cssi/SciSciGPT-SciSciNet huggingface dataset:
Ubiquitin Immunostaining in Thyroid Neoplasms Marks True Intranuclear Cytoplasmic Pseudoinclusions and May Help Differentiate Papillary Carcinoma from NIFTP.

Papillary thyroid carcinoma (PTC) is defined by an invasive growth pattern and classic nuclear features: enlarged, grooved, overlapping nuclei with chromatin clearing and intranuclear cytoplasmic pseudoinclusions (INCP). True INCPs are characteristic of PTC, but may infrequently be seen in noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Nuclear abnormalities that mimic INCP (“pseudo-pseudoinclusions”) are common in a variety of thyroid lesions. H&E and ubiquitin-stained whole tissue sections of classic PTC (n = 25) and NIFTP (n = 35) were evaluated. On H&E, true INCPs were present in all (100%) PTCs and absent in all NIFTPs (0%). Pseudo-pseudoinclusions were present in 13 (37%) NIFTPs. In 24 (96%) PTCs, ubiquitin was strongly expressed within INCPs. In NIFTPs, optically clear nuclei or pseudo-pseudoinclusions did not express ubiquitin (0/35). Occasionally, nuclear vacuoles in NIFTP demonstrated a marginated staining pattern, in which strong ubiquitin expression was seen at the periphery of the nucleus, but the central pale area was negative. In addition, 2 NIFTPs demonstrated intrafollicular psammomatoid calcifications which were strongly ubiquitin-positive. Psammoma bodies in PTC were ubiquitin-negative in the majority of cases. We report a previously undescribed finding: strong ubiquitin expression in true INCPs in PTC, absence of true INCPs in NIFTP, and absence of ubiquitin expression in pseudo-pseudoinclusions in NIFTP. This finding supports the difference between true INCPs (found only in PTC) and pseudo-pseudoinclusions (found in NIFTP). Using strict histologic criteria and ubiquitin immunostaining, the presence of true pseudoinclusions may exclude a diagnosis of NIFTP. Caution should be exercised when interpreting nuclear vacuoles or pseudo-pseudoinclusions.
In-vivo analysis of sliding distance and cross-shear in Bi-cruciate retaining total knee arthroplasty.

Abstract Polyethylene remains the most popular bearing material for total knee arthroplasty (TKA). Despite its widespread use, wear continue to be one of major factors implicated in revision surgery. Sliding distance, cross-shear, and contact stress are the major factors influencing polyethylene wear. As previous studies have either relied on wear simulations, computational modeling, or in vitro measurements to quantify sliding distance and cross-shear, in vivo subject-specific sliding distance and cross-shear after bi-cruciate retaining (BCR) TKA has not been previously reported. The objective of this study was to quantify the 6°-of-freedom (6DOF) in vivo kinematics, sliding distance, and cross-shear in BCR TKA patients during gait. Twenty-nine unilateral BCR TKA patients performed level walking on a treadmill under dual fluoroscopic imaging system (DFIS) surveillance. Cumulative normalized sliding distances between the lateral and medial compartments did not change significantly (p > 0.05) during the gait cycle. Although the total normalized sliding distance was similar between the lateral and medial compartments, the cross-shear at the lateral compartment differed significantly from that at the medial compartment (p
A new method for protein tertiary structure prediction

In this paper, we propose a new method for protein structure prediction based on the mini-threading approach. It has two main components, relevant protein fragment retrieval and protein 3-D structure construction. First, we develop new computational techniques to identify useful fragments in Protein Data Bank (PDB) for a given query protein. Then, different from the angular restraints used in most existing mini-threading methods, we formulate spatial restraints derived from the alignments between a query sequence and its fragment hits of known structures in Cartesian coordinates. We include additional information for the scoring function, such as pair-wise contact potential and apply classical multidimensional scaling method for 3-D structure construction. The structure is further refined by local optimization algorithms. The new method represents a novel framework that can utilize the information in the known protein structure database more effectively and efficiently than existing methods.
Catastrophic polarization in twisted excited states

When π-electron systems twist, their polarizability commonly increases. In photo-excited states, dramatic charge shifts can develop when a twist of 90° produces two nearly degenerate π subsystems. We review here the literature on the subject that is particularly relevant to the development of polarization catastrophes.
DAMAGE MECHANICS AND NDE OF COMPOSITE LAMINATES

ABSTRACT The mechanics of the response of composite laminates with damage is discussed in the context of damage initiation, damage growth, stress redistribution, fracture, and nondestructive testing.
INCOMPLETE GAMMA FUNCTIONS

This chapter discusses incomplete gamma functions. It discusses the effective use of the tables provided, to evaluate the incomplete gamma function throughout the complex z and ν planes, each suitably cut. For the common special cases of the incomplete gamma functions, the given Chebyshev expansions afford the best method of computation. For the values of ν not covered in the tables, one can develop Chebyshev coefficients by the appropriate use of recurrence relations in the backward direction. For general ν and z , the rational and Pade approximations are superb for moderate values of ν .
Beyond Allegiance: Toward A Right to Canadian Citizenship Status

Canada grants citizenship expansively to most persons born subject to its territorial jurisdiction. Canada’s Charter of Rights and Freedoms also treats naturalized and native-born citizens as equal...
Hospital admission and readmission among homeless patients with neurologic disease.

Objective To characterize the most common neurologic diagnoses leading to hospitalization for homeless compared to housed individuals and to assess whether homelessness is an independent risk factor for 30-day readmission after an admission for a neurologic illness. Methods We performed a retrospective serial cross-sectional study using data from the Healthcare Cost and Utilization Project California State Inpatient Database from 2006 to 2011. Adult patients with a primary neurologic discharge diagnosis were included. The primary outcome was 30-day readmission. We used multilevel logistic regression to examine the association between homelessness and readmission after adjustment for patient factors. Results We identified 1,082,347 patients with a neurologic primary diagnosis. The rate of homelessness was 0.37%. The most common indications for hospitalization among homeless patients were seizure and traumatic brain injury, both of which were more common in the homeless compared to housed population (19.3% vs 8.1% and 31.9% vs 9.2%, respectively, p p Conclusion The most common neurologic reasons for admission among homeless patients are seizure and traumatic brain injury; these patients are at high risk for readmission. Future interventions should target the drivers of readmissions in this vulnerable population.
Pion Elastic Scattering on a Polarized 13C Target

Calculations of cross sections and asymmetries for pion elastic scattering on polarized 13C are presented. Transition density amplitudes from different nuclear structure models are used to demonstrate the strong sensitivity of the asymmetry to the nuclear structure details. None of the models reproduces the recent data satisfactorily.
Enhancing optical transmission of multilayer composites using interfacial nanostructures

We demonstrate the suppression of light reflections at solid-solid interfaces in multilayer thin and thick films using interfacial nanostructures. The embedded nanostructures have subwavelength features and function as a gradient-index medium to eliminate Fresnel losses induced by refractive index mismatch between dissimilar materials. Suppressing the interfacial reflection can reduce interference effects in thin films, and the transmittance measurement of a polymer on a silica substrate demonstrates a two-fold decrease in interference fringe contrast. A thick multilayer composite consisting of three fused silica and two polymer layers has also been fabricated and demonstrates the enhancement of optical transmission up to 30% at high incident angles. The effects of the interfacial structure geometry are examined by theoretical models based on rigorous coupled-wave analysis methods. The experimental results agree well with simulation models, which predicts that further improvements can be achieved using the optimized tapered profile. This work indicates that interfacial nanostructures can improve the broadband and wide-angle response of multilayers and can find applications in thin-film optics, optoelectronic devices, and composite windows.
Inhibition of Escherichia coli O157:H7 and Salmonella enterica Isolates on Spinach Leaf Surfaces Using Eugenol-Loaded Surfactant Micelles.

Spinach and other leafy green vegetables have been linked to foodborne disease outbreaks of Escherichia coli O157:H7 and Salmonella enterica around the globe. In this study, the antimicrobial activities of surfactant micelles formed from the anionic surfactant sodium dodecyl sulfate (SDS), SDS micelle-loaded eugenol (1.0% eugenol), 1.0% free eugenol, 200 ppm free chlorine, and sterile water were tested against the human pathogens E. coli O157:H7 and Salmonella Saintpaul, and naturally occurring microorganisms, on spinach leaf surfaces during storage at 5 °C over 10 days. Spinach samples were immersed in antimicrobial treatment solution for 2.0 min at 25 °C, after which treatment solutions were drained off and samples were either subjected to analysis or prepared for refrigerated storage. Whereas empty SDS micelles produced moderate reductions in counts of both pathogens (2.1–3.2 log10 CFU/cm2), free and micelle-entrapped eugenol treatments reduced pathogens by >5.0 log10 CFU/cm2 to below the limit of detection (<0.5 log10 CFU/cm2). Micelle-loaded eugenol produced the greatest numerical reductions in naturally contaminating aerobic bacteria, Enterobacteriaceae, and fungi, though these reductions did not differ statistically from reductions achieved by un-encapsulated eugenol and 200 ppm chlorine. Micelles-loaded eugenol could be used as a novel antimicrobial technology to decontaminate fresh spinach from microbial pathogens.
Hydrogen Atom Transfer Reaction Free Energy as a Predictor of Abiotic Nitroaromatic Reduction Rate Constants: A Comprehensive Analysis.

A linear free energy model is presented that predicts the second-order rate constant for the abiotic reduction of nitroaromatic compounds (NACs). Previously presented models use the one-electron reduction potential E H 1 ( ArNO 2 ) of the NAC reaction ArNO 2 + e - → ArNO 2 • - . If E H 1 ( ArNO 2 ) is not available, it has been proposed that E H 1 ( ArNO 2 ) be computed directly or estimated from the gas-phase electron affinity (EA). The model proposed uses the Gibbs free energy of the hydrogen atom transfer (HAT) reaction ArNO 2 + H • → ArNOOH • as the parameter in the linear free energy model. Both models employ quantum chemical computations for the required thermodynamic energies. The available and proposed models are compared using experimentally determined second-order rate constants from 5 investigations from the literature in which a variety of NACs were exposed to a variety of reductants. A comprehensive analysis utilizing all the NACs and reductants demonstrate that the HAT energy model and the experimental one-electron reduction potential model have similar root mean square errors and residual error probability distributions. In contrast, the model using the computed EA has a more variable residual error distribution with a significant number of outliers. The results suggest that a linear free energy model utilizing computed HAT reaction free energy produces a more reliable prediction of the NAC abiotic reduction second-order rate constant than previously available methods. The advantages of the proposed HAT energy model and its mechanistic implications are discussed as well. Environ Toxicol Chem 2020;39:1678-1684. © 2020 SETAC.
Shifting-balance Theory of Evolution

The shifting balance theory was put forward by the great population geneticist Sewall Wright in the 1930s as providing, in his opinion, the optimal scenario for evolution to occur in a biological population. It relies on the assumption that the population is divided into a number of more or less isolated subpopulations, or ‘demes’, with some level of migration between them. Favorable gene complexes are assumed to arise by random genetic drift within one or more of the subpopulations and are then fixed in those subpopulations by selection, and subsequently exported to the remaining subpopulations by migration and selection. The theory has always been controversial, but discussion of the merits of the theory has died down in recent years as attention has moved to questions raised by molecular genetic data.
Doping graphene with carbon-based cage molecules for optoelectronic devices

Hybrid graphene photodetectors were prepared with endohedral fullerenes deposited on graphene using electrophoretic methods. Endohedral Sc3N@C80, which acts as an electron acceptor was used, and the ensuing electronic and optoelectronic properties were measured. Another endohedral fullerene, La@C82 adsorbed on graphene acted as an electron donor. Upon optical illumination, for the Sc3N@C80-graphene hybrid, the photoinduced free holes are injected into graphene, increasing the hole carrier concentration in graphene, while the photoexcited electrons remain in Sc3N@C80. We will discuss the photodetector response of these 0D-2D systems with both Sc3N@C80-graphene and La@C82-graphene hybrids. The exceptional performance gains achieved with both types of hybrid structures confirms the potential of endohedrals to dope graphene for high performance optoelectronic devices using a facile and scalable fabrication process.
A Review and Roadmap of the Skin, Lung, and Gut Microbiota in Systemic Sclerosis.

As our understanding of the genetic underpinnings of systemic sclerosis (SSc) increases, questions regarding the environmental trigger(s) that induce and propagate SSc in the genetically predisposed individual emerge. The interplay between the environment, the immune system, and the microbial species that inhabit the patient's skin and gastrointestinal tract is a pathobiological frontier that is largely unexplored in SSc. The purpose of this review is to provide an overview of the methodologies, experimental study results, and future roadmap for elucidating the relationship between the SSc host and his/her microbiome.
Data Integration for Diet Sustainability Analyses

Diet sustainability analyses are stronger when they incorporate multiple food systems domains, disciplines, scales, and time/space dimensions into a common modeling framework. Few analyses do this well: there are large gaps in food systems data in many regions, accessing private and some public data can be difficult, and there are analytical challenges, such as creating linkages across datasets and using complex analytical methods. This article summarizes key data sources across multiple domains of food system sustainability (nutrition, economic, environment) and describes methods and tools for integrating them into a common analytic framework. Our focus is the United States because of the large number of publicly available and highly disaggregated datasets. Thematically, we focus on linkages that exist between environmental and economic datasets to nutrition, which can be used to estimate the cost and agricultural resource use of food waste, interrelationships between healthy eating and climate impacts, diets optimized for cost, nutrition, and environmental impacts, and others. The limitations of these approaches and data sources are described next. By enhancing data integration across these fields, researchers can be better equipped to promote policy for sustainable diets.
Estimating nuisance parameters often reduces the variance (with consistent variance estimation)

In many applications, to estimate a parameter or quantity of interest psi, a finite-dimensional nuisance parameter theta is estimated first. For example, many estimators in causal inference depend on the propensity score: the probability of (possibly time-dependent) treatment given the past. theta is often estimated in a first step, which can affect the variance of the estimator for psi. theta is often estimated by maximum (partial) likelihood. Inverse Probability Weighting, Marginal Structural Models and Structural Nested Models are well-known causal inference examples, where one often posits a (pooled) logistic regression model for the treatment (initiation) and/or censoring probabilities, and estimates these with standard software, so by maximum partial likelihood. Inverse Probability Weighting, Marginal Structural Models and Structural Nested Models have something else in common: they can all be shown to be based on unbiased estimating equations. This paper has four main results for estimators psi-hat based on unbiased estimating equations including theta. First, it shows that the true limiting variance of psi-hat is smaller or remains the same when theta is estimated by solving (partial) score equations, compared to if theta were known and plugged in. Second, it shows that if estimating theta using (partial) score equations is ignored, the resulting sandwich estimator for the variance of psi-hat is conservative. Third, it provides a variance correction. Fourth, it shows that if the estimator psi-hat with the true theta plugged in is efficient, the true limiting variance of psi-hat does not depend on whether or not theta is estimated, and the sandwich estimator for the variance of psi-hat ignoring estimation of theta is consistent. These findings hold in semiparametric and parametric settings where the parameters of interest psi are estimated based on unbiased estimating equations.
Soluble very low-density lipoprotein receptor (sVLDLR) inhibits fibrosis in neovascular age-related macular degeneration

Subretinal fibrosis is a key pathological feature in neovascular age-related macular degeneration (nAMD). Previously, we identified soluble very low-density lipoprotein receptor (sVLDLR) as an endogenous Wnt signaling inhibitor. This study investigates whether sVLDLR plays an anti-fibrogenic role in nAMD models, including Vldlr-/- mice and laser-induced choroidal neovascularization (CNV). We found that fibrosis factors including P-Smad2/3, α-SMA, and CTGF were upregulated in the subretinal area of Vldlr-/- mice and the laser-induced CNV model. The antibody blocking Wnt co-receptor LRP6 significantly attenuated the overexpression of fibrotic factors in these two models. Moreover, there was a significant reduction of sVLDLR in the interphotoreceptor matrix (IPM) in the laser-induced CNV model. A transgenic strain (sVLDLR-Tg) with sVLDLR overexpression in the IPM was generated. Overexpression of sVLDLR ameliorated the profibrotic changes in the subretinal area of the laser-induced CNV model. In addition, Wnt and TGF-β signaling synergistically promoted fibrogenesis in human primary retinal pigment epithelium (RPE) cells. CRISPR/Cas9-mediated LRP6 gene knockout (KO) attenuated this synergistic effect. The disruption of VLDLR expression promoted, while the overexpression of sVLDLR inhibited TGF-β-induced fibrosis. These findings suggest that overactivated Wnt signaling enhances the TGF-β pathway in subretinal fibrosis. sVLDLR confers an antifibrotic effect, at least partially, through the inhibition of Wnt signaling and thus, has therapeutic potential for fibrosis.
Imatinib mesylate (STI-571, Gleevec®) offers combinatorial benefit with temozolomide (Temodar®) against gliomas

5979 Malignant gliomas are highly lethal tumors that display resistance to conventional therapies. Temozolomide is an orally available methylator now widely used in glioma therapy. Although temozolomide has activity against malignant gliomas, development of resistance is common. We have sought to increase the activity of temozolomide in these cancers. Imatinib mesylate is a novel low molecular weight ATP-mimetic inhibitor of several tyrosine kinases, including platelet derived growth factor receptors (PDGFRs). Although imatinib mesylate has been relatively inactive in monotherapy trials against gliomas, imatinib mesylate may offer in benefit in increasing the efficacy of temozolomide through increased tumor accumulation by decreasing interstitial fluid pressure and blocking retrograde blood-brain barrier transporters as well as disrupting tumor survival mechanisms. The combination of imatinib mesylate (200 mg/kg x 5 days starting two days before temozolomide dosing) and temozolomide (single dose at 0.1 LD10) was well tolerated by athymic mice without significant weight loss. Athymic nude mice bearing established subcutaneous human glioma xenografts displayed additive benefit in time to reach 5x original tumor volume (24.8 days temozolomide alone, 2.6 imatinib alone, 26.3 with the combination). The impact of the combination was significantly greater on the survival of mice bearing intracranial xenografts (control 22 days, imatinib mesylate 25 (p>.1), temozolomide 49 (p
Economic Development and Promotion of Rule of Law Internationally Through Reforms in Commercial Law

Legal reforms, either general or reforms in institutions, are carried out in specialized sectors of law in the form of technical assistance which largely fall under broader sector of rule of law. This has been is one of the approach of major development agencies for the international development. Countries around the world have been prompted to promote rule of law as sine qua non to realize their development objectives. Virtually every country in the world espouse to the rule of law, even dictatorial regime of North Korea claims as democratic peoples’ republic.Paper tries to identify the most important aspects of commercial law reforms which may directly promote the culture of rule of law. Paper also examines general legal reforms to draw up on some insights from those reform initiatives. Paper does not critique the commercial law reforms initiatives, instead tries to appreciate the general trends in commercial law reforms by examining commercial law reform initiatives undertaken by various development agencies in different countries.First part of the paper examines the genesis and aspects of commercial law reforms. In second part it examines the representative projects and project areas of the development agencies which are closely related to commercial law reforms either directly or indirectly. In this respect paper examines projects data from some development agencies. In last part, paper examines the implications of commercial law reforms to the rule of law and development.
Take-off ground roll of propeller driven aircraft

using a heater-burner to simulate the engine exhaust, seemed to indicate that the two-dimensional CD nozzle with exit aspect ratios less than 10 would not produce less IR signature than the equivalent axisymmetric nozzle (see Fig. 67 of Ref. 5). The effect of the engine swirl is expected to be more important when external streams are present, since in such cases external mixing due to shear is otherwise reduced because of the lowered velocity differences between the plume and external stream. In conclusion, a simple modeling technique has been developed to provide economical yet adequate prediction of two-dimensional-nozzle plume properties for IR signature analysis. Successful models were developed for ADEN, twodimensional CD, and two-dimensional plug nozzles with and without bypass flow and/or engine swirl. A 10-deg engine swirl was found to reduce the predicted plume temperature dramatically. Therefore the inherent engine swirl, though undesirable from the performance point of view, appears to be highly effective in reducing the IR signature of a twodimensional-nozzle plume.
Heat transfer analysis of the Bridgman-Stockbarger configuration for crystal growth: II. Analytical treatment of radial temperature variations

Abstract The parametric behavior of radial temperature variations within the charge during crystal growth in a Bridgman-Stockbarger configuration is derived by a two-dimensional heat transfer model. By treating the charge and the crucible as a series of concentric fins which exchange heat radially with each other, useful solutions in analytical form are obtained. The model considers the effects of the length of an insulating zone between hot and cold regions of the furnace, thickness and thermal conductivity of a charge confining crucible, thermal coupling between the charge and the furnace, change in the thermal conductivity at the crystal-melt interface, and the generation of latent heat. Results show that the presence of a crucible diminishes the ability to control the shape of the growth interface through its position within the insulating zone and, for semiconductors, leads to a growth interface shape for which the crystal is concave.
Swell-based in-situ oxide removal methods for PDMS-copper particle composite corrosion sensing elements

A micro -corrosion sensor technology utilizing PDMS (polydimethylsiloxane) and micro/nano -metal particles, as the sensing element, was proposed and currently under -development. One of the key challenges encountered is the removal of the native oxides inherently existing on the metal particles. Numerous techniques were experimented to counter this problem, with swell -based protocols being identified as the most promising solution. Swelling of the composite enhances the diffusion of oxide etchants into and etched oxide s out of the material ma trix. Two different swelling characterizations, utilizing liquid -based solven ts and supercritical CO2 emersions, will be presented here. In terms of compatibility, common microfabrication solvents were used to evaluate the former, while supercritical CO2 is often used in the release of stiction sensitive microstructures. Both met hods are classified as low temperature techniques (less than 100 degrees Celcius). Commonly, the composite exhibits a swelling ratio of 10 -20%, exhibiting more sensitive to the percentage content of the metal particles albeit well below those reported in literature for pure cross -linked PDMS. The swelling time -constant is found to be on the order of minutes (CO2) to tens of minutes (liquid solvent) while oxide removal for cubed coupons with 6.35mm on each side is on the order of hours. Also in both cases , the oxide etching performance is dependent on the amount of dilation of the material and the mixing compatibility between the swelling agent and the etchant (such as acetic acid and hexafluoroacetylacetone, respectively for copper oxides). The etching experiments are currently undergoing, with preliminary liquid -based etching using acetic acid also presented here. Keywords: swelling, corrosion sensing, oxide removal, PDMS, MEMS
Learned helplessness, attributional style, and depression in epilepsy

Summary: Purpose: We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy. Methods: Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale. Results: Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance]. Conclusions: The results indicate that the concepts of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.
Social function in multiple X and Y chromosome disorders: XXY, XYY, XXYY, XXXY

Klinefelter syndrome (47,XXY) was initially described in the context of its endocrinologic and physical features; however, subsequent studies have revealed specific impairments in verbal skills and social functioning. Males with sex chromosomal aneuploidies are known to have variability in their developmental profile with the majority presenting with expressive language deficits. As a consequence of language delays, they have an increased likelihood of language-based learning disabilities and social-emotional problems that may persist through adulthood. Studies on males with 47,XXY have revealed unique behavioral and social profiles with possible vulnerability to autistic traits. The prevalence of males with more than one extra sex chromosome (e.g., 48,XXYY and 48,XXXY) and an additional Y (e.g., 47,XYY) is less common, but it is important to understand their social functioning as it provides insight into treatment implications.
The Mercury laser: a diode-pumped, gas-cooled Yb:S-FAP solid-state laser

Summary form only given.Gas-cooled, diode-pumped, Yb:crystal lasers are envisioned to be the next-generation inertial confinement fusion (ICF) solid state laser system producing high energy per pulse at modest rep-rates. Innovative solutions for building ICF lasers with high repetition rate and efficiency include: trading the flashlamps for large, low-cost laser diode arrays; using Yb:crystals for greater energy storage and thermal conductivity than Nd:glass; and employing near-sonic helium for cooling of the laser slabs.
Nucleophile activation in PD…(D/E)xK metallonucleases: An experimental and computational pKa study

Metallonucleases conduct metal-dependent nucleic acid hydrolysis. While metal ions serve in multiple mechanistic capacities in these enzymes, precisely how the attacking water is activated remains unclear for those lacking an obvious general base. All arguments hinge on appropriate pK(a)s for active site moieties very close to this species, and measurement of the pK(a) of a specific water molecule is difficult to access experimentally. Here we describe a computational approach for exploring the local electrostatic influences on the water-derived nucleophile in metallonucleases featuring the common PD...(D/E)xK motif. We utilized UHBD to predict the pK(a)s of active site groups, including that of a water molecule positioned to act as a nucleophile. The pK(a) of a Mg(II)-ligated water molecule hydrogen bonded to the conserved Lys70 in a Mg(II)-PvuII enzyme complex was calculated to be 6.5. The metal and the charge on the Lys group were removed in separate experiments; both resulted in the elevation of the pK(a) of this water molecule, consistent with contributions from both moieties to lowering this pK(a). This behavior is preserved among other PD...(D/E)xK metallonucleases. pK(a)s extracted from the pH dependence of the single turnover rate constant are compared to previous experimental data and the above predicted pK(a)s.
A Vorticity Source for Large-Scale Dust Devils and Other Comments on Naturally Occurring Columnar Vortices

Abstract Several miscellaneous topics are presented, all connected with the dynamics of concentrated atmospheric vortices. The main topic is concerned with a vorticity source for dust devils in which we show that one possible source is the turning of the horizontal vorticity in the atmospheric boundary layer into the vertical direction. Comments on the existence of “vortex-jump” phenomena in atmospheric vortices and the cause of tornado skipping complete the discussion.
Locating Transportation Terminals to Serve an Expanding Demand

This paper develops a continuous approximation model of a general freight carrier serving a fixed region with an increasing density of demand. Terminal, transportation and relocation costs are considered. As the demand for service by a freight carrier increases, transportation terminals are added to decrease transportation costs. The vehicle routing scheme includes economies of scale for linehaul transportation between terminals. Although the optimal strategy for adding and locating terminals may require knowledge of future demand, myopic strategies may be nearly optimal. Three strategies are considered that provide upper and lower bounds on the distribution cost from the optimal strategy. Terminal locations are found for each strategy. A myopic strategy with limited capability for relocation is shown to be nearly optimal unless terminal relocation costs are large.
Sessions Focus on Diversity

Education and outreach play a significant role in AGU's mission; one of our major strategic goals is developing and nurturing the next generation of Earth and space scientists. Particular emphasis is placed on exploring ways to strengthen the numbers and diversity of the Earth and space science workforce and helping to strengthen Earth and space science departments and undergraduate teaching at the college and university levels.
A simulation method for accurately determining DC and dynamic offsets in comparators

A simulation method that has proven valuable in the design of high-speed regenerative comparators such as those used in pipeline and flash analog-to-digital converters is presented. This method yields an input-referred offset voltage for the comparator while it is operating at speed, including both DC and dynamic effects such as charge injection and capacitive coupling. The speed and efficiency of the method allows the circuit designer to more fully explore the design space, and provides important insights into comparator operation.
A GREEN RIVER (EOCENE) POLYCHROTID (SQUAMATA: REPTILIA) AND A RE-EXAMINATION OF IGUANIAN SYSTEMATICS

A pleurodontan iguanian from the Green River Formation (Eocene) is described in detail and named. The new taxon is known only from a single specimen preserving all areas of the body. Although many of the bone surfaces are eroded, almost all of the skeleton is present and some cartilaginous elements are preserved. The new taxon shares important characteristics with the extant anisolepines and leiosaurines, including the morphology and placement of the caudal autotomy planes, the postxiphisternal inscriptional ribs, and notched or fenestrated clavicles that are expanded proximally. This is the earliest complete iguanian known from the Americas and the earliest known iguanian that may be confidently referred to an extant “family.” A phylogenetic analysis including this taxon and other fossil and extant iguanians offers some support for the monophyly of Polychrotidae sensu lato, Tropiduridae sensu lato, and non-acrodont iguanians (Pleurodonta).
Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy.

BACKGROUND: Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined. METHODS: Patients with advanced HIV-associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m2 intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m2 iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle. RESULTS: The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression-free survival (17.5 months vs 12.2 months; P = .66), and 2-year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077). CONCLUSIONS: Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV-associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society.
A Comparison of Unsteady RANS Simulations With PIV Data in an Axial Turbomachine

This paper presents a comparison of 2D unsteady Reynolds Averaged Navier-Stokes (RANS) simulations using two standard turbulence models, i.e. RNG k-e and a Reynolds Stress Transport Model, with experimental data, obtained using two-dimensional Particle Image Velocimetry (PIV) measurements within an entire stage of an axial turbomachine. The computations are performed using the commercial flow solver FLUENT™. A sliding mesh interface between the rotor and stator domains is used. The PIV measurements are performed in a refractive-index-matched facility that provides unobstructed view, and cover the entire 2nd stage of a two-stage axial pump. The inlet velocity and turbulence boundary conditions are provided from the experimental data. Detailed side-by-side comparisons of computed and measured phase-averaged velocity as well as turbulence fields within the entire stage are presented. Quantitative comparisons between the experiments and the computations are also included in terms of line distributions within the rotor-stator gap and the stator wake regions. The results show that, although there is reasonable agreement in general between the experimental results and the computational simulations, some critical flow features are not correctly predicted. The turbulent kinetic energy levels are generally too high in the simulations, with substantial amount of unphysical turbulence generation near the blade leading edges, especially in the case of RNG k-e model.© 2005 ASME
A new tetracycline-resistance determinant, class E, isolated from Enterobacteriaceae.

Abstract A fifth tetracycline(Tc)-resistance determinant, designated class E, has been identified on a transferable plasmid found in a fecal strain of Escherichia coli. This determinant does not show homology by DNA-DNA hybridization at high stringency with any of four other Tc resistance determinants (classes A, B, C and D) previously described among the Enterobacteriaceae. Resistance is inducible by 1 μg Tc/ml and increases the minimum inhibitory concentration 130-fold for Tc and 3.5-fold for minocycline. The mechanism, like that of the other four determinants examined, appears to involve an active efflux of the drug. Using a 32P-labeled cloned fragment containing the resistance determinant, we have found the determinant in Aeromonas, but not in any of over 200 other E. coli strains tested.
Role of cyclic nucleotides in fetal hemoglobin induction in cultured CD34+ cells.

Objective In vivo, several drugs have been shown to increase fetal hemoglobin (HbF), including 5-azacytidine (AZA), sodium butyrate (SB), and hydroxyurea (HU). Studies in K562 cells suggest that cyclic guanosine monophosphate (cGMP) is required for HbF induction; however, the role of cyclic nucleotides in HbF induction in primary erythroid cultures has not been established. Methods CD34-selected peripheral blood monocytes cultured in a semi-solid serum-free system that mimics in vivo F-cell production are utilized to explore the role of cyclic adenosine monophosphate (cAMP) and cGMP in HbF induction in response to HU, AZA, and SB. Results In serum-free CD34 cultures, HU, SB, and AZA all markedly stimulate FNRBC production up to 30-fold, associated with induction of γ-globin mRNA and total HbF protein. Guanylate cyclase inhibition results in only minimal blunting of HbF induction by each agent. In contrast, adenylate cyclase inhibition markedly reduces HU, SB, and AZA-mediated FNRBC induction and γ-globin mRNA induction. The adenylate cyclase activator forskolin modestly induces FNRBC production and augments the action of standard induction agents. HU, AZA, and SB, however, fail to significantly stimulate adenylate cyclase themselves. Conclusions In human CD34 + cultures, cAMP production is required for full induction of HbF by HU, SB, and AZA, while perturbation of cGMP production has only minimal effects. These findings are in marked contrast to data in K562 cells where cGMP production is critical for HbF induction while cAMP stimulation blunts HbF response, and suggest that these agents may share a common induction pathway.
Excimer-laser-induced densification of fused silica:laser-fluence and material-grade effects on the scaling law

Abstract We present results of the study of 193 nm laser-induced densification of fused silica as a function of incident laser fluence and pulse count. We describe an internally self-consistent experiment involving the simultaneous irradiation of 12 samples of two different grades, at fluences varying by two orders of magnitude and pulse counts exceeding 1.5 × 109. We are able to establish the existence of a dose-rate dependence of the densification phenomenon and to characterize the empirical rate constants as a function of fluence for two different grades of fused silica.
Quantification of Flavor-Related Compounds in the Unburned Contents of Bidi and Clove Cigarettes

Bidi cigarettes, small hand-rolled cigarettes produced primarily in India, are sold in the United States in a wide variety of candy-like flavors (e.g. dewberry, chocolate, clove) and are popular with adolescents. Many flavored bidis contain high concentrations of compounds such as eugenol, anethole, methyleugenol, pulegone, and estragole; several of these compounds have known toxic or carcinogenic properties. Clove cigarettes, or kreteks, are another highly flavored tobacco product with high levels of eugenol due to clove buds present in the tobacco filler. In this study, compounds in the burnable portion-the filler and wrapper material actually consumed during the smoking of bidis, kreteks, and U.S. cigarettes-were analyzed. Flavor-related compounds were solvent extracted from the burnable portion of each cigarette with methanol. An aliquot of the methanol extract was heated, and the sample headspace was sampled with a solid-phase microextraction fiber and introduced into a gas chromatograph-mass spectrometer for analysis in selected-ion monitoring mode. High levels of eugenol were detected in five clove-flavored bidi brands ranging from 78.6 to 7130 microg/cigarette (microg/cig), whereas diphenyl ether (128-3550 microg/cig) and methyl anthranilate (154-2360 microg/cig) were found in one grape-flavored bidi brand. A nontobacco herbal bidi brand contained the greatest variety of compounds, including anethole (489-665 microg/cig), eugenol (1670-2470 microg/cig), methyleugenol (27.7-36.6 microg/cig), safrole (32.4-34.4 microg/cig), myristicin (170-247 microg/cig), and elemicin (101-109 microg/cig). Filler from kreteks was found to contain high levels of eugenol, anethole, and coumarin. Flavored bidis and clove cigarettes contain a number of compounds that are present at levels far exceeding those reported in U.S. cigarette tobacco. Research is underway to determine the levels of these compounds delivered in smoke. It is not known what effect inhalation of these compounds has on smokers.
Rotational bands of 166Ho

Abstract Nuclear states of 166 Ho were studied by means of the average-resonance-capture method of neutron-capture γ - ray spectroscopy. An exceptionally large number of states were observed and their spins and parities determined. These states form 16 rotational bands that are in generally good agreement with what is expected from the collective model.
Parameter estimation in approximate enzyme kinetics models

Abstract Enzyme kinetic modeling is based on a very specific approximation to a more detailed model; this approximation is often called the Michaelis-Menten approximation. Its success lies not only in an initial concentration difference that is set experimentally, but also in a certain difference among kinetic rate constants. Other differences among these constants lead to additional model approximations, often much simpler than the Michaelis-Menten approximation. Under the conditions where these alternate approximations apply, the Michaelis-Menten approximation would give misleading parameter estimates.
Operations on orbits of unimodular vectors

Abstract Taking the m-power of an entry is a well-defined operation on the unimodular vectors in An modulo addition operations, if n is at least 3, for an arbitrary commutative ring A and any integer m.
VOLUME RESPONSES TO MEDICARE PAYMENT REDUCTIONS WITH MULTIPLE PAYERS : A TEST OF THE MCGUIRE-PAULY MODEL

The effects of changing financial incentives on physician's practice behaviour have long been of interest to researchers and policy makers. We test a model of physician volume response within the context of multiple payers developed by Thomas McGuire and Mark Pauly. A panel data set covering discharges from about 200 hospitals in the US over 45 months is used to carry out the empirical investigation. A fixed-effect model with generalized least squares and instrumental variable specifications is used to compute empirical evidence of volume responses from eight specialties experiencing varying degrees of Medicare payment reductions following the implementation of Omnibus Budget Reconciliation Acts of 1989 and 1990. The empirical findings are compared with McGuire and Pauly's simulated predictions. We note that in examining physician responses to Medicare payment reductions in the context of a multi-payer environment, it becomes evident that only fixing one payer's reimbursement policy is at best a partial solution to cost containment. We echo observations made by other analysts that physician responses to payment changes can be quite complex. Physicians do not all respond to payment reduction in the same way.
Ginkgo Biloba: A Review of Quality, Safety, and Efficacy

Results from randomized, controlled clinical trials support the use of standardized leaf extracts of Ginkgo biloba for the symptomatic treatment of age-associated memory impairment, dementia (including Alzheimer's disease), and intermittent claudication. Product selection is extremely important, as much of the published safety and efficacy data are based on 2 standardized extracts, both available in the US. The recommended dose of a Ginkgo biloba leaf extract (standardized to contain 24–26% flavonoid glycosides, 5–7% terpene lactones, and less than 5 parts per million ginkgolic acids) is 40 mg to 60 mg, 3 to 4 times a day. Daily administration of the extract for at least 4 to 6 weeks is required before the full therapeutic effects may be observed. While there are no known contraindications, due to potential platelet-activating factor antagonism and inhibition of platelet aggregation, Ginkgo extracts should be used cautiously in patients receiving anticoagulant or antiplatelet therapy or having bleeding disorders. A number of bleeding episodes due to co-administration of aspirin or warfarin have been reported. Other adverse reactions, such as nausea, vomiting, headaches, and dizziness have also been observed in clinical trials. Administration of Ginkgo biloba preparations to children or during pregnancy or nursing is not currently recommended.