cssi/SciSciGPT-SciSciNet huggingface dataset:
Previously infected vaccinees broadly neutralize SARS-CoV-2 variants

We compared the serum neutralizing antibody titers before and after two doses of the BNT162b2 COVID-19 vaccine in ten individuals who recovered from SARS-CoV-2 infection prior to vaccination to 20 individuals with no history of infection, against clinical isolates of B.1.1.7, B.1.351, P.1, and the original SARS-CoV-2 virus. Vaccination boosted pre-existing levels of anti-SARS-CoV-2 spike antibodies 10-fold in previously infected individuals, but not to levels significantly higher than those of uninfected vaccinees. However, neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees against every variant tested: 5.2-fold against B.1.1.7, 6.5-fold against B.1.351, 4.3-fold against P.1, and 3.4-fold against original SARS-CoV-2. Our study indicates that a first-generation COVID-19 vaccine provides broad protection from SARS-CoV-2variants in individuals with previous infection.
Ranking Data Slices for ML Model Validation: A Shapley Value Approach

To make ML systems deployment ready, one of the prominent challenges is to debug the performance issues of the trained ML models. This can be done by associating the issues with a set of Data Slices - aggregates of validation data records - to help the developers investigate these technical issues at a deeper level of granularity. Since the possible number of data slices are exponential in number, there is a need to prioritize the order (i.e. ranking) of slices before presenting to the users. However, there does not exist any work that deals with ranking these automatically generated slices and we refer to this problem as the data slice ranking problem (DSRP). This problem is challenging to address as the top ranked slices should contain significant error concentration (i.e. number of mis-classified data points), be statistically significant (i.e. having large size), and be non-redundant (i.e. contain unique mis-classified data points).In this paper, we tackle this challenging problem by proposing a novel game theoretic framework building upon Shapley value concept to derive a rank order for a given collection of data slices. In particular, we formally present a scheme that explicitly accounts only for the error concentration and we refer to this as Shapley Slice Ranking with Error concentration (SSR-E). We then prove a few useful properties of this scheme. Using thorough experimentation on 7 open source data sets, we demonstrate the superior performance of SSR mechanism vis-a-vis two baseline methods.
1 LOCAL ORIGINS

What does it mean to say, “All data are local”? Before proceeding to the main cases of the book, let me further unpack the title claim. It relies on two concepts, data and local, that are pervasive in contemporary popular and academic writing, but less commonly seen together. In order to explain their pairing for the purposes of my argument, I need to address a number of misconceptions about each term independently. In the process, I will take the opportunity to acknowledge the contributions of other scholars who have laid the substantial foundations for this work. Let me turn to conceptions of data first.
PTEN and HER2 regulate self-renewal and invasion of human mammary stem cells.

1287 There is increasing evidence in breast cancers as well as other malignancies that tumorigenesis is driven by a cell population that retains stem cell properties. The key property of stem cells is their ability to self-renew. Thus, the elucidation of pathways which regulate stem cell self-renewal is important in understanding mammary carcinogenesis and of developing agents which can target the tumor stem cell pool. Two genes frequently deregulated in human breast cancers are HER2 and PTEN. HER2 is amplified in approximately 20-25% of human breast carcinomas and is associated with a poor clinical outcome. The lipid phosphatase PTEN is deregulated in approximately 40% of human breast carcinomas and is associated with increased Akt activation and poor clinical outcome. Patients with a combined loss of PTEN and HER2 amplification have a worse prognosis than either molecular defect alone. In order to study the effect of deregulation of these pathways we utilized both MCF7 human mammary carcinoma cells as well as normal human mammary epithelium isolated from reduction mammoplasties. Knockdown of PTEN expression in MCF7 cells utilizing a lenti-viral siRNA increased tumor formation in NOD-SCID mice 4 fold compared to GFP transfected cells. HER2 overexpression by lenti-viral infection in these cells increased their tumorigenicity 6 fold whereas the combination of HER2 overexpression and PTEN knockdown increased tumorigenicity 10 fold compared to GFP transfected controls. In order to determine whether these effects on tumorigenicity resulted from changes in stem cell populations, we utilized both mammosphere formation assay as well as the expression of the stem cell marker ALDH1. Deletion of PTEN and overexpression of HER2 increased the proportion of cells expressing the stem cell marker ALDH1 by 2-4 fold whereas the combination of PTEN deletion and HER2 overexpression placed the stem cell population up to 8 fold. Similar effects were observed when these genes genes were deregulated in normal human mammary epithelial cells. In order to determine whether this increase in stem cell populations produced changes in tumor characteristics we examined the ability of transfected MCF7 cells to invade utilizing the matrigell Boyden Chamber assay. PTEN deletion or HER2 overexpression led to an increase of up to 2-4 fold in the number of cells invading the matrix, with cells with combined PTEN knockdown and HER2 overexpression increasing their invasion up to 10 fold compared to MCF7 GFP cells. Furthermore, cells invading the matrix expressed the stem cell marker ALDH1. These experiments suggest that two genes commonly deregulated in sporadic breast cancer and associated with poor clinical outcome. HER2 and PTEN modulate stem cell function leading to increased invasion and tumorigenicity.
Probing the thermodynamics and kinetics of ethylene carbonate reduction at the electrode-electrolyte interface with molecular simulations.

Understanding the formation of the solid–electrolyte interphase (SEI) in lithium-ion batteries is an ongoing area of research due to its high degree of complexity and the difficulties encountered by experimental studies. Herein, we investigate the initial stage of SEI growth, the reduction reaction of ethylene carbonate (EC), from both a thermodynamic and a kinetic approach with theory and molecular simulations. We employed both the potential distribution theorem and the Solvation Method based on Density (SMD) to EC solvation for the estimation of reduction potentials of Li+, EC, and Li+-solvating EC (s-EC) as well as reduction rate constants of EC and s-EC. We find that solvation effects greatly influence these quantities of interest, particularly the Li+/Li reference electrode potential in EC solvent. Furthermore, we also compute the inner- and outer-sphere reorganization energies for both EC and s-EC at the interface of liquid EC and a hydroxyl-terminated graphite surface, where total reorganization energies are predicted to be 76.6 and 88.9 kcal/mol, respectively. With the computed reorganization energies, we estimate reduction rate constants across a range of overpotentials and show that EC has a larger electron transfer rate constant than s-EC at equilibrium, despite s-EC being more thermodynamically favorable. Overall, this manuscript demonstrates how ion solvation effects largely govern the prediction of reduction potentials and electron transfer rate constants at the electrode–electrolyte interface.
Outcomes of a Multi-Component School-Based Nutrition Program.

BACKGROUND This paper presents the effectiveness of a multi-component elementary school-based nutrition education program, the Integrated Nutrition Education Program (INEP), which has been in existence for over 25 years. INEP includes components to address multiple layers of influence: hands-on nutrition education lessons in the classroom (student-level), parent education, and outreach (home-level), and facilitation of a planning process to implement policy, system, and environmental (PSE) school changes (school-level). METHODS Three evaluation tools assessed the effectiveness of the program: (1) classroom plate waste measurement in intervention (N = 149 students) and demographically-matched comparison schools (N = 131 students), (2) pre/post classroom surveys completed by students who participated in INEP (N = 204), and (3) PSE change data from participating schools (N = 47 schools). RESULTS Students who participated in the nutrition education program were more likely to consume vegetable-based recipes and vegetables included in classroom nutrition lessons compared to students in comparison classrooms (Chinese vegetable salad: p < .001; couscous salad: p < .001; snap peas: p = .001). Classroom survey analyses showed improvements in student self-efficacy (p < .001), preference for vegetables (p = .005), and knowledge (p < .001). In addition, through a wellness planning process, schools implemented an average of 3.7 PSE changes per school. CONCLUSIONS Results demonstrate a multi-component school-based nutrition education program improves student nutrition-related outcomes.
The Tympanic Plate in Forensic Discrimination Between American Blacks and Whites

Skeletal material of forensic nature is often accompanied by relatively diagnostic cultural goods which can be used to infer provenience and help in the determination of race. However, when the skeletal material is recent or without associated cultural material, the racial assessment becomes more difficult. When only a cranium is recovered, one usually employs subjective criteria for determination of race. These might include prognathism, the existence of a depression posterior to the coronal suture, the relative flaring of the zygomata, or the morphology of the nasal roots. Inevitably, the cranium comes to light which does not permit a differential diagnosis of race based on such subjective assessments. The necessity for accuracy becomes most critical when the analysis is to be used for forensic purposes [1]. In such case, a quantitative tool can be of great value in the identification of a single cranium. Several multivariate approaches to this problem have been developed [2].
Illustrations of Failure of Domestic Jurisdiction to Prevent an Increase in Obligations

Although the plea of domestic jurisdiction has been entered with great frequency in discussions of disputes and situations before international organs, the development of its effectiveness, or ineffectiveness, has been confined to a few leading cases. Beginning with the Tunis-Morocco Nationality Decrees case during the League period, these cases will be described in this and the following chapter. They are presented as an elaboration and substantiation of the failure of the plea of domestic jurisdiction as a means of avoiding international obligations which has been described in the preceding chapter. Since the cases in this chapter collectively describe the trend in international organs to expand their jurisdiction horizontally to include additional topics that are subject to the discussion and recommendation functions of international organs, each can be described with some brevity. The subtleties by which the Congo crisis illustrates a vertical expansion, or direct international organ involvement in the affairs of a state, require the more detailed coverage of the following chapter.
Relational Data Base Systems: A Tutorial

Data independence may be achieved by providing users with a simple model of the data base and a simple language for operating on that model. The advantages of relations as the basis for such a model and language are considered with respect to alternative approaches based on hierarchies and on networks.
The politics of public pension reform

Public old-age pension programs are the largest single item of public expenditures in most advanced industrial countries. These pension systems have been buffeted by a number of pressures for change in recent years, however, notably an aging population, slower revenue growth, and competitive pressures to limit payroll taxes. Thus it is hardly surprising that pensions have received much attention from policymakers, and caused enormous political conflict, both in the United States and abroad. Policymakers have three very broad sets of options for responding to the increased funding demands of their pension systems: they can cut back on the generosity of specific provisions of their pension programs through retrenchment, refinance their pension programs, or restructure their pension programs. This paper attempts to understand cross-national patterns of pension policymaking as well as distinctive patterns in the United States.
Measuring Implied Volatility: is an Average Better?

Based on the law of large numbers, several options researchers have proposed using (different) weighted averages of the implied standard deviations, ISD, calculated from numerous options with the same expiry to obtain a single best ISD measure. However, most commercial providers use an average (and often an equally weighted average) of just a few at-the-money ISDs. We find that the practitioners' restricted averages forecast slightly better than the broader weighted averages from the academic literature but that neither group forecasts actual volatility very well. We suggest an adjustment to the extant models which improves their forecasting ability considerably. We also suggest a new weighting scheme which yields better estimates on an out-of-sample basis than any of the existing models (adjusted or unadjusted). However, we also find that because there is little independent noise in individual options ISDs (at least in the S&P 500 options market), there is little gain to averaging. Consequently, individual option ISDs and averages of just a few ISDs forecast almost as well as weighted averages of many ISDs and the weighting scheme choice is relatively unimportant.
Investing in people investing in education

Many institutions are now attempting to demonstrate publicly their commitment to their staff and staff development, in pursuit of institutional goals, by measuring themselves against national standards, most notably, at present, the Investors in People (IIP) standard. Investigates the degree of readiness for such status in an education department within a college of higher education. Discusses of the relationship between appraisal, IIP status and Office for Standards in Education (OFSTED) inspection. Follows with examination of the perceptions of staff towards a variety of motivational strategies. Asks staff to rate, in their view, how close the college is to meeting the demands of key criteria in the IIP standard. Uses the results to identify potential areas for further development prior to attaining IIP status.
In vivo removal of protein from tobacco mosaic virus after inoculation of tobacco leaves: III. Studies on the location on virus particles for the initial removal of protein☆

Abstract Tobacco leaves were inoculated with three types of protein-labeled TMV: particles labeled at the 3′-end, at the 5′-end, and completely labeled. In each case, labeled protein which was released from such virus particles was found in extracts of leaves a few minutes after inoculation. Approximately the same percentage of the labeled protein contained in each type of particle was released. The results indicate that the in vivo removal of protein molecules from TMV begins in a manner quite different from in vitro stripping caused by treatments which remove protein in a polar fashion from the 3′-ends of the particles. The most obvious interpretation of the results is an initial release of protein molecules from many positions along the length of the TMV particle. Other locations from which they may possibly be removed are also discussed.
3D printing: On its historical evolution and the implications for business

Additive manufacturing technologies have gained prominence in the recent past, and are increasingly entering the mainstream. Extant research on these technologies is typically focused on the mechanics, and user analysis is largely theoretical. Minimal applied research exists regarding why these technologies transform underlying business models, and how users (both business and consumer) approach them as they consider adoption. In this paper, we briefly describe the historical evolution of additive manufacturing technologies, highlight current 3D printing applications in both the consumer and business markets, and evaluate current skill sets of business users and potential consumers. We identify five factors that may affect users' understanding of 3D printing technologies, thereby influencing users' likelihood of adoption. The results from an exploratory study are then presented.
Solution of the coupled-channel schrödinger equation using constant, linear and quadratic reference potentials

Systems of coupled second order differential equations arise in many problems in molecular quantum physics. In this paper we investigate approximate potential methods that solve these differential equations. A series method for the evaluation of the propagators is developed for the multichannel Schrodinger equation where the reference potential is expressed as a polynomial. The case of a linear approximate potential is treated in detail and the results are compared with the Magnus and Bessel methods which approximate the potential as a constant in each interval. The importance of fitting the potentials at the zeroes of a Legendre polynomial is shown. Optimum fitting of the potential results in second and fourth order global convergence respectively for constant and linear fits. Richardson extrapolation is used to increase the accuracy of the low order methods. Explicit formulae are presented for the first order perturbative corrections to the Magnus propagators. The importance of adding the leading terms ...
Tau pathogenesis is promoted by Aβ1-42 but not Aβ1-40

The relationship between the pathogenic amyloid β-peptide species Aβ1–42 and tau pathology has been well studied and suggests that Aβ1–42 can accelerate tau pathology in vitro and in vivo. The manners if any in which Aβ1–40 interacts with tau remains poorly understood. In order to answer this question, we used cell-based system, transgenic fly and transgenic mice as models to study the interaction between Aβ1–42 and Aβ1–40. In our established cellular model, live cell imaging (using confocal microscopy) combined with biochemical data showed that exposure to Aβ1–42 induced cleavage, phosphorylation and aggregation of wild-type/full length tau while exposure to Aβ1–40 didn’t. Functional studies with Aβ1–40 were carried out in tau-GFP transgenic flies and showed that Aβ1–42, as previously reported, disrupted cytoskeletal structure while Aβ1–40 had no effect at same dose. To further explore how Aβ1–40 affects tau pathology in vivo, P301S mice (tau transgenic mice) were injected intracerebrally with either Aβ1–42 or Aβ1–40. We found that treatment with Aβ1–42 induced tau phosphorylation, cleavage and aggregation of tau in P301S mice. By contrast, Aβ1–40 injection didn’t alter total tau, phospho-tau (recognized by PHF-1) or cleavage of tau, but interestingly, phosphorylation at Ser262 was shown to be significantly decreased after direct inject of Aβ1–40 into the entorhinal cortex of P301S mice. These results demonstrate that Aβ1–40 plays different role in tau pathogenesis compared to Aβ1–42. Aβ1–40 may have a protective role in tau pathogenesis by reducing phosphorylation at Ser262, which has been shown to be neurotoxic.
Time-dependent effects of lithium on the agonist-stimulated accumulation of second messenger inositol 1,4,5-trisphosphate in SH-SY5Y human neuroblastoma cells

In order to approach the molecular mechanism of Li+9s mood-stabilizing action, the effect of Li+ (LiCl) on inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] mass was investigated in human neuroblastoma SH-SY5Y cells, which express muscarinic M3 receptors, coupled to PtdIns hydrolysis. Stimulation of these cells, with the cholinergic agonist acetylcholine, resulted in a rapid and transient increase in Ins(1,4,5)P3 with a maximum at 10 s. This was followed by a rapid decline in Ins(1,4,5)P3 within 30 s to a plateau level above baseline, which gradually declined to reach a new steady state, which was significantly higher than resting Ins(1,4,5)P3 at 30 min. Li+ had no effect on Ins(1,4,5)P3 in resting cells, as well as on the acetylcholine-dependent peak of Ins(1,4,5)P3. However, Li+ caused a transient reduction (at 45 s), followed by a long lasting increase in the Ins(1,4,5)P3 (30 min), as compared with controls. The Li+ effects were dose-dependent and were observed at concentrations used in the treatment of bipolar disorders. Supplementation with inositol had no effect on the level of Ins(1,4,5)P3, at least over the time periods studied. Stimulation of muscarinic receptors with consequent activation of phospholipase C were necessary for the manifestation of Li+ effects in SH-SY5Y cells, Li+ did not interfere with degradation of Ins(1,4,5)P3 after receptor-blockade with atropine, suggesting that Li+ has no direct effect on the Ins(1,4,5)P3-metabolizing enzymes. A direct effect of Li+ on the phospholipase C also is unlikely. Blockade of Ca2+ entry into the cells by Ni2+, or incubation with EGTA, which reduces agonist-stimulated accumulation of Ins(1,4,5)P3, had no effect on the Li(+)-dependent increase in Ins(1,4,5)P3.
Elevation of superoxide dismutase in Halobacterium halobium by heat shock.

Abstract Exposure of Halobacterium halobium to 50 degrees C for 2.5 h in an aerobic environment resulted in a greater than twofold increase in the activity of the manganese-containing superoxide dismutase. Nondenaturing polyacrylamide gels stained for enzymatic activity did not reveal any additional isozymes of superoxide dismutase induced by the heat shock. The maximal effect was observed at 50 degrees C, and the elevated levels of activity remained constant during 5 h of recovery at 40 degrees C. The induction of enzymatic activity was sensitive to protein synthesis inhibitors. The results are discussed relative to heat shock and stress-related proteins as well as alterations in metabolism brought about by elevated temperatures.
Siliciclastic Sequence Stratigraphy—Concepts and Applications‐SEPM Series‐Concepts in Sedimentology and Paleontology #7

Sequence stratigraphy is branch of stratigraphy that is based upon using stratal patterns and stratal termination patterns to identify groups of strata that were deposited within the same interval and therefore genetically related. Its wide application in the 1980s and 1990s has provided new insight into the history and architecture of basin fill. In this book, H.W. Posamentier and G.P. Allen take sequence stratigraphic models developed in the 1970s and modified in the 1980s to a higher level. The authors state that their goal is to focus on remaining flexible and pragmatic in their presentation of how to conduct sequence stratigraphic analyses and to operate using the premise that any geologic interpretation that does not violate stratigraphic first principles is a reasonable solution. They emphasize that the nature of sequence development is controlled by a combination of variation in accommodation, sediment supply, and physiography, and that each can have a significant impact on sequence architecture. This is a departure from earlier work, where eustasy was assumed to be the dominant force in sequence development.
Evaluation of a macro encapsulated repellent to reduce risk of white phosphorous ingestion by waterfowl foraging in a contaminated marsh

Abstract White Phosphorous contamination of a marsh at a U.S. Army artillery training range in Alaska is a causative agent for waterfowl mortality. We developed an encapsulated bird repellent containing the active ingredient, methyl anthranilate, and evaluated the formulations efficacy in reducing feeding activity by ducks, reducing mortality of ducks feeding in contaminated sediments, and the repellents ability to move ducks from contaminated areas. The formulation has a limited life span of about 4 days. However, in pen trials feeding activity of mallards can be reduced by up to 80%. Long term exposure to treated sediments confers a survival advantage to mallards tested in pens, and free-ranging mallards can be moved off of treated sections of marsh. This prototype formulation may have utility in the short-term remediation of contaminated sediments for the protection of waterfowl.
Finite deformation constitutive equations and a time integrated procedure for isotropic hyperelastic—viscoplastic solids

Abstract Constitute equations for finite deformation, isotropic, elastic-viscoplastic solids are formulated. The concept of a multiplicative decomposition of the deformation gradient into an elastic and a plastic part is used. The constitutive equation for stress is a hyperelastic relation in terms of the logarithmic elastic strain. Since the material is assumed to be isotropic in every local configuration determined by the plastic part of deformation gradient, the internal variables are necessarily scalars. We use a single scalar as an internal variable to represent the isotropic resistance to plastic flow offered by the internal state of the material. The constitutive equation for stress is often expressed in a rate form, and for metals it is common to approximate this rate equation, under the assumption of infinitesimal elastic strains, to arrive at a hypoelastic equation for the stress. Here, we do not express the stress constitutive equation in a rate form, nor do we make this approximative assumption. For the total form of the stress equation we present a new implicit procedure for updating the stress and other relevant variables. Also, the principle of virtual work is linearized to obtain a consistent, closed-from elasto-viscoplastic tangent operator (the ‘Jacobian’) for use in solving for global balance of linear momentum in implicit, two-point, deformation driven finite element algorithms. The time integration algorithm is implemented in the finite element program ABAQUS. To check the accuracy and stability of the algorithm, some representative problems involving large, pure elastic and combined elastic-plastic deformations are solved.
User as catalyst

User interface (UI) development is a complex process that involves the cooperation and input from both the developer and the user population. It is also an iterative process that requires continuous feedback and possibly peer review. Usability is a primary concern for user interface development, and there are several methods that can be used to test the efficacy of UIs in the digital library context. UI design is critical for the effective presentation and manipulation of digital data in virtually every context of the digital library.
The reaction of 16α‐hydroxyestrone with erythrocytes in vitro and in vivo

16 alpha-Hydroxyestrone (16 alpha OHE ) has been shown previously to react with albumin, forming stable covalent adducts with lysine residues. The incubation of [3H]16 alpha OHE with whole blood also results in the incorporation of tritium into cells, with the rate of incorporation paralleling that of 16 alpha OHE -protein adduct formation. 32% of erythrocyte acid-precipitable radioactivity was found to be present within membrane proteins and electrophoresis demonstrated that several of these proteins are modified by [3H]16 alpha OHE . Membrane proteins from the red cells of ten individuals were reduced with sodium borohydride, acid hydrolyzed, and the 16 alpha OHE -lysine adducts purified by hydrophobic chromatography and reverse-phase high-pressure liquid chromatography. The amount of these adducts was quantitated by radioimmunoassay and found to be five times higher than the plasma levels of free 16 alpha OHE . This reflects most likely the accumulation of 16 alpha OHE -protein adducts during the course of the red cell life. Quantitation of 16 alpha OHE -protein adducts with other cellular proteins may contribute to our understanding of systemic lupus erythematosus, an autoimmune disease in which elevated levels of 16 alpha OHE occur.
SIMULTANEOUS MEASUREMENT OF MASS FLUX AND STEAM QUALITY IN GEOTHERMAL WELLS USING HOMOGENEOUS AND SEPARATED FLOW MODELS

Abstract This paper discusses the simultaneous prediction of mass flux and steam quality from two measurements, critical flow lip pressure and pressure drop across an orifice. The James equation for predicting mass flux during two-phase critical flow of steam and water in geothermal wells from lip pressure and stagnation enthalpy data is used. For two-phase flow across an orifice, the separated flow model proposed by Chisholm is used, with modification to account for the upstream fluid momentum. These predictions are compared with the data gathered by James and with the predictions of the James orifice correlation. The study indicates that for low qualities (quality < 40%), the modified separated flow model is as good as the James correlation in predicting the James data. However, the prediction accuracy of both the approaches are unacceptably low at higher steam quality. A sensitivity analysis is done which indicates that the inaccuracy in prediction arises from the coupled nature of the critical flow eq...
Evaluation of neuropathy in patients on suramin treatment

Suramin, a promising chemotherapeutic agent, causes a dose-limiting sensorimotor polyneuropathy. We undertook a phase 1 study of suramin that included serial neurologic and electrophysiologic examinations as part of the safety evaluation. We found that 6 of 41 (15%) patients developed suramin-induced demyelinating neuropathy which resembled Guillain-Barre syndrome clinically. There was 1 asymptomatic patient with electrophysiologic abnormalities suggestive of a demyelinating neuropathy. In addition, 1 patient with mild axonal neuropathy at baseline had deterioration of his symptoms during suramin treatment. Four asymptomatic patients developed electrophysiologic findings suggestive of a mild axonal neuropathy. We conclude that: (1) serial electrophysiologic monitoring is helpful for early detection of suramin-induced neuropathy; and (2) fixed dosing schedule of suramin without adaptive control does not lead to an increased incidence of demyelinating neuropathy when compared to adaptively controlled dosing schedules.
Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain.

Abstract The epidermal growth factor receptor plays crucial roles throughout the development of multicellular organisms, and inappropriate activation of the receptor is associated with neoplastic transformation of many cell types. The receptor is thought to be activated by ligand-induced homodimerisation. Here, however, we show by chemical cross-linking and sucrose density-gradient centrifugation that in the absence of bound ligand the receptor has an ability to form a dimer and exists as a preformed dimer on the cell surface. We also analysed the receptor dimerisation by inserting cysteine residues at strategic positions about the putative α-helix axis of the extracellular juxtamembrane region. The mutant receptors spontaneously formed disulphide bridges and transformed NIH3T3 cells in the absence of ligand, depending upon the positions of the cysteine residue inserted. Kinetic analyses of the disulphide bonding indicate that EGF binding induces flexible rotation or twist of the juxtamembrane region of the receptor in the plane parallel with the lipid bilayer. The binding of an ATP competitor to the intracellular domain also induced similar flexible rotation of the juxtamembrane region. All the disulphide-bonded dimers had flexible ligand-binding domains with the same biphasic affinities for EGF as the wild-type. These results demonstrate that ligand binding to the flexible extracellular domains of the receptor dimer induce rotation or twist of the juxtamembrane regions, hence the transmembrane domains, and dissociate the dimeric, inactive form of the intracellular domains. The flexible rotation of the intracellular domains may be necessary for the intrinsic catalytic kinase to become accessible to the multiple tyrosine residues present in the regulatory domain and various substrates, and may be a common property of many cell-surface receptors, such as the insulin receptor.
Biological and Biochemical Characterization of Variant A Subunits of Cholera Toxin Constructed by Site-Directed Mutagenesis

Cholera toxin (CT) is the prototype for the Vibrio cholerae-Escherichia coli family of heat-labile enterotoxins having an AB5 structure. By substituting amino acids in the enzymatic A subunit that are highly conserved in all members of this family, we constructed 23 variants of CT that exhibited decreased or undetectable toxicity and we characterized their biological and biochemical properties. Many variants exhibited previously undescribed temperature-sensitive assembly of holotoxin and/or increased sensitivity to proteolysis, which in all cases correlated with exposure of epitopes of CT-A that are normally hidden in native CT holotoxin. Substitutions within and deletion of the entire active-site-occluding loop demonstrated a prominent role for His-44 and this loop in the structure and activity of CT. Several novel variants with wild-type assembly and stability showed significantly decreased toxicity and enzymatic activity (e.g., variants at positions R11, I16, R25, E29, and S68+V72). In most variants the reduction in toxicity was proportional to the decrease in enzymatic activity. For substitutions or insertions at E29 and Y30 the decrease in toxicity was 10- and 5-fold more than the reduction in enzymatic activity, but for variants with R25G, E110D, or E112D substitutions the decrease in enzymatic activity was 12- to 50-fold more than the reduction in toxicity. These variants may be useful as tools for additional studies on the cell biology of toxin action and/or as attenuated toxins for adjuvant or vaccine use.
An elementary proof of the MacWilliams theorem on equivalence of codes

In this paper, we prove the following theorem due to MacWilliams. Two codes are equivalent if and only if there is a weight preserving linear isomorphism between them. The proof we give is a simplification and extension of her proof to the most general case.
Treatment of warfarin-associated coagulopathy: a physician survey.

Study objectives (1) To determine physician preferences in the management of warfarin-induced excessive anticoagulation (AC); and (2) to assess compliance with the American College of Chest Physicians (ACCP) guidelines for the reversal of excessive AC. Design Cross-sectional physician survey. Participants Members of the Canadian Society of Internal Medicine practicing in Ontario, Canada. Measurements and results Physicians were asked to provide management preferences in six clinical scenarios describing warfarin-induced excessive AC. The scenarios represent various combinations of international normalized ratio (INR) value, treatment setting, and presence and severity of bleeding. In scenarios with INRs ie ,> 7.1) and/or bleeding, the selection of vitamin K in any form ranged between 71% and 82%. However, compliance with the ACCP-recommended doses and the routes of vitamin K administration ranged from 1 to 10%. In five of the six scenarios, subcutaneous injection, a route not recommended by the ACCP, was the most common method of vitamin K delivery. Conclusions Physician preferences for the reversal of warfarin-induced excessive AC were highly variable and, in most cases, did not follow the recommendations of the ACCP consensus guidelines. Furthermore, the widespread reported use of subcutaneous vitamin K is concerning because this route of vitamin K administration has been demonstrated to be less effective than IV administration of vitamin K. These findings highlight the need for randomized controlled trials to compare the efficacy of different routes of administration of vitamin K for warfarin-associated coagulopathy.
Thermally gated liposomes.

The combined use of a pore-forming amphiphile, 1 (derived from lysine, cholic acid, and spermine), and thermally sensitive liposomes (made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) to create “thermally gated liposomes” (TGLs) has been demonstrated. Thus, at temperatures that lie above the gel to liquid−crystalline phase transition temperature of DPPC (i.e., 41 °C), 1 creates pores within DPPC membranes through which entrapped aqueous solutes, such as carboxyfluorescein, can readily pass. Below this temperature, efflux rates are greatly reduced. The potential of TGLs as devices for the targeted delivery of therapeutic agents is briefly discussed.
Digital video blue-screen editing in compressed domain

Chroma-keying or blue screen matting is an important video editing operational. In blue screen matting, everything in the image that has the 'user specified level for the blue channel' is 'keyed' out and replaced by either another image or a color from a color generator. We develop a technique for blue screen matting that manipulates the image when the information for the image is available only in compressed form such as a JPEG or MPEG bitstream. Specifically, for the compressed domain approach, we show that the matting process is a convolution operation; hence, we develop a DCT convolution theorem. The DCT convolution theorem can be used to show that the compressed domain approach proposed in this paper provides a significant reduction in computation complexity compared to previously developed approaches which were mostly adhoc techniques. The convolution theorem exploits the sparseness as well as the orthogonality of the data available in the DCT domain and thus yields an efficient algorithm for he chroma-keying or blue screen matting. The algorithm extends to the DCT domain concepts such as alpha channel and premultiplied alpha. The method is also extended to MPEG video domain wherein we explore the efficiency of the matting process when interframe coding is used.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Interchange of autoinhibitory domain conformations in plasma-membrane Ca2+-ATPase–calmodulin complexes

The Ca2+ signaling protein calmodulin (CaM) stimulates Ca2+ pumping in the plasma-membrane Ca2+-ATPase (PMCA) by binding to an autoinhibitory domain, which then dissociates from the catalytic domain of PMCA to allow full activation of the enzyme. We measured single-molecule fluorescence trajectories with polarization modulation to track the conformation of the autoinhibitory domain of PMCA pump bound to fluorescently labeled CaM. Interchange of the autoinhibitory domain between associated and dissociated conformations was detected at a physiological Ca2+ concentration of 0.15 μM, where the enzyme is only partially active, but not at 25 μM, where the enzyme is fully activated. In previous work we showed that the conformation of the autoinhibitory domain in PMCA–CaM complexes could be monitored by the extent of modulation of single-molecule fluorescence generated with rotating excitation polarization. In the present work, we determined the timescale of association and dissociation of the autoinhibitory domain with the catalytic regions of the PMCA. Association of the autoinhibitory domain was rare at a high Ca2+ concentration (25 μM). At a lower Ca2+ concentration (0.15 μM), conformations of the autoinhibitory domain interchanged with a dissociation rate of 0.042 ± 0.011 sec−1 and an association rate of 0.023 ± 0.006 sec−1. The results indicate that the response time of PMCA upon a reduction in Ca2+ is limited to tens of seconds by autoinhibitory dynamics. This property may reduce the sensitivity of PMCA to transient reductions in intracellular Ca2+. We suggest that the dynamics of the autoinhibitory domain may play a novel role in regulating PMCA activity.
Suppression of the Preovulatory Luteinizing Hormone Surge in the Rat by 2-Hydroxyestrone: Relationship to Endogenous Estradiol Levels

Injection of 100 micrograms 2-hydroxyestrone (2OHE1) at various times on the morning of proestrus into normal 4-day-cycling rats results in abolition of the preovulatory LH surge in a number of animals tested. The greatest response was observed when the administration of 2OHE1 coincided with endogenous estradiol (E2) levels that were close to but not at their maximal proestrous levels. The catechol estrogen failed to abolish the LH surge if given much earlier or after the E2 maximum had already been reached. The effectiveness of 2OHE1 inhibition of the LH surge was greatly increased by the administration of 1 microgram E2 1 h before the catechol estrogen. 2OHE1 did not interfere with LH secretion in response to LHRH administration, indicating that the inhibitory action of the catechol estrogen is exercised at the hypothalamic level. In contrast to its inhibition of the positive feedback, 2OHE1 administered either before or after the injection of E2 to ovariectomized rats had no effect on the negative feedback of the hormone on pituitary LH secretion. The narrow and specific "time window" on proestrus when an injection of 2OHE1 results in the abolition of the preovulatory LH surge and its relation to the endogenous E2 preovulatory secretion suggest that the catechol estrogen interferes with a brief neuronal triggering event obligatory for LHRH release. The evidence also indicates that this action does not involve conventional competition for the E2 receptor.
Thermotropic liquid-crystalline copolyesters containing substituted phenylene terephthalate and ethylene terephthalate units

Three series of aromatic, thermotropic copolyesters, based on terephthalic acid (TA), ethylene glycol (EG), and another diol were prepared. The third monomer was selected from three different hydroquinones including, ethoxyhydroquinone (EHQ), phenylhydroquinone (PHQ), and hydroquinone itself (HQ). The amounts of the different hydroquinone terephthalate units were varied while the amounts of ethylene terephthalate units remained constant. The copolymers and terpolymers were characterized for solubility, for morphology by polarized light microscopy (PLM), for molecular weight by solution viscometry, and by NMR, DSC, and TGA. At elevated temperatures all samples, when observed by PLM, displayed the characteristic texture of a nematic phase. The melting transition temperatures, Tm, were found to vary from 255 to 325°C, while the 5 wt % loss temperatures, Td, were found to vary from 330 to 440°C. The inherent viscosities varied from 0.6 to 1.9 dL/g. Increases in the HQ monomer content caused a decreased solubility and an increase in melting point. Copolymer compositions determined by NMR showed that only about one-half of the EG added was incorporated into the copolymers. © 1997 John Wiley & Sons, Inc.
Obstructive Sleep Apnea in Patients Undergoing Bariatric Surgery—A Tertiary Center Experience

Background The patient population that is evaluated for bariatric surgery is characterized by a very high body mass index (BMI). Since obesity is the most important risk factor for obstructive sleep apnea (OSA), sleep disordered breathing is highly prevalent in this population. If undiagnosed before bariatric surgery, untreated OSA can lead to perioperative and postoperative complications. Debate exists whether all patients that are considered for bariatric surgery should undergo polysomnography (PSG) evaluation and screening for OSA as opposed to only those patients with clinical history or examination concerning sleep disordered breathing. We examined the prevalence and severity of OSA in all patients that were considered for bariatric surgery. We hypothesized that, by utilizing preoperative questionnaires (regarding sleepiness and OSA respiratory symptoms) in combination with menopausal status and BMI data, we would be able to predict which subjects did not have sleep apnea without the use of polysomnography. In addition, we hypothesized that we would be able to predict which subjects had severe OSA (apnea–hypopnea index (AHI) > 30).
Raising the active site of factor VIIa above the membrane surface reduces its procoagulant activity but not factor VII autoactivation

Tissue factor, the physiologic trigger of blood clotting, is the membrane-anchored protein cofactor for the plasma serine protease, factor VIIa. Tissue factor is hypothesized to position and align the active site of factor VIIa relative to the membrane surface for optimum proteolytic attack on the scissile bonds of membrane-bound protein substrates such as factor X. We tested this hypothesis by raising the factor VIIa binding site above the membrane surface by creating chimeras containing the tissue factor ectodomain linked to varying portions of the membrane-anchored protein, P-selectin. The tissue factor/P-selectin chimeras bound factor VIIa with high affinity and supported full allosteric activation of factor VIIa toward tripeptidyl-amide substrates. That the active site of factor VIIa was raised above the membrane surface when bound to tissue factor/P-selectin chimeras was confirmed using resonance energy transfer techniques in which appropriate fluorescent dyes were placed in the active site of factor VIIa and at the membrane surface. The chimeras were deficient in supporting factor X activation by factor VIIa due to decreased kcat. The chimeras were also markedly deficient in clotting plasma, although incubating factor VII or VIIa with the chimeras prior to the addition of plasma restored much of their procoagulant activity. Interestingly, all chimeras fully supported tissue factor-dependent factor VII autoactivation. These studies indicate that proper positioning of the factor VII/VIIa binding site on tissue factor above the membrane surface is important for efficient rates of activation of factor X by this membrane-bound enzyme/cofactor complex.
Development of angiotensin II-sensitive OVLT neurons in SHR and WKY rats.

Abstract Angiotensin II (AII) sensitivity of neurons in the region of the organum vasculosum laminae terminalis (OVLT) was examined electrophysiologically using in vitro hypothalamic brain slices taken from 4-, 9- and 14-week-old spontaneously hypertensive (SHR) and normotensive Wintar-Kyoto (WKY) rats. Micropressure application of AII, its competitive antagonist saralasin, and l -glutamate revealed that neurons in this region of SHR were significantly more sensitive to AII than cells in age-matched WKY preparations. Neuronal sensitivity to l -glutamate was similar between SHR and WKY rats at all ages. Following electrophysiological study, hypothalamic and cortical brain slices were assayed for 125 I-labelled AII binding. AII receptor binding in the hypothalamic slices from SHR was elevated significantly above binding in WKY hypothalamic slices at 4, 9, and weeks of age. In contrast. AII binding in cortical slices taken from SHR and WKY rats was similar. These data suggest that altered neuronal AII-sensitivity is not a consequence of hypertension development in SHR and may contribute to its development.
Note: Hollow cathode lamp with integral, high optical efficiency isolation valve: a modular vacuum ultraviolet source.

The design and operating conditions of a hollow cathode discharge lamp for the generation of vacuum ultraviolet radiation, suitable for ultrahigh vacuum (UHV) application, are described in detail. The design is easily constructed, and modular, allowing it to be adapted to different experimental requirements. A thin isolation valve is built into one of the differential pumping stages, isolating the discharge section from the UHV section, both for vacuum safety and to allow lamp maintenance without venting the UHV chamber. The lamp has been used both for ultraviolet photoelectron spectroscopy of surfaces and as a “soft” photoionization source for gas-phase mass spectrometry.