cssi/SciSciGPT-SciSciNet huggingface dataset:
Structure and mechanism of MT-ADPRase, a Nudix hydrolase from Mycobacterium tuberculosis

Abstract Nudix hydrolases are a family of proteins that contain the characteristic sequence G X 5 E X 7 REU X EE X G (I/L/V), the Nudix box. They catalyze the hydrolysis of a variety of nucleoside diphosphate derivatives such as ADP-ribose, Ap n A (3 ≤ n ≤ 6), NADH, and dATP. A number of Nudix hydrolases from several species, ranging from bacteria to humans, have been characterized, including, in some cases, the determination of their three-dimensional structures. The product of the Rv1700 gene of M. tuberculosis is a Nudix hydrolase specific for ADP-ribose (ADPR). We have determined the crystal structures of MT-ADPRase alone, and in complex with substrate, with substrate and the nonactivating metal ion Gd 3+ , and in complex with a nonhydrolyzable ADPR analog and the activating metal ion Mn 2+ . These structures, refined with data extending to resolutions between 2.0 and 2.3 A, showed that there are sequence differences in binding site residues between MT-ADPRase and a human homolog that may be exploited for antituberculosis drug development.
Computation and Comparison of Dynamic Viscosity Based on Quasi-Static and Dynamic FEM Analysis for AL7050-T7451

Coefficients of dynamic viscosity for AL7050-T7451 at room temperature is extracted by creep and stress relaxation simulations in Ansys. An analogy has been established for both creep and stress relaxation, with simple Maxwell Model. The stress relaxation curve thus obtained is then used to generate the Prony series coefficients which are then used to run some dynamic analysis in Ansys to see the effect of loading at different frequencies on the value of η (i.e dynamic viscosity). This will be verified with the simple analytical dynamic formulation based on the Maxwell Model. A good agreement has been found for both quasi-static and dynamic tests with Maxwell model.
Adsorption of metallic radionuclides on plastic phantom walls

Metal radionuclide solutions at neutral pH adhere to plastic containers. Adsorption of radionuclides on the walls of phantoms leads to a nonuniform activity distribution, which could adversely affect imaging studies, as well as phantom-based validations of absorbed dose calculations used in radioimmunotherapy, requiring accurate knowledge of the underlying activity distribution. In the work reported here, the authors determined the degree of metal chelation required to minimize metallic radionuclide oxide formation and adsorption on phantom walls in order to yield more reliable experimental data for validating image-based dosimetry. Using hollow spherical plastic phantoms, the authors evaluated three different radionuclides, I-131, In-111, and Y-90, in solutions containing three different concentrations of the chelator, ethylenediaminetetraacetate (EDTA). Adsorption to plastic walls was determined using microSPECT imaging and/or by counting aliquots of solutions. Reconstructed images and measurements of I-131 activity showed that it was uniformly distributed within all spheres; however, images of In-111 in 0.25-microM EDTA indicated that the activity concentration near the wall was much higher than that in the middle of the sphere. The decrease in activity concentration near the center of the spheres was approximately 47%. Y-90 in 0.25-microM EDTA behaved similarly; the activity concentration of Y-90 decreased by 46%. For an In-111 or Y-90 radioactivity concentration of 0.74 MBq/mL, a 2.5-microM EDTA solution was required to achieve a uniform distribution, suggesting that, under our experimental conditions, approximately 700 EDTA molecules were required for each radiometal atom to prevent precipitation and adsorption on poly(methylmethacrylate). For certain radiometals, e.g., In-111 or Y-90, adequate chelation is essential to achieve uniform activity concentration values and homogeneous distribution within the phantom compartments.
Pericardial Diseases, With a Focus on Etiology, Pathogenesis, Pathophysiology, New Diagnostic Imaging Methods, and Treatment

Recent advances in the study of pericardial disorders have opened new diagnostic windows to the heart through the pericardial sac, with the development of pericardioscopy and thoracoscopy. Specific diagnosis of inflammatory, postinflammatory, autoreactive, or neoplastic pericardial disease can now be made by epicardial and pericardial biopsy and by cytologic analysis of the pericardial fluid. In perimyocarditis, optically guided epicardial biopsy gives more disease-specific results than does endomyocardial biopsy in the same patients. For viral and tuberculous pericarditis, molecular techniques such as polymerase chain reaction and in situ hybridization are available. Immunologic characterization of lymphocytic cells and antibodies demonstrates increased reactivity in viral, autoimmune, and neoplastic disorders of the heart. Doppler echocardiographic features in tamponade are reviewed thoroughly. Advantages and problems of pericardectomy in constrictive disease are noted, and finally, a pragmatic clinical and scientific approach for improved diagnosis of pericardial diseases is outlined.
Enabling bone formation in the aged skeleton via rest-inserted mechanical loading.

The mild and moderate physical activity most successfully implemented in the elderly has proven ineffective in augmenting bone mass. We have recently reported that inserting 10 s of unloaded rest between load cycles transformed low-magnitude loading into a potent osteogenic regimen for both adolescent and adult animals. Here, we extended our observations and hypothesized that inserting rest between load cycles will initiate and enhance bone formation in the aged skeleton. Aged female C57BL/6 mice (21.5 months) were subject to 2-week mechanical loading protocols utilizing the noninvasive murine tibia loading device. We tested our hypothesis by examining whether (a) inserting 10 s of rest between low-magnitude load cycles can initiate bone formation in aged mice and (b) whether bone formation response in aged animals can be further enhanced by doubling strain magnitudes, inserting rest between these load cycles, and increasing the number of high-magnitude rest-inserted load cycles. We found that 50 cycles/day of low-magnitude cyclic loading (1200 μe peak strain) did not influence bone formation rates in aged animals. In contrast, inserting 10 s of rest between each of these low-magnitude load cycles was sufficient to initiate and significantly increase periosteal bone formation (fivefold versus intact controls and twofold versus low-magnitude loading). However, otherwise potent strategies of doubling induced strain magnitude (to 2400 μe) and inserting rest (10 s, 20 s) and, lastly, utilizing fivefold the number of high-magnitude rest-inserted load cycles (2400 μe, 250 cycles/day) were not effective in enhancing bone formation beyond that initiated via low-magnitude rest-inserted loading. We conclude that while rest-inserted loading was significantly more osteogenic in aged animals than the corresponding low-magnitude cyclic loading regimen, age-related osteoblastic deficits most likely diminished the ability to optimize this stimulus.
Institutional mapping of Oregon coastal watershed management options

Institutional mapping is a technique that builds on the logic of Geographic Information Systems (GIS). In GIS, coverages placedover a base map show spatial relations. Social institutions are more difficult to ‘‘map’’ physically. Institutional mapping uses three social coverages—scale, power, andcapital. Four sets of institutions affecting watershedmanagement—salmon restoration, water quality improvement, forest management, andland -use planning—illustrate the institutional mapping process. Analysis indicates that water quality institutions under the Clean Water Act (CWA) have a slightly higher ranking on scale, power, andcapital. Basedon these rankings, CWA requirements are pred ictedto have greater potential for improving watershedhealth in coastal settings than institutions associatedwith salmon restoration, forest management, or land-use planning. The differences are not large, andoverlapping goals for protecting salmon, improving water quality, sustainable forest management, andeffective land -use planning institutions offers the strongest prospect for
Non-cooperative, semi-cooperative, and cooperative games-based grid resource allocation

In this paper we consider, compare and analyze three game theoretical grid resource allocation mechanisms. Namely, 1) the non-cooperative sealed-bid method where tasks are auctioned off to the highest bidder, 2) the semi-cooperative n-round sealed-bid method in which each site delegate its work to others if it cannot perform the work itself, and 3) the cooperative method in which all of the sites deliberate with one another to execute all the tasks as efficiently as possible. To experimentally evaluate the above mentioned techniques, we perform extensive simulation studies that effectively encapsulate the task and machine heterogeneity. The tasks are assumed to be independent and bear multiple execution time deadlines. The simulation model is built around a hierarchical grid infrastructure where machines are abstracted into larger computing centers labeled "federations", each of which are responsible for managing their own resources independently. These federations are then linked together with a primary portal to which grid tasks would be submitted. To measure the effectiveness of these game theoretical techniques, the recorded performance is evaluated against a conventional baseline method in which tasks are randomly assigned to the sites without any task execution guarantee.
Using personal global positioning system devices in paratransit

An innovative solution to improve the current service efficiency in paratransit is introduced. The conventional pickup procedure requires reservations in advance for the paratransit operator to meet passengers at designated locations and missed pickups may occur due to the ambiguity of the address information or the inability of finding a specific location. With the availability of existing mobile global positioning system (GPS) devices, passengers can be located instantly, which ensures a successful pickup. This research explores the potential feasibility of using mobile GPS devices to reduce the number of missed pickups. Two GPS-tracking devices were tested and a prototype was also developed. Under this prototype, the agency dispatcher can see both the vehicle and the passenger and therefore instantly supervise the pickup if any errors occur. As new features can be added to the prototype system and new technologies become available, opportunities for future work are also presented.
Survival and precopulatory guarding behavior of Hyalella azteca (Amphipoda) exposed to nitrate in the presence of atrazine.

Nitrate is one of the most commonly detected contaminants found in aquatic systems with other pesticides such as atrazine. The current study examined potential combined effects of nitrate and atrazine on adults of the freshwater amphipod Hyalella azteca, using survival and precopulatory guarding behavior as toxic endpoints. Although significant differences in acute toxicity with nitrate alone and in binary combination with atrazine (200 µg/L) in water-only tests were not consistently observed for each time point, potential biologically relevant trends in the data were observed. Posttest growth and behavioral observations (10-day period) conducted after 96-hour exposure suggested that atrazine and nitrate at these concentrations did not result in delayed effects on H. azteca. However, when test conditions were modified from standard toxicity tests by feeding amphipods, nitrate was found to be more toxic, with a reduction in median lethal concentration (LC50) values of approximately 80%. We also demonstrated that nitrate exhibits a dose–response effect on precopulatory guarding behavior of H. azteca, suggesting that reproductive effects may occur at environmentally relevant concentrations. Environ. Toxicol. Chem. 2011; 30:1170–1177. © 2011 SETAC
THE USE OF THE TERM “HYPOTHESIS” IN GEOGRAPHY∗

Stating a hypothesis is becoming a common procedure in geographic writing, but the meaning and function of the term “hypothesis” have a wide array of interpretations. Some geographers use the term to pose fairly specific, directional relationships between phenomena, others use it to state more general relationships, and still others equate it with question, explanation, conclusion, contention, assumption, and model. This confused state of affairs is interpreted as the result of scientific faddism and pretentiousness.
Well-Being of Caregivers of Spouses with Parkinson's Disease:

This study examined the relationship among stages of Parkinson's disease (PD), elderly care receivers' physical and social functioning, and spousal caregivers' physical, social. psychological, and economic well-being. The nonrandom convenience study sample comprised 30 spousal caregivers of elderly individuals diagnosed with PD; all attended group support sessions. Findings indicated a statistically significant linear relationship between stages of PD and care receivers' functional ability and between care receivers' functional and social ability and caregivers' hours of caregiving. Caregivers' health was associated with diminished physical functioning of care receivers. Caregivers' age, years of marriage, and educational level were associated with their social, psychological, and financial well-being. The main implication for nursing practice is that elderly family caregivers must be included in mutually developed care plans; they are at high risk for diminished well-being because of the time and energy ...
DEFECTS IN LIQUID CRYSTALS: SURFACE AND INTERFACIAL ANCHORING EFFECTS

This review discusses static properties of topological defects, such as line defectsdisclinations and dislocations, point defects — hedgehogs (monopoles) and boojums; focal conic domains and tilt grain boundaries in basic types of liquid crystals: uniaxial and biaxial nematics, cholesterics and smectics. We present the most popular experimental techniques to study defects in soft matter, namely, polarizing microscopy and fluorescence confocal polarizing microscopy. The role of bounding surfaces and the so-called surface anchoring that lifts the degeneracy of the order parameter in stability of defects is discussed. Because of the surface anchoring, the equilibrium state of a bounded liquid crystal might contain topological defects. For example, nematic bubbles nucleating during the first-order phase transition from the isotropic melt, might contain point defects (hedgehogs and boojums) and disclination loops when their size is larger than the anchoring extrapolation length defined by the ratio of the Frank elastic constant of the director curvature and the (polar) anchoring coefficient. Depending on the strength of surface anchoring, an edge dislocation might be expelled from the system with ID positional order or be stabilized in the bulk. Furthermore, focal conic domains play the role of “surface anchoring facets” by providing the necessary orientation of the liquid crystal director at the smectic boundary.
Alcohol and tobacco: clinical and treatment issues.

T COMMENTARY ADDRESSES talks presented at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) conference on Alcohol and Tobacco: Mechanisms and Treatment, Clinical and Treatment Issues session. Overall, it was clear from the proceedings that the field has made considerable advances since the first conference a decade ago (Fertig and Allen, 1995). Rather than summarize the presentations, because summaries appear as part of these proceedings, this commentary examines gaps in our knowledge base.
Post-Traumatic Stress Disorder (PTSD) in Victims of Domestic Violence A Review of the Research

The objectives of this research were to analyze data from literature based on studies of battered women to determine (a) the correlation of domestic violence and post-traumatic stress disorder (PTSD), (b) the best treatment strategies for PTSD, and (c) the evidence of PTSD treatment effectiveness with battered women. Findings were (a) symptoms of battered women are consistent with PTSD symptoms; (b) certain populations are at higher risk of developing PTSD symptoms; (c) intensity, duration, and perception of the battering experience is a significant factor in the severity of the PTSD symptoms; (d) demographic variables influence PTSD severity; (e) standardized PTSD assessment is needed by professionals working with women experiencing domestic violence; (f) there is a need for greater public health involvement for prevention, identification, and medical treatment of domestic violence and PTSD; and (g) certain treatment strategies are recommended for PTSD but lack rigorous testing of their efficacy.
Micromechanical and tribological characterization of alternate pole tip materials for magnetic recording heads

Pole tip recession or PTR (relative wear of the pole tip with respect to the air bearing surface) causes signal loss when using inductive heads. Loss of signal caused by spacing between a head gap and the recording medium is magnified in high-density short wavelength recording. Nickel iron (NiFe) is the most commonly used pole material. NiFe is softer than the head substrate material (typically NiZn ferrite or Al2O3TiC) which leads to PTR as a result of differential wear of the materials. Alternate pole tip materials which are more wear resistant and superior in magnetic properties (such as high saturation magnetization), as compared with NiFe, need to be developed. In this research, NiFe, cobalt zirconium tantalum (CoZrTa) and iron aluminum nitride (FeAlN) materials were studied. In the first phase of this study, micromechanical characterization of the three pole tip materials, the alumina (Al2O3) insulating under/overcoat and gap material and the Al2O3TiC substrate was conducted using a depth-sensing nanoindenter. The nanohardness of NiFe, CoZrTa and Al2O3 are similar and about one half that of FeAlN, and the hardness of the Al2O3TiC substrate is about twice that of FeAlN. Microscratch studies showed that the critical load required to cause failure of the NiFe and CoZrTa films are similar and about one fourth that of FeAlN, and the critical load for FeAlN is comparable with that of the Al2O3 and Al2O3TiC substrate. Thus, FeAlN is superior in mechanical properties to NiFe and CoZrTa. In the second phase of this study, dummy tape heads fabricated with the three pole materials were run against metal particle (MP) tape in a linear tape drive. The PTR was measured by atomic force microscope (AFM) imaging before and after the sliding tests. Any nonuniformities in the thin-film region gets removed in the first few kilometres of sliding. FeAlN poles exhibited a low (∼10 nm) and constant PTR over 1 000 km of tape sliding distance, whereas the NiFe and CoZrTa poles exhibited growth in recession to about 30 and 40 nm, respectively, over the same sliding distance. The superior wear resistance and high saturation magnetization of FeAlN are ideal for high-density thin-film inductive heads.
The distribution of life-saving medical resources: equality, life expectancy, and choice behind the veil.

In this essay, I survey egalitarian and utilitarian approaches to the distribution of scarce life-saving medical resources. In my view, the major criterion for the distribution of scarce life-saving medical resources (hereinafter sometimes the “distribution of life”) should be life expectancy: we should distribute life so as to maximize life-years. In Section II, I discuss the life-year maximization approach and situate it within utilitarian theory.
Consistency in a model for distributed learning with specialists

Motivated by sensor networks and traditional methods of statistical pattern recognition, a model for distributed learning is formulated. The model is in line with learning models considered in the context of Stone-type classifiers, but differs in the dependency structure of the sampling process; questions of universal consistency are addressed.
The brain at high altitude.

The sport of high-altitude climbing encompasses a number of factors of stress that supersede the usual endurance activities at lower altitudes. The effect of hypoxia on both physical and mental performance can be profound and, therefore, compound the risk. Much is yet to be known, particularly about the brain. Hopefully, a better understanding of the effect of hypoxia on neurotransmitters, the effect of hypoxemia on blood flow to all areas of the brain, and the potential subsequent anatomic changes that may take place are all yet to be discovered. Perhaps the more we know about it, the more appropriate it will be to call climbing a "no-brainer." Language: en
Magnetic field data: Thin atmosphere on Saturn's moon Dione

A new study indicates that Dione, one of Saturn's moons, probably has a tenuous atmosphere. NASA's Cassini spacecraft has conducted only two close flybys of Dione. Magnetic field observations from one of those flybys, described by Simon et al., show evidence of an atmospheric interaction with magnetospheric plasma. The authors used a model to demonstrate that a low-density atmosphere would explain the magnetic field data. (Geophysical Research Letters, doi:10.1029/2011GL048454, 2011)
Outcome of cases of de novo structural rearrangements diagnosed at amniocentesis

The frequency of de novo rearrangements at amniocentesis was determined in 76952 prenatal diagnoses from centres in the United States. Rates for balanced rearrangements are slightly greater than rates previously reported in the newborn, possibly because banding studies were not used in the latter. Rates for unbalanced rearrangements are considerably higher in the amniocentesis data not only because banding was used but also because a substantial loss of abnormal conceptions is to be expected between amniocentesis and birth. The higher frequency of cases with supernumerary markers at amniocentesis is unexplained. A review of 66 apparently balanced de novo rearrangements found at amniocentesis revealed evidence of abnormality in five; in four of these the abnormality was noted in the abortus. The number of cases observed is still too small to rule out a risk of abnormality no greater than the usual rate of abnormalities at birth. Abnormalities were detected in 6 of 10 cases with unbalanced de novo rearrangements. In 33 cases of non-familial supernumerary chromosomes 6 (18.2 per cent) showed abnormality. Non-satellited markers appeared to have a higher rate of abnormality than satellited markers but the difference is not statistically significant. Further studies and improved follow-up of de NOVO cases diagnosed at amniocentesis are required.
Scanning Tunneling Microscopy of Chemical Vapor Deposition Diamond Film Growth on Highly Oriented Pyrolytic Graphite and Silicon

We report scanning tunneling microscopy (STM) studies of chemical vapor deposition (CVD) diamond film growth on highly oriented pyrolytic graphite (HOPG) and Si. The films were grown using hot-tungsten filament CVD. Using conditions typical for CVD diamond growth, we find that HOPG is etched by atomic hydrogen such that oriented hexagonal pits 50–5,000 A in diameter are produced on the surface. Diamond crystallites are observed to nucleate on the walls of these pits and not on the smooth sp 2 bonded parts of the surface. At lower sample temperatures, HOPG is etched such that large circular pits approximately 10,000 A in diameter and 7 A deep are produced. Nanoscale linear structures, which we conjecture are hydrocarbon chains, are observed in these pits. These structures orient themselves when a voltage of 10 V is applied to the tip. The initial stages of diamond film growth on Si were studied. Polycrystalline films on Si approximately 2 µ thick were imaged in air from a micron to atomic resolution scale. The micrometer scale images show that these films consist of diamond crystallites with (100) or (111) oriented faces. Atomic resolution images of the (100) surface in air showed a 2 × 1 dimer reconstruction with a distance between dimer rows of approximately 5.1 A.
Interferometric Near-Infrared Spectroscopy (iNIRS) for determination of optical and dynamical properties of turbid media

We introduce and implement interferometric near-infrared spectroscopy (iNIRS), which simultaneously extracts optical and dynamical properties of turbid media through analysis of a spectral interference fringe pattern. The spectral interference fringe pattern is measured using a Mach-Zehnder interferometer with a frequency-swept narrow linewidth laser. Fourier analysis of the detected signal is used to determine time-of-flight (TOF)-resolved intensity, which is then analyzed over time to yield TOF-resolved intensity autocorrelations. This approach enables quantification of optical properties, which is not possible in conventional, continuous-wave near-infrared spectroscopy (NIRS). Furthermore, iNIRS quantifies scatterer motion based on TOF-resolved autocorrelations, which is a feature inaccessible by well-established diffuse correlation spectroscopy (DCS) techniques. We prove this by determining TOF-resolved intensity and temporal autocorrelations for light transmitted through diffusive fluid phantoms with optical thicknesses of up to 55 reduced mean free paths (approximately 120 scattering events). The TOF-resolved intensity is used to determine optical properties with time-resolved diffusion theory, while the TOF-resolved intensity autocorrelations are used to determine dynamics with diffusing wave spectroscopy. iNIRS advances the capabilities of diffuse optical methods and is suitable for in vivo tissue characterization. Moreover, iNIRS combines NIRS and DCS capabilities into a single modality.
Ultrafast Structural Evolution and Chromophore Inhomogeneity inside a Green-Fluorescent-Protein-Based Ca2+ Biosensor

Understanding excited-state structural dynamics of fluorescent-protein-based biosensors for Ca2+ imaging is crucial for developing new in vivo Ca2+ indicators and advancing bioimaging. We implemented wavelength-tunable femtosecond stimulated Raman spectroscopy (FSRS) with a 530 nm Raman pump to uncover the working mechanism of an intensiometric fluorescent-protein biosensor, G-GECO1.1, highlighting the deprotonation process of its embedded chromophore. Besides confirming the dynamic difference of excited-state proton transfer (ESPT) in the Ca2+-free/bound protein, we revealed a chromophore two-ring twisting process with time constants of 36/60 ps that competes with ESPT. In contrast with FSRS data collected using the 800 nm Raman pump, the bluer Raman pump enables us to access a subset of reactant population with partially deprotonated character that exhibits an additional ESPT component on the ∼5 ps time scale. These findings provide deep mechanistic insights into the inhomogeneity and subpopulation-spec...
A Family of Homo- and Heteroscorpionate Ligands: Applications to Bioinorganic Chemistry

In this brief review we focus on a few examples of how a family of homo- and heteroscorpionate ligands allow us to examine how changes in reactivity, structure, or physical/chemical properties around biologically interesting N2X coordinated metal centers vary as a function of donor atom, charge, hydrophobicity, hydrogen bonding, etc., in a way previously unavailable. Such a family of ligands is the bioinorganic chemists answer to site-directed mutagenesis. Here we focus on two bioinorganic examples i.e. models for molybdoenzymes and zinc metalloproteins.
Mechanism of Homogeneous Reduction of CO2 by Pyridine: Proton Relay in Aqueous Solvent and Aromatic Stabilization

We employ quantum chemical calculations to investigate the mechanism of homogeneous CO2 reduction by pyridine (Py) in the Py/p-GaP system. We find that CO2 reduction by Py commences with PyCOOH0 formation where: (a) protonated Py (PyH+) is reduced to PyH0, (b) PyH0 then reduces CO2 by one electron transfer (ET) via nucleophilic attack by its N lone pair on the C of CO2, and finally (c) proton transfer (PT) from PyH0 to CO2 produces PyCOOH0. The predicted enthalpic barrier for this proton-coupled ET (PCET) reaction is 45.7 kcal/mol for direct PT from PyH0 to CO2. However, when PT is mediated by one to three water molecules acting as a proton relay, the barrier decreases to 29.5, 20.4, and 18.5 kcal/mol, respectively. The water proton relay reduces strain in the transition state (TS) and facilitates more complete ET. For PT mediated by a three water molecule proton relay, adding water molecules to explicitly solvate the core reaction system reduces the barrier to 13.6–16.5 kcal/mol, depending on the number ...
Broad frequency acoustic response of ground/floor to human footsteps

The human footstep is one of several signatures that can serve as a useful parameter for human detection. In early research, the force of footsteps was measured on load cells and the input energy from multiple footsteps was detected in the frequency range of 1-4 Hz. Cress investigated the seismic velocity response of outdoor ground sites to individuals that were crawling, walking, and running. In his work, the seismic velocity response was shown to be site-specific and the characteristic frequency range was 20-90 Hz. The current paper will present vibration and sound pressure responses of human footsteps in a broad frequency range. The vibration and sound in the low-frequency band are well known in the literature and generated by the force component normal to the ground/floor. This force is a function of person's weight and a manner of motion (e.g. walking, running, etc). Forces tangential to the ground/floor from a footstep and the ground reaction generate the high frequency responses. The interactions of foot and the ground/floor produce sliding contacts and the result is a friction signal. The parameters of this friction signal, such as frequency band and vibration and sound magnitudes as functions of human walking styles, were studied. The results of tests are presented and discussed.
Supplemental fat and ionophores in finishing diets: feedlot performance and ruminal digesta kinetics in steers.

One feedlot trial (116 d; 192 steers) with a factorial arrangement of treatments was conducted to determine effects of supplemental fat and ionophores in corn-based finishing diets. Factors were level of fat (0 or 4% tallow) and ionophore type (none [N], lasalocid [L], monensin plus tylosin [MT], or daily rotation of L and MT [LMT]); L, M, and T were fed at 31, 25, and 10 ppm (DM basis), respectively. Fat and ionophore interacted for DMI (P .30) by the addition of fat or ionophores to the diet. Fat and ionophore interacted (P < .05) for molar proportions of ruminal acetate and propionate.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 4419: Exploration of alternative pathways mediated by IFNL4 and related to cell proliferation and death in a hepatoma cell line

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA The ability to generate interferon lambda 4 (IFNL4), the most recently discovered member of the type-III interferon family, has been associated with impaired clearance of hepatitis C virus (HCV). IFNL4 signals through an IFNL receptor complex that serves all type-III interferons and consists of receptors IFNLR1 and IL10R2. Signaling through IFNL receptor complex leads to activation of the JAK-STAT pathway and transcriptional activation of interferon-stimulated genes (ISG). Intracellular expression of IFNL4 also causes reduced proliferation and increased cell death in human hepatic cells but it remains unclear if this is a result of JAK-STAT signaling through IFNL receptor complex or through some other alternative mechanisms. To address this question, we used CRISPR-CAS9 system to knock-out IFNLR1 in a hepatoma HepG2 cells. We designed and tested six guide RNAs (gRNAs) for IFNLR1 exons. CAS9 protein and gRNAs that most efficiently induced mutations in IFNLR1 were introduced into HepG2 cells to generate stable cell lines. No obvious defects were observed in IFNLR1-KO-HepG2 cells, indicating that loss of IFNLR1 had no deleterious effects on cell viability. We selected three stable clones which had sequencing-confirmed inactivating IFNLR1 mutations and Western blot-confirmed lack of IFNLR1 protein expression. Compared to the parental HepG2 cells the IFNLR1-KO-HepG2 cells were deficient in the ability to induce the luciferase-tagged interferon-stimulated response element (ISRE-Luc) reporter after treatment with recombinant IFNL4 and IFNL3 proteins, which signal through the same receptor complex. At the same time, response to IFNa treatment was not affected because IFNa signals through its own receptor complex. These results indicate that, as other type-III interferons, IFNL4 induces ISRE signaling through IFNL receptor complex. INFLR1-KO-HepG2 cells provide a highly efficient model for studies of factors involved in signaling of type-III interferons, including IFNL4. Next, we will investigate alternative pathways involved in anti-proliferative and cell death-related phenotypes induced by IFNL4 in HepG2 cell. We will perform RNA-seq on parental and IFNLR1-KO-HepG2 cells treated with or without IFNL4, IFNL3 and IFNa. These results will contribute to a better understanding of IFNL4 function, which can be relevant for viral infections and cancer. Citation Format: Fang Wang, Olusegun O. Onabajo, Nina Rao, Ludmila Prokunina-Olsson. Exploration of alternative pathways mediated by IFNL4 and related to cell proliferation and death in a hepatoma cell line. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4419.
Keeping the Republic: Reading Arendt’s on Revolution After the Fall of the Berlin Wall

Democracy won the Cold War by default. The Berlin Wall seemed simply to collapse, its authority dissolved, its legitimacy faded, its power shriveled. There was no revolutionary act; the conflicts of the past just faded away, almost before anyone was aware that they had gone.1 The once-dominant ruling communist parties and still more their ideologies were discredited seemingly over-night. But a revolution without revolutionaries left a political space without participants. As a result, triumphant democracy has become a threat to itself. It acts before it thinks. Alone on the political stage, it runs the classical risk of pleonaxia, overreaching. From the other side, so to speak, the Bush administration’s attempt to impose democracy world-wide threatened to destroy its foundations at home, by its so-called “Patriot Act,” and the creation of the extra-territorial camp at Guantanamo. But many of the critics of what they saw as another round of “imperialist” adventurism fail to take seriously the very real evils that the American crusade seeks to eradicate. The democratic warriors have a valid point when they oppose tyrants like Saddam Hussein, but they cannot claim that their leftist critics are therefore anti-democratic. If democracy “won” the Cold War, what does its victory mean? These questions provide the background for a rereading of Hannah Arendt’s On Revolution, a book that tried to understand the uniqueness of the American form of democracy, the kind of revolution that was at its origin, and the spirit which it bequeathed to contemporary Americans.
Obesity, Vascular Disease, and Lumbar Disk Degeneration: Associations of Comorbidities in Low Back Pain.

Abstract Low back pain and obesity are both rising epidemics. This article will examine global trends in obesity, contributory lifestyle and societal factors, and morbidity and mortality associated with cardiovascular disease. With this background information, this article will explore the complex physiological process of atherosclerosis and the association between impaired lumbar perfusion and low back pain. It also will provide specific guidance on exercise and nutrition to help treat these potential underlying and contributory mechanisms of spine pathology. Collectively, the article will highlight the necessity of a broader prescriptive to treat the epidemic of low back pain ideally. Level of Evidence Not applicable.
Managing Requirements for E-Voting Systems: Issues and Approaches

This paper discusses our approach and experiences on structuring and maintaining requirements for an e-voting system we have built and deployed for elections. Issues related to integrating laws and recommendation for e-voting systems, managing different elections and configurations, supporting a spiral development, yielded problems and approaches to help maintain integrity of requirements and a coherent view of the system. Moreover, the relationship between requirements and system architecture is based on finite state machines, that bridge the gap between the laws and the actual behavior of the machine.
How common road salts and organic additives alter freshwater food webs: in search of safer alternatives

Summary The application of deicing road salts began in the 1940s and has increased drastically in regions where snow and ice removal is critical for transportation safety. The most commonly applied road salt is sodium chloride (NaCl). However, the increased costs of NaCl, its negative effects on human health, and the degradation of roadside habitats has driven transportation agencies to seek alternative road salts and organic additives to reduce the application rate of NaCl or increase its effectiveness. Few studies have examined the effects of NaCl in aquatic ecosystems, but none have explored the potential impacts of road salt alternatives or additives on aquatic food webs. We assessed the effects of three road salts (NaCl, MgCl2 and ClearLane™) and two road salts mixed with organic additives (GeoMelt™ and Magic Salt™) on food webs in experimental aquatic communities, with environmentally relevant concentrations, standardized by chloride concentration. We found that NaCl had few effects on aquatic communities. However, the microbial breakdown of organic additives initially reduced dissolved oxygen. Additionally, microbial activity likely transformed unusable phosphorus from the organic additives to usable phosphorus for algae, which increased algal growth. The increase in algal growth led to an increase in zooplankton abundance. Finally, MgCl2 – a common alternative to NaCl – reduced compositional differences of zooplankton, and at low concentrations increased the abundance of amphipods. Synthesis and applications. Our results indicate that alternative road salts (to NaCl), and road salt additives can alter the abundance and composition of organisms in freshwater food webs at multiple trophic levels, even at low concentrations. Consequently, road salt alternatives and additives might alter ecosystem function and ecosystem services. Therefore, transportation agencies should use caution in applying road salt alternatives and additives. A comprehensive investigation of road salt alternatives and road salt additives should be conducted before wide-scale use is implemented. Further research is also needed to determine the impacts of salt additives and alternatives on higher trophic levels, such as amphibians and fish.
Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.
Cannabinoid Receptor 1 and Fatty Acid Amide Hydrolase Contribute to Operant Sensation Seeking in Mice

A large body of evidence in humans and preclinical models supports a role for the endocannabinoid system in the proper execution of motivated or goal-directed behaviors. Operant sensation seeking (OSS) is a task that uses varied sensory stimuli as a reinforcer to maintain operant responding in mice. The purpose of the studies in this report was to begin to explore the role of endocannabinoid signaling in OSS utilizing cannabinoid receptor 1 (CB1R) and fatty acid amide hydrolase (FAAH) knock out mice. Compared to wild type littermate controls, CB1R knock out mice exhibited significantly fewer active responses and earned significantly fewer reinforcers in fixed ratio and progressive ratio schedules. On the other hand, FAAH knock out mice exhibited increased active responses and earned more reinforcers than wild type littermates in fixed ratio but not progressive ratio schedules. These findings support the role of endocannabinoid signaling in motivated behaviors and also expand our understanding of the signaling processes involved in OSS.
Local Government Fragmentation and the Local Public Sector: A Panel Data Analysis

This study analyzes the influence of fragmentation and concentration variables on per capita direct expenditures for all counties in the United States from 1982 to 2002. Building on recent research, fragmentation and concentration variables are developed to incorporate the horizontal as well as the vertical dimensions. This analysis explicitly takes into account the potential simultaneity between individual preferences for the spatial arrangement of local governments and the size of the local public sector using the element of time. The findings suggest that increased levels of fragmentation lead to an enlargement of the local public sector; however, the results are more complex than expected. Similarly, the concentration of service delivery responsibilities into counties and single purpose districts tends to increase the size of the local public sector.
Audit quality across non-audit service fee benchmarks: Evidence from material weakness opinions

Abstract Regulators have voiced concerns regarding the impact of auditor provided non-audit services (NAS) on auditor independence, and by extension, audit quality. This study considers whether the provision of various levels of (NAS) influences the auditor's propensity to issue material weakness opinions (MWO). The results indicate that audit clients that purchase zero NAS, and clients that purchase NAS less than Sarbanes-Oxley's benchmark of NAS fees less than 5% of total fees, are more likely to receive a MWO than clients with a NAS at higher levels.
Rules for Flight Paths and Time of Flight for Flows in Porous Media with Heterogeneous Permeability and Porosity

Porous media like hydrocarbon reservoirs may be composed of a wide variety of rocks with different porosity and permeability. Our study shows in algorithms and in synthetic numerical simulations that the flow pattern of any particular porous medium, assuming constant fluid properties and standardized boundary and initial conditions, is not affected by any spatial porosity changes but will vary only according to spatial permeability changes. In contrast, the time of flight along the streamline will be affected by both the permeability and porosity, albeit in opposite directions. A theoretical framework is presented with evidence from flow visualizations. A series of strategically chosen streamline simulations, including systematic spatial variations of porosity and permeability, visualizes the respective effects on the flight path and time of flight. Two practical rules are formulated. Rule 1 states that an increase in permeability decreases the time of flight, whereas an increase in porosity increases the time of flight. Rule 2 states that the permeability uniquely controls the flight path of fluid flow in porous media; local porosity variations do not affect the streamline path. The two rules are essential for understanding fluid transport mechanisms, and their rigorous validation therefore is merited.
GRB 080319B: A Naked-Eye Stellar Blast from the Distant Universe

On behalf of a large international collaboration [1], we present the unprecedented broadband observations of GRB 080319B, whose prompt optical emission peaked at a visual magnitude of 5.3, making it briefly visible with the naked eye. GRB 080319B was discovered by Swift and captured in exquisite detail by ground based wide‐field telescopes, imaging the burst location from before the time of the explosion. The combination of these unique optical data with simultaneous γ‐ray observations provides powerful diagnostics of the detailed physics of this explosion within seconds of its formation. We show that the prompt optical and γ‐ray emissions from this event arise from different spectral components within the same physical region located at a large distance from the source, implying an extremely relativistic outflow. Our observations also provide good evidence for a bright reverse shock component. The chromatic behavior of the broadband afterglow is consistent with viewing the GRB down the very narrow inner core of a two‐component jet that is expanding into a wind‐like environment consistent with the massive star origin of long GRBs.
Coastal Erosion and Land Loss: Causes and Impacts

The margins of the sea are encroaching landward throughout most of the world. This is happening not simply because of sea level rise but also because the solid material- sand, mud, gravel-composing the shore and the subaerial and subaqueous lands immediately adjacent to it is being displaced. In addition to physical erosion by wave, thermal erosion in the Arctic and loss of wetlands through ecological processes are also active. The expected rate of sea level is predicted to exceed critical “tipping points” for wetlands destruction in many regions.
The G2019S mutation in LRRK2 imparts resiliency to kinase inhibition.

Abstract The G2019S mutation in LRRK2 is one of the most common known genetic causes of neurodegeneration and Parkinson disease (PD). LRRK2 mutations are thought to enhance LRRK2 kinase activity. Efficacious small molecule LRRK2 kinase inhibitors with favorable drug properties have recently been developed for pre-clinical studies in rodent models, and inhibitors have advanced to safety trials in humans. Rats that express human G2019S-LRRK2 protein and G2019S-LRRK2 knock-in mice provide newly characterized models to better understand the ostensible target for inhibitors. Herein, we explore the relationships between LRRK2 kinase inhibition in the brain and the periphery to establish the link between LRRK2 kinase activity and protein stability, induction of lysosomal defects in kidney and lung, and how G2019S-LRRK2 expression impacts these phenotypes. Using a novel ultra-sensitive scalable assay based on protein capillary electrophoresis with LRRK2 kinase inhibitors included in-diet, G2019S-LRRK2 protein was resilient to inhibition compared to wild-type (WT)-LRRK2 protein, particularly in the brain. Whereas WT-LRRK2 kinase activity could be completed blocked without lowering LRRK2 protein levels, higher inhibitor concentrations were necessary to fully reduce G2019S-LRRK2 activity. G2019S-LRRK2 expression afforded robust protection from inhibitor-induced kidney lysosomal defects, suggesting a gain-of-function for the mutation in this phenotype. In rodents treated with inhibitors, parallel measurements of phospho-Rab10 revealed a poor correlation to phospho-LRRK2, likely due to cells that express Rab10 but poorly express LRRK2 in heterogenous tissues and cell isolates. In summary, our results highlight several challenges associated with the inhibition of the G2019S-LRRK2 kinase that might be considered in initial clinical efforts.