cssi/SciSciGPT-SciSciNet huggingface dataset:
Use of the piggyBac transposon for germ-line transformation of insects

Germ-line transformation of insects is now possible with four independent transposable element vector systems. Among these, the TTAA-insertion site specific transposon, piggyBac, discovered in Trichoplusia ni, is one of the most widely used. Transformations have been achieved in a wide variety of dipterans, lepidopterans, and a coleopteran, and for many species, piggyBac transposition was first tested by plasmid-based mobility assays in cell lines and embryos. All plasmid and genomic insertions are consistent with the duplication of a TTAA insertion site, and most germ-line integrations appear to be stable, though this is largely based on stable marker phenotypes. Of the vector systems presently in use for non-drosophilids, piggyBac is the only one not currently associated with a superfamily of transposable elements, though other elements exist that share its TTAA insertion site specificity. While functional piggyBac elements have only been isolated from T. ni, nearly identical elements have been discovered in a dipteran species, Bactrocera dorsalis, and closely related elements exist in another moth species, Spodoptera frugiperda. It appears that piggyBac has recently traversed insect orders by horizontal transmission, possibly mediated by a baculovirus or other viral system. This interspecies movement has important implications for the practical use of piggyBac to create transgenic insect strains for field release.
The History of Myeloproliferative Disorders: Before and After Dameshek

In 1951, William Dameshek described the concept of 'myeloproliferative disorders (MPDs)' by grouping together chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and erythroleukemia; he reasoned that a self-perpetuating trilineage myeloproliferation underlined their pathogenesis. Pre-Dameshek luminaries who laid the foundation for this unifying concept include Bennett, Virchow, Heuck, Vaquez, Osler, Di Guglielmo and Epstein. In 1960, Nowell and Hungerford discovered the Philadelphia (Ph) chromosome in CML. In 1967, Fialkow and colleagues used X-linked polymorphisms to establish CML as a clonal stem cell disease. Also in 1967, the PV Study Group was summoned by Louis Wasserman to study the natural history of PV and conduct large-scale clinical trials. In 1972, Janet Rowley deciphered the Ph chromosome as a reciprocal translocation between chromosomes 9 and 22, thus paving the way for its subsequent characterization as an oncogenic BCR-ABL mutation. In 1996, Brian Druker discovered imatinib-a small molecule ABL inhibitor with exceptional therapeutic activity in CML. In 2005, a gain-of-function JAK2 mutation (JAK2V617F) was described in BCR-ABL-negative MPDs, raising the prospect of a CML-like treatment strategy in PV, ET and PMF. The current review considers these and other landmark events in the history of MPDs.
Accurate High-Resolution Measurements of 3-D Tissue Dynamics With Registration-Enhanced Displacement Encoded MRI

Displacement fields are important to analyze deformation, which is associated with functional and material tissue properties often used as indicators of health. Magnetic resonance imaging (MRI) techniques like DENSE and image registration methods like Hyperelastic Warping have been used to produce pixel-level deformation fields that are desirable in high-resolution analysis. However, DENSE can be complicated by challenges associated with image phase unwrapping, in particular offset determination. On the other hand, Hyperelastic Warping can be hampered by low local image contrast. The current work proposes a novel approach for measuring tissue displacement with both DENSE and Hyperelastic Warping, incorporating physically accurate displacements obtained by the latter to improve phase characterization in DENSE. The validity of the proposed technique is demonstrated using numerical and physical phantoms, and in vivo small animal cardiac MRI.
Remotely sensed estimates of surface salinity in the Chesapeake Bay: A statistical approach

Abstract In coastal and estuarine environments, near-surface salinity varies significantly in space and time. As absolute salinity and salinity gradients are central to many physical and ecological processes in these environments, reliable and consistent salinity estimates are a priority for marine research and application communities. Satellite remote sensing has a great potential to meet this need, yet sensors and algorithms designed to monitor open ocean salinity are typically ill-suited for high resolution applications to coastlines and estuaries. Here we present results of multiple statistical models that predict daily, gridded surface salinity at 1 km resolution across Chesapeake Bay as a function of level 2 surface reflectance estimates from the NASA Moderate Resolution Imaging Spectroradiometer (MODIS), onboard the Aqua platform. Eight statistical methods were tested and it was found that sea surface salinity can be accurately predicted via remote sensed products with an accuracy that is more than sufficient for many physical and ecological applications. For the best-performing statistical model, mean absolute error was 1.82 relative to mean Chesapeake Bay salinity of 16.5.
Microstructure and microsegregation in directionally solidified Mg–4Al alloy

Abstract Directional solidification (DS) of a binary Mg–4Al (wt.%) alloy was carried out to investigate the microstructures and microsegregation under controlled solidification conditions. In directional solidification the microstructure depends on the growth rate V because the cooling rate, which governs the solidification microstructure, is the product of the growth rate and the temperature gradient. The ability to produce simple and uniform microstructures in directional solidification enables us to correlate the formation of the microstructure and its characteristic length scales quantitatively with processing parameters. The morphology of the solid–liquid interface and the microstructure of both the mushy zone and the steady-state region were characterized at different levels of growth rates. With the help of an electron microprobe, microsegregation was determined in a specimen directionally solidified with cooling rates ranging from 0.06 to 0.8 K/s. The calculated microsegregation results based on the Scheil model deviated significantly from the experimental data, which is anticipated since back diffusion was not included due to the lack of diffusivity data.
SCIENCE AND VALUES: MY DEBT TO ERNAN McMULLIN

Abstract Ernan McMullin's 1982 presidential address to the Philosophy of Science Association dealt with the issue of science and values, arguing that although scientists are rightfully wary of the infiltration of cultural and social values, their work is guided by “epistemic values,” such as the drive for consistency and predictive fertility. McMullin argued that it is the pursuit of these epistemic values that drives nonepistemic values (like religious yearnings) from science. Using the case study of the fate of the nonepistemic value of progress in the history of evolutionary theorizing, I show that, vital though McMullin's thinking was for my own scholarship, in fact the study shows that the connections between epistemic and nonepistemic values in science are more complex than either of us supposed.
The Environmental, Social, and Health Dimensions of Urban Expansion

This article was originally written as the background paper for a cyberseminar held from 29 November–15 December 2004 under the auspices of Population-Environment Research Network or PERN a joint activity of the International Union for the Scientific Study of Population (IUSSP) and the International Human Dimensions Programme (IHDP) on Global Environmental Change. Originally posted online at the PERN website it has been revised and updated to take into account contributions of participants in the cyberseminar. The article focuses upon the environmental social and health dimensions of urban expansion. Our goal is to compare and contrast the processes of urban expansion and transformation in developing and developed countries. We expect a research agenda to emerge that will foster understanding of the processes contexts and outcomes of urbanization as well as the understanding that will ultimately contribute to policy solutions. Our article benefits from and hopefully will contribute to parallel projects being developed by IHDP Urbanization Science Project the IUSSP Urbanizations and Health Working Group the U.S. National Academies’ Panel on Urban Population Dynamics the U.S. National Academies’ Roundtable on Science and Technology for Sustainability’s Task Force on Rapid Urbanization The Millennium Ecosystem Assessment the World Bank’s Cities Alliance and Cities in Transition and other initiatives that recognize the importance of examining the urban transformation we are experiencing in a comprehensive integrated manner. (excerpt)
Fault-tolerant optimal routing of trust nodes in smart grid communications

The complex structure of the smart grid calls for a secure and reliable real-time communication network on top of the physical power system. The security of the smart grid communication system can be guaranteed by deploying the trust nodes to monitor the network traffic for malicious attacks. In order for trust nodes to function, an intelligent routing algorithm which is aware of the placement and status of trust nodes and can provide optimal routes at all times is needed. In this paper, we design and present such an algorithm. In addition, scenarios of searching for the optimal routes between the communicating nodes at different layers of smart grid network are illustrated in case of fault conditions, e.g., some trust nodes along the route fail to work. Simulation results show that the algorithm is promising by providing secure, efficient, and reliable communications in the smart grid network.
A LANT6-like substance that is distinct from neuromedin N is present in pallidal and striatal neurons in monkeys

The basal ganglia of rhesus and squirrel monkeys were examined using immunohistochemical techniques with antibodies against the neurotensin-related hexapeptides Lys8-Asn9-Neurotensin(8–13) (LANT6) and Neuromedin N. A high percentage of neurons in both segments of globus pallidus and many large neurons of the striatum were found to label for LANT6, but not Neuromedin N. Previous studies have shown that LANT6 or a LANT6-like substance is present in many pallidal neurons in a wide range of vertebrate species. The current results indicate that a LANT6-like substance that is distinct from Neuromedin N is also present in many pallidal neurons in primates. This raises the possibility that this substance may be involved in neurotransmission between the pallidum and its projection targets.
Cancer: More than kin and less than kind.

A gene that is found to be mutated in a type of blood cancer exhibits properties of both a growth-suppressing tumour suppressor and a growth-promoting oncogene.
A note on the Sobolev consistency of linear symmetric values

In van den Brink et al. (Soc Choice Welf 40:693–714, 2013) it is demonstrated that every \(\alpha \)-egalitarian value (Joosten in Dynamics, equilibria and values dissertation, Maastricht University, Maastricht, 1996) is consistent with respect to the well-known Sobolev reduced game function. However, the authors did not consider the question of whether or not these were the only Sobolev-consistent values. In this note we delineate, in the context of cooperative games with transferable utility and linear, symmetric and efficient values, the entire set of solutions that are consistent with respect to the Sobolev function.
Association with HSP90 Inhibits Cbl-Mediated Down-regulation of Mutant Epidermal Growth Factor Receptors

Activating mutations in the epidermal growth factor receptor (EGFR), localized in the activation loop within the kinase domain, have been discovered in non-small cell lung cancers (NSCLC). Most of these mutants are exquisitely sensitive to EGFR tyrosine kinase inhibitors, suggesting that they generate receptor dependence in the cancers that express them. 32D cells stably expressing EGFR-L861Q and EGFR-L858R but not wild-type EGFR exhibited ligand-independent receptor phosphorylation and viability. Ligand-induced receptor down-regulation (LIRD) was impaired in mutant-expressing cells. The EGFR mutants were constitutively associated with the E3 ubiquitin ligase Cbl but did not associate with the adaptor protein CIN85 on the addition of ligand. Inhibition of HSP90 activity with geldanamycin restored Cbl function as indicated by receptor ubiquitination and LIRD. These results suggest that EGFR mutants form defective endocytic complexes. In addition, HSP90 plays a role in maintaining the functional conformation of EGFR mutants and protecting activated receptors from LIRD.
High incidence of venous thromboembolic events in lung transplant recipients.

Background Previous studies have reported a 12% incidence of venous thromboembolic events (VTEs) in lung transplant recipients (LTRs). Characterization of risk factors for VTEs in LTRs is lacking. We identified the incidence and risk factors associated with post-transplant VTEs. Methods A retrospective review of 153 LTRs from 1994 to 2006 was performed. Patients were categorized by age, race, gender, weight, underlying diagnosis, procedure, ischemic time, length of stay (LOS), cardiopulmonary bypass (CPB), location and number of VTEs, mobility, immunosuppression, renal, hepatic, hematologic and coagulation profiles and nutritional status. Results A single VTE occurred in 29% of LTRs within the study period. Fifty-eight percent had multiple VTEs and 7% had a radiologically confirmed pulmonary embolism. Median time from transplant to first VTE was 69 days. Sixty percent of VTEs occurred within 1 year, 20% of which occurred within the first month, 19% between 2 and 5 years, and 13% at beyond 5 years post-transplant. Seventy-six percent of VTEs occurred during hospitalization, 19% during outpatient status. Forty-eight percent were of the upper extremity and 47% were of the lower extremity. Sixty-one percent of LTRs were taking cyclosporine and 39% tacrolimus. VTE and non-VTE groups were similar in age, weight, body mass index (BMI), ischemic time, procedure or underlying diagnosis precipitating the need for transplant. Univariate analysis revealed LOS and CPB as significant predictors of a single VTE ( p = 0.036, hazard ratio [HR] 1.006 and p = 0.045, HR 1.91, respectively). Multivariate analysis revealed only CPB as a significant predictor ( p = 0.047, HR 1.929). Conclusions Analysis of a cohort of LTRs for a median period of 1.5 years revealed a VTE incidence much higher than previously reported, especially within the first month after transplantation.
Longitudinal study of platelet indices during normal pregnancy

The purpose of this longitudinal, prospective study was to define platelet indices during normal pregnancy and to compare them to normal nonpregnant values. Indices evaluated included platelet count, mean platelet volume, and platelet distribution width. No significant change occurred in the mean platelet count or mean platelet volume from the second to the third trimester; however, platelet distribution width increased progressively and significantly during this interval (p less than 0.0001). Mean platelet volume versus platelet count showed a significant inverse relationship (p less than 0.0001) and was congruent with normal nonpregnant values. Mean platelet volume versus platelet distribution width exhibited a significant direct relationship (p less than 0.03) that differed remarkably from normal nonpregnant values. These data support the concept of normal pregnancy as a compensated state of progressive platelet consumption. These findings may have important diagnostic and prognostic applications in discerning acute states of platelet consumption superimposed on the compensated consumption of normal pregnancy.
Languages of the World: An Introduction

What do all human languages have in common and in what ways are they different? How can language be used to trace different peoples and their past? Assuming no prior knowledge of linguistics, the new edition of this engaging textbook introduces readers to the rich diversity of human languages, familiarizing students with the variety and typology of languages around the world. Linguistic terms and concepts are explained, in the text and in the glossary, and illustrated with simple, accessible examples. Numerous language family charts enable students to place a language geographically or genealogically. Updated and revised throughout, the second edition includes two new chapters and new pedagogical features, such as 'Advanced' sections, textboxes and 'Did you know?' boxes. Important websites are integrated into the text, and each chapter includes a 'Do it yourself' section, comprising assignments, questions and problem sets. Supplementary online resources include illustrations, key term flashcards and useful links. This introduction is an essential resource for undergraduate courses on language typology, historical linguistics and general linguistics.
Image based background magnetic field correction for aortic and pulmonary artery flow measurement using phase contrast

Methods Twelve volunteers underwent breath-hold through-plane phase contrast (PC) imaging of cross sectional view of the ascending aorta and PA. PC imaging was immediately repeated on a static fluid-filled phantom. Phase images were analyzed using QFlow (Medis, Leiden, Netherlands.). Phase shift was also analyzed in static background and in surrounding tissues including chest wall fat and muscle, lung and vertebral body. For PA flow Images only lung and static background were consistently present. Since background phase shift is linearly decreased from anterior to posterior, we calculated background phase shift at the aortic position using linear regression against distance of the aorta from anterior chest wall. Given the proximity of the aortic and PA in z direction the calculated aortic background phase was applied to the PA as well.
Central metabolism of β-endorphin in different species of temperature acclimated rodents

The purpose of this study was to characterize the central metabolism/processing of beta-endorphin in wild, desert rodents and to study the effect of heat and cold acclimation on central metabolism/processing and beta-endorphin half-life. This report suggests that a shift occurs in the processing of beta-endorphin in desert rodents acclimated to heat and cold leading to an accumulation of gamma-type endorphins. The data support a significant difference in beta-endorphin half-life between the rodents and the laboratory white rat.
Governance and Democracy: Public Policy in Modern America

Each stage of our national development has had a distinctive form of public policy. And each has faced a core tension between the dictates of governance and the constraints of democracy. Economic or social interests, and advantage-seeking politicians, forge policies. Countervailing interests, or changing times, or the limits of state capacity see to it that those policies rarely if ever live up to the expectations of their progenitors. But then no one ever said that the American polity, to say nothing of its democratic ideal, is a neat or orderly thing.
Indole diterpenoid synthetic studies. Construction of the heptacyclic core of (-)-nodulisporic acid D.

Construction of the heptacyclic core of (−)-nodulisporic acid D, a representative member of a recently discovered class of architecturally complex, ectoparasiticidal indole alkaloids, has been achieved. The modular synthetic strategy comprises an expedient, stereocontrolled synthesis of a tricyclic western hemisphere, in conjunction with union of an eastern hemisphere, exploiting the 2-substituted indole synthetic protocol introduced and developed in our laboratory.
Synthesis of [8,9-2H2]Apomorphine and [1,3,8,9-2H4]Apomorphine for PMR, 13C-NMR, and Mass Spectral Studies

Methods are described for the preparation of [8,9-2H2]-apomorphine and [1,3,8,9-2H4]apomorphine based on reaction of apomorphine in trifluoroacetic acid-d. The mass spectral properties of these compounds and of the O,O-bis(heptafluorobutyrate) ester and the O,O-bis(trimethylsilyl) and O,O-bis(tert-butyldimethylsilyl) ethers of apomorphine, using electron impact and chemical ionization, are reported. [1,3,8,9-2H4]Apomorphine was used to elaborate the 13C-NMR chemical shifts of the proton-bearing carbons of apomorphine.
Validation of an all-atom protein force field: From dipeptides to larger peptides

New experimental techniques are capable of determining the relative population of conformations adopted by short alanine peptides in water. Most of the existing all-atom force fields used to model proteins fail to reproduce the relative population of the most relevant conformations of peptides. The calculated relative population of conformations varies significantly depending on the force field chosen, thus urging the need to check the validity and consistency of force fields over a range of peptide lengths. Here, we show how the applicability of a modified version of AMBER force field (A94/MOD) can extend from short to large peptides. It is also capable of reproducing the expected shift in conformational preference with increasing peptide length and temperature. Importantly, the consistency of the force field is judged by direct comparison to experiments rather than to the relative energies of conformations obtained from ab initio calculations. Importantly, this study illustrates that many aspects of protein force fields are already well refined and may only require minor refinements to accurately reproduce experimental observations over a range of systems.
Effects of salinity on photosynthesis and respiration of the seagrass Zostera japonica: A comparison of two established populations in North America

a b s t r a c t Photosynthetic responses were quantified for two Zostera japonica Aschers. and Graebn. populations from the northern and southern limits of distribution exposed to a range of salinities along the Pacific Coast of North America. Plants were collected from Padilla Bay, Washington (northern) and Coos Bay, Oregon, USA (southern) and cultured together in experimental tanks at 3 salinities (5, 20 and 35) under saturating irradiance for 3 weeks. Subsequently, photosynthesis-irradiance (P vs. E curves) relationships for leaf segments from the two populations were assessed using an oxygen electrode system. We found no evidence for diel rhythms in either light saturated photosynthesis (Pmax) or dark respiration (Rd). For the Padilla Bay population, Pmax ranged from 192 to 390 mol O2 g DW −1 h −1 ; for the Coos Bay population Pmax ranged from 226 to 774 mol O2 g DW −1 h −1 . Photosynthetic maxima of the Coos Bay plants occurred at a salinity of 20, whereas salinity had no effect on the photosynthetic maxima of the Padilla Bay plants. There were significant differences in leaf tissue Rd among salinity treatments but the two populations responded similarly to salinity. North American populations of Z. japonica are best adapted to intermediate salinities, displaying minimum Rd rates, lower compensation irradiance, higher saturation irradiance, and greater Pmax rates at a salinity of 20. Additionally, the southern population may be better adapted to southward expansion along the Pacific Coast and changes associated with global climate change. Published by Elsevier B.V.
Examining verbal style in presidential campaign spots

Presidential candidates rely on political television spots to communicate their messages to voters, and the language used in spots conveys the verbal style of the candidate. This analysis of 1267 presidential spot units from 1952 through 1996 uses computerized content analysis to identify the presence of verbal style previously identified by Roderick Hart: optimism, realism, activity, and certainty. Findings show different patterns for different presidential candidates, but overall trends suggest that optimism, realism, and certainty has been decreasing. Differences in verbal style for political parties, incumbents and challengers, and winners and losers are also explored.
Surrogacy assessment using principal stratification with multivariate normal and Gaussian copula models

BackgroundThe validation of intermediate markers as surrogate markers (S) for the true outcome of interest (T) in clinical trials offers the possibility for trials to be run more quickly and cheaply by using the surrogate endpoint in place of the true endpoint.PurposeWorking within a principal stratification framework, we propose causal quantities to evaluate surrogacy using a Gaussian copula model for an ordinal surrogate and time-to-event final outcome. The methods are applied to data from four colorectal cancer clinical trials, where S is tumor response and T is overall survival.MethodsFor the Gaussian copula model, a Bayesian estimation strategy is used and, as some parameters are not identifiable from the data, we explore the use of informative priors that are consistent with reasonable assumptions in the surrogate marker setting to aid in estimation.ResultsWhile there is some bias in the estimation of the surrogacy quantities of interest, the estimation procedure does reasonably well at distinguishi...
Fracture of fiber glass laminates

The applicability of fracture mechanics to the description of initial notch extension under tension in quasi-isotropic fiberglass laminates is tested experimentally. It is found that classical elastic fracture mechanics, without modifications of couple stress effects, as represented in the theory of Muki and Sternberg, is sufficient to describe initial notch extension in prenotched specimens which are sufficiently thick to avoid transplanar bucklings of the specimen under tension. The fracture toughness (KIC) is found to be 15 ksi √in. However, it is noted that in these specimens (0.035 in. thick) transplanar postbuckling deformation becomes pronounced well before fracture, and that different modes of buckling seen in externally notched and internally notched specimens have opposite effects on the apparent fracture toughness of the specimen. It is pointed out that the effect of transplanar buckling on fracture of fiber glass, with its high compliance and high strength, is a potential source of serious problems in design with this material.
Postoperative perineal hernia.

Eight patients (seven male and one female) with symptomatic postoperative perineal hernias treated at the Cleveland Clinic Foundation from 1975 to 1986 are reviewed. The patients ranged in age from 43 to 68 years (mean, 61 years). Seven had previous abdominoperineal resections of the rectum and one had a pelvic exenteration. The first two patients underwent repair via a perineal approach and both had recurrences of their hernias. These recurrences, as well as the presenting hernias in the six later patients, were repaired with mesh placed through an abdominal approach. Of these, there was one recurrence, which was repaired via an abdominal approach. There was no operative mortality. Based on experience, the authors believe that the best method of repair for this uncommon problem, involves placement of Marlex® mesh across the pelvic inlet through an abdominal approach. This allows attachment to the mesh to the lateral musculature and posterior sacral periosteum under direct vision. The anterior borders of the mesh can be secured to the apex of the vaginal or prostatic tissue. The placement of metallic clips to the edges of the mesh allows for confirmation of the mesh position by radiographic examination during follow-up.
Repeated epitaxial growth and transfer of arrays of patterned, vertically aligned, crystalline Si wires from a single Si(111) substrate

Multiple arrays of Si wires were sequentially grown and transferred into a flexible polymer film from a single Si(111) wafer. After growth from a patterned, oxide-coated substrate, the wires were embedded in a polymer and then mechanically separated from the substrate, preserving the array structure in the film. The wire stubs that remained were selectively etched from the Si(111) surface to regenerate the patterned substrate. Then the growth catalyst was electrodeposited into the holes in the patterned oxide. Cycling through this set of steps allowed regrowth and polymer film transfer of several wire arrays from a single Si wafer.
Prevention of “irreversible” hemorrhagic shock by the preservation of cellular integrity

The clinically encountered state of hypovolemic shock results from a series of metabolic and cardiovascular responses to tissue hypoperfusion. Recent advances have increased our understanding of the consequences of tissue hypoxia, and identified at the cellular level those changes which cause the damage to be "irreversible", or refractory to treatment. To be successful, therapeutic interventions should be designed to 1) limit, if not reverse, the subcellular alterations in membrane stability and mitochondrial function which herald the transition from compensated to decompensated shock, and 2) re-hydrate the individual to restore normal circulatory dynamics and to prevent further cellular damage. It is proposed that calcium channel blocking agents and/or high energy phosphate compounds may delay the positive feedbacks which cause irreversible tissue damage, and thus may be useful initial interventions in the treatment of hypovolemic shock.
Improving degenerate oligonucleotide primed PCR-comparative genomic hybridization for analysis of DNA copy number changes in tumors.

Combining degenerate oligonucleotide-primed PCR (DOP-PCR) with comparative genomic hybridization (CGH) has made it possible to analyze genomic changes in single cells. Although DOP-PCR-CGH methodology has been reported, the reproducibility of the method has been uncertain. We have developed a reproducible DOP-PCR-CGH protocol by systematically evaluating different labeling methods (including nick translation, PCR incorporation, and random-primed labeling) and different hybridization mixtures (including amplified test DNA vs. amplified reference DNA, termed homo-hybridization; and amplified test DNA vs. unamplified reference DNA or vice versa, termed hetero-hybridization). We have analyzed DNA samples obtained from 16 tissue sources including fresh/frozen normal and tumor samples, formalin fixed and paraffin embedded tumor tissue, and tumor cell lines by using differently labeled probes and hybridization combinations, and we calculated the corresponding rate (CR) of DOP-PCR-CGH with standard CGH. We found that homo-hybridization produced reproducible results with high CRs as compared to standard CGH (91–100% CR, mean 97%); In contrast, hetero-hybridization failed to generate reproducible hybridization with low CRs (57–97% CR, mean 80%; χ2 = 1245.8, P < 0.0001), high background, uneven hybridization, and false deletions or amplifications. In addition, our improved DOP-PCR protocol raised the amplification efficiency at least five times as compared to previously reported protocols, allowing for the detection of genomic imbalances in as little as 12.5 pg of starting DNA. In conclusion, the DOP-PCR-CHG homo-hybridization method, especially when combined with labeling by nick translation, is reliable and reproducible. The method can be used in screening for genomic imbalances using minute amounts of tumor DNA, thereby facilitating CGH application. Genes Chromosomes Cancer 28:395–403, 2000. © 2000 Wiley-Liss, Inc.
Establishing the Learning Curve of Robotic Sacral Colpopexy in a Start-up Robotics Program

Abstract Study Objective To determine the learning curve of the following segments of a robotic sacral colpopexy: preoperative setup, operative time, postoperative transition, and room turnover. Design A retrospective cohort study to determine the number of cases needed to reach points of efficiency in the various segments of a robotic sacral colpopexy (Canadian Task Force II-2). Setting A university-affiliated community hospital. Patients Women who underwent robotic sacral colpopexy at our institution from 2009 to 2013 comprise the study population. Interventions Patient characteristics and operative reports were extracted from a patient database that has been maintained since the inception of the robotics program at Winthrop University Hospital and electronic medical records. Based on additional procedures performed, 4 groups of patients were created (A–D). Measurements and Main Results Learning curves for each of the segment times of interest were created using penalized basis spline (B-spline) regression. Operative time was further analyzed using an inverse curve and sequential grouping. A total of 176 patients were eligible. Nonparametric tests detected no difference in procedure times between the 4 groups (A–D) of patients. The preoperative and postoperative points of efficiency were 108 and 118 cases, respectively. The operative points of proficiency and efficiency were 25 and 36 cases, respectively. Operative time was further analyzed using an inverse curve that revealed that after 11 cases the surgeon had reached 90% of the learning plateau. Sequential grouping revealed no significant improvement in operative time after 60 cases. Turnover time could not be assessed because of incomplete data. Conclusions There is a difference in the operative time learning curve for robotic sacral colpopexy depending on the statistical analysis used. The learning curve of the operative segment showed an improvement in operative time between 25 and 36 cases when using B-spline regression. When the data for operative time was fit to an inverse curve, a learning rate of 11 cases was appreciated. Using sequential grouping to describe the data, no improvement in operative time was seen after 60 cases. Ultimately, we believe that efficiency in operative time is attained after 30 to 60 cases when performing robotic sacral colpopexy. The learning curve for preoperative setup and postoperative transition, which is reflective of anesthesia and nursing staff, was approximately 110 cases.
Endogenous interleukin-4 regulates glutathione synthesis following acetaminophen-induced liver injury in mice.

In a recent study, we reported that interleukin (IL)-4 had a protective role against acetaminophen (APAP)-induced liver injury (AILI), although the mechanism of protection was unclear. Here, we carried out more detailed investigations and have shown that one way IL-4 may control the severity of AILI is by regulating glutathione (GSH) synthesis. In the present studies, the protective role of IL-4 in AILI was established definitively by showing that C57BL/6J mice made deficient in IL-4 genetically (IL-4−/−) or by depletion with an antibody, were more susceptible to AILI than mice not depleted of IL-4. The increased susceptibility of IL-4−/− mice was not due to elevated levels of hepatic APAP-protein adducts, but was associated with a prolonged reduction in hepatic GSH that was attributed to decreased gene expression of γ-glutamylcysteine ligase (γ-GCL). Moreover, administration of recombinant IL-4 to IL-4−/− mice post-acetaminophen treatment diminished the severity of liver injury and increased γ-GCL and GSH levels. We also report that the prolonged reduction of GSH in APAP-treated IL-4−/− mice appeared to contribute towards increased liver injury by causing a sustained activation of c-Jun-N-terminal kinase (JNK), since levels of phosphorylated JNK remained significantly higher in the IL-4−/− mice up to 24 hours after APAP treatment Conclusion Overall these results show for the first time that IL-4 has a role in regulating the synthesis of GSH in the liver under conditions of cellular stress. This mechanism appears to be responsible at least in part for the protective role of IL-4 against AILI in mice and may have a similar role not only in AILI in humans, but also in pathologies of the liver caused by other drugs and etiologies.
Toward De Novo Recapitulation of Cytoskeleton Dynamics with DNA Nanotubes

The polymerization and depolymerization of cytoskeleton can transduce chemical energy into mechanical energy that drives cellular motility, such as chromosome segregation to cell protrusion. De novo recapitulation of the cytoskeletal phenomena with synthetic material would test our understanding of the design principles of polymerization motors. In the DNA nanotechnology tool box, DNA nanotubes are arguably the closest counterparts of cytoskeleton and we aim to utilize such structures to synthesize artificial cytoskeletons with various levels of complexity. DNA nanotube polymerization was monitored using total internal reflection microscopy at the single molecule level. We observed that DNA nanotubes exhibit asymmetric polymerization, similar to actin and microtubule polymerizations. We measured the association and dissociation rates of DNA nanotube polymerization at different monomer concentrations and temperatures and compared our measurements with the polymerization theory developed for the cytoskeleton and the kinetic DNA tile assembly model. Finally, the coupling between DNA nanotube polymerization and a DNA nanotechnology analog of nucleotide hydrolysis could potentially recapitulate cytoskeleton-based dynamics, such as treadmilling and dynamic instability, where the polymerization and depolymerization co-exist at steady state without ever reaching equilibrium.
Structural Material Selection for the General Motors' Experimental Truck Cab

This paper describes the utility of SMC in structural grade applications, more particularly, in GM truck cabs. The material chosen by GM was fiber glass reinforced, calcium carbonate filled commercially available SMC resin. Field tests to date on completely assembled truck cabs have been favorable. Based on the observed property retention of the resin with respect to temperature variation and cyclic loading, as well as resistance to stress crazing, the establish ment of structural grade SMC as a thoroughly effective substitute for metals is fully expected when all testing is com pleted.
Detection of Bacillus endospores using total luminescence spectroscopy.

Abstract Detection and analysis of bacteria from environmental samples (e.g. water, air, and food) are usually accomplished by standard culture techniques or by analyses that target specific DNA sequences, antigens or chemicals. For large cell numbers in aqueous suspensions, an alternative technique that has proven useful is total luminescence spectroscopy (TLS). TLS is the acquisition of fluorescence data that records the unique excitation–emission matrix (EEM) of compound fluorophores. Past work has shown that one type of bacterial endospore, Bacillus megaterium, possessed a distinct EEM pattern useful for differentiating it in complex biological fluids and suspensions. The work described here extends those observations to establish some limits on the sensitivity and specificity of TLS for the detection and analysis of bacterial endospores versus (bacterial) vegetative cells in aqueous culture. Our findings show Bacillus endospores exhibit a dramatic blue shift of 130 nm in excitation and a smaller shift of 50 nm in emission when compared to ancillary endospore and non-endospore forming bacterial cells.
Phosphatidylinositol 3-kinase inhibition down-regulates survivin and facilitates TRAIL-mediated apoptosis in neuroblastomas.

Abstract Background/purpose Recent findings have correlated neuroblastoma development with aberration of apoptosis. In particular, increased levels of survivin, a member of the inhibitor of apoptosis protein (IAP) family, have been associated with increased resistance to apoptosis in neuroblastomas. The purpose of this study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt pathway can alter the expression of survivin and facilitate tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in neuroblastoma cells. Methods Human neuroblastoma cells (SK-N-SH, BE[2]C, LAN-1 and IMR-32) were treated with LY294002 or wortmannin, inhibitors of PI3K, for 24 hours. Transient transfection of a dominant negative PI3K expression plasmid, pCGNN-Δp85, was performed to inhibit PI3K activation. Cells were treated with TRAIL, caspase-3, or pan-caspase inhibitors. RNase protection assay was performed to assess mRNA changes in IAP family members, including survivin. Western blot analysis was performed to measure changes in the levels of procaspases and survivin. Apoptosis was assessed by a DNA fragmentation ELISA assay. Results The authors found that survivin and cIAP1 mRNA as well as protein expression were decreased after PI3K inhibition. Combination treatment with LY294002 and TRAIL increased apoptosis of SK-N-SH cells compared with TRAIL alone; these results were further corroborated by complete inhibition of apoptosis by caspase-3 or pan-caspase inhibitor. Conclusions The authors report that PI3K pathway inhibition down-regulates survivin expression and enhances TRAIL-mediated apoptosis in neuroblastomas. PI3K pathway may play a crucial role in neuroblastoma cell survival; therefore, treatment with inhibitors of PI3K may provide potential novel therapeutic options.
Religious Roots of Political Orientations: Variations Among American Catholic Parishioners

Social scientists have formulated several theories or prototheories to account for party identification, political ideology, and issue positions of Americans and, by extension, of American Catholics. These include ethnic assimilation and communalism, social class, regional political culture, political generations, and recently gender. At the same time, some scholars have argued that religious values profoundly affect these political variables. But their measures have never been convincing or their findings strong. This paper formulates a new measure of foundational religious beliefs and, controlling for measures of other theoretically relevant variables, estimates the impact of such beliefs on political variables. Data are drawn from the 2,667 registered Catholic parishioners included in the Notre Dame Study of Catholic Parish Life. The overall model appears modestly powerful, but individual findings are of interest. Interpreting results through theories of partisanship, this paper argues that the traditi...
Physical metallurgy and magnetic behavior of Cd-stabilized b.c.c. β-Gd alloys

Abstract The metallurgical and magnetic properties of Cd-stabilized b.c.c. β-Gd alloys were studied. The b.c.c. β-Gd phase could be retained at room temperature by alloying with Cd and liquid quenching. Single-phase alloys were obtained for Cd concentrations from 15 to 19 at.% Cd. Experimental data from these alloys were used to predict the physical properties of the pure b.c.c. Gd, such as the lattice parameter and the Curie temperature. Differential thermal analysis of the GdCd alloys revealed a two-step revision process on heating in which the b.c.c. alloy first transformed into an intermediate h.c.p. phase and then completely transformed to the equilibrium α-Gd + CdGd phases. The GdCd alloys exhibit a Gabay-Toulouse-type spin glass transition from a ferromagnetic state into a spin glass + ferromagnetic mixed state about 30 K. The occurrence of spin glass behavior at 81–85 at.% Gd is unique in that this is the highest concentration of a magnetic ion observed in a crystalline, metallic spin glass system.
Modeling stratification in two-dimensional sandpiles

Abstract When a mixture of small and large grains is poured between two vertical slabs, the mixture spontaneously stratifies in alternating layers of small and large grains. We describe a possible mechanism and we develop a model that reproduces stratification of the large and small grains in alternating layers. We find that the requirement for stratification is that the angle of repose of the large pure species is larger than the angle of repose of the small pure species, a prediction confirmed by the experimental findings.
The Ultra-Violet Light of the Sun as the Origin of Auroræ and Magnetic Storms

A THEORETICAL investigation has been made of the outlying regions of the atmosphere of the earth and of the effect of sunlight on these regions; certain of the conclusions are given in this preliminary note. By the usual methods the temperatures and the pressures of the atmosphere to great heights were calculated for a quiet sun, that is, the sun in its normal state, with no terrestrial aurorae or magnetic storms. Because of the unequal balance at cold temperatures between the solar energy absorbed in the ultra-violet by the atmospheric gases and the energy re-emitted in the infra-red by the gases, the daytime temperatures above 100 km. were found to increase with the height above the surface of the earth, until at 300 km. or 400 km. temperatures of 1000° Kelvin seem reasonable. (There is, of course, nothing novel in this, although we have been interested in working the matter out more exactly perhaps than has been done heretofore.)
Resource allocation to extracellular enzyme production: A model for nitrogen and phosphorus control of litter decomposition

Abstract Most models for plant litter decomposition link degradation rates to measures of climate or litter composition, rather than directly to microbial activity. We developed a model based on the premise that saprotrophic microbial communities maximize their productivity by optimizing their allocation of resources in the production of extracellular carbon, nitrogen and phosphorus-acquiring enzymes. In this model, enzyme activity indicators are used to estimate decomposition rates and to assess relative N and P availability. This approach may facilitate estimation of decomposition rates in the field and improve ecological forecasting.
Cell-free and Cellular Activities of a DNA Sequence Selective Hairpin Polyamide-CBI Conjugate

Alkylating agents are generally highly reactive with DNA but demonstrate limited DNA sequence selectivity. In contrast, synthetic pyrrole-imidazole polyamides recognize specific DNA sequences with high affinity but are unable to permanently damage DNA. An eight-ring hairpin polyamide conjugated to the alkylating moiety cyclopropylpyrroloindole, related to the natural product CC-1065, affords a conjugate 1-CBI (polyamide 1-CBI (1-(chloromethyl)-5-hydroxyl-1,2-dihydro-3H-benz[e]indole) conjugate), which binds to specific sequences in the minor groove of DNA and alkylates a single adenine flanking the polyamide binding site. In this study, we show that 1-CBI alkylates DNA in both plasmid and intracellular minichromosomal form and inhibits DNA replication under both cell-free and cellular conditions. In addition, it inhibits cell growth and arrests cells in the G2/M phase of the cell cycle.
Demonstration of a word design strategy for DNA computing on surfaces.

A strategy for DNA computing on surfaces using linked sets of 'DNA words' that are short oligonucleotides (16mers) is proposed. The 16mer words have the format 5'-FFFFvvvvvvvvFFFF-3' in which 4-8 bits of data are stored in 8 variable ('v') base locations, and the remaining fixed ('F') base locations are used as a word label. Using a template and map strategy, a set of 108 8mers each of which possesses at least a 4 base mismatch with the complements to all the other members of the set (4bm complements) are identified for use as a variable base sequence set. In addition, sets of 4 and 12 word labels of the form ABCD....DCBA that are respectively 8bm and 6bm complements with each other are identified. The 16mers are chosen to have a G/C content of 50% in order to make the thermodynamic stability of the perfectly matched hybridized DNA duplexes similar; a simple pairwise additive method is used to estimate the perfect match and mismatch hybridization thermodynamics. A series of preliminary experiments are presented that use small arrays of 16mers attached to chemically modified gold surfaces and fluorescently labeled complements to study the hybridization adsorption and enzymatic manipulation of the oligonucleotides.