cssi/SciSciGPT-SciSciNet huggingface dataset:
Applications of RNA structure analysis to retroviral packaging and anti-retroviral therapeutic discovery

Our laboratory is blending new RNA chemistries, largely directed at the ribose 2'-hydroxyl group, with quantitative interpretation to create new kinds of chemical microscopes for accurate RNA structure analysis. This seminar will focus on two examples from retroviral biology. All retroviral RNAs contain a packaging element that directs the genome into nascent virus particles through a mechanism that has been unclear. Using SHAPE, we probed the structure of murine leukemia virus RNA inside virus particles and identified the binding site for the nucleocapsid domain of Gag. The RNA structural context is critical: High-affinity binding requires two specific UCUG-UR-UCUG motifs flanked by base-paired elements. Mutation of four guanosine residues in these two motifs - only 4 nucleotides per genomic RNA - reduced packaging to non-specific levels. These motifs only form in genomic RNA dimers; thus analysis of authentic full-length RNA was critical. This work illustrates how local context and RNA structure can create information-rich recognition signals from simple single-stranded sequence elements. In the second example, we discovered strong correlations between shRNA-mediated inhibition of HIV-1 replication in a cell-based assay and both the energetic cost of breaking secondary structures and the overall annealing energy between guide strand and folded target RNA. These correlations were only apparent when the energetic cost of disrupting pre-existing structure in the HIV-1 RNA was calculated using a secondary structure model derived from SHAPE probing information. We verified these correlations by design and evaluation of additional shRNAs and could achieve consistent inhibition of HIV-1 production by 90%. This approach emphasizes the profound, but ultimately predictable, role of RNA structure in tuning RNAi function and is likely to prove broadly useful in understanding large-scale biological recognition involving RNA.
Further analysis of the expectations hypothesis using very short-term rates

Abstract Longstaff [Longstaff, F., 2000. The term structure of very short-term rates: new evidence for the expectations hypothesis. Journal of Financial Economics 58, 397–415] finds support for the expectations hypothesis at the very short end of the repurchase agreement (repo) term structure while other studies find calendar-time-based regularities cause rejection of the expectations hypothesis. Using Longstaff’s methods on a sample of repo rates that pre-dates Longstaff’s sample, we reject the expectations hypothesis for every maturity. The pre-Longstaff-sample repo data comes from a time period where the behavior of short-term interest rates is similar to the long-run average behavior of short-term interest rates. Our results imply that expectations hold when rates are less volatile and/or that we may be entering a period of lower volatility.
Survey of simulation and diagnostic techniques for hypersonic nonequilibrium flows

The possible means of simulating nonequilibrium reacting flows in hypersonic environments, and the required diagnostic techniques, are surveyed in two categories: bulk flow behavior and determination of chemical rate parameters. Flow visualization of shock shapes for validation of computational-fluid dynamic calculations is proposed. The facilities and the operating conditions necessary to produce the required nonequilibrium conditions, the suitable optical techniques, and their sensitivity requirements, are surveyed. Shock-tubes, shock-tunnels, and ballistic ranges in a wide range of sizes and strengths are found to be useful for this purpose, but severe sensitivity requirements are indicated for the optical instruments, which can be met only by using highly-collimated laser sources. Likewise, for the determination of chemical parameters, this paper summarizes the quantities that need to be determined, required facilities and their operating conditions, and the suitable diagnostic techniques and their performance requirements. Shock tubes of various strengths are found to be useful for this purpose. Vacuum ultraviolet absorption and fluorescence spectroscopy and coherent anti-Stokes Raman spectroscopy are found to be the techniques best suited for the measurements of the chemical data.
Antigenic diversity in the periodontopathogen, Actinobacillus actinomycetemcomitans

We have identified a significant level of variation in antibody responses to Actinobacillus actinomycetemcomitans outer membrane antigens (OMA). This study was designed to verify A. actinomycetemcomitans antigenic diversity that could contribute to maintaining this chronic infection despite the host immune response. A. actinomycetemcomitans strains (5 from different patients and 3 the same patient) were cultured and OMA prepared for Western immunoblotting studies. Antigen bands in the OMA were identified using 7 sera obtained from 3 adult periodontitis (AP) and 4 localized juvenile periodontitis (LJP) patients that were documented with elevated A. actinomycetemcomitans antibody and infection. Differences/similarities in the antigen patterns among the A. actinomycetemcomitans strains were assessed using a kappa similarity coefficient. Antigen bands in the A. actinomycetemcomitans strains ranged from 11–150 kDa; however, variation in antigen patterns were noted among the strains. Utilizing the human sera as...
Investor Expectations and the Performance of Value Stocks versus Growth Stocks

Investment decision making is often categorized according to style: growth or value. Value stocks are typically characterized as having low P/Es. Studies from the late 1970s conclude that stocks with low P/Es produce positive risk-adjusted returns. Subsequent studies have found positive returns associated with other methods of categorizing a stock as a value stock, such as low price to book value and low price to cash flow. Growth stocks have opposite characteristics, such as high P/Es.
An extension of Harvey's formula

We generalize Harvey's formula from n+2 spheres orthogonal to a sphere in \( R^n \) to any \( m\ge n+2 \) points in \( R^n \).
DEVELOPING K–16 STUDENT STANDARDS FOR LANGUAGE LEARNING: A CRITICAL EXAMINATION OF THE CASE OF ESPERANTO

In light of the ongoing attention to standards-based education in U.S. schools and the concern over how to effectively develop literacy skills in a first, let alone a second, language, this article reports on the drafting of the K–16 Student Standards for Learning Esperanto in the United States. Esperanto is ideally suited to aid children in the primary grades develop accurate phonemic awareness and an understanding of the parts of speech because of its absolutely regular sound-symbol correspondence and the transparency of it morphosyntactic structure. In addition to improved first language (L1) literacy skills, the early successful second language (L2) acquisition experience that Esperanto can provide leaves students more inclined and better prepared to study French, Italian, German, Spanish, or other ethnic languages when the opportunity becomes available to them. It is in this spirit that the Task Force on Standards for the Learning of Esperanto K–16, an international group of Esperanto educators, stan...
Host plant density and territorial behavior of the seed bug, Neacoryphus bicrucis (Hemiptera: Lygaeidae)

Adults of the seed bug, Neacoryphus bicrucis, are most numerous in large host plant patches and where host plants are most dense within patches. Males patrol small territories composed of host plants and expel other males and unreceptive females. Larger males aggressively exclude smaller males from high quality territories where both host plants and females are most dense. Consequently, large males mate more frequently than small males. Males remain for longer time in areas where host plants are more dense. However, mating experience influences tenure within a host plant patch such that males tend to remain where they have recently mated. Courtship is aggressive and male territorial behavior is similar to courtship behavior. Preference for territories in areas of high host plant density appears to have been selected to increase the rate of encounter with females which preferentially oviposit in areas of high host plant density.
Salivary fluoride levels following application of fluoride varnish or fluoride rinse.

Abstract – Objectives: This study examined the concentration of fluoride in whole saliva over time following the application of a fluoride varnish or a single rinse with a fluoride solution. Methods: A two-period, two-treatment randomized cross-over experimental trial with a 2-week washout period was used with 16 adult subjects. In the first period, eight subjects rinsed once with a 0.05% NaF solution and 8 subjects had 5.0% NaF varnish applied to facial and lingual surfaces of 20 teeth. Stimulated whole saliva was collected at baseline, 5 and 15 min, 1, 2, 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, 104 h. After the washout period each subject was switched to the other treatment and saliva was collected at the same intervals. Salivary fluoride content was measured with the micro-diffusion method. Results: The NaF levels peaked at 5 min after application for both varnish (mean ± SE 24.5 ± 5.0 ppm) and rinse (3.2 ± 0.8 ppm). Mean NaF levels returned to baseline, on average, within 2 h for the rinse and within 24 h for the varnish. The maximum fluoride levels were significantly greater (P < 0.01) with the varnish than with the rinse and remained above baseline levels for a longer duration. Conclusions: Salivary fluoride levels with the rinse returned to baseline, on average, in 2 h while they remained elevated for, on average, 24 h with the varnish. Salivary fluoride levels from the varnish were found to be comparable with those in previous studies for 1.1% neutral NaF.
Titelbild: Angew. Chem. 18/2002

Das Titelbild zeigt das jungste Mitglied eines „elitaren“ Klubs von aromatischen Molekulen. Das Platinabenzol, in dem eine CH-Einheit durch ein isoelektronisches Platin-Fragment ersetzt ist, vervollstandigt die Serie von Metallaarenen mit Elementen der dritten Reihe der Gruppe VIII (Os, Ir, Pt). Ehemals im Klub nicht zugelassen, verschaffte es sich dank der Ahnlichkeit vieler seiner Eigenschaften mit denen sechsgliedriger Heteroarene – darunter Ringplanaritat, delokalisierte Bindungen, tieffeldverschobene Signale im 1H-NMR-Spektrum – Zutritt zu dem erlesenen Kreise. Den Metallabenzolen dieser Reihe ist gemeinsam, dass sie keine zusatzliche Stabilisierung durch Koordination an ein weiteres Metallzentrum benotigen. Mehr zu der Stuktur und den Eigenschaften dieses Molekuls erfahren Sie in der Zuschrift von M. M. Haley et al. auf S. 3620 ff.
The Complexity Era in Economics

This article argues that the neoclassical era in economics has ended and is being replaced by a new era. What best characterizes the new era is its acceptance that the economy is complex, and thus that it might be called the complexity era. The complexity era has not arrived through a revolution. Instead, it has evolved out of the many strains of neoclassical work, along with work done by less orthodox mainstream and heterodox economists. It is only in its beginning stages. The article discusses the work that is forming the foundation of the complexity era, and how that work will likely change the way in which we understand economic phenomena and the economics profession.
Study of proton translocation in chloroplasts--a new approach.

Summary Measurement of O 2 evolution in coupled pea chloroplasts in the presence of proton sponge [1,8-bis(dimethylamino)-naphthalene] and DABCO (1,4-diazabicyclo[2,2,2]octane), which are lipophilic and hydrophilic proton trapping agents, showed an increase in the electron transport rate in H 2 O to Methylviologen, Ferricyanide, Dichlorodimethoxy-p-benzoquinone, Dimethylquinone, Tetramethyl-p-phenylenediamine Hill reactions and in Dichlorophenol indophenol/ascorbate to Methylviologen Hill reaction. This increase in the electron transport rate in the presence of proton scavengers was not observed in uncoupled chloroplasts (in the presence of methylamine) and in Tetramethyl-p-phenylenediamine/ ascorbate to Methylviologen Hill reaction which is not coupled to ATP formation.
Interaction of acoustic waves and microwave radiation fields in ferroelectric insulators

A theoretical description of the phonon echo phenomenon in ferroelectric insulators is presented. Numerical results for both the paraelectric and ferroelectric phases of BaTi${\mathrm{O}}_{3}$ indicate that this process is enhanced in ferroelectric materials relative to the situation in nonferroelectric materials. The analysis of the paraelectric phase of BaTi${\mathrm{O}}_{3}$ also yields the general result that in the absence of a uniform (dc) electric field an echo wave cannot be generated via the proposed mechanism in any crystalline solid (whether it be an insulator or a semiconductor) that possesses a center of inversion symmetry. This gives rise to the possibility of utilizing the interaction as a tool for obtaining measurements of one of the nonlinear material coefficients at microwave frequencies.
Development of a charge adjustment model for cardiac catheterization.

A methodology that would allow for compari- son of charges across institutions has not been developed for catheterization in congenital heart disease. A single institution catheterization database with prospectively collected case characteristics was linked to hospital charges related and limited to an episode of care in the catheteri- zation laboratory for fiscal years 2008-2010. Catheteriza- tion charge categories (CCC) were developed to group types of catheterization procedures using a combination of empiric data and expert consensus. A multivariable model with outcome charges was created using CCC and addi- tional patient and procedural characteristics. In 3 fiscal years, 3,839 cases were available for analysis. Forty cath- eterization procedure types were categorized into 7 CCC yielding a grouper variable with an R 2 explanatory value of 72.6 %. In the final CCC, the largest proportion of cases was in CCC 2 (34 %), which included diagnostic cases without intervention. Biopsy cases were isolated in CCC 1 (12 %), and percutaneous pulmonary valve placement alone made up CCC 7 (2 %). The final model included CCC, number of interventions, and cardiac diagnosis (R 2 = 74.2 %). Additionally, current financial metrics such as APR-DRG severity of illness and case mix index dem- onstrated a lack of correlation with CCC. We have devel- oped a catheterization procedure type financial grouper that accounts for the diverse case population encountered in catheterization for congenital heart disease. CCC and our multivariable model could be used to understand financial characteristics of a population at a single point in time, longitudinally, and to compare populations.
Toward a revised evolutionary adaptationist analysis of depression: the social navigation hypothesis.

Evolutionary biologists use Darwinian theory and functional design (''reverse engineering'') analyses, to develop and test hypotheses about the adaptive functions of traits. Based upon a consideration of human social life and a functional design analysis of depression's core symptomatology we offer a comprehensive theory of its adaptive significance called the Social Navigation Hypothesis (SNH). The SNH attempts to account for all intensities of depression based on standard evolutionary theories of sociality, communication and psychological pain. The SNH suggests that depression evolved to perform two complimentary social problem-solving functions. First, depression induces cognitive changes that focus and enhance capacities for the accurate analysis and solution of key social problems, suggesting a social rumination function. Second, the costs associated with the anhedonia and psychomotor perturbation of depression can persuade reluctant social partners to provide help or make concessions via two possible mechanisms, namely, honest signaling and passive, unintentional fitness extortion. Thus it may also have a social motivation function.  2002 Elsevier Science B.V. All rights reserved.
Setting Boundaries: Examining Borders and Borderlands

Between Frontiers: Nation and Identity in a Southeast Asian Borderland. By Ishikawa Noboru. Athens, OH: Ohio University Press, 2010. 275 pp., $28.00 paperback (ISBN 978-0-89680-273-5). Territorial Choice: The Politics of Boundaries and Borders. Edited by Baldersheim Harald, E. Rose Lawrence. New York: Palgrave Macmillan, 2010. 288 pp., $90.00 hardcover (ISBN 978-0-230-23333-1). Understanding Life in the Borderlands: Boundaries in Depth and Motion. Edited by William Zartman I.. Athens, GA: The University of Georgia Press, 2010. 256 pp., $24.95 paperback (ISBN 978-0-8203-3407-3). Borders and territory have been the subject of much research within international affairs. Territory has long been seen as a source of conflict between people and states and disputes over borders have been frequent. While conflicts over territory and borders have been highly researched, there has been less analysis of the borderlands themselves. Two of the works reviewed here contribute to the underdeveloped, yet growing, body of literature on the nature of borderlands. The final reviewed book focuses on the politics of territorial choice within national policymaking and thus discusses boundaries within states rather than the borderlands between states. Understanding Life in the Borderlands: Boundaries in Depth and Motion , edited by I. William Zartman, brings together academics from a broad range of fields of study (such as anthropology, history, political science, religious studies, and archeology) in an attempt to understand the dynamic nature of borderlands. Overall, the volume offers a cohesion that is rare in an edited volume. The introduction is well written and outlines the theses of the book; several cases are presented throughout the book illustrating aspects of these theses. The conclusion offers lessons from these various experiences to help policymakers deal with the dynamic nature of borderlands. One key aspect of the volume is that the authors see borderlands as identifiable units in and of themselves that warrant scholarly attention. In the introduction to the volume, Zartman utilizes Hansen's 1981 definition of borderlands as “subnational areas whose economic and social life is directly and significantly affected by proximity to an international border” (Zartman 2). Further, he argues that borderlands are characterized by movement and “need to be understood, not as places or even events, but as social processes” (2). In this opening chapter, Zartman introduces several key concepts and themes that are discussed throughout the book. …
Retrospective Study of Testicular Degeneration in Raccoons with Canine Distemper Infection

A 6-year (1985-1990) retrospective survey of raccoons with canine distemper infection and an outbreak of the disease in 1988 on South Island, South Carolina, are described. During this epizootic, 3 male raccoons with the clinical disease had gross testicular lesions that, on histopathologic examination, revealed severe diffuse degeneration and mineralization of seminiferous tubules. The testicular pathology of canine distemper in raccoons has not been previously reported.
Developments of a Generalized Theory of Jet Noise

Following a generalized theory of supersonic jet noise, explicit analytical expressions for identifying jet noise mechanisms and numerical calculations of high-speed jet noise characteristics have been obtained. This new theory is uniformly valid in the transonic and supersonic speed ranges, and it includes implicitly refraction and convection of sound through the jet flow. Given results include the transition from U-law to the U-law, differences in directivity for high and low frequencies, sound source distribution, noise spectrum, and the coupled effects of refraction and convection. The implications of these results and their correspondences with results in the existing literature are discussed.
Medieval Japan: Taking the Middle Ages Outside Europe

What does it mean to claim that a nation has had a medieval period? And, given how closely associated the concept is with a specifically European history, how might a non-Western country claim the period for its own past? This article will look at what historians have labeled Japan's Middle Ages in order to investigate these issues. We will consider how Japan came to have a medieval period, examine what historians regard as its key features, and investigate some problems associated with taking the concept of the Middle Ages to Japan.
Melt extrusion: process to product

Introduction: Niche applicability and industrial adaptability have led hot melt extrusion (HME) techniques to gain wide acceptance and have, therefore, solidified their place in the array of pharmaceutical research and manufacturing operations. Melt extrusion's momentum has resulted in extensive research publications, reviews and patents on the subject for over a decade. Currently, > 50% of the new drug candidates are speculated to be highly lipophilic and thus poorly bioavailable. HME is a key technology for these and other formulation and processing issues. Areas covered: Various approaches have been addressed using HME in developing solid molecular dispersions and have demonstrated viability to provide sustained, modified and targeted drug delivery resulting in improved bioavailability. This review provides a holistic perspective on HME from equipment, processing and materials to its varied applications in oral delivery (immediate release, sustained release, taste masking, enteric and targeted release,...
Effect of the Pore Region of a Transmembrane Ion Channel on the Physical Properties of a Simple Membrane

The effect of membrane proteins and peptides on their surrounding lipids is crucial for the structure, dynamics, and function of complex biological membranes as well as the interplay between membrane proteins and their environment. Here, we present a study of the influence of the transmembrane pore region of an ion channel on the physical properties of a phospholipid bilayer. We performed multinanosecond molecular dynamics simulations of the pore-forming aggregate of R-helical transmembrane peptides, which constitutes a model for the channel region of the nicotinic acetylcholine receptor, inserted in a simple lipid bilayer at conditions similar to those of the recent NMR experiments [Opella, S. J.; et al. Nature Struct. Biol. 1999, 6, 374]. The results obtained are compared with simulations of the pure lipid bilayer membrane. In particular, we consider here the simplest possible model membrane: a fully hydrated dimyristoyl-sn-glycerophosphocholine lipid bilayer, which is in the biologically relevant fluid lamellar phase at room temperature. Our analysis reveals that the peptides affect the properties of the lipid bilayer in several ways: (1) the bilayer thickness increases, (2) the number of gauche defects of the hydrocarbon chains decreases, (3) the orientational order of the hydrocarbon chains increases, (4) the orientational probability distribution of the lipid headgroup dipole moments becomes broader (more disordered), and (5) the lipid headgroup dipole moments are on average more oriented toward the water phase. Some of these effects depend on the specific properties of the case studied, such as the hydrophobic length of the bundle and the charges at the interface. Interestingly, the pore does not affect the two different sides of the membrane in the same way.
Multiple NSAID-induced hits injure the small intestine: underlying mechanisms and novel strategies

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) injury including jejunal/ileal mucosal ulceration, bleeding, and even perforation in susceptible patients. The underlying mechanisms are largely unknown, but they are distinct from those related to gastric injury. Based on recent insights from experimental models, including genetics and pharmacology in rodents typically exposed to diclofenac, indomethacin, or naproxen, we propose a multiple-hit pathogenesis of NSAID enteropathy. The multiple hits start with an initial pharmacokinetic determinant caused by vectorial hepatobiliary excretion and delivery of glucuronidated NSAID or oxidative metabolite conjugates to the distal small intestinal lumen, where bacterial β-glucuronidase produces critical aglycones. The released aglycones are then taken up by enterocytes and further metabolized by intestinal cytochrome P450s to potentially reactive intermediates. The "first hit" is caused by the NSAID and/or oxidative metabolites that induce severe endoplasmic reticulum stress or mitochondrial stress and lead to cell death. The "second hit" is created by the significant subsequent inflammatory response that would follow such a first-hit injury. Based on these putative mechanisms, strategies have been developed to protect the enterocytes from being exposed to the parent NSAID and/or oxidative metabolites. Among these, a novel strategy already demonstrated in a murine model is the selective disruption of bacteria-specific β-glucuronidases with a novel small molecule inhibitor that does not harm the bacteria and that alleviates NSAID-induced enteropathy. Such mechanism-based strategies require further investigation but provide potential avenues for the alleviation of the GI toxicity caused by multiple NSAID hits.
Overview of DMSP nightime lights and future possibilities

The Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS) has a unique capability to collect low-light imaging data of the earth at night. The OLS and its predecessors have collected this style of data on a nightly global basis since 1972. The digital archive of OLS data extends back to 1992. Over the years several global nighttime lights products have been generated. NGDC has now produced a set of global cloud-free nighttime lights products, specifically processed for the detection of changes in lighting emitted by human settlements, spanning 1992-93 to 2008. While the OLS is far from ideal for observing nighttime lights, the DMSP nighttime lights products have been successfully used in modeling the spatial distribution of population density, carbon emissions, and economic activity.
Indulgences in Late Medieval England: Passports to Paradise? – By R. N. Swanson

This is an important book on late medieval religious practice, economics, and society; it is, however, especially important as a study of indulgences: what they were, how they were obtained, who ob...
Transparent shaping of existing software to support pervasive and autonomic computing

The need for adaptability in software is growing, driven in part by the emergence of pervasive and autonomic computing. In many cases, it is desirable to enhance existing programs with adaptive behavior, enabling them to execute effectively in dynamic environments. In this paper, we propose a general programming model called transparent shaping to enable dynamic adaptation in existing programs. We describe an approach to implementing transparent shaping that combines four key software development techniques: aspect-oriented programming to realize separation of concerns at development time, behavioral reflection to support software reconfiguration at run time, component-based design to facilitate independent development and deployment of adaptive code, and adaptive middleware to encapsulate the adaptive functionality. After presenting the general model, we discuss two specific realizations of transparent shaping that we have developed and used to create adaptable applications from existing programs.
Parametric Uncertainty in Intra-Herd Foot-and-Mouth Disease Epidemiological Models

Epidemiological models that simulate the spread of Foot-and-Mouth Disease within a herd are the foundation of decision support tools used by governments to help advise and inform strategy to combat outbreaks. Contact transmission data used to parameterize these models, contrary to assumption, contain a significant amount of variability and uncertainty. The implications of this finding suggest that the resultant model output might not accurately simulate the spread of an outbreak. If this is true, the potential impact due to uncertainty inherent to the decision support tools used by governments might be significant.
Oscillator death in populations of “all to all” coupled nonlinear oscillators

Abstract The behavior of finitely many and infinitely many coupled weakly nonlinear oscillators is studied and it is shown that the uniform rest state can become stable if the coupling is sufficiently strong and the frequencies are sufficiently disparate. Numerical results show that the phenomenon is robust and occurs when many of the hypotheses are relaxed.
Comparison of Germ Cell Mutagenicity in Male CYP2E1-Null and Wild-Type Mice Treated with Acrylamide: Evidence Supporting a Glycidamide-Mediated Effect

Acrylamide is an animal carcinogen and probable human carcinogen present in appreciable amounts in heated carbohydraterich foodstuffs. It is also a germ cell mutagen, inducing dominant lethal mutations and heritable chromosomal translocations in postmeiotic sperm of treated mice. Acrylamide’s affinity for male germ cells has sometimes been overlooked in assessing its toxicity and defining human health risks. Previous investigations of acrylamide’s germ cell activity in mice showed stronger effects after repeated administration of low doses compared with a single high dose, suggesting the possible involvement of a stable metabolite. A key oxidative metabolite of acrylamide is the epoxide glycidamide, generated by cytochrome P4502E1 (CYP2E1). To explore the role of CYP2E1 metabolism in the germ cell mutagenicity of acrylamide, CYP2E1-null and wild-type male mice were treated by intraperitoneal injection with 0, 12.5, 25, or 50 mg acrylamide (5 ml saline)21 kg 21 day 21 for 5 consecutive days. At defined times after exposure, males were mated to untreated B6C3F1 females. Females were killed in late gestation and uterine contents were examined. Dose-related increases in resorption moles (chromosomally aberrant embryos) and decreases in the numbers of pregnant females and the proportion of living fetuses were seen in females mated to acrylamide-treated wild-type mice. No changes in any fertility parameters were seen in females mated to acrylamide-treated CYP2E1-null mice. Our results constitute the first unequivocal demonstration that acrylamide-induced germ cell mutations in male mice require CYP2E1-mediated epoxidation of acrylamide. Thus, CYP2E1 polymorphisms in human populations, resulting in variable enzyme metabolic activities, may produce differential susceptibilities to acrylamide toxicities.
Engineering software engineering teams

This paper presents novel ideas for understanding how software engineering teams communicate and coordinate. We utilize these ideas to understand how these teams should be constructed and what individuals and managers can do to ensure that teams perform at high levels. Our view is based on numerous observations and interactions with enterprise software engineering teams and influenced by economic models of information sharing. We propose that neither a fully top-down nor bottom-up approach is entirely suitable for teams; rather teams must be cognizant of this issue and work to embrace both models of information flow. This, in turn, can be facilitated by the role of intercessor who seeks to properly guide, direct, and curate both top-down and bottom-up information flows.
Incidence and prognostic impact of high-risk HPV tumor infection in cervical esophageal carcinoma

Background: Cervical esophageal carcinoma (CEC) is an uncommon malignancy. Limited data supports the use of definitive chemoradiotherapy (CRT) as primary treatment. Furthermore, the role of human papillomavirus (HPV) tumor infection in CEC remains unknown. This study retrospectively analyzes both outcomes of CEC patients treated with CRT and the incidence and potential role of HPV tumor infection in CEC lesions. Methods: A total of 37 CEC patients were treated with definitive CRT at our institution between 1987 and 2013. Of these, 19 had tumor samples available for high-risk HPV (types 16 and 18) pathological analysis. Results: For all patients (n=37), 5-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 34.1%, 40.2%, and 65.6%, respectively. On pathological analysis, 1/19 (5.3%) patients had an HPV-positive lesion. Conclusions: Definitive CRT provides disease-related outcomes comparable to surgery. Moreover, HPV tumor infection in CEC is uncommon and its prognostic role is unclear. Our data contribute to the construction of an anatomical map of HPV tumor infection in squamous cell carcinomas (SCC) of the upper aerodigestive tract, and suggest a steep drop in viral infection rates at sites distal to the oropharynx, including the cervical esophagus.
An Estimation of the Load Rate Imparted to a Climbing Anchor During Fall Arrest

The strength of ice anchors is, in part, a function of the load rate; increasing the jerk of the decelerating climber reduces anchor strength in brittle ice. To provide a rule of thumb estimate of the load rate imparted to a climbing anchor during fall arrest, a simple, algebraic formula for load rate is derived. As a first approximation, the load rate is proportional to both the rope modulus and the square root of the fall factor and is inversely proportional to the square root of the length of rope between the belayer and the falling climber. Load rate considerations suggest that ice climbers should use low modulus ropes and avoid high fall factor falls close to the anchor.
What's the Difference Between Cantor Sets?

(1994). What's the Difference Between Cantor Sets? The American Mathematical Monthly: Vol. 101, No. 7, pp. 640-650.
Nonsurgical management of primary skin malignancies.

Advances in cryosurgery, electrosurgery, radiation therapy, topical chemotherapy, and interferon therapy have resulted in cure rates in excess of 95% for selected skin malignancies. These nonsurgical methods use field therapy for their mechanism of treatment. Field therapy uses known tumor growth characteristics to treat a defined area containing both tumor and a surrounding area of normal tissue. Each of these therapies combines high cure rates with cost-effective use of time, space, and equipment.
Overview of important design issues for a National Human Exposure Assessment Survey

Exposure issues have important consequences for regulatory decisions. Reliable answers to exposure questions are critical for site cleanup, model validation, and cumulative risk issues, as well as giving perspective on our risk estimates. This paper discusses some of the important issues in designing the National Human Exposure Assessment Survey (NHEXAS) and, by implication, other exposure-monitoring-based studies as well. Sampling design issues are discussed in terms useful to exposure assessors. These issues include simple random sample designs versus more complex multistage designs, design efficiency, how to determine the sample size for the desired precision of the estimate, and the effects of stratification and oversampling on the needed sample size. This paper also discusses several important nonsampling issues such as population definition, response rates, and several potential sources of error in interpreting the monitoring results.
Diet and Gut Microbial Function in Metabolic and Cardiovascular Disease Risk

Over the past decade, the gut microbiome has emerged as a novel and largely unexplored source of variability for metabolic and cardiovascular disease risk, including diabetes. Animal and human studies support several possible pathways through which the gut microbiome may impact health, including the production of health-related metabolites from dietary sources. Diet is considered important to shaping the gut microbiota; in addition, gut microbiota influence the metabolism of many dietary components. In the present paper, we address the distinction between compositional and functional analysis of the gut microbiota. We focus on literature that highlights the value of moving beyond surveys of microbial composition to measuring gut microbial functioning to delineate mechanisms related to the interplay between diet and gut microbiota in cardiometabolic health.
MicroRNA Expression Analysis in Multiple Myeloma.

Introduction: The analysis of what goes awry in a malignant cell has focused primarily on mutations of protein-encoding genes and their regulatory sequences. However, recent work on microRNA (miRNA) has shed light on the possible involvement of miRNA genes in human disease. miRNA are small “noncoding” or “non-messenger” RNAs of about 21–25 nucleotides in length that function as regulators of gene expression essentially by pairing to the mRNA of protein-coding genes to initiate mRNA degradation or repression of translation. We are interested in characterizing miRNA expression profiles in human myeloma cell lines (HMCLs) and myeloma patient samples. Multiple myeloma (MM) is a plasma cell tumor characterized by frequent chromosomal translocations. Materials and methods: The expression of miRNA in HMCLs, primary MM cells (hyperdiploid samples) and normal plasma cells was determined using human microRNA chips. The GenoExporer TM Human microRNA chips were developed by GenoSensor (Tempe, AZ) and the microarray contains 226 human microRNA sequences in addition to control sequences. The DNA oligo probes are synthesized and immobilized on the chips (1”x 3” standard glass microslide). The probes are designed based on the active mature miRNA sequences and some of their flanking sequences. Our analysis included seven myeloma patients (hyperdiploid MM), eight different HMCLs (MM1, 8226 with t(14;16); SKMM2, U266, INA-6 with t(11;14) and H929, KMS11, UTMC-2 with t(4;14)), and eight normal human plasma cells. The normal human plasma cells were collected at Mayo Clinic Rochester from bone samples of patients undergoing orthopedic surgery. For the assay 5–10 μg of total RNA per sample were used at a concentration of 1 μg/μL. The RNA is directly labeled with biotin and used as a target for the on-chip hybridization assays. A streptavidin-Alexa dye is used to stain the hybridized targets and the fluorescent signals are captured and analyzed. The gene signal intensities were normalized to tRNA signal intensity. Results: The primary MM cells and HMCLs displayed a distinctive miRNA expression profile compared with normal plasma cells. Using the GeneSpring 7 (Agilent Technologies, Palo Alto, CA) for gene expression analysis we have identified miRNA genes with significant variation in expression levels between tumor and normal samples including miR-125b, miR-133a, miR1, and miR-124a (p Stat3 and angiopoietin-1 precursor as targets of miR-124a (Lewis et al. 2003). Of note, miR-15 and miR-16, previously identified to be downregulated in CLL, were expressed at low levels in some MM patients and HMCLs, but not in the normal plasma cells. Further analysis will be carried out to validate the data from miRNA profiling using northern blot analysis or real-time RT-PCR to measure expression levels of miRNA genes and that of their target genes. Conclusion: Analysis of miRNA expression pattern (along with aCGH and gene expression profiling studies) will undoubtedly refine our understanding of the various genotypic subtypes of multiple myeloma.
Longitudinal study of cerebral surface morphology in youth with 22q11.2 deletion syndrome, and association with positive symptoms of psychosis

Background 22q11.2 deletion syndrome (22q11DS) is a genetic disorder that greatly increases risk of developing schizophrenia. We previously characterized cerebral surface morphology trajectories from late childhood to mid adolescence in a cohort of youth with 22q11DS. Herein, we extend the study period into early adulthood, and describe further the trajectories associated with severe psychiatric symptoms in this cohort. Methods Participants included 76 youth with 22q11DS and 30 unaffected siblings, assessed at three timepoints, during which high resolution, anatomic magnetic resonance images were acquired. High-dimensional, nonlinear warping algorithms were applied to images in order to derive characteristics of cerebral surface morphology for each participant at each timepoint. Repeated-measures, linear regressions using a mixed model were conducted, while covarying for age and sex. Results Alterations in cerebral surface morphology during late adolescence/early adulthood in individuals with 22q11DS were observed in the lateral frontal, orbitofrontal, temporal, parietal, occipital, and cerebellar regions. An Age x Diagnosis interaction revealed that relative to unaffected siblings, individuals with 22q11DS showed age-related surface protrusions in the prefrontal cortex (which remained stable or increased during early adulthood), and surface indentations in posterior regions (which seemed to level off during late adolescence). Symptoms of psychosis were associated with a trajectory of surface indentations in the orbitofrontal and parietal regions. Conclusions These results advance our understanding of cerebral maturation in individuals with 22q11DS, and provide clinically relevant information about the psychiatric phenotype associated with the longitudinal trajectory of cortical surface morphology in youth with this genetic syndrome.
Maturity and age influence chief cell ability to transdifferentiate into metaplasia

Previous investigations have indicated that spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach arises from transdifferentiation of chief cells. Nevertheless, the intrinsic properti...
Analysis of upstream creeping reaction zones in catalytic monolith reactors

Abstract Monolith reactors are widely used in catalytic after-treatment systems (e.g. TWC, DOC, LNT and SCR). One major challenge in exhaust after-treatment is reducing cold-start emissions which account for a significant fraction of the total emissions. While front-end ignition is technically possible with high PGM loading and/or transient heating of the monolith, it may not be economical or feasible, especially for low exhaust gas temperature. In such cases, back-end ignition followed by a fast upstream creeping reaction zone provides a feasible way to reduce cold-start emissions. In this work, the upstream creeping reaction zone is investigated in detail using modeling approach. The influence of various design parameters (e.g. solid thermal conductivity and heat capacity) and operating conditions (gas velocity, inlet temperature/concentrations) on the creep velocity is determined and summarized. Phase diagrams and analytical criteria for reaction zones to creep upstream are also presented. The phase diagrams and criteria can provide guidance for design and control of reactors used in after-treatment systems.
Designing a Moral Compass for the Future of Computer Vision Using Speculative Analysis

In this paper we discuss and analyze possible futures for technologies in the field of computer vision (CV). Using a method we have coined speculative analysis we take a broad look at research trends in the field to categorize risks, analyze which ones are most threatening and likely, and ultimately summarize conclusions for how the field may attempt to stem future harms caused by CV technologies. We develop narrative case studies to provoke dialogue and deeply explore possible risk scenarios we found to be most probable and severe. We arrive at the position that there are serious potentials for CV to cause discriminatory harm and exacerbate cybersecurity issues.
Patterns of intermuscular inhibitory force feedback across cat hindlimbs suggest a flexible system for regulating whole limb mechanics

Feedback from Golgi tendon organs project widely among extensor motor nuclei in the spinal cord. The distributed nature of force feedback suggests these pathways contribute to the global regulation...
Haptic stroke testbed for pharmacological evaluation of dynamic allodynia in mouse models

Dynamic mechanical allodynia is an aggravating neuropathological condition in which light, physical touch leads to pain. Developing pharmaceutical agents to treat this condition requires extensive animal trials using a mouse model, and a laborious process of manually stroking inflicted mouse paws, with a brush or cotton swab, while recording responses to that stimulus. In this paper, we developed an autonomous testing mechanism to create repeatable stroking sensations for mice during dynamic allodynia testing. The chamber consists of a belt driven brush mechanism and light and dark chambers. Additionally, we conducted a human subjects study to determine the baseline variability in human-performed dynamic allodynia testing. Our tactile stoke display is capable of stroking a mouse paw between 1–5 mm/s with a repeatable force. In our human subject experiments, the user applied force ranged from 0.1–9.0 gF with a maximum standard deviation of 4.13 gF. In contrast, our device is capable of producing repeatable brush strokes at 0.69 gF (SD = 0.13 gF) and 1.78 gF (SD = 0.16 gF) for two brushes. Preliminary animal studies show that normal mice are not disturbed by the stroking sensation; however, mice afflicted with allodynia move away from it. On average the injured mice spent 90% of their time in a bright, adverse environment to avoid the brush, whereas normal mice only spent 40% of their time in the bright environment.
Scalable and Robust Bayesian Inference via the Median Posterior

Many Bayesian learning methods for massive data benefit from working with small subsets of observations. In particular, significant progress has been made in scalable Bayesian learning via stochastic approximation. However, Bayesian learning methods in distributed computing environments are often problem- or distributionspecific and use ad hoc techniques. We propose a novel general approach to Bayesian inference that is scalable and robust to corruption in the data. Our technique is based on the idea of splitting the data into several non-overlapping subgroups, evaluating the posterior distribution given each independent subgroup, and then combining the results. Our main contribution is the proposed aggregation step which is based on finding the geometric median of subset posterior distributions. Presented theoretical and numerical results confirm the advantages of our approach.
Structure and Biosynthesis of Meprins

Meprins are cell surface and secreted metalloendopeptidases that are expressed in kidney and intestine of mice, rats, and humans (Jiang et al., 1992; Gorbea et al., 1993; Corbeil et al., 1992; Johnson and Hersh, 1992; Sterchi et al., 1988; Yamaguchi et al., 1994). The enzymes are capable of hydrolyzing a variety of proteins and biologically active peptides, such as bradykinin, glucagon, transforming growth factor-α, and parathyroid hormone (Butler et al., 1987; Choudry and Kenny, 1991; Wolz et al., 1991). Meprins are implicated in the degradation of extracellular and membrane-bound proteins and peptides, and it has been suggested that they are involved in the processing and inactivation of peptide hormones in vivo (Kenny et al., 1989; Yamaguchi et al., 1994).
4-Cyanoindole-2′-deoxyribonucleoside (4CIN): A Universal Fluorescent Nucleoside Analogue

The synthesis and characterization of a universal and fluorescent nucleoside, 4-cyanoindole-2′-deoxyribonucleoside (4CIN), and its incorporation into DNA is described. 4CIN is a highly efficient fluorophore with quantum yields >0.90 in water. When incorporated into duplex DNA, 4CIN pairs equivalently with native nucleobases and has uniquely high quantum yields ranging from 0.15 to 0.31 depending on sequence and hybridization contexts, surpassing that of 2-aminopurine, the prototypical nucleoside fluorophore. 4CIN constitutes a new isomorphic nucleoside for diverse applications.