cssi/SciSciGPT-SciSciNet huggingface dataset:
Contingency and entrenchment in protein evolution under purifying selection

The phenotypic effect of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations and shape the patterns of protein divergence across species. Whereas epistasis between adaptive substitutions has been studied extensively, relatively little is known about epistasis under purifying selection. Here we use computational models of thermodynamic stability in a ligand-binding protein to explore the structure of epistasis in simulations of protein sequence evolution. Even though the predicted effects on stability of random mutations are almost completely additive, the mutations that fix under purifying selection are enriched for epistasis. In particular, the mutations that fix are contingent on previous substitutions: Although nearly neutral at their time of fixation, these mutations would be deleterious in the absence of preceding substitutions. Conversely, substitutions under purifying selection are subsequently entrenched by epistasis with later substitutions: They become increasingly deleterious to revert over time. Our results imply that, even under purifying selection, protein sequence evolution is often contingent on history and so it cannot be predicted by the phenotypic effects of mutations assayed in the ancestral background.
GroupBased BCU Method

This chapter contains sections titled: Introduction Group-Based BCU Method for Accurate Critical Energy Group-Based BCU Method for CUEPs Numerical Studies Concluding Remarks
Chapter 67 - The Historical Geography of European Cities: An Interpretive Essay

Abstract Over a millennium Europe has become largely urban. While urban growth, absolute and as a percentage of a growing population, has been as dramatic as economic change, many elements of continuity tie the present to the past. This evolution with path dependence is highlighted if one looks at European urban economies in terms of a dual systems model combining central place and network relationships. After the medieval push of town creation and differentiation, the early modern period saw a slowing of the increase in urban population and proportion, even as cities anchored the growth of overseas trade and of integrated territorial states. Growth was concentrated in major ports and capital or court cities. The role of cities in the rise of a market economy capable of sustained growth in output per head is tied to ongoing debates about how and why growth began in Europe, and within Europe in England. Industrialization led to enormous increases in urban agglomeration driven by transport improvements and increasing returns to scale in manufacturing as well as distribution. However, leadership functions tended to concentrate in giant capital cities rather than in the new industrial towns and conurbations. Within cities, rapid in-migration and lags in institutions and technology for urban management aggravated crowding and squalor. Conditions improved toward the turn of the 20th century, thanks in part to electricity and to more responsive and active government, as well as to slower urbanization. The depression and destruction of the 1914—1945 period was followed by great prosperity and enormous building. The information age appears to have conflicting impacts on agglomeration in Europe, with policy leaning toward sustaining dense cities (relative at least to the U.S.). The shift from older to newer industries, as well as growth in leisure and high human capital pursuits, has shifted activity away from many 19th century industrial centers and toward revitalized older cities and urbanized regions with higher amenity levels.
LIPID METABOLISM IN CULTURED CELLS. IV. SERUM ALPHA GLOBULINS AND CELLULAR CHOLESTEROL EXCHANGE.

Abstract Cholesterol in cultured mammalian cells is in a state of dynamic exchange with the outside medium, the process being catalyzed by certain serum proteins. A cellular system using 14 C-cholesterol was developed for quantitative assay of this exchange process. Serum fractions isolated by ion exchange chromatography on DEAE cellulose were assayed for ability to catalyze cellular cholesterol exchange. The activity was concentrated in those fractions (α-globulins) which normally transport cholesterol in plasma. Analysis of human serum fractions prepared by the Cohn procedure also gave a similar distribution. It is concluded that cholesterol continuously enters and is excreted from cells under the influence of, and in all probability in combination with, certain of the serum α-globulins.
Organizational Form Coexistence: Stock and Mutual Financial Firms

Customer owned mutual firms coexist with stock firms in the financial sector. Elsewhere, mutuals are rare. The coexistence is stable. Mutual firms have higher costs and lower risk than stock firms. This work offers the first joint explanation of these facts. It employs an equilibrium model of financial firms. In equilibrium, mutual firms sell expensive, safe products to customers with high risk aversions. Stock firms sell inexpensive, risky products to customers with low risk aversions. Illiquid ownership claims give mutuals high costs of capital. Contracting costs give stock firms extra risk. Recent life insurer demutualization activity is discussed.
Designing and managing intervention methods to promote Self-Regulated Learning

Many students in higher education do not effectively manage large class projects and term papers to complete the assigned work on time, while meeting quality and completeness requirements. One of the serious consequences of this is missing a significant portion of learning associated with the assigned work. We propose and investigate intervention methods based on Self-Regulated Learning (SRL) theory and aimed at increasing student learning through "process feedback" within the context of out-of-class projects. The proposed method was evaluated with two field experiments. The results showed that the method is effective in promoting SRL, improving test performance, and producing more successful learners.
Interpreting female genital cutting: moving beyond the impasse.

Abstract Female genital cutting has been practiced in many parts of the world but is now most prevalent in sub-Saharan Africa. Particularly in the last half-century, genital cutting ceremonies have attracted significant scientific and media attention. I review some of the most frequently referenced interpretations of female genital cutting and suggest that ways of explaining such practices are limited. I indicate that the study of genital cutting practices is at an impasse—with absolutists arguing that intervention to stop the procedure is required and relativists asserting that outsiders have either no right or no ability to impose such change upon others. Data from fieldwork conducted among the Sara, an ethnic group from the south of Chad, highlight the diversity in genital cutting ceremonies that is not currently represented in the literature or acknowledged in popular discourse. Some of the Sara subgroups have only recently adopted female genital cutting. Young girls have been at the forefront of this...
New insights into the regulation of protein kinase C and novel phorbol ester receptors

Protein kinase C (PKC), a family of related serine-threonine kinases, is a key player in the cellular responses mediated by the second messenger diacylglycerol (DAG) and the phorbol ester tumor promoters. The traditional view of PKCs as DAG/phospholipid-regulated proteins has expanded in the last few years by three seminal discoveries. First, PKC activity and maturation is controlled by autophosphorylation and transphosphorylation mechanisms, which includes phosphorylation of PKC isozymes by phosphoinositide-dependent protein kinases (PDKs) and tyrosine kinases. Second, PKC activity and localization are regulated by direct interaction with different types of interacting proteins. Protein-protein interactions are now recognized as important mechanisms that target individual PKCs to different intracellular compartments and confer selectivity by associating individual isozymes with specific substrates. Last, the discovery of novel phorbol ester receptors lacking kinase activity allows us to speculate that some of the biological responses elicited by phorbol esters or by activation of receptors coupled to elevation in DAG levels could be mediated by PKC-independent pathways.
Total Stability of Scalar Differential Equations Determined from Their Limiting Functions

Stability properties of the zero solution of a scalar ordinary differential equation are studied using functions, called fences, which act as bounds to the solutions of the differential equation. It is shown, under simple restrictions, that these fences are bounds for the solutions of the perturbed differential equations as well. Hence one finds that total stability of the zero solution of a scalar ordinary differential equation is equivalent to the existence of these functions.
Transmutation of Mercury by Fast Neutrons

The products of the transmutation of mercury by fast (Li+D) neutrons were investigated. Three radioactive gold isotopes were found to be formed by the $n\ensuremath{-}p$ reactions: 65-hour ${\mathrm{Au}}^{198}$, 78-hour ${\mathrm{Au}}^{199}$, and a new unassigned electron emitter with a period of 48 min. Three radioactive platinum isotopes were observed and attributed to $n\ensuremath{-}\ensuremath{\alpha}$ reactions in mercury: 29-min. ${\mathrm{Pt}}^{199}$, 19-hour ${\mathrm{Pt}}^{197}$, and a new activity with an 80-min. half-life. The latter period was also observed in deuteron and fast neutron bombardment of platinum, but was not found in slow neutron irradiation of platinum. Radioactive mercury isotopes with 43-min., 25-hour, and 50-day periods were observed in the fast neutron irradiation of mercury. The 43-min. and 25-hour activities were also formed by bombarding platinum with $\ensuremath{\alpha}$-particles. Difficulties in the assignment of the 80-min. Pt and the 43-min. and 25-hour Hg activities are discussed.
Reflectivity And Roughness Of Layered Synthetic Microstructures

The effect of uncorrelated roughness on the reflectivity of layered synthetic microstructures (LSM's) is studied. A computer code which includes uncorrelated roughness is developed allowing the subtraction of roughness from experimental measurements. This allows the use of LSM's to measure the optical constants of materials in the x-ray region of the spectrum. The method is applied to an V/C LSM to measure the resonance correction to the atomic factor, f', across the vanadium K-absorption edge.© (1984) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Existence of a positive solution for a-Laplacian semipositone problem

We consider the boundary value problem in satisfying on , where on , is a parameter, is a bounded domain in with boundary , and for . Here, is a nondecreasing function for some satisfying (semipositone). We establish a range of for which the above problem has a positive solution when satisfies certain additional conditions. We employ the method of subsuper solutions to obtain the result.
Structural and magnetic properties of MCl2 (M = Fe, Mn, Co) : Acetonitrile solvates

MIICl2 (M = Mn, Fe, Co) as their acetonitrile solvates were isolated, and their structural, spectroscopic, and magnetic properties were studied. MCl2(NCMe)2 (M = Fe, Mn) form 1-D chains of octahedral MII ions with four bridging chlorides and two axial MeCN's. The presence of an axial distortion for MFe causes a significant magnetic anisotropy that increases significantly below 150 K; however, χav [=(χ∥ + 2χ⊥)/3] almost coincides with the value obtained on a polycrystalline sample. MnCl2(NCMe)2 is a paramagnet with a weak antiferromagnetic coupling. Annealing FeCl2(NCMe)2 at 55 °C forms the monosolvate of FeCl2(NCMe) composition in which two chains collapse into a double chain with formation of Fe−Cl bonding such that half of the μ-Cl's becomes μ3-Cl's. This material orders magnetically below Tc = 4.3 K. For M = Co, paramagnetic tetrahedral [CoCl3(NCMe)]- anions are isolated.
Dynamic changes after murine digit amputation: The MRL mouse digit shows waves of tissue remodeling, growth, and apoptosis

Digit regrowth following amputation injury proximal to the first phalangeal joint is not a property of mammalian wound healing. However, the regenerative potential observed in the MRL mouse invites a reexamination of this rule. In this study, healing was assessed in three mouse strains after amputation midway through the second phalangeal bone. Three distinct outcomes were observed though evidence for regrowth was observed only in the MRL mouse. Here, a blastema-like structure was seen along with apparent chondrogenesis, consistent with a histological profile of a regenerative response to injury. Analysis of trichrome staining and basement membrane changes, proliferation and apoptosis indicated that these processes contributed to the formation of new digit tissue. On the other hand, SW and B6 digits did not show evidence of growth with little mesenchymal BrdU incorporation or phosphorylation of H3.
Analysis of Contoured Anatomic Plate Fixation versus Intramedullary Rod Fixation for Acute Midshaft Clavicle Fractures

The recent trend has been toward surgical fixation of displaced clavicle fractures. Several fixation techniques have been reported yet it is unclear which is preferable. We retrospectively reviewed one hundred one consecutive patients with acute midshaft clavicle fractures treated operatively at a level-1 trauma center. Thirty-four patients underwent intramedullary pin fixation and 67 had anatomic plate fixation. The outcomes we assessed were operative time, complications, infection, implant failure, fracture union, range of motion, and reoperation rate. There were 92 males and 9 females with an average age of 30 years (range: 14–68 years). All patients were followed to healing with an average followup of 20 months (range: 15–32 months). While fracture union by six months and range of motion at three months were similar, the overall healing time for pin fixation was shorter . The pin group had more infections and implant failures than the plate group. Intramedullary pin fixation may have improved early results, but there was no long term difference in overall rate of union and achievement of full shoulder motion. The higher rate of implant failure with pin fixation may indicate that not all fracture patterns are amenable to fixation using this device.
Activation of guinea pig macrophages by cell walls of Mycobacterium bovis, strain BCG.

Abstract BCG cell walls have immunopotentiating activity as determined by regression of tumors and protection against tuberculosis. Since macrophages may be important effector cells in these systems, the effect of B CG cell walls on macrophage function was examined. BCG cell wells activated strain 2 guinea pig macrophages in vivo to produce an extracellular factor which kills Listeria monocytogenes. Association of cell walls with a small amount of mineral oil, which is required for immunopotentiating activity, resulted in earlier and more prolonged macrophage activation, and large numbers of these activated cells accumulated. BCG cell walls also induced macrophage activation in vitro as determined by stimulation of macrophage glucosamine incorporation. Lymphocytes participated in macrophage activation by BCG cell walls both in vivo and in vitro. The results suggest that macrophage activation may be an important component of the immunopotentiating activity of BCG cell walls.
Computing Orbits of Minimal Parabolic k -subgroups Acting on Symmetric k -varieties

In this paper we present an algorithm to compute the orbits of a minimal parabolic k -subgroup acting on a symmetric k -variety and most of the combinatorial structure of the orbit decomposition. This algorithm can be implemented in LiE, GAP4, Magma, Maple or in a separate program. These orbits are essential in the study of symmetric k -varieties and their representations. In a similar way to the special case of a Borel subgroup acting on the symmetric variety, (see A. G. Helminck. Computing B -orbits on G/H. J. Symb. Comput.,21 , 169?209, 1996.) one can use the associated twisted involutions in the restricted Weyl group to describe these orbits (see A. G. Helminck and S. P. Wang. On rationality properties of involutions of reductive groups. Adv. Math., 99, 26?96, 1993). However, the orbit structure in this case is much more complicated than the special case of orbits of a Borel subgroup. We will first modify the characterization of the orbits of minimal parabolic k -subgroups acting on the symmetric k -varieties given in Helminck and Wang (1993), to illuminate the similarity to the one for orbits of a Borel subgroup acting on a symmetric variety in Helminck (1996). Using this characterization we show how the algorithm in Helminck (1996) can be adjusted and extended to compute these twisted involutions as well.
Computer anxiety and perception of task complexity in learning programming-related skills

Abstract The purpose of the study was to investigate how computer anxiety is associated with computer task complexity in teaching and learning computer programming and related skills. The study also examined the effects of computer confidence and computer liking on user perception of task complexity. The study referred to the literature concerning whether enhancing computer experience may be the remedy of computer anxiety. Based on the data regarding different computer task levels, the study identified and tested the regression models using path analysis. The result of the study indicates that computer confidence had significant effects on user perception of task complexity while the effects of computer liking were minimal. At various task levels, increasing computer experience may help reduce computer anxiety. The individuals at a lower task level had less adequate estimation of task complexity than those at higher task levels, and thus were more likely to be subject to occurrence of computer anxiety. The study recommends that in teaching and learning computer programming and related skills, enhancing the knowledge and understanding of task complexity is necessary. It can help computer learners and users, especially at lower skill levels, in dealing with computer anxiety.
Aromatic amino acids in the Rieske iron-sulfur protein do not form an obligatory conduit for electron transfer from the iron-sulfur cluster to the heme of cytochrome c1 in the cytochrome bc1 complex.

Abstract We have changed nine conserved aromatic amino acids by site-directed mutagenesis of the cloned iron–sulfur protein gene to determine if any of these residues form an obligatory conduit for electron transfer within the iron–sulfur protein of the yeast cytochrome bc1 complex. The residues include W111, F117, W152, F173, W176, F177, H184, Y205 and F207. Greater than 70% of the catalytic activity was retained for all of the mutated iron–sulfur proteins, except for those containing a W152L and a W176L–F177L double mutation, for which the activity was ∼45%. The crystal structures of the bc1 complex indicate that F177 and H184 are at the surface of the iron–sulfur protein near the surface of cytochrome c1, but not directly in a linear pathway between the iron–sulfur cluster and the c1 heme. The pre-steady-state rates of reduction of cytochromes b and c1 in mutants in which F177 and H184 were changed to non-aromatic residues were approximately 70–85% of the wild-type rates. There was a large decrease in iron–sulfur protein levels in mitochondrial membranes resulting from the W152L mutation and the W176L–F177L double mutation, and a small decrease for the Y205L, W176L and F177L mutations. This indicates that the decreases in activity resulting from these amino acid changes are due to instability of the altered proteins. These results show that these aromatic amino acids are unnecessary for electron transfer, but several are required for structural stability.
Spatial patterns and sampling plans for cereal aphids [Hom.: Aphididae] killed by entomophthoralean fungi and hymenopterous parasitoids in spring wheat

Cereal aphids infesting spring wheat in southwestern Idaho were surveyed during 1988 and 1989 for the presence of entomophthoralean fungi and hymenopterous parasitoids. Cereal aphids killed by the fungi (cadavers) and parasitoids (mummies) includedDiuraphis noxia (Mordvilko),Metopolophium dirhodum (Walker),Sitobion avenae (F.), andSchizaphis graminum (Rondani). Taylor's power law was used to describe the relationships between mean densities of cadavers or mummies (number per tiller) and associated variances. Except forS. graminum mummies, which were at low levels throughout the growing seasons and tended to be randomly distributed, Taylor's slopes exceeded 1.0 for all the aphid cadavers and mummies, indicating varying degrees of clumping in spatial pattern. The spatial patterns ofD. noxia andM. dirhodum cadavers were similar, simply reflecting those of their own populations, but more aggregated than were their respective mummies resulting from parasitoid attack. The intercepts and slopes from the power law analysis were used to generate functional relationships between the proportion of wheat tillers bearing cadavers or mummies of each aphid species and the mean density, and develop optimal numerical (direct counting) and binomial (presence or absence) sample size curves for both cadavers and mummies of each aphid species.
The zonal centrifuge applied to the purification of a low‐yield virus in human leukemia cells

The herpes-type virus found in certain cell cultures derived from Burkitt's lymphoma, other human leukemias, and normal human leukocytes, was concentrated and partially purified by large-volume density gradient centrifugation using zonal centrifuge systems. Using the Jiyoye (P-3) cell line as a model, rate-zonal runs on disrupted cell suspensions in sucrose gradients yielded concentrates with high virus particle counts when 10–15 ml of packed cells were processed per liter of gradient. Isolation and removal of cell nuclei or fluorocarbon treatment of cell sonicates permitted virus recovery from larger volumes of cells per experiment. Zonal centrifugation of concentrated cell-free spent media from highly infected cell cultures yielded more purified virus than obtained from cells. Viral concentrates were prepared with particle counts of 1010–1011/ml and total protein concentrations of 0.2–0.5 mg/ml. Subsequent isopyenie-zonal centrifugation of the various high-count virus fractions from the zonal centrifuge showed a heterogeneity in buoyant virus density ranging from 1.18 to 1.27 in potassium tart rate. The spread in virus density was attributed to the different morphological forms of the virus observed by electron microscopy.
Probe angioplasty of total coronary occlusion using the Probing Catheter technique.

Coronary angioplasty (PTCA) of total coronary occlusion is limited by the inability of guidewires and conventional dilating catheters to cross all such lesions. A new technique was therefore prospectively evaluated for PTCA of these lesions using the ultra-low-profile Probe™ “balloon on a wire” device. An intracoronary Probing Catheter™ was used to facilitate crossing the stenosis with a guidewire and then to deliver a Probe™ Into the obstruction for balloon dilatation. This technique was utilized in 64 consecutive patients with “absolute” coronary occlusions demonstrating no angiographically detectable antegrade coronary flow. Successful dilatation was achieved in 47 (73%). Among 33 occlusions of less than 3 mo duration 31 (94%) were successfully dilated whereas only 16 of 31 more chronic occlusions were dilated (P<.01). Chronic occlusions with a tapered morphology and those located more than 1 cm from a branch point were more frequently dilatable. There were no Serious complications including no vessel perforations with this technique. The Probing Catheter™ technique offers a safe and effective method for the dilatation of recent coronary occlusions by using balloon on a wire technology.
A simple synthesis of thieno[2,3-b]pyrazine and thieno[2,3-b] pyridine †

A facile synthesis of thieno[2,3-b]pyrazine (1) and thieno[2,3-b]pyridine (9) is reported. Furthermore, convenient preparations of a variety of synthetically useful compounds derived from these ring systems is also presented.
Experimental Verification of the Overhauser Nuclear Polarization Effect

The experimental verification of Overhauser's proposal for polarizing nuclear spins is described. The effect on the nuclear magnetic resonance of saturating the electron spin resonance in several appropriate systems was observed at low fields and room temperatures. The systems investigated were: metallic Li, metallic Na, and Na dissolved in anhydrous liquid ammonia. The nuclear resonances of ${\mathrm{Li}}^{7}$, ${\mathrm{Na}}^{23}$, and ${\mathrm{H}}^{1}$ (in the ammonia) were observed at 50 kc/sec in fields of 30.3 gauss, 44.2 gauss, and 11.7 gauss, respectively, and the electron spin resonances were saturated with the corresponding applied frequencies of 84, 124, and 33 Mc/sec. The detailed predictions of Overhauser were confirmed as far as nuclear polarization is concerned, although other relaxation processes in Li reduce the polarization, and the difficulty in completely saturating the metallic Na electron resonance leads to a partial effect. Only in fairly concentrated solutions of Na in ammonia was a substantially complete effect observed in which the proton nuclear polarization increased by the ratio of the electron gyromagnetic ratio to the nuclear gyromagnetic ratio. The proton line widths in the Na-ammonia solutions further verify the theory of Kaplan and Kittel.
Harnessing the Sensor Web Through Model-based Observation

This paper introduces the notion of model-based observing, a process of coordinating resources in a sensor web based on goals generated from Earth science or other investigations. Model-based observing will transform a sensor web into a cognitive web, a distributed, goal-directed sensing system. For a collection of remote sensors to be a cognitive web, an information infrastructure with the following features must be developed. First, there needs to be a representation of current observation goals and the tasks being performing to accomplish these goals. Second, there must be a means to recognize when changes to the sensing environment threaten to prevent the accomplishment of those goals. Third, a cognitive web must adapt to changes in its own configuration; it must be able to recognize opportunities for modifying its data acquisition plans in order to improve overall performance. It must act as a coordinator of resources, an optimizer of tasks, and a broker for data products. An architecture for a cognitive web is proposed that would utilize continuous planning and scheduling, plan execution and monitoring, and model-based goal generation. Portions of this architecture exist in extant systems.
An Energy-Based Method for Uni-Axial Fatigue Life Calculation

An energy based fatigue life prediction framework has been developed for calculation of remaining fatigue life of in-service gas turbine materials. The purpose of the life prediction framework is to account for the material aging effect on fatigue strength of gas turbine engines structural components which are usually designed for infinite life. Previous studies [1–7] indicate the total strain energy dissipated during a monotonic fracture process and a cyclic process is a material property that can be determined by measuring the area underneath the monotonic true stress-strain curve and the sum of the area within each hysteresis loop in the cyclic process, respectively. The energy-based fatigue life prediction framework consists of the following entities: (1) development of a testing procedure to achieve plastic energy dissipation per life cycle and (2) incorporation of an energy-based fatigue life calculation scheme to determine the remaining fatigue life of in-service gas turbine materials. The accuracy of the remaining fatigue life prediction method was verified by comparison between model approximation and experimental results of Aluminum 6061-T6 (Al 6061-T6). The comparison shows promising agreement, thus validating the capability of the framework to produce accurate fatigue life prediction.Copyright © 2009 by ASME
Assessment of contamination from arsenical pesticide use on orchards in the Great Valley region, Virginia and West Virginia, USA.

Lead arsenate pesticides were widely used in apple orchards from 1925 to 1955. Soils from historic orchards in four counties in Virginia and West Virginia contained elevated concentrations of As and Pb, consistent with an arsenical pesticide source. Arsenic concentrations in approximately 50% of the orchard site soils and approximately 1% of reference site soils exceed the USEPA Preliminary Remediation Goal (PRG) screening guideline of 22 mg kg -1 for As in residential soil, defined on the basis of combined chronic exposure risk. Approximately 5% of orchard site soils exceed the USEPA PRG for Pb of 400 mg kg -1 in residential soil; no reference site soils sampled exceed this value. A variety of statistical methods were used to characterize the occurrence, distribution, and dispersion of arsenical pesticide residues in soils, stream sediments, and ground waters relative to landscape features and likely background conditions. Concentrations of Zn, Pb, and Cu were most strongly associated with high developed land density and population density, whereas elevated concentrations of As were weakly correlated with high orchard density, consistent with a pesticide residue source. Arsenic concentrations in ground water wells in the region are generally <0.005 mg L -1 . There was no spatial association between As concentrations in ground water and proximity to orchards. Arsenic had limited mobility into ground water from surface soils contaminated with arsenical pesticide residues at concentrations typically found in orchards.
Text Annotation for Political Science Research

Digitization is dramatically altering research demands and opportunities in political science, and in the social sciences more generally. To cite just a few examples, the advent of e-government has...
Event-related FMRI study of context processing in dorsolateral prefrontal cortex of patients with schizophrenia.

Context processing is conceptualized as an executive function involved in voluntary, complex actions such as overcoming automatic responses. The present study tested the hypothesis that context-processing deficits in patients with schizophrenia are associated with a dysfunction of left dorsolateral prefrontal cortex (DLPFC). Using event-related functional magnetic resonance imaging (fMRI), 17 controls and 17 medicated patients performed a version of the AX task in which a learned, automatic response had to be inhibited. In controls, left DLPFC activity increased when preparing to overcome an automatic response, whereas patients with schizophrenia showed no differential activation. In controls, context processing appeared to be associated with the differential representation of cues associated with the need to provide top-down support for overcoming automatic responses. This mechanism appeared to be impaired in patients with schizophrenia.
A working distinction: Vagrants, beggars, and the laboring poor in mid‐Victorian England

(1995). A working distinction: Vagrants, beggars, and the laboring poor in mid‐Victorian England. Prose Studies: Vol. 18, No. 1, pp. 74-104.
Nitric oxide synthase I mediates osteoclast activity in vitro and in vivo.

Bone resorption is responsible for the morbidity associated with a number of inflammatory diseases such as rheumatoid arthritis, orthopedic implant osteolysis, periodontitis and aural cholesteatoma. Previous studies have established nitric oxide (NO) as a potentially important mediator of bone resorption. NO is a unique intercellular and intracellular signaling molecule involved in many physiologic and pathologic pathways. NO is generated from L-arginine by the enzyme nitric oxide synthase (NOS). There are three known isoforms of NOS with distinct cellular distributions. In this study, we have used mice with targeted deletions in each of these isoforms to establish a role for these enzymes in the regulation of bone resorption in vivo and in vitro. In a murine model of particle induced osteolysis, NOS I-/- mice demonstrated a significantly reduced osteoclast response. In vitro, osteoclasts derived from NOS I-/- mice were larger than wild type controls but demonstrated decreased resorption. Although NOS I has been demonstrated in osteoblasts and osteocytes as a mediator of adaptive bone remodeling, it has not previously been identified in osteoclasts. These results demonstrate a critical role for NOS I in inflammatory bone resorption and osteoclast function in vitro.
Accountable Accounting: Carbon-Based Management on Marginal Lands

Substantial discussion exists concerning the best land use options for mitigating greenhouse gas (GHG) emissions on marginal land. Emissions-mitigating land use options include displacement of fossil fuels via biofuel production and afforestation. Comparing C recovery dynamics under these different options is crucial to assessing the efficacy of offset programs. In this paper, we focus on forest recovery on marginal land, and show that there is substantial inaccuracy and discrepancy in the literature concerning carbon accumulation. We find that uncertainty in carbon accumulation occurs in estimations of carbon stocks and models of carbon dynamics over time. We suggest that analyses to date have been largely unsuccessful at determining reliable trends in site recovery due to broad land use categories, a failure to consider the effect of current and post-restoration management, and problems with meta-analysis. Understanding of C recovery could be greatly improved with increased data collection on pre-restoration site quality, prior land use history, and management practices as well as increased methodological standardization. Finally, given the current and likely future uncertainty in C dynamics, we recommend carbon mitigation potential should not be the only environmental service driving land use decisions on marginal lands.
Aspergillus fumigatus rasA and rasB regulate the timing and morphology of asexual development

Expression of rasA plays an important role in conidial germination in Aspergillus nidulans. Conidial germination is required to initiate both infection and asexual development in the opportunistic pathogen Aspergillus fumigatus. Therefore, we sought to determine the requirements for Ras proteins in conidial germination and asexual development of A. fumigatus. A second homolog, rasB, has been identified that characterizes a new subclass of Ras genes. Dominant active (DA) and dominant negative (DN) mutations of each gene were introduced into protoplasts as transgenes. DArasA expression led to reduced conidiation, malformed conidiophores, and altered mitotic progression, whereas expression of DNrasA caused a significant reduction in the rate of conidial germination. In contrast, expression of DNrasB slightly delayed the initiation of germination and caused the development of conidiophores in submerged culture. DArasB expression led to reduced conidiation. RasA and RasB appear to play different, but overlapping, roles in the vegetative growth and asexual development of A. fumigatus.
Tumor classification ranking from microarray data

Gene expression profiles based on microarray data are recognized as potential diagnostic indices of cancer. Molecular tumor classifications resulted from these data and learning algorithms have advanced our understanding of genetic changes associated with cancer etiology and development. However, classifications are not always perfect and in such cases the classification rankings (likelihoods of correct class predictions) can be useful for directing further research (e.g., by deriving inferences about predictive indicators or prioritizing future experiments). Classification ranking is a challenging problem, particularly for microarray data, where there is a huge number of possible regulated genes with no known rating function. This study investigates the possibility of making tumor classification more informative by using a method for classification ranking that requires no additional ranking analysis and maintains relatively good classification accuracy. Microarray data of 11 different types and subtypes of cancer were analyzed using MDR (Multi-Dimensional Ranker), a recently developed boosting-based ranking algorithm. The number of predictor genes in all of the resulting classification models was at most nine, a huge reduction from the more than 12 thousands genes in the majority of the expression samples. Compared to several other learning algorithms, MDR gives the greatest AUC (area under the ROC curve) for the classifications of prostate cancer, acute lymphoblastic leukemia (ALL) and four ALL subtypes: BCR-ABL, E2A-PBX1, MALL and TALL. SVM (Support Vector Machine) gives the highest AUC for the classifications of lung, lymphoma, and breast cancers, and two ALL subtypes: Hyperdiploid > 50 and TEL-AML1. MDR gives highly competitive results, producing the highest average AUC, 91.01%, and an average overall accuracy of 90.01% for cancer expression analysis. Using the classification rankings from MDR is a simple technique for obtaining effective and informative tumor classifications from cancer gene expression data. Further interpretation of the results obtained from MDR is required. MDR can also be used directly as a simple feature selection mechanism to identify genes relevant to tumor classification. MDR may be applicable to many other classification problems for microarray data.
The Unfolded State of the C-terminal Domain of the Ribosomal Protein L9 Contains Both Native and Non-Native Structure

Interest in the structural and dynamic properties of unfolded proteins has increased in recent years owing to continued interest in protein folding and misfolding. Knowledge of the unfolded state under native conditions is particularly important for obtaining a complete picture of the protein folding process. The C-terminal domain of protein L9 is a globular alpha, beta protein with an unusual mixed parallel and antiparallel beta-strand structure. The folding kinetics and equilibrium unfolding of CTL9 strongly depend on pH, and follow a simple two state model. Both the native and the unfolded state can be significantly populated at pH 3.8 in the absence of denaturant, allowing the native state and the unfolded state to be characterized under identical conditions. Backbone (15)N, (13)C, (1)H and side-chain (13)C(beta), (1)H(beta) chemical shifts, amide proton NOEs, and (15)N R(2) relaxation rates were obtained for the two conformational states at pH 3.8. All the data indicate that the pH 3.8 native state is well folded and is similar to the native state at neutral pH. There is significant residual structure in the pH 3.8 unfolded state. The regions corresponding to the two native state alpha-helices show strong preference to populate helical phi and psi angles. The segment that connects alpha-helix 2 and beta-strand 2 has a significant tendency to form non-native alpha-helical structure. Comparison with the pH 2.0 unfolded state and the urea unfolded state indicates that the tendency to adopt both native and non-native helical structure is stronger at pH 3.8, demonstrating that the unfolded state of CTL9 under native-like conditions is more structured. The implications for the folding of CTL9 are discussed.
Implementing and Evaluating a Writing Course for Psychology Majors

In this article, I describe Writing in Psychology, a semester-length 3-credit elective course designed to improve students' writing skills, familiarize them with psychology's writing conventions, and teach them American Psychological Association (APA) style. Students produced a case report, a report of an empirical study, a conference abstract, and a literature review. An attitude inventory and tests over grammar and APA style revealed significant precourse versus postcourse improvement, providing evidence that the course can be a valuable addition to the undergraduate curriculum.
CORR Insights®: Is there a difference in TKA risk of revision in highly crosslinked versus conventional polyethylene?

This CORR Insights® is a commentary on the article “Is There a Difference in TKA Risk of Revision in Highly Crosslinked versus Conventional Polyethylene?” by Paxton and colleagues available at: DOI: 10.1007/s11999-014-4046-3. The author certifies that he, or any member of his immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR ® or the Association of Bone and Joint Surgeons®. This CORR Insights® comment refers to the article available at DOI: 10.1007/s11999-014-4046-3.
A learning algorithm for the classification of dynamic events using a neuron‐like dynamic tree

The use of neuron-like networks (NN) for pattern recognition has a well-established history and numerous current applications. Most such applications are to static patterns while the theory developed for temporally changing visual patterns usually assumes rigid objects with well-defined boundaries. In applications such as analysis of cardiac movement, however, the object is flexible and the images are often imperfect. the authors current model for NN activity captures the dynamic nature of the signal processing of the neural dendritic tree, allowing both faster learning of dynamic patterns and a very reduced number of receptors required for distinguishing diverse types of motion or changes. the design of the NN model is presented and a training algorithm which exhibits in practice extremely fast convergence (as few as 15 iterations) to near optimal recognition behavior is introduced. © 1993 John Wiley & Sons, Inc.
Ten‐Year Experience in Porto‐Caval Hemitransposition for Liver Transplantation in the Presence of Portal Vein Thrombosis

Porto-caval hemitransposition (PCH) in liver transplantation allows revascularization of the liver when the porto-mesenteric axis is thrombosed. We, here, review our experience over an 11-year period. A total of 23 patients underwent liver transplantation using PCH. Immunosuppression was based on tacrolimus, with sirolimus used in case of renal insufficiency. Most common diagnoses were hepatitis C, Laennec's, Budd-Chiari and cryptogenic cirrhosis. Six patients needed splenectomy prior to transplant, 5 during transplant, 1 post-transplant, 11 had no splenectomy. Overall survival was 60% at 1 year and 38% at 3 years, with 10 of 23 patients currently alive and the longest survivor at 9.3 years. Most common cause of death was sepsis/multisystem organ failure, followed by pulmonary embolism. A total of 7/23 patients experienced post-operative gastrointestinal bleeding episodes, 6/23 patients developed thrombosis of the vena cava (median 162 days post-op). Post-operative ascites was noted in almost all patients. Renal dysfunction was commonly seen even after the first month post-transplant. PCH offers a feasible option for liver transplantation in those patients with complex thrombosis of the mesenteric and portal circulation.
A Causal Perspective on OSIM2 Data Generation, with Implications for Simulation Study Design and Interpretation

Research by the Observational Medical Outcomes Partnership (OMOP) has focused on developing and evaluating strategies to exploit observational electronic data to improve post-market prescription drug surveillance. A data simulator known as OSIM2 developed by the OMOP statistical methods group has been used as a testbed for evaluating and comparing different estimation procedures for detecting adverse drug-related events from data similar to that found in electronic insurance claims data. The simulation scheme produces a longitudinal dataset with millions of observations designed to closely match marginal distributions of important covariates in a known dataset. In this paper we provide a non-parametric structural equation model for the data generating process and construct the associated directed acyclic graph (DAG) depicting the causal structure. These representations reveal key differences between simulated and real-world data, including a departure from longitudinal causal relationships, absence of (presumed) sources of bias and time ordering of covariates that conflicts with reality. The DAG also reveals the presence of unmeasured baseline confounding of the causal effect of a drug on a subsequent medical condition. Conclusions naively drawn from this simulation study could mislead an investigator trying to gain insight into estimator performance on real data. Applying causal inference tools allows us to draw more informed conclusions and suggests modifications to the simulation scheme that would more closely align simulated and real-world data.
Heat transfer enhancement by slurry of phase change material through rectangular porous channel

This study attempts to take advantage of porous media with high conductivity and the latent heat capacity of phase change material together to enhance the overall heat transfer rate. A 3-D laminar model of a rectangular porous channel with high thermal conductivity and constant wall heat flux is chosen to see the enhancement of heat transfer when used in conjunction with the phase change material slurry. Numerical simulations for various wall heat fluxes and inlet velocities are carried out. The heat transfer coefficient along the heated surface of the channel is compared when adding micro-encapsulated phase change material to the flow passing through porous channel. There is a significant heat transfer enhancement when using phase change material slurry through porous channel, only under specific conditions of heat fluxes, inlet velocities and the particle concentrations. This study also investigates the effect of various porous media properties e.g. porosity and permeability on the heat transfer coefficient when applied with slurry of phase change material.© 2011 ASME
Cutaneous gene therapy

Gene therapy efforts in a variety of tissues have foundered on fundamental technologic barriers, such as difficulties in achieving high-efficiency gene transfer to diseased tissues and in sustaining delivered transgene production. The skin offers an attractive tissue for development of approaches to therapeutic gene delivery by virtue of its accessibility for regulation by topical agents, the ease of gene transfer into cutaneous tissues, and the ready ability to monitor the impact of somatic gene transfer. With the ability of the skin to deliver therapeutic polypeptides to the systemic circulation and the recent molecular characterization of monogenic skin diseases, efforts to target genes to the skin are expected to accelerate. The current status of gene therapy efforts is reviewed, with a special focus on the skin.
The Plasma Chromatograph as a Separation-Identification Technique

Abstract The plasma Chromatograph is evaluated as a separation and identification device using binary mixtures of ketones. Discrimination of components is not encouraging and the ion-molecule spectra of a mixtu not always the sum of the spectra of the individual components.