cssi/SciSciGPT-SciSciNet huggingface dataset:
Iterative chromosome mutation and selection as a mechanism of complete transformation of human diploid fibroblasts by SV40 T antigen

The acquisition of an extended lifespan and of neoplastic properties, including anchorage independence, ability to grow in low serum-containing media, morphological transformation, immortalization and tumorigenicity in nude mice were studied in 31 human fibroblast lineages transfected with plasmids containing the SV40 early genes. Plasmids were used that contained sequences for large T alone, or large T plus small t or large T plus small t plus the SV40 origin. Cells expressing large T antigen gradually acquired the ability to form colonies in low serum or to form anchorage-independent colonies. Large T antigen was sufficient to cause complete transformation to tumorigenicity if multi-step lineage evolution was obtained by prolonged serial passage and if in vivo progression was assisted by means of a gelatin sponge implantation technique. Cells derived from progressive tumors initiated in sponges showed enhanced tumorigenicity as measured by ability to obtain tumors without using sponges and with reduced latent period, higher incidence and with fewer cells inoculated. Multiple lineages of human fibroblasts have been converted to tumorigenicity without additional treatments such as transfection with activated oncogenes or exposure to carcinogens. These data, taken in conjunction with earlier studies showing that T antigen causes chromosome mutation preceding and accompanying the accumulation of the neoplastic phenotype, suggests that the T protein drives the transformation process by acting as a mutagen and cells with growth advantages were selected for in vitro and in vivo. With the possible exception of morphological transformation, the presence or absence of genes for small t and the SV40 origin were not critical for the process.
Comprehensive Two-Dimensional High-Speed Gas Chromatography with Chemometric Analysis

High-speed comprehensive two-dimensional gas chromatography (GC×GC) is performed, in which a polar second column performs separations every half second on portions of the effluent from a nonpolar first column. Chemometric techniques that are traditionally used on chromatographic separations with multichannel detection are applied to two-dimensional chromatographic data, for the purpose of quantifying incompletely resolved peaks. Generalized rank annihilation method (GRAM) is evaluated in the quantification of varying amounts of selected overlapped analytes in a GC×GC analysis of modified white gasoline. GRAM requires a sample and standard data set for quantification, and the high retention time precision arising from use of shortened GC columns aids in the analysis. Results from GRAM analysis of GC×GC data are compared with a reference GC method. The test analytes ethylbenzene and m-xylene, existing in various proportions in white gasoline samples, were successfully deconvoluted despite having resolutions...
Resolving signals to cohesion: Two models of bridging inference

This study employs reading time and eye‐fixation paradigms to test two models of how readers create bridging inferences to resolve signals to textual cohesion (e.g., too, as in Juan is a shortstop. Maria is athletic too). One model views bridges as stand‐alone propositions that are minimally necessary to maintain the coherence of the text. The other model views bridges as the result of a form of deduction in which the reader tacitly establishes premises that provide rational support for the bridging inferences. Students were timed as they read pairs of sentences, half of which were related by a signal to cohesion. Following each sentence pair, students verified a statement that probed verbatim recall or inference from the sentence pair. Readers’ responses to probe statements were consistent with having supplied an unstated premise in addition to the inferential bridge when reading sentences that contained a signal to cohesion but not when reading unsignaled sentences. These response measures correlate wit...
The Structural Basis of Phenylketonuria

Abstract The human phenylalanine hydroxylase gene (PAH) (locus on human chromosome 12q24.1) contains the expressed nucleotide sequence which encodes the hepatic enzyme phenylalanine hydroxylase (PheOH). The PheOH enzyme hydroxylates the essential amino acid l -phenylalanine resulting in another amino acid, tyrosine. This is the major pathway for catabolizing dietary l -phenylalanine and accounts for approximately 75% of the disposal of this amino acid. The autosomal recessive disease phenylketonuria (PKU) is the result of a deficiency of PheOH enzymatic activity due to mutations in the PAH gene. Of the mutant alleles that cause hyperphenylalaninemia or PKU 99% map to the PAH gene. The remaining 1% maps to several genes that encode enzymes involved in the biosynthesis or regeneration of the cofactor ((6R)- l -erythro-5,6,7,8-tetrahydrobiopterin) regenerating the cofactor (tetrahydrobiopterin) necessary for the hydroxylation reaction. The recently solved crystal structures of human phenylalanine hydroxylase provide a structural scaffold for explaining the effects of some of the mutations in the PAH gene and suggest future biochemical studies that may increase our understanding of the PKU mutations.
Phenomenology and information studies

Purpose – To examine work on phenomenology and determine what information studies can learn and use from that work.Design/methodology/approach – The paper presents a literature‐based conceptual analysis of pioneering work in phenomenology (including that of Edmund Husserl, Martin Heidegger, Paul Ricoeur, and others), application of such ideas as intentionality and being in information studies work, and the potential for greater application of the information seeker as other.Findings – The literature on phenomenology contains thought that is directly relevant to information studies and information work. Close examination of perception, intentionality, and interpretation is integral to individuals’ activities related to searching for and retrieving information, determining relevance, and using technology. Essential to the realization of phenomenology's potential is adoption of communication by dialogue so that an information seeker is able both to conceptualize need and to articulate that need. Some promisi...
Theoretical calculations of the melting points of H2, D2, and 4He at room temperature☆

Abstract Theoretical calculations were made of the room temperature melting points of H2, D2, and 4He. We obtained melting pressures of 54, 57 and 94 kbar, respectively, which are compared with the experimental values of 57, 53 and 115 kbar.
Substrate Heating Effects in Excimer Laser Planarization of Aluminum

Substantial improvements in excimer laser planarization processes are observed with substrate heating. Cavities, associated with filling of high aspect ratio vias at low substrate temperature, can be eliminated by substrate heating. Damage associated with pulse overlap regions can be temperature sensitive, and is reduced as substrate temperatures areincreased. While required fluences for planarization and sample damage both decrease as the sample temperature increases, the relative insensitivity of the damage threshold generally results in larger process windows at higher temperatures. We also report model calculations of the effect of substrate heating on sample temperature distributions and the durations of the laser driven melts.
Stress and velocity fields in two- and three-dimensional hoppers

Abstract We present a numerical method for solving the equations governing the flow of a granular material. Previous work has been limited to plane-strain hoppers. The method used here can be applied to three-dimensional hoppers. Numerical solutions, in two and three dimensions, are given.
Minor Fitness Benefits for Edge Avoidance in Nesting Grassland Birds in the Northeastern United States

ABSTRACT. Grassland birds are often affected negatively by habitat fragmentation. Outcomes include greater nest predation and brood parasitism, decreased colonization rates of small, isolated patches, and greater nest density in remnant core habitats. These effects have been well documented in the Midwest, but little is known about fragmentation and edge effects on grassland birds in the fragmented agricultural fields within the forested landscapes of the northeastern United States. From 2002 to 2010, we assessed how edges and edge types affected nest-site location and daily nest survival (DNS) of Savannah Sparrows (Passerculus sandwichensis) and Bobolinks (Dolichonyx oryzivorus) breeding in 11 fields (range: 13.2–38.3 ha; mean = 21.1 ha) within a large agricultural region of Vermont. Mean (± SD) distance to edge was 80.3 ± 39.6 m for Savannah Sparrows (n = 995) and 94.5 ± 56.5 m for Bobolinks (n = 652). Both species nested significantly less than expected within 50 m of the edge. For Savannah Sparrows ne...
Clinical case report: efficacy of yogic techniques in the treatment of obsessive compulsive disorders.

The aim of this study was to investigate the clinical efficacy of yogic techniques in the treatment of eight adults with obsessive-compulsive disorder (OCD). A specific yogic breathing pattern has been prescribed for the treatment of OCD, as well as others for treating generalized anxiety. A one year course of therapy was followed. Subjects improved on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) comparing baseline with three, six, nine, & 12 month results (one-way ANOVA for repeated measures, F(4,12) = 3.343, p < or = .046). Five patients completed the study (Y-BOCS results were 83%, 79%, 65%, 61% improvement, and one at-18%), group mean improvement of +54%. The Symptoms Checklist-90-R showed significant improvement comparing baseline and 12 months using two-tailed T-tests for OCD (t = 13.856, p < .001), anxiety (t = 3.167, p < .051), and global severity indexes (t = 7.314, p = .005). Perceived Stress Scale scores showed significant improvement for the five test periods (one-way ANOVA for repeated measures, F(4,12) = 9.114, p < or = .001). Five patients were well stabilized on fluoxetine prior to the study, three stopped medication after seven months or less, and two significantly reduced it, one by 25% and the other by 50%. These techniques, merit further study under controlled conditions and could help lead to new approaches for the treatment of OCD and perhaps other impulse control and anxiety-related disorders.
A review of mechanisms and models for dynamic failure, strength, and fragmentation

Abstract Modeling of catastrophic disruption requires understanding the processes of dynamic failure and fragmentation. This paper summarizes current mechanisms and models for dynamic failure, strength, and fragmentation, reviewing these from a mechanics perspective and with an emphasis on making links to the developing advances in these areas in the engineering and computational mechanics communities. We describe dynamic failure processes, examine size and rate effects, articulate the scaling concepts that arise naturally from these processes, and examine the influences of these processes on effective strength and fragmentation.
Scalable media streaming in large peer-to-peer networks

We design a peer-to-peer technique for single-source media streaming. This technique allows the media server to distribute content to many clients by organizing them into an appropriate tree rooted at the server. This application-layer multicast tree has a height O(logN)where N is the number of clients, and a node degree bounded by a constant. This helps reduce the number of processing hops on the delivery path to a client while avoiding network bottleneck. Consequently, the end-to-end delay is kept small. Although one could build a tree satisfying such properties easily, an efficient control protocol between the nodes must be in place to maintain the tree under the effects of network dynamics and unpredictable client behaviors. Our technique handles such situations gracefully requiring a constant amortized control overhead. Especially, failure recovery can be done regionally with little impact on the existing clients.
The Cohomological Dimension of a Resultant Variety in Prime Characteristicp

Ž . 2 2 Ž . Let F s, t s X s q 2 X st q X t 1 F i F 3 be a collection of bii i0 i1 i2 nary quadratic forms with indeterminate coefficients over a field k and let w x R s k X . The aim of this paper is to compute the cohomoi, j 1F iF 3, 0 F jF 2 logical dimension of the ideal I ; R generated by the following Sylvester Ž . Ž . Ž . Ž . resultants: Res F , F , Res F , F , Res F , F , and Res F q F , F . 1 2 1 3 2 3 1 2 3 The closed points of the affine variety defined by I correspond to coefficients of the three forms having a common zero. Thus, in the w x Ž terminology of L1 , I is a resultant system for F , F , and F compare 1 2 3 w x. with Theorem 1.b in L1 . In general, if F , . . . , F are binary forms of 1 s degrees d G d G ??? G d , one can show that a resultant system is 1 2 s s Ž . Ž w x. generated by at least 1 q Ý 1 q d elements Theorem 1 in L1 and ts3 t one would like to know if this lower bound is sharp. In our case, where s s 3 and d s d s d s 2, the question is whether 1 2 3 4Ž . I can be generated by three elements. This would imply that H R s 0 I and this is the motivation behind the main result of this paper. 4Ž . It turns out that it is possible to show that H R s 0 working in the I Ž . subring of joint invariants of G s GL 2, k acting on R via change of Ž . variables in s, t . This calculation is based on some recent results by Lyubeznik on F-modules, which include an algorithm for deciding whether local cohomology modules over regular rings of prime characteristic p vanish. To the best of the author’s knowledge, Theorem 9 in this paper is the first application of this algorithm. Yan has recently produced a 4Ž . w x topological argument showing that H R vanishes in characteristic 0 Y . I
Reversal of multidrug resistance‐associated protein‐mediated drug resistance in cultured human neuroblastoma cells by the quinolone antibiotic difloxacin

BACKGROUND We have recently shown that high-level expression of the multidrug resistance-associated protein (MRP) gene is a powerful independent predictor of poor outcome in neuroblastoma. The clinical implication of these findings is that MRP modulators may prove therapeutically useful. PROCEDURE We therefore investigated the ability of difloxacin, a quinolone antimicrobial antibiotic, to increase drug cytotoxicity in unselected cultured human neuroblastoma cells. Drug cytotoxicity was determined using a microtiter assay in neuroblastoma cells expressing low (SH-EP), intermediate (NBL-S), or high [BE(2)-C] levels of MRP. RESULTS Difloxacin (50 microg/ml) increased sensitivity to the MRP substrates, vincristine, doxorubicin, daunorubicin, and potassium antimony tartrate to an extent directly proportional to their level of MRP expression. No change in the response to cisplatin, which is not a substrate for MRP, was observed in any of the cell lines. CONCLUSIONS The data demonstrate that difloxacin can reverse drug resistance in unselected human neuroblastoma cells and is therefore a potential candidate for future clinical trials.
Anticipatory Behavior in Blood Glucose Control: Using Meal Prior Probabilities to Prepare for Future Meal Disturbances

Abstract Automatic regulation of blood glucose in patients with Type 1 Diabetes is challenged by unknown or unannounced food consumption. Yet we know most food is ingested in discrete meals, spaced by brief periods of fasting. Treating meals as discrete events, this paper proposes a set of prior probabilities relating distinct meals independently of daily patterns. Using these prior probabilities, closed-loop blood glucose control can attain anticipatory behavior, implicitly lowering glucose levels when patients should be hungry and meals are most likely to occur. This improves overall performance and individual meal responses. The benefits occur because blood glucose prediction, which anticipates future food intake, can achieve near zero mean errors even over a long prediction horizon. As a side effect, such predictors can easily be tuned or tested against unrestricted out-patient data which, by definition, contains unknown meals. We validate our approach in both prediction and control of blood glucose levels. We see improved prediction accuracy over 1-4 hour horizons and a significant reduction in the blood glucose risk index for simulated closed-loop control.
In vitro synergism between berberine and miconazole against planktonic and biofilm Candida cultures.

Abstract Objectives To investigate the antimycotic activity of the plant alkaloid berberine (BBR), alone and in combination with antifungal azoles, against planktonic and biofilm Candida cultures. Design The minimum inhibitory concentrations (MICs) of BBR, miconazole (MCZ), and fluconazole (FLC) towards Candida albicans, Candida glabrata, Candida kefyr, Candida krusei, Candida parapsilosis, and Candida tropicalis were determined by a microdilution method. For C. albicans, the synergistic effects of BBR combined with MCZ or FLC were examined in a paper disc agar diffusion assay and checkerboard microdilution assay. The effect of the BBR/MCZ combination was further investigated in a C. albicans biofilm formation model with a dual-chamber flow cell. The effect on metabolic activity of biofilm cells was established using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)/menadione. Results Berberine inhibited the growth of various Candida species (MICs 0.98–31.25 mg/L) in the following order of susceptibility: C. krusei > C. kefyr > C. glabrata > C. tropicalis > C. parapsilosis and C. albicans. Synergism between BBR and MCZ or FLC was observed in the disc diffusion assay as well as in suspension showing an FIC index 91% after 24 h, as established from the reduction in surface area coverage (P Conclusion Berberine exhibits synergistic effects with commonly used antimycotic drugs against C. albicans, either in planktonic or in biofilm growth phases.
Modified Tangent Modulus Approach, A Contribution to Plastic Hinge Analysis

A fundamental aim of developing and applying nonlinear analysis is to improve the quality of design by providing the engineer with a more reliable prediction of the performance of a structural system that is under design or investigation. This paper describes a modification to the second-order inelastic hinge method that can produce the accuracy of more sophisticated plastic zone methods in the analysis of in-plane behavior of compact doubly symmetric sections. As a basis for comparison, results are provided for an established set of benchmark problems.
A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels

Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal, and sensitization. These nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient receptor potential canonical) channels are defective in their response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role for TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses.
Statin Treatment and Functional Outcome After Ischemic Stroke: Case–Control and Meta-Analysis

Background and Purpose—Multiple studies suggest that statin use before acute ischemic stroke is associated with improved functional outcome. However, available evidence is conflicting, and several published reports are limited by small sample sizes. We therefore investigated the effect of antecedent use of statins on stroke outcome by performing a meta-analysis of all results from published studies as well as our own unpublished data. Methods—We performed a systematic literature search and meta-analysis of studies investigating the association between prestroke statin use and clinical outcome and included additional data from 126 prestroke statin users and 767 nonusers enrolled at our institution. A total of 12 studies, comprising 2013 statin users and 9682 nonusers, was meta-analyzed using a random effects model. We also meta-analyzed results for individual Trial of ORG 10172 in Acute Stroke Treatment stroke subtypes to determine whether the effect of statin use differed across subtypes using the Breslow...
Stress and ano-colorectal surgery in newborn/infant: role of anesthesia

The best anesthesia for newborns/infants necessitating colorectal surgery remains questionable. Endovenous and locoregional anesthesiological approaches were compared to determine the influence on stress response. Patients with anorectal malformations or Hirschsprung’s disease were randomized to inhalatory/epidural anesthesia (IPA) or inhalatory/endovenous anesthesia (IEA). Heart rate, blood pressure, oxygen saturation, serum concentrations of dehydroepiandrosterone, cortisol, and glucose were recorded 24 h before operation (T0), after tracheal intubation (T1), 120 min after skin incision (T2), 60 min (T3) and 24 h after operation (T4). Seventeen patients were enrolled in the study, 8 receiving IPA, and 9 IEA. Heart rate, blood pressure, oxygen saturation remained stable and normal, without statistical differences between the two groups, during the study period. Similar cortisol and glucose levels showed no statistical differences between groups. Dehydroepiandrosterone values were significantly higher in IEA during anesthesia (T1–T3) compared with IPA (T1: 494.0 vs. 266.5, p < 0.05; T2: 444.0 vs. 201.0, p < 0.05; T3: 385.0 vs. 305.0, p < 0.05). This study suggests that epidural and endovenous anesthesia are both effective in intra- and postoperative period. This preliminary report suggests that IPA is more efficient compared to IEA in controlling stress reaction related to surgery. Further larger studies are needed to confirm these findings.
Impacts of climate change on the formation and stability of late Quaternary sand sheets and falling dunes, Black Mesa region, southern Colorado Plateau, USA

Abstract Detailed geomorphic mapping and analysis of soil-stratigraphy and optically stimulated luminescence (OSL) dating of eolian sand dunes on Black Mesa, Arizona, reveal eolian sediment deposition occurred from 30 to 16 ka, followed by a period of widespread dune stabilization from 12 to 8 ka. Localized reactivation of the previously stabilized dune forms or local changes in sediment supply have occurred in the middle to late Holocene in this region. Cooler, wetter, and more variable climatic conditions during MIS 3 and 2 led to increased channel and floodplain sediment supply. Eolian sediment derived from these sources was transported up to 60 km. Deposition of this material has reduced regional topographic roughness by filling tributary canyon ‘traps’ oriented perpendicular to the dominant wind and sediment transport direction. Topographically controlled falling dunes and sand ramps in this region are preserved because of their geomorphic position and provide evidence of the paleoenvironmental state of the fluvial and eolian systems before, during, and immediately after the last glacial maximum on the southern Colorado Plateau. Widely used predictive models of eolian system dynamics are typically based entirely on climatic variables and do not account for landscape complexity and geomorphic history. Climate-only assumptions fail to give accurate predictions of the dynamics of this and many other dune fields. A growing body of work suggests that eolian deposits in wind-driven semiarid climates may be more strongly related to increases in sediment supply than to increases in aridity.
Recognition of Letters in Words and Nonwords

Summary Two visual search experiments were conducted to clarify the processes underlying the “word superiority” effect. Ss in both experiments (18 college students in Experiment 1; 18 college students and 18 older adults in Experiment 2) searched six, 50-item stimulus lists for the letters “a” and “r.” Each item consisted of a string of four letters forming either a word or a nonword anagram of that word. Items were printed in either uppercase letters, lowercase letters, or mixed-case letters (e.g., wOrD), resulting in the six stimulus lists. Significant main effects were obtained in the two experiments. Search times were shorter for words than for nonwords, regardless of case. Thus, the word superiority effect was demonstrated even when the visual configuration of the word was disrupted. Search times were also shorter for uppercase and lowercase items (i.e., same-case items) than for mixed-case items, regardless of the word/nonword condition. In addition, older persons (Experiment 2) evidenced slower pro...
Equilibrium in International Trade: A Diagrammatic Analysis

I. The problem, 748. — II. One country acts as a monopolist and sets a price which the other accepts, 749. — III. The same, continued, 752. — IV. One country acts as a discriminating monopolist, making an all-or-none offer which the other accepts, 756. — V. The case of pure competition, 759. — VI. Comparison of the three cases, 761.
High-throughput fluorescence assay of cytochrome P450 3A4

Cytochrome P450 mono-oxygenases (P450s) are the principal enzymes involved in the oxidative metabolism of drugs and other xenobiotics. In this protocol, we describe a fluorescence-based, high-throughput assay for measuring the activity of P450 3A4, one of the key enzymes involved in drug metabolism. The assay involves the oxidative debenzylation of a substituted coumarin, yielding an increase in fluorescence on reaction. The entire procedure can be accomplished in 1 h or less.
Adipogenic effect of alcohol on human bone marrow-derived mesenchymal stem cells.

Background: In addition to a decrease in bone mass in alcoholics their osteopenic skeletons show an increase in bone marrow adiposity. Human bone marrow mesenchymal stem cells (hMSC) in vivo differentiate into several phenotypes including osteogenic and adipogenic cells, both of which remain as resident populations of bone marrow. In vitro, the lineage commitment and differentiation of hMSC toward the adipogenic pathway can be promoted by alcohol. Methods: Human male and female mesenchymal stem cells from joint replacement surgery were cultured. Cells were grouped as: 1) Control (no additions to the culture medium), 2) EtOH (50 mm alcohol added to the culture medium), 3) OS (osteogenic inducers added to the culture medium), and 4) OS + EtOH (osteogenic inducers and 50 mm alcohol added to the culture medium). Cultures stained with Nile Red confirmed the development of differentiated adipocytes. Population analysis was performed using fluorescence-activated cell sorting. Gene expression of early, middle, late, and terminal differentiation stage markers (PPAR)γ2, lipoprotein lipase, adipsin, leptin, and adipocyte P2 (aP2)] was studied by Northern hybridization, and protein synthesis of aP2 was determined by Western analysis. Results: Nile red staining confirmed increased adipocyte development 10 days after the onset of treatment with 50 mm alcohol and osteogenic induction. By day 21 the number of adipocytes increased to 13.6% of the total population. Alcohol up-regulated the gene expression of PPARγ2 whereas no up-regulation was observed for the other genes. Protein production of aP2 was significantly increased in hMSC cells by culture in the presence of alcohol. Conclusions: The data suggest that alcohol's adipogenic effect on cultured hMSC is through up-regulation of PPARγ2 at the point of lineage commitment as well as through enhancement of lipid transport and storage through increased aP2 synthesis. The alcohol-induced expression and synthesis changes account for the increased Nile red staining of cultured hMSC.
Epistatic Suppression of Systemic Lupus Erythematosus: Fine Mapping of Sles1 to Less Than 1 Mb

Sle is a susceptibility locus for systemic autoimmunity derived from the lupus-prone NZM2410 mouse. The New Zealand White-derived suppressive modifier Sles1 was identified as a specific modifier of Sle1 and prevents the development of IgG anti-chromatin autoantibodies mediated by Sle1 on the C57BL/6 (B6) background. Fine mapping of Sles1 with truncated congenic intervals localizes it to a ∼956-kb segment of mouse chromosome 17. Sles1 completely abrogates the development of activated T and B cell populations in B6. Sle1 . Despite this suppression of the Sle1 -mediated cell surface activation phenotypes, B6. Sle1 Sles1 splenic B cells still exhibit intrinsic ERK phosphorylation. Classic genetic complementation tests using the nonautoimmmune 129/SvJ mouse suggests that this strain possesses a Sles1 allele complementary to that of New Zealand White, as evidenced by the lack of glomerulonephritis, splenomegaly, and antinuclear autoantibody production seen in (129 × B6. Sle1 Sles1 )F1s. These findings localize and characterize the suppressive properties of Sles1 and implicate 129 as a useful strain for aiding in the identification of this elusive epistatic modifier gene.
Object orientated automated image analysis: quantitative and qualitative estimation of inflammation in mouse lung

Historically, histopathology evaluation is performed by a pathologist generating a qualitative assessment on thin tissue sections on glass slides. In the past decade, there has been a growing interest for tools able to reduce human subjectivity and improve workload. Whole slide scanning technology combined with object orientated image analysis can offer the capacity of generating fast and reliable results. In the present study, we combined the use of these emerging technologies to characterise a mouse model for chronic asthma. We monitored the inflammatory changes over five weeks by measuring the number of neutrophils and eosinophils present in the tissue, as well as, the bronchiolar associated lymphoid tissue (BALT) area on whole lungs sections. We showed that inflammation assessment could be automated efficiently and reliably. In comparison to human evaluation performed on the same set of sections, computer generated data was more descriptive and fully quantitative. Moreover optimisation of our detection parameters allowed us to be to more sensitive and to generate data in a larger dynamic range to traditional experimental evaluation, such as bronchiolar lavage (BAL) inflammatory cell counts obtained by flow cytometry. We also took advantage of the fact that we could increase the number of samples to be analysed within a day. Such optimisation allowed us to determine the best study design and experimental conditions in order to increase statistical significance between groups. In conclusion, we showed that combination of whole slide digital scanning and image analysis could be fully automated and deliver more descriptive and biologically relevant data over traditional methods evaluating histopathological pulmonary changes observed in this mouse model of chronic asthma.
Progress in Melanoma Histopathology and Diagnosis

The past 15 years have seen rapid advances in both our understanding of hereditary melanoma genetics and the technologies that enable scientists to make discoveries. Despite great efforts by many groups worldwide, other high-risk melanoma loci besides CDKN2A still remain elusive. A panel of polymorphisms that appears to confer low-to-moderate risk for melanoma has been assembled through functional and genome-wide association studies. The goal of personalized melanoma risk prediction is within our reach, although true clinical use has yet to be established.
Palladium catalyzed aryl C–H amination with O2via in situ formation of peroxide-based oxidant(s) from dioxane

(DAF)Pd(OAc)2 (DAF = 4,5-diazafluorenone) catalyzes aerobic intramolecular aryl C–H amination with N-benzenesulfonyl-2-aminobiphenyl in dioxane to afford the corresponding carbazole product. Mechanistic studies show that the reaction involves in situ generation of peroxide species from 1,4-dioxane and O2, and the reaction further benefits from the presence of glycolic acid, an oxidative decomposition product of dioxane. An induction period observed for the formation of the carbazole product correlates with the formation of 1,4-dioxan-2-hydroperoxide via autoxidation of 1,4-dioxane, and the in situ-generated peroxide is proposed to serve as the reactive oxidant in the reaction. These findings have important implications for palladium-catalyzed aerobic oxidation reactions conducted in ethereal solvents.
Increased elasticity of a low-bandgap conjugated copolymer by random segmentation for mechanically robust solar cells

Despite the necessity of organic electronic materials to undergo large deformations in flexible, ultra-thin, and stretchable applications, many high-performance organic semiconductors are mechanically fragile. This paper describes an approach to increase the elasticity of low-bandgap conjugated polymers by statistical incorporation of unlike monomers. The material under study is PDPP2FT, an alternating copolymer. Synthesized by the Stille polymerization, it comprises an N-alkylated diketopyrrolopyrrole (DPP) unit flanked by two furan rings (2F) alternating with thiophene (T). In the modified (“segmented”) polymer, PDPP2FT-seg-2T, the DPP is exchanged for a tail-to-tail coupled unit of two 3-hexylthiophene rings (bithiophene, 2T) in an average of one of approximately five repeat units. 1H NMR spectroscopy, ultraviolet-visible spectroscopy, and gel-permeation chromatography confirm the presence and covalent incorporation of the 2T units within the conjugated backbone of the segmented polymer. The tensile modulus of the segmented polymer, 0.93 ± 0.16 GPa, is lower than that of the homopolymer, 2.17 ± 0.35 GPa. When blended with PC61BM, the segmented material produces devices with power conversion efficiencies of 2.82 ± 0.28%, which is similar to that of PDPP2FT, 2.52 ± 0.34%. These results suggest that it is possible to increase the mechanical resiliency of semiconducting polymers for solar cells without having a deleterious effect on the photovoltaic properties.
The Epidermal Growth Factor Receptor: A Missing Link Between Endoplasmic Reticulum Stress and Diabetic Complications?

See related article, pp 71–80 The endoplasmic reticulum (ER) is recognized as an organelle in which protein folding, calcium homeostasis, and lipid biosynthesis occur. The ER responds to stresses such as oxidative stress, ischemic insult, and disturbances in calcium homeostasis by upregulating ER chaperones, inhibiting protein translation, and accelerating degradation of unfolded proteins via signaling pathways collectively termed the “unfolded protein responses” (UPRs). Thus, UPRs are considered a form of cellular protection. On ER stress, the ER chaperone immunoglobulin heavy chain–binding protein (also known as HSPA5 or GRP78) binds to unfolded or misfolded proteins and dissociates from 3 well-characterized ER stress sensors, inositol-requiring 1α, double-stranded RNA-dependent protein kinase–like ER kinase, and activating transcription factor 6 to initiate the UPR pathways. However, prolonged and excessive ER stress leads to inflammation and cell apoptosis via the UPR pathways.1 In addition to the protective roles of the UPR, the literature increasingly suggests that prolonged ER stress and subsequent UPR activation likely contribute to the development and progression of various disease processes, including cardiovascular diseases such as heart failure, ischemic heart diseases, and atherosclerosis.2 Moreover, recent studies reveal that prolonged ER stress associated with metabolic syndrome leads to persistent UPRs and reduced insulin secretion, invokes oxidative stress and insulin resistance, and activates an apoptotic pathway.3 Therefore, there is strong scientific, as well as clinical, interest regarding the regulatory mechanisms and therapeutic applications of the UPR pathways associated with cardiovascular diseases. The “trans”-activation of epidermal growth factor receptor (EGFR) …
Haplotype structures of cyclooxygenase genes in human ethnic populations

Background In spite of the critical role of the COX genes in inflammation, influence of their genetic variation on pain has not been clearly elucidated. The haplotype, a particular combination of alleles observed in populations, focuses on patterns of a few single nucleotide polymorphisms (SNPs) that define each haplotype and has recently contributed to the identification of genes for disorders that are common but complex in inheritance. Methods Normal subjects (426 females and 285 males) from 4 major ethnic populations were genotyped for genes encoding COX-1 (N= 5 SNPs) and COX-2 (N= 9 SNPs). For genotyping of genomic DNA, 5' exonuclease allelic discrimination assay with the ABI Prism 7900 Sequence Detection System was used. The haploblocks based on four gamete rules were generated by Haploview version 2.05 with SNPs whose minor allele frequency> 0.1, genotype success rate> 0.9 and P> 0.05 in the Hardy-Weinberg equilibrium (HWE) test. Results In the present human cohort, ethnic populations showed differences in HWE, haploblocks and haplotype tag SNPs (htSNPs) from COX-1 and COX-2 genes. Two SNPs from COX-1 gene and COX-2 gene are out of HWE in Asian Americans while 2 SNPs from COX-2 gene are out of HWE in other ethnic populations. One or two haploblocks were found in COX genes with 3 to 7 htSNPs. Conclusions Our observation provides basic ethnic background information for analysis of genetic effects of COX-1 and COX-2 genes on individual variance in pain sensitivity and responses to drugs. Clinical Pharmacology & Therapeutics (2005) 77, P64–P64; doi: 10.1016/j.clpt.2004.12.137
The global financial customer and the spatiality of exclusion after the ‘end of geography’

This paper evaluates O’Brien’s assertion that freer global financial flows and movement will eliminate the significance of geography for financial processes because enhanced global choice will create the global financial customer. We argue here, contra O’Brien, that expanded global choice in finance has contributed to the widening global income/wealth divide, both in the global North and the global South. Financial globalization has not made geography immaterial: instead, spatial location, informed by each area’s historical and institutional background, continues to demarcate who has access to which financial services at what price. The US subprime crisis demonstrates dramatically that vulnerability to economically devastating financial crises varies dramatically across space at the national and sub-national levels.
Controlled pulse-etching with xenon difluoride

A gas-phase, room-temperature, plasmaless isotropic etching system has been used for bulk and thin film silicon etching. A computer controlled multi-chambered etcher is used to provide precisely metered pulses of xenon difluoride (XeF/sub 2/) gas to the etch chamber. Etch rates as high as 15 microns per minute have been observed. The etch appears to have infinite selectivity to many common thin films, including silicon dioxide, silicon nitride, photoresist, and aluminum. The etch rate, profile, and roughness are reported as a function of mask aperture, etch pressure, and duration.
Modeling the Effects of Choice-Set Size on the Processing of Letters and Words

Letters and words are better identified when there are fewer available choices. How do readers use choice-set restrictions? By analyzing new experimental data and previously reported data, the author shows that Bayes theorem-based models overestimate readers’ use of choice-set restrictions. This result is discordant with choice-similarity models such as R. D. Luce’s (1963a) similarity choice model, G. Keren and S. Baggen’s (1981) letter recognition model, and D. W. Massaro and G. C. Oden’s (1979) fuzzy logical model of perception. Other models posit that choice restrictions affect accuracy only by improving guessing (e.g., J. L. McClelland & D. E. Rumelhart’s, 1981, interactive activation model). It is shown that these models underestimate readers’ use of choice-set restrictions. Restriction of choice set does improve perception of letters and words, but not optimally. Decision models that may be able to explain this phenomenon are discussed.
Kinematics of prey capture and chewing in the lizard Agama agama (squamata: Agamidae)

High speed video recordings (200 fields per second) of prey capture and food processing in Agama agama permit the identification of strikes, chews and transport movements. Ten variables from strike movements and seven variables from chewing sequences are digitized; transport movements are inspected only. Univariate and multivariate statistical analyses disclose significant interindividual differences for three variables (maximum gape distance, maximum head angle, and maximum throat distance); but neither these nor principal components analysis show differences between strikes and chews for any of the gape change and hyoid depression variables. However, strikes and chews obviously differ in tongue protrusion and body movements. Chewing may be divided into four stages, comparable to those of transport cycles of other lizards and the generalized tetrapod model. Transport differs from chewing by having a shorter power stroke and relatively more cranial and less jaw movement. The kinematics of feeding in Agama agama are compared with those of other lizards studied previously.
Determinants of human apolipoprotein [a] secretion from mouse hepatocyte cultures

Efforts to develop an in vitro model system to analyze apolipoprotein [a] (apo[a]) gene transcription, mRNA translation, and protein secretion have been complicated by the limited tissue and species distribution of apo[a] and the presence of regulatory DNA sequences remote from the apo[a] transcription start site. In the current study we examined primary hepatocytes cultured from apo[a] transgenic mice as a model system for analyzing apo[a] biogenesis. Hepatocytes from mice transgenic for a yeast artificial chromosome (YAC) encoding the entire apo[a] gene in its own genomic context (YAC-apo[a] hepatocytes) were unable to maintain apo[a] expression beyond 48 h of culture. This suggests that the apo[a] promoter was not active in cultured YAC-apo[a] hepatocytes. In contrast, apo[a] expression was maintained for at least 7 days in hepatocytes cultured from mice transgenic for an apo[a] cDNA under control of the mouse transferrin promoter (transferrin-apo[a] hepatocytes). Pulse-chase experiments established that more than 80% of apo[a] synthesized by both transferrin-apo[a] and YAC-apo[a] hepatocytes was degraded prior to secretion, independently of the coexpression of human apoB. Thus, low secretion efficiency appears to be a general characteristic of human apo[a] proteins in mouse liver. Apo[a] secretion was increased somewhat (from 18% to 32%) in the presence of lipoprotein-containing serum. Transformed cell lines derived from transferrin apo[a] hepatocytes retained characteristics of apo[a] secretion similar to those observed in primary cells. Primary and transformed apo[a] transgenic hepatocytes may provide valuable additional models with which to study posttranslational mechanisms regulating apo[a] secretion
Reliability and Usefulness of Clinical Encounter Cards for a Third-Year Surgical Clerkship

Background Third-year medical students (MS3) were given clinical encounter cards (CECs) to stimulate feedback during their surgery clerkship. This study analyzes the feedback given on their clinical performance using CECs. Methods Two hundred one students enrolled in the 12-week surgery clerkship were given CECs. Each card contained the chief focus of the encounter, which was rated on a six-point Likert scale. The CECs were analyzed to determine if they provided reliable formative information, identified marginal performances, and identified differences between raters, settings, rotations, and aspects of clinical performance evaluated. Results Seven thousand three hundred eight CECs were submitted from 201 students. The CECs were completed most often (65%) in the inpatient setting. Technical skills were evaluated on 49% of CECs, history/physical examinations on 40%, and case presentations on 30%. There were comments written on half of the CECs and 89% of these were strictly positive. Women (52.8%) and faculty (63.3%) were more likely to provide written comments. The students were most likely to seek feedback from the interns and faculty who gave significantly higher ratings. The Cronbach-alpha reliability coefficient was 0.69, based on 12 raters per student. There was a significant positive correlation ( P r = 0.356), NBME score ( r = 0.258), and the final grade ( r = 0.250). Conclusions The implementation of CECs in a surgery clerkship provided a large quantity of positive feedback. The quality was limited because there were minimal recommendations for improvement and they were a poor predictor of overall clinical performance.
Más allá del “conflicto”: Palestina y las estructuras profundas de la colonización global

This article seeks to relocate the analysis of violence in Palestine within an alternative paradigm that emphasizes long-term processes of global colonization. Beginning from the premise that Palestine is a site of an ongoing settler-colonial project (Zionism) rather than a simple “conflict,” it views contemporary realities as overdetermined by the deep structures that this project has put in place. Using the work of Paul Virilio as a key theoretical touchstone, it explores Palestine’s microcosmic and often prophetic embeddedness in three overlapping colonial modes: exocolonization (the colonization of territories outside one’s own), endocolonization (the colonization of specific populations within the territory under one’s control in the context of permanent or “pure” war), and dromocolonization (the colonization of humanity by techno-scientific acceleration). Examination of these three modes not only sheds light on Zionism’s specific colonial practices (e.g., the exclusion and confinement of Palestinians), but also encourages us to think beyond actor-centered conceptions of politics and consider the impact of processes (e.g., militarization or acceleration) that stretch beyond the control of rational actors. In particular, we see how Palestine has become a laboratory for new forms of warfare and social control whose global implications cannot be overestimated. With this in mind, the article concludes by arguing that an exploration of the challenges and possibilities of decolonization in Palestine can help us think through what global decolonization might mean.