cssi/SciSciGPT-SciSciNet huggingface dataset:
Evaluation of the Effect of Proton Pump Inhibitors on the Efficacy of Dacomitinib and Gefitinib in Patients with Advanced Non-Small Cell Lung Cancer and EGFR-Activating Mutations.

Dacomitinib and gefitinib are irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) indicated for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Pharmacokinetic (PK) studies in healthy volunteers suggested that acid-reducing drugs such as proton pump inhibitors (PPI) decreased dacomitinib and gefitinib exposure by limiting the pH-dependent absorption. This analysis retrospectively evaluates the effect of concomitant PPI use on dacomitinib exposure and on progression-free survival (PFS) and overall survival (OS) in patients treated with dacomitinib 45 mg QD or gefitinib 250 mg QD in a 1:1 randomized phase 3 study (ARCHER 1050). The analysis grouped all patients (n = 452) treated in each arm of the study as non-PPI users, PPI users, or extensive PPI users. PFS and OS data were presented by Kaplan–Meier plots and analyzed using Cox proportional hazards models. Dacomitinib exposure was compared using a linear mixed-effects model. Results showed that dacomitinib PFS and OS did not differ significantly when comparing PPI users (N = 59) to non-PPI users (N = 152), while extensive PPI users (N = 24) had shorter PFS [hazard ratio (HR): 1.94, p = 0.011] and OS (HR: 1.77, p = 0.027) when compared to non-PPI users. For patients treated with gefitinib, PFS did not differ significantly when comparing PPI users (N = 51) and extensive PPI users (N = 19) to non-PPI users (N = 159); however, both PPI users (HR: 1.65, p = 0.007) and extensive PPI users (HR: 1.70, p = 0.050) had shorter OS when compared to non-PPI users. Further analysis by adjusting potential confounders indicated no statistically significant differences in PFS or OS between any PPI user vs. non-PPI user groups in the dacomitinib and gefitinib arms. PPI use did not appear to affect dacomitinib exposure. In conclusion, PPI use in patients with NSCLC likely has minimal impact on dacomitinib or gefitinib efficacy despite decreased absorption of these drugs observed in PK studies. ClinicalTrials.gov identifier, NCT01774721
Atmospheric Pressure Radio Frequency Glow Discharges in Argon: Effects of External Matching Circuit Parameters

Numerical simulations of radio frequency atmospheric pressure argon glow discharges were performed using a one-dimensional hybrid model. The discharge simulations were carried out for a parallel plate electrode configuration with an inter-electrode gap of 1.0 mm together with an external matching circuit. The external matching circuit parameters were found to have significant effect on the discharge characteristics. The results indicate that the discharge can operate at either the α or γ mode depending on the matching circuit parameters. The two modes of operation were found to be distinctly different. The predicted Ar∗ density was considered to provide qualitatively the visual appearance of the α or γ mode discharge. The α mode was found to have a luminous region in the center of the discharge. On the other hand, the γ mode had luminous regions very close to the electrodes which were followed by alternating dark and bright regions. The appearance of the simulated γ mode was found to resemble that of an atmospheric pressure direct current glow discharge. The predicted gas temperature indicated the γ mode to have higher gas temperature compared with the α mode.
Beyond Versus: The Struggle to Understand the Interaction of Nature and Nurture

If everyone now agrees that human traits arise not from nature or nurture but from the interaction of nature and nurture, why does the "nature versus nurture" debate persist? In Beyond Versus, James Tabery argues that the persistence stems from a century-long struggle to understand the interaction of nature and nurture -- a struggle to define what the interaction of nature and nurture is, how it should be investigated, and what counts as evidence for it. Tabery examines past episodes in the nature versus nurture debates, offers a contemporary philosophical perspective on them, and considers the future of research on the interaction of nature and nurture. From the eugenics controversy of the 1930s and the race and IQ controversy of the 1970s to the twenty-first-century debate over the causes of depression, Tabery argues, the polarization in these discussions can be attributed to what he calls an "explanatory divide" -- a disagreement over how explanation works in science, which in turn has created two very different concepts of interaction. Drawing on recent developments in the philosophy of science, Tabery offers a way to bridge this explanatory divide and these different concepts integratively. Looking to the future, Tabery evaluates the ethical issues that surround genetic testing for genes implicated in interactions of nature and nurture, pointing to what the future does (and does not) hold for a science that continues to make headlines and raise controversy.
Corneal development. V. Treatment of five-day-old embryos of domestic fowl with 6-diazo-5-oxo-L-norleucine (DON).

Abstract The embryogenesis of the corneal stroma of the domestic fowl was studied following the injection of the glutamine analog DON (6-diazo-5-oxo- l -norleucine) into the chorioallantoic veins of 5-day-old chick embryos. The 44 survivors were cilled between 1 hr and 13 days following injection. Their corneas were examined histologically and compared with those of untreated animals of similar age. All of the experimentally-treated corneas examined developed abnormally. The defects included: a temporary disappearance of portions of the endothelium; the deposition of disordered arrays of collagen fibers beneath the corneal epithelium, including a reversal in the direction of rotation of the axes of affected portions of the stromal lamellae; the appearance of stromal cysts; and the accumulation, beginning 6 days after injection, of pools of Gomori-silver-positive material within the epithelium. Abnormalities in corneal development following treatment with DON were compared with those previously obtained following administration of l -azetidine-2-carboxylic acid. The findings demonstrated that: (1) the characteristic, progressive rotation of fibril orientation which normally occurs in the outer lamellae of the avian, corneal, primary stroma is not a rigidly-determined configuration since its direction can be reversed consistently following treatment with DON; and (2) the primary stroma dictates the collagenous structure of the secondary stroma deposited within it.
Casu an consulto? Evolutio atque epistemologia in recenti philosophia religionis tractata

El autor, empenado desde hace algun tiempo en recuperar la ensenanza de la filosofia en Latin, pone frente a frente en este estudio la teoria evolucionista de Darwin y la �quinta via� tomistica. Ello es ocasion para unas disquisiciones sobre la finalidad teleologica del mundo, la admiracion aristotelica como principio del filosofar, y la verosimilitud.
Rich Morphology Generation Using Statistical Machine Translation

We present an approach for generation of morphologically rich languages using statistical machine translation. Given a sequence of lemmas and any subset of morphological features, we produce the inflected word forms. Testing on Arabic, a morphologically rich language, our models can reach 92.1% accuracy starting only with lemmas, and 98.9% accuracy if all the gold features are provided.
Applications of Fourier transform infrared spectroscopy to quality control of the epoxy matrix

The object of the paper is to demonstrate the utility of Fourier transform infrared (FT-IR) difference spectra for investigating the composition of a neat epoxy resin, hardener, and catalysts. The composition and degree of cross-linking of the cured matrix is also considered.
Measuring Onset of Antidepressant Action in Clinical Trials: An Overview of Definitions and Methodology

This article discusses 4 critical questions that must be addressed in any valid analysis of comparative onset of therapeutic effect among antidepressant drugs: (1) how is onset defined, (2) how is onset measured, (3) how can the treatment groups be compared statistically with regard to onset of effect, and (4) how do these issues affect protocol design? A rigorous study of differential onset of effect should include an estimation of the portion of patients that respond, the timing of the onset of response, and the duration of response and an examination of the dynamic process of the onset of action. Methods for measuring symptom severity changes over time also will be reviewed.
Comparison of Indirect CsI/a:Si and Direct a: Se Digital Radiography

Purpose: To assess and quantify the image quality at two dose levels for an amorphous Silicon (a:Si) Cesium Iodide (CsI) flat panel system compared with a direct amorphous Selenium (a:Se) digital radiography system. Material and Methods: A contrast detectability test was performed employing the CDRAD-phantom at mAs-values leading to approximately equal phantom entrance doses of 41.4, 57.9, 75.1 and 120.8 µGy for the a:Se and 39.9, 58.4, 75.6 and 117.9 µGy for the CsI system. Images were presented to 4 independent observers. For quantitative comparison, the image quality figure (IQF) was calculated. Statistical analysis was performed using Pearson's correlation and the Wilcoxon test. A ROC-analysis was performed employing the TRG-phantom in a high- and a low-dose setting leading to entrance doses of 126.2 and 35 µGy for the direct, and 125.9 and 34.4 µGy for the indirect system. Statistical significance was evaluated using the Wilcoxon test Results: The flat panel a:Si digital system provided superior results compared with the a:Se drum digital system with respect to low-dose settings for CDRAD-phantom and ROC-analysis, ensuring a better image quality with respect to contrast and detail detectability. Higher-dose settings provided similar results for both systems. Conclusion: Image quality of a:Si flat panel digital radiography proved to be superior to a:Se drum digital radiography using low-dose settings. If the primary target is dose reduction indirect flat panel technology should be used.
Enzymatic release of a surface-adsorbed RGD therapeutic from a cleavable peptide anchor.

Means to attenuate this inflammatory response at the implantsite are of significant interest and currently include strategiesbased on surface morphology, chemical modification, or drugdelivery. This response is particularly evident at the site ofstent deployment, where the overproliferation of smoothmuscle cells can lead to restenosis—a re-narrowing of thelumen.
Phase control of a laser beam by supersonic gas jets

Active phase control of high power density lasers could be achieved by using gas jets with controllable optical density variations. Experiments have been carried out on a double jet system in which the effective optical density of one of the jets is made variable by using a simple mechanical control system. Interferometric data are used to study the structure of the jets and to measure the phase shifts. When operated with combinations of He and a He-Ar mixture, the phase shifts introduced into a HeNe laser beam range from pi to 3 pi. Photographs of the asymmetric far field diffraction patterns which result from passing a clean laser beam through the jets are presented and are shown to compare well with theoretical predictions. Additional far field photographs are used to show that good compensation is achieved when a simply distorted laser beam is passed through the jets.
The Role of Functional Imaging in Radiotherapy Planning and Management for Gynecologic Malignancies

In addition to allowing much greater technical precision, the modern era allows investigation of target physiology and it is the potential incorporation of physiologic information into the treatment-planning rubric that gives modern PET-CT its allure and promise. Although oncologic PET scanning has been clinically available for more than 10 years, it is only recently that sufficient investigative and retrospective data have become available to confidently assert that future radiotherapy treatment planning will include functional imaging as an obligatory dimension of clinical characterization for most gynecologic tumors. This article explores the role of functional imaging in radiotherapy planning and management of gynecologic malignancies.
Experimental Considerations for Determining the Damping Coefficients of Hard Coatings

This paper attempts to characterize the various methods that may be used in defining the vibration features of a plate dimensionally proportioned to represent a turbine compressor blade. The comparison is specifically devoted towards certain damping properties of a titanium plate coated with magnesium aluminate spinel (mag spinel). Two different coating thicknesses were tested: 0.13 mm (.005 in.) per side and 0.25 mm (.010 in.) per side [total thicknesses of 0.25 mm (.010 in.) and 0.51 mm (.020 in.)]. In order for the reader to appreciate the experimental variations possible in this undertaking, the writers define various tests performed. Dynamic ping tests were conducted on all specimens to determine their resonance frequencies. Laser vibrometry was used to determine the mode at each resonance frequency. Damping ratios were determined through the use of sine sweeps. It is important that damping characteristics be measured very precisely. Thus, in the approach using a sine sweep, one must make sure that the rate of sweep is sufficiently slow to evaluate the proper frequency response function. A discussion of the proper rate is provided. This project demonstrated that, in order to represent the basic damping properties of a coating, one must consider the rate of the dynamic load application. The usual method associated with the damping coefficient evaluation is referred to as the half-power method. The true value of the damping coefficient is directly associated with the rate of experimental power versus frequency.
Expression of osteopontin in the head process late in gastrulation in the rat

Osteopontin (OPN) is a secreted, glycosylated phosphoprotein. Previous studies have implicated OPN in calcification/decalcification and inflammation. We became interested in developmental expression of OPN because of our previous findings that suggest OPN may play a role in formation of new vascular layers after injury, and because of our observation of developmental regulation in vascular smooth muscle cells. While OPN was expressed at low levels in vessels, only late in development, examination of very early expression patterns revealed a surprising finding. OPN was expressed exclusively in the head process, on day 9.0, late in gastrulation in the rat. In vitro studies of vascular smooth muscle cells have previously demonstrated that OPN promotes cell adhesion and migration. It is suggested that OPN may promote migration of cells, during gastrulation, via integrins which may be present in the head process or overlying ectoderm. © 1995 Wiley-Liss, Inc.
Amino acid nitrogen in atmospheric aerosols: Occurrence, sources and photochemical modification

The presence of amino acids in atmospheric precipitation and aerosols has been noted for many years, yet relatively little is known about these or other nitrogen containing organic compounds in the atmosphere. Marine and continental rainwater analyses indicate that atmospheric aerosols, and subsequently atmospheric precipitation, may contain substantial levels of free and combined amino acids. The most likely source of amino N in the remote marine atmosphere appears to be the injection of proteinaceous material through the action of bursting bubbles at the sea-air interface or the long range transport from terrestrial sources. The capacity of these substrates to undergo photooxidation and photodegradation in the atmosphere to simpler species, such as ammonium ions, carboxylic acids, and for the S containing amino acids, oxidized forms of sulfur, has received little attention from atmospheric chemists. The photochemistry of covalently bound amino groups, particularly as found in peptides and amino acids, is discussed here with the purpose of summarizing what is known of their occurrence and their possible importance to atmospheric chemistry.
On The Edge Geodetic Number Of A Graph

Many graph-theoretic concepts have both vertex and edge versions. Examples are cut-vertex , cut-edge , vertex-integrity ( integrity ), edge-integrity , vertex coloring , edge coloring , and vertex-connectivity , edge-connectivity . Frank Harary et al. defined the geodetic number of a graph for vertices in [Chartrand, G., Harary, F. and Zhang, P. (2002). On the geodetic number of a graph. Networks , 39 , 1-6; Chartrand, G., Harary, F. and Zhang, P. (2000). Geodetic sets in graphs. Discussions Mathematicae Graph Theory , 20 , 129-138; Harary, F., Loukakis, E. and Tsours, C. (1993). The geodetic number of a graph. Mathl. Comput. Modelling , 17 (11), 89-93]. In this study we give a definition of the edge geodetic number for a graph and derive some results.
Multi-scale variation in spatial heterogeneity for microbial community structure in an eastern Virginia agricultural field.

To better understand the distribution of soil microbial communities at multiple spatial scales, a survey was conducted to examine the spatial organization of community structure in a wheat field in eastern Virginia (USA). Nearly 200 soil samples were collected at a variety of separation distances ranging from 2.5 cm to 11 m. Whole-community DNA was extracted from each sample, and community structure was compared using amplified fragment length polymorphism (AFLP) DNA fingerprinting. Relative similarity was calculated between each pair of samples and compared using geostatistical variogram analysis to study autocorrelation as a function of separation distance. Spatial autocorrelation was found at scales ranging from 30 cm to more than 6 m, depending on the sampling extent considered. In some locations, up to four different correlation length scales were detected. The presence of nested scales of variability suggests that the environmental factors regulating the development of the communities in this soil may operate at different scales. Kriging was used to generate maps of the spatial organization of communities across the plot, and the results demonstrated that bacterial distributions can be highly structured, even within a habitat that appears relatively homogeneous at the plot and field scale. Different subsets of the microbial community were distributed differently across the plot, and this is thought to be due to the variable response of individual populations to spatial heterogeneity associated with soil properties.
Tolerance of iohexol, iopamidol, and metrizamide in lumbar myelography.

Abstract Iohexol and iopamidol, two new nonionic contrast media, have been extensively studied in comparison with metrizamide for lumbar myelography. Review of the literature with statistical analysis indicates both agents are superior to metrizamide in terms of number of patients with adverse reactions (p
Effects of Hot Streaks on Adiabatic Effectiveness for a Film Cooled Turbine Vane

Turbine guide vanes in gas turbine engines are typically subjected to localized “hot streaks” emanating from the combustor. This experimental program examined how these hot streaks affect the film cooling performance for these vanes. Adiabatic effectiveness tests were conducted on the showerhead and suction side regions of the vane. Particular attention was placed on how to scale that adiabatic effectiveness data obtained with a hot streak to correctly predict the adiabatic effectiveness. Thermal field measurements were made to determine the temperature gradients for the hot streak near the wall. These experiments showed that the effect of the hot streak on the adiabatic effectiveness could be accounted for by using an “adjusted” mainstream temperature equal to the hot streak temperature at the wall of the vane.Copyright © 2004 by ASME
Silica Gel as a Preserving Agent for the Cellular Slime Mold Acrasis rosea

SYNOPSIS. Modifications of the silica gel technic of Perkins and Ogata have been successfully used to preserve Acrasis rosea for 6–13 months and Dictyostelium purpureum for 31 months. The technic is simple, reliable and inexpensive and is recommended for its possible application for the general preservation of certain fungi and protozoa.
An R2criterion based on optimal predictors

Abstract: The predictor that minimizes mean-squared prediction error is used to derive a goodness-of-fit measure that offers an asymptotically valid model selection criterion for a wide variety of regression models. In particular, a new goodness-of-fit criterion (cr2) is proposed for censored or otherwise limited dependent variables. The new goodness-of-fit measure is then applied to the analysis of duration.
Inverse maximum gross bedform-normal transport 2: Application to a dune field in Ganges Chasma, Mars and comparison with HiRISE repeat imagery and MRAMS

Abstract Inverse maximum gross bedform-normal transport (IMGBNT) analysis has been applied to Context Camera (CTX) images of the largest dune field in Ganges Chasma on Mars. The dune field was selected for its position in a likely complex, multi-directional wind regime. Results indicate that four main winds are responsible for simultaneous construction of the dune field, including along-chasma winds from the ESE, winds blowing down a nearby re-entrant from the NE, winds blowing down the adjacent chasma wall from the NW, and chasma floor winds from the SW. Each wind represents a transport vector that dominates dune morphology at its respective edge of the dune field, such that the central axis of the dune field reflects the convergence of the three most prominent winds (ESE, NW, and SW). The Mars Regional Atmospheric Modeling System (MRAMS) was run at twelve times throughout the martian year to provide context for the local wind patterns. Potential sand fluxes calculated from MRAMS output show that three major air flows from the ENE–E, NNE–NE, and NNW–N converge near the location of the dune field. These flows likely correspond to the ESE, NE, and NW winds identified from IMGBNT analysis, respectively. MRAMS output shows that the flows with major northerly components are produced by larger-scale Hadley return flow constructively combining with nighttime downslope winds; the flow with a major easterly component is likely produced by equatorial easterly “trade” winds constructively combining with the diurnal tide and/or local topography. Although the model correctly predicts the major elements of the local wind pattern, some aspects are either over- or underrepresented, demonstrating the value of using aeolian morphological analysis to conclusively constrain the major sand-moving winds on Mars. Overlapping High Resolution Imaging Experiment (HiRISE) images of barchanoid dunes at the northernmost edge of the dune field indicate that these dunes are currently migrating southward at ∼5 m/Mars year (∼2.6 m/Earth year); the direction of migration is consistent with both MRAMS predictions in this location and the NW/NE winds found from IMGBNT analysis. Dune morphology suggests that sand in the northwestern part of the dune field is likely to be derived from the adjacent chasma wall to the north and northwest, and sand in the southeastern part of the dune field was probably transported from farther east along the main chasma floor.
Estimating Heading During Real and Simulated Eye Movements

The ability to judge heading during tracking eye movements has recently been examined by several investigators. To assess the use of retinal-image and extra-retinal information in this task, the previous work has compared heading judgments with executed as opposed to simulated eye movements. For eye movement velocities greater than 1 deg/sec, observers seem to require the eye-velocity information provided by extra-retinal signals that accompany tracking eye movements. When those signals are not provided, such as with simulated eye movements, observers perceive their self-motion as curvilinear translation rather than the linear translation plus eye rotation being presented. The interpretation of the previous results is complicated, however, by the fact that the simulated eye movement condition may have created a conflict between two possible estimates of the heading: one based on extra-retinal solutions and the other based on retina-image solutions. In four experiments, we minimized this potential conflict by having observers judge heading in the presence of rotations consisting of mixtures of executed and simulated eye movements. The results showed that the heading is estimated more accurately when rotational flow is created by executed eye movements alone. In addition, the magnitude of errors in heading estimates is essentially proportional to the amount of rotational flow created by a simulated eye rotation (independent of the total magnitude of the rotational flow). The fact that error magnitude is proportional to the amount of simulated rotation suggests that the visual system attributes rotational flow unaccompanied by an eye movement to a displacement of the direction of translation in the direction of the simulated eye rotation.
Transplantation: The promise of co-stimulatory blockade in transplantation.

A new study by Lo et al. presents a novel immunosuppressive combination in a clinically relevant primate model of renal allografting. Using belatacept, a fusion protein that inhibits CD28–CD80/CD86 co-stimulation, plus the mammalian target of rapamycin inhibitor sirolimus, they were able to achieve rejection-free allograft survival without the induction of memory T cells or alloantibody.
Diagnostic validity of hospital discharge codes in the ascertainment of amyotrophic lateral sclerosis

In a recent publication, Pisa et al. [1] assessed the validity of hospital discharge data as a method of identifying cases of amyotrophic lateral sclerosis (ALS). After a review of hospital charts from 511 patients, they concluded that a discharge code for ALS had a sensitivity of 93% and a specificity of 99% for the diagnosis of ALS. A detailed exam of the study design, however, suggests that sensitivity and specificity could not be adequately estimated. Sensitivity of a diagnostic test can be defined as the probability that a diseased person in the population tested will be identified as diseased by the test [2]. In the study by Pisa et al., then, sensitivity should be calculated as the probability that a person with ALS in the population of study, probably the reference population for the hospital, had a hospital discharge code of ALS. Therefore, to estimate sensitivity, having an enumeration of all the true cases in the population is necessary. Unfortunately, Pisa et al. do not have this information, since no population-based registry of ALS cases was available. They could not calculate sensitivity (or specificity, for that matter). In fact, with their study design, the only measure of diagnostic accuracy properly calculated is the positive predictive value. To have an unbiased estimate of the negative predictive value, they should have selected a random sample of all hospital discharges, not only discharges with a selected group of diagnostic codes. References
Framing the Need for Active Management for Wildfire Mitigation and Forest Restoration

We present results of a Q-methodology study of how diverse stakeholders in northern Colorado framed the need for immediate, active management on federal lands to mitigate wildfire risk and restore forest conditions. From the factor analysis of the Q-sorts, three significant themes emerged that represent distinct perspectives about active management: (1) The region's forests are unhealthy and should be actively managed; (2) active management should comply with existing laws; and (3) in-depth studies and public subsidies are needed before making decisions. Because the need for active management is not universally shared at the local level, agencies should not assume that issue frames are shared. A process of negotiation, shared learning, and adaptation should be pursued to minimize stakeholder conflict and maximize collaborative opportunities.
Determining the Optimal Landfill Size: Is Bigger Always Better?

A model of landfill costs is developed that accounts for construction, operating, externality and political costs. Simulations based on the model suggest a few provisos to the conventional wisdom that disposing of larger volumes of waste in regional landfills is desirable on cost minimization grounds. In particular, the cost advantages stemming from increasing the size of the waste stream may be reversed by transport costs, increased political costs of siting regional facilities, or difficulties for potential host communities to recover political and externality costs from regional partners.
Laser-Clad NiAICrHf alloys with improved alumina scale retention

A new mechanism for the improved retention of alumina scales formed on laser-clad NiAICrHf alloys has been observed. Laser cladding is the process where fine metal powders are rapidly melted and fused to a solid substrate using a CO2 laser. The effects of laser cladding upon scale retention on NiAICrHf alloys after cyclic and isothermal exposure to air were investigated using thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The calculated compressive stress in the scale due to constrained cooling exceeded the probable compressive strength of alumina. Additions of up to ≈ 2.5 wt pct Hf increasingly promote retention of scales grown at 1200 °C, with laser-clad samples of ≈ 2.5 wt pct Hf alloy retaining almost completely intact scales. The improvement in scale retention is due to improved toughness in scales containing hafnia polycrystallites, possiblyvia microcracking initiated by anisotropic thermal contraction of the hafnia. Laser cladding the 2.5 wt pct Hf alloy provides a large concentration of ~ 1 µm Hf-rich particles that are precursors of the hafnia in the scale as well as a finer dendrite spacing that reduces the mean free distance between particles.
An initial map of insertion and deletion (INDEL) variation in the human genome

Although many studies have been conducted to identify single nucleotide polymorphisms (SNPs) in humans, few studies have been conducted to identify alternative forms of natural genetic variation, such as insertion and deletion (INDEL) polymorphisms. In this report, we describe an initial map of human INDEL variation that contains 415,436 unique INDEL polymorphisms. These INDELs were identified with a computational approach using DNA re-sequencing traces that originally were generated for SNP discovery projects. They range from 1 bp to 9989 bp in length and are split almost equally between insertions and deletions, relative to the chimpanzee genome sequence. Five major classes of INDELs were identified, including (1) insertions and deletions of single-base pairs, (2) monomeric base pair expansions, (3) multi-base pair expansions of 2–15 bp repeat units, (4) transposon insertions, and (5) INDELs containing random DNA sequences. Our INDELs are distributed throughout the human genome with an average density of one INDEL per 7.2 kb of DNA. Variation hotspots were identified with up to 48-fold regional increases in INDEL and/or SNP variation compared with the chromosomal averages for the same chromosomes. Over 148,000 INDELs (35.7%) were identified within known genes, and 5542 of these INDELs were located in the promoters and exons of genes, where gene function would be expected to be influenced the greatest. All INDELs in this study have been deposited into dbSNP and have been integrated into maps of human genetic variation that are available to the research community.
Chemical oxidation of the FMO antenna protein from Chlorobaculum tepidum.

Effect of chemical oxidation by ferricyanide on bacteriochlorophyll a (BChl a) in the Fenna–Matthews–Olson protein (FMO) was studied using absorbance and fluorescence spectroscopy at ambient and cryogenic temperatures. Partially selective oxidation of pigments bound to the antenna complex was achieved and the probable absorption wavelength corresponding to the recently discovered bacteriochlorophyll No. 8 of 806 nm was obtained by comparative analysis of the effect of chemical oxidation and the effect of different isolation procedures. Formation of a stable product identified as a chlorophyll a derivative occurred upon chemical oxidation. This new pigment remained bound within the pigment–protein complex, and exhibited an efficient energy transfer to BChl a. Furthermore, complex effects of the pigment oxidation upon the fluorescence yield of the FMO protein were observed. Utility of this approach based on chemical modifications for the investigation of the native regulatory mechanisms involved in the energy transfer in the FMO protein is discussed.
Efficient Operational Space Sensitivity Analysis of Dynamic Multibody Systems

This paper presents a generalization of the divide and conquer algorithm for sensitivity analysis of dynamic multibody systems based on direct differentiation. While similar sensitivity analysis approach has been demonstrated for multi-rigid and multi-flexible systems in tree topologies and a limited set of kinematically closed loop topologies, this paper presents the generalization of these approaches to systems in generalized topologies including many coupled kinematically closed loops. This generalization retains the efficient complexity of the underlying formulations i.e. linear and logarithmic complexity in serial and parallel implementation. Other than the computational efficiency, the advantages of this method include concurrent sensitivity analysis with forward dynamics, no numerical artifacts arising from parametric perturbation and significantly reduced data storage compared to traditional methods. An interesting application of this work in control of multibody systems is discussed.Copyright © 2011 by ASME
A case study of project management practices in virtual settings: lessons from working in and managing virtual teams

In this paper we report a case study examining the communication processes engaged in by virtual project teams and their management. Twenty-two teams, using widely available groupware to communicate, work together, share documents, discuss ideas, and solve problems, designed and implemented a database. These teams were managed by a geographically-distributed management team. The case study is analyzed qualitatively and quantitatively, from two perspectives--working in, and managing, virtual teams--using a framework that integrates virtual team dynamics and project management practices. Through the critical examination of communication content from the longitudinal experiences of multiple virtual project teams and their virtual management team, we identify successful project practices and uncover underlying interaction processes. Specifically, we found that high performing project teams differed from low performing teams in terms of process management, relational development, and proactive technology use behaviors. The five-person management team paralleled the project teams in evolving its own process management and relational development over time.
Energetics of coupled Na+ and Cl- entry into epithelial cells of bullfrog small intestine.

Abstract Na+, K+ and Cl− concentrations ( c j i ) and activities ( a j i ), and mucosal membrane potentials ( E m ) were measured in epithelial cells of isolated bullfrog (Rana catesbeiana) small intestine. Segments of intestine were stripped of their external muscle layers, and bathed (at 25°C and pH 7.2) in oxygenated Ringer solutions containing 105 mM Na+ and Cl− and 5.4 mM K+. Na+ and K+ concentrations were determined by atomic absorption spectrometry and Cl− concentrations by conductometric titration following extraction of the dried tissue with 0.1 M HNO3. 14C-labelled inulin was used to determine extracellular volume. E m was measured with conventional open tip microelectrodes, a Cl i with solid-state Cl−-selective silver microelectrodes and a Na i and a K i with Na+- and K+-selective liquid ion-exchanger microelectrodes. The average E m recorded was −34 mV. c Na i , c K i and c Cl i were 51, 105 and 52 mM. The corresponding values for a Na i , a K i and a Cl i were 18, 80 and 33 mM. These results suggest that a large fraction of the cytoplasmic Na+ is ‘bound’ or sequestered in an osmotically inactive form, that all, or virtually all the cytoplasmic K+ behaves as if in free solution, and that there is probably some binding of cytoplasmic Cl−. a Cl i significantly exceeds the level corresponding to electrochemical equilibrium across the mucosal and baso-lateral cell membranes. Earlier studies showed that coupled mucosal entry of Na+ and Cl− is implicated in intracellular Cl− accumulation in this tissue. This study permitted estimation of the steady-state transapical Na+ and Cl− electrochemical potential differences (ΔμNa and ΔμCl). ΔμNa (−7000 J · mol−1; cell minus mucosal medium) was energetically more than sufficient to account for ΔμCl (1000–2000 J · mol−1).
Short microwave pulses cause ultrastructural membrane damage in neuroblastoma cells

Investigations on the biological hazards of microwave radiation (MWR) have become necessary because of the increasing domestic and industrial use of microwave equipment and the need to establish meaningful and realistic safety standards. Ultrastructural changes in mouse neuroblastoma cells, grown in vitro and exposed to MWR and to heat, are reported. Cells were exposed to 1- μ sec pulses at 330 pulses/sec at field strengths from 1.7 to 3.9 kV/cm at 2.7 GHz. The most striking damage occurs in the form of breaks in the cell and mitochondrial membranes. Parts of the cell membrane are expelled and appear as membrane-bound sacs outside the cell surface. Cristae lose their normal pattern and form myelinated figures inside mitochondria. It is suggested that these effects may be of a nonthermal nature: (1) because cells exposed to heat alone at temperatures equivalent or considerably higher than the calculated temperature-rise in microwave exposed cells do not show similar changes, and (2) because of the differential heating, the membranes are expected to undergo thermal relaxation too rapidly to allow a significant temperature differential between the membranes and the surrounding material. The observed changes in the cell membrane may explain the increase in cell membrane permeability after MWR exposure.
The Strength of Electrical Synapses

Electrical synapses have a rich and sometimes controversial history. During the early 20th century, the question of whether chemical or electrical synapses underlie the main mode of signaling in the mammalian central nervous system (CNS) was hotly debated ( 1 ). However, after the discovery of neuronal inhibition in the early 1950s, it was accepted that transmission of information via neurotransmitter molecules (chemical synapses) represents the major form of signaling among CNS neurons. Although a consensus developed that electrical synapses are present in a subset of neuronal connections, it was unknown whether these synapses exhibit selectivity and plasticity as shown for most chemical synapses, or whether neuronal activity can result in long-term change of synaptic strength of electrical synapses ( 2 ) in the mammalian CNS. On page 389 of this issue, Haas et al. ( 3 ) demonstrate that the strength of electrical synapses among specific neurons in the thalamus of the mammalian brain affects long-term depression (LTD), a process important for learning and memory. Given the proposed role that electrical synapses play in synchronizing neuronal activity, these findings suggest a mechanism for controlling the coordination of neuronal activity.
Remote switching of cellular activity and cell signaling using light in conjunction with quantum dots

Stimulating cells by using light is a non-invasive technique that provides flexibility in probing different locations while minimizing unintended effects on the system. We propose a new way to make cells photosensitive without using genetic or chemical manipulation, which alters natural cells, in conjunction with Quantum Dots (QDs). Remote switching of cellular activity by optical QD excitation is demonstrated by integrating QDs with cells: CdTe QD films with prostate cancer (LnCap) cells, and CdSe QD films and probes with cortical neurons. Changes in membrane potential and ionic currents are recorded by using the patch-clamp method. Upon excitation, the ion channels in the cell membrane were activated, resulting in hyperpolarization or depolarization of the cell.
Nucleotide sequence of cDNA for nuclear encoded subunit Vb of mouse cytochrome-c oxidase.

Abstract We have used a polyclonal antibody probe to isolate cDNA clones for mouse cytochrome oxidase subunit Vb from a bone marrow tumor cell mRNA library in λgt11 expression vector. The mouse cDNA contains an open reading frame of 128 amino acids, which shows 81% positional identity with the predicted amino acid sequences of the human subunit. Northern blot analysis and sequencing of cDNA from a mouse kidney library show no tissue specific variations in subunit Vb.
Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and Delays Plaque Formation in Virus-Infected Cells

Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication.
LOCUS-SPECIFIC CONSERVATION OF THE HLA CLASS I INTRONS BY INTRA-LOCUS HOMOGENIZATION

The protein-coding sequences of the major histocompatibility complex (MHC) genes are characterized by extraordinarily high polymorphism, apparently maintained by balancing selection, which favors diversity in the peptide-binding domains of the MHC glycoproteins. Here we report that the introns flanking the polymorphic exons of the human MHC class I loci HLA-A, -B, and -C genes have been relatively conserved and have become locus-specific apparently as a result of recombination and subsequent genetic drift, leading to homogenization within loci over evolutionary time. Thus, HLA class I genes have been shaped by contrasting evolutionary forces maintaining polymorphism in the exons and leading to conservation in the introns. This study provides the first extensive analysis of the introns of a highly polymorphic gene family.
Electron backscattering diffraction investigation of focused ion beam surfaces

A focused ion beam (FIB) instrument has been used to mill surfaces in single-crystal Si and single-crystal Cu for subsequent electron backscattering diffraction (EBSD) analysis. The FIB cuts were performed using a 30 keV and a 5 keV Ga+ ion beam at a stage tilt of 20° to provide a readily obtainable 70° surface for direct EBSD investigation in a scanning electron microscope (SEM). The quality of the patterns is related to the amount of FIB damage induced in the Cu and Si. These or similar methods should be directly transferable to a FIB/SEM dual beam instrument equipped with an EBSD detector.
Presidents, Precedents, Provocation, and Prerogative--Are Geologists Scientists?: ABSTRACT

It is the prerogative, in fact the duty, of a president of a scientific society to break precedents, at the certain risk of provocation of society members. Utilization of the exploration geologist as a decision maker and representative of industry in the development of natural resources has led some geologists who search the earth's crust for enormously valuable fossil fuels and minerals to downgrade themselves as scientists. Because profit is involved, some academic colleagues and administrators assume that our application of geology is an impure utilization of pure scientific principles. Industrial administrators, clients, and geologists themselves have noted that obsolescence comes quickly to anyone whose scientific work becomes routine rather than an exciting adventure in continuous learning. To break this insidious syndrome of security, the exploration scientist must fight apathy, lethargy, and inertia. At every turn, it is the geologist with pride in his work who must reestablish the fact that he is a true scientist first, a professional second, and a dedicated member of his scientific associations third. The American Association of Petroleum Geologists, classed as a learned professional society, is also a business league made up of scientists. As such, all petroleum geologists and geophysicists can be willfully provocative, must break hampering precedents, and should assume their rightful prerogatives as pure scientists. We End_Page 661------------------------------ are neither professional sinners nor philosophical saints, but if we allow the development of professional unionism within our Association, our value as scientific, economic, and political decision makers in the search for, discovery, and production of our natural resources will be greatly impaired. Personal pride in profession is the outstanding characteristic of excellence among scientists. Are geologists scientists? I say emphatically, Yes! End_of_Article - Last_Page 662------------
Three dimensional analysis of longitudinal plasma oscillations in a thermal relativistic electron beam: Application to an initial value problem

In this paper, we study the initial value problem of longitudinal plasma oscillations in a relativistic electron beam. Our analysis is based on the formalism developed in Marinelli et al. [Phys. Plasmas 18, 103105 (2011)]. We study the evolution of an arbitrary six-dimensional phase-space perturbation under the effect of longitudinal space-charge forces, with the inclusion of three-dimensional effects due to the finite size of the beam, transverse betatron motion, and longitudinal thermal motion induced by both energy-spread and transverse emittance. We expand the phase-space perturbation in a series of eigenmodes of a Schrodinger-like equation, corresponding to a set of propagating space-charge waves. We develop a general formalism, which we use to find explicit expressions for the evolution of an initial perturbation coupled to the fundamental plasma eigenmode. This work has important applications in the theory of space-charge instabilities in high brightness electron beams and control of shot-noise in seeded free-electron lasers. We discuss the application of the present theory to a specific experimental scenario corresponding to a shot-noise suppression scheme at optical wavelengths.