cssi/SciSciGPT-SciSciNet huggingface dataset:
Binding of Host Cell Surface Protein Disulfide Isomerase by Anaplasma phagocytophilum Asp14 Enables Pathogen Infection.

ABSTRACT Diverse intracellular pathogens rely on eukaryotic cell surface disulfide reductases to invade host cells. Pharmacologic inhibition of these enzymes is cytotoxic, making it impractical for treatment. Identifying and mechanistically dissecting microbial proteins that co-opt surface reductases could reveal novel targets for disrupting this common infection strategy. Anaplasma phagocytophilum invades neutrophils by an incompletely defined mechanism to cause the potentially fatal disease granulocytic anaplasmosis. The bacterium’s adhesin, Asp14, contributes to invasion by virtue of its C terminus engaging an unknown receptor. Yeast-two hybrid analysis identified protein disulfide isomerase (PDI) as an Asp14 binding partner. Coimmunoprecipitation confirmed the interaction and validated it to be Asp14 C terminus dependent. PDI knockdown and antibody-mediated inhibition of PDI reductase activity impaired A. phagocytophilum infection of but not binding to host cells. Infection during PDI inhibition was rescued when the bacterial but not host cell surface disulfide bonds were chemically reduced with tris(2-carboxyethyl)phosphine-HCl (TCEP). TCEP also restored bacterial infectivity in the presence of an Asp14 C terminus blocking antibody that otherwise inhibits infection. A. phagocytophilum failed to productively infect myeloid-specific-PDI conditional-knockout mice, marking the first demonstration of in vivo microbial dependency on PDI for infection. Mutational analyses identified the Asp14 C-terminal residues that are critical for binding PDI. Thus, Asp14 binds and brings PDI proximal to A. phagocytophilum surface disulfide bonds that it reduces, which enables cellular and in vivo infection. IMPORTANCEAnaplasma phagocytophilum infects neutrophils to cause granulocytic anaplasmosis, an emerging potentially fatal disease and the second-most common tick-borne illness in the United States. Treatment options are limited, and no vaccine exists. Due to the bacterium’s obligatory intracellular lifestyle, A. phagocytophilum survival and pathogenesis are predicated on its ability to enter host cells. Understanding its invasion mechanism will yield new targets for preventing bacterial entry and, hence, disease. We report a novel entry pathway in which the A. phagocytophilum outer membrane protein Asp14 binds host cell surface protein disulfide isomerase via specific C-terminal residues to promote reduction of bacterial surface disulfide bonds, which is critical for cellular invasion and productive infection in vivo. Targeting the Asp14 C terminus could be used to prevent/treat granulocytic anaplasmosis. Our findings have broad implications, as a thematically similar approach could be applied to block infection by other intracellular microbes that exploit cell surface reductases.
Updated and outdated reservations about research into stratospheric aerosol injection

In this paper, we seek to ground discussions of the governance of stratospheric aerosol injection research in recent literature about the field including an updated understanding of the technology’s deployment logistics and scale, pattern of effects, and research pathways. Relying upon this literature, we evaluate several common reservations regarding the governance of pre-deployment research and testing including covert deployment, technological lock-in, weaponization, slippery slope, and the blurry line between research and deployment. We conclude that these reservations are no longer supported by literature. However, we do not argue that there is no reason for concern. Instead, we enumerate alternative bases for caution about research into stratospheric aerosol injection which are supported by an up-to-date understanding of the literature. We conclude that in order to establish the correct degree and type of governance for stratospheric aerosol injection research, the research community must focus its attention on these well-grounded reservations. However, while these reservations are supported and warrant further attention, we conclude that none currently justifies restrictive governance of early-stage stratospheric aerosol injection research.
Integrating Metacognitive Regulation into the Online Classroom Using Student-Developed Learning Plans

Students and instructors have been faced with unexpected challenges that presented rapidly due to the COVID-19 pandemic The pandemic forced students into an unfamiliar learning ecosystem to which they had to quickly adapt in order to continue to be successful in their courses Literature supports the importance of metacognition and self-regulated learning in the success of students in an online environment More importantly, the concept of metacognitive regulation, which includes monitoring, planning, executing, and adapting learning strategies, is vital to student academic success These strategies have been shown to close the opportunity gap observed specifically in persons excluded because of their ethnicity or race (PEERs) in STEM Outlined here is the use of student-developed learning plans as a guided process to enhance students' metacognitive regulation of their learning These learning plans provide students a template to assist them in time management, practical study skills and planned study sessions, that are designed to increase their self-efficacy, motivation, and performance in online classes Moreover, the iterative nature of the learning plan encourages students to continue to use and expand this plan in other academic courses
Angle-of-Arrival of a Radio-Frequency Field from Sub-wavelength Rydberg Atom-based Phase Measurements

Rydberg atoms in a vapor cell are used to measure the angle-of-arrival (AoA) of an incident radio-frequency plane wave through sub-wavelength phase measurements using a heterodyne technique.
Cone photoreceptor dysfunction in retinitis pigmentosa revealed by optoretinography.

Retinitis pigmentosa (RP) is the most common group of inherited retinal degenerative diseases, whose most debilitating phase is cone photoreceptor death. Perimetric and electroretinographic methods are the gold standards for diagnosing and monitoring RP and assessing cone function. However, these methods lack the spatial resolution and sensitivity to assess disease progression at the level of individual photoreceptor cells, where the disease originates and whose degradation causes vision loss. High-resolution retinal imaging methods permit visualization of human cone cells in vivo but have only recently achieved sufficient sensitivity to observe their function as manifested in the cone optoretinogram. By imaging with phase-sensitive adaptive optics optical coherence tomography, we identify a biomarker in the cone optoretinogram that characterizes individual cone dysfunction by stimulating cone cells with flashes of light and measuring nanometer-scale changes in their outer segments. We find that cone optoretinographic responses decrease with increasing RP severity and that even in areas where cone density appears normal, cones can respond differently than those in controls. Unexpectedly, in the most severely diseased patches examined, we find isolated cones that respond normally. Short-wavelength-sensitive cones are found to be more vulnerable to RP than medium- and long-wavelength-sensitive cones. We find that decreases in cone response and cone outer-segment length arise earlier in RP than changes in cone density but that decreases in response and length are not necessarily correlated within single cones.
Introduzione Di che cosa tratta questo libro

Sei un giovane chirurgo strutturato alla prima notte di guardia in un movimentato trauma center, oppure sei un chirurgo di un piccolo ospedale periferico che deve affrontare da solo un caso di grave trauma, oppure ancora sei un ufficiale medico di un’unita chirurgica mobile: qualunque sia il tuo incarico, prima o poi ti troverai in sala operatoria con un paziente con emorragia massiva che ti sta morendo fra le mani.
Coarse-Grained Modeling of the HIV---1 Protease Binding Mechanisms: II. Folding Inhibition

Evolutionary and structurally conserved fragments 24---34 and 83---93 from each of the HIV---1 protease (HIV---1 PR) monomers constitute the critical components of the HIV---1 PR folding nucleus. It has been recently discovered that the peptide with the amino acid sequence NIIGRNLLTQI identical to the corresponding segment 83---93 of the HIV---1 PR monomer, can inhibit folding of HIV---1 PR. We have previously shown that this peptide can form stable complexes with the folded HIV---1 PR monomer by targeting the conserved segment 24---34 of the folding nucleus (folding inhibition) and by interacting with the antiparallel termini β ---sheet region (dimerization inhibition). In this follow-up study, we propose a generalized, coarse---grained model of the folding inhibition based simulations with an ensemble of both folded and partially unfolded HIV---1 PR conformational states. Using a dynamic equilibrium between low---energy complexes formed with the folded and partially unfolded HIV---1 PR monomers, the NIIGRNLLTQI peptide may effectively intervene with the HIV---1 PR folding and dimerization. The performed microscopic analysis reconciles the experimental and computational results and rationalizes the molecular basis of folding inhibition.
Antepartum pulmonary embolism.

Abstract Antepartal thromboembolic disease appears to be increasing during the prenatal period and decreasing in the puerperium. Antepartal pulmonary thromboembolism, although rare, may be commoner than expected and in our series of 20 cases half of them appear in the first trimester. Once a firm diagnosis is made, which is usually possible, the patient is treated with anticoagulants. Intravenous heparin is used for the first 7 to 10 days followed by sodium warfarin until term, at which time it is stopped and heparin is again started and maintained through delivery and the early puerperium. Maternal complications of anticoagulant therapy have not been a problem. One fetus died in utero and was macerated at delivery without evidence of hemorrhage. Others have described this phenomenon. Four patients had adjunctive operations—femoral thrombectomy, vena caval ligation, and pulmonary thrombectomy when anticoagulants failed to control the disease. There were 2 maternal deaths. One death followed complete anticoagulation therapy and pulmonary arterial thrombectomy, the other patient died before treatment could be instituted.
Developmental and tissue-specific expression of CaMV 35S promoter in cotton as revealed by GFP

The CaMV 35S promoter is the most commonly used promoter for driving transgene expression in plants. Though it is presumed to be a constitutive promoter, some reports suggest that it is not expressed in all cell types. In addition, the information available on its expression profile in all possible cell and tissue types and during early stages of development is incomplete. We present here a detailed expression profile of this promoter investigated using the green fluorescent protein (GFP) gene as a reporter system in cotton during embryo development, and in all the vegetative and floral cell and tissue types. GFP expression was not detected during the early stages of embryogenesis. The first perceptible GFP expression was observed in a small area at the junction of hypocotyl and cotyledons in embryos at around 13 days after anthesis. The GFP fluorescence progressively became stronger and expanded throughout the cotyledon and hypocotyl as embryo development advanced. After germination, varying levels of promoter activity were observed in all cell and tissue types in the hypocotyl, cotyledon, stem, leaf, petiole, and root. The promoter was also expressed in all floral parts. Although cotton pollen exhibited a low level of greenish autofluorescence, it was possible to discern GFP-dependent fluorescence in some of the pollen from all the T0 plants examined. Developing cotton fibers also exhibited GFP fluorescence suggesting that the 35S promoter was active in these specialized epidermal cells. Thus, we show that the expression of the 35S promoter was developmentally regulated during embryogenesis and that beyond a certain stage during embryogenesis, the promoter was expressed in most cell and tissue types in cotton albeit at different levels.
How Exemplary Computer-Using Teachers Differ From Other Teachers: Implications for Realizing the Potential of Computers in Schools

AbstractUsing national survey data from 3rd- through 12th-grade teachers of academic subjects, 45 teachers out of 516 were identified as being exemplary computer-using teachers. Four factors in the teaching environment made exemplary computer users more likely to be present: collegiality among users, school support for using computers for consequential activities, resources allocated to staff development and computer coordination, and smaller class sizes. Also found were certain factors in teachers’ backgrounds that were related to the probability of their being designated as exemplary users (e.g., if they were liberal arts majors rather than education majors) and showed that only among exemplary users were major changes in content coverage accomplished. The presence of exemplary users in a school did not result in fewer problems for administrators—just different ones. Contrary to expectations, exemplary teachers were not overrepresented in high socioeconomic communities, nor did they disproportionately t...
Iteratively training classifiers for circulating tumor cell detection

The number of Circulating Tumor Cells (CTCs) in blood provides an indication of disease progression and tumor response to chemotherapeutic agents. Hence, routine detection and enumeration of CTCs in clinical blood samples have significant applications in early cancer diagnosis and treatment monitoring. In this paper, we investigate two classifiers for image-based CTC detection: (1) Support Vector Machine (SVM) with hard-coded Histograms of Oriented Gradients (HoG) features; and (2) Convolutional Neural Network (CNN) with automatically learned features. For both classifiers, we present an effective and efficient training algorithm, by which the most representative negative samples are iteratively collected to accurately define the classification boundary between positive and negative samples. The two iteratively trained classifiers are validated on a challenging dataset with high performance.
Explorations of voltage-dependent conformational changes using cysteine scanning.

Publisher Summary Sodium, calcium, and potassium channels belong to a superfamily of membrane proteins that are exquisitely sensitive to changes of membrane potential. Depolarization causes a movement of positive charge outward across the membrane electric field, and tends to open and subsequently inactivate these ion channels. Both the charge movement and the consequent effects on the gates of the channel involve conformational rearrangements of the protein. The movement of charge has been studied using gating current measurements and the effect of voltage on the opening and closing of channels has been examined extensively since the development of the voltage-clamp technique in the 1950s. However, the effect of voltage on the secondary or tertiary structure of these ion channel proteins was largely unknown until very recently, when conformational changes of proteins were explored using the method of cysteine scanning mutagenesis. This technique has the potential to reveal changes in the surface accessibility of specific residues mutated to cysteine and then reacted with hydrophilic cysteine reagents. If the accessibility of a specific residue is affected by membrane potential and the reaction of the introduced cysteine with a reagent produces a measurable biophysical effect, then the rate of cysteine modification can be used to determine features of the voltage-dependent exposure of this residue, including both the steady-state voltage dependence and the kinetics of the underlying conformational changes. It may also be possible to determine whether the residue of interest lies in the membrane electric field and the local electrostatic potential in the vicinity of the thiol group.
Influence of prolonged fasting in the dog on glucose turnover and blood metabolites.

Glucose turnover and blood metabolites were measured in eight adult female beagles in the fed state, at 1 day of fasting, and at 7, 14, and 21 days of fasting. Glucose utilization decreased significantly from 1 to 7 days of fasting, but remained constant from 7 to 21 days, while blood ketones and plasma free fatty acids rose significantly during the same period. Plasma alanine, serine, and glycine fell with fasting, with the greatest decrease in alanine levels occurring between 7 to 14 days. Plasma branched chain amino acids rose significantly with fasting. It was con cluded that the shifts in plasma metabolites and decreased glucose utiliza tion could be indicative of decreased energy demands of the fasting dogs and/or a shift in substrate utilization with progressive fasting. J. Nutr. 107: 1053-1061,1977.
Vector quantizer design for memoryless noisy channels

To handle the effect of transmission errors on the performance of vector quantization (VQ) in source coding, a channel index assignment function is proposed that can be incorporated into a source/channel model of VQ. Using this model, conditions for the optimality of a vector quantizer for a given distortion measure are obtained which generalize the familiar centroid and nearest neighbor conditions. The optimal codevectors are linear combinations of those for the noiseless case, weighted by the a posteriori channel transition probabilities. The optimal encoder selects the codevector that minimizes a weighted sum of the distortion between the input and each codevector, where the weights are channel transition probabilities. A derivation of the conditions for a memoryless channel is given, and an iterative design algorithm is described where at each step the average distortion monotonically decreases. Each iteration consists of three steps which separately modify the encoder, decoder, and the channel index assignment. >
Contact angle of unset elastomeric impression materials

Abstract Statement of problem Some elastomeric impression materials are hydrophobic, and it is often necessary to take definitive impressions of teeth coated with some saliva. New hydrophilic materials have been developed. Purpose The purpose of this in vitro study was to compare contact angles of water and saliva on 7 unset elastomeric impression materials at 5 time points from the start of mixing. Material and methods Two traditional polyvinyl siloxane (PVS) (Aquasil, Take 1), 2 modified PVS (Imprint 4, Panasil), a polyether (Impregum), and 2 hybrid (Identium, EXA'lence) materials were compared. Each material was flattened to 2 mm and a 5 μL drop of distilled water or saliva was dropped on the surface at 25 seconds (t 0 ) after the start of mix. Contact angle measurements were made with a digital microscope at initial contact (t 0 ), t 1 =2 seconds, t 2 =5 seconds, t 3 =50% working time, and t 4 =95% working time. Data were analyzed with a generalized linear mixed model analysis, and individual 1-way ANOVA and Tukey HSD post hoc tests (α=.05). Results For water, materials grouped into 3 categories at all time-points: the modified PVS and one hybrid material (Identium) produced the lowest contact angles, the polyether material was intermediate, and the traditional PVS materials and the other hybrid (EXA'lence) produced the highest contact angles. For saliva, Identium, Impregum, and Imprint 4 were in the group with the lowest contact angle at most time points. Conclusion Modified PVS materials and one of the hybrid materials are more hydrophilic than traditional PVS materials when measured with water. Saliva behaves differently than water in contact angle measurement on unset impression material and produces a lower contact angle on polyether based materials.
Current treatment for lobular carcinoma in situ

Background: We thought that observation for patients with lobular carcinoma in situ (LCIS) had been generally accepted by the mid-1980s. A questionnaire mailed to oncologic surgeons in 1988 revealed that 33% of the respondents still advised unilateral mastectomy, although a slim majority (54%) advised observation. New studies have been published in the intervening 8 years, and we decided it would be worth recirculating the 1988 questionnaire. Methods: The identical questionnaire was mailed to members of the same oncologic societies (Society of Surgical Oncology [SSO] and Society for the Study of Breast Disease), but changes in membership necessitated new mailing lists. Results: Observation has yet to be universally accepted by the oncologic community, but at this time 85% of the respondents suggest it as the preferred option for their patients. Conclusions: Recent studies have questioned some of the tenets laid down by Haagensen in 1978, but it appears clear that his formulation of LCIS as a marker of increased risk continues to gain ground over the original concept of inevitable progression to invasive disease.
Shear of rubber tube springs

Abstract Rubber tube springs consist basically of cylindrical rubber tubes bonded on their inner and outer curved surfaces to rigid cylindrical tubes. They are widely used as flexible linkages, for example in vehicle suspensions. Rotation of one rigid tube with respect to the other about their common axis subjects the rubber tube to azimuthal shear. Displacement of one rigid tube with respect to the other along their common axis puts the rubber tube into axial shear. Using FEA, we have calculated the stresses set up in both cases, for a long rubber tube of a non-linearly elastic (neo-Hookean) material. The results are compared for the two modes of deformation, and with analytical predictions where available. For a long tube the shear stresses are substantially independent of the end conditions, but the normal stresses are strongly affected, as found previously for sheared rectangular blocks [A.N. Gent, J.B. Suh, S.G. Kelly III, Mechanics of rubber shear springs, Int. J. Nonlinear Mech. 42 (2007) 241–249]. If the end surfaces are stress-free, unexpectedly large normal stresses are generated, even in azimuthal shear. These high tensile stresses are attributed to restraints at the inner and outer cylindrical boundaries that compensate for the absence of stresses on the end surfaces that would be needed to maintain a simple shear deformation. Thus, the boundary conditions affect the stresses everywhere (in contrast to an “end effect” that would diminish away from the ends). Small departures from complete incompressibility are found to lower the internal stresses markedly, and even cause the sign of the stresses to be reversed.
Time course and action spectrum of vibrotactile adaptation.

In a series of experiments designed to explore the processes underlying adaptation of the sense of flutter-vibration, vibrotactile threshold was measured on the pad of the index finger, using Bekesy tracking. Unadapted thresholds were first measured, for a number of frequencies (4-90 Hz) and contactor sizes (1-8 mm diameter). As expected, these measurements indicated the presence of (1) a Pacinian system possessing spatial summation and increasing in sensitivity, as frequency was raised, at the rate of 12 dB/octave; and (2) a non-Pacinian system showing little spatial summation, and with a frequency characteristic matching that of the NP I mechanism of Bolanowski et al. (1988). These baseline data of Experiment 1 guided the selection of stimulus parameters for subsequent experiments, in which threshold for a test stimulus was measured before, during, and after periods of vibrotactile adaptation. In Experiment 2, test stimuli of 10 Hz and 50 Hz were combined factorially with 30-dB SL adapting stimuli of the same two frequencies. When the test stimulus was 10 Hz, the two adapting frequencies were equally effective in raising threshold; however, when the 50-Hz test stimulus was used, the 50-Hz adapting stimulus raised threshold by a greater amount than did the 10-Hz adapter. These results confirm on the finger the independence of adaptation in Pacinian and non-Pacinian channels, a result previously established on the thenar by other workers. For all four frequency combinations, threshold rose exponentially with a time constant of 1.5-2 min. In Experiment 3, an action spectrum was determined, showing the adapting amplitude needed at each of a series of frequencies to raise the threshold of a 10-Hz stimulus by 10 dB; this spectrum was essentially flat from 30 to 90 Hz. The results, taken in conjunction with what is known about rapidly adapting cutaneous mechanoreceptors, imply that the effectiveness of an adapting stimulus is not determined solely by the amount of activity it generates in first-order afferents.
The Family in the Waiting Room

A web of filaments binds these eyes, hands, tongues, and spirits flashing like silver sunfish in the flood of words and looks, a net too thin to be felt, too tough and tight to be torn, error-knotted, stained with blood, and soft as the fog of love.
On-chip millionfold sample stacking using transient isotachophoresis.

We present a simple and robust isotachophoresis (ITP) method that can be integrated with microchip-based capillary electrophoresis (CE) devices to achieve millionfold sample stacking. We performed an experimental parametric study to show the effects of initial sample ion concentration, leading ion concentration, and trailing ion concentration on ITP stacking. We also discuss the usefulness and limitations of a simple one-dimensional nondispersive model and a scaling analysis for dispersion rate. We found that a single-column ITP configuration together with electroosmotic flow suppression and high leading ion concentration provide high-performance ITP and can be integrated readily with CE separation. We demonstrated detection of trace of 100 fM Alexa Fluor 488 (signal-to-noise ratio of 11) with a concentration increase of a factor of 2 × 106. Application of our ITP/CE protocol to the stacking and separation of negatively charged fluorescent tracers (Alexa Fluor 488 and bodipy) resulted in a concentration i...
Evidence for the noneikonal effects in the tensor and vector analyzing powers in p-d elastic scattering at 800 MeV☆

Abstract Deuteron tensor and vector analyzing powers have been measured for the first time in p- d elastic scattering at 800 MeV proton laboratory energy for a - t range between 0.032 and 1.038 (GeV/ c ) 2 . The data provide a very sensitive test of the multiple scattering theory at intermediate energies. The inclusion of the noneikonal correction in the Glauber diffraction theory is essential in the description of the data, especially for -t ⪆0.2 (GeV/ c 2 ), where discrepancies of up to 150% are observed with the theory based on the eikonal approximation.
A Note on the Zeuthen-Harsanyi Theory of Bargaining:

This article shows that the conclusions of the Zeuthen-Harsanyi theory of bargaining, which is widely regarded as an alternative justification for Nash's solution of the bargaining problem, can be extremely sensitive to small changes in the assumption that both bargainers have identical perceptions of the costs of disagreement. Whether this is the case depends on whether bargainers' priors about those costs are optimistic, in a sense made precise in this article. An axiomatic framework for modeling bargaining outcomes when bargainers perceive the costs of disagreement differently is proposed, and it is shown that a class of solutions that generalize Nash's satisfy the natural generalizations of Nash's axioms.
Imaging techniques for cable network structures

Imaging techniques are presented for developing interactive computer display of cable network structures on a microcomputer such as the IBM PS/2®. These structures create surfaces formed by an orthogonal mesh of cables and are primarily loaded normal to the surface. A three-dimensional perspective representation of network structures is developed for fast drawing of cable structures on microcomputers.
On Learning a Foreign Language

Author's Summary— A critical examination of the problems now facing American teachers and administrators as a result of the Army's Specialized Training Program, such as: methods of instruction, intensive courses, the “scientific-conversational” approach, the use of informants, etc.
Metabolism of a pharmacologically active pyrrolidine derivative (prolintane) by lactam formation

Prolintan, N-1-(α-Benzylbutyl)-Pyrrolidin, wurde in Kaninchen durch ein Mikrosomensystem der Leber in das entsprechende Laktam, N-1-(α-Benzylbutyl)-Pyrrolidin-2-on, umgebaut. Das gleiche Stoffwechselprodukt fand sich auch im Gewebe von Ratten, denen das Medikament gegeben wurde; allenfalls Spuren davon wurden im Urin der Ratten ausgeschieden.
Sagnac interferometer for gravitational-wave detection.

We have investigated a zero-area Sagnac interferometer as a broad band gravitational-wave detector. Frequency response measurements of a laboratory-scale interferometer are in excellent agreement with theory. The measured contrast ratio, 0.996, is insensitive to induced birefringence, laser-frequency variation, arm imbalance, and dc mirror displacement. A near shot-noise-limited phase sensitivity of $3\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}9}\mathrm{rad}/\sqrt{\mathrm{Hz}}$ was measured at the interferometer's maximum sensitivity frequency, 90.9 MHz.
Double loop figure-of-8 reentry as the mechanism of multiple atrioventricular node reentry tachycardias☆

Seven patients with multiple atrioventricular node reentry tachycardia were analyzed to unravel the mechanism of these tachycardias. Six of the seven patients showed anterograde dual atrioventricular node pathways and one showed anterograde conduction through the fast pathway. Three types of retrograde pathways were noted among these seven patients: (1) the fast pathway with the earliest atrial activation at the His bundle area; (2) the intermediate pathway with the earliest atrial activation at the ostium of the coronary sinus; and (3) the slow pathway with the earliest atrial activation at the ostium of the coronary sinus. All seven patients used the intermediate pathway for retrograde conduction. However, one patient showed evidence of retrograde slow pathway conduction with demonstrable retrograde dual pathways, and another showed evidence of retrograde fast pathway conduction with a shift of atrial activation sequence when conduction switched to the intermediate pathway. Four different types of reentry circuits using either the fast or the slow pathway as the anterograde limb and one of the three retrograde pathways as the retrograde limb were demonstrated in these seven patients, resulting in two types of tachycardias in four patients and three types of tachycardias in three patients. A change in tachycardia type could be induced with atrial or ventricular stimulation. A radiofrequency current delivered to the inferior aspect of Koch's triangle along the tricuspid anulus in five patients resulted in selective ablation or modification of the intermediate pathway or the slow pathway, with preservation of anterograde atrioventricular conduction and abolition of tachycardias. The findings suggest that a double loop figure-of-8 reentry circuit including a fast pathway, a slow pathway, and an intermediate pathway is responsible for multiple atrioventricular node reentry tachycardias.
The other side of trust in health care: prescribing drugs with the potential for abuse.

Defining a nonpaternalistic yet achievable form of trust in medicine in an era of simultaneous patient empowerment and institutional control has been and remains an important task of bioethics. The ‘crisis of trust’ in medicine has been viewed mainly as the problem of getting patients to trust their health care providers, especially physicians. However, since paradigmatic cases of trust are mutual, bioethicists must pay more attention to physician trust in patients. A physician’s view of the reasonableness of trust in a particular patient is affected not just by his or her relationship with that patient, but also by what is going on institutionally, professionally, legally, and politically with regard to a given treatment or intervention. Since general moral principles are insufficient in determining the moral value and reasonableness of trust in particular instances, I discuss in detail the role of trust and distrust in the specific case of treating patients with medications implicated in drug abuse. I conclude that it is important to become aware, first, of the clinical significance of physician trust and distrust in patients, and second, of the many factors which inform both of these moral attitudes. These two claims together suggest that a central, but overlooked, virtue of medical practice is reflective, context-responsive trust in patients.
Controlled actuation of Nafion-based ionic polymer-metal composites (IPMCs)with ethylene glycol as solvent

Ionic polymer-metal composites (IPMCs) consist of a perfluorinated ionomer membrane (usually Nafion or Flemion). The ionomer is plated on both faces with a noble metal such as gold or platinum. It is neutralized with a certain amount of counterions that balance the electrical charge of anions covalently fixed to the backbone membrane. IPMCs are electroactive materials that can be used as actuators and sensors. Their electrical-chemical-mechanical response is highly dependent on the cations used, the nature and the amount of solvent uptake, the morphology of the electrodes, and other factors. When a cantilever strip of solvated Nafion-based IPMC sample is subjected to a suddenly applied and sustained (DC) electric potential of several volts (1-3 V) across its faces, it bends towards the anode. For Nafion-based IPMCs with alkali metals, actuation towards the anode is followed by a slow back relaxation towards the cathode. If the electric potential is removed and the two electrodes are shorted during this back relaxation, the sample displays a fast bending deformation towards the cathode and then slowly relaxes back towards the anode, attaining a new equilibrium position generally distinct from its initial state. One way to change various phases of IPMC actuation is achieved by changing input potential. The electric potential inputs may be used to control the actuation of IPMCs. We present the results of a series of tests on Nafion-based IPMCs with ethylene glycol as solvent, actuated under electric potential inputs other than DC electric potential. We present experimental results for increasing ramp and sinusoidal electric potential waveforms.
Cysteine proteases of parasites: A remarkable diversity of function

Papain family cysteine proteases function primarily intracellularly in higher eukaryotes, but are often extracellular proteases in protozoan helminths. The utility of this class of enzymes is reflected in the diversity of functions they perform in both parasite life cycles and the pathogenesis of parasitic diseases. Examples include secretion of proteases into the gut of parasitic worms for hemoglobin degradation, release from the surface of nematodes to degrade cuticular proteins during molting, and facilitating excystment of protozoa.
Earning stripes: myosin binding protein-C interactions with actin

Myosin binding protein-C (MyBP-C) was first discovered as an impurity during the purification of myosin from skeletal muscle. However, soon after its discovery, MyBP-C was also shown to bind actin. While the unique functional implications for a protein that could cross-link thick and thin filaments together were immediately recognized, most early research nonetheless focused on interactions of MyBP-C with the thick filament. This was in part because interactions of MyBP-C with the thick filament could adequately explain most (but not all) effects of MyBP-C on actomyosin interactions and in part because the specificity of actin binding was uncertain. However, numerous recent studies have now established that MyBP-C can indeed bind to actin through multiple binding sites, some of which are highly specific. Many of these interactions involve critical regulatory domains of MyBP-C that are also reported to interact with myosin. Here we review current evidence supporting MyBP-C interactions with actin and discuss these findings in terms of their ability to account for the functional effects of MyBP-C. We conclude that the influence of MyBP-C on muscle contraction can be explained equally well by interactions with actin as by interactions with myosin. However, because data showing that MyBP-C binds to either myosin or actin has come almost exclusively from in vitro biochemical studies, the challenge for future studies is to define which binding partner(s) MyBP-C interacts with in vivo.
Warren Felt Evans and mental healing: romantic idealism and practical mysticism in nineteenth-century America.

Warren Felt Evans was the first American mental healer to publish his ideas extensively. Phineas Parkhurst Quimby (1802–1866), the father of mental healing in America, bequeathed only scattered manuscripts to his followers. Evans, however, wrote six books that decisively influenced the growth of New Thought, a loosely organized religious movement concerned with health and spiritual integration. This essay contends that Evans' thought and therapy united idealistic philosophy and practical mysticism, thus extending one species of American romanticism, rooted in the Transcendentalist movement, into the latter half of the nineteenth century.
A Unique Case of Intraventricular Hemorrhage Associated With Posterior Reversible Encephalopathy Syndrome in an Adolescent

Intraventricular hemorrhage is a rare finding in patients with the posterior reversible encephalopathy syndrome and generally carries a poor prognosis. We report a unique case of an 18-year-old girl with glomerulonephritis who developed posterior reversible encephalopathy syndrome without hypertension but with a primary intraventricular hemorrhage and subarachnoid blood without demonstrable parenchymal blood. The normotensive presentation of posterior reversible encephalopathy syndrome and intraventricular hemorrhage in association with systemic vasculitis is rare. Our patient had a good initial outcome and was discharged with resolution of her symptoms and signs of raised intracranial pressure.
Targeted gene therapy to antigen-presenting cells in the central nervous system using hematopoietic stem cells.

Abstract Background: Hematopoietic stem cells (HSC) have been previously used as vectors for gene therapy of systemic disease. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. In the present study, we examined the feasibility of using HSC transduced with self-inactivating (SIN) lentiviral vectors for the delivery of gene therapy to the central nervous system (CNS). Material and methods: We constructed two SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1α or the human HLA-DRα gene, which is selectively expressed in antigen-presenting cells. Results: We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting NOD/SCID mice. Only the DR.GFP vector mediated transgene express...
T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice.

C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to study immunologic responsiveness to the human MUC1 tumor-associated antigen. In the present studies, MUC1.Tg mice were immunized with purified human MUC1 antigen and irradiated MUC1-positive (MC38/MUC1) tumor cells. Immunization with MUC1 antigen was associated with induction of an anti-MUC1 antibody response and no detectable cytotoxic T cell reactivity. Similar findings were obtained after immunization with irradiated MC38/MUCl tumor cells. The results also demonstrate that immunization of MUC1.Tg mice with MUCl is associated with decreased levels of CD8+ T cells. In addition, expression of αβ T cell receptors and CD28 were down-regulated on CD8+ T cells as a consequence of MUC1 immunization. These findings support a role for T cell suppression in tolerance to MUC1 antigen in MUC1.Tg mice.
Changes in oil‐type sunflowerseed stored at 20 C at three moisture levels

Oil-type hybrid sunflowerseed held at 63%, 83% and 93% relative humidities (RH) at 20 C attained equilibrium moisture contents (mc) of 6.7 ± 0.1%, 9.8 ± 0.1% and 13.4 ± 0.3%, respectively, and were stored under these conditions for up to 60 weeks (wk). Germinability was inversely related to both storage duration and RH. Initially, the seed contained only field fungi (mainlyAlternaria spp. andPhoma macdonaldii) and 0.5% free fatty acids (FFA). At 6.7% mc, the amount ofAlternaria spp. andP. macdonaldii isolated declined slowly with time, storage fungi did not invade the seed, and FFA in extracted oil did not change significantly during 60 wk storage. No significant correlation was found between FFA, germination, mold count (cfu/g) or fungi recovered. At 9.8% mc, field fungi declined more rapidly than at 6.7% mc, storage fungi (mainlyEurotium rubrum andE. repens) were isolated from the seed after 4 wk, and FFA increased to 2.5% after 40 wk. FFA content was negatively correlated with germination (r=−0.91) and withAlternaria alternata (r=−0.90) but was positively correlated withE. rubrum (r=0.78). At 13.4% mc, field fungi vanished and storage fungi invaded the seed more rapidly than at 9.8% mc, and FFA increased to 6.3% after 24 wk storage. FFA content was positively correlated with storage fungi such asAspergillus versicolor (r=0.74) and negatively correlated with germination (r=−0.88) andA. alternata (r=−0.82). After 14 wk storage the fungus recovered most frequently wasA. versicolor, followed byEurotium rubrum, E. repens, A. alternata, E. amstelodami, Penicillium spp. andMalbranchea sulphurea.
Preparation of Highly Impermeable Hyperbranched Polymer Thin-Film Coatings Using Dendrimers First as Building Blocks and Then as in Situ Thermosetting Agents

This report describes the synthesis, characterization, and passivation properties of durable, polyfunctional, and highly cross-linked hyperbranched dendrimer/polyanhydride composite thin films. Such films are prepared from either amine- or hydroxyl-terminated poly(amidoamine) (PAMAM) dendrimers or amine-terminated poly(iminopropane-1,3-diyl) dendrimers (64-Cascade), and the copolymer poly(maleic anhydride)-c-poly(methyl vinyl ether), Gantrez. The dendrimers serve two roles in these composite films. First, they serve as building blocks, which permeate into and covalently cross-link a chemisorbed Gantrez copolymer. Then, in a separate thermal processing step, the dendrimers form highly impermeable monolithic films. In the case of amine-terminated dendrimers, the amic acid groups that attach the dendrimers to the original Gantrez network polymer form imides. Additionally, internal β-amino groups within both the amine- and hydroxyl-terminated PAMAM dendrimers undergo retro-Michael reactions. Subsequently, a c...
Computer simulations of self-organized wind ripple patterns

Abstract A variety of surficial patterns including beach cusps, sand dunes, wind ripples, stone stripes and sorted circles have been reproduced successfully with computer simulations in which the patterns develop via self-organization and both transporting agents and transported material are discretized. As an example, three-dimensional, grain-level computer simulations of wind ripple formation are described. The results of these simulations demonstrate that a model that includes only incremental transport of surface grains by impacts from wind-propelled hopping (saltating) grains is sufficient to produce self-organized wind ripples whose size, cross-sectional shape, plan-view geometry and time evolution from an original flat surface fall within observed ranges for natural ripples. Simulated wind ripples are initiated from a flat sand bed because of an instability deriving from a dependence of transport rate on slope. A characteristic ripple spacing that is proportional to the grain diameter and increases slowly with time develops as a result of interactions and mergers between ripples. Imperfections to the ripple pattern play a significant role in the determination and evolution of the spacing of simulated ripples.
Solution to level 3 dismantling of gas-cooled reactors : the graphite incineration

Abstract This paper presents an approach developed to solve the specific decommissioning problems of the G2 and G3 gas-cooled reactors at Marcoule, and the strategy applied with emphasis on incinerating the graphite core components, using a fluidized-bed incinerator developed jointly between the French Atomic Energy Commission (CEA), Electricite de France and FRAMATOME. The incineration option was selected over subsurface storage for technical and economic reasons. Environmental studies have shown that gaseous incineration releases are environmentally acceptable. By using a pilot plant of a fluidized-bed incinerator (30–50 kg h−1), it has been demonstrated that it is possible to incinerate moderator blocks or other graphite components of gas-cooled power reactors, and to reduce significantly the residual amount of waste to be stored after incineration. More than 20 tons of nuclear-grade graphite was incinerated in a fluidized-bed incinerator pilot plant located at the FRAMATOME research centre. The volume of secondary waste after incineration is about 1%–2% of the original mass, and the combustion efficiency is very high at more than 99.8%.
Diffusion MRI studies in vascular cognitive impairment and dementia

Since its introduction more than two decades ago, Magnetic Resonance Imaging (MRI) has not only allowed for visualization of the macrostructure of the CNS, but also has been able to study dynamic processes which constitute the substrate of currently available MRI variants. While conventional Diffusion Weighted Imaging (DWI) permits a robust visualization of lesions just a few minutes after the onset of cerebral ischemia, Diffusion Tensor Imaging (DTI) measures the magnitude and direction of diffusion, leading to the characterization of cerebral white matter (WM) microstructural integrity. In this paper, the potential role of MRI techniques, particularly DTI, for the study of the relationship between changes in the microstructural integrity of WM and cognitive impairment in the context of cerebrovascular disease are discussed. Significant correlations between scores of behavioral measures of cognitive function and regional anisotropy values are an example of the potential efficacy of DTI for in vivo studies of brain connectivity in vascular neurodegenerative conditions.
Adsorption‐Mediated Electrochemical Sensing of Halides

A new strategy for detecting halides is presented that employs gold electrodes plated to expose a monolayer of silver atoms. Cl- , Br- , and I- ions each adsorb onto this surface and stochastically produce electrochemical changes (see picture; upd=underpotentially deposited) in the stripping characteristic of the silver layer that reflect the identity and surface coverage of these halides. The latter provides measurements that relate to the solution concentrations of the halides.
Deficit finance and monetary dynamics in Brazil and Mexico

Abstract The paper develops a model of seigniorage in an open economy, linking inflation, the government budget and the external balance. It introduces financial markets and interest rates in the traditional Cagan style model of inflationary dynamics and it evaluates the experiences of Brazil and Mexico. The model relates inflation in the 1980s to interest payments on the external public debt. The paper also argues that inflationary finance has been combined with very fast growth of domestic debt, setting the stage in Brazil for unsustainable domestic debt growth in the Sargent-Wallace style. The Collor Plan stopped this process, temporarily.