cssi/SciSciGPT-SciSciNet huggingface dataset:
Directed polymerase evolution

Polymerases evolved in nature to synthesize DNA and RNA, and they underlie the storage and flow of genetic information in all cells. The availability of these enzymes for use at the bench has driven a revolution in biotechnology and medicinal research; however, polymerases did not evolve to function efficiently under the conditions required for some applications and their high substrate fidelity precludes their use for most applications that involve modified substrates. To circumvent these limitations, researchers have turned to directed evolution to tailor the properties and/or substrate repertoire of polymerases for different applications, and several systems have been developed for this purpose. These systems draw on different methods of creating a pool of randomly mutated polymerases and are differentiated by the process used to isolate the most fit members. A variety of polymerases have been evolved, providing new or improved functionality, as well as interesting new insight into the factors governing activity.
Modes of Interannual Tropical Ocean–Atmosphere Interaction—a Unified View. Part III: Analytical Results in Fully Coupled Cases

Abstract The parameter-space dependence of the eigenmodes of the coupled tropical ocean-atmosphere system, linearized about a climatological basic state, is further examined in a stripped-down intermediate coupled model using the formulation derived in Part II of this study to permit analytical treatment for a finite ocean basin. Part II examined the limit of weak coupling and showed the rapid transition to the mixed SST/ocean dynamics modes of Part I, where it was argued that realistically coupled modes are best understood from strong coupling. Here cases with order unity and larger coupling are explored to provide analytical prototypes for the fully coupled case from a system that explicitly treats spatial structure in a finite basin. The coupled dynamics is explored for several regions of parameter space where simplifications are possible, as well as for the transition from the well-separated case to mixed modes. The case of surface-layer processes only provides a simple example of westward-propagating...
A Computational Study of Transformation Methods for Optimal Design

In this paper computational aspects of transformatio n methods are studied. Transformation methods, which include sequential unconstrained minimization techniques (SUMTs) and multiplier methods, are based on solving a sequence of unconstrained minimization problems. An efficient technique is given to compute gradients of the transformation function. An operations count is given to demonstrate savings of the suggested technique over two other techniques used in the literature. Computer programs implementing the use of this technique in SUMTs and multiplier algorithms are developed. Applications of these programs on a set of structural design problems are given. Multiplier methods are found to be very stable and reliable, even on some relatively difficult problems, and they perform better than SUMTs. Some ways of improving the efficiency of transformation methods are given, together with possible extensions of using the suggested approach to compute gradients of implicit functions.
Comparison of Finitely and Infinitely Composite Models for High-Energy Proton-Proton Scattering

We have extended the Glauber theory of high-energy scattering to the collision of two clusters with $N=2, 3, 4, \mathrm{and} \mathrm{infinitely}$ many constitutents each. For the special case of Gaussian scattering amplitudes and form factors, a convenient matrix formula is derived which reduces the evaluation of the multiple Gaussian integrals to the diagonalization of a symmetric matrix which can be read off from each graph and allows complete summation (by computer) of the multiple-scattering series. The convergence of the Glauber series is investigated and found to be excellent for most of the parameter values of interest. These results have been derived with the intention of comparing the hadronic differential cross sections in different quark-type models. We find that all the models discussed lead to excellent fits to the experimental proton-proton differential cross section. While the $N=3$ quark model or the $N=\ensuremath{\infty}$ droplet model may be preferred on other grounds, we find that the limited freedom one has in deciding to what degree the shape of the scattering amplitude is due to the form factors and to what degree to the elementary scattering amplitudes makes it impossible to differentiate between the two models on the basis of the structure of the differential cross section alone.
Electromechanical effects of leukotriene D4 on ferret tracheal muscle and its muscarinic responsiveness.

We investigated the possible electrophysiological processes by which leukotriene D4 (LTD4) affects airway smooth muscle and its responsiveness to acetylcholine (ACh). For study in vitro, preparations of ferret tracheal muscle (dissected free of overlying mucosal and submucosal layers) were used. These preparations were arranged so that force transducers and glass intracellular microelectrodes (having tip resistances of 35–60 megohm) could be used to measure isometric force generation and cell membrane potential (Em) simultaneously from muscle stimulated by LTD4. At rest, the muscle was electrically and mechanically quiescent and had an Em of −59±0.2 mV (mean±SEM). We found that ferret tracheal muscle cells were relatively sensitive to LTD4, and that both the resulting depolarization (beginning at 10−10 M LTD4) and force generation (produced by higher concentrations) progressed in a concentration-dependent manner. Depolarization by 10−9 M LTD4 elicited electrical oscillations. These oscillations were accompanied by phasic contractile activity at 5 × 10−9 M LTD4. Verapamil abolished these oscillations and diminished force substantially. We also found that ACh depolarized and contracted the muscle in a concentration-dependent manner. It caused electrical oscillations at ≥ 10−6 M. Diltiazem abolished these oscillations and markedly diminished force generation without affecting Em. Preexposure of airway muscle preparations for 20 min to a concentration (10−10 M) of LTD4 that, by itself, did not produce significant force, substantially augmented the voltage-tension relationship of the muscle upon ACh stimulation. We conclude that there is an electrical basis for the slow, prolonged force generation of airway muscle caused by LTD4, and that LTD4 potentiates the electromechanical responsiveness of the airway muscle to muscarinic stimulation.
ATTACHMENT THEORY AND ADJUSTMENT DIFFICULTIES IN SIBLINGS OF CHILDREN WITH CANCER

The demands of the childhood cancer experience on children and their parents has been investigated for a number of years. Despite this research, very little emphasis has been placed on well siblings. In the health care profession today, there is a growing perception that the psychosocial needs of the healthy siblings of children with cancer are less sufficiently met than those of other members of the family system. Previous research proposes that well siblings are especially susceptible to a number of adjustment difficulties (such as depression, anger, anxiety, feelings of guilt, and social isolation) (Murray, 1999). Given these findings, the question arises as to whether the adjustment difficulties seen in siblings are a result of the loss of, or separation from, the attachment figure--the mother who is busy caring for the child with cancer. The purpose of this article is to use attachment theory as a conceptual framework to try to understand the effects of the childhood cancer experience on siblings. Recent findings regarding siblings of children with cancer and some speculations regarding clinical implications are provided.
Elinor Ostrom (1933–2012): Pioneer in the Interdisciplinary Science of Coupled Social-Ecological Systems

​EarlyEarly exploration of environmental problems often cast them in terms of the inescapable tragedy of the commons. The “tragedy” refers to the subtle challenge associated with a fundamental disconnect between what is good for the individual and what is good for the group. The tragedy is a sad irony: in trying to serve their own self-interests, individuals end up hurting themselves—and the public good—in the long run. This “commons dilemma,” a core puzzle in the social sciences, is ubiquitous in both social and natural systems. Elinor Ostrom, who died June 12, 2012, at the age of 78, challenged the assumption that communities were incapable of developing their own strategies to avoid tragic outcomes.
Nanomechanical Properties of Dentin Treated with a CO2 Laser for Potential Caries Inhibition

The effect of pulsed CO 2 -laser treatments on the microstructure and nanomechanical properties was studied using atomic force microscopy and nanoindentation. The microstructure and roughness of dentin specimens treated by a 9.3 μm CO 2 laser at fluences of 0.5; 0.75; 1.0; and 1.5 J/cm 2 were evaluated and the elastic modulus and hardness before and after a nine days demin/remin application for laser treatments at 0.75 and 1.5 J/cm 2 were determined. The hypothesis that CO 2 -laser-treatments reduce or inhibit the demineralization process was tested. Surface cracks were observed at fluences of 0.75 J/cm 2 and higher. Surface roughness increased strongly after laser irradiation and was about 10 times higher at maximum fluence. Mechanical properties profiles from the laser treated surface to sound dentin showed increased modulus and hardness values at dentin surfaces treated, indicating removal of organic phases and reinforcement of the tissue by increased mineral content. Mechanical properties decreased after demin/remin application in all groups and the hardened surface layer disappeared for samples treated at 0.75 J/cm 2 . While increased properties were still observed in the laser affected surface zone for treatments at 1.5 J/cm 2 , demineralization was severe underneath these layers as indicated by a sharp drop in properties. The depth of demineralization was slightly decreased in the laser-treated group compared to the untreated controls. We conclude that CO 2 -laser treatments produce dentin surfaces with increased nanomechanical properties. These surface layers do not, however, provide protection against demineralization due to surface cracking and possible delamination. Moreover, the surface cracks induced by the laser-irradiation raise concerns about a clinical potential for caries inhibition in dentin.
Matrix stiffness drives epithelial–mesenchymal transition and tumour metastasis through a TWIST1–G3BP2 mechanotransduction pathway

Matrix stiffness potently regulates cellular behaviour in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional outputs to drive tumour progression. Here we report that TWIST1 is an essential mechanomediator that promotes epithelial-mesenchymal transition (EMT) in response to increasing matrix stiffness. High matrix stiffness promotes nuclear translocation of TWIST1 by releasing TWIST1 from its cytoplasmic binding partner G3BP2. Loss of G3BP2 leads to constitutive TWIST1 nuclear localization and synergizes with increasing matrix stiffness to induce EMT and promote tumour invasion and metastasis. In human breast tumours, collagen fibre alignment, a marker of increasing matrix stiffness, and reduced expression of G3BP2 together predict poor survival. Our findings reveal a TWIST1-G3BP2 mechanotransduction pathway that responds to biomechanical signals from the tumour microenvironment to drive EMT, invasion and metastasis.
Immunosuppression by human gangliosides: I. Relationship of carbohydrate structure to the inhibition of T cell responses.

Abstract Causes of cellular immunodeficiency frequently associated with cancer remain poorly understood. One possible mechanism is tumor cell membrane shedding of immunosuppressive molecules, such as the sialic acid-containing glycosphingolipids, gangliosides. To explore this interesting hypothesis and establish structure-activity relationships, we examined the effects of a series of highly purified human gangliosides on T cell function. In all, ten individual molecular species of two major biosynthetic pathways were compared for their ability to inhibit human T cell proliferative responses. They include GM1, GD1a, GD1b, and GT1b (the predominant normal brain species), and GM4, GM3, GM2, GD3, GD2 and GQ1b. Strikingly, each HPLC-purified molecule, from the simplest monosialoganglioside to the most complex polysialoganglioside, had potent inhibitory activity; even the ganglioside with the most elemental carbohydrate structure (GM4, one sialic acid linked to a monosaccharide) strongly inhibits T cell proliferative responses to tetanus toxoid (ID90 = 1.5 μM). The data also reveal a complex interplay between elements of oligosaccharide structure in determining immunosuppressive activity. Sialic acid is critical to maximal activity, and (i) immuno-suppression is most potent in gangliosides containing a terminal sialic acid, (ii) Total desialylation almost abolishes activity and (iii) partial alteration (lactone formation) reduces activity, (iv) Activity is generally but not always higher with higher numbers of sialic acid residues molecule , and (v) some larger neutral glycosphingolipids retain measurable immunosuppressive activity. Overall, the potent inhibition by gangliosides supports the hypothesis that shedding of these molecules by tumors creates a highly immunosuppressive microenvironment around the tumor, thereby inhibiting the function of infiltrating host leukocytes and contributing to diminished T cell responses in cancer.
Work alienation and politics among clergy

Abstract The neo-Marxian supposition that alienated work has effects for politics was investigated. Unlike Seeman's (1967) study which found no relationship, in the present sample work alienation explained 10% of the variance for politics. By utilizing clergy respondents the present study suggested the importance of respondents' ideological orientation for interpreting relationships between work alienation and politics. Among clergy with generally conservative ideology, i.e., classify their theology as “conservative” or “fundamentalist,” there was no relationship between work alienation and politics. The strength of the relationship between work alienation and liberal politics for theologically liberal clergy was about the same as for the entire sample. The strongest relationship was among moderately theological liberal clergy, i.e., “neoorthodox.” The greatest increase in political liberalism or leftism was among neoorthodox theologians who attributed a relatively smaller percentage of their total life interest to their work.
On the systematics of the enthalpy and volume of solution of hydrogen in transition metals

Abstract The enthalpy and volume of hydrogen solution in transition metals can be systematized by approximating the solution energy as the sum of an electronic bonding term, the same for all metals and essentially equal to the chemisorption energy, and a deformation energy, approximated by a simple elastic continuum model.
Whose Interests? Gender issues and wood-fired cooking stoves

This article examines the role of the welfare state with reference to the design and dissemination of improved models of wood-fired cooking stoves in rural India. Drawing from the feminist sociolog...
Facile Formation of an Intrastrand Cross-Link Lesion between Cytosine and Guanine upon Pyrex-Filtered UV Light Irradiation of d(BrCG) and Duplex DNA Containing 5-Bromocytosine

Pyrex-filtered UV light irradiation of d(BrCG) and 5-bromocytosine-containing duplex DNA leads to facile formation of a cross-link lesion between the C5 carbon atom of cytosine and the C8 carbon atom of its adjacent guanine. A similar cross-link lesion has been previously found in the X-ray irradiation mixture of d(CGTA).
Reduced net atmospheric CH4 consumption is a sustained response to elevated CO2 in a temperate forest

We compared, from 2004 through 2006, rates of soil–atmosphere CH4 exchange at permanently established sampling sites in a temperate forest exposed to ambient (control plots; ∼380 μL L−1) or elevated (ambient + 200 μL L−1) CO2 since August 1996. A total of 880 observations showed net atmospheric CH4 consumption (flux from the atmosphere to the soil) from all static chambers most of the time at rates varying from 0.02 mg m−2 day−1 to 4.5 mg m−2 day−1. However, we infrequently found net CH4 production (flux from the soil to the atmosphere) at lower rates, 0.01 mg m−2 day−1 to 0.08 mg m−2 day−1. For the entire study, the mean (±SEM) rate of net CH4 consumption in control plots was higher than the mean for CO2-enriched plots, 0.55 (0.03) versus 0.51 (0.03) mg m−2 day−1. Annual rates of 184, 196, and 197 mg m−2 for net CH4 consumption at control plots during the three calendar years of this study were 19, 10, and 8% higher than comparable values for CO2 enriched plots. Differences between treatments were significant in 2004 and 2005 and nearly significant in 2006. Volumetric soil water content was consistently higher at CO2-enriched sites and a mixed-effects model identified a significant soil moisture x CO2 interaction on net atmospheric CH4 consumption. Increased soil moisture at CO2-enriched sites likely increases diffusional resistance of surface soils and the frequency of anaerobic microsites supporting methanogenesis, resulting in reduced rates of net atmospheric CH4 consumption. Our study extends our observations of reduced net atmospheric CH4 consumption at CO2-enriched plots to nearly five continuous years, suggesting that this is likely a sustained negative feedback to increasing atmospheric CO2 at this site.
Construct Validity of the Self-Directed Search Using Hierarchically Nested Structural Models.

Abstract This study used the hierarchically nested structural models proposed by Widaman (1985) and further developed by Marsh (1989) and Kenny and Kashy (1992) to investigate the multitrait-multimethod matrix structure of the Self-Directed Search (SDS; Holland, 1985b). The complete model, six correlated trait and five correlated method factors, attained an acceptable level of practical fit. This model was used as an anchor to test convergent and discriminant validity and degree of method covariance. The data supported both the convergent and discriminant validity of the SDS. A moderate degree of method covariation also was evident in male and female samples. Despite inconsistencies specific to certain subscale scores, data generally supported the theoretical model. Contradictory conclusions regarding the construct validity of the SDS based on traditional confirmatory procedures may be attributable to the use of data-driven confirmatory factor analytic procedures and the failure to examine theoretically sound alternative models. Theoretical and methodological implications of these findings ae discussed.
Autoradiographic estimation of the extent of reversible inactivation produced by microinjection of lidocaine and muscimol in the rat.

Abstract We used autoradiography to examine the extent of reversible inactivation produced by microinjection of lidocaine (40 μg/μl saline) and muscimol (1 μg/μl saline). We measured intracortical spread of tracer amounts of labelled drug and local changes in uptake of [1- 14 C]glucose produced by the microinjection. The maximal average radii of regions of drug spread were 1.7 mm for both [ 14 C]lidocaine and [ 3 H]muscimol and were achieved within the first 20 min postinjection. The width of lidocaine injections decreased at longer postinjection times (30–60 min) but the width of muscimol injections remained relatively constant (30–120 min). Lidocaine radioactivity decreased faster from the injection site than muscimol radioactivity. Glucose autoradiograms showed a discrete region of maximally reduced glucose uptake (1.4 mm for lidocaine and 1.0 mm for muscimol) surrounded by a region of less reduced glucose uptake (up to approximately 3 mm). These findings suggest that, in the cortex, the effects of focal inactivation extend beyond the region of drug spread. Diffuse effects may be mediated of disfacilitation of cortico-cortical circuits.
Binary adsorption of globular proteins on ion-exchange media

Adsorption equilibrium of binary pairs of lysozyme (LYS), cytochrome c (CYC) and ribonuclease A (RNase) has been measured on different cation-exchange media at various solution conditions. Adsorption patterns largely follow the intrinsic protein-surface interactions, but can differ significantly for different pairs or even for one pair at different solution conditions. LYS/CYC adsorption shows similar behavior on all the adsorbents examined, with competitive adsorption dominated by LYS and the presence of LYS reducing the adsorption of CYC significantly. Simultaneous and sequential measurements for LYS/CYC show that the order of adsorption does not have a significant effect on the adsorption equilibrium. For LYS/RNase, LYS is consistently more strongly adsorbed. For CYC/RNase, both proteins can display significant adsorption, depending on the pH and salt concentration. A model based on colloidal energetics is developed to calculate the binary adsorption isotherms using parameter values obtained from single-component isotherms. The calculated adsorption is in good agreement with experimental results, with significantly better representation than for other commonly used binary isotherms.
Review Essay: Changing Lawbreakers—What Have We Learned Since the 1950s?

During the 1950s and 1960s, considerable enthusiasm was voiced for treatment programs directed at delinquents and criminals. However, since 1970, the “nothing works” view became dominant and support for correctional treatment waned among the general public and many criminal justice workers. But, in recent years, a number of studies have indicated that some treatment programs have a positive impact on some offenders at least some of the time. Two volumes published in 1998 and reviewed in detail in this article offer considerable encouragement to advocates of the rehabilitative ideal.
A statistical model for the analysis of ordinal level dependent variables

This paper develops a model, with assumptions similar to those of the linear model, for use when the observed dependent variable is ordinal. This model is an extension of the dichotomous probit model, and assumes that the ordinal nature of the observed dependent variable is due to methodological limitations in collecting the data, which force the researcher to lump together and identify various portions of an (otherwise) interval level variable. The model assumes a linear eflect of each independent variable as well as a series of break points between categories for the dependent variable. Maximum likelihood estimators are found for these parameters, along with their asymptotic sampling distributions, and an analogue of R 2 (the coefficient of determination in regression analysis) is defined to measure goodness of fit. The use of the model is illustrated with an analysis of Congressional voting on the 1965 Medicare Bill.
Experimental study of hydraulic engine mounts using multiple inertia tracks and orifices: Narrow and broad band tuning concepts

Abstract Hydraulic engine mount tuning concepts with one inertia track and one decoupler are well understood. However, the dynamic response with multiple tracks or orifices is not. To overcome this void in the literature, dynamic tuning concepts of hydraulic engine mounts, with emphasis on multiple (n-)inertia tracks/orifices, are experimentally examined. A new prototype mount concept is designed, built, and experimentally evaluated in a controlled manner. Refined linear time-invariant models of fixed decoupler-type designs are developed to critically assess the dynamic stiffness measurements and to explore a family of alternate designs. Three narrowband devices are investigated for accurately predicting the frequencies corresponding to peak loss angles for the first time, in addition to examining and validating an n = 3 track mount. Two broadband devices are also successfully evaluated by tuning damping introduced by orifice-type tracks. A special broad-tuned design utilizing a controlled ‘leakage’ path flow area is then suggested, and the role of fluid resistance in achieving the desired performance is clarified. Finally, a production mount with unknown configuration is diagnosed using the proposed models with n tracks.
Nonlinear Meissner effect in unconventional superconductors

We examine the long-wavelength current response in anisotropic superconductors and show how the field dependence of the Meissner penetration length can be used to detect the structure of the order parameter. Nodes in the excitation gap lead to a nonlinear current-velocity constitutive equation at low temperatures that is distinct for each symmetry class of the order parameter. The effective Meissner penetration length is linear in H and exhibits a characteristic anisotropy for fields in the ab plane that is determined by the positions of the nodes in momentum space. The nonlinear current-velocity realtion also leads to an intrinsic magnetic torque for in-plane fields that are not parallel to a nodal or antinodal direction. The torque scales as ${\mathit{H}}^{3}$ for T\ensuremath{\rightarrow}0 and has a characteristic angular dependence. We analyze the effects of thermal excitations, impurity scattering and geometry on the current response of a ${\mathit{d}}_{\mathit{x}}^{2}$-${\mathit{y}}^{2}$ superconductor, and discuss our results in light of recent measurements of the low-temperature penetration length and in-plane magnetization of single-crystals of ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$ and ${\mathrm{LuBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$.
Effects of irradiating peats on their ability to extract BTEX and cadmium from contaminated water

Abstract This paper reports on research designed to investigate the effects of increasing amounts of gamma radiation on the abilities of peats with different chemical, physical, and microbiological properties to extract gasoline‐derived contaminants (BTEX's) and cadmium from water. Unaltered and irradiated peats were slurried under controlled conditions in aqueous solutions of gasoline and of cadmium. All peat types were also examined by various analytical methods for physical, chemical, or microbiological changes that might have occurred due to the radiation. Radiation was found to increase BTEX sorption capacity by 10–65%, depending on the peat type. A maximum BTEX sorption capacity was reached somewhere between 4.5 and 6.5 megarads of radiation. The more fibric peats tended to reach their BTEX sorption maximum more quickly than the more sapric peats. In contrast to the hydrocarbons, cadmium sorption capacity tended to be decreased by radiation, for the more fibric peats (by as much as 80%); while, the ...
Effects of nucleic acid specific dyes on centrioles of mammalian cells.

Ethidium bromide and propidium iodide are fluorescent dyes possessing high binding affinities for charged phosphate groups of nucleic acids. In previous studies addition of these dyes to cultured fibroblasts resulted in nucleolar segregation, chromosome stickiness, and mitochondrial complex formation; alterations in cell morphology induced by the intercalation of dye with specific cellular nucleic acids. In cells from fibroblast and stimulated lymphocyte cultures receiving 5–50 μ g/ml of nucleic acid dye for 4 to 24 hr, striking changes in centriole structure were also observed. Cross-sections of centrioles revealed triplet blade abnormalities including deleted or misaligned tubules and breaks in wall structure producing open-ring centriole configurations. Other sections displayed unusual numbers of central vesicles, threadlike material associated with A tubules, and structures thought to be abnormally formed central vesicles and procentrioles. Mitotic abnormalities which have previously been related to abnormal centriole behavior including multipolar spindle and polyploid cells were also found to be markedly increased in ethidium bromide-treated cultures. Thus, the data suggests that treatment of cells with nucleic acid specific dyes induces morphological and functional changes in centrioles and this effect may be due to intercalaction of dye with centriolar nucleic acid.
Synthesis of Farnesol Analogues Containing Triazoles in Place of Isoprenes through 'Click Chemistry'

A solid-phase three-component Huisgen reaction has been used to generate polar farnesol and farnesyl diphosphate analogues. The Cu(I)-catalyzed 1,3-cycloadditions of various azides with solid supported (E)-3-methylhept-2-en-6-yn-1-ol provided only the 1,4-disubstituted 1,2,3-triazole regioisomers. The organic azides were generated in situ to minimize handling of potentially explosive azides. We have employed this powerful ‘click chemistry’ to make farnesol analogues where both β- and γ-isoprenes were replaced by triazole and substituted aromatic rings, respectively.
Single-Molecule Studies of Origin Licensing Reveal Mechanisms Ensuring Bidirectional Helicase Loading

Loading of the ring-shaped Mcm2-7 replicative helicase around DNA licenses eukaryotic origins of replication. During loading, Cdc6, Cdt1, and the origin-recognition complex (ORC) assemble two heterohexameric Mcm2-7 complexes into a head-to-head double hexamer that facilitates bidirectional replication initiation. Using multi-wavelength single-molecule fluorescence to monitor the events of helicase loading, we demonstrate that double-hexamer formation is the result of sequential loading of individual Mcm2-7 complexes. Loading of each Mcm2-7 molecule involves the ordered association and dissociation of distinct Cdc6 and Cdt1 proteins. In contrast, one ORC molecule directs loading of both helicases in each double hexamer. Based on single-molecule FRET, arrival of the second Mcm2-7 results in rapid double-hexamer formation that anticipates Cdc6 and Cdt1 release, suggesting that Mcm-Mcm interactions recruit the second helicase. Our findings reveal the complex protein dynamics that coordinate helicase loading and indicate that distinct mechanisms load the oppositely oriented helicases that are central to bidirectional replication initiation.
Manometric and spectrophotometric procedures for measurement of procaine hydrolysis by mouse liver in vitro

Abstract A decrease in absorbance at 313 nm was used to determine procaine hydrolysis by mouse liver. Results suggested that procaine hydrolysis was not linearly dependent upon the amount of tissue added to the incubate. This resulted from the fact that p-aminobenzoic acid, one of procaine's hydrolysis products, also absorbed at 313 nm. A dual wavelength analysis procedure is described which permitted accurate measurement of procaine hydrolysis by mouse liver without physical separation of procaine from its hydrolysis products. Measurements by the dual wavelength and manometric methods of inhibition of procaine hydrolysis in livers from mice treated with triorthotolyl phosphate indicated that both methods yielded quantitatively comparable results. The dual wavelength procedure is recommended for future studies of procaine hydrolysis by mammalian tissues.
Pathogenesis and Prophylaxis of Postlaminectomy Deformity of the Spine after Multiple Level Laminectomy: Difference between Children and Adults

The pathogenesis of postlaminectomy spinal deformity and instability in children was evaluated by reviewing appropriate roentgenographic findings. First, we reviewed spine roentgenograms of patients below 40 years of age who underwent spinal fusion for deformity and instability of the spine developing after a multiple level laminectomy. Two types of deformity were recognized on the roentgenograms: increased mobility between the vertebral bodies and wedging deformity of the ventral aspect of the vertebral bodies. Second, we did a follow-up study of another group of patients who had undergone laminectomy. We found the same two types of deformity in children, but not in adult patients. The incidence of deformity was higher after laminectomies of the cervical or cervicothoracic region than after lumbar laminectomies. Our data suggest that postlaminectomy spinal deformity can develop in children without irradiation or facet injury. The deformity is due to a wedging change in the cartilaginous portion of the vertebral body and to the viscoelasticity of ligaments in children. When treatment of this complication becomes necessary, anterior fusion may be effective in arresting progression. Prophylactic measures against the development of deformity are discussed. Our hypothesis concerning the mechanism of development of this complication supports the rationale of osteoplastic laminar resection and reconstruction instead of laminectomy, particularly in the management of children.
Bioprospecting the Public Domain

"I expect that my potatoes will make you rich," asserted one of the farmers whom I had interviewed about nomenclature and preferences for the native potatoes of the Tulumayo Valley in Peru. The comment was not unanticipated, but it still baffled me. The obvious contrasts between us made objection inappropriate. I was not going to use the potatoes I had collected in the valley to breed a new potato variety that might make me rich or famous, but it was possible that others might do so. Plant collectors had previously combed the area for genetic resources, and my collections for research on knowledge systems might someday end up in a breeding program. Scientific curiosity and an abiding fascination about the complexities of Andean cultural ecology had brought me to the Tulumayo, but I also hoped that my research would enhance my career. At the same time, I believed that Andean farmers could benefit from agricultural research, including my work on folk taxonomy and cultural ecology. This same farmer had planted his mahuay (short-cycle) fields in the variety renacimiento (renaissance), bred from native varieties. The farmer expected that renacimiento would provide income that native types would not yield. The Peruvian breeder of the variety had not become wealthy from its public release, but he had attained international recognition. Finally, the conjecture that the farmer's potatoes might increase my wealth implied a personal transfer of resources. But whose resources were these? My bafflement about how to respond to the farmer's assertion that his potatoes might enrich me resulted from the numerous layers that it touched. One was our shared knowledge that the potatoes in his field were useful to many people. They were part of an evolutionary heritage that has given the world one of its great staple foods, benefiting farmers and consumers around the world, as well as seed companies and scientists. The value of these resources is greater now because of the declining supply of native varieties and the increased demand to use this germ plasm to breed new potato varieties. Despite the value of the potato's genetic resources in Peru, farmers who maintain them remain among the poorest in the nation. The loss of native crop varieties before the tidal wave of modern agricultural technology has led to conservation in gene banks. Many conservationists are also concerned about preserving the agricultural
Optical equivalence ratio sensors for gas turbine combustors

Chemiluminescence sensing is shown to be a useful approach for monitoring local, reaction zone equivalence ratios. For natural gas combustion, the ratio of CH∗ to OH∗ chemiluminescence is shown to be a useful indicator of equivalence ratio (ϕ). The ratio of peak intensities (CH∗/OH∗) is shown to monotonically increase with ϕ for the operating regime studied (0.6 0.8) mixtures. In addition, the sensitivity of CH∗/OH∗ to changes in ϕ decreases with pressure. A swirl-stabilized, liquid-fueled (n-heptane) combustor was also investigated. Volume-integrated measurements in this nonpremixed combustor show that C2∗/OH∗ is a more sensitive measure of ϕ for complex fuels, compared to CH∗/OH∗, with measurable C2∗ signals even in lean mixtures (unlike the natural gas results). In addition, the chemiluminescence sensing technique successfully tracts the variation of fuel–air ratio with axial location in this nonpremixed combustor.
Prevalence and Activation Phenotype of Sendai Virus-Specific CD4+ T Cells

The relative prevalence of Sendai virus-specific CD4+ T helper precursors (Thp) has been assessed by limiting dilution analysis (LDA). Within 10 days after intranasal inoculation of C57BL/6 mice, Thp prevalence increased from < 1 in 10(5) to approximately 1 in 200 in CD4+ T-cell-enriched spleen and mediastinal lymph node populations. These frequencies remained elevated relative to naive animals, with the majority of the Thp recovered at 2-3 months after infection being found in the spleen. The "memory" Thp express an "activated" L-selectin-low, CD44-high, alpha 4-integrin-high phenotype, comparable to that described previously for CD8+ cytotoxic T lymphocyte precursors (CTLp) specific for Sendai virus. Background effects for the IL-2-based Thp analysis are, however, less predictable than those found previously for the 51Cr release CTLp LDA, as the extent of non-virus-specific lymphokine production varies. However, provided the analysis is appropriately controlled, the approach does allow useful comparisons between phenotypically different subsets of antigen-specific CD4+ T cells.
The Molecular Pathology of Melanoma: An Integrated Taxonomy of Melanocytic Neoplasia

Melanomas comprise multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ-line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain-of-function mutations in one of several primary oncogenes, which typically lead to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor-suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about the pathogenesis and clinical, histologic, and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework.
Practice management performance indicators in academic radiology departments.

PURPOSE: To determine the management performance indicators most frequently utilized in academic radiology departments in the United States. MATERIALS AND METHODS: This investigation met the criteria for an exemption from institutional review board approval. A cross-sectional study in which a validated national survey was sent to members of the Society of Chairmen of Academic Radiology Departments (SCARD) was conducted. The survey was designed to examine the following six categories of 28 performance indicators: (a) general organization, (b) volume and productivity, (c) radiology reporting, (d) access to examinations, (e) customer satisfaction, and (f) finance. A total of 158 variables were included in the analysis. Summary statistics, the χ2 test, rank correlation, multiple regression analysis, and analysis of variance were used. RESULTS: A response rate of 42% (55 of 132 SCARD members) was achieved. The mean number of performance indicators used by radiology departments was 16 ± 6.35 (standard deviation...
The Americans With Disabilities Act and Medical Providers: Ten Years After Passage of the Act

This article discusses the impact of the Americans With Disabilities Act (ADA) on health care providers in the last decade. Even though some ADA training has been provided for health care providers, more education will help to improve access to their offices, improve health care practices for their patients with disabilities, and be an incentive for the providers to help raise the consciousness of the rest of the community about the ADA.
Transcriptional control mechanisms associated with the nucleotide receptor P2X7, a critical regulator of immunologic, osteogenic, and neurologic functions.

The nucleotide receptor P2X7 is an attractive therapeutic target and potential biomarker for multiple inflammatory and neurologic disorders, and it is expressed in several immune, osteogenic, and neurologic cell types. Aside from its role in the nervous system, it is activated by ATP released at sites of tissue damage, inflammation, and infection. Ligand binding to P2X7 stimulates many cell responses, including calcium fluxes, MAPK activation, inflammatory mediator release, and apoptosis. Much work has centered on P2X7 action in cell death and mediator processing (e.g., pro-interleukin-1 cleavage by the inflammasome), but the contribution of P2X7 to transcriptional regulation is less well defined. This review will focus on the growing evidence for the importance of nucleotide-mediated gene expression, highlight several animal models, human genetic, and clinical studies that support P2X7 as a therapeutic target, and discuss the latest developments in anti-P2X7 clinical trials.
Cooperative transnationalism in contemporary Europe: Europeanization and political opportunities for LGBT mobilization in the European Union

This article builds on previous research on Europeanization and political opportunity structures (POS) for mobilization, to explore the processes of transnational LGBT (Lesbian, Gay, Bisexual, and Transgender) mobilization in the European Union (EU). In the case of LGBT activism, European integration affects contentious politics by altering POS – both vertically and horizontally – for mobilization and changing the tactics of LGBT activism. Using the cases of Germany and Poland to trace cross-border connections between norm entrepreneur and target state, the findings suggest that LGBT activism relies on transnational resources – primarily, social spaces and organizational capacity – that are scarce in many member states but readily available in others. These horizontal opportunities among member states, alongside top-down vertical ones provided by Brussels, serve as mobilizing structures that bring together distinct groups of international actors. Europeanization also alters the tactics that transnational actors use when engaging with authorities in the target state. Employing socialization mechanisms that highlight appropriate behavior, actors tactically frame their demands in a European discourse by associating the issue of LGBT acceptance with democratic responsibilities as members of the EU community.
X-ray fluoroscopy system design: lessons from image perception studies

Our goal is to minimize X-ray dose and maximize image quality by optimizing the acquisition and processing of X-ray fluoroscopy images. We use quantitative image quality techniques incorporating objective target detection experiments and models of human perception. Several recent results have practical implications for X-ray fluoroscopy system design.
The Misuse of Chayanov: “Chayanov's Rule” and Empiricist Bias in Anthropology

Sahlins's “Chayanov's Rule”–the more consumers each worker has to support the more work each worker does-has characterized Chayanov's analysis for most anthropologists. I examine the relationship between the consumer/worker ratio and product per worker for the Shan community of Thongmakhsan in northwestern Thailand. Since there is no systematic relationship between these variables even when the population is divided into production strategy groups, I go on to examine the relationship between Sahlins's “Chayanov's Rule” and Chayanov's own analysis. In conclusion I raise the issue of the continuing identification of Chayanov with “Chayanov's Rule” and consider a number of possible reasons for this.
Analog rank extractors

This paper focuses on continuous-time analog rank extractors, with an emphasis on MOS circuits. Sources of errors in previous analog implementations are analyzed, and an improved multiple-input min/max circuit configuration is proposed. A generalized analog rank extractor is discussed as well as its limitations on the number of inputs and rank. In a sorting network approach, the presorting and path combination techniques are used to reduce the rank selector implementation.
Fault-tolerant computing: fundamental concepts

The basic concepts of fault-tolerant computing are reviewed, focusing on hardware. Failures, faults, and errors in digital systems are examined, and measures of dependability, which dictate and evaluate fault-tolerance strategies for different classes of applications, are defined. The elements of fault-tolerance strategies are identified, and various strategies are reviewed. They are: error detection, masking, and correction; error detection and correction codes; self-checking logic; module replication for error detection and masking; protocol and timing checks; fault containment; reconfiguration and repair; and system recovery. >
Psychology and Metaphysics

The term “psychology” is recent, but the problems and researches which this name recall are as old as philosophy and could scarcely avoid occupying a large place therein from its very beginning. Philosophy has always aimed at being the science of all things. Now life, feeling, thought are things or, if one should prefer, facts which are just as real as the movements of the stars. Although these facts are not produced in space and are outside of material objects, they constitute a kind of interior existence, broadly speaking, which is no less interesting to the philosopher than external and visible existences.
Evaluation of Fractional Regional Ventilation Using 4D-CT and Effects of Breathing Maneuvers on Ventilation

Purpose Current implementations of methods based on Hounsfield units to evaluate regional lung ventilation do not directly incorporate tissue-based mass changes that occur over the respiratory cycle. To overcome this, we developed a 4-dimensional computed tomography (4D-CT)-based technique to evaluate fractional regional ventilation (FRV) that uses an individualized ratio of tidal volume to end-expiratory lung volume for each voxel. We further evaluated the effect of different breathing maneuvers on regional ventilation. The results from this work will help elucidate the relationship between global and regional lung function. Methods and Materials Eight patients underwent 3 sets of 4D-CT scans during 1 session using free-breathing, audiovisual guidance, and active breathing control. FRV was estimated using a density-based algorithm with mass correction. Internal validation between global and regional ventilation was performed by use of the imaging data collected during the use of active breathing control. The impact of breathing maneuvers on FRV was evaluated comparing the tidal volume from 3 breathing methods. Results Internal validation through comparison between the global and regional changes in ventilation revealed a strong linear correlation (slope of 1.01, R 2 of 0.97) between the measured global lung volume and the regional lung volume calculated by use of the "mass corrected" FRV. A linear relationship was established between the tidal volume measured with the automated breathing control system and FRV based on 4D-CT imaging. Consistently larger breathing volumes were observed when coached breathing techniques were used. Conclusions The technique presented improves density-based evaluation of lung ventilation and establishes a link between global and regional lung ventilation volumes. Furthermore, the results obtained are comparable with those of other techniques of functional evaluation such as spirometry and hyperpolarized-gas magnetic resonance imaging. These results were demonstrated on retrospective analysis of patient data, and further research using prospective data is under way to validate this technique against established clinical tests.