, LnBa$M$${}_{4}$O${}_{7}$ ($M=$ Co, Fe). Our calculation shows that the strong orthorhombic distortion of the structure weakens the geometrical frustration and establishes the ferrimagnetic order, in good agreement with that reported by Caignaertet al. [Phys. Rev. B 81, 094417 (2010)]. Our calculated magnetic exchanges show strong Co-O-Co interactions both within the kagome layer and that connecting kagome with the triangular layer, thereby establishing the observed three-dimensional ordering. The reported magnetic ordering temperature is found to be smaller than that expected from the calculated magnetic exchanges, indicating the frustration being operative.
Science team for Obama's second term shaping up

The science team for the second term of the Obama administration continues to take shape, with several key people announcing plans to leave and others being nominated to fill key positions.
Extrapolation of Mutagenicity Testing to the Human

Agricultural genetic toxicology is typical of the challenging problems now being encountered in the rapidly growing field of environmental mutagenesis. Both fields involve a rich diversity of important chemicals, some already known mutagens, a few known carcinogens; both have some hints of human toxicity, but by and large no concrete human data; and both are floundering in the scientific and legal definition of human risk, as well as in regulatory confusion over when and to what degree to control.
Infrared spectroscopy-based property-reactivity correlations for predicting environmental fate of organic chemicals

A conventional structure-activity relationship (SAR) has been established between the alkaline hydrolysis rate constants (koh) of 12 alkyl and aryl formates and acetates and the linear combination of the frequencies of the C=o and C—o infrared (IR) absorbance peaks. The inability of this relationship to predict koh values for more structurally diverse carboxylic acid esters led to the development of a prototype of a prediction system that employs multiple linear regression analysis, using points from the Fourier transforms (FTs) of IR spectra. Conventional SARs have also been observed between single IR peak parameters and the microbial degradation rate constants of amides (C=O peak frequencies), 2,4-dichlorophenoxyacetate esters (CH peak intensities), phenols (OH peak frequencies), and anilines (NH stretching peak intensities). These observations indicate the feasibility of extending the FT-based prediction system to microbial degradation when reliable rates are available for additional compounds.
Are you Wittfogel or against him? Geophilosophy, hydro-sociality, and the state

Abstract Recent explorations of the “hydrosocial” cycle draw inspiration from Wittfogel’s basic concern with politics, power, and centralized authority, but move well beyond the limitations of previous scholarship. Most importantly, they have (re)introduced a conception of the social into the hydrological, and grappled with water’s materiality in ecumenical and creative ways. Understanding hydro-sociality requires an ontological approach to matter, flux, and flow. Water is the “universal solvent,” which makes it infinitely capable of mutation and connection. Yet, such indeterminacy proves difficult to capture in research and writing. Here I pinpoint some of the politico-discursive strengths of the hydrosocial approach, and also where I think its already strong ontological inclinations could be further developed. I draw from work in the area of “geophilosophy” as a way to explore hydro-sociality as a nonlinear process, developing a historicized account of irrigation politics, the flows of matter, and nonlinear dynamics in northwest Mexico’s Rio Mayo Valley.
A graphical method of solving simultaneous nonlinear differential equations of growth

Simultaneous nonlinear differential equations of growth of two variables x and y with time can be readily solved graphically by a method in which two directrices are used in the determination of the slope of curves relating y and x.
The inheritance of a defective lipopolysaccharide response locus in C3H/HeJ mice

F1 hybrid mice from crosses between the lipopolysaccharide (LPS) nonresponder strain C3H/HeJ and a variety of LPS responder strains show quantitative or codominant inheritance of mitogenic responsiveness to LPS. Backcross segregation ratios indicate that a defect at a single locus is responsible for the lack of responsiveness in C3H/HeJ mice. Autoradiographic studies show that the number of LPS-responsive cells in F1 cultures is approximately half the number of responsive cells in parent cultures. Kinetic patterns of mitogenic responsiveness to LPS differ in F1 hybrid and parent cultures. The kinetic patterns of responsiveness vary with the cell concentrations of the culture and appear to correlate with the number of LPS-responsive cells in F1 and parent cultures.
Laser fired contact for n-type crystalline Si solar cell

Ohmic contacts to n-type crystalline silicon created by local laser firing was studied in this paper. A novel metal stack of Al-Sb-Ti was fired through a dielectric layer or opposite doped amorphous silicon layer. Specific contact resistances of less than 1.9 mΩcm2 and 0.31 mΩcm2 using a pseudo transfer length method and a vertical test structure, respectively, are demonstrated. Recombination loss due to laser damage was consistent with an extracted local Surface Recombination Velocity (SRV) ~20,000 cm/s similar to values for laser fired base contact for p-type crystalline silicon. Hetero-junction devices were fabricated with laser fired back contact and proof-of-concept efficiencies of 14.4% on front silicon hetero-junction and 13.1% on interdigitated back contact silicon hetero-junction (IBC-SHJ) cells were achieved. This localized base contact technique will enable low cost back contact patterning and innovative design for n type crystalline solar cells.
An intrinsically disordered peptide from ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

Summary During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNP NTD complex, solved to 3.7 A resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.
Modeling of a free-burning, high-intensity arc at elevated pressures

A previously established model has been applied to a free-burning high-intensity argon arc at elevated pressures for simulating the situations experienced, for example, in plasma processing or in underwater welding. With the calculated thermodyanmic and transport properties and appropriate boundary conditions, solutions of the entire arc are obtained with exception of the electrode sheath regions. The results show that the arc contracts as the pressure increases. As a consequence of this contraction, the current density, the enthalpy flux, and the voltage drop increase also while the velocity of the induced cathode jet decreases.
E4orf6 variants with separate abilities to augment adenovirus replication and direct nuclear localization of the E1B 55-kilodalton protein.

The E4orf6 protein of group C adenovirus is an oncoprotein that, in association with the E1B 55-kDa protein and by E1B-independent means, promotes virus replication. An arginine-faced amphipathic α-helix in the E4orf6 protein is required for the E4orf6 protein to direct nuclear localization of the E1B 55-kDa protein and to enhance replication of an E4 deletion virus. In this study, E4orf6 protein variants containing arginine substitutions in the amphipathic α-helix were analyzed. Two of the six arginine residues within the α-helix, arginine-241 and arginine-243, were critical for directing nuclear localization of the E1B 55-kDa protein. The four remaining arginine residues appear to provide a net positive charge for the E4orf6 protein to direct nuclear localization of the E1B 55-kDa protein. The molecular determinants of the arginine-faced amphipathic α-helix that were required for the functional interaction between the E4orf6 and E1B 55-kDa proteins seen in the transfected cell differed from those required to support a productive infection. Several E4orf6 protein variants with arginine-to-glutamic acid substitutions that failed to direct nuclear localization of the E1B 55-kDa protein restored replication of an E4 deletion virus. Additionally, a variant containing an arginine-to-alanine substitution at position 243 that directed nuclear localization of the E1B 55-kDa protein failed to enhance virus replication. These results indicate that the ability of the E4orf6 protein to relocalize the E1B 55-kDa protein to the nucleus can be separated from the ability of the E4orf6 protein to support a productive infection.
A Numerical Model of Ratcheting in Thermal Barrier Systems

Morphological instabilities in thermally grown oxide, observed in a range of thermal barrier systems, have been simulated by developing and using a numerical code. The simulations are based on a range of phenomena and constituent properties, such as plasticity in the bond coat and growth strains in the TGO at high temperature. One of the key implications is that the incidence of reverse yielding upon reheating is a necessary condition for morphological instabilities. That is, whenever the condition for reverse yielding is satisfied during the initial cycles, the imperfection amplitude increases with thermal cycling (ratcheting). Otherwise, shakedown occurs, i.e., the imperfection amplitude stops growing.
Diversity of woody species in forest, treefall gaps, and edge in Kibale National Park, Uganda

If specialization influences species presence, then high tropical tree and shrub diversity should correspond with high environmental heterogeneity. Such heterogeneity may be found among different successional communities (i.e., canopy types). We explore species associations in three forest-dominated canopy types, forest, gap, and edge, in Kibale National Park, Uganda and determine environmental, soil and light, differences among canopy types. To determine the strength of differences among forested canopy types, they are also compared to grasslands. Tree and shrub density and species richness using rarefaction analysis were determined based on data from 24 small plots (5 x 5 m) in all four canopy types and 16 large plots (10 x 50 m) in forest and grassland canopy types. Environmental variables were determined along 10 (20 m) transects in the four canopy types. Using analysis of variance and principal components analysis, we demonstrate that forest and gap environments had similar soils, but forest had lower light levels than gap. We also found that grassland and edge were more similar to one another than to forest and gap, but differed in a number of important biotic and abiotic factors controlling soil water availability (e.g., edge had higher root length density of small roots <2 mm diameter in the top 20 cm than grassland). Using principal components analysis to assess similarities in community composition, we demonstrate that gap and forest had indistinguishable communities and that edge was similar to but distinct from both com munities. Complete species turnover only occurred between grassland and the three forested canopy types. Even though overall community composition was similar in the three forested canopy types, in analyses of individual species using randomization tests, many common species were most frequently found in only one canopy type; these patterns held across size classes. These results suggest that despite differences among environments, community composition was similar among forested canopy types, which are likely inter grading into one another. Interestingly, individual species are more frequently found in a single canopy type, indicating species specialization.
Towards improving access to math and science lecture material for visually impaired students via iOS support: a convergence of the student, instructor, and classroom

In this paper we describe a series of exploratory studies conducted as part of the development of AccessLacture, an iOS-based system that is designed to help visually impaired students access math or science lecture material in and out of the classroom. The instructor writes material on the whiteboard, via the Mimio Capture system, using standard whiteboard markers. The lecture material is sent as written strokes that the iOS app displays for the student in real-time. Students can adjust the size and contrast of the material, as well as write notes on the lecture itself for later viewing. The access to lecture provided by the system provides students the ability to follow an active lecture that can facilitate more class participation. In order to support student needs, students, instructors and the classroom environment itself were studied.
Antiretroviral therapy: time to think strategically.

In this issue, Henry argues the case for a more conservative, individualized approach to antiretroviral therapy and challenges some of the foundations on which guidelines have been built. Guideline...
Computer Methods in Electric Network Analysis

The computational algorithms utilized in power system analysis have more than just a minor overlap with those used in electronic circuit computer aided design. This paper describes the computer methods that are common to both areas and highlights the differences in application through brief examples. Recognizing this commonality has stimulated the exchange of useful techniques in both areas and has the potential of fostering new approaches to electric network analysis through the interchange of ideas.
GPR30 activation is neither necessary nor sufficient for acute neuroprotection by 17β-estradiol after an ischemic injury in organotypic hippocampal slice cultures.

Abstract In this study, we investigated the role of GPR30 in 17β-estradiol- (E2) mediated neuroprotection after an ischemic injury in an organotypic hippocampal slice culture (OHSC) model. We report that after oxygen–glucose deprivation (OGD), a physiological concentration of 100 pM E2 provided the greatest significant reduction in cell death while supra-physiological levels were less effective. The canonical estrogen receptor (ER) inhibitor ICI 182,780 completely abrogated the therapeutic effect of E2 while the GPR30 antagonist G−15 effected a slight but not significant reduction in neuroprotection. Only supra-physiological levels of E2 led to significantly increased phosphorylation of Akt and Erk which are well known downstream effects of GPR30 activation. We conclude that GPR30 activation may facilitate acute E2 mediated neuroprotection after OGD, but is neither necessary nor sufficient.
Satellite remote sensing and ozonesonde observation of ozone vertical profile and severe storm development

Two year ozonesonde data, January 1981 to December 1982, observed at four Canadian stations, and two-and-a-half year backscattered ultraviolet experiment data on the Nimbus-4 satellite, April 1970 to August 1972, observed over five U.S. stations, were used to study the relationship between the total ozone, vertical distribution of the ozone mixing ratio, height of half the total ozone, and the variation of local tropopause height. In view of the correlation between the variation of the tropopause height and the possible development of severe storms, a better understanding of the effect of the vertical distribution of the local ozone profile on the variation of the tropopause height can give considerable insight into the development of severe storms.
Changes in telomere length associated with antigenic variation in Trypanosoma brucei.

Abstract In the IsTaR 1 serodeme, we have identified variant surface glycoprotein (VSG) genes in nine different telomeric sites. We have measured the distance from the 3′ end of these VSG genes to the end of the chromosome (the ‘telomere length’) in 20 variant antigen types (VATs) of the serodeme. Analyses of the changes in telomere length during 19 antigenic switches involving eight telomeric sites indicate a median increase in telomere length of 0.6 kilobase pairs during each switch. This may be accounted for by the 6–10 bp increase in telomere length per generation associated with DNA replication described by others. The changes in telomere lengths do not form a normal distribution since a substantial fraction show unusually large increases in telomere length or decreases in telomere length during an antigenic switch. These changes are probably caused by recombinations 3′ to the VSG gene. No significant differences were detected in the behavior of telomeres at each of the eight different telomeric sites, nor were changes in telomere lengths significantly different between different antigenic switches. However, it was found that those telomeres where transcription was activated during the antigenic switch showed a significantly greater increase in telomere length than those telomeres not involved in regulation of VSG gene expression. Conversely, there was a strong correlation between transcriptional inactivation of a telomeric expression site and a decrease in telomere length. These findings suggest that processes (possibly genomic recombinations) 3′ to the VSG gene coding region may be associated with a change in the transcriptional status of the VSG gene.
Incorporating small fatigue crack growth in probabilistic life prediction: Effect of stress ratio in Ti–6Al–2Sn–4Zr–6Mo

Abstract The effect of stress ratio on the statistical aspects of small fatigue crack growth behavior was studied in a duplex microstructure of Ti–6Al–2Sn–4Zr–6Mo (Ti-6-2-4-6) at 260 °C with particular emphasis on incorporating small-crack data into probabilistic life prediction and the influence of stress ratio on probabilistic lifetime limits. A Focused Ion Beam (FIB) was used to machine micro-notches in test specimens, which served as crack-initiation sites and enabled the acquisition of multiple small-crack growth data sets from single experiment. Stress ratios of −0.5, 0.05, and 0.5 were employed, and small-crack growth was monitored by the acetate replication method. Qualitatively, change in the stress ratio produced almost negligible influence on the small-crack growth behavior when plotted as crack growth rate (d a /d N ) vs. applied stress intensity factor range (Δ K ). A probabilistic method was employed to represent the variability in the small-crack growth behavior and the statistical differences with respect to stress ratio where a method of optimization of the small-crack growth model parameters, based on a minimization of the error between the predicted and the measured crack length vs. cycles ( a vs. N ) data, was used. In spite of qualitative similarity, differences in the statistical parameters of small-crack growth as a function of stress ratio were found to be significant in life prediction. The methods for representation and probabilistic treatment of small-crack data were also shown to be important factors in incorporation of the small-crack regime in probabilistic life prediction.
Identifying students' errors in administering the WAIS-R

This study was conducted to investigate specific problems caused by the traditional method of teaching students to administer the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Analysis of 180 protocols provided by 26 graduate students revealed an average of 8.8 mistakes per protocol. When these errors were corrected, 81% of the Full Scale IQs were changed. The types of examiner errors most frequently made by students were identified, as were the subtests and items on which the most numerous mistakes occurred. Students' performance showed no improvement over five practice administrations, but did improve over eight. Even so, students continued to exhibit a high rate of errors. These findings suggest that traditional methods of teaching assessment specialists need to be examined.
Echocardiography-derived variables predict outcome in patients with nonischemic dilated cardiomyopathy with or without a restrictive filling pattern

Abstract Background Despite recent therapeutic advances, patients with heart failure caused by dilated cardiomyopathy (DCM) still have high morbidity and mortality rates. In this study, we sought to assess the prognostic value of echocardiographic variables in patients with DCM and to assess the impact of a restrictive left ventricle filling pattern. Design We conducted a retrospective cohort study of 337 patients with DCM, using the Royal Brompton Hospital Echocardiography database for the years 1994 to 1998. Methods and Results There were 337 patients with a mean age of 53 ± 15 years. One hundred ninety-five patients (58%) had a restrictive left ventricle filling pattern (RFP). There was a total of 74 deaths (22%) during the follow-up period (43 ± 25 months). RFP more than tripled the risk of death (adjusted hazard ratio 3.2, 95% CI 1.8-5.7, P =.003). RFP is correlated with isovolumic relaxation time, incoordinate wall-motion, amplitude of right ventricular long axis excursion on M-mode echocardiography, and mitral regurgitation. Conclusion RFP is a powerful independent predictor of mortality in patients with nonischemic DCM. The risk associated with RFP is greatest among patients who had short isovolumic relaxation time, mitral regurgitation, incoordinate wall-motion, and depressed amplitude of right ventricular long axis excursion. Thus, echocardiography-derived variables may stratify patients with heart failure with DCM who are at high risk, for whom aggressive medical treatment or heart transplantation should be considered early. (Am Heart J 2002;144:343-50.)
Reversible Inhibition of α-Ketoglutarate Dehydrogenase by Hydrogen Peroxide: Glutathionylation and Protection of Lipoic Acid†

We have previously demonstrated that when cardiac mitochondria were challenged with H2O2, NADH production and oxidative phosphorylation declined. Upon consumption of H2O2, mitochondrial function was restored. These alterations were due, in large part, to reversible glutathionylation and inhibition of the Krebs cycle enzyme alpha-ketoglutarate dehydrogenase. The current study was undertaken to identify the site and consequences of alpha-ketoglutarate dehydrogenase glutathionylation. Mitochondria were treated with H2O2 for varying periods of time. Protein sulfhydryls that had undergone H2O2 mediated glutathionylation were specifically derivatized with N-ethylmaleimide-biotin. Subsequent purification of biotin labeled (glutathionylated) protein and Western blot analysis revealed that the E2 subunit of alpha-ketoglutarate dehydrogenase was reversibly glutathionylated. Further analysis revealed that lipoic acid, a required cofactor covalently attached to the E2 subunit, was the site of glutathionylation. The relative level of glutathionylated lipoic acid closely paralleled the degree of enzyme inhibition and reactivation. Glutathionylation of alpha-ketoglutarate dehydrogenase protected lipoic acid from modification by the electrophilic lipid peroxidation product 4-hydroxy-2-nonenal. Glutathionylation of alpha-ketoglutarate dehydrogenase can therefore be viewed as an antioxidant response protecting the enzyme from oxidative damage.
Effects of sulfur and phosphorus on the creep ductility of a CrMoV steel

Abstract In this paper the results of creep rupture tests performed at 550°C on a high purity 1Cr1.5Mo0.25V steel containing residual sulfur and deliberately added phosphorus and manganese are described. The effects of impurities, hardness, grain size and step cooling were examined. The material with deliberately added phosphorus and manganese showed the highest ductility, the high purity (undoped) material with residual sulfur showed the lowest ductility and that of the material with deliberately added phosphorus was intermediate. The effects of hardness on the creep ductility are due to the change in the relative cavitation rates in the grain boundaries and matrix. The effect of prior austenite grain size is actually due to the effect of different austenitization temperatures (which affects the grain boundary chemical composition). The results obtained here are quite consistent with our previous tensile test results and are interpreted in terms of the effects of sulfur and phosphorus segregation on grain boundary cavitation.
Introduction to the Special Issue on Theory Development in Operations Management

Rigorous development of theory in operations management has been lacking. Although many theories have been proposed, they are often not developed in a format and depth that can be falsified, refined, or supported. This special issue includes three papers that illustrate rigorous development of theory for future testing using mathematical, simulation, or managerial approaches.
Effects on groundwater microbial communities of an engineered 30-day in situ exposure to the antibiotic sulfamethoxazole.

Effects upon microbial communities from environmental exposure to concentrations of antibiotics in the μg L–1 range remain poorly understood. Microbial communities from an oligotrophic aquifer (estimated doubling rates of only once per week) that were previously acclimated (AC) or unacclimated (UAC) to historical sulfamethoxazole (SMX) contamination, and a laboratory-grown Pseudomonas stutzeri strain, were exposed to 240–520 μg L–1 SMX for 30 days in situ using filter chambers allowing exposure to ambient groundwater, but not to ambient microorganisms. SMX-exposed UAC bacterial communities displayed the greatest mortality and impairment (viable stain assays), the greatest change in sensitivity to SMX (dose–response assays), and the greatest change in community composition (Terminal Restriction Fragment Length Polymorphism; T-RFLP). The sul1 gene, encoding resistance to SMX at clinically relevant levels, and an element of Class I integrons, was not detected in any community. Changes in microbial community ...
Recent knowledge: Concepts of dermal absorption in relation to skin decontamination

Skin decontamination is an important step mitigating percutaneous absorption through the stratum corneum (SC), which is also a highly complex process. Thus, understanding diffusion mechanisms and measuring dermal absorption rates are critical to protect humans from toxic exposures. Here, highly varied literature is placed in a biological and clinical perspective in regards to decontamination. Literature from PubMed and Surge Laboratory library files were searched and reviewed for relevance. Recent data have shown multiple layers of SC structural heterogeneity, which results in unique substance partitioning characteristics across the membrane. As such, attempts to model and understand this behavior in alternative in vitro membranes prove difficult. More synthetic and natural membranes are being explored as models for in vivo behavior. In addition, commonly accepted decontamination methods are undergoing risk assessment. These recent and varied literature findings update available knowledge regarding skin decontamination and its challenges, with a focus on dermal absorption.
A novel method for preparing poly(alkyl methacrylates) and poly(methacrylic acids) of varying tacticity

In order to synthesize poly(methacrylic acid) and poly(alkyl methacrylates) over a wide range of polymer tacticity, the anionic polymerization of the following alkyl methacrylates (ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-amyl, n-hexyl, n-octyl, n-decyl, n-lauryl, and n-octadecyl) in toluene using phenylmagnesium bromide initiation was studied. It was found that the amount of isotactic polymer structure generally decreased as the size of the ester group increased. In all cases, the polymers had greater than 50% isotactic triad structure. Whether the polymerization was carried out at 0° or −78°C had little or no effect on the tacticity of the polymer produced. It was found that the poly(alkyl methacrylates) produced could be hydrolyzed in concentrated sulfuric acid to poly(methacrylic acid). The poly(methacrylic acid) produced in the hydrolysis could be esterified with diazomethane to give poly(methyl methacrylate) or with diazoethane to give poly(ethyl methacrylate) with the same tacticity as the poly(alkyl methacrylate) from which the poly(methacrylic acid) was derived. It is possible, therefore, to produce poly(alkyl methacrylates) of a desired tacticity by polymerizing the appropriate monomer, hydrolyzing, and reesterifying the resultant poly(methacrylic acid) with a diazoalkane to give the desired poly(alkyl methacrylate).
Report on the workshop on research issues in data mining and knowledge discovery workshop (DMKD 2001)

This short article summarizes the program of the Sixth Workshop on Research Issues in Data Mining and Knowledge Discovery Workshop (DMKD 2001).
A web‐based restriction endonuclease tool for mycobacteriophage cluster prediction

A recent explosion in the amount of genomic data has revealed a large genetic diversity in the bacteriophages that infect Mycobacterium smegmatis. In an effort to assess the novelty of newly described mycobacteriophage isolates and provide a preliminary determination of their probable cluster assignment prior to full genome sequencing, we have developed a systematic approach that relies on restriction endonuclease analysis. We demonstrate that a web-based tool, the Phage Enzyme Tool (or PET), is capable of rapidly facilitating this analysis and exhibits reliability in the putative placement of mycobacteriophages into specific clusters of previously sequenced phages. We propose that this tool represents a useful analytical step in the initial study of phage genomes and that this tool will increase the efficiency of phage genome characterization and enhance the educational activities involving mycobacteriophage discovery.
Glucose utilization by 6pgd genotypes in Lolium perenne

To gain a deeper understanding of the mechanisms underlying associations between allozyme genotypes and rates of respiration in Lolium perenne, Vmax Km and rates of glucose flux through glycolysis and the pentose phosphate pathway were estimated for the three genotypes of the 6pgd locus. Km Vmax and Vmax/Km differed significantly among genotypes. Values of Km for the 11, 12, and 22 genotypes were 0.29, 0.25, 0.13, while the values of Vmax/Km for die 11, 12, and 22 genotypes were 3.79, 3.85, 6.70. Flux through the pentose shunt did not differ among genotypes at 20 °C, but at 35 °C the rates of flux for the 11, 12, and 22 genotypes were 0.15, 0.25 and 0.42, respectively. Thus, the 6PGD allozyme genotypes differ markedly in both enzyme kinetic characteristics and in flux through a metabolic pathway. These associations reveal potentially causal relationships between allozyme genotypes and rates of respiration.
Transcendentalism and Religion: The State of Play

This essay surveys the scholarship on American Transcendentalism for the last fifty years, focusing on its treatment of the place of religion in the movement. It finds that after an initial period when interest in religion, defined in terms of the history of ideas and institutions, was high, the 1970s and 1980s saw a neglect or exclusion of religion as a factor in Transcendentalism. More recently, there has been a resurgence of interest, however, with emphasis on such topics as spirituality and multiculturalism.
Emerging concepts and approaches for chemokine-receptor drug discovery.

Importance of the field: Chemokine receptors are most noted for their role in cell migration. However, inappropriate utilization or regulation of these receptors is implicated in many inflammatory diseases, cancer and HIV, making them important drug targets.Areas covered in this review: Allostery, oligomerization and ligand bias are presented as they pertain to chemokine receptors and their associated pathologies. Specific examples of each are described from the recent literature and their implications are discussed in terms of drug discovery efforts targeting chemokine receptors.What the reader will gain: Insight into the expanding view of the multitude of pharmacological variables that need to be considered or that may be exploited in chemokine receptor drug discovery.Take home message: Since 2007, two drugs targeting chemokine receptors have been approved by the FDA, Maraviroc for preventing HIV infection and Mozobil™ for hematopoietic stem cell mobilization. While these successes permit optimism for c...
The Organizational Correlates of Terrorism Response Preparedness in Local Police Departments

Since the development of homeland security, scholars have debated the relationship between community-oriented policing and homeland security innovations in local police departments. Most of the lit...
Tactical Conict Resolution using Vertical Maneuvers in Enroute Airspace

An algorithm is presented for computing vertical resolution maneuvers to resolve imminent air trac conicts in which loss of separation could occur within two minutes. Several procedures are used, including rejection of altitude amendments that could cause a conict, temporary altitudes, step altitudes, and critical-levelo conrmation. These methods are tested on archived data from 100 actual operational errors (loss of separation due to controller error), which tend to be more dicult to detect and resolve than routine conicts that get resolved successfully. Successful resolution was achieved in simulation for 84 of them using vertical maneuvers only. Augmented altitude amendments are then added to the input les to simulate altitude amendments that should have been entered by the controller but were not, or to correct amendments to make them consistent with the pilot’s understanding. The number of successful resolutions increased to 94 of the 100 cases. The reasons for the failures are discussed.
Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor–induced angiogenesis

Many patients with cancer receive combinations of drug treatments that include 5-fluorouracil (5-FU) and bevacizumab. Therapeutic doses of 5-FU are often associated with unwanted side effects, and bevacizumab is costly. Therefore, we explored potential agents that can reduce the therapeutic concentration of these drugs. Our data indicate that methylnaltrexone (MNTX), a peripheral antagonist of the μ-opioid receptor, exerts a synergistic effect with 5-FU and bevacizumab on inhibition of vascular endothelial growth factor (VEGF)–induced human pulmonary microvascular endothelial cell (EC) proliferation and migration, two key components in cancer-associated angiogenesis. MNTX inhibited EC proliferation with an IC50 of ∼100 nmol/L. Adding 100 nmol/L MNTX to EC shifted the IC50 of 5-FU from ∼5 μmol/L to ∼7 nmol/L. Further, adding 50 ng/mL MNTX shifted the IC50 of bevacizumab on inhibition of EC migration from ∼25 to ∼6 ng/mL. These synergistic effects were not observed with naltrexone, a tertiary μ-opioid receptor antagonist. On a mechanistic level, we observed that treatment of human EC with MNTX, but not naltrexone, increased receptor protein tyrosine phosphatase μ activity, which was independent of μ-opioid receptor expression. Silencing receptor protein tyrosine phosphatase μ expression (small interfering RNA) in human EC inhibited both synergy between MNTX and bevacizumab or 5-FU and increased VEGF-induced tyrosine phosphorylation of Src and p190 RhoGAP with enhanced activation of Akt and the actin cytoskeletal regulatory protein, RhoA, whereas silencing Src, Akt, or RhoA blocked VEGF-induced angiogenic events. Therefore, addition of MNTX could potentially lower the therapeutic doses of 5-FU and bevacizumab, which could improve index. [Mol Cancer Ther 2008;7(6):1669–79]
Incremental meta-data construction for VLSI design databases

VLSI design databases are typically based on object-oriented data models, which provide primitives for modeling and manipulating design objects and their inter-relationships. However, in practice it is rather difficult for end users (i.e. circuit designers) to understand these primitives, let alone interact with them directly. Unfortunately, existing systems assume that it is the user's responsibility to explicitly build up the meta-data, by which is meant attribute and relationship information. This paper presents a novel incremental meta-data construction paradigm, which is based on (1) a structured design history model, and (2) the specifications of tool-specific execution semantics. Using this paradigm, the authors design and implement algorithms that automatically establish per-object attributes and inter-object relationships as a side effect of CAD tool execution. Consequently the rich modeling capability of an object-oriented database can be fully exploited in a design environment without circuit designers' participation in meta-data construction. >
Aminoglutethimide Inhibits Extraglandular Estrogen Production in Postmenopausal Women with Breast Carcinoma

Extraglandular aromatization of androstenedione (δ4-A) to estrone (E1) provides the primary source of estrogen production in spontaneously postmenopausal or surgically castrate women. Estrogens produced by this enzymatic reaction in peripheral tissues can be biologically important, particularly in women with metastatic breast carcinoma. In such patients, an aromatase inhibitor would have potential usefulness clinically. In vitro studies demonstrated that aminoglutethimide (AG), a drug previously used as an adrenal steroidogenesis inhibitor, is also a potent aromatase blocker. A similar in vivo effect of AG was suggested by clinical observations of suppressed plasma E1 without concomitant reductions in δ4-A concentrations in postmenopausal women given this drug. Based upon these considerations, we examined the in vivo effects of AG on the rate of aromatization of δ4-A to E1 by direct radioisotopic kinetic methods. AG inhibited the fractional conversion of δ4-A to E1 in blood from 1.65 ± 0.28% (se) before t...
Inhibin-B as a test of ovarian reserve for infertile women

The objective of the study was to compare a standard clomiphene citrate challenge test with inhibin-B serum concentrations also obtained on cycle days 3 and 10 as a negative predictor of pregnancy in a group of 106 women at risk for compromised ovarian function. Mean duration of follow-up was 8.25 months in 95 patients with 30 pregnancies recorded (plus one biochemical). Inhibin-B concentrations on cycle days 3 and 10 were correlated only with each other and not with serum oestradiol, follicle stimulating hormone (FSH) and/or pregnancy rates. Pregnancy occurred in 34.5% (10/29) of all patients with inhibin-B values >/=45 pg/ml on cycle day 3 and in 31.8% (21/66) of those with values 11 mIU/ml on either day, pregnancy rate was 13.6% versus 38.4% for FSH of </=9 mIU/ml (P = 0.03). This study reconfirmed the usefulness of a clomiphene citrate challenge test as an indication of ovarian reserve but failed to find clinical value for inhibin-B testing.
Vandetanib for the Treatment of Symptomatic or Progressive Medullary Thyroid Cancer in Patients with Unresectable Locally Advanced or Metastatic Disease: U.S. Food and Drug Administration Drug Approval Summary

On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24-0.53; P 5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease.
Mechanical properties of sand, silt, and clay containing tetrahydrofuran hydrate

[1] The mechanical behavior of hydrate-bearing sediments subjected to large strains has relevance for the stability of the seafloor and submarine slopes, drilling and coring operations, and the analysis of certain small-strain properties of these sediments (for example, seismic velocities). This study reports on the results of comprehensive axial compression triaxial tests conducted at up to 1 MPa confining pressure on sand, crushed silt, precipitated silt, and clay specimens with closely controlled concentrations of synthetic hydrate. The results show that the stress-strain behavior of hydrate-bearing sediments is a complex function of particle size, confining pressure, and hydrate concentration. The mechanical properties of hydrate-bearing sediments at low hydrate concentration (probably 50% of pore space), the behaviorbecomesmoreindependentofstressbecausethehydratescontrolbothstiffnessand strength and possibly the dilative tendency of sediments by effectively increasing interparticle coordination, cementing particles together, and filling the pore space. The cementation contribution to the shear strength of hydrate-bearing sediments decreases with increasing specific surface of soil minerals. The lower the effective confining stress, the greater the impact of hydrate formation on normalized strength.