cssi/SciSciGPT-SciSciNet huggingface dataset:
Heavy metal concentration in forage grasses and extractability from some acid mine spoils

Laboratory and greenhouse studies were conducted on several forage grasses, bermudagrass (Cynodon dactylon), creeping red fescue (Festuca rubra), Kentucky 31-tall fescue (Festuca arundinacea), oat (Avena sativa), orchardgrass (Dactylis glomerata), perennial ryegrass (Lolium perenne), sorghum (Sorghum bicolor), triticale (X. triticosecale Wittmack), and winter wheat (Triticum aestivum) grown on three Alabama acid mine spoils to study heavy metal accumulation, dry matter yield and spoil metal extractability by three chemical extractants (Mehlich 1, DTPA, and 0.1 M HCl). Heavy metals removed by these extractants were correlated with their accumulation by several forage grasses. Among the forages tested, creeping red fescue did not survive the stressful conditions of any of the spoils, while orchard grass and Kentucky 31-tall fescue did not grow in Mulberry spoil. Sorghum followed by bermudagrass generally produced the highest dry matter yield. However, the high yielding bermudagrass was most effective in accumulating high tissue levels of Mn and Zn from all spoils (compared to the other grasses) but did not remove Ni. On the average, higher levels of metals were extracted from spoils in the order of 0.1 M HCl>Mehlich 1>DTPA. However, DTPA extracted all the metals from spoils while Mehlich 1 did not extract Pb and 0.1 M HCl did not extract detectable levels of Ni. All of the extractants were quite effective in determining plant available Zn from the spoils. For the other metals, the effective determination of plant availability depended on the crop, the extractant, and the metal in concert.
Thermochemistry of the Pd + B system at 1400 K

Abstract New information is reported on the enthalpies of mixing at 1400 K of solid boron and solid palladium to form liquid Pd-B alloys with mole fractions X gB of boron, between 0.24 and 0.37; the minimum value of ΔH mix s − s is about −12.9 kJ mol −1 near X B = 0.27. The standard enthalpy of formation of Pd 5 B 2 , which melts congruently at 1388 K, was measured to be −179.3 ± 6.3 kJ mol −1 . This result is compared with previously published data for Ni 2 B and with an approximate value for Pt 2 B determined in the course of the present work.
Female Genito-genital Rubbing in a Group of Captive Chimpanzees

Wild and captive female bonobos exhibit a form of noncopulatory sexual behavior—genito-genital (GG) rubbing—in which 2 individuals rub their genital regions together. GG-rubbing in bonobos occurs in several contexts and may serve several functions, including tension reduction and reconciliation. It has not been reported for chimpanzees. In a study of captive, adolescent chimpanzees at the New Iberia Research Center, I observed that females rubbed genital regions at rates equivalent to those of bonobos, though the form of the behavior differed in significant ways from classic bonobo GG-rubbing. I describe the pattern of GG-rubbing in the chimpanzees and provide preliminary tests of 5 hypotheses for why the behavior occurs. All 4 females in the study group participated in GG-rubbing, though the frequency with which they initiated and participated varied. Females that GG-rubbed the most also groomed each other the most, supporting the hypothesis that GG-rubbing reinforces or at least reflects social bonds. The data do not support the hypothesis that females GG-rub to reconcile conflicts, to reduce tension during feeding, to signal social status, or to attract mates.
Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

It is the relentless invasion and growth into surrounding tissue that characterize oral squamous cell carcinoma. Metastasis is perhaps the most challenging and important aspect of cancer progression, in that it generally signifies limited survival and ineffective therapy. Inherent in metastasis is invasion, the process by which cells infiltrate into adjacent tissues, degrading basement membranes and extracellular matrix and disrupting tissue architecture and sometimes organ function. The factors that regulate these processes are complex and likely involve loss of the controls that are normally in place in physiologic tissue modeling. Adhesion receptors and their ligands are important in modulating not only invasion of oral squamous cell carcinoma cells but also their survival and proliferation. Normal oral mucosal epithelial cells use integrins to maintain their anchorage to the basement membrane, whereas the formation of stratifying cell layers depends on the formation of intercellular adhesions mediated...
The problem of nonadherence to therapy in the management of duodenal ulcer recurrences.

Investigations on 24 patients hospitalized for treatment of duodenal ulcer recurrences at the Massachusetts General Hospital revealed that none considered that he had adhered to the prescribed therapy in its entirety. The factors found operative in nonadherence to therapy were presented under four headings: (1) the patient's attitude toward the diagnosis of ulcer; (2) the patient's attitude toward the recommended treatment; (3) the patient's attitude toward the physician; and (4) the response of guilt in the patient who does not adhere to therapy. Cases were presented illustrating the various components in each category, and methods of handling were described.
Effects of multi-family housing on marital fertility in Iran: population policy implications.

Abstract The hypothesis of the relationship between housing types and fertility, which was originally developed and tested in Bogota, Colombia's housing study, is reexamined using Iranian data of urban married women of reproductive age. The findings of the study clearly and consistently show that women living in single‐family housing units have significantly higher actual and desired fertility than women living in multi‐family housing units, regardless of their major social, economic and demographic differences. Furthermore, the analysis of the relative effects of socioeconomic and demographic variables on fertility indicate that housing types have greater effects on fertility than wife and husband's level of education, when the effects of other variables are controlled. This study implies that crowding and density, which generally are the outcome of high fertility, do have feedback effects causing fertility to decline. This provides some evidence for the hypothesis of self‐generating fluctuations in popu...
Assessing A.L. 288-1 femur length using computer-aided three-dimensional reconstruction.

Fossil reconstruction remains a requisite task for many types of paleoanthropological research. While reconstructions are traditionally accomplished by hand, computer modeling offers a novel and mathematically rigorous approach while providing advantages over the manual process. Computer models of fossil specimens can be reflected, scaled, and aligned in virtual space with relative ease; therefore, it is simple to generate multiple reconstructions to find the “best” one. Here we report on the reconstruction of A.L. 288-1ap (left femur) using three-dimensional computer models. Our “best” reconstruction has a maximum length of 277 mm, which is very near both the 280 mm originally estimated and the frequently cited 281 mm.
The Search for Extraterrestrial Life

Present knowledge does not permit the conclusion that, if life ever existed on Mars, it is now extinct.
A review of the challenges and opportunities in estimating above ground forest biomass using tree-level models

Accurate biomass measurements and analyses are critical components in quantifying carbon stocks and sequestration rates, assessing potential impacts due to climate change, locating bio-energy processing plants, and mapping and planning fuel treatments. To this end, biomass equations will remain a key component of future carbon measurements and estimation. As researchers in biomass and carbon estimation, we review the present scenario of aboveground biomass estimation, focusing particularly on estimation using tree-level models and identify some cautionary points that we believe will improve the accuracy of biomass and carbon estimates to meet societal needs. In addition, we discuss the critical challenges in developing or calibrating tree biomass models and opportunities for improved biomass. Some of the opportunities to improve biomass estimate include integration of taper and other attributes and combining different data sources. Biomass estimation is a complex process, when possible, we should make use of already available resources such as wood density and forest inventory databases. Combining different data-sets for model development and using independent data-sets for model verification will offer opportunities to improve biomass estimation. Focus should also be made on belowground biomass estimation to accurately estimate the full forest contribution to carbon sequestration. In addition, we suggest developing comprehensive biomass estimation methods that account for differences in site and stand density and improve forest biomass modeling and validation at a range of spatial scales.
Unemployment in dynamic general equilibrium economies

Abstract A tractable approach to modelling unemployment fluctuations in dynamic general equilibrium economies with non-Walrasian labor markets is presented and discussed.
Sound spectrographic diagnosis of aortic ball variance

Abnormalities in the silastic poppets of cardiac valve prostheses have been detected with increasing frequency. Ball variance can cause serious mechanical dysfunction of the prosthesis and can result in sudden death. Contour sound spectrograms were recorded on 12 patients with ball variance confirmed by operation and 25 controls. In ball variance the frequency of the aortic opening sound at the second right intercostal space was decreased, with the peak frequency recorded being below 1,300 cycles/sec in 11 of the 12 patients. The peak frequency was greater than 1,300 cycles/sec in 24 of the 25 control patients. The remaining patient had peak frequencies in both the normal and abnormal range. The diagnosis of aortic ball variance in patients with triple valve replacement remains difficult because of the nearly synchronous tricuspid closing and aortic opening sounds. The sound spectrographic findings have been the most reliable objective evidence of ball variance in patients with Starr-Edwards aortic prostheses of the Model 1000 series.
Document hierarchies from text and links

Hierarchical taxonomies provide a multi-level view of large document collections, allowing users to rapidly drill down to fine-grained distinctions in topics of interest. We show that automatically induced taxonomies can be made more robust by combining text with relational links. The underlying mechanism is a Bayesian generative model in which a latent hierarchical structure explains the observed data --- thus, finding hierarchical groups of documents with similar word distributions and dense network connections. As a nonparametric Bayesian model, our approach does not require pre-specification of the branching factor at each non-terminal, but finds the appropriate level of detail directly from the data. Unlike many prior latent space models of network structure, the complexity of our approach does not grow quadratically in the number of documents, enabling application to networks with more than ten thousand nodes. Experimental results on hypertext and citation network corpora demonstrate the advantages of our hierarchical, multimodal approach.
Behaviour and adjustment problems of young developmentally delayed children

ABSTRACT As part of an ongoing longitudinal study of developmental delay (DD), 35 six‐year‐old children with delays of unknown aetiology were assessed with measures of cognitive, language and educational competence. Their parents provided detailed information about their self‐help and personal‐social competencies, behaviour problems and temperament. As a group, the DD children evidenced high rates of behaviour problems, but there was considerable within‐group variability in intensity and pattern of problems. Low relationships were found between the intensity of behaviour problems and children's chronological age (CA), IQ, language level and self‐help competencies. The child variable most strongly associated with behaviour problems was temperament, or behavioural style.
Current and potential sustainable corn stover feedstock for biofuel production in the United States

Abstract Increased demand for corn (Zea mays L.) stover as a feedstock for cellulosic ethanol raises concerns about agricultural sustainability. Excessive corn stover harvesting could have long-term impacts on soil quality. We estimated current and future stover production and evaluated the potential harvestable stover amount (HSA) that could be used for biofuel feedstock in the United States by defining the minimum stover requirement (MSR) associated with the current soil organic carbon (SOC) content, tillage practices, and crop rotation systems. Here we show that the magnitude of the current HSA is limited (31 Tg y−1, dry matter) due to the high MSR for maintaining the current SOC content levels of soils that have a high carbon content. An alternative definition of MSR for soils with a moderate level of SOC content could significantly elevate the annual HSA to 68.7 Tg, or even to 132.2 Tg if the amount of currently applied manure is counted to partially offset the MSR. In the future, a greater potential for stover feedstock could come from an increase in stover yield, areal harvest index, and/or the total planted area. These results suggest that further field experiments on MSR should be designed to identify differences in MSR magnitude between maintaining SOC content and preventing soil erosion, and to understand the role of current SOC content level in determining MSR from soils with a wide range of carbon contents and climatic conditions.
Relationship between anemia and health care costs in heart failure.

Background Anemia is associated with higher morbidity and mortality in patients with heart failure (HF), but its implications for heath care costs are not well described.
SALSA: a synthesis array for lunar submillimeter astronomy

A conceptual design is described for a lunar submillimeter wavelength interferometer called SALSA, a Synthesis Array for Lunar Submillimeter Astronomy. Its design is greatly simplified over conventional submillimeter wavelength arrays because it takes advantage of a beam waveguide to relay signals to a centrally-located receiver system. The array is optimized to synthesize images at wavelengths between 60 and 300 microns, and it has an angular resolution of 10 milliarcsecs at 60 microns. Observations in this region provide unique insights into fundamental issues in astrophysics such as star formation, but are impossible from the earth's surface because of atmospheric absorption. The baseline design for SALSA consists of twelve, 3.5-meter diameter antennas arranged in a Y-shaped configuration consisting of three 0.5-km long arms, each with four antennas distributed according to a power-law function of distance. Such a beam-waveguide approach has significant advantages, since all the high-power-consumption items (active cryogenics, correlator) are at a central location and could share a single power source. In addition, the antennas can be quite simple and maintenance is greatly reduced. The primary technology challenges for developing such an array are the coherent detectors (mixers and local oscillator sources), and ensuring the dimensional stability of the optical elements under the extreme lunar thermal environment (85-385 K).
Providing developmentally competent care for adolescents during labor and birth.

In 2002 there were nearly half a million births in the United States to adolescent girls 19 or younger. Although nurses strive diligently to provide culturally competent care to women of differing ethnic backgrounds sometimes nurses can forget that developmentally competent care is also essential for providing optimal care to adolescents. A review of the literature found few studies documenting adolescent responses to labor and birth. Thurman and Hulsey documented adolescents preferences for and use of labor pain management and found that significantly less primiparous adolescents choose regional anesthesia compared to older primiparous women but the researchers could not explain why. Low et al contrasted adolescents experiences of childbirth with the experiences reported by adults. They found that adolescents put limited time into planning for their birth have a greater focus on planning for the baby and use the media as a significant source of information. Work has been done on providing social support to teens during pregnancy but little research has been published on providing support to adolescents during labor and birth. (excerpt)
Guest Editor’s Introduction to the Special Section on Nonverbal Aspects of Mate Choice and Courtship

The invited articles in this special section were initially part of a symposium entitled ‘‘Nonverbal Aspects of Mate Choice and Courtship,’’ which occurred at the Fifth International AnthropologicalCongressofAlesHrdlicka inPrague,CzechRepublic, September 2–5, 2009. The main aim of the symposium was to bring together scholars who use evolutionary theory as a conceptual framework for their research on mate choice and courtship. Represented disciplines included anthropology, psychology, human ethology, and biology. The symposium included 2 plenaries, 20 oral presentations, 12 poster presentations, 2 round table discussions, and one workshop. The symposium was convened by Jan Havlicek of Charles University and Vladimir Blažek of the University of West Bohemia. Articles were reviewed by the Guest Editor and the Editor and other members of the Editorial Board.
Observations on the small-scale distribution of estuarine phytoplankton

Analyses of phytoplankton collections from Narragansett Bay, Rhode Island and the Damariscotta River, Maine, USA showed that statistically significant differences in population density can usually be demonstrated within any series of collections when the collecting interval is more than 10 cm. Individual species in any series are in general over-dispersed. Phytoplankton patches ranging in size from <1 m to 12 m were tentatively identified. No correlation was found between temperature or salinity and the small-scale distribution of individual species. Possible causes of the inhomogeneities observed in phytoplankton distributions are considered.
Molecular Identification of Veterinary Yeast Isolates by Use of Sequence-Based Analysis of the D1/D2 Region of the Large Ribosomal Subunit

Conventional methods of yeast identification are often time-consuming and difficult; however, recent studies of sequence-based identification methods have shown promise. Additionally, little is known about the diversity of yeasts identified from various animal species in veterinary diagnostic laboratories. Therefore, in this study, we examined three methods of identification by using 109 yeast samples isolated during a 1-year period from veterinary clinical samples. Comparison of the three methods—traditional substrate assimilation, fatty acid profile analysis, and sequence-based analysis of the region spanning the D1 and D2 regions (D1/D2) of the large ribosomal subunit—showed that sequence analysis provided the highest percent identification among the three. Sequence analysis identified 87% of isolates to the species level, whereas substrate assimilation and fatty acid profile analysis identified only 54% and 47%, respectively. Less-stringent criteria for identification increased the percentage of isolates identified to 98% for sequence analysis, 62% for substrate assimilation, and 55% for fatty acid profile analysis. We also found that sequence analysis of the internal transcribed spacer 2 (ITS2) region provided further identification for 36% of yeast not identified to the species level by D1/D2 sequence analysis. Additionally, we identified a large variety of yeast from animal sources, with at least 30 different species among the isolates tested, and with the majority not belonging to the common Candida spp., such as C. albicans, C. glabrata, C. tropicalis, and the C. parapsilosis group. Thus, we determined that sequence analysis of the D1/D2 region was the best method for identification of the variety of yeasts found in a veterinary population.
PRIVATE PRACTICE AND THE PURCHASE OF SERVICES: Who Are the Practitioners?

Psychiatrists, psychologists, social workers, and nurses in private practice were surveyed with a view to the feasibility of referring patients from the public sector as part of comprehensive mental health planning. As a first step, information was secured about these clinicians' practices. Comparisons are made among the disciplines, with emphasis on practitioners' and patients' characteristics.
Development of a High-Performance Concrete to Store Thermal Energy for Concentrating Solar Power Plants

Researchers in their quest to find a suitable candidate material for solid sensible heat storage have identified concrete as an acceptable medium. However, at temperatures of 500°C and beyond the thermo-mechanical properties of ordinary concrete change significantly. This paper presents seven concrete mixtures of various material components and proportions that were developed and tested for resistance to temperatures up to 500°C. After exposure to 10 thermal cycles from ambient temperature to 500°C, six of the seven mixtures maintained in excess of 50% of their mechanical properties. This result is favorable for concrete to be used as a thermal energy storage medium. With concrete exhibiting acceptable mechanical and thermal properties at very high temperatures, the amount of energy stored per unit volume is increased, higher steam temperatures are available to facilitate power generation and the concrete can last for the design lifetime of the power generating system into which it is integrated.© 2011 ASME
Structural State of Relict Calcium-Bearing Plagioclases of Volcanic Origin from Metamorphosed and Propylitically Altered Rocks

Chemically unaltered calcium-bearing plagioclase (An 20 –An 60 ) of volcanic origin is found in propylitically altered and low-grade metamorphosed volcanic rocks from several areas. Although parts of the relict plagioclase phenocrysts are replaced by albite or by other secondary minerals, perfectly preserved igneous oscillatory zoning shows that the unaltered parts had not reacted chemically with the remainder of the rock nor undergone solid-state diffusion on a microscopically apparent scale. Universal stage and X-ray-diffraction measurements show that the chemically unaltered plagioclases in propylitically altered rocks and prehnite-pumpellyite metagraywacke facies and lower green-schist facies rocks are in their original high or high-intermediate structural states, whereas relict chemically unaltered plagioclases in middle greenschist facies rocks have inverted to the low structural state. The data suggest that natural quenched high plagioclase will not begin to invert to the low structural state until certain conditions of temperature and probably of water pressure have been exceeded. Temperatures of from 250° to 450° C appear to be required for inversion to proceed at water pressures of 1000–2000 bars. Experimental determination of the minimum inversion temperature at various water pressures may provide a method for inferring the temperature-pressure conditions of low-grade metamorphism and hydrothermal alteration and for estimating the depth of emplacement of certain magmatic bodies.
ACP Journal Club. Review: Evidence for the effectiveness of prophylactic drugs for tension-type headache in adults is limited.

Source Citation Verhagen AP, Damen L, Berger MY, Passchier J, Koes BW. Lack of benefit for prophylactic drugs of tension-type headache in adults: a systematic review. Fam Pract. 2010;27:151-65. 200...
Exercise induced compartment syndrome of the pectoralis major/deltoid in a professional tree climber.

Department of Orthopaedic Surgery, Division of Traumatology, University of Pittsburgh Medical Center,Kaufmann Medical Building, Pittsburgh, PAAn unusual case of compartment syndrome involvingthe pectoralis major and deltoid caused by intense exercisein a professional tree climber is presented. Although thepatient presented in extremis with established rhabdo-myolysis and impending renal failure, successful surgicaland medical management outlined in this report led to anuneventful recovery and return to previous function.
A new principle of polymer structure

With many types of linear polymer the helical or other type of chain structure which satisfies best the intrachain forces can give orientations (relative to neighboring chains) of atoms or groups having strong interchain interactions, which are favorable only over a limited region. When the limits of this region are reached, a change of structure is to be expected. This change may be a shift to a different type of crystalline structure or to an amorphous structure, a folding of the chains, or a change in chemical composition (e.g., in the sequence of residues, in proteins). It is suggested that this principle is responsible for the long x-ray spacings observed with many polymers and for the uniform folding of the chains in polymer single crystals. It is proposed that the zigzag chains in polymethamer (linear polyethylene) crystals are slightly twisted, primarily because of repulsions between the hydrogen atoms in successive methylene groups on the same side of the chain axis, and that these twisted chains can pack together without too strong interchain repulsions only over limited distances in the direction of the chain axes. The length of the segments between folds is presumed to be determined by the requirements (1) that the zigzags be suitably oriented for unstrained bonding at the segment ends and (2) that the interchain repulsions be not too great. Bei vielen Arten linearer Polymerer fuhrt die Helixstruktur oder irgendeine andere Kettenkonformation, die am besten innerkettigen Kraften genugt, bezuglich der Nachbarketten zu Anordnungen der Atome oder Atomgruppen, die starke zwischenkettige Wechselwirkungen haben, die nur uber einen begrenzten Bereich begunstigt sind. Werden die Grenzen dieses Bereiches erreicht, ist eine Strukturumwandlung zu erwarten. Diese Umwandlung kann das Auftreten eines anderen Kristallgitters oder des amorphen Zustandes sein, eine Faltung der Ketten oder eine Umwandlung in der chemischen Zusammensetzung (z.B. in der Sequenz der Grundbausteine in den Proteinen). Es wird nahegelegt, das dieses Prinzip mit der Langperiode der Rontgenstrukturanalyse zusammenhangt, die sich bei vielen Polymeren zeigt und mit der einheitlichen Faltung der Ketten in Einkristallen der Polymeren. Es wird angenommen, das die Zickzackketten in linearen Polyathylen-(Polymethamer-) Kristallen leicht verdreht sind; zunachst wegen der gegenseitigen Abstosung der Wasserstoffatome in aufeinanderfolgenden Methylengruppen auf der selben Seite der Kettenachse und weil diese verdrehten Ketten ohne zu stake gegenseitige, zwischenkettige Abstosung nur uber begrenzte Abstande in Richtung der Kettenachsen zusammengepackt werden konnen. Die Segmentlange zwischen den Falten wird vermutlich durch folgende Faktoren bestimmt : 1. das die Zickzackketten bei ungespannter Bindung an den Segmentenden passend orientiert sind und 2. das die zwischenkettige Abstosung nicht zu gros ist.
Determining Safety Stock in the Presence of Stochastic Lead Time and Demand

We consider the problem of setting safety stock when both the demand in a period and the lead time are random variables. There are two cases to consider. In the first case the parameters of the demand and lead time distributions are known; in the second case they are unknown and must be estimated. For the case of known parameters a standard procedure is presented in the literature. In this paper, examples are used to show that this procedure can yield results that are far from the desired result. A correct procedure is presented. When the parameters are unknown, it is assumed that a simple exponential smoothing model is used to generate estimates of demand in each period and that a discrete distribution of the lead time can be developed from historical data. A correct procedure for setting safety stocks that is based on these two inputs is given for two popular demand models. The approach is easily generalized to other models of demand. Safety stock calculation is simplified when certain normality assumptions are valid. Simulation results in the Appendix indicate when these assumptions about normality are reasonable.
Fractal solids, product measures and fractional wave equations

This paper builds on the recently begun extension of continuum thermomechanics to fractal porous media that are specified by a mass (or spatial) fractal dimension D, a surface fractal dimension d and a resolution length scale R. The focus is on pre-fractal media (i.e. those with lower and upper cut-offs) through a theory based on a dimensional regularization, in which D is also the order of fractional integrals employed to state global balance laws. In effect, the governing equations are cast in forms involving conventional (integer order) integrals, while the local forms are expressed through partial differential equations with derivatives of integer order but containing coefficients involving D, d and R. This procedure allows a specification of a geometry configuration of continua by ‘fractal metric’ coefficients, on which the continuum mechanics is subsequently constructed. While all the derived relations depend explicitly on D, d and R, upon setting D = 3 and d = 2, they reduce to conventional forms of governing equations for continuous media with Euclidean geometries. Whereas the original formulation was based on a Riesz measure—and thus more suited to isotropic media—the new model is based on a product measure, making it capable of grasping local fractal anisotropy. Finally, the one-, two- and three-dimensional wave equations are developed, showing that the continuum mechanics approach is consistent with that obtained via variational energy principles.
All-atom molecular dynamics simulations of actin-myosin interactions: a comparative study of cardiac α myosin, β myosin, and fast skeletal muscle myosin.

Myosins are a superfamily of actin-binding motor proteins with significant variations in kinetic properties (such as actin binding affinity) between different isoforms. It remains unknown how such kinetic variations arise from the structural and dynamic tuning of the actin–myosin interface at the amino acid residue level. To address this key issue, we have employed molecular modeling and simulations to investigate, with atomistic details, the isoform dependence of actin–myosin interactions in the rigor state. By combining electron microscopy-based docking with homology modeling, we have constructed three all-atom models for human cardiac α and β and rabbit fast skeletal muscle myosin in complex with three actin subunits in the rigor state. Starting from these models, we have performed extensive all-atom molecular dynamics (MD) simulations (total of 100 ns per system) and then used the MD trajectories to calculate actin–myosin binding free energies with contributions from both electrostatic and nonpolar fo...
Model-based parameters and indices for assessing the cardiovascular state

Parameters and indices derived from direct measurements and models have their limitations in characterizing the cardiovascular state under varied intrinsic alterations. Various approaches are presented to obtain such indices, and the necessity of normalization for extending their usefulness is discussed. >
LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model

The immune co-inhibitory receptors lymphocyte activation gene-3 (LAG3) and programmed cell death 1 (PD1) synergistically contribute to autoimmunity and tumor evasion. Here we demonstrate how they collaborate and interact to regulate T cell function. We first show that LAG3 and PD1 are co-expressed on both OVA-specific and non-specific T cells infiltrating murine ovarian tumors. Dual antibody blockade or genetic knockout of LAG3 and PD1 significantly enhanced T effector function and delayed tumor growth. LAG3 and PD1 co-localized in activated CD8+ T cells in vitro at the trans-Golgi vesicles, early/recycling endosomal compartments, lysosomes, and microtubule organizing center. Importantly, LAG3 and PD1 cluster with pLck at the immunological synapse. Reciprocal immunoprecipitation of T cell extracts revealed physical interaction between LAG3 and PD1. Mutational analyses indicate that the cytoplasmic domain of LAG3 is not absolutely required for its association with PD1, while the ITIM and ITSM of PD1 are necessary for its association with LAG3. Finally, LAG3 protein also associates with the Src-homology-2 domain-containing phosphatases (SHP1/2) which are known to be recruited by PD1 during T cell signaling. Our data indicate that the association of LAG3 with PD1 contributes to their rapid trafficking to the immunological synapse, leading to a synergistic inhibitory effect on T cell signaling.
Milton in the Library

Fulton describes how this special issue was inspired by a spring 2011 exhibit in the Alexander Library at Rutgers which consisted of about 150 books, pamphlets, broadsides, and manuscripts, and other artifacts having to do with John Milton, his political and cultural contexts, and his literary afterlife.Â He summaries the contents of each article in this issue and how they fit together.Â He also outlines ways in which the actual artifact reveals far more about the conditions of writing and reading than can be reproduced in modern editions or in digital form. As we move forward in the centuries after Miltonâ€™s death, we encounter many different Miltons â€”the young but proper Milton of the eighteenth century, replaced by the bold, powerful, prophetic, Blakean Milton early in the nineteenth century.
Patellofemoral Instability in Skeletally Immature Athletes

Acute patellofemoral dislocation is the most common acute knee disorder in children and adolescents. The predisposing factors for acute patellar dislocation are multifactorial. Unless associated with substantial articular cartilage damage, nonsurgical management is typically used to treat a first-time acute patellofemoral dislocation in a skeletally immature athlete. In the setting of recurrent instability, surgical reconstruction is usually recommended. Surgical treatment of patellofemoral instability in the skeletally immature athlete is evolving from nonanatomic extensor mechanism surgical procedures to anatomic restorative procedures based on reconstitution of the medial patellofemoral ligament. The current goal of surgery is to restore the normal anatomy of the patellofemoral joint. Proper patient selection and attention to technical details are important in achieving good outcomes.
Pros and cons of antioxidant use during radiation therapy

Radiation therapy is one of the major treatment modalities in the management of human cancer. While impressive progress like more accurate dosimetry and more precise methods of radiation targeting to tumor tissue has been made, the value of radiation therapy in tumor control may have reached a plateau. At present, two opposing hypotheses regarding the use of antioxidants during radiation therapy have been proposed. One hypothesis states that supplementation with high doses of multiple micronutrients including high dose dietary antioxidants (vitamins C and E, and carotenoids) may improve the efficacy of radiation therapy by increasing tumor response and decreasing some of its toxicity on normal cells. The other hypothesis suggests that antioxidants (dietary or endogenously made) should not be used during radiation therapy, because they would protect cancer cells against radiation damage. Each of these hypotheses is based on different conceptual frameworks that are derived from results obtained from specific experimental designs, and thus, each may be correct within its parameters. The question arises whether any of these concepts and experimental designs can be used during radiation therapy to improve the management of human cancer by this modality. This review has analyzed published data that are used in support of each hypothesis, and has revealed that the current controversies can be resolved, if the results obtained from one experimental design are not extrapolated to the other. This review has also discussed the scientific rationale for a micronutrient protocol that includes high doses of dietary antioxidants (vitamin C, vitamin E succinate and natural beta-carotene) which can be used adjunctively with radiation therapy.
Pharmacogene regulatory elements: from discovery to applications

Regulatory elements play an important role in the variability of individual responses to drug treatment. This has been established through studies on three classes of elements that regulate RNA and protein abundance: promoters, enhancers and microRNAs. Each of these elements, and genetic variants within them, are being characterized at an exponential pace by next-generation sequencing (NGS) technologies. In this review, we outline examples of how each class of element affects drug response via regulation of drug targets, transporters and enzymes. We also discuss the impact of NGS technologies such as chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq), and the ramifications of new techniques such as high-throughput chromosome capture (Hi-C), chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) and massively parallel reporter assays (MPRA). NGS approaches are generating data faster than they can be analyzed, and new methods will be required to prioritize laboratory results before they are ready for the clinic. However, there is no doubt that these approaches will bring about a systems-level understanding of the interplay between genetic variants and drug response. An understanding of the importance of regulatory variants in pharmacogenomics will facilitate the identification of responders versus non-responders, the prevention of adverse effects and the optimization of therapies for individual patients.
Human rights and American bioethics: resistance is futile.

1. Annas GJ. American Bioethics: Crossing Human Rights and Health Law Boundaries. New York: Oxford University Press; 2005:24. 2. See note 1, Annas 2005:24. 3. Baker R. Bioethics and human rights: A historical perspective. Cambridge Quarterly of Healthcare Ethics 2001;10:241–52. Roberto Andorno shares this view, calling human rights ‘‘the last expression of a universal ethics,’’ and ‘‘a ‘lingua franca’ of international relations’’; Andorno R. Biomedicine and international human rights law: In search of a global consensus. Bulletin of the World Health Organization 2002;8012:959–63. 4. For example, the United Nations’ International Covenant on Economic, Social, and Cultural Rights (1966), and the corresponding Covenant on Civil and Political Rights (1966). 5. See note 1, Annas 2005:40. 6. Lomasky L. Persons, Right, and the Moral Community. Oxford: Oxford University Press; 1987:3. 7. Arras JD, Fenton EM. Bioethics and human rights: Access to health-related goods. Hastings Center Report 2009:39(5):27–38. 8. This section of the paper is drawn largely from Fenton EM. Genetic enhancement—A threat to human rights? Bioethics 2009;22(1): 1–7. 9. See note 1, Annas 2005:37. 10. See note 1, Annas 2005:51. 11. Warren MA. Moral Status: Obligations to Persons and Other Living Things. Oxford: Clarendon Press; 1997:19. 12. Griffin J. First steps in an account of human rights. European Journal of Philosophy 2001;9: 306–27. 13. Nussbaum MC. Frontiers of Justice: Disability, nationality, species membership. Cambridge, MA: The Belknap Press; 2006. See also Nussbaum M. Capabilities and human rights. In: de Greiff P, Cronin C, eds. Global Justice and Transnational Politics: Essays on the Moral and Political Challenges of Globalization. Cambridge, MA: MIT Press; 2002. 14. Some level of physical similarity is assumed in claiming that two individuals stand in a relationship of justice to one another. But genetic enhancement technology will not produce humans so different from us that this relationship of justice will not obtain. We may be more different from an unenhanced and severely mentally disabled individual than we are from an enhanced individual with a better memory, yet, because we recognize the severely disabled person as standing in the relationship of justice to us, then we will also recognize the enhanced individual as a subject of justice. 15. Not all fictional accounts of a genetically engineered future are pessimistic. The XMen comics, for example, portray the social and political conflicts between humans and ‘‘mutants,’’ who are said to represent the next stage of human evolution. Importantly, the nonhumans and X-characters are portrayed, like the humans, as full agents, and peaceful coexistence among them all is viewed as possible and desirable in spite of prejudice against the mutants on the part of the unmodified humans. 16. Wikler D, Brock DW. Population-level bioethics: Mapping a new agenda. In: Dawson A, Verweij M. Ethics, Prevention, and Public Health. Oxford, UK: Clarendon Press; 2007.
Synthesis of operation-centric hardware descriptions

Most hardware description frameworks, whether schematic or textual, use cooperating finite state machines (CFSM) as the underlying abstraction. In the CFSM framework, a designer explicitly manages the concurrency by scheduling the exact cycle-by-cycle interactions between multiple concurrent state machines. Design mistakes are common in coordinating interactions between two state machines because transitions in different state machines are not semantically coupled. It is also difficult to modify one state machine without considering its interaction with the rest of the system. This paper presents a method for hardware synthesis from an "operation centric" description, where the behavior of a system is described as a collection of "atomic" operations in the form of rules. Typically, a rule is defined by a predicate condition and an effect on the state of the system. The atomicity requirement simplifies the task of hardware description by permitting the designer to formulate each rule as if the rest of the system is static. An implementation can execute several rules concurrently in a clock cycle, provided some sequential execution of those rules can reproduce the behavior of the concurrent execution. In fact, detecting and scheduling valid concurrent execution of rules is the central issue in hardware synthesis from operation-centric descriptions. The result of this paper shows that an operation-centric framework offers significant reduction in design time, without loss in implementation quality.
Active GPIIb-IIIa conformations that link ligand interaction with cytoskeletal reorganization

Glycoprotein (GP) IIb-IIIa plays a critical role in platelet aggregation and platelet-mediated clot retraction. This study examined the intramolecular relationship between GPIIb-IIIa activation and fibrinogen binding, platelet aggregation, and platelet-mediated clot retraction. To distinguish between different high-affinity activation states of GPIIb-IIIa, the properties of an antibody (D3) specific for GPIIIa that induces GPIIb-IIIa binding to adhesive protein molecules and yet completely inhibits clot retraction were used. Clot retraction inhibition by D3 was not due to altered platelet-fibrin interaction; however, combination treatments of D3 and adenosine diphosphate (ADP) inhibited full-scale aggregation and decreased the amounts of GPIIb-IIIa and talin incorporated into the core cytoskeletons. Morphologic evaluation of the D3/ADP aggregates showed platelets that were activated but to a lesser extent when compared to ADP only. ADP addition to platelets caused an increase in the number of D3 binding sites indicating that ligand had bound to the GPIIb-IIIa receptor. These data suggest that high-affinity GPIIb-IIIa– mediated ligand binding can be separated mechanistically from GPIIb-IIIa–mediated clot retraction and that clot retraction requires additional signaling through GPIIb-IIIa after ligand binding. The conformation recognized by D3 represents the expression of a GPIIb-IIIa activation state that participates in full-scale platelet aggregation, cytoskeletal reorganization, and clot retraction.
Retrospective evaluation of palliative care and hospice utilization in hospitalized patients with metastatic breast cancer

Background:Hospitalizations in patients with metastatic cancer occur commonly at the end of life but have not been well-described in individuals with metastatic breast cancer.Aim:To describe the re...
Abstract 3878: A highly sensitive assay for the discovery of inhibitors of the histone methyltransferase DOT1L to treat MLL-rearranged leukemia

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL MLL-rearranged leukemia is an aggressive form of cancer characterized by specific chromosomal rearrangements of the mixed lineage leukemia (MLL) gene. In normal cells, MLL, a histone methyltransferase, methylates the lysine 4 residue on histone 3 (H3K4) and thereby regulates the expression of genes which control hematopoietic development. In leukemic cells, chromosomal rearrangements fuse the N-terminus of MLL with one of more than 50 partner proteins, giving rise to oncogenic fusion proteins that lack H3K4 methyltransferase activity. These fusion proteins inappropriately recruit DOT1L, which methylates H3K79, producing an abnormal methylation pattern and activation of genes normally suppressed during differentiation. Elevated expression of HOXA9 in particular leads to a block in normal hematopoetic differentiation and the onset of leukemia. A solid body of evidence has shown DOT1L to be crucial for the development and maintenance of MLL-rearranged leukemias; consequently, it is a promising target for therapeutic intervention. We have focused on developing an assay suitable for high-throughput screening (HTS) to detect compounds that inhibit DOT1L enzymatic activity. DOT1L catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to H3K79 and generates S-adenosylhomocysteine (SAH) as a byproduct. The enzyme displays a very low rate of methylation of histone octamers or nucleosomes and no activity towards individual histones or histone-derived peptides. Thus DOT1L HTS requires a highly sensitive assay that is able to accommodate protein-protein and protein-DNA complexes as substrates. An assay using radiolabeled SAM has sufficient sensitivity, but is relatively laborious and not well-suited for HTS. We tested several previously reported non-radioactive assay formats, but none enabled robust detection of DOT1L activity. Therefore, we developed a coupled enzyme assay in which SAH is converted to homocysteine and adenosine using SAH hydrolase. In a second enzyme-coupled step, adenosine kinase generates AMP and ADP from the SAH-derived adenosine and added ATP. Finally, ADP is detected using the luciferase-based Promega ADP-Glo assay. The luminescent signal provides a highly sensitive measure of ADP at a concentration as low as 10 nM. The readout is directly proportional to SAH production; thus DOT1L inhibitors are identified by a reduction in this signal. We report development of the assay, including careful optimization of the activity of adenosine kinase to enhance sensitivity, and assay validation demonstrating DOT1L inhibition by the non-selective SAM-competitive inhibitor sinefungin, and pilot HTS of a 2,000-compound library. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3878. doi:1538-7445.AM2012-3878
OUTCOMES FOR SURGICAL AND TRANSCATHETER AORTIC VALVE REPLACEMENT IN NONAGENARIANS

Transcatheter aortic valve replacement (TAVR) may offer extreme-age patients a treatment alternative to surgical aortic valve replacement (SAVR). We aim to describe outcomes of TAVR and SAVR in nonagenarians in a large nationwide inpatient sample (NIS). The NIS was used to identify patients>90 year