cssi/SciSciGPT-SciSciNet huggingface dataset:
Interspersed repetitive and tandemly repetitive sequences are differentially represented in extrachromosomal covalently closed circular DNA of human diploid fibroblasts

Extrachromosomal covalently closed circular DNA (cccDNA) was isolated from human diploid fibroblasts by alkaline denaturation/renaturation and CsCl-ethidium bromide isopycnic centrifugation. Probing across these gradient fractions showed a higher proportion of cccDNA sequences homologous to the interspersed highly repetitive Alu I and Kpn I sequences than to the human tandemly-repetitive Eco RI (alphoid) DNA. Cloning of these cccDNAs was then carried out following digestion with restriction endonucleases Hind III, Bam HI or Pst I, and ligation into plasmid pBR322. Many isolated recombinant clones were unstable as seen by a high rate of loss over four cycles of antibiotic selection, and frequent plasmid modifications including deletions adjoining the site of insertion. Of 107 cloned sequences which appeared relatively stable, i.e., survived four cycles of antibiotic selection without incurring detectable deletions, 28% and 11% showed homology to Alu I and Kpn I families, respectively, while 4% contained sequences homologous to both. In contrast, less than one percent hybridized to probes for tandemly-repetitive sequences, Eco RI and Satellite III. The average insert size of cloned cccDNA derived from human fibroblasts, 2.52 Kbp, was larger than previously reported for similar clones derived from genetically less stable permanent lines, which may reflect differences in the process of cccDNA generation.
Multicontrast x-ray computed tomography imaging using Talbot-Lau interferometry without phase stepping.

Purpose: The purpose of this work is to demonstrate that multicontrast computed tomography (CT) imaging can be performed using a Talbot-Lau interferometer without phase stepping, thus allowing for an acquisition scheme like that used for standard absorption CT. Methods: Rather than using phase stepping to extract refraction, small-angle scattering (SAS), and absorption signals, the two gratings of a Talbot-Lau interferometer were rotated slightly to generate a moire pattern on the detector. A Fourier analysis of the moire pattern was performed to obtain separate projection images of each of the three contrast signals, all from the same single-shot of x-ray exposure. After the signals were extracted from the detector data for all view angles, image reconstruction was performed to obtain absorption, refraction, and SAS CT images. A physical phantom was scanned to validate the proposed data acquisition method. The results were compared with a phantom scan using the standard phase stepping approach. Results: The reconstruction of each contrast mechanism produced the expected results. Signal levels and contrasts match those obtained using the phase stepping technique. Conclusions: Absorption, refraction, and SAS CT imaging can be achieved using the Talbot-Lau interferometer without the additional overhead of long scan time and phase stepping.
Effects of anonymity and retaliatory potential on student evaluations of faculty performance

The present study, employing a 2×2 design, examines the independent and interactive effects of two experimentally manipulated variables, Anonymity (A) and Retaliatory Potential (RP), on students' ratings of faculty performance. Data were obtained from 188 students at a large midwestern university using an instrument that had been specially developed for the study. A hypothesized main effect was found for A: The professor was rated more positively by students completing signed ratings than those completing ratings anonymously. The data showed no support, however, for the hypothesized RP main effect or the A×RP interactive effect. Practical implications of the study's findings are discussed.
Antibody synthesis induced by endogenous internal images

In this study, immunization with a vaccine consisting of multiple F(abt’)2 fragments of affinity-purified antitetanus toxoid antibodies covalently bound to a carrier protein successfully induced antitetanus toxoid antibodies. Further studies showed that this vaccine preparation contained no biologically detectable tetanus antigen. The induced antitetanus antibody (Ab1t’) titer was higher than the titer of antibodies binding control antigens. The immunizing F(abt’)2 preparation did not elicit a secondary antitetanus response from mice primed with tetanus toxoid and, hence, appeared free of tetanus epitopes. The specificity of Ab1t’ was established by absorption and inhibition with antigen. Immunization with antitetanus F(abt’)2 (Ab1t’) fragments appears to have elicited naturally occurring autologous antitetanus toxoid antibody (Ab1t’) through an idiotypic pathway. As predicted by network theory, anti-idiotype (Ab2) and antitetanus (Ab1t’) cycled reciprocally. Clonotypic characterization of Ab1t’ using isoelectric focusing and affinity immunoblotting showed increases in Ab1t’ titer to be the result of increased synthesis by limited subsets of antitetanus toxoid B-cell clones and not increased synthesis by multiple clones, as is characteristic of antigen-driven Ab1 responses. Many Ab1 and Ab1t’ clonotypes had identical pIs, suggesting that they either share V region genes or are the product of the same B-cell clones. These findings indicate that immunization with polyclonal multivalent Ab1 preparations can trigger active synthesis of antibodies with the same specificity. The results provide further evidence for naturally occurring idiotypic cascades that could be exploited for studies of catalytic antibodies.
Trust in inter-organizational exchanges: a case study in business to business electronic commerce

Given the uncertainties of online transactions, e-commerce encourages the creation of institutional structures for online exchange relationships. Building upon the notion of institutional trust, this research examines how institutional structures develop through governance mechanisms leading to technology trust derived from structural assurances for online dyadic relationships. Technology trust is defined as the subjective probability by which organizations believe that the underlying technology infrastructure is capable of facilitating transactions according to their confident expectations. Using a cognitive process framework, we discuss four perspectives of trust, namely technological, economic, behavioral, and organizational perspectives, to show how technology trust evolves into relationship trust. We examine the impact of technology trust within an inter-organizational dyad between Cisco and Compaq. The findings posit that technology trust contributes and evolves into relationship trust. The study provides evidence on how specific structural assurances in Cisco Connection Online help to build initial online technology trust in B2B marketplaces that in turn promotes relationship trust and builds trustworthy e-commerce relationships. The paper discusses theoretical and managerial implications of this study, while proposing suggestions for future research.
Frequency response analysis of oxygen evolution by algae

Abstract Common photosynthetic organisms were excited with steps, pulses, or sine waves of light as dissolved oxygen was measured with a microelectrode. Frequency response analysis revealed two fundamental time constants of 4 and 16 s. These time constants are assigned provisionally to processes for mass transfer and to the biochemical reactions of reduction of carbon dioxide.
Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of “euthyroid sick” or “low T3” syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values: eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.
Limitations of spin-wave theory in T=0 spin dynamics

The $T=0$ dynamics of a family of one-dimensional quantum spin systems with fully ordered (ferromagnetic or spin-flop) ground states is investigated. By rigorous calculations, it is demonstrated that the $T=0$ dynamic structure factor is, in general, not a $\ensuremath{\delta}$ function as predicted by linear spin-wave theory but characterized by more complicated structures with nonzero linewidths. The exact result approaches the spin-wave result in the classical limit $s\ensuremath{\rightarrow}\ensuremath{\infty}$. The results of this study demonstrate how quantum effects may invalidate spin-wave theory even in the presence of saturated magnetic long-range order. Hence the failure of spin-wave theory is not necessarily linked to the absence or strong reduction of long-range order typical for one-dimensional quantum spin systems. The unreliability of spin-wave theory has therefore to be suspected also for the dynamics of three-dimensional quantum spin systems where the long-range order is always strong at $T=0$.
External cavity beam combining of 21 semiconductor lasers using SPGD

Active coherent beam combining of laser oscillators is an attractive way to achieve high output power in a diffraction limited beam. Here we describe an active beam combining system used to coherently combine 21 semiconductor laser elements with an 81% beam combining efficiency in an external cavity configuration compared with an upper limit of 90% efficiency in the particular configuration of the experiment. Our beam combining system utilizes a stochastic parallel gradient descent (SPGD) algorithm for active phase control. This work demonstrates that active beam combining is not subject to the scaling limits imposed on passive-phasing systems.
In vivo study of the human long chain acyl-CoA dehydrogenase(LCAD) gene regulation of expression. † 640

LCAD is a mitochondrial flavoenzyme encoded on nuclear genome which catalyzes the first reaction in fatty acid β-oxidation. Transient transfection study of the human LCAD gene promoter revealed minimal promoter function within bp -200 to +1 upstream of the cap site. Two suppressor sequences are present at -288 to -259, and -1048 to -1010 respectively. To further define the function of the human LCAD suppressor elements in vivo, constructs containing the LCAD 5′-flanking region, -1800/+1 and-200/+1, linked with the luciferase reporter gene were micro-injected into mouse oocytes. F1 mice positive for the incorporated LCAD-luciferase fusion gene were tested for luciferase expression. In vivo transgenic mice study revealed same results as discovered by in vitro transfection study. To delineate the endogenous LCAD mRNA expression in mouse tissues, normal mouse heart, brain, kidney, and soleus tissue sections were studied byin situ hybridization with mouse LCAD RNA probes. The cardiac ventricle contained abundant LCAD mRNA. Kidney and soleus expressed intermediate levels of LCAD mRNA. To our surprise, mouse brain expressed LCAD transcripts heterogeneously. Although the cerebral cortex did not express detectable LCAD mRNA most of the brain, including the cerebellar cortex and choroid plexus contained large amount LCAD transcripts. These results suggest for the first time that mitochondrial β-fatty acid oxidation may be essential for energy production in some parts of the brain.
Site-specific Cleavage of BMP4 by Furin, PC6, and PC7

Bone morphogenetic proteins (BMPs) require proteolytic activation by members of the proprotein convertase (PC) family. Pro-BMP4 is initially cleaved at a site adjacent to the mature ligand domain (S1) and then at an upstream site (S2) within the prodomain. Cleavage at the S2 site, which appears to occur in a tissue-specific fashion, regulates the activity and signaling range of mature BMP4. To test the hypothesis that tissue-specific cleavage of pro-BMP4 is regulated by differential expression of a site-specific protease, we identified the PCs that cleave each site in vivo. In Xenopus oocytes, furin and PC6 function redundantly to cleave both the S1 and S2 sites of pro-BMP4, as evidenced by the results of antisense-mediated gene knockdown and the use of the furin- and PC6-selective inhibitor α1-PDX. By contrast, α1-PDX blocked cleavage of the S2 but not the S1 site of pro-BMP4 in embryos, suggesting the existence of a developmentally regulated S1 site-specific convertase. This protease is likely to be PC7 based on knowledge of its required substrate cleavage motif and resistance to α1-PDX. Consistent with this prediction, an α1-PDX variant engineered to target PC7, in addition to furin and PC6, completely inhibited cleavage of BMP4 in oocytes and embryos. Further studies showed that pc7 transcripts are expressed and polyadenylated, and that the PC7 precursor protein undergoes efficient autocatalytic activation in both oocytes and embryos. These results suggest that PC7, or a convertase with similar substrate specificity, functions to selectively cleave the S1 site of pro-BMP4 in a developmentally regulated fashion.
A technique for using memory cores as logical elements

Over the years there have been many outstanding papers which can be assembled under the collective title "Component Failure Analysis." Included in this group are the tube-life prediction tables, the derating charts for condensors, the maximum current versus useful life curves for diodes, etc.; and each company that has a customer service organization has in its files records loosely titled "Plug-in Failures, Their Cause and Cure." An examination of the records will show that in the majority of cases the "active" elements are at fault. Active elements are defined here as those elements which amplify a changed state of their inputs. It would seem, then, that the path to reliability is to remove as many active elements as possible from the system; that is, given some specific design problem, to time-share the active elements as much as possible in keeping with the flexibility required of the overall design. But this philosophy is not without its attendant apparent disadvantage. To use a minimum of active elements, a maximum of switching elements is required. To utilize the minimum active elements concept, a switching element approaching the ideal is required.
Colorectal cancer staging by endoscopic ultrasonography

The prognosis of patients with cancers of the colon or rectum is strongly correlated with the stage of disease at the time of diagnosis. This staging is determined by an assessment of the depth of local penetration (T classification) and the presence or absence of nodal or distant metastases (N and M classification, respectively). For tumors of the proximal colon, decisions regarding surgical technique are, in most instances, made independently of stage. Optimal management of rectal neoplasms, however, is critically dependent upon accurate preoperative localization and staging. At present, endoscopic ultrasound represents the only imaging modality that can directly visualize the individual tissue layers of bowel wall. As such, endoscopic ultrasound is uniquely suited to the preoperative evaluation of these tumors. This article describes the techniques involved in performing accurate preoperative endosonographic evaluation of colorectal malignancies and other miscellaneous lesions of the colon and rectum.
Acetylcholinesterase molecular forms in muscle and non-muscle cells of rat heart

Experiments were performed to determine the cellular associations of the molecular forms of acetylcholinesterase (AChE) in adult rat heart. For this purpose, a cardiac muscle and a non-muscle fraction were isolated from rat heart ventricles after perfusion with collagenase and hyaluronidase, extracts of these fractions were subjected to ultracentrifugation on linear density gradients of sucrose (5-20%), and fractions of these gradients were analyzed for AChE activity. The results show that only globular AChE molecular forms were present in isolated cardiac muscle cells. Globular AChE forms were also present in the non-muscle cells fraction but in different proportions. The proportions of globular AChE forms plus the high specific activity of choline acetyltransferase in the non-muscle cell fraction suggest that this fraction contains cholinergic nerve fragments. The results of this study also show that asymmetric AChE is released during the perfusion of heart with the digestive enzymes, which suggests that asymmetric AChE is bound to the extracellular matrix of heart.
Interferometric Upper Limits on Millimeter Polarization of the Disks around DG Tau, GM Aur, and MWC 480

Millimeter-wavelength polarization measurements offer a promising method for probing the geometry of magnetic fields in circumstellar disks. Single dish observations and theoretical work have hinted that magnetic field geometries might be predominantly toroidal, and that disks should exhibit millimeter polarization fractions of 2-3%. While subsequent work has not confirmed these high polarization fractions, either the wavelength of observation or the target sources differed from the original observations. Here we present new polarimetric observations of three nearby circumstellar disks at 2" resolution with the Submillimeter Array (SMA) and the Combined Array for Research in Millimeter Astronomy (CARMA). We reobserve GM Aur and DG Tau, the systems in which millimeter polarization detections have been claimed. Despite higher resolution and sensitivity at wavelengths similar to the previous observations, the new observations do not show significant polarization. We also add observations of a new HAeBe system, MWC 480. These observations demonstrate that a very low ( 100 AU) scales in bright circumstellar disks. We suggest that high-resolution observations may be worthwhile to probe magnetic field structure on linear distances smaller than the disk scale height, as well as in regions closer to the star that may have larger MRI-induced magnetic field strengths.
Reinforcement of an alternative behavior as a model of recovery and relapse in the rat

A preclinical model that includes measures of alternative behavior and drug-seeking could improve our understanding of the processes involved in successful recovery; however current preclinical models of relapse do not measure alternative behavior. We assessed the persistence of food-maintained responding and the resumption of ethanol-maintained responding after ethanol-maintained responding was reduced by changing the response requirement for concurrently available food. Ethanol (10%, w/v) was always available following 5 responses (FR5). A 16 kHz tone indicating food delivery followed 150 responses (FR150) resulted in ethanol-predominate responding and substantial amounts of ethanol were earned (0.47 g/kg per 30-min session) and consumed. An 8 kHz tone indicating food delivery followed 5 responses (FR5) for 1, 2, 4, or 16 consecutive sessions reduced ethanol-maintained responding despite unchanged ethanol availability. Ethanol-maintained responding resumed upon subsequent presentation of the 16 kHz tone. However, more responses occurred on the food lever before 5 responses occurred on the ethanol lever as the number of preceding FR5 food sessions increased. These results suggest that alternative reinforcement may reduce control by discriminative stimuli that occasion ethanol-seeking and is consistent with the risk of relapse declining with longer periods of recovery because of the strengthening of alternative behavior.
ANNIHILATION OF ANTIBARYONS

The pi mesons surrounding any nucleon or antinucleon can have any charge; the strange meson cloud of a nucleon (antinucleon), however, may contain only K/sup +/ and K/sup 0/ mesons (K/sup -/ and K/sup 0/ mesons), at least for dissociation to single mesons. Some consequences of this type of asymmetry in the strange-meson clouds surrounding baryons and antibaryons are discussed. Effects on the distributions of strange and normal particles from annihilation of particles on antiparticles are described. (T.F.H.)
Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins.

Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and tricarboxylic acid (TCA) cycle intermediates into biosynthetic pathways. Because the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell’s ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to nutrient stress that kills cancer cells by becoming quiescent and catabolic. We show that FTY720, a water soluble sphingolipid drug that is effective in many animal cancer models, selectively starves cancer cells to death by down-regulating nutrient transporter proteins. Consistent with a bioenergetic mechanism of action, FTY720 induced homeostatic autophagy. Cells were protected from FTY720 by cell permeable nutrients or by reducing nutrient demand, but blocking apoptosis was ineffective. Importantly, AAL-149, an FTY720 analog that lacks FTY720’s dose limiting toxicity, also triggered transporter loss and killed patient-derived leukemias while sparing cells isolated from normal donors. Because they target the metabolic profile of cancer cells rather than specific oncogenic mutations, FTY720 analogs like AAL-149 should be effective against many different tumor types, particularly in combination with drugs that inhibit autophagy.
Frequency of acquired coronary-cameral fistula after ventricular septal myectomy in hypertrophic cardiomyopathy.

Abstract Acquired coronary-cameral fistulas are considered rare. A recent review mentions only 30 published cases between 1956 and 1986. 1 All were post-traumatic and 29 of them involved the right heart. Fistulas between a coronary artery and the left ventricle are even more rare and have been published as sporadic case reports. Iatrogenic fistulas between a coronary artery and the left ventricle after cardiac surgery have been reported lately. 1–3 Prompted by a follow-up echocardiogram, a coronary artery-to-left ventricle fistula was demonstrated by coronary angiography in a patient 7.5 years after myectomy for hypertrophic cardiomyopathy.
Practical Implementation Science: Developing and Piloting the Quality Implementation Tool

According to the Interactive Systems Framework for Dissemination and Implementation, implementation is a major mechanism and concern in bridging research and practice. The growing number of implementation frameworks need to be synthesized and translated so that the science and practice of quality implementation can be furthered. In this article, we: (1) use the synthesis of frameworks developed by Meyers et al. (Am J Commun Psychol, 2012) and translate the results into a practical implementation science tool to use for improving quality of implementation (i.e., the Quality Implementation Tool; QIT), and (2) present some of the benefits and limitations of the tool by describing how the QIT was implemented in two different pilot projects. We discuss how the QIT can be used to guide collaborative planning, monitoring, and evaluation of how an innovation is implemented.
Temporal subtraction technique for detection of interval changes on digital chest radiographs by using an elastic matching technique

We have been developing a temporal subtraction technique to assist radiologists in the detection of interval changes of pulmonary abnormalities on digital chest radiographs. By subtracting a previous image from a current one, a temporal subtraction image is obtained, in which the lesions can be enhanced because skeletal structures such as ribs and clavicles are eliminated. Although the quality of the subtraction images obtained with our previous technique is relatively good, minor misregistration artifacts were observed in many cases because of the use of polynomial fitting of shift values. In this study, we employed three new techniques to reduce the misregistration artifacts in the temporal subtraction images. The first was a rib edge matching technique which was used to align the rib structures approximately in the two images. The second was an increase in the number of template and search area regions of interest (ROIs) in the two images. The third was the use of an elastic matching technique for the replacement of the polynomial fitting technique employed in the previous subtraction technique. With the new techniques, the quality of subtraction images was improved significantly. In particular, the number of subtraction images with excellent quality was greatly increased from 37% to 57%.
Cost of Being Poor: Retail Price and Consumer Price Search Differences across Inner-City and Suburban Neighborhoods

This research undertakes a carefully designed and detailed empirical study to gain insights into (1) the extent of price differentials between wealthy and poor neighborhoods; (2) what induces such differentials, especially the nature and intensity of competitive environments, including mass merchandisers like Wal-Mart; and (3) their relative impacts. It finds a price differential of about 10%–15% for everyday items. Even after controlling for store size and competition, prices are found to be 2%–5% higher in poor areas. It also finds that it is not the poverty level per se but access to cars that acts as a key determinant of consumers' price search patterns.
Combined immunodeficiency in a 3-year-old boy with 16p11.2 and 20p12.2-11.2 chromosomal duplications.

We report for the first time on a 3-year-old boy with paternally inherited 212.85 kb—16p11.2 and 7.8 Mb—20p12.2-11.23 interstitial microduplications associated with having congenital cardiac defect, dysmorphic facial features, and combined T-, B-, and NK cell immunodeficiency. In addition the 7.8 Mb—20p12.2-11.23 microduplication is unique showing novel breakpoints among all partial trisomy/duplication 20p reported to date, narrowing down the critical region for trisomy 20p syndrome. © 2013 Wiley Periodicals, Inc.
Redox regulation of the rat hepatocyte iNOS promoter.

Abstract Background: The purpose of this study was to define the redox sensitive cis-acting transcriptional mechanisms that regulate inducible nitric oxide synthase (iNOS) promoter function in the hepatocyte. Methods: Clonal deletion constructs of the rat hepatocyte iNOS promoter (Genbank X95629; 1845 base pair)–reporter plasmid were transiently transfected into HepG2 cells treated with IL-1β and IL-1β + hydrogen peroxide. Results: A segment of the promoter upstream from nucleotide –1126 was associated with redox-sensitive augmentation of promoter activity. Site-directed mutagenesis of 2 antioxidant response elements (AREs) was combined with transfection analysis to demonstrate that mutation of the ARE at nt–1347 ablated oxidant stress-mediated activation of the iNOS promoter. Conclusions: This ARE conveys the redox-sensitive response of the rat iNOS promoter. Hepatocyte iNOS expression is a novel and, as yet, poorly described antioxidant mechanism that is cytokine and redox sensitive and that plays a pleuripotent regulatory role in hepatocellular function in the face of sepsis and shock. (Surgery 1999:126:450-5.)
The Correction of Aphakia in Infants with Hydrogel Extended-wear Contact Lenses Corneal Studies

Although hydrogel extended-wear contact lenses (EWCLs) have been used extensively in the correction of aphakia in neonates, little is known about the effects of these lenses on infant corneas. Recent studies have demonstrated that long-term contact lenses can induce endothelial morphometric changes, including an increased coefficient of variation (CV) of mean endothelial cell area. Using wide-field specular microscopy, the authors studied 11 eyes of 10 patients, 1 to 3 years of age who, after lensectomy for congenital cataracts, wore EWCLs for the correction of aphakia. Except for two corneas in which increased pachometric readings and CV developed after repeated episodes of lens loss and inflammation, the EWCL were well tolerated and associated with few complications in this study.
Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall-cell lung cancer.

BACKGROUND. Preclinical studies have demonstrated that the inhibition of the PI3K/Akt/mTOR pathway restores gefitinib sensitivity in resistant cancer cell lines. A phase 1 study was conducted of the combination of everolimus, an mTOR inhibitor, and gefitinib to determine a daily dose of everolimus with gefitinib in patients with advanced nonsmall-cell lung cancer (NSCLC). METHODS. Oral everolimus and gefitinib were both administered daily to patients with progressive NSCLC. Patients were enrolled in 3-patient cohorts at everolimus dose levels of 5 and 10 mg daily. All patients received gefitinib 250 mg daily. RESULTS. Ten patients were enrolled. The maximum tolerated dose of everolimus was 5 mg when administered daily with gefitinib 250 mg. Two patients who were treated at the 10 mg dose level of everolimus experienced dose-limiting toxicity, including grade 5 hypotension and grade 3 stomatitis. Pharmacokinetic studies demonstrated no consistent, significant interaction on the tmax, Cmax, and AUC0-8h of either agent. Two partial radiographic responses were identified among the 8 response-evaluable patients. CONCLUSIONS. For further study, everolimus at a dose of 5 mg daily in combination with daily gefitinib 250 mg is recommended. The 2 radiographic responses identified are encouraging. A phase 2 trial in patients with NSCLC is under way. Cancer 2007. © 2007 American Cancer Society.
Ephrin type-B receptor 4 activation reduces neointimal hyperplasia in human saphenous vein in vitro

Background Vein bypass is an essential therapy for patients with advanced peripheral and coronary artery disease despite development of neointimal hyperplasia. We have shown that stimulation of the receptor tyrosine kinase ephrin type-B receptor 4 (Eph-B4) with its ligand ephrin-B2 prevents neointimal hyperplasia in murine vein grafts. This study determines whether Eph-B4 in adult human veins is capable of phosphorylation and activation of downstream signaling pathways, as well as functional to release nitric oxide (NO) and prevent neointimal hyperplasia in vitro. Methods Discarded human saphenous veins were taken from the operating room and placed in organ culture without or with ephrin-B2/Fc (2 μg/mL) for 14 days, and the neointima/media ratio was measured in matched veins. Primary human umbilical vein endothelial cells were treated with ephrin-B2/Fc (2 μg/mL) and examined with quantitative polymerase chain reaction, Western blot, immunoassays, and for release of NO. Ephrin-B2/Fc (2 μg/mL) was placed on the adventitia of saphenous veins treated with arterial shear stress for 24 hours in a bioreactor and activated Eph-B4 examined with immunofluorescence. Results The baseline intima/media ratio in saphenous vein rings was 0.456 ± 0.097, which increased to 0.726 ± 0.142 in untreated veins after 14 days in organ culture but only to 0.630 ± 0.132 in veins treated with ephrin-B2/Fc (n = 19, P = .017). Ephrin-B2/Fc stimulated Akt, endothelial NO synthase and caveolin-1 phosphorylation, and NO release ( P = .007) from human umbilical vein endothelial cells (n = 6). Ephrin-B2/Fc delivered to the adventitia stimulated endothelial Eph-B4 phosphorylation after 24 hours of arterial stress in a bioreactor (n = 3). Conclusions Eph-B4 is present and functional in adult human saphenous veins, with intact downstream signaling pathways capable of NO release and prevention of neointimal hyperplasia in vitro. Adventitial delivery of ephrin-B2/Fc activates endothelial Eph-B4 in saphenous veins treated with arterial shear stress in vitro. These results suggest that stimulation of Eph-B4 function may be a candidate strategy for translation to human clinical trials designed to inhibit venous neointimal hyperplasia.
The Precambrian–Cambrian boundary problem: magnetostratigraphy of the Amadeus Basin, Central Australia

A magnetostratigraphic study of Upper Proterozoic to early Cambrian sediments at 4 localities in Central Australia reveals the presence of a magnetic polarity pattern composed of 2 long quiet intervals, first of reversed then of normal polarity, which is then succeeded by a long mixed interval. Lithologic comparisons suggest that this pattern is a reflection of the behaviour of the geomagnetic field at that time, and probably is not a result of varying sedimentation rates. Two sampled sections in the Arumbera Sandstone separated by 80 km both contain the long normal interval followed by the interval of mixed polarity, the detailed comparison of which demonstrates that the Arumbera-Box Hole boundary is unconformable. Elements from the late Precambrian Mt Skinner fauna in the Arumbera Sandstone indicate that the long normal interval is entirely pre-Cambrian, and that the base of the Cambrian occurs within the interval of mixed polarity.A comparison with an additional site sampled across a fossil occurrence in the Central Mount Stuart Formation at Central Mount Stuart indicates that at least 1 of the Upper Proterozoic fossils, Hallidaya brueri, has a considerable vertical distribution in time.If used properly, the magnetic polarity pattern discussed herein offers the possibility of precise intercontinental correlations of stratigraphic sequences near the base of the Cambrian. It is suggested that a stratotype sequence for the base of the Cambrian be chosen in such a manner that the boundary position corresponds to a geomagnetic reversal.
Heats of physisorption and the predictions of chi theory

It is demonstrated that the heats of physical adsorption as a function of amount adsorbed may be calculated using the quantum mechanically based chi theory. This calculation is compared to that which utilizes the Dubinin ‘‘thermodynamic criterion’’ for which there exists a mappingrelationship between the isotherm and the heats of physisorption, qst ¼ RT lnðP =PsÞ. This latter method, however, does not yield the functional form of either the isotherm or qst. The chi theory, on the other hand, utilizes the isotherm to determine the number of moles in a monolayer, nm, and an energy value, Ev, which is unique for any particular adsorbate–adsorbent pair. This determination is possible provided the background gas pressure is low enough during the measurement. Once determined from the isotherm, nm and Ev are used to precisely calculate the heat of adsorption as a function of coverage. Such parameterless calculations have never before been reported in the literature. In examiningthe literature where both the isotherm and the heats of adsorption are presented together, usually Ev cannot be obtained from the isotherm due to the presence of background gases. In spite of the background gases, the value for nm is extractable and excellent one-parameter fits to the heats of adsorption are possible. In several cases, both nm and Ev are extractable from the isotherm. In these cases the calculation for the heats of adsorption with no parameters what-so-ever are in excellent agreement with the experimental values and well within experimental error. 2002 Published by Elsevier Science Inc.
Aspergillus Blepharitis and Dermatitis in a Peregrine Falcon-Gyrfalcon Hybrid (Falco peregrinus × Falco rusticolus)

Abstract A 3-year-old female peregrine falcon-gyrfalcon hybrid (Falco peregrinus × Falco rusticolus) was presented for evaluation of a lesion below the right eye. Initial examination revealed an abraded, crusty lesion on the right lower eyelid that was believed to be consistent with trauma and a secondary bacterial infection. Despite initial diagnostic procedures and treatment, the condition progressed to severe blepharitis and dermatitis involving the upper and lower eyelids of both eyes and the head. Septated fungal hyphae were identified by histopathologic analysis in specimens obtained from the lesions and an Aspergillus species was cultured. The blepharitis and dermatitis were treated successfully with oral itraconazole (15 mg/kg q12h) and topical miconazole cream, applied twice daily.
The value relevance of announcements of transformational information technology investments

In this paper, we examine the influence of IT strategic role to extend the findings of Im et al. (2001), Chatterjee et al. (2002) and Dos Santos et al. (1993). Specifically, we demonstrate that IT strategic role can explain how IT investments in each of the IT strategic roles might affect the firm's competitive position and ultimately firm value. We find positive, abnormal returns to announcements of IT investments by firms making transformative IT investments, and with membership in industries with transform IT strategic roles. The results of previous research are not found to be significant when IT strategic role is included as an explanatory variable. These results provide support for the value of capturing the IT strategic role of a firm's IT-related competitive maneuvering in studies striving to understand the conditions under which IT investments are likely to produce out-of-the-ordinary, positive returns.
More on glucose transporters: The acinar organization for hepatic glucose transport

The “erythroid/brain” glucose transporter (GT) isoform is expressed only in a subset of hepatocytes, those forming the first row around the terminal hepatic venules, while the “liver” GT is expressed in all hepatocytes. After 3 d of starvation, a three- to fourfold elevation of expression of the erythroid/brain GT mRNA and protein is detected in the liver as a whole; this correlates with the expression of this GT in more hepatocytes, those forming the first three to four rows around the hepatic venules. Starvation-dependent expression of the erythroid/brain GT on the plasma membrane of these additional hepatocytes is lost within 3 h of glucose refeeding; however, by immunoblotting we show that the protein is still present. Its loss from the surface is possibly explained by internalization.
ADP-Ribosylation Factors Modulate the Cell Surface Transport of G Protein-Coupled Receptors

ADP-ribosylation factors (ARFs) regulate vesicular traffic through recruiting coat proteins. However, their functions in the anterograde transport of nascent G protein-coupled receptors (GPCRs) from the endoplasmic reticulum to the plasma membrane remain poorly explored. Here we show that treatment with brefeldin A, an inhibitor of guanine nucleotide exchange on ARFs, markedly attenuated the cell surface numbers of α2B-adrenergic receptor (AR), β2-AR, angiotensin II type 1 receptor, and chemokine (CXC motif) receptor 4. Functional inhibition of individual ARF GTPases by transient expression of the GDP-bound, GTP-bound, and guanine nucleotide-deficient mutants showed that the five human ARFs differentially modulated receptor cell surface expression and that the ARF1 mutants produced the most profound inhibitory effect. Furthermore, expression of the ARF1 GTPase-activating protein (GAP) ARFGAP1 significantly blocked receptor transport. Interestingly, the GDP- and GTP-bound ARF1 mutants arrested the receptors in distinct intracellular compartments. Consistent with the reduced receptor cell surface expression, extracellular signal-regulated kinase 1 and 2 activation by receptor agonists was significantly attenuated by the GDP-bound mutant ARF1T31N. Moreover, coimmunoprecipitation showed that α2B-AR associated with ARF1 and glutathione transferase pull-down assay indicated that the α2B-AR C terminus directly interacted with ARF1. These data show that ARF1 GTPase is involved in the regulation of cell surface expression of GPCRs at multiple transport steps.
Picosecond-rise-time pulse applications of electron-beam-semiconductor devices

In this paper basic analytical and experimental results are presented for ultrafast amplifiers, pulse generators, and pulse-detection systems in which a modulated electron beam controls the current in a semiconductor target. The lumped target amplifier is discussed frst, and results are summarized from a simplified analysis of target response to step-function beam excitation. The optimization of amplifier rise time and peak output level is illustrated and predicted target gain, rise time, peak output current, voltage, and power capabilities are shown graphically. The feasibility of a subnanosecond-rise-time pulse amplifier with a peak output power of 100 kW is shown.
Intraluminal fluorescence spectroscopy catheter with ultrasound guidance.

We demonstrate the feasibility of a time- resolved fluorescence spectroscopy TRFS technique for intraluminal investigation of arterial vessel composition under intravascular ultrasound IVUS guidance. A proto- type 1.8-mm 5.4 Fr catheter combining a side-viewing optical fiber SVOF and an IVUS catheter was con- structed and tested with in vitro vessel phantoms. The pro- totype catheter can locate a fluorophore in the phantom vessel wall, steer the SVOF in place, perform blood flush- ing under flow conditions, and acquire high-quality TRFS data using 337-nm wavelength excitation. The catheter steering capability used for the coregistration of the IVUS image plane and the SVOF beam produce a guiding pre- cision to an arterial phantom wall site location of 0.53±0.16 mm. This new intravascular multimodal cath- eter enables the potential for in vivo arterial plaque com- position identification using TRFS. © 2009 Society of Photo-
The role of digestive enzymes in orally induced immune tolerance.

The influence of digestive enzymes on the tolerogenic properties of an orally administered protein antigen, Bovine Serum Albumin (BSA), in the mouse has been investigated. A non-immunogenic peptic digest of BSA was found to be immunosuppressive when administered orally or directly injected into the mouse ileum. In contrast, untreated BSA was tolerogenie when administered orally but immunogenie following ileal administration. As determined by precipitin analysis of the proteins recovered from mouse feces, orally administered BSA was thoroughly degraded by the digestive system while the degradation in the ileum was quite limited. We conclude that to acquire tolerogenic properties, an orally administered protein must be first degraded by the proteolytic enzymes of the gastrointestinal digestive system.
Reflections on graduate programs in communications media

Last year, with APBE help, Robert Crawford prepared a 64‐page report on “Graduate Programs in Communications Media.” The investigation was concerned with the collection of opinions and reactions as to the effectiveness, need, and quality of graduate programs in communications. The sources for this information were working executives in broadcasting, film, and print organizations, public and private, in New York City and Washington, D.C. In the present article, the author moves from the more or less objective reporting of his research data to a more personal analysis of the implications inherent in the study. Because the original report was distributed to the APBE membership, Dr. Crawford attempts an interpretation of the data as it reflects on graduate programs directed to training in the mass media, rather than merely summarizing the opinions of his respondents. Robert Crawford (Ph.D., University of Utah) has been actively engaged in commercial and educational broadcasting for more than 35 years. He is a...
Fast Parallel Suffix Array on the GPU

We implement two classes of suffix array construction algorithms on the GPU. The first, skew, makes algorithmic improvements to the previous work of Deo and Keely to achieve a speedup of 1.45 \(\times \) over their work. The second, a hybrid skew and prefix-doubling implementation, is the first of its kind on the GPU and achieves a speedup of 2.3–4.4 \(\times \) over Osipov’s prefix-doubling and 2.4–7.9 \(\times \) over our skew implementation on large datasets. Our implementations rely on two efficient parallel primitives, a merge and a segmented sort. We also demonstrate the effectiveness of our implementations in a Burrows-Wheeler transform and a parallel FM index for pattern searching.
S-MARKS: A Middleware Secure by Design for the Pervasive Computing Environment

Portable devices have become day-to-day necessities in our lives. These devices have several critical constraints due to their small size and environment, relying on the importance of middleware in the pervasive computing environment. The significance of security is well-known in this field and it is long overdue to have middleware in the pervasive computing environment that deals with security. In this paper, we present S-MARKS, middleware that is secure by design. Features of S-MARKS include validating devices, discovering resources, modeling trust, handling malicious recommendations, and avoiding privacy violation
Effects of woody debris, microtopography, and organic matter amendments on the biotic community of constructed depressional wetlands

Abstract To increase wetland acreage and biodiversity, Delaware agencies constructed >220 depressional wetlands. During construction, agencies included amendments thought to increase biodiversity. Because the efficacy of amendments is unknown, we investigated their effects on macroinvertebrate and vegetative communities. We selected 20 standardized wetlands (five contained coarse woody debris (CWD) and microtopography amendments (land surface ridges and furrows), five had neither, five had CWD only, and five had microtopography only). Additionally, 12 wetlands had received organic matter amendments (i.e., straw). Insect richness ( P = 0.010; r 2 = 0.16), insect biomass ( P = 0.023; r 2 = 0.13), intolerant insect biomass ( P = 0.033, r 2 = 0.03), Ephemeroptera biomass ( P = 0.027; r 2 = 0.12), and Odonata biomass ( P = 0.046; r 2 = 0.10) increased with CWD volume. Obligate plant percent cover increased with microtopographic variation ( P = 0.029; r 2 = 0.120). Although organic matter amendments did not increase percent soil organic matter ( t 13.7 = −1.16, P = 0.264), total ( P = 0.027; r 2 = 0.12), native ( P = 0.036; r 2 = 0.11), and facultative ( P = 0.001; r 2 = 0.24) plant richness increased with percent soil organic matter. To enhance biodiversity, constructed wetlands should contain CWD, but additional research is needed to understand the benefits of microtopography and organic matter amendments.