cssi/SciSciGPT-SciSciNet huggingface dataset:
Considering the Efficacy of Digital Technology as a Means of Evangelization in Christian Religious Education

This essay attends to how digital technology is shaping Christian religious education and its efforts of evangelization. It proposes that, while the use of digital technology has promise, an unrefl...
Guiding center and gyrokinetic orbit theory for large electric field gradients and strong shear flows

The guiding center and gyrokinetic theory of magnetized particle motion is extended to the regime of large electric field gradients perpendicular to the magnetic field. A gradient in the electric field directly modifies the oscillation frequency and causes the Larmor orbits to deform from circular to elliptical trajectories. In order to retain a good adiabatic invariant, there can only be strong dependence on a single coordinate at lowest order, so that resonances do not generate chaotic motion that destroys the invariant. When the gradient across magnetic flux surfaces is dominant, the guiding center drift velocity becomes anisotropic in response to external forces and additional curvature drifts must be included. The electric polarization density remains gyrotropic, but both the polarization and magnetization are modified by the change in gyrofrequency. The theory can be applied to shear flows that are even stronger than those observed in the edge transport barrier of a high-performance tokamak (H-mode) pedestal, even if the toroidal field is as small as or even smaller than the poloidal field. Yet, the theory retains a mathematical form that is similar to the standard case and can readily be implemented within existing simulation tools.
MR based attenuation correction and µ map production in PET/MR breast imaging.

2143 Objectives: Attenuation correction (AC) is necessary for data quantification in PET imaging. PET reconstructions without AC appear to show areas of low attenuation (patient surface and lungs) as having increased uptake. A transmission-based AC map (µ-map), obtained from rotating rod sources or through CT, is created and utilized during the PET emission data reconstruction. Traditional methods for µ-map creation are unavailable in PET/MR imaging, therefore, MR imaging sequences (DIXON) are utilized to generate the required µ-map. Voxel intensities in an MR image decrease as their distance from the radio frequency coil increases. This can lead to the creation of incomplete µ-maps. Initial investigation of breast PET/MR imaging with a Siemens Biograph mMR has inspired this discussion. Methods: Diagnostic MR imaging of the breasts is generally performed with only a dedicated breast coil. A volunteer was initially imaged utilizing a DIXON sequence with only a breast coil. A second scan was then completed utilizing both the breast coil and a surface coil on the subject’s back. To simulate lesions in a patient, conical 1.5 mL vials containing a clinically relevant concentration of F-18 FDG were placed in the axillary and mediastinal regions of the volunteer. Standardized uptake values (SUVs) were obtained from regions of interest drawn around the axillary and mediastinal sources to compare the effects on PET AC images derived from an incomplete µ-map (breast coil only) versus a complete µ-map (breast and surface coils). Results: The DIXON sequence with the breast coil alone generated an incomplete µ-map, as anticipated. SUVs of the axillary source increased from 2.08 to 10.48 when a complete µ-map was generated with the addition of a surface coil. SUVs of the mediastinal source increased from 1.30 to 3.30. Conclusions: In PET/MR imaging, care must be taken to ensure that the DIXON sequence has adequate MR signal to generate complete µ-maps. Incomplete µ-maps result in PET reconstructions having uncompensated PET counting losses, inaccurate quantification, and underestimated SUVs.
Finding balance with deep eutectic solvents: High concentrations and improved conductivities for the off-the-shelf nitroxide TEMPOL

Abstract Viologens and the stable, water-soluble nitroxide radical known as TEMPOL have been studied extensively with respect to applications in energy storage. Here we report formulations wherein high concentrations of both are achieved in a single solution and the reversible electrochemistry of each is retained. We demonstrate one of several potential applications by constructing a high optical density electrochromic device.
Hegel and Durkheim: Contours of an Elective Affinity

The aim of my contribution is to outline three points of overlap between Hegel’s Philosophy of Right and Durkheim’s sociology of morality in their respective views on social ethics: I will start by characterizing their shared conviction that the foundation of any form of morality cannot be found in some abstract principles but in actually existing, institutionalized normative rules that inform us about our role-obligations (i). In the second step I will show that Hegel and Durkheim also share the social-theoretical conviction that we should differentiate modern societies into three different spheres (family—civil society/market—state) all entailing different sorts of role-obligations; a part of this step will also specifically deal with the question of how both thinkers conceive of the problems raised by the modern, capitalist market economy (ii). In the third part of my contribution I will consider the question of whether we find in Hegel’s Philosophy of Right a placeholder for what Durkheim refers to as a kind of cosmopolitan ethics, a standpoint beyond the role-obligations connected to membership in individual states (iii). In my conclusion I will raise the question of the relevance of Hegel’s and Durkheim’s shared views on the basis for social ethics for contemporary discussions in political and social philosophy.
Group B Streptococcal Infections: An Obstetrical Viewpoint

Group B Streptococcus (GBS) was first identified as a cause of puerperal sepsis during the late 1930s. However, concern regarding GBS was diminished in part by the greater pathogenicity of the group A Streptococcus, which was described in the same studies. Clinical research regarding GBS infections resumed during the 1960s. Data regarding the perinatal transmission of GBS have now accumulated to an extent that education of all obstetric and pediatric care providers is imperative. During the past 2 years, committees of both the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) have considered the issues of perinatal transmission of GBS. Each group had input from the other by a series of meetings and document exchanges.
Using Reading Guides and On-line Quizzes to Improve Reading Compliance and Quiz Scores

This study compared students’ daily in-class reading quiz scores in an introductory Child Development course across five conditions: control, reading guide only, reading guide and on-line practice quiz, reading guide and on-line graded quiz, and reading guide and both types of on-line quizzes. At the beginning of class, students completed a 5-item quiz over the assigned readings. With the exception of the control section, all students had access to an instructor-designed reading guide for each of the 20 assigned readings. Results revealed that reading guides significantly increased student learning as demonstrated by increased scores on the in-class reading quizzes, with marginal additional gains when practice quizzes were also utilized. The addition of online graded quizzes resulted in lower scores on in-class quizzes. Results held even after multiple subsidiary analyses controlling for time spent studying. These findings suggest that reading guides may be a valuable study aid for improving student learning.
COMPLEX-PROPAGATOR INSERTIONS IN THE SQUARE DIAGRAM.

The problem of inserting a complex propagator in the crossed channel of the square diagram is considered. The propagator is spectrally represented and the square diagram with full propagator insertion is expressed as a spectral integral of square diagrams over an internal mass variable. The analytic properties of such diagrams in two complex variables, one internal mass and one external energy, are investigated in detail. These properties are then used to find the analytic properties of the full diagram with propagator insertions.
Burst arbitrary millimeter waveform generation via a direct space-to-time optical pulse shaper

We demonstrate a novel, direct space-to-time optical pulse shaping technique for the generation of burst millimeter-wave signals at center frequencies approaching 50 GHz. By appropriately tailoring the optical pulse sequences driving a high-speed optical-to-electrical converter, we generate arbitrarily phase- and frequency-modulated millimeter waveforms.
Optimization of an extracellular protease of Chrysosporium keratinophilum and its potential in bioremediation of keratinic wastes

Chrysosporium keratinophilum IMI 338142 isolated from a waste site containing organopollutants was studied for its ability to produce extracellular proteases on glucose-gelatin medium. Fungus was observed to be a potent producer of such enzymes. Enzyme secretion was best at 15 days of incubation period at pH 8 and temperature 40 °C. Asparagine was repressive to protease expression. No relationship existed between the enzyme yield and increase in biomass. Exogenous sugars suppressed enzyme production in the descending order as follows: glucose > arabinose > maltose > mannose > fructose. The enzyme released showed the ability to decompose two keratin substrates tested. Buffalo skin was the most actively degraded substrate when exogenous glucose was absent. Presence of glucose suppressed both enzyme production and degradation of keratin. However, the rate of keratin degradation was independent of enzyme production.
Dual-Polarization Radar Data Analysis of the Impact of Ground-Based Glaciogenic Seeding on Winter Orographic Clouds. Part I: Mostly Stratiform Clouds

AbstractThe impact of ground-based glaciogenic seeding on wintertime orographic, mostly stratiform clouds is analyzed by means of data from an X-band dual-polarization radar, the Doppler-on-Wheels (DOW) radar, positioned on a mountain pass. This study focuses on six intensive observation periods (IOPs) during the 2012 AgI Seeding Cloud Impact Investigation (ASCII) project in Wyoming. In all six storms, the bulk upstream Froude number below mountaintop exceeded 1 (suggesting unblocked flow), the clouds were relatively shallow (with bases below freezing), some liquid water was present, and orographic flow conditions were mostly steady. To examine the silver iodide (AgI) seeding effect, three study areas are defined (a control area, a target area upwind of the crest, and a lee target area), and comparisons are made between measurements from a treated period and those from an untreated period. Changes in reflectivity and differential reflectivity observed by the DOW at low levels during seeding are consistent...
Comparisons among some tetraalkoxysilanes in the hydrolytic precipitation of silica into elastomeric networks

Four tetraalkoxysilanes Si(OR)4 were absorbed into networks of polydimethylsiloxane and then hydrolyzed, using a variety of catalysts, to give reinforcing silica particles. On the basis of the amount of silica precipitated and the extent of reinforcement, the (decreasing) order of effectiveness was found to be tetraethoxysilane, tetrapropoxysilane, tetrabutoxysilane, and tetramethoxysilane.
Mouse lung volume reconstruction from efficient groupwise registration of individual histological slices with natural gradient

Mouse lung models facilitate the study of the pathogenesis of various pulmonary diseases such as infections and inflammatory diseases. The co-registration of ex vivo histological data and pre-excised magnetic resonance imaging (MRI) in preclinical mouse models would allow for determination and validation of imaging signatures for different pathobiologies within the lung. While slice-based co-registration could be used, this approach assumes that (a) slice correspondences between the two different modalities exist, and (b) finding slice correspondences often requires the intervention of an expert and is time consuming. A more practical approach is to first reconstruct the 3D histological volume from individual slices, then perform 3D registration with the MR volume. Before the histological reconstruction, image registration is required to compensate for geometric differences between slices. Pairwise algorithms work by registering pairs of successive slices. However, even if successive slices are registered reasonably well, the propagation of registration errors over slices can yield a distorted volumetric reconstruction significantly different in shape from the shape of the true specimen. Groupwise registration can reduce the error propagation by considering more than two successive images during the registration, but existing algorithms are computationally expensive. In this paper, we present an efficient groupwise registration approach, which yields consistent volumetric reconstruction and yet runs equally fast as pairwise registration. The improvements are based on 1) natural gradient which speeds up the transform warping procedure and 2) efficient optimization of the cost function of our groupwise registration. The strength of the natural gradient technique is that it could help mitigate the impact of the uncertainties of the gradient direction across multiple template slices. Experiments on two mouse lung datasets show that compared to pairwise registration, our groupwise approach runs faster in terms of registration convergence, and yields globally more consistent reconstruction.
Private self-consciousness, self-awareness, and the reliability of self-reports.

Two studies found that individuals high in private self-consciousness provide self-reports of greater reliability across time than individuals low in private self-consciousness. In addition, Study 2 found that a successful manipulation of self-awareness did not affect test-retest reliability of self-reports among Ss either high or low in private self-consciousness. The hypothesis that individuals high in private self-consciousness have articulated self-schemata of greater temporal stability than individuals low in private self-consciousness received support. The discussion considers (a) how private selfconsciousness, but not self-awareness, influenced test-retest reliability of self-reports, (b) how private self-consciousness and self-awareness may both influence, albeit differentially, the eriterionrelated validity of self-reports, and (c) the possibility that current models of self-consciousness-selfawareness require reformulation.
Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice

There are several studies supporting the role of HMG-CoA reductase inhibitors such as atorvastatin against carcinogenesis, in which inhibiting the generation of prenyl intermediates involved in protein prenylation plays the crucial role. Mutation of Kras gene is the most common genetic alteration in pancreatic cancer and the Ras protein requires prenylation for its membrane localization and activity. In the present study, the effectiveness of atorvastatin against pancreatic carcinogenesis and its effect on protein prenylation were determined using the LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mouse model (called Pankras/p53 mice). Five-week-old Pankras/p53 mice were fed either an AIN93M diet or a diet supplemented with 100 ppm atorvastatin. Kaplan-Meier survival analysis with Log-Rank test revealed a significant increase in survival in mice fed 100 ppm atorvastatin (171.9 ± 6.2 d) compared to the control mice (144.9 ± 8.4 d, P < 0.05). Histologic and immunohistochemical analysis showed that atorvastatin treatment resulted in a significant reduction in tumor volume and Ki-67-labeled cell proliferation. Mechanistic studies on primary pancreatic tumors and the cultured murine pancreatic carcinoma cells revealed that atorvastatin inhibited prenylation in several key proteins, including Kras protein and its activities, and similar effect was observed in pancreatic carcinoma cells treated with farnesyltransferase inhibitor R115777. Microarray assay on the global gene expression profile demonstrated that a total of 132 genes were significantly modulated by atorvastatin; and Waf1p21, cyp51A1, and soluble epoxide hydrolase were crucial atorvastatin-targeted genes which involve in inflammation and carcinogenesis. This study indicates that atorvastatin has the potential to serve as a chemopreventive agent against pancreatic carcinogenesis.
Toxicity of hexavalent chromium to the alveolar macrophage in vivo and in vitro

Abstract In vivo and in vitro systems were used to evaluate hexavalent chromium toxicity to alveolar macrophages. Rat alveolar macrophages were exposed to 2 μg calcium chromate (CaCrO 4 , insoluble) or 2 μg chromium trioxide (CrO 3 , soluble) in live animals, in vivo , and in tissue culture, in vitro , collected by lavage from the lung. Chemiluminescence and oxygen consumption were measured as indicators of toxicity. Trypan blue dye exclusion was used to determine macrophage viability. In vivo exposure of the macrophage to either chromium compound showed no toxic effects at a 2-μg dose. Macrophages exposed in tissue culture, however, had values significantly different from controls. The untreated controls for both exposure methods were compared to evaluate differences resulting from methods alone.
SU‐GG‐J‐112: A Retrospective Single Institution Patient Population Study of I.G.R.T. Shifts and Their Implications for Non‐IGRT Treatment Set‐Up Margins, as Both an Internal and External Q.A. Tool

Purpose: To establish a population based set of margins from I.G.R.T. patients to account for set‐up uncertainties based on published formulas for use with non‐I.G.R.T. patients locally and potentially for QA purposes outside of our institution; as well as potentially identify any systematic errors in the patient treatment chain. Method and Materials: All kV and C.B.C.T. based I.G.R.T. patient's shifts were recorded over a 3+ year period and divided into general anatomy based categories. The set‐up uncertainty margin formula proposed by Van Herk et al of 2.5Σ +0.7σ was applied to each category. In addition, all averages and block check sessions were analyzed for systematic problems. Results: Thorax set‐up margins: 0.84 cm vertical, 1.21 cm Longitudinal, 0.89 cm Lateral; Pelvis: 0.94 cm vert., 0.87 cm long., 0.69 cm lat.; Abdomen: 0.94 cm vert., 1.3 cm long., 0.82 cm lat; Head/Neck: 0.34 cm vert., 0.49 cm long, 0.39 cm lat.; extremities: 0.62 cm vert, 0.69 cm long, 0.68 cm lat; and Spine: 1.10 cm vert., 1.25 cm long, 0.87 cm lat. Conclusion: Population based margins can be used as a portion of a total PTV margin formula when designing a treatment plan. If margins the size of those calculated would be clinically unacceptable, I.G.R.T. would be indicated and the patient set up uncertainty would be reduced to the uncertainty of the IGRT process only. Since this population of patients is large and represents a wide variety of diseases, it should also have Q.A. value to other institutions that either do not have I.G.R.T. or are just starting a program as a baseline with which to compare. Machine uncertainties, imaging uncertainties (mostly longitudinal), block edge/penumbra margins and other patient or case specific uncertainties should also be considered when designing margins.
Ratings and confirmation

We present a formalism which makes explicit and precise the confirming effect of multiple observers and repeated trials on composite ratings, considering the relevant subjective inputs.
A CAD approach to helical groove machining—I. mathematical model and model solution

The problem of helical groove machining in practice is still predominantly approached from an empirical trial and error standpoint. For the analytical resolution of this problem through a CAD approach, a generalized helical groove machining model, utilizing the principles of differential geometry and kinematics, has been formulated. The approach is based on the establishment of the fundamental analytical conditions of engagement between the generating tool surface and generated helical groove surface. The general mathematical relationships established facilitate the determination of the resulting tool or helical groove profile for a given helical groove or cutting tool profile, respectively.
Outsourcing, vertical integration, and price vs. quantity competition☆

Abstract We show that standard conclusions about duopoly competition can be reversed when the production of key inputs is outsourced to a vertically integrated retail competitor with upstream market power. Under such outsourcing, Bertrand competition can produce higher prices, higher industry profit, lower consumer surplus, and lower total surplus than Cournot competition. In addition to limiting the intensity of retail competition, Bertrand competition can limit the extent of wholesale competition by reducing the incentive of retail providers to produce key inputs themselves.
Patient-reported outcome measures for patients with cerebral aneurysms acquired via social media: data from a large nationwide sample

Background With greater survival rates, patientreported outcome measures (PROMs) among survivors of ruptured cerebral aneurysm should be an increasing concern among neurointerventionalists. Prior studies were limited in scale and generalizability. Our study aims were to (1) evaluate the validity of cerebral aneurysm PROMs obtained from social media; (2) determine the persistence of PROMs over time; and (3) determine what PROMs still exist in those with no physical impairments. Methods By engaging national brain aneurysm support groups and using an online questionnaire modeled after the generic EQ-5D instrument, we asked respondents to classify their health in five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/ depression using a 3-point Likert scale. Results In 2 months we received 604 responses from 46 states in the USA. Our cohort of ruptured aneurysm respondents reported PROMs similar to previously published series. Over time, headache and anxiety improved while depression, level of exercise, and return to work remained unchanged. We found that memory worsened after 2 years. Among those without any physical impairment, rates of 20.6%, 14.9%, 12.6%, and 23% were seen for significant headaches, significant memory loss, significant depression, and sense of life being negatively affected, respectively. Conclusions Despite this novel study design, we obtained results comparable to prior studies. These results suggest that many patients with ruptured cerebral aneurysms, regardless of whether they are >2 years after the event and/or free of physical impairment, struggle with a poor quality of life. The latency, scale, and low cost of this study design may accelerate future cerebral aneurysm PROM research.
Transient axisymmetric motion of a floating cylinder

A linear theory is developed in the time domain for vertical motions of an axisymmetric cylinder floating in the free surface. The velocity potential is obtained numerically from a discretized boundary-integral-equation on the body surface, using a Galerkin method. The solution proceeds in time steps, but the coefficient matrix is identical at each step and can be inverted at the outset.Free-surface effects are absent in the limits of zero and infinite time. The added mass is determined in both cases for a broad range of cylinder depths. For a semi-infinite cylinder the added mass is obtained by extrapolation.An impulse-response function is used to describe the free-surface effects in the time domain. An oscillatory error observed for small cylinder depths is related to the irregular frequencies of the solution in the frequency domain. Fourier transforms of the impulse-response function are compared with direct computations of the damping and added-mass coefficients in the frequency domain. The impulse-response function is also used to compute the free motion of an unrestrained cylinder, following an initial displacement or acceleration.
Hypervariable Domain of Nonstructural Protein nsP3 of Venezuelan Equine Encephalitis Virus Determines Cell-Specific Mode of Virus Replication

Venezuelan equine encephalitis virus (VEEV) is one of the most pathogenic members of the Alphavirus genus in the Togaviridae family. This genus is divided into the Old World and New World alphaviruses, which demonstrate profound differences in pathogenesis, replication, and virus-host interactions. VEEV is a representative member of the New World alphaviruses. The biology of this virus is still insufficiently understood, particularly the function of its nonstructural proteins in RNA replication and modification of the intracellular environment. One of these nonstructural proteins, nsP3, contains a hypervariable domain (HVD), which demonstrates very low overall similarity between different alphaviruses, suggesting the possibility of its function in virus adaptation to different hosts and vectors. The results of our study demonstrate the following. (i) Phosphorylation of the VEEV nsP3-specific HVD does not play a critical role in virus replication in cells of vertebrate origin but is important for virus replication in mosquito cells. (ii) The VEEV HVD is not required for viral RNA replication in the highly permissive BHK-21 cell line. In fact, it can be either completely deleted or replaced by a heterologous protein sequence. These variants require only one or two additional adaptive mutations in nsP3 and/or nsP2 proteins to achieve an efficiently replicating phenotype. (iii) However, the carboxy-terminal repeat in the VEEV HVD is indispensable for VEEV replication in the cell lines other than BHK-21 and plays a critical role in formation of VEEV-specific cytoplasmic protein complexes. Natural VEEV variants retain at least one of the repeated elements in their nsP3 HVDs.
A client-based QoS approach using generalized extreme value theorem in multi-hop network environments

Client-side QoS monitoring allows mobile clients to participate in the service evaluation process. Through this approach, mobile clients play proactive role to collect and measure network parameters (e.g., delay, bandwidth) and report any potential service degradation back to the service providers. Adopting this model provides a major enhancement to the service evaluation process by allowing service providers to tune their network resources for a better service performance. In this paper, we present a novel approach that evaluates service performance through collecting service measurements from mobile clients (MCs) in a multi-hop network environment. The proposed approach utilizes a System of Linear Equations (SLE) and Generalized Extreme Value Theorem (GEV) techniques to predict network link performance degradation by estimating the delay extremes on each hop of a given network topology. Consequently, service performance can be evaluated and improved through a continuous assessment process of the network's links behavior over time. Our experimental analysis indicates that our proposed approach provides better prediction of the link delays.
Information on the Internet: How selective should we be?

Vast amounts of information are available on the Internet, and programs such as Mosaic provide users with easy access to text and multimedia files. Once a user has set up a host system, consideration must be given to what information will be made available. In addition to legal restrictions, the interests of potential users (those accessing the host system) should be considered when determining the kinds of information to be made available. If those maintaining these host systems are somewhat selective when making information availability decisions, the potential information “glut” may be attenuated.
An Analysis of Direct Practice Social Work Perspectives and Behaviors in Middle Management

Social service organizations often promote social workers from direct practice to middle management positions or ask them to add administrative responsibilities to their existing roles to retain internal expertise, meet regulatory requirements, utilize them as clinical supervisors, and cultivate new leadership. The literature identifies problems with the transition and with social workers relinquishing their clinical identities and behaviors to adopt administrative ones. This article compares clinical and middle management perspectives and practices, illustrates how employing direct practice perspectives and behaviors can undermine middle management responsibilities, and offers theoretically grounded propositions to improve the transition.
Gefitinib (Iressa) trials in non-small cell lung cancer

Gefitinib (Iressa) is a synthetic anilinoquinazoline capable of inhibiting the epidermal growth factor receptor tyrosine kinase in vitro at nanomolar concentrations. In phase I trials, gefitinib was well tolerated at doses above that required to induce antitumor effects in vitro. Notably, antitumor activity was observed in lung cancer patients. These findings resulted in the initiation of phase II trials employing gefitinib monotherapy in patients with recurrent non-small cell lung cancer (the so-called IDEAL trials). Study participants were randomized to 250 mg or 500 mg of gefitinib per day. Objective response rates between 10 and 20% were achieved with minimal host related toxicity (mainly acne like rash and mild diarrhea). Median survivals ranged between 6 and 8 months. Subsequently, phase III trials (the so-called INTACT trials) combined gefitinib and chemotherapy in chemonaive patients with advanced non-small cell lung cancer. These trials failed to demonstrate a survival advantage with the addition of gefitinib to standard platinum-based chemotherapy regimens. However, overall host related toxicities were not substantially worsened with the addition of gefitinib to chemotherapy. Further studies employing single agent gefitinib as well as regimens employing a different sequencing of chemotherapy and gefitinib are planned in recurrent and previously untreated lung cancer patients.
Qualitative and Quantitative Evaluation of Indirect Immuno- fluorescent H-2 Stain on Tissue Sections

We have utilized H-2 specific antisera from congenic resistant donor recipient combinations to localize H-2 antigens in tissue sections using the indirect immunofluorescent technique. H-2 specific immunofluorescence is observed in spleen, kidney, and liver sections: however, especially with liver sections, there are cases in which the expected specific stain is weak or absent. In addition to microscopic evaluation by eye, we have employed a microscope attached photometer; recordings from this instrument differentiate positive from control stained spleen sections.
Absolute Bioavailability of Phenytoin After 3‐Phosphoryloxymethyl Phenytoin Disodium (ACC‐9653)Administration to Humans

3-Phosphoryloxymethyl phenytoin disodium (ACC-9653) is a water-soluble investigational phenytoin (PHT) prodrug for parenteral administration. The objectives of this investigation were to determine the absolute bioavailability and free fraction of PHT after intravenous (i.v.) administration of ACC-9653. Twelve healthy male volunteers received PHT sodium (250 mg/5 ml; 229.95 mg free acid) and ACC-9653 (375 mg/5 ml; 232.87 mg free acid) i.v. in 30 min in a randomized, double-blind cross-over fashion. The conversion half-life (t 1/2) of ACC-9653 to PHT was 9.3 +/- 2.7 min. ACC-9653 was not detected in urine and greater than 99% of ACC-9653 was converted to PHT. The PHT area under the curve (AUC) was not statistically different between treatments; the bioavailability of PHT after ACC-9653 was 99 +/- 11%. The fraction of unbound converted PHT at the end of the prodrug infusion, in the presence of 44 micrograms/ml ACC-9653, was significantly higher than at 180 min, when the concentration of ACC-9653 was 0.1 microgram/ml. ACC-9653 was shown to be a bioequivalent PHT prodrug exhibiting less irritation at the injection site than the current marketed PHT.
Suppression of FVIII inhibitor formation in hemophilic mice by delivery of transgene modified apoptotic fibroblasts.

The development of inhibitory antibodies to factor VIII (FVIII) is currently the most significant complication of FVIII replacement therapy in the management of patients with severe hemophilia A. Immune tolerance protocols for the eradication of inhibitors require daily delivery of intravenous FVIII for at least 6 months and are unsuccessful in 20–40% of treated patients. We hypothesize that tolerance can be induced more efficiently and reliably by delivery of FVIII antigen within autologous apoptotic cells (ACs). In this study, we demonstrated suppression of the T cell and inhibitor responses to FVIII by infusion of FVIII expression vector modified apoptotic syngeneic fibroblasts in both naive and preimmunized hemophilia A mice. ACs without FVIII antigen exerted modest generalized immune suppression mediated by anti-inflammatory signals. However, FVIII expressing apoptotic syngeneic fibroblasts produced much stronger antigen-specific immune suppression. Mice treated with these fibroblasts generated CD4+ T cells that suppressed the immune response to FVIII after adoptive transfer into naive recipients and antigen-specific CD4+CD25+ regulatory T cells (Tregs) that inhibited the proliferation of FVIII responsive effector T cells in vitro. These preclinical results demonstrate the potential for using FVIII vector modified autologous ACs to treat high-titer inhibitors in patients with hemophilia A.
Multi-cathode unbalanced magnetron sputtering systems

Ion bombardment of a growing film during deposition is necessary in many instances to ensure a fully dense coating, particularly for hard coatings. Until the recent advent of unbalanced magnetron (UBM) cathodes, reactive sputtering had not been able to achieve the same degree of ion bombardment as other physical vapor deposition processes. The amount of ion bombardment of the substrate depends on the plasma density at the substrate, and in a UBM system the amount of bombardment will depend on the degree of unbalance of the cathode. In multi-cathode systems, the magnetic fields between the cathodes must be linked to confine the fast electrons that collide with the gas atoms. Any break in this linkage results in electrons being lost and a low plasma density. Modeling of the magnetic fields in a UBM cathode using a finite element analysis program has provided great insight into the interaction between the magnetic fields in multi-cathode systems. Large multi-cathode systems will require very strong magnets or many cathodes in order to maintain the magnetic field strength needed to achieve a high plasma density. Electromagnets offer the possibility of independent control of the plasma density. Such a system would be a large-scale version of an ion beam enhanced deposition (IBED) system, but, for the UBM system where the plasma would completely surround the substrate, the acronym IBED might now stand for Ion Blanket Enhanced Deposition.
Induction of a protective immune response in rats by injection of live or killed S. mansoni worms.

Summary Resistance to S. mansoni cercarial challenge, induced by prior infection of rats with cercariae, is analysed by substitution of alternatives to the primary cercarial exposure. Intravenous injections of either live or killed 4-week stage worms have been examined, utilizing two different routes of injection, one or two injected doses, and two different methods to kill worms. In addition to assessing peripheral blood eosinophil levels, anti-schistosome antibody titres, and challenge worm burdens in the injected and control recipients, sera from these rat groups collected 3 weeks after challenge were used for passive immunization studies in rats. Recipients of intravenous live worm injections were resistant to a cercarial challenge and yielded sera capable of passively immunizing rats. Recipients of intravenous killed worm injections were not significantly resistant to a challenge infection, yet paradoxically, yielded sera capable of passively immunizing rats. Serum from challenge control rats was not significantly protective in the passive immunization assay. There were no correlations between peripheral blood eosinophil levels or anti-schistosome antibody titres and resistance (either active or passive). We conclude that killed worms induce an immune response which, although insufficient to provide protection by itself, can be recalled or augmented by a challenge infection to result in significant levels of serum protective activity.
Pyruvate kinase isoenzymes in progressive muscular dystrophy and in acute myocardial infarction

Abstract The activity of pyruvate kinase was measured in serum from patients with muscular dystrophy, other muscle diseases, acute myocardial infarction and hepatitis. In Duchenne and limb-girdle type dystrophy, activity was elevated 28-fold; elevations were found even when serum aldolase and CPK activities were not elevated. In the late stages of progressive muscular dystrophy, the activity tended to diminish, but remained elevated. In acute myocardial infarction, the activity rose within the first 2 days. The duration and magnitude of this rise (average sevenfold) were similar to those of the SGOT rise. Hepatitis patients who exhibited high levels of SGOT and LDH showed much smaller changes in pyruvate kinase activity. Pyruvate kinase from liver could be differentiated from the isoenzyme present in myocardial and skeletal muscle by appropriate alterations in assay conditions.
Computationally Focusing the Directed Evolution of Proteins

Directed evolution has proven to be a successful strategy for the modification of enzyme properties. To date, the preferred experimental procedure has been to apply mutations or crossovers randomly throughout the gene. With the emergence of powerful computational methods, it has become possible to develop focused combinatorial searches, guided by computer algorithms. Here, we describe several computational methods that have emerged to aid the optimization of mutant libraries, the targeting of specific residues for mutagenesis, and the design of recombination experiments.
Collection and analysis of multi-modal airport land side probe data from Bluetooth enabled mobile devices

The landside arrival experience of passengers begins on the approaching highways and transitions to a variety of other modes such as shuttle buses and walking. Probe data from mobile phones provides an important data source for collecting system performance data that can be used as feedback to improve the management of the various transportation and queuing systems used by airport travelers. This paper reports on a study using Bluetooth sensors to quantitatively evaluate the operations of airport security checkpoints. Bluetooth sensors were deployed at George Bush Intercontinental Airport from 30 August to 13 September, 2010 and collected over 100,000 travel time records between data collection stations located along access roads, parking garages, non-sterile areas of terminals, and sterile areas of terminals. In addition, hourly checkpoint passenger volumes were collected. The large volume of this data necessitated the development of statistical characterization procedures and graphics that characterize both the travel time records and checkpoint information. These checkpoint operations reports provide dashboard level reports useful for management to rapidly assess operations, and identify opportunities for improved allocation of staffing. The paper concludes by providing examples of how the checkpoint operations report concept can be extended to characterize the movement of traffic through the airport, the entire passenger arrival experience, and numerically characterize user delay in person-hours. A final overview procedure using pareto sorting to identify correctable periods where airports have opportunity to improve their utilization is shown.
Charge transfer goes the distance

The strong covalent and ionic bonds that hold molecules together form through the sharing or transfer of electrons among the constituent atoms. The dynamics of the making and breaking of chemical bonds on the natural time scale of molecular vibrations (femtoseconds) can be followed by exciting the valence electrons in molecules with ultrafast pulses from lasers operating in the near-infrared, visible, and near-ultraviolet ( 1 – 3 ). However, valence electrons tend to be delocalized within molecules, so it is difficult to obtain site-specific information about bonding in this way. Ultrafast extreme ultraviolet and x-ray sources ( 4 , 5 ), as well as complementary ultrafast sources of electrons, now provide access to the more localized inner-shell electrons of selected atoms ( 6 – 8 ). As reported on page 288 of this issue, Erk et al. ( 9 ) have determined the distance at which electron or charge transfer between the fragments of a dissociating molecule becomes negligible by using a combination of ultrafast x-ray pulses, an ultrafast near-infrared laser, and a high-resolution ion-imaging spectrometer.
Expression of TMEM16 paralogs during murine embryogenesis.

The TMEM16 protein family has recently been identified through several different experimental strategies including bioinformatic and microarray-based approaches. In mice and humans, there exist 10 paralogs with each containing eight putative transmembrane domains and a conserved C-terminal domain of unknown function. Mutation of at least one member of this family is associated with a human disorder, and several members of this gene family are overexpressed in different types of cancer. Despite their apparent relevance to normal development and disease, little is known about the expression of TMEM16 paralogs during embryonic development. Here, we provide a phylogenetic analysis of mouse and human TMEM16 paralogs and report the expression of Tmem16a, Tmem16b, Tmem16c, Tmem16f, Tmem16h, Tmem16j, and Tmem16k during murine embryogenesis with an emphasis on the respiratory, digestive, skeletal, and integumentary systems. These data should encourage investigations into the functions of TMEM16 paralogs in vertebrate development. Developmental Dynamics 237:2566–2574, 2008. © 2008 Wiley-Liss, Inc.
Kinetocardiographic findings of myocardial infarction.

A study of the precordial pulsations (kinetocardiograms) in patients with acute myocardial infarctions is presented. A paradoxic pulsation (bulge) over either the precordium or the epigastric area was noted in all patients studied.
Systematic desensitization, therapeutically oriented instructions and selective positive reinforcement

Abstract The relative contributions of therapeutically oriented instructions and selective positive verbal reinforcement to systematic desensitization therapy were investigated. Thirty-two female college students with marked fear of snakes were divided into four treatment groups. All Ss were given systematic desensitization therapy. In addition, Group 1 was given therapeutic instructions and praise; Group 2 was given instructions but no praise; Group 3 was given no therapeutic instructions but was given praise; and Group 4 was given neither instructions nor praise. All four groups improved significantly in their ability to approach the snake; however, an analysis of variance for a factorial design indicated that only instructions had a significant effect; the reinforcement and interaction factors were not significant.
TGF‐β1‐induced Smad 3 binding to the Smad 7 gene: Knockout of Smad 7 gene transcription by sense phosphorothioate oligos, autoregulation, and effect on TGF‐β1 secretion: Bleomycin acts through TGF‐β1

Bleomycin produces its fibrogenic effect, at least in part, by TGF-beta1 secretion. Treatment of IMR-90 human embryonic lung fibroblasts with bleomycin at 0.5 microg/ml results in a 1.6-fold increase of TGF-beta1 as determined by a specific ELISA assay for TGF-beta1 after acidification of the conditioned media. This elevation of TGF-beta1 secretion is furthermore enhanced in vivo by TGF-beta1 autoinduction of the TGF-beta1 gene. To demonstrate TGF-beta1 autoinduction, the fibroblasts were pretreated with 12.5 ng/ml TGF-beta1, washed extensively to remove any residual TGF-beta1, and then allowed to incubate for 24 h in AIM V synthetic serum-free media. The media when assayed using the ELISA assay contained a 1.6-fold increase of TGF-beta1. The distal promoter of the human TGF-beta1 gene contains a Smad 3 element (CAGGACA), which is homologous to the Smad 3 binding element motif (CAGA). The nuclear extracts of human embryonic lung fibroblasts treated for either 15 min or 24 h with TGF-beta1 did not demonstrate specificity of binding of a protein(s) to the homologous Smad 3 element as determined by cold wild-type oligodeoxynucleotide competition experiments. However, specific Smad 3 binding to the Smad 3 element (GTCTAGAC) found in proximal promoter of the Smad 7 gene was observed by cold oligo competition and supershift assays using a goat polyclonal Smad 3 antibody in the presence and absence of an N-terminal Smad 3 peptide. To determine the functionality of this Smad 3 binding to the Smad 3 element in the proximal promoter of the Smad 7 inhibitory gene to TGF-beta1 secretion, fibroblasts were transiently pretransfected with double-stranded phosphorothioate oligo "decoys" containing the Smad 7/Smad 3 element in the presence of plasmin to convert latent TGF-beta1 to active TGF-beta1. Under these conditions, which simulate the in vivo situation of 2.2-fold increase of total active TGF-beta1 was observed. Fibroblasts were also pretransfected with these double-stranded oligo "decoys," washed, then treated with TGF-beta1, washed and incubated in AIM V for an additional 24 h. In this latter experiment, a superinduction of TGF-beta1 secretion was observed. We propose that these oligo "decoys" bind Smad 3 preventing this initiation factor from binding to the Smad 7/Smad 3 element thereby decreasing the transcription of the Smad 7 gene. The decrease of the inhibitory Smad 7 would result in less binding of this Smad inhibitor to the Type I TGF-beta receptor and less antagonism of active TGF-beta1, more autoinduction of the TGF-beta1 gene, and more of the fibrogenic effects of TGF-beta1.
Mothers' reactions to prenatal diagnostic procedures and dexamethasone treatment of congenital adrenal hyperplasia

A retrospective survey of mothers' attitudes toward and experiences of chorionic villus sampling, amniocentesis and dexamethasone (DEX) treatment was conducted in 38 women who underwent a prenatal diagnostic procedure for congenital adrenal hyperplasia because of a previously affected child (n = 37) or because the mother herself was affected (n = 1). Both diagnostic procedures were well tolerated and almost every woman said that the anxiety or discomfort associated with the procedure was far outweighed by the value of knowing whether or not her fetus was affected. The earlier diagnostic information provided by chorionic villus sampling was highly valued. Maternal side-effects of DEX were common (75%) and more than one-third of the women rated one or more side-effects as "severe' (weight gain, fatigue, stomach pain, irritability, facial hair growth). Many women expressed anxiety about possible short- and long-term side-effects of DEX on their unborn children and themselves but all said they would undergo DEX treatment again to prevent virilization.