cssi/SciSciGPT-SciSciNet huggingface dataset:
Papanicolaou test interpretations of "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" : an investigation of requisite duration and number of colposcopic procedures to a definitive diagnosis of high-grade dysplasia in routine practice.

BACKGROUND. Management guidelines for women with Papanicolaou (Pap) test interpretations of ASC-H (atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion) reflect substantial risk, which ranges from 10% to 68%, of a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in their follow-up histologic samples. The present study was initiated to determine the number of colposcopic procedures and the time frame that are typically required for a definitive diagnosis of a CIN2+ lesion after a Papanicolaou (Pap) test interpretation of ASC-H in routine practice. METHODS. Clinicopathologic data on consecutive ASC-H interpretations, 97% of which were on liquid-based preparations, were reviewed. The number of biopsies (which was used in this context as a surrogate indicator for the number of colposcopic procedures) as well as the average duration required for a follow-up histologic diagnosis of CIN2+ were determined. RESULTS. Of 500 ASC-H interpretations, 75 were excluded for a variety of reasons and 165 lacked follow-up in our records. The average age and follow-up duration for the remaining 260 patients was 35.6 years and 18.5 months, respectively. CIN2+ was diagnosed in 49 (40%) of the 122 patients with at least 1 histologic follow-up. Of these 49 patients, 72% (35 of 49) were diagnosed on the first follow-up cervical biopsy, 14% (7 of 49) and 8% (4 of 49) were diagnosed on the second and third follow-up biopsies, respectively; in only 6% (3 of 49) was a fourth follow-up biopsy required. Overall, an average of 1.53 biopsies (range, 1–4) was required to attain a definitive diagnosis of CIN2+, and 28% of patients required more than 1 follow-up biopsy. The average period between the index ASC-H interpretations and CIN2+ diagnoses was 5.5 months. The average time to CIN2+ diagnoses by the first follow-up biopsy was 3 months; for diagnoses made on subsequent biopsies, the average additional follow-up duration was 8 months. Of the eventual CIN2+ diagnoses, 84% were rendered within 12 months of their associated index ASC-H interpretations. CONCLUSIONS. 1) A substantial subset—28%—of patients with biopsy-proven CIN2+ after ASC-H interpretations required more than 1 colposcopy for a definitive diagnosis of a high-grade dysplastic lesion. 2) If a CIN2+ lesion is present, the vast majority can be diagnosed in a biopsy performed within 1 year of the ASC-H interpretation. Cancer (Cancer Cytopathol) 2007. © Published 2007 by the American Cancer Society.
Small-Grain Aphid Parasitoids (Hymenoptera: Aphelinidae and Aphidiidae) of Washington: Distribution, Relative Abundance, Seasonal Occurrence, and Key to Known North American Species

New information is provided on the small-grain aphid parasitoids of eastern Washington—species population diversity, relative abundance, hosts, and spatial and temporal distribution across differing precipitation and cropping zones. In total 13 species of primary parasitoids were discovered attacking grain aphids: Aphelinus albipodus Hayat & Fatima, A. asychis Walker, A. varipes (Foerster), Aphidius avenaphis (Fitch), A. ervi Haliday, A. matricariae Haliday, Diaeretiella rapae (M'Intosh), Ephedrus sp., Lysiphlebus testaceipes (Cresson), Monoctonus washingtonensis Pike & Star´y, Praon unicum Smith, P. occidentale Baker, and P. yakimanum Pike & Starý. The predominant parasitoids were D. rapae on Russian wheat aphid, Diuraphis noxia (Kurdjumov); L. testaceipes on bird cherry-oat aphid, Rhopalosiphum padi (L.) and corn leaf aphid, R. maidis (Fitch); and A. avenaphis, A. ervi , and D. rapae on English grain aphid, Sitobion avenae (F.). This study provides baseline information essential for assessing future changes in aphid parasitoid species dynamics for eastern Washington. A comprehensive key to the known primary and secondary parasitoids associated with grain aphids in North America also is provided.
Abstract C137: Pinpointing a protein‐protein interaction site of focal adhesion kinase and VEGFR‐3 suppresses cancer growth in vivo

Tumor cell survival depends on activation of signaling pathways that suppress the apoptotic stimuli of invasion and metastasis. FAK and VEGFR‐3 are tyrosine kinases that have been identified as critical signaling molecules for these processes. Previously we have shown that VEGFR‐3 and FAK physically interact and are overexpressed in cancer cells to provide a significant survival advantage for the tumor cells. We subsequently identified a novel small molecule inhibitor that targeted VEGFR‐3‐FAK site of interaction and disrupted the survival function of these two proteins. We utilized the crystal structure of the FAK focal adhesion targeting (FAT) domain for molecular docking of small molecules that targeted the VEGFR‐3 binding site on FAK. We identified a small molecule C4 (Chloropyramine hydrochloride), that disrupted VEGFR‐3‐FAK binding, and abrogated the phosphorylation of VEGFR‐3 while reducing the phosphorylation of FAK. In vitro testing of this compound resulted in the selective growth inhibition, reduction in motility and invasion, and induction of apoptosis in a time‐ and dose‐dependent manner in many cancer cell lines, especially those that overexpressed VEGFR‐3. In vivo, C4 showed a marked reduction of tumor growth and was synergistic with doxorubicin chemotherapy in breast cancer xenograft models, with dacarbazine in melanoma xenograft models, and with gemcitabine in pancreatic cancer xenograft models. These results demonstrate that targeting the FAK‐VEGFR‐3 interaction with a small molecules inhibited the survival function of these two tyrosine kinases, representing a unique approach for molecular‐targeted highly‐specific cancer therapeutics. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C137.
The Origin and Physical Properties of the Cometary Knots in NGC 7293

On the basis that the cometary knots observed in the Helix Nebula form as a result of larger parent clouds breaking up due to Rayleigh-Taylor instability induced by radiative acceleration of the clouds, we compute characteristics of the cometary knots and of the parent clouds as well. Present observations place constraints on the positions, velocities, and sizes of the parent clouds. Requiring the clouds to produce cometary knots that are stable places further constraints on the properties of parent clouds. We formulate those constraints and show how they further limit the predicted properties of the cometary knots and bring them into agreement with their observed properties.
Nonlinear wavelet shrinkage with Bayes rules and Bayes factors

Abstract Wavelet shrinkage, the method proposed by the seminal work of Donoho and Johnstone is a disarmingly simple and efficient way of denoising data. Shrinking wavelet coefficients was proposed from several optimality criteria. In this article a wavelet shrinkage by coherent Bayesian inference in the wavelet domain is proposed. The methods are tested on standard Donoho-Johnstone test functions.
Mercury accumulation by Myriophyllum spicatum L.

Abstract An investigation of the magnitude and rate of Hg accumulation by a rooted aquatic plant—Myriophyllum spicatum L. (watermilfoil)—from solution culture and from Hg-contaminated lake sediments was conducted. As determined by solution culture experiments, Hg accumulation was much greater with inorganic than organic Hg carriers. Mercury accumulation from nutrient solution was rapid and approached maximum values in 2 hours. Organo-Hg compounds were more available than inorganic compounds from lake sediments likely because of precipitation of inorganic Hg as sulfides. Mercury accumulates in rooted aquatic plants by physical adsorption and by metabolic uptake and translocation, the latter occurring mainly with organo-Hg compounds. Rooted aquatic plants might prove to be an important link in the uptake and cycling of Hg derived from contaminated sediments.
Accurate load and generation scheduling for linearized DC models with contingencies

This paper studies the applicability of the linearized DC model in optimizing power restoration after significant network disruptions. In such circumstances, no AC base-point solution exists and the objective is to maximize the served load. The paper demonstrates that the accuracy of the linearized DC model degrades with the size of the disaster and that it can significantly underestimate active and apparent power. To remedy these limitations, the paper proposes an Angle-Constrained DC Power Flow (ACDCPF) model that enforces constraints on the line phase angles and has the ability to shed load and generation across the network. Experimental results on N-3 contingencies in the IEEE30 network and power restoration instances from disaster recovery show that the ACDCPF model provides significantly more accurate approximations of active and apparent power. In the restoration context, the ACDCPF model is shown to be much more reliable and produces significant reduction in the size of the blackouts.
Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening

Exercise is vital for maintaining bone strength and architecture. Follistatin-like 3 (FSTL3), a member of follistatin family, is a mechanosensitive protein upregulated in response to exercise and is involved in regulating musculoskeletal health. Here, we investigated the potential role of FSTL3 in exercise-driven bone remodeling. Exercise-dependent regulation of bone structure and functions was compared in mice with global Fstl3 gene deletion (Fstl3-/-) and their age-matched Fstl3+/+ littermates. Mice were exercised by low-intensity treadmill walking. The mechanical properties and mineralization were determined by μCT, three-point bending test and sequential incorporation of calcein and alizarin complexone. ELISA, Western-blot analysis and qRT-PCR were used to analyze the regulation of FSTL3 and associated molecules in the serum specimens and tissues. Daily exercise significantly increased circulating FSTL3 levels in mice, rats and humans. Compared to age-matched littermates, Fstl3-/- mice exhibited significantly lower fracture tolerance, having greater stiffness, but lower strain at fracture and yield energy. Furthermore, increased levels of circulating FSTL3 in young mice paralleled greater strain at fracture compared to the lower levels of FSTL3 in older mice. More significantly, Fstl3-/- mice exhibited loss of mechanosensitivity and irresponsiveness to exercise-dependent bone formation as compared to their Fstl3+/+ littermates. In addition, FSTL3 gene deletion resulted in loss of exercise-dependent sclerostin regulation in osteocytes and osteoblasts, as compared to Fstl3+/+ osteocytes and osteoblasts, in vivo and in vitro. The data identify FSTL3 as a critical mediator of exercise-dependent bone formation and strengthening and point to its potential role in bone health and in musculoskeletal diseases.
Time course of early delayed blood-brain barrier changes in individual cats after lonizing radiation

Abstract Cats were given 6000 rads to a volume of approximately 0.25 cm3 and followed for blood-brain barrier (B-BB) breakdown by the penicillin-EEG method. They showed a variation of about 1 to 20 days before the onset of B-BB breakdown and of 20 to 80 days for recovery. This demonstrates the central role of endothelium damage and loss of B-BB function in the pathogenesis of radiation damage to the central nervous system.
spice -Based Optoelectronic System Simulation

spiceis a widely used simulation tool for electrical circuits and systems. When optoelectronic elements, such as lasers, detectors, modulators, etc., and optical elements, such as lenses, gratings, beam splitters, etc., are incorporated into spice, optoelectronic system simulation can be combined with that of electronic systems, facilitating hybrid system design and analysis. We discuss an optoelectronic spice implementation that includes time-, power-, and wavelength-domain behaviors. Examples of optical component simulation and optical interconnect system simulation by use of spice are included and compared with the results from a conventional ray-tracing optical analysis tool.
A dynamic population of stromal cells contributes to the follicle stem cell niche in the Drosophila ovary

Epithelial stem cells are maintained within niches that promote self-renewal by providing signals that specify the stem cell fate. In the Drosophila ovary, epithelial follicle stem cells (FSCs) reside in niches at the anterior tip of the tissue and support continuous growth of the ovarian follicle epithelium. Here, we demonstrate that a neighboring dynamic population of stromal cells, called escort cells, are FSC niche cells. We show that escort cells produce both Wingless and Hedgehog ligands for the FSC lineage, and that Wingless signaling is specific for the FSC niche whereas Hedgehog signaling is active in both FSCs and daughter cells. In addition, we show that multiple escort cells simultaneously encapsulate germ cell cysts and contact FSCs. Thus, FSCs are maintained in a dynamic niche by a non-dedicated population of niche cells.
A condition equivalent to linear dependence for functions with vanishing Wronskian

Abstract It is well known that though the vanishing of the Wronskian W[Φ] of a set {Φ} of functions on an interval I is a necessary condition for it to be linearly dependent, it is not a sufficient one. Since Peano in 1989 expressed an interest in finding classes of functions for which W [Φ] ≡ 0 is sufficient for dependence and offered one such example himself, others (M. Bǒcher, D. R. Curtiss, W. Hurewicz, and G. H. Meisters) have provided related results. Here the author gives a final answer to the question by first generalizing Peano's result using the order of a critical point, thereby obtaining a dense set of intervals of dependence. He then shows that W[Φ] ≡ 0 together with a condition that the intersection of certain subspaces of En is nontrivial is equivalent to the linear dependence of {Φ} on I. The above results are used to establish the dynamical theorem that motion of a particle under the action of a central force field is planar so long as the particle is restricted from the origin. The author provides a counterexample for the case in which the particle passes through the origin.
Vegetation Burned Areas Derived from Multiple Satellite-based Active Fires

Biomass burning releases a significant amount of trace gases and aerosol emissions into the atmosphere. If unaccounted for in the modeling of climate, carbon cycle, and air quality, it leads to large uncertainties. The amount of biomass burning emissions depends significantly on burned areas. This study estimates near-real time burned areas from multiple satellite-based active fires in Hazard Mapping System (HMS) developed in NOAA, which capitalizes automated fire detections from Geostationary Operational Environmental Satellite (GOES) Imager, Advanced Very High Resolution Radiometer (AVHRR), Moderate Resolution Imaging Spectroradiometer (MODIS). The HMS fire counts are compared with a set of Landsat ETM+ burn scars for various ecosystems to investigate the rate of burned area in a fire count. The fire size and fire duration derived from multiple satellites are then used to calculate burned area every half hour. The estimated burned areas are evaluated using national inventory of burned area across the United States for 2005.
An open letter to President Bush.

ZDG)g ytwelve year old son and I have just returned from a G c} two week visit to Vietnam. I was last in Vietnam 25 years ago, when I served at the 3d Marine Division field hospital outside of Danang. I returned to Vietnamhwit mixed emotions-to visit health departments, &? clinics, schools and hospitals. Everyone was very friendly, including hundreds of people we met in public places. The visit convinced me that the United States must take a leadership role to close the festering wounds from the Vietnam War in our country and in Vietnam. It surprised me that the Vietnamese were so friendly toward Americans, despite the magnitude of destruction caused by our country during the war. There are over iO million Vietnamese "war victims," including those suffering from mental and physical disabilities, orphans, and elderly people whose children were killed. In addition, many US and Vietnamese veterans, their families, and z8 million Vietnamese children born after the war, continue to suffer. Words cannot describe the impact of the war.
NITROGEN SOURCES AND ‘A’ VALUES FOR VESICULAR–ARBUSCULAR AND NON-MYCORRHIZAL SORGHUM GROWN AT THREE RATES OF 15N-AMMONIUM SULPHATE*†

Summary Mycorrhizal and non-mycorrhizal sorghum [Sorghum bicolor (L.) Moench] plants were grown in soil treated with one of three rates of (15NH4)2SO4, fertilizer. Mycorrhizal plants did not significantly differ from non-mycorrhizal plants in total plant dry weight, total plant N, or percent utilization of the applied N by the whole plant at any fertilizer rate. However, the atom percent 15N excess in shoots, roots and the whole plant, and percent N derived from fertilizer were significantly higher for non-mycorrhizal plants at the intermediate level of fertilizer N. The percent N derived from native soil sources, and ‘A’ values were significantly higher for mycorrhizal plants, compared to non-mycorrhizal plants, at the intermediate but not low or high fertilizer rates. The results suggest that, at the intermediate fertilizer rate, where plants produced the most growth, mycorrhizal sorghum plants derived N from a source that was less available to non-mycorrhizal plants.
Reinventing the Matron: The Continued Importance of Gendered Images and Division of Labor in Modern Policing

The current research examines the workplace images and responsibilities of female police officers in 3 departments. Ethnographic interviews with 28 officers in 3 midwestern communities indicate that women in law enforcement are still viewed through a gendered lens, which shapes relations with fellow officers and the community. Images of female officers correspond to their early role in law enforcement as matrons charged with the care of female offenders and juvenile delinquents. Results indicate that female officers are expected to care for children, delinquents, and female victims regardless of personal preference or individual skills, and institutional practices tend to maintain women officers in the devalued position historically held by police matrons. Subtle interactions between officers and the belief in so-called natural feminine instincts are utilized to maintain patrol work as a masculine enterprise.
Redefining global health-care delivery

Summary Initiatives to address the unmet needs of those facing both poverty and serious illness have expanded significantly over the past decade. But many of them are designed in an ad-hoc manner to address one health problem among many; they are too rarely assessed; best practices spread slowly. When assessments of delivery do occur, they are often narrow studies of the cost-effectiveness of a single intervention rather than the complex set of them required to deliver value to patients and their families. We propose a framework for global health-care delivery and evaluation by considering efforts to introduce HIV/AIDS care to resource-poor settings. The framework introduces the notion of care delivery value chains that apply a systems-level analysis to the complex processes and interventions that must occur, across a health-care system and over time, to deliver high-value care for patients with HIV/AIDS and cooccurring conditions, from tuberculosis to malnutrition. To deliver value, vertical or stand-alone projects must be integrated into shared delivery infrastructure so that personnel and facilities are used wisely and economies of scale reaped. Two other integrative processes are necessary for delivering and assessing value in global health: one is the alignment of delivery with local context by incorporating knowledge of both barriers to good outcomes (from poor nutrition to a lack of water and sanitation) and broader social and economic determinants of health and wellbeing (jobs, housing, physical infrastructure). The second is the use of effective investments in care delivery to promote equitable economic development, especially for those struggling against poverty and high burdens of disease. We close by reporting our own shared experience of seeking to move towards a science of delivery by harnessing research and training to understand and improve care delivery.
Constitutive analysis of thin biological membranes with application to radial stretching of a hollow circular membrane

The constitutive analysis of the mechanical response of thin elastic membranes under inplane deformation is presented by using the multiplicative decomposition of the deformation gradient into its areal and distortional parts. Specific results are obtained for the Evans–Skalak form of the strain energy function. The solution to the problem of radial stretching of a hollow circular membrane obeying this constitutive model is then derived. The stress concentration factor is determined as a function of the relative hole size and the magnitude of the applied tension. The tension boundary is identified above which no compressive stress appears in the membrane. The limit boundary is introduced below which the membrane cannot support the applied loading without unstable wrinkling. For the loading between the tension and the limit boundary, nonuniformly distributed infinitesimal wrinkles appear within the inner portion of the membrane, carrying radial tension but no circumferential stress (tension field). The specific form of the strain energy function is used to describe this behavior, and to calculate the amount of the membrane area absorbed by infinitesimal wrinkles. The wrinkled portion is surrounded by the outer portion of the membrane carrying both radial and circumferential stresses. The limit boundary is reached when wrinkles spread throughout the membrane. It is shown that for a sufficiently large tension at the outer boundary, the wrinkling does not spread throughout the membrane no matter how large the applied tension at the inner boundary of the membrane is, provided that no rupture takes place. The limiting extent of the tension field in such cases is calculated. The linearized version of the analysis is characterized by a closed form solution.
Bleeding complications of glycoprotein IIb-IIIa receptor inhibitors.

Abstract Large clinical studies have demonstrated an unequivocal clinical benefit of antithrombotic therapy with inhibitors of the platelet surface-membrane glycoprotein (GP) IIb-IIIa receptor in a broad range of patients with ischemic heart disease. Potent antiplatelet effects of these agents, however, may increase the risk of bleeding complications, as occurred in the first large evaluation of this therapy, the Evaluation of c7E3 for Prevention of Ischemic Complications (EPIC) trial with abciximab (c7E3 Fab; ReoPro ® ; Centocor, Malvern, Pa). Although the incidence of bleeding events in subsequent studies has been reduced through the use of a low-dose, weight-adjusted heparin regimen and early removal of vascular sheaths in patients who have undergone percutaneous coronary interventions, hemorrhage continues to be the most common complication of GP IIb-IIIa inhibitor therapy. This review summarizes current experience related to bleeding complications with various GP IIb-IIIa inhibitors and suggests strategies for improved management of bleeding in patients receiving these agents. (Am Heart J 1999;138:S287-S296)
Heterozygote detection through bleomycin-induced G2 chromatid breakage in dyskeratosis congenita families.

Abstract We determined the mean number of chromatid breaks per cell (b/c) in the bleomycintreated lymphocytes of 10 patients with dyskeratosis congenita (DC) and 26 of their relatives to ascertain whether bleomycin sensitivity would distinguish DC heterozygotes from normal individuals. We observed a significantly higher mean number of chromatid b/c in DC patients and obligate heterozygotes (patients versus controls, p p = 0.0076, Mann-Whitney rank-sum test). Unequivocal heterozygote detection was not possible owing to overlap of the b/c values of patients, heterozygotes, and controls, but our findings provided strong evidence of a link between autosomal recessive as well as X-linked recessive DC mutations and bleomycin sensitivity in homozygous, hemizygous, and heterozygous individuals.
Natural deduction in connectionist systems

The relation between logic and thought has long been controversial, but has recently influenced theorizing about the nature of mental processes in cognitive science. One prominent tradition argues that to explain the systematicity of thought we must posit syntactically structured representations inside the cognitive system which can be operated upon by structure sensitive rules similar to those employed in systems of natural deduction. I have argued elsewhere that the systematicity of human thought might better be explained as resulting from the fact that we have learned natural languages which are themselves syntactically structured. According to this view, symbols of natural language are external to the cognitive processing system and what the cognitive system must learn to do is produce and comprehend such symbols. In this paper I pursue that idea by arguing that ability in natural deduction itself may rely on pattern recognition abilities that enable us to operate on external symbols rather than encodings of rules that might be applied to internal representations. To support this suggestion, I present a series of experiments with connectionist networks that have been trained to construct simple natural deductions in sentential logic. These networks not only succeed in reconstructing the derivations on which they have been trained, but in constructing new derivations that are only similar to the ones on which they have been trained.
Data-based predictions of line strengths in alkali-metal-like isoelectronic sequences.

The empirically observed isoelectronic linearization of alkali-metal-like line strengths [ital Z][sup 2][ital S]=[ital A]+[ital B]/([ital Z][minus][ital C]) is examined for the Li, Na, Cu, and Ag sequences. It is found that small deviations from this linearity observed at high [ital Z] can be removed by use of a correction factor obtained from the relativistic formulation of the hydrogenlike line strength. With this correction, low-[ital Z] data can be linearly interpolated to the nonrelativistic hydrogenic value in the high-[ital Z] limit. The linearization is tested in the data-rich Li, Na, and Cu sequences and is utilized to make precise predictions for the Ag sequence on the basis of a small number of accurate measurements.
Predictors of acceptance of H1N1 influenza vaccination by FDNY firefighters and EMS workers

Abstract Background There is a widely recognized need for vaccination of health care workers (HCWs). We undertook this study to assess the 2009–2010 H1N1 vaccination rates in ∼14,000 firefighters and emergency medical service (EMS) workers at the Fire Department of New York (FDNY) and to determine predictors of H1N1 vaccine acceptance. Methods After 9/11/01, FDNY developed a bio-preparedness drill where units are dispatched to FDNY-BIOPOD (biologic points of distributions) for rapid distribution of medications/vaccines in the event of a biological disaster. Since 2005, FDNY offers free, voluntary seasonal influenza vaccination during routine medical monitoring/treatment examinations and at FDNY-BIOPOD. In 2009, FDNY-BIOPOD instead offered the H1N1 vaccine. We report on FDNY H1N1 vaccination rates and on predictors of acceptance using bivariate and multivariable techniques. Results Overall, 10,612 (77%) FDNY workers were offered H1N1 vaccination, of whom 5831 (55%) accepted. Acceptance was 57.2% during FDNY-BIOPOD compared with 34.4% during medical monitoring/treatment exams ( p = 0.0001). Workers who accepted prior seasonal influenza vaccinations were 4 times more likely to accept H1N1 vaccination (AOR = 4.4, CI 95 = 4.0–4.8). Conclusion FDNY offered H1N1 vaccination to 77% of its workforce during the 2009–2010 season. Prior seasonal vaccine acceptance and vaccination in a group setting such as FDNY-BIOPOD dramatically increased acceptance of the H1N1 vaccine. However, within a voluntary program, additional strategies are needed to further increase vaccine acceptance in first responders and other HCWs.
Structural Basis for DNA-Hairpin Promoter Recognition by the Bacteriophage N4 Virion RNA Polymerase

Coliphage N4 virion-encapsidated RNA polymerase (vRNAP) is a member of the phage T7-like single-subunit RNA polymerase (RNAP) family. Its central domain (mini-vRNAP) contains all RNAP functions of the full-length vRNAP, which recognizes a 5 to 7 base pair stem and 3 nucleotide loop hairpin DNA promoter. Here, we report the X-ray crystal structures of mini-vRNAP bound to promoters. Mini-vRNAP uses four structural motifs to recognize DNA sequences at the hairpin loop and stem and to unwind DNA. Despite their low sequence similarity, three out of four motifs are shared with T7 RNAP that recognizes a double-stranded DNA promoter. The binary complex structure and results of engineered disulfide linkage experiments reveal that the plug and motif B loop, which block the access of template DNA to the active site in the apo-form mini-vRNAP, undergo a large-scale conformational change upon promoter binding, explaining the restricted promoter specificity that is critical for N4 phage early transcription.
Effects of Electrical and Structural Remodeling on Atrial Fibrillation Maintenance: A Simulation Study

Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength - electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely.
The effect of market conduct on international steam coal trade

Abstract This paper is concerned with the determinants of international steam coal trade. Most quantitative work in explaining such trade has been stymied by the apparent failure of the competitive model to account for observed and anticipated trade flows. In general, authors have sought institutional explanations for this failure. The hypothesis explored by this paper is that the exercising of market power by certain agents in the market can lead to trade patterns consistent with those observed and anticipated. This hypothesis is explored through a simple model of imperfect market equilibrium. In addition to perfect competition, we examine Cournot-Nash monopoly (South Africa), duopoly (South Africa, Australia) and duopoly/monopsony (South Africa, Australia, Japan) with a competitive fringe of producers (US, Canada, Poland, China, Colombia). Using the equilibrium model of coal trade, we examine these market structures and evaluate the extent to which they can explain existing and anticipated trade patterns.
Increased catalytic efficiency following gene fusion of bifunctional methionine sulfoxide reductase enzymes from Shewanella oneidensis.

Methionine sulfoxide reductase enzymes MsrA and MsrB have complementary stereospecificies that respectively reduce the S- and R-stereoisomers of methionine sulfoxide (MetSO), and together function as critical antioxidant enzymes. In some pathogenic and metal -reducing bacteria these genes are fused to form a bifunctional methionine sulfoxide reductase (i.e., MsrBA) enzyme. To investigate how gene fusion affects the substrate specificity and catalytic activities of Msr, we have cloned and expressed the MsrBA enzyme from Shewanella oneidensis, a metal-reducing bacterium and fish pathogen. For comparison, we also cloned and expressed the wild-type MsrA enzyme from Shewanella oneidensis and a genetically engineered MsrB protein. MsrBA is able to completely reduce (i.e., repair) MetSO in the calcium regulatory protein calmodulin (CaM); while only partial repair is observed using both MsrA and MsrB enzymes together at 25 °C. A restoration of the normal protein fold is observed coincident with the repair of MetSO in oxidized CaM by MsrBA, as monitored by the time-dependent increases in the anisotropy associated with the rigidly bound multiuse affinity probe 4′5′-bis(1,3,2-dithoarsolan-2yl)fluorescein (FlAsH). Underlying the efficient repair of MetSO in oxidized CaM is the coordinate activity of the two catalytic domains in the MsrBA fusion protein, which results in an order of magnitude rate enhancement in comparison to the individual MsrA or MsrB enzymes alone. The coordinate binding of both domains of MsrBA permits the full repair of all MetSO in CaMox. The common expression of Msr fusion proteins in bacterial pathogens is consistent with an important role for this enzyme activity in the maintenance of protein function necessary for bacterial survival under highly oxidizing conditions associated with pathogenesis or bioremediation.
Dry granulite mineral assemblages in the contact aureoles of the Nain complex, Labrador

Thermal aureoles surrounding intrusions of the Nain complex, Labrador, contain many unique or unusual mineral assemblages in aluminous gneisses and granulites, ironstones, and ultramafic rocks. Some of the limiting assemblages are (in addition to feldspars±pyrrhotite±ilmenite±graphite ±biotite±magnetite): Ga-Ol-Hy-Sp, Ga-Cd-Hy-Sp, Ga-Hy-Ol-Qz, Cd-Hy-Os-Qz, Ga-Cd-Sp-Si, Cd-Sp-Co-Si, Ga-Ol-Hy-Sp, Ga-Cd-Hy-Sp, Hy-Ol-Qz-Aug, and Ol-Hy-Sp(±Chl±Ca-amph±Aug). On the basis of some of these assemblages are (in addition to feldspars±pyrrhotite±ilmenite±graphite from 3.7–6.6 kbar and temperatures from 645–915 ° C. The paucity of hydrous phases, the preponderance of Ksp-Plag-Qz or even Cd-Ksp-Qz without evidence of a melt at these temperatures, the stable occurrence of osumilite, and the common presence of graphite suggest that $$P_{{\text{H}}_{\text{2}} {\text{O}}}$$ was extremely low. The presence of graphite-pyrrhotite, the compositions of ilmenites, the compositions of coexisting Fe-Ti oxides, and other mineralogical data indicate the $$f_{{\text{O}}_{\text{2}} }$$ was relatively low and, despite the wide range in bulk compositions and rock types, may have followed an approximately buffered trend. It is possible that the magmas of the Nain complex may have acted as an “external” $$f_{{\text{O}}_{\text{2}} }$$ buffer for the aureole rocks. The unique nature of these mineral assemblages appears to be a function of the extremely low $$P_{{\text{H}}_{\text{2}} {\text{O}}}$$ .
Exact test size and power of a Gaussian error linear model for an internal pilot study

Wittes and Brittain recommended using an 'internal pilot study' to adjust sample size. The approach involves five steps in testing a general linear hypothesis for a general linear univariate model, with Gaussian errors. First, specify the design, hypothesis, desired test size, power, a smallest 'clinically meaningful' effect, and a speculated error variance. Second, conduct a power analysis to choose provisionally a planned sample size. Third, collect a specified proportion of the planned sample as the internal pilot sample, and estimate the variance (but do not test the hypothesis). Fourth, update the power analysis with the variance estimate to adjust the total sample size. Fifth, finish the study and test the hypothesis with all data. We describe methods for computing exact test size and power under this scenario. Our analytic results agree with simulations of Wittes and Brittain. Furthermore, our exact results apply to any general linear univariate model with fixed predictors, which is much more general than the two-sample t-test considered by Wittes and Brittain. In addition, our results allow for examination of the impact on test size of internal pilot studies for more complicated designs in the framework of the general linear model. We examine the impact of (i) small samples, (ii) allowing the planned sample size to decrease, (iii) the choice of internal pilot sample size, and (iv) the maximum allowable size of the second sample. All affect test size, power and expected total sample size. We present a number of examples including one that uses an internal pilot study in a three-group analysis of variance.
Streptavidin-Phycoerythrin Conjugated Proteins Bound to Biotin on Langmuir-Blodgett Films of Biotinylated Lipid Monolayers

Studies involving the specific and non-specific surface recognition of biotin on biotinylated LB lipid monolayers by streptavidin and avidin conjugated phycoerythrin are presented. Both streptavidin and avidin conjugates were injected under the monolayer and found to preferentially adsorb to the biotinylated monolayers at the air-water interface. Pressure-area isotherms displayed a biotin-streptavidin/avidin complex dependent increase in surface pressure at expanded areas indicating protein adsorption. The binding of protein was confirmed by transferring the monolayer films to solid supports and measuring the characteristic intense phycoerythrin fluorescence at 576 nm. The effect of protein charge, monolayer packing density and structure, and activation of the tetramer proteins towards specific and non-specific binding are discussed. These results suggest a novel and general methodology for the two-dimensional ordering of protein monolayers with potential bioelectronic, optical and protein structure research applications.
Water movement across split frog skin

A net inward fluid reabsorption (salt-linked flow) has been observed in isolated skin epithelium (split skin) with the same magnitude as in whole skin when identical NaCl Ringer solutions were used to bathe both sides. Split skins also respond to a hyperosmotic sucrose solution bathing the outer (epithelial) surface by generating an outward osmotic flow. A non-linear relationship between osmotic flow and the osmotic gradient has been found in split skin similar to that found in whole skin.
Microarray Analysis of Gene Expression in Cultured Skin Substitutes Compared with Native Human Skin

Cultured skin substitutes (CSS), prepared using keratinocytes, fibroblasts, and biopolymers, can facilitate closure of massive burn wounds by increasing the availability of autologous tissue for grafting. But because they contain only two cell types, skin substitutes cannot replace all of the functions of native human skin. To better understand the physiological and molecular differences between CSS and native skin, we undertook a comprehensive analysis of gene expression in native skin, cultured keratinocytes, cultured fibroblasts, and skin substitutes using Affymetrix gene chip microarrays. Hierarchical tree clustering identified six major clusters of coordinately regulated genes, using a list of 1030 genes that were the most differentially expressed between groups. These clusters correspond to biomarker pools representing expression signatures for native skin, fibroblasts, keratinocytes, and cultured skin. The expression analysis revealed that entire clusters of genes were either up- or downregulated upon combination of fibroblasts and keratinocytes in cultured skin grafts. Further, several categories of genes were overexpressed in CSS compared with native skin, including genes associated with hyperproliferative skin or activated keratinocytes. The observed pattern of expression indicates that CSS in vitro, which display a well-differentiated epidermal layer, exhibit a hyperproliferative phenotype similar to wounded native skin.
The Dirichlet-to-Neumann map for two-dimensional crack problems

A coupled analytic/finite-element method is presented for two-dimensional crack problems. Two classes of problems are studied. The first considers problems where non-linear constitutive processes occur in a region near the crack tip and the remotely applied loading can be characterized by the linear elastic K-field and perhaps the T-stress. In this case, the finite-element method is applied in a circular region around the crack tip where non-linear constitutive response is occurring, and stiffness contributions associated with a numerically implemented Dirichlet-to-Neumann map are imposed on the circular boundary to account for the large surrounding elastic domain and the remote applied loading. The second class of problems considers entirely linear elastic domains with irregular external boundaries and/or complex applied loadings. Here, the discrete Dirichlet-to-Neumann map is used to represent a circular region surrounding the crack tip, and finite-elements are used for the external region. In this case the mixed mode stress intensity factors and the T-stress are retrieved from the map.
Optoacoustic sensing for target detection inside cylindrical catheters

Optoacoustic sensing is a hybrid technique that combines the advantages of high sensing depth of ultrasound with contrast of optical absorption. In this study a miniature optoacoustic probe that can characterize the target properties located at the distal end of a catheter is investigated. The probe includes an optical fiber to illuminate the target with the pulsed laser light and a hydrophone to detect the generated optoacoustic signal. The probe is designed for the forwardsensing and therefore the acoustic signal propagates along the tube before being detected. Due to the circular geometry, the waves inside the tube are highly complex. A three dimensional numerical simulation is performed to model the optoacoustic wave generation and propagation inside the water filled cylindrical tubes. The effect of the boundary condition, tube diameter and target size on the detected signal is systematically evaluated. A prototype of the probe is made and tested for detecting an absorbing target inside a 2mm diameter tube submerged in water. The preliminary experimental results corresponding to the simulation is acquired. Although many different medical applications for this miniature probe may exist, our main focus is on detecting the occlusion inside the ventricular shunts. These catheters are used to divert the excess cerebrospinal fluid to the absorption site and regulate inter cranial pressure of hydrocephalous patients. Unfortunately the malfunction rate of these catheters due to blockage is very high. This sensing tool could locate the occluding tissue non-invasively and can potentially characterize the occlusion composites by scanning at different wavelengths of the light.
Flow-Based Isolation and Neutralization of Circulating Tumor Cells

Circulating tumor cells (CTC) have the potential to be used clinically as a diagnostic tool and a treatment tool in the field of oncology. As a diagnostic tool, CTC may be used to indicate the presence of a tumor before the tumor is large enough to cause noticeable symptoms. As a treatment tool, CTC isolated from patients may be used to test the efficacy of chemotherapy options to personalize patient treatment. One way for tumors to spread is through metastasis via the circulatory system. CTC are able to exploit the natural leukocyte recruitment process that is initially mediated by rolling on transient selectin bonds. Our capture devices take advantage of this naturally occurring recruitment step to isolate CTC from whole blood by flowing samples through selectin and antibody-coated microtubes. Whole blood was spiked with a known concentration of labeled cancer cells and then perfused through pre-coated microtubes. Microtubes were then rinsed to remove unbound cells and the number of labeled cells captured on the lumen was assessed. CTC were successfully captured from whole blood at a clinically relevant level on the order of 10 cells per mL. Combination tubes with selectin and antibody coated surface exhibited higher capture rate than tubes coated with selectin alone or antibody alone. Additionally, CTC capture was demonstrated with the KG1a hematopoietic cell line and the Du145 epithelial cell line. Thus, the in vivo process of selectin-mediated CTC recruitment to distant vessel walls can be used in vitro to target CTC to a tube lumen. The microtube device can also be used to capture CTC of hematopoietic and epithelial tumor origin and is demonstrated sensitivity down to the order of 10 CTC per mL. In a related study aimed at reducing the blood borne metastatic cancer load, we have shown that cells captured to a surface can be neutralized by a receptor-mediated biochemical signal (Rana et al. 2008). In the proposed method we have shown that using a combined selecting and TRAIL (TNF Related Apoptosis Inducing Ligand or Apo 2L) functionalized surface we are able to kill about 30% of the captured cells in a short duration of 1 hour whereas it took about 4 hours to kill the same proportion of cells without flow on a similarly functionalized. Here we have taken the approach a step further by showing that with very small doses of chemotherapeutic agents like Bortezomib, we can increase the kill rate of CTCs., thus allowing the device to function in senarios where the patient is undergoing treatment. We show here with leukemic cells that are treated with Bortezomib that we are able kill about 41% of the captured cells.Copyright © 2009 by ASME
Effect of separate sampling on classification and the minimax criterion

It is commonplace in bioinformatics (and elsewhere) to build a classifier from sample data in which the sample sizes of the classes are not random; that is, they are selected prior to sampling. The result is that there is no estimate of the prior class probabilities available from the data. In this paper, we find an analytic result for the minimax solution for the class prior probabilities for a general Neyman-Pearson induced classifier. From that we derive Anderson's classical minimax prior probability “estimate.” Using synthetic and real data, we demonstrate the degradation in classifier performance from using inaccurate values for the prior probabilities.
The Busemann¿Petty problem via spherical harmonics

Abstract The Busemann–Petty problem asks whether symmetric convex bodies in R n with smaller central hyperplane sections necessarily have smaller n-dimensional volume. The solution has recently been completed, and the answer is affirmative if n⩽4 and negative if n⩾5. In this article we present a short proof of the affirmative result and its generalization using the Funk–Hecke formula for spherical harmonics.