cssi/SciSciGPT-SciSciNet huggingface dataset:
Furin inhibitors: Importance of the positive formal charge and beyond

Furin is the prototype member of the proprotein convertases superfamily. Proprotein convertases are associated with hormonal response, neural degeneration, viral and bacterial activation, and cancer. Several studies over the last decade have examined small molecules, natural products, peptides and peptide derivatives as furin inhibitors. Currently, subnanomolar inhibition of furin is possible. Herein, we report the analysis of 115 furin inhibitors reported in the literature. Analysis of the physicochemical properties of these compounds highlights the dependence of the inhibitory potency with the total formal charge and also shows how the most potent (peptide-based) furin inhibitors have physicochemical properties similar to drugs. In addition, we report docking studies of 26 furin inhibitors using Glide XP. Inspection of binding interactions shows that the two putative binding modes derived from our study are reasonable. Analysis of the binding modes and protein-ligand interaction fingerprints, used here as postdocking procedure, shows that electrostatic interactions predominate on S1, S2 and S4 subsites but are seldom in S3. Our models also show that the benzimidamide group, present in the most active inhibitors, can be accommodated in the S1 subsite. These results are valuable for the design of new furin inhibitors.
Revisiting the Task/Achievement Analysis of Teaching in Neo-Liberal Times.

In 1975 I published an article on Gilbert Ryle's task/achievement analysis of teaching (), arguing that teaching was in Ryle's sense of the distinction a task verb. Philosophers of education were appealing to a distinction between tasks and achievements in their discussions of teaching, but they were often also appealing to Ryle's work on the analysis of task and achievement verbs. Many philosophers of education misunderstood Ryle's distinction as teaching was often claimed to be a term with both an achievement sense and a task sense. In terms of Ryle's distinction a verb could not have both a task and an achievement sense. It will be argued that in recent (neo‐liberal) discussions of education, teaching is treated more as an achievement verb than as a task verb, contrary to my original claim that teaching was a task verb. ‘Teaching’ then would appear to have changed its meaning. If that is so, it is a function of altered approaches to teaching (and its teaching in Teacher Education), whereby unless some...
TDHF with two-body dissipation

Abstract A modification of the time-dependent Hartree-Fock (TDHF) formalism is proposed in order to incorporate two-body dissipation. For this purpose a relaxation time, τ, is defined for a statistical redistribution of nucleon momenta due to the nucleon-nucleon scatterings. This process drives the nuclear system at each point towards isotropic Fermi distributions. The method is illustrated by showing results for the collision of one-dimensional nuclear slabs and comparison with TDHF is made. Microscopic calculations show τ to be of the order of 10 −21 s. For this value of τ and collisions of a few MeV/nucleon the two-body dissipation is comparable with one-body dissipation.
The Spack package manager: bringing order to HPC software chaos

Large HPC centers spend considerable time supporting software for thousands of users, but the complexity of HPC software is quickly outpacing the capabilities of existing software management tools. Scientific applications require specific versions of compilers, MPI, and other dependency libraries, so using a single, standard software stack is infeasible. However, managing many configurations is difficult because the configuration space is combinatorial in size. We introduce Spack, a tool used at Lawrence Livermore National Laboratory to manage this complexity. Spack provides a novel, recursive specification syntax to invoke parametric builds of packages and dependencies. It allows any number of builds to coexist on the same system, and it ensures that installed packages can find their dependencies, regardless of the environment. We show through real-world use cases that Spack supports diverse and demanding applications, bringing order to HPC software chaos.
Acute Carotid Rupture Associated with Postoperative Staphylococcus Aureus Infection

A. The medial wall of the carotid artery demonstrates extensive disruption. Numerous polymorphonuclear leukocytes are present (inset). B. The elastic layer of the tunica media is extensively disrupted (asterisk) with focal transmural necrosis (arrow). The internal elastic lamina (arrowheads) is mostly preserved. D. Proximal area of carotid wall disruption was only focal (asterisk) but required emergency reintervention. (A. C. Hematoxylin-eosin, 20x; inset, 100x. B. D. Elastic stain, 20x)
Evolution of the optical functions of thin-film aluminum: A real-time spectroscopic ellipsometry study

We report a comprehensive study of the optical functions of thin-film aluminum from initial nucleation through continuous film growth. This study relies on ellipsometric spectra from 1.3 to 4.0 eV collected in real time with a multichannel instrument during both thermal evaporation and magnetron sputtering of Al onto ${\mathrm{SiO}}_{2}$ substrates at room temperature. The spectra for all films in the particle growth regime can be modeled with a Maxwell-Garnett-type effective medium theory, modified to include dipole interactions between spheroidal particles arranged on a square grid. The dielectric functions of the Al particles themselves, as well as those of continuous films, are interpreted assuming variable relaxation times for both Drude and interband electronic contributions. The relaxation times are determined by a common value of the mean free path, reduced from its bulk film value owing to electron scattering at defects, particle surfaces, and grain boundaries. For all films in the particle regime of growth, i.e., for thicknesses \ensuremath{\sim}50 \AA{}, the deduced relaxation times are independent of thickness (and hence particle size), and are more than an order of magnitude lower than bulk film values. This suggests a defective structure in which electron scattering at internal particle defects limits the relaxation time and determines the particle optical functions. For Al prepared by high-rate evaporation, a transition is observed at a thickness of 55--60 \AA{}, just after continuous film formation. At the transition, the interband electron relaxation time increases abruptly, signaling the development of higher-quality crystalline grains that extend throughout the film thickness. Only after this transition is the (200) parallel-band absorption feature visible in the Al dielectric function at 1.5 eV. For thicknesses g60 \AA{}, the interband relaxation time increases with thickness, providing evidence that grain-boundary scattering is the dominant mechanism controlling the optical properties in the bulk film stage.
Stimulation of collagen and glycosaminoglycan production by phenytoin 5,5-diphenylhydantoin in monolayer cultures of mesenchymal cells derived from embryonic chick sternae.

Abstract Cultures grown with or without phenytoin (PHT) at a concentration of 5 μg/ml from the fifth to the eighth day after plating were labelled with [14C]-proline (0.2 μCi/ml) from the sixth to eighth day. Collagenase digestion indicated that collagen content increased approx. 2-fold after PHT exposure. Increases in sulphated glycosaminoglycan product in response to PHT were approx. 1.5-fold; PHT also stimulated protein production. Both actinomycin D and cycloheximide blocked incorporation of [3H]-leucine, [3H]-proline, and H235SO4 approx. 90 per cent with or without PHT. Continuous sucrose density-gradient fractionation indicated that PHT produced quantitative but not qualitative changes in cellular RNA.
Finite element modelling of thermoviscous acoustics in closed cavities

A numerical methodology is presented to compute the acoustic field in a closed domain filled by a thermoviscous fluid, using the finite element method. The formulation based upon temperature variation and particle velocity is well suited for both (i) modelling the acoustic, thermal and viscous effects in the fluid bulk and (ii) accounting for the non‐slip and thermal boundary conditions on the solid. The set of coupled equations presents usual scalar‐ and vector‐ operators for finite element modelling. Due to the development of thin thermal‐ and viscous‐ boundary layers compared to the acoustic wavelength, very different scales are present in the computed fields: the finite‐element mesh needs to be dramatically refined along the direction normal to the boundary, while a coarse mesh is often sufficient along the directions parallel to the boundary, and far from the boundaries. The optimised mesh is obtained iteratively, using a loop procedure computing (a) the thermoviscous solution, (b) the metric map suited for this field, and (c) the unstructured anisotropic adapted mesh based on this metric, until convergence. Results are presented for two‐dimensional and axisymmetric three‐dimensional applications, illustrating thermoviscous effects for various geometries of cavities.
Preliminary study of a web-based tool for enhancing the informed consent process in schizophrenia research

Printed research consent forms serve to legally document what has been disclosed, but are usually suboptimal as a means of actually communicating that information to potential participants. We conducted a preliminary study of web-based multimedia consent. Participants included 19 patients with schizophrenia and 16 normal comparison (NC) subjects randomly assigned to a routine or web-media consent. Although comprehension among NCs was excellent regardless of consent condition, the web-based consent was associated with better comprehension and satisfaction among patients with schizophrenia. Findings suggest that web-aided multimedia consent is feasible and potentially more effective than printed consent forms in schizophrenia research.
Digit Ratio: A Pointer to Fertility, Behavior, and Health

The main message of this book is simple and John Manning does an excellent job of delivering it clearly. The ratio of second and fourth (finger) digit lengths (2D:4D) appears to be affected by foetal testosterone exposure, may be fixed before birth, and so may be a reliable indicator of early prenatal conditions and subsequent health factors.
Why and How to Use Customer Opinions: A Quality-of-Life and Customer Satisfaction-Oriented Foundation for Performance-Based Decision-Making

AbstractThe concepts of ‘customer satisfaction’ (CS) and ‘quality of life’ (QOL) have both been used, on a limited basis, in strategic planning and performance measurement at state departments of transportation. However, the meanings and usefulness of these concepts are still unclear or evolving to many practitioners. Based on a review of the literature and customer opinion data collected for various transportation studies in the USA and Europe, this paper offers two important contributions to the transportation literature. The paper clarifies the relationship between the CS and QOL concepts, placing CS in the broader context of customer opinions and subjective well-being. The paper then identifies six categories of survey tools for collecting customer opinions, describing how each can be used within a performance management framework to reveal the QOL impacts of transportation decisions. Agencies can use the definitions, conceptual relationships, performance measures, and decision-making processes discus...
SU-FF-T-197: In Vivo Dose Reconstruction Using a 2D Array Dosimeter Via Transit Dosimetry

Purpose: To determine if a commercially available 2D array dosimeter can be used for the application of in vivo dose reconstruction. Method and Materials: An empirical‐based back‐projection dose reconstruction algorithm was developed for the purpose of in vivo dose reconstruction. The algorithm reconstructed a 2D dose distribution by raytracing the transit fluence to a desired depth in a phantom/patient. The algorithm was evaluated using homogeneous and heterogeneous phantoms. For the homogeneous phantom, 20 cm thick solid water was used to evaluate six conformal fields and five IMRT fields. A planar dose from Pinnacle3treatment planning system was used as the reference (3 % / 3 mm gamma index criteria). For the heterogeneous phantoms, there were three rectangular shaped solid water phantoms with air cavities that were varying in shapes and sizes. Two anthropomorphic head and neck and pelvis phantoms were also considered. A combination of radiochromic films and planar dose from Pinnacle3treatment planning system was used as the reference (5 % / 3 mm gamma index criteria). Results: For conformal fields, the algorithm showed passing rates of better than 99%. Similar passing rates were observed for the five IMRT fields. For the three rectangular shaped solid water phantoms, the dose distributions not in the air cavities had a passing rate ranging from 89.9% to 100%. The passing rates for the dose distribution in the air cavity ranged from 87.4% to 94.9%. For the head and neck and pelvis phantoms, the passing rates were 93.3% and 99.9%, respectively. Conclusions: A 2D array dosimeter can be used for high precision back‐projection dose reconstruction for in vivo dosimetry for homogeneous phantoms. For the heterogeneous phantoms, it has proven to have an acceptable agreement.
Covariance Mapping in the Analysis of Ignitable Liquids by Gas Chromatography/Mass Spectrometry

The covariance matrix computed from the retention time−ion abundance data matrix from gas chromatography/mass spectrometry analysis of ignitable liquids is shown to be a useful tool for automated identification of ignitable liquids in a database. The absolute value of the element-by-element difference between two normalized covariance matrices is shown to quantitatively differentiate between ignitable liquids composed of complex mixtures of hydrocarbons and is amenable to automated searching of ignitable liquid databases. The covariance mapping method is applied to a matrix-contaminated postburn sample, allowing the determination of a high degree of similarity between the ignitable liquid and a heavily evaporated gasoline.
Picosecond Stokes shift studies of solvent friction: Experimental measurements of time-dependent band shape and integrated intensity

Abstract The dynamic Stokes shift of the emission from a charge transfer excited state is examined in ethanol solutions over the temperature range from − 10°C to −60°C. Measurements of the time-dependent band shape and integrated intensity suggest that there is strong coupling between the electronic structure of the probe molecule and the time-dependent solvation. The time-dependent integrated intensity exhibits a biexponential decay in which the fast component is equivalent to solvation times determined from the Stokes shift correlation function, C(t). This data reflects the time-dependent contribution of the pure LE and TICT states to the excited electronic state as solvation occurs. In addition, over the temperature range studied, the time-dependent shape of the emission spectrum is found to depend solely on the motion along the solvent coordinate, suggesting that the initial decrease in integrated intensity is not the result of the presence of an inhomogeneous distribution of solvated molecules following photolysis.
On the generation and ownership of alpha in medical studies

Much is known about how to split alpha between or among several comparisons, or how to preserve the nominal alpha level with an exact analysis, but the issue of how alpha is generated, or where it comes from, has not received a commensurate degree of attention. It would seem that there is little point in working out methods to allocate or conserve alpha if it is unlimited in supply. Moreover, there seems to be a logical inconsistency in requiring that a given amount of alpha, generally 0.05, be split among the primary comparisons performed by a given set of researchers, yet allowing other researchers to analyze the same data with a new 0.05 to work with. We will address these inconsistencies, and ask more generally where alpha comes from, how it can be generated, and under what conditions it should be one-tailed or two-tailed.
Windowless Low Temperature Unit for Use in Evacuated Spectrophotometers

This article describes accessory apparatus to utilize the Beckman variable temperature unit without windows for obtaining low temperature spectra in the evacuated Perkin-Elmer FIS-3 far infrared spectrophotometer. The windowless feature of this low temperature unit allows spectra to be recorded without energy loss and interfering absorption that arise from windows in conventional low temperature units.
Using the FFT to determine digital straight line chain codes

Some ideal properties of digital straight lines, such as the chord property, are often missing in real applications. It is emphasized in this note that the most important characteristic of a digital straight line chain code is its periodicity. A method of using the FFT to detect the periodicity of an input chain code is proposed. It is used for the determination of the straightness of the input chain code. Initial experimental results are satisfactory.
The linear T dependence of the specific heat and the saturation of the susceptibility for T to 0 in dilute magnetic alloys

The magnetic specific heat CM and susceptibility chi are calculated for dilute magnetic alloys based on theoretical results previously obtained by Riess and Mavroyannia (Physica, vol.75, p.483, 1974). Those results indicated that a broad maximum in CM and chi was not associated with internal magnetic fields but rather magnetic 'fluctuations' about zero field. A computer simulation of a dilute alloy gives the distribution function, n(v), of those 'fluctuations' from which CM and chi are obtained. A nearest neighbour (NN) approximation for n(v) yields better results for CM and chi than the full computer-generated expression. In particular in the NN approximation, CM varies as T and chi is finite for T to 0. In both cases chi has a rounded maximum which is not associated with antiferromagnetism but is due to the 'fluctuations'.
Software for neural networks

Neural networks "compute" though not in the way that traditional computers do. It is necessary to accept their weaknesses to use their strengths. We discuss some of the assumptions and constraints that govern operation of neural nets, describe one particular non-linear network---the BSB model---in a little detail, and present two applications of neural network computations to illustrate some of the peculiarities inherent in this architecture. We show how a network can be trained to estimate answers to simple multiplication problems and how a network can be used to disambiguate lexical items by context. In both examples, the way information is represented in the pattern of system unit activities is at least as important as the details of the learning and retrieval algorithms used.
Determination of glycuronic acids by high-performance anion chromatography with pulsed amperometric detection

Acid hydrolysis (0.25M H2SO4) coupled with enzyme catalysis (pectolyase and β-D-glucuronidase) were employed to extract galacturonic and glucuronic acids from microbial polysaccharides, plant residues, animal wastes, sewage sludge and soil. The glycuronic acids were separated by high-performance anion chromatography (HPAC) on a strong anion-exchange column using 0.1M sodium hydroxide with 0.25M sodium acetate as the mobile phase and determined by pulsed amperometric detection (PAD). HPAC-PAD was found to be superior to high-performance liquid chromatography with ultra-violet (UV) detection in terms of resolution and sensitivity of glycuronic acids. HPAC-PAD was not subject to interferences present with low UV detection (210 nm) and was highly selective for glycuronic acids. Enzymatic hydrolysis after treatment with mild acid (0.25M H2SO4) released galacturonic acids from organge peel and pectin, while glucuronic acid was released from Acacia powder. Large amounts of glycuronic acids were also extracted from plant materials. Low levels of uronic acids were detected in poultry manure, sewage sludge and organic-amended soils.
Parametric formulation of the general integer linear programming problem

A parametric approach to the general integer programming problem is explored. If a solution to the general integer linear programming problem exists, it can be expressed as a convex combination of the extreme points of the convex polytope of the associated linear programming relaxation. The combination may or may not be unique for the convex polytope and will depend on the extreme points used in the determination. Therefore, a heuristic approach to solving the general integer programming problem can be taken by generating extreme points of the convex polytope and reformulating a mixed integer linear programming problem over these extreme points. This approach guarantees a feasible solution in a reasonable time frame. Further, such a technique can be used to provide quick lower bound information for an optimal search procedure.
Relaying for multiple sources in the absence of codebook information

This work investigates the optimality of compress-and-forward (CF) type relaying in wireless networks when the relay does not know the codebooks used by the sources. The relay is called oblivious for this reason. The relay-destination links are assumed to be out-of-band with finite capacity. We study two multi-source relay networks, namely the multiple access relay channel (MARC) and the interference relay channel (IFRC), both with an oblivious relay. For the MARC with an oblivious relay, we derive a new outerbound and show that the capacity region can be established using a generalized CF (GCF) scheme, where the destinations jointly decode the compression indices and the source messages. In particular, we observe that, for multi-source relay networks, GCF scheme achieves higher individual rates than the conventional CF scheme with sequential decoding of compression indices and source messages. For the IFRC with an oblivious relay, we focus on the case where the destinations know all the codebooks used by the sources. We establish a new strong interference condition, under which we derive a new outerbound and show that it is achievable using GCF scheme, thus establishing the capacity region of IFRC with an oblivious relay.
Biochemical and immunological comparisons between the human and boar proacrosin-acrosin proteinase systems

Abstract Biochemical and immunochemical methods have been used to examine the proacrosin-acrosin system of human and boar spermatozoa. Marked biochemical similarities including the relative molecular weights of proacrosin (approx. 55 000), alpha-acrosin (45 000–49 000) and beta-acrosin (34 000–38 000) were observed for both species. In addition, the time course of proacrosin autoconversion between 0 to 60 min revealed that the purified proacrosin from both species autoconverted to alpha-acrosin and then to beta-acrosin at approximately the same time intervals. Despite these apparent biochemical similarities, distinct immunological differences between the human and boar proacrosin-acrosin systems were observed. The human proacrosin antibody immunoreacted with purified human proacrosin and alpha-acrosin but not with beta-acrosin. The antibodies to boar proacrosin cross-reacted with the purified boar proacrosin, alpha-acrosin and beta-acrosin. The antibodies to human proacrosin also cross-reacted with boar proacrosin and to a weak extent with boar alpha-acrosin but not with the boar beta-acrosin. While antibodies to boar proacrosin did not react with any of the components of the human proacrosin system. Additionally, in the non-purified sperm extracts the human proacrosin antibody preparation reacted with several proteins larger than proacrosin and one with a molecular weight of approximately 34 000. In the non-purified boar sperm extracts, the antibodies to boar proacrosin only cross-reacted with the known components of the proacrosin-acrosin system suggesting a high degree of specificity. Thus, immunochemical evidence is presented that indicates there are specific structural differences which occur in the proacrosin-acrosin system of mammalian sperm.
Global Gene Expression of Listeria monocytogenes to Salt Stress

Outbreaks of listeriosis caused by the ingestion of Listeria-contaminated ready-to-eat foods have been reported worldwide. Many ready-to-eat foods, such as deli meat products, contain high amounts of salt, which can disrupt the maintenance of osmotic balance within bacterial cells. To understand how Listeria monocytogenes adapts to salt stress, we examined the growth and global gene expression profiles of L. monocytogenes strain F2365 under salt stress using oligonucleotide probe-based DNA array and quantitative real-time PCR (qRT-PCR) analyses. The growth of L. monocytogenes in brain heart infusion (BHI) medium with various concentrations of NaCl (2.5, 5, and 10%) was significantly inhibited (P < 0.01) when compared with growth in BHI with no NaCl supplementation. Microarray data indicated that growth in BHI medium with 1.2% NaCl upregulated 4 genes and down-regulated 24 genes in L. monocytogenes, which was confirmed by qRT-PCR. The transcript levels of genes involved in the uptake of glycine betaine/(L)-proline were increased, whereas genes associated with a putative phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), metabolic enzymes, and virulence factor were down-regulated. Specifically, the expression levels of PTS transport genes were shown to be dependent on NaCl concentration. To further examine whether the down-regulation of PTS genes is related to decreased cell growth, the transcript levels of genes encoding components of enzyme II, involved in the uptake of various sugars used as the primary carbon source in bacteria, were also measured using qRT-PCR. Our results suggest that the decreased transcript levels of PTS genes may be caused by salt stress or reduced cell growth through salt stress. Here, we report global transcriptional profiles of L. monocytogenes in response to salt stress, contributing to an improved understanding of osmotolerance in this bacterium.
Computed tomographic demonstration of obstruction of the inferior vena cava caused by hepatocellular carcinoma

A case of hepatocellular carcinoma obstructing the hepatic portion of the inferior vena cava by extrinsic compression demonstrated on computerized tomography is presented. To our knowledge, only one previous case has been reported which demonstrates actual invasion of the inferior vena cava by hepatic tumor. The signs of obstruction include: nonvisualization of the intrahepatic portion of the IVC, dilatation of the infrahepatic IVC with paravertebral venous collaterals and lack of changes in the diameter of the IVC after Valsalva maneuver.
Echocardiography-Guided Biventricular Pacemaker Optimization

Optimization of atrioventricular delay (AVD) and interventricular delay (VVD) in patients with a biventricular (Biv) pacemaker has been associated with improvement in cardiac output acutely, a reduction in heart failure symptoms, and improved exercise capacity. Several individual echocardiography (echo) Doppler parameters have been used for pacemaker optimization. In this review, pacemaker optimization based on echocardiographic evaluation of cardiac hemodynamics is presented. The goals of this paper are to discuss studies in echo-guided pacemaker optimization, provide a systemic guide to pacemaker interrogation and optimization in patients after Biv pacing who may have complex hemodynamic derangement, and finally, to discuss studies in optimization with exercise or atrial pacing. Case examples highlighting hemodynamic derangement in heart failure, tailoring of Biv pacemaker optimization to the underlying physiologic derangement, and its improvement with optimization are presented.
Maintaining continuity of care for nursing home residents: effect of states' Medicaid bed-hold policies and reimbursement rates.

Objective Recent public concern in response to states’ intended repeal of Medicaid bed-hold policies and report of their association with higher hospitalization rates prompts examination of these policies in ensuring continuity of care within the broader context of Medicaid policies.
Integrated analysis of policy options for protection of groundwater quality

This paper is directed at providing an integrated framework that a regional authority should use when assessing the potential impacts of any policy initiative directed at improving groundwater quality. In particular, a policy model is developed relying on three decision components (a farm-level production decisions model, a household decisions model and a regional policy decision model) where the objective is one of identifying the trade-offs that a regional authority will be confronted with as it strives to balance the preferences of farmers and households while endeavoring to maximize net economic welfare. The basic rule developed indicates that the regional authority must choose a policy whereby any increase (decrease) in regional income is just equal to the decrease (increase) in net benefits to households.
A viscous-inviscid interactive procedure for rotational flow in cascades of two-dimensional airfoils of arbitrary shape

A viscous-inviscid interactive calculation procedure is developed for application to flow in cascades of two-dimensional airfoils. This procedure has essentially three components. First, a numerical solution of the Euler equations which can accommodate an arbitrarily specified cascade geometry is carried out on a nonorthogonal curvileanear grid mesh that is fitted to the geometry of the cascade. A method of grid generation has been used which relies in part on a succession of conformal mappings. Second, a viscous solution for use in boundary layer and wake regions has been programmed. Finally, an interactive scheme which takes the form of a source-sink distribution along the blade surface and wake centerline is employed. Results have been obtained with this procedure for several cascade flow situations, and some comparisons with experiment are presented.
A Rare Case of Nonobstructive Membrane of the Left Atrial Appendage

The left atrial appendage (LAA) is a blind-ending, complex structure distinct from the body of the left atrium and is sometimes regarded as a minor extension of the atrium. However, it should routinely be evaluated as part of a transesophageal echocardiographic examination. In this study we describe the presence of a nonobstructive membrane traversing the cavity of the LAA, found incidentally on transesophageal echocardiography.
Abnormal gallbladder emptying in patients with gallstones.

In this study, gallbladder and gastric emptying were compared in 15 normal subjects and 15 patients with gallstones. A noninvasive technique which uses two gamma-emitting radiopharmaceutical agents to image the gallbladder and stomach simultaneously was employed. Technetium-99m-HIDA was used as a gamma-emitting marker for the gallbladder and indium-111-DTPA was mixed with a standard liquid meal in order to stimulate gallbladder emptying and to measure gastric emptying. In patients with gallstones, gallbladder emptying was diminished significantly compared to normal subjects. In contrast, emptying of the stomach was normal. The gallbladder emptying responses to octapeptide of cholecystokinin, administered either as bolus or infusion doses, were similar in normal subjects and patients with gallstones. These studies suggest that gallbladder emptying may be abnormal in patients with gallstones. The explanation for this abnormality and its relationship to the development of gallstones has not been determined.
CMR Imaging: Creating Contrast Without Cosmetics...

One of the strengths of cardiac magnetic resonance (CMR) is its versatility and ability to answer important pathophysiological questions as novel pulse sequences are developed. This issue of iJACC is an excellent example of this phenomenon. Three papers in this issue ([1–3][1]) propose techniques
Compression- and Shear-Induced Polymerization in Model Diacetylene-Containing Monolayers

Molecular dynamics simulations have been used to examine the response of monolayers composed of alkyne chains, which contain diacetylene moieties, to compression and shear. The simulations show that both compression and shear result in cross-linking, or polymerization, between chains. Irregular polymerization patterns appear among the carbon backbones. The vertical positioning of the diacetylene moieties within the alkyne chains (spacer length) and the sliding direction have an influence on the pattern of cross-linking and friction. In addition, chemical reactions between the chains of the monolayer and the amorphous carbon tip occur when diacetylene moieties are located at the ends of the chains closest to the tip. These adhesive interactions increase friction.
A Matrixed Approach to Long-Term Stability Testing of Pharmaceutical Products

A matrixed approach to long-term stability testing of pharmaceutical products is presented. The basic matrix design, suitable for testing three lots at one storage condition, may be extended to multiple product presentations or storage conditions. The design has full testing at the endpoints (0 and 36 months) and partial testing at the interim time points (3, 6, 9, 12, 18, and 24 months). The test points were selected with the assistance of a statistical search algorithm. The proposed matrix design provides a 37.5% reduction in analytical testing, while still permitting a reliable interim expiry estimate based on 12-month stability data. The expiration dating periods estimated using the matrixed approach are typically more conservative than estimates derived from a full-testing approach. A comparison of expiration dating period estimates for a metered-dose inhaler and capsule drug product using the matrixed and full-testing approaches is presented.
Comparison of the E-test with the NCCLS M38-P Method for Antifungal Susceptibility Testing of Common and Emerging Pathogenic Filamentous Fungi

The National Committee for Clinical Laboratory Standards (NCCLS) M38-P method describes standard parameters for testing the fungistatic antifungal activities (MICs) of established agents against filamentous fungi (molds). The present study evaluated the in vitro fungistatic activities of itraconazole and amphotericin B by the E-test and the NCCLS M38-P microdilution method against 186 common and emerging pathogenic molds (123 isolates of Aspergillus spp. [five species], 16 isolates of Fusarium spp. [two species], 4 Paecilomyces lilacinus isolates, 5 Rhizopus arrhizus isolates, 15 Scedosporium spp., 18 dematiaceous fungi, and 5 Trichoderma longibrachiatum isolates). The agreement between the methods for amphotericin B MICs ranged from 70% for Fusarium solani to ≥90% for most of the other species after the first reading; agreement was dependent on both the incubation time and the species being evaluated. Major discrepancies between the amphotericin B MICs determined by the E-test and the NCCLS M38-P method were demonstrated for three of the five species of Aspergillus tested and the two species of Fusarium tested. This discrepancy was more marked after 48 h of incubation; the geometric mean MICs determined by the E-test increased between 24 and 48 h from between 1.39 and 3.3 μg/ml to between 5.2 and >8 μg/ml for Aspergillus flavus, Aspergillus fumigatus, and Aspergillus nidulans. The agreement between the itraconazole MICs determined by the E-test and the NCCLS M38-P method ranged from 83.3% for A. nidulans to ≥90% for all the other species tested; the overall agreement was higher (92.7%) than that for amphotericin B (87.9%). The agreement was less dependent on the incubation time. Clinical trials need to be conducted to establish the role of the results of either the E-test or the NCCLS M38-P method in vitro for molds with the two agents as predictors of clinical outcome.
Democracy and Religious Politics Evidence from Belgium

This article questions a widely shared assumption that posits the incompatibility of religious politics and democracy. Using evidence from an analytically significant case, Belgium, it explores the political and institutional conditions under which religiously motivated aliberal political actors integrate successfully into democratic institutions. The interaction of three factors is shown to be crucial: a political shift affecting the religious actor negatively, the existence of competitive institutions, and a centralized religious structure. The main theoretical implication is that democratic consolidation can be the contingent outcome of self-interested political strategy rather than the result of the pursuit of normative principles. The article underlines the institutional and political context in which religious movements are embedded (as opposed to their political theologies) and the centrality of agency and strategic calculation. It advocates placing the study of religion and politics in a more broa...
Innocent Infants or Abusive Patriarchs? Spousal Homicides, the Punishment of Indians and the Law in Colonial Mexico, 1740s–1820s

This article examines numerous spousal homicides occurring all over New Spain (colonial Mexico) during the last seven decades of the colonial period. After killing their spouses, sometimes in an extremely brutal manner, a considerable number of the defendants managed to get away with little more than a slap on the wrist. I argue here that this was not due to the fact that written laws were dead letters. After examining general patterns of spousal homicides, I focus on the legal treatment and punishment afforded to indigenous criminals, several of who were drunk at the time of their crimes. Being an ‘Indian’ or committing a crime while drunk – both characteristics of many defendants in the records – were treated as a mitigating circumstance under law and led to the acquittal of several of the accused. Royal graces, an important legal mechanism, also played a significant role in easing the severity of the treatment of these and other domestic criminals. The judicial treatment of spousal murders thus did not reflect a considerable gap between law and practice at the time. Punishment derived from a complex combination of socio-cultural factors and longstanding legal prescriptions, doctrines and traditions.
In meso structure of the cobalamin transporter, BtuB, at 1.95 A resolution.

Crystals of the apo form of the vitamin B12 and colicin receptor, BtuB, that diffract to 1.95 A have been grown by the membrane-based in meso technique. The structure of the protein differs in several details from that of its counterpart grown by the more traditional, detergent-based (in surfo) method. Some of these differences include (i) the five N-terminal residues are resolved in meso, (ii) residues 57–62 in the hatch domain and residues 574–581 in loop 21–22 are disordered in meso and are ordered in surfo, (iii) residues 278–287 in loop 7–8 are resolved in meso, (iv) residues 324–331 in loop 9–10, 396–411 in loop 13–14, 442–458 in loop 15–16 and 526–541 in loop 19–20 have large differences in position between the two crystal forms, as have residues 86–96 in the hatch domain, and (v) the conformation of residues 6 and 7 in the Ton box (considered critical to signal transduction and substrate transport) are entirely different in the two structures. Importantly, the in meso orientation of residues 6 and 7 is similar to that of the vitamin B12-charged state. These data suggest that the “substrate-induced” 180° -rotation of residues 6 and 7 reported in the literature may not be a unique signalling event. The extent to which these findings agree with structural, dynamic and functional insights gleaned from site-directed spin labelling and electron paramagnetic resonance measurements is evaluated. Packing in in meso grown crystals is dense and layered, consistent with the current model for crystallogenesis of membrane proteins in lipidic mesophases. Layered packing has been used to locate the transmembrane hydrophobic surface of the protein. Generally, this is consistent with tryptophan, tyrosine, lipid and CαB-factor distributions in the protein, and with predictions based on transfer free energy calculations.
Narrative review: lack of evidence for recommended low- density lipoprotein treatment targets : A solvable problem

Recent national recommendations have proposed that physicians should titrate lipid therapy to achieve low-density lipoprotein (LDL) cholesterol levels less than 1.81 mmol/L (<70 mg/dL) for patients at very high cardiovascular risk and less than 2.59 mmol/L (<100 mg/dL) for patients at high cardiovascular risk. To examine the clinical evidence for these recommendations, the authors sought to review all controlled trials, cohort studies, and case-control studies that examined the independent relationship between LDL cholesterol and major cardiovascular outcomes in patients with LDL cholesterol levels less than 3.36 mmol/L (<130 mg/dL). For those with LDL cholesterol levels less than 3.36 mmol/L (<130 mg/dL), the authors found no clinical trial subgroup analyses or valid cohort or case-control analyses suggesting that the degree to which LDL cholesterol responds to a statin independently predicts the degree of cardiovascular risk reduction. Published studies had avoidable limitations, such as a reliance on ecological (aggregate) analyses, use of analyses that ignore statins' other proposed mechanisms of action, and failure to account for known confounders (especially healthy volunteer effects). Clear, compelling evidence supports near-universal empirical statin therapy in patients at high cardiovascular risk (regardless of their natural LDL cholesterol values), but current clinical evidence does not demonstrate that titrating lipid therapy to achieve proposed low LDL cholesterol levels is beneficial or safe.
Helicobacter pylori: Consensus and Controversy

Helicobacter pylori is uniquely adapted to colonize the human stomach. Infection leads to a range of subclinical and clinical outcomes that depend on properties of the infecting strain, the host, and the environment. Eradication therapy is indicated for infected persons who develop peptic ulcer disease or gastric lymphoma or who are beginning long-term treatment with nonsteroidal anti-inflammatory drugs. However, treatment may worsen gastroesophageal reflux disease and increase the risk of esophageal cancer. H. pylori infections can be diagnosed noninvasively and can be eradicated with approximately 85% success by a variety of multidrug, 7-14-day regimens. Unfortunately, antibiotic resistance is affecting treatment effectiveness in the United States and abroad. A more complete understanding of the variation in H. pylori pathogenesis should lead to clearer recommendations about treatment for infected persons who have neither peptic ulcer disease nor gastric lymphoma.
Student Performance in Online and Traditional Sections of an Undergraduate Management Course

Few previous studies comparing online and traditional courses have focused on undergraduate management courses. Our results complement previous analyses finding that, when we control for factors such as class, major, and GPA, students in online courses do as well in objective measures of performance, but not better than students in traditional courses. We also found that in the online sections, females performed at least as well as males. We discuss these results in relation to some changes in online education and the persistent perception by some that online education is somewhat problematic because students need more discipline in online courses.
Latent transition analysis: Inference and estimation

Parameters for latent transition analysis (LTA) are easily estimated by maximum likelihood (ML) or Bayesian method via Markov chain Monte Carlo (MCMC). However, unusual features in the likelihood can cause difficulties in ML and Bayesian inference and estimation, especially with small samples. In this study we explore several problems in drawing inference for LTA in the context of a simulation study and a substance use example. We argue that when conventional ML and Bayesian estimates behave erratically, problems often may be alleviated with a small amount of prior input for LTA with small samples. This paper proposes a dynamic data-dependent prior for LTA with small samples and compares the performance of the estimation methods with the proposed prior in drawing inference.
Testing the importance of auditory detections in avian point counts

Recent advances in the methods used to estimate detection probability during point counts suggest that the detection process is shaped by the types of cues available to observers. For example, models of the detection process based on distance-sampling or time-of-detection methods may yield different results for auditory versus visual cues because of differences in the factors that affect the transmission of these cues from a bird to an observer or differences in an observer's ability to localize cues. Previous studies suggest that auditory detections predominate in forested habitats, but it is not clear how often observers hear birds prior to detecting them visually. We hypothesized that auditory cues might be even more important than previously reported, so we conducted an experiment in a forested habitat in North Carolina that allowed us to better separate auditory and visual detections. Three teams of three observers each performed simultaneous 3-min unlimited-radius point counts at 30 points in a mixed-hardwood forest. One team member could see, but not hear birds, one could hear, but not see, and the third was nonhandicapped. Of the total number of birds detected, 2.9% were detected by deafened observers, 75.1% by blinded observers, and 78.2% by nonhandicapped observers. Detections by blinded and nonhandicapped observers were the same only 54% of the time. Our results suggest that the detection of birds in forest habitats is almost entirely by auditory cues. Because many factors affect the probability that observers will detect auditory cues, the accuracy and precision of avian point count estimates are likely lower than assumed by most field ornithologists.
Relationships between narrow band directional energy spectra and probability densities of deep and shallow water waves

Definitions of wave directional energy density spectra and joint probability distribution of wave amplitude, period and direction are given. Relationships between deep water directional spectra and shallow water spectra are recalled. Then the joint probability density of shallow water wave is established as function of the deep water probability density for narrow band spectra. Universal relationships between deep and shallow wave spectra, and deep and shallow water probability density are established through shoaling, refraction and friction coefficients. A method is proposed to establish equivalence between energy spectrum and probability density at any depth, based on the knowledge of this relationship in deep water. It is shown that the probability density of wave amplitude of a unidirectional sea for a given wave period is Rayleigh in shallow water as well as in deep water, but the marginal probability density of wave period (for a given wave amplitude) is no longer Gaussian. The case of broadband spectra with results of measurements is presented as the Appendix.