cssi/SciSciGPT-SciSciNet huggingface dataset:
Differential regulation of gene expression by protein kinase C isozymes as determined by genome-wide expression analysis

Protein kinase C (PKC) isozymes are key signal transducers involved in normal physiology and disease and have been widely implicated in cancer progression. Despite our extensive knowledge of the signaling pathways regulated by PKC isozymes and their effectors, there is essentially no information on how individual members of the PKC family regulate gene transcription. Here, we report the first PKC isozyme-specific analysis of global gene expression by microarray using RNAi depletion of diacylglycerol/phorbol ester-regulated PKCs. A thorough analysis of this microarray data revealed unique patterns of gene expression controlled by PKCα, PKCδ, and PKCϵ, which are remarkably different in cells growing in serum or in response to phorbol ester stimulation. PKCδ is the most relevant isoform in controlling the induction of genes by phorbol ester stimulation, whereas PKCϵ predominantly regulates gene expression in serum. We also established that two PKCδ-regulated genes, FOSL1 and BCL2A1, mediate the apoptotic effect of phorbol esters or the chemotherapeutic agent etoposide in prostate cancer cells. Our studies offer a unique opportunity for establishing novel transcriptional effectors for PKC isozymes and may have significant functional and therapeutic implications.
Methods of Language Assessment: A Survey of California Public School Clinicians.

Public school clinicians in California were surveyed regarding methods for assessing the language of children between 4 and 9 years old. Information was obtained about the use of informal and forma...
Amorphization of nanocrystalline 3C−SiC irradiated with Si+ ions

Irradiation induced amorphization in nanocrystalline and single crystal 3C-SiC has been studied using 1 MeV Si+ ions under identical irradiation conditions at room temperature and 400 K. The disordering behavior has been characterized using in-situ ion channeling and ex-situ x-ray diffraction methods. The results show that, compared to single crystal 3C-SiC, full amorphization of small 3C-SiC grains (~3.8 nm in size) at room temperature occurs at a slightly lower dose. Grain size decreases with increasing dose until a fully amorphized state is attained. The amorphization dose increases at 400 K relative to room temperature. However, at 400 K, the dose for amorphization for 2.0 nm grains is about a factor of 4 and 8 smaller than for 3.0 nm grains and bulk single crystal 3C-SiC, respectively. The behavior is attributed to the dominance of defect-stimulated interfacial amorphization.
Implications of newly recognized relationships between mutagenicity, genotoxicity and carcinogenicity of molecules.

Abstract The CASE structure-activity relational method was used to predict the mutagenicity, cytogenotoxicity, carcinogenicity, sensory irritation, male rat-specific α2μ-nephrotoxicity and maximum tolerated dose of a population of molecules ( N ⩾1300). These chemicals were then sorted out by their predicted responses to specific tests and sub-populations of molecules with different prevalence with respect to described endpoints were constructed, i.e. 0–100% prevalences of mutagens, rodent carcinogens and SCE inducers. The predited properties of these populations were analyzed and the ovelap among tests was determined. The false-positive and false-negative predictions.
Optimal output inventory decisions in stochastic markets

Recent economic applications of optimal inventory control models to aggregate industry data (Hay and Holt 1975, Belsley 1969, Sengupta and Sfeir 1979) have been restricted to Linear Quadratic Gaussian (LQG) models and the associated linear decision rules (LDR). For perfect markets with competitive exchange of information, where no individual agent has the monopolistic power to influence the price or the market demand, the LQG model may hold very well as an approximation; this is unlikely to be so for imperfect markets, where imperfection may be due to several sources, e.g., (a) asymmetry in the distribution of market demand, where the third and fourth moments may be as important as the mean and variance, (b) the price may be useable in part as a control variable along with output, (c) the inventory cost function may be partly convex and partly concave and (d) the sensitivity to risk parameters in stochastic demand may modify the LDR and its updating characteristics. Our object here is to formulate in a simplified framework a set of dynamic inventory control models, which incorporates in an approximate sense some of the imperfections of stochastic markets as above. These models are illustrative of the deficiencies of the LDR approach, as they suggest the need for stochastic demand conditions.
Control of acid-base status in active and dormant land snails, Otala lactea (Pulmonata, Helicidae)

Control of extracellular acid-base status was examined during activity and dormancy inOtala lactea (Pulmonata, Helicidae). Active snails showed little variation in hemolymph pH and $$P_{CO_2 } $$ at constant temperature. With increase of temperature, hemolymph $$P_{CO_2 } $$ increased from about 6 Torr at 5°C to 13 Torr at 24°C and pH decreased by about 0.017 pH units/°C, a pattern consistent with alphastat regulation of pH via ventilatory control of $$P_{CO_2 } $$ . During dormancy, mean hemolymph $$P_{CO_2 } $$ increased to about 50 Torr. Venous pH declined by about 0.4 units due to hypercapnia and fluctuated more widely than in active snails due to variability of $$P_{CO_2 } $$ . Hemolymph pH declined further in prolonged dormancy due to progressive metabolic acidosis; after one year of dormancy the mean hemolymph pH was about 0.8 units lower than that of active snails at similar temperature. Active snails exposed experimentally to high $$P_{CO_2 } $$ showed a large increase in hemolymph [HCO 3 − ]. However, [HCO 3 − ] declined by up to 50% during dormancy, despite the naturally occurring hypercapnia. Hemolymph osmolality and the concentrations of solutes other than [HCO 3 − ] increased with increasing duration of dormancy. Concentrations of magnesium and calcium increased about 2.5 times more rapidly than those of sodium and chloride, indicating that acidosis is partially offset by the dissolution of carbonates from the shell or tissues.
Activation of 5-HT1C/2 receptors depresses polysynaptic reflexes and excitatory amino acid-induced motoneuron responses in frog spinal cord.

Abstract Sucrose gap recordings from the ventral roots of isolated, hemisected frog spinal cords were used to evaluate the effects of high concentrations of serotonin (5-HT) and α-methyl-5-HT (α-Me-5-HT) on the changes in motoneuron potential produced by dorsal root stimulation and by excitatory amino acids and agonists. Bath application of 5-HT in concentrations of 10 μM or greater produced a concentration-dependent motoneuron depolarization. Polysynaptic ventral root potentials evoked by dorsal root stimuli were reduced in both amplitude and area by 5-HT or α-Me-5-HT (both 100 μM). This may result from a reduction of the postsynaptic sensitivity of motoneurons to excitatory amino acid transmitters because 5-HT significantly depressed motoneuron depolarizations produced by addition of l -glutamate and l -aspartate to the superfusate. Similarly, 5-HT reduced depolarizations produced by the excitatory amino acid agonists N-methyl- d -aspartate (NMDA), quisqualate, α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate. α-Me-5-HT reduced NMDA depolarizations. Tetrodotoxin (TTX) did not affect the ability of 5-HT to attenuate NMDA or kainate depolarizations, but did eliminate the 5-HT-induced attenuation of quisqualate and AMPA depolarizations. The glycine receptor site associated with the NMDA receptor did not appear to be affected by 5-HT because saturation of the site by excess glycine did not alter the 5-HT-induced depression of NMDA responses. The 5-HT1C/2 antagonist ketanserin and the 5-HT1A/2 antagonist spiperone significantly attenuated the 5-HT-induced depression of NMDA NMDA-depolarizations. The relatively selective 5-HT1A antagonist spiroxatrine and the selective 5-HT3 blocker MDL 72222 were without effect against the depressive effects of 5-HT. These observations support the notion that 5-HT putatively released from descending bulbospinal fibers can alter frog motoneuronal output. The data indicate that 5-HT1C/2 receptors affect the afferent input to motoneurons and do so by attenuation of NMDA receptor-mediated synaptic processes.
A note on mean square spline approximation

Abstract A method of obtaining the mean-square spline approximation by the use of dynamic programming is indicated.
TESTING RESISTANCE OF ENAMELED SURFACES TO SCRATCHING GOUGING, AND ABRASION

Seven types of cover-coat enamels were tested for resistance to scratching, gouging, and abrasion by various methods. These methods were (a) P.E.I. abrasion test, (b) P.E.I. gouge test, (c) variations of the gouge test, (d) Taber Abraser, and (e) a scratch test. Chemical durability and reflectance were found to have little or no correlation with the resistance of the enamels to abrasion. The bubble structure of the enamel layer seemed to have the greatest effect on abrasion and scratch resistance of the enamel layer.
UV disinfection of biologically active carbon filter effluent

2012 © American Water Works Association Permitting the proliferation of bacteria at any stage of drinking water treatment is counterintuitive to many water plant operators. A majority of surveyed public water supply and regulatory personnel are uncertain about the public health implications of biological processes (Evans, 2009). Logsdon et al cited the production of bacteria as a disadvantage of biological activated carbon (BAC) filtration (2006). The heterotrophic plate count (HPC) bacteria found in biological processes, similar to the flora found in conventionally treated water (Norton & LeChevallier, 2000), may include opportunistic pathogens that pose a risk to some populations (Geldreich et al, 1972) and may even be resistant to antibiotics (Xi et al, 2009), though evidence linking drinking water HPC concentrations and public health is lacking (Bartram et al, 2003). Nevertheless, water treatment has always coexisted with bacteria that colonize submerged surfaces throughout water facilities, chlorinated distribution systems (Evans, 2000), and even ultrapure laboratory water purification systems (McFeters, 1993). The benefits of biological processes such as BAC filtration may be achieved with diminished concern if the multiple-barrier approach to treatment is practiced and a microbiological barrier is installed between the biological process and final disinfection. Some utilities have used ultrafiltration processes for this purpose (Juhna & Melin, 2006); others have investigated or installed ultraviolet (UV) light disinfection (Kashinkunti et al, 2004; Toivanen, 2000). Although UV exposure does not appear suitable as a single barrier to bacterial proliferation, its use in conjunction with a disinfectant residual provides a dual barrier to bacterial growth in BAC effluent (Mofidi & Linden, 2004). The biological activated carbon (BAC) filters at the Central Lake County Joint Action Water Agency (CLCJAWA; Lake Bluff, Ill.) shed heterotrophic plate count (HPC) bacteria, especially when water temperatures exceed 15oC (59oF). Chlorine, previously the only disinfectant applied to BAC filter effluent at CLCJAWA, was augmented with the addition of ultraviolet (UV) reactors in 2004, creating a multiple barrier. An average collimated beam UV dosage of 12 mJ/cm2 was established for 3-log inactivation of indigenous HPC bacteria, but the equivalent effective reactor dosage was difficult to determine with certainty. This unique UV application reduced 95th percentile BAC filter effluent HPC concentrations from 233 to 3 cfu/mL and the percentage of coliform-positive samples from 25 to 0.07%. The reactors’ medium-pressure UV lamps remained efficacious at seven times their recommended replacement interval of 3,000 h. This article documents full-scale HPC and total coliform inactivation in a water plant, describes the use of indigenous HPC concentrations to monitor UV reactor performance, and demonstrates the potential for extended lamp life. UV disinfection of biologically active carbon filter effluent
One Size Does Not Fit All Projects: Exploring Classical Contingency Domains

Not many authors have attempted to classify projects according to any specific scheme, and those who have tried rarely offered extensive empirical evidence. From a theoretical perspective, a traditional distinction between radical and incremental innovation has often been used in the literature of innovation, and has created the basis for many classical contingency studies. Similar concepts, however, did not become standard in the literature of projects, and it seems that theory development in project management is still in its early years. As a result, most project management literature still assumes that all projects are fundamentally similar and that "one size fits all." The purpose of this exploratory research is to show how different types of projects are managed in different ways, and to explore the domain of traditional contingency theory in the more modern world of projects. This two-step research is using a combination of qualitative and quantitative methods and two data sets to suggest a conceptual, two-dimensional construct model for the classification of technical projects and for the investigation of project contingencies. Within this framework, projects are classified into four levels of technological uncertainty, and into three levels of system complexity, according to a hierarchy of systems and subsystems. The study provides two types of implications. For project leadership it shows why and how management should adapt a more project-specific style. For theory development, it offers a collection of insights that seem relevant to the world of projects as temporary organizations, but are, at times, different from classical structural contingency theory paradigms in enduring organizations. While still exploratory in nature, this study attempts to suggest new inroads to the future study of modern project domains.
Glucose-Insulin-Potassium Use in Acute Myocardial Infarction

To the Editor: I read with interest the study of Diaz et al1 regarding the ECLA Glucose-Insulin-Potassium Pilot trial. The provocative conclusions may potentially affect the care of patients with acute myocardial infarction (MI) and need to be substantiated by larger randomized trials, as the authors of both the study1 and the accompanying editorial2 have suggested. In addition, several aspects of the ECLA study need to be clarified in …
Learning Through Symbol, Myth, Model, and Ritual

An interdisciplinary course entitled “Religious and Spiritual Issues in Health Care” was offered for nursing students, medical students, and seminary students. The course was designed to explore religious responses to human suffering and to examine the role of different health care professionals with regard to spiritual concerns of patients.
Stimulation of a calcium-dependent actin nucleation activity by phorbol 12-myristate 13-acetate in rabbit macrophage cytoskeletons.

Cytoskeletons of detergent-extracted quiescent macrophages have nucleation sites that increase the rate of pyrene-labeled actin assembly in vitro. Cytochalasin D, which inhibits actin assembly at the fast-exchanging ends of filaments (barbed with respect to heavy meromyosin decorated filaments), only partially inhibits the increased assembly rate, demonstrating that pyrene-actin monomers add to both ends of filaments present in the cytoskeletons. Cytoskeletons prepared from macrophages treated with phorbol 12-myristate 13-acetate for 20–30 s before permeabilization, markedly stimulated (300% of control) the rate of actin assembly, and this increment was completely cytochalasin-sensitive, indicating that exposure to phorbol leads to formation of free barbed ends. Nucleation activity required more than 5 nM free calcium only in the assay and was maximal in the presence of 200 nM calcium. Concentrations of calcium of at least 30 nM dissociate the nucleation activity from the cytoskeleton, and it is recovered fully active in the calcium wash.
The Living Body as the Origin of Culture: What the Shift in Husserl’s Notion of “Expression” Tells us About Cultural Objects

Husserl’s philosophy of culture relies upon a person’s body being expressive of the person’s spirit, but Husserl’s analysis of expression in Logical Investigations is inadequate to explain this bodily expressiveness. This paper explains how Husserl’s use of “expression” shifts from LI to Ideas II and argues that this shift is explained by Husserl’s increased understanding of the pervasiveness of sense in subjective life and his increased appreciation for the unity of the person. I show how these two developments allow Husserl to better describe the bodily expressiveness that is the source of culture. Husserl’s account of culture is thoroughly intentionalistic, but it does not emphasize thought at the expense of embodiment. Culture originates not in an abstract subjectivity, but by persons’ expressing themselves physically in the world. By seeing how Husserl develops his mature position on bodily expressiveness, we can better appreciate the meaningfulness and the bodily concreteness of cultural objects.
Three-dimensional structural evolution and kinematics of the Piedemonte Llanero, Central Llanos foothills, Eastern Cordillera, Colombia

The Piedemonte Llanero is a wedge duplex zone in the Llanos foothills on the eastern flank of the Eastern Cordillera of Colombia. It is located northeast of the Cusiana and Cupiagua hydrocarbon fields. The area is characterized by a series of moderate to high-angle duplexes with east-southeast verging thin-skinned and thick-skinned tectonics. We present a structural model constrained by 2-D and 3-D seismic reflection data, surface geology, and well data. The structural analysis is based on backward modeling (kinematic restoration) and forward modeling using transfer-flexural slip and fault slip fold algorithms. The structures are significantly tighter in the northern segment compared to the southern segment of the overthrust trend. We estimate approximately 17 km of shortening in the northern duplex zone, and about 26 km total shortening for the southern duplex zone. We propose that thin-skinned in-sequence imbricate thrust stack deformation produced most of the shortening. The main Andean deformation (80% of the total shortening) commenced in the Piedemonte area about 6 Ma with rapid shortening and uplift in the area resulting in the development of an active-roof duplex structure as the cover was bulldozed forward by a horse block (Monterralo anticline) ramping up to a detachment at the base of C2, then ramping to the surface as the Yopal thrust. Later the horse blocks in the wedge rose, underthrusting the cover in a passive-roof duplex triangle zone. This was followed by an out-of-sequence Laramide-style thick-skinned basement-uplift of the range which produced much of the structural relief of the Eastern Cordillera. Cenozoic deformation in the Eastern Cordillera has been primarily range-normal, but has involved an increasing component of mountain-parallel right-lateral shear in the last 2 Ma.
Defensiveness, cynical hostility and cardiovascular reactivity: a moderator analysis

We examined the interaction of a defensive need for approval with cynical hostility, in the prediction of pressor and heart rate reactivity to a stressful mental arithmetic task. For both systolic blood pressure and heart rate, analyses revealed the predicted interaction between defensiveness and cynical hostility; subsequent analyses showed significant correlations of defensiveness with systolic blood pressure and heart rate reactivity only among the high cynical hostility subjects. These analyses support the theory and empirical findings linking the conflicting traits of cynical hostility and defensiveness to cardiovascular reactivity and, quite possibly, to stress-related coronary disease.
Local feature extraction and matching partial objects

Abstract A primary shortcoming of existing techniques for hree-dimensional (3D) model matching is the reliance on global information of the model’s structure. Models are matched in their entirety, depending on overall topology and geometry information. A currently open challenge is how to perform partial matching. Partial matching is important for finding similarities across part models with different global shape properties and for the segmentation and matching of data acquired from 3D scanners. This paper presents a Scale–Space feature extraction technique based on recursive decomposition of polyhedral surfaces into surface patches. The experimental results presented in this paper suggest that this technique can potentially be used to perform matching based on local model structure. In our previous work, Scale–Space decomposition has been used successfully to extract features from mechanical artifacts. Scale–Space techniques can be parameterized to generate decompositions that correspond to manufacturing, assembly or surface features relevant to mechanical design. One application of these technique is to support matching and content-based retrieval of solid models. This paper shows how a Scale–Space technique can extract features that are invariant with respect to the global structure of the model as well as small perturbations that 3D laser scanning process introduce. In order to accomplish this, we introduce a new distance function defined on triangles instead of points. We believe this technique offers a new way to control the feature decomposition process, which results in the extraction of features that are more meaningful from an engineering viewpoint. The new technique is computationally practical for use in indexing large models. Examples are provided that demonstrate effective feature extraction on 3D laser scanned models. In addition, a simple sub-graph isomorphism algorithm was used to show that the feature adjacency graphs, obtained through feature extraction, are meaningful descriptors of 3D CAD objects. All of the data used in the experiments for this work is freely available at: http://www.designrepository.org/datasets/ .
Living on higher ground reduces child neurodevelopment-evidence from South America.

Objective To study the effects of altitude on infant neurodevelopment in the first 2 years of life. Study design Data from a unique study of normal infant neurodevelopment in 5 South American countries were used. The sample included 2116 infants 3-24 months of age who were evaluated for neurodevelopmental problems by study physicians during their routine well-child visits at 31 pediatric practices. We used regression models with country fixed-effects that compare the neurodevelopment of children born at different altitudes within the same country to avoid confounding. The regressions adjust for several socioeconomic and demographic factors. We also evaluated altitude effects stratifying by sex, age, and household wealth. Infant neurodevelopment was evaluated by physicians by using the Bayley Infant Neurodevelopmental Screener. The primary outcome is an indicator for whether the infant is at high risk for neurodevelopmental problems based on the Bayley Infant Neurodevelopmental Screener norms. Results Altitude significantly increases the probability of being at high risk for neurodevelopmental problems (100-meter increase in altitude: OR 1.02; 95% CI 1.001-1.037; high altitude greater than 2600 meters vs low altitude less than 800 meters: OR 2.01; 95% CI 1.36-2.973). The effects are larger for females and for second than first year of life. The largest effect is for females 12-24 months of age (high vs low altitude: OR 4.147; 95% CI 1.466-12.013). There are no significant differences in altitude effects by household wealth. Conclusions Altitude may significantly increase the risk of neurodevelopmental problems during the first 2 years of life, especially for females during their second year of life.
Two cases of medically and surgically intractable SUNCT: a reason for caution and an argument for a central mechanism.

We report two cases of SUNCT that demonstrate the medically and surgically refractory nature of this disorder and support the hypothesis that the causative ‘lesion’ lies within the central nervous system. After both patients had failed medical therapies, the first underwent a glycerol rhizotomy, gammaknife radiosurgery and microvascular decompression of the trigeminal nerve. The second patient underwent gammaknife radiosurgery of the trigeminal root exit zone and two microvascular decompression surgeries. Neither patient benefited from these procedures. Currently, the first patient suffers from anaesthesia dolorosa and the second patient from unilateral deafness, chronic vertigo and dysequilibrium as a result of surgical trauma. These cases of SUNCT highlight the uncertainty regarding the role of surgery given the potential for significant morbidity. These cases also suggest that SUNCT originates and may be maintained from within the CNS and this central locus explains why SUNCT is not typically amenable ...
Route of ethanol administration and gastric acid output during chronic conditions.

The effect of intravenous or intragastric ethanol on gastric secretion was determined in chronic ethanol-fed and matched control rats.In vivo, basal and histamine-stimulated acid outputs were inhibited by acute intragastric ethanol to a greater extent in chronic control rats than in ethanol-fed rats. In contrast, intravenous ethanol stimulated basal and potentiated histamine (H)-stimulated acid output (blocked by cimetidine but not atropine) in ethanol-fed rats but not in chronic control rats. Serum gastrin levels were not significantly altered by ethanol.In vitro, mucosal ethanol inhibited basal and H-stimulated acid secretion by mucosae from chronic control and ethanol-fed rats, but serosal ethanol did not signifcantly alter acid secretion. In conclusion, chronic ethanol intake results in higher acid outputs following acute exposure to intravenous or intragastric ethanol orin vitro exposure to mucosal ethanol as compared to studies using matched control rats.
Advanced Glycation End Products Inhibit Glucose-Stimulated Insulin Secretion through Nitric Oxide-Dependent Inhibition of Cytochrome c Oxidase and Adenosine Triphosphate Synthesis

Advanced glycation end products (AGEs) are implicated in diabetic complications. However, their role in β-cell dysfunction is less clear. In this study we examined the effects of AGEs on islet function in mice and in isolated islets. AGE-BSA or BSA was administered ip to normal mice twice a day for 2 wk. We showed that AGE-BSA-treated mice exhibited significantly higher glucose levels and lower insulin levels in response to glucose challenge than did BSA-treated mice, although there were no significant differences in insulin sensitivity and islet morphology between two groups. Glucose-stimulated insulin secretion by islets of the AGE-BSA-treated mice or AGE-BSA-treated normal islets was significantly lower than that by islets isolated from the BSA-treated mice or BSA-treated normal islets. Furthermore, AGE treatment of islet β-cells inhibited ATP production, and glimepiride, a sulfonylurea derivative, restored glucose-stimulated insulin secretion. Further investigation indicated that AGEs inhibited cytochrome c oxidase activity by inducing the expression of inducible nitric oxide synthase (iNOS). Blocking the formation of nitric oxide with an iNOS selective inhibitor aminoguanidine reversed the inhibitory effects of AGEs on ATP production and insulin secretion. We conclude that AGEs inhibit cytochrome c oxidase and ATP production, leading to the impairment of glucose-stimulated insulin secretion through iNOS-dependent nitric oxide production.
Private Manufacturers’ Thresholds to Invest in Comparative Effectiveness Trials

The recent rush of enthusiasm for public investment in comparative effectiveness research (CER) in the US has focussed attention on these public investments. However, little attention has been given to how changing public investment in CER may affect private manufacturers’ incentives for CER, which has long been a major source of CER. In this work, based on a simple revenue maximizing economic framework, we generate predictions on thresholds to invest in CER for a private manufacturer that compares its own product to a competitor’s product in head-to-head trials. Our analysis shows that private incentives to invest in CER are determined by how the results of CER may affect the price and quantity of the product sold and the duration over which resulting changes in revenue would accrue, given the time required to complete CER and the time from the completion of CER to the time of patent expiration. We highlight the result that private incentives may often be less than public incentives to invest in CER and may even be negative if the likelihood of adverse findings is sufficient. We find that these incentives imply a number of predictions about patterns of CER and how they will be affected by changes in public financing of CER and CER methods. For example, these incentives imply that incumbent patent holders may be less likely to invest in CER than entrants and that public investments in CER may crowd out similar private investments. In contrast, newer designs and methods for CER, such as Bayesian adaptive trials, which can reduce ex post risk of unfavourable results and shorten the time for the production of CER, may increase the expected benefits of CER and may tend to increase private investment in CER as long as the costs of such innovative designs are not excessive. Bayesian approaches to design also naturally highlight the dynamic aspects of CER, allowing less expensive initial studies to guide decisions about future investments and thereby encouraging greater initial investments in CER. However, whether the potential effects we highlight of public funding of CER and of Bayesian approaches to trial design actually produce changes in private investment in CER remains an empirical question.
Selenium's importance in regulatory issues regarding mercury

Abstract Current seafood safety and health risk assessment criteria use mercury concentrations as their sole basis. This unfortunate limitation omits consideration of selenium, an essential trace element that appears to be the primary molecular target of mercury toxicity. Although selenium has been recognized for decades as a means of counteracting mercury toxicity, its effects have often been overlooked or misunderstood. Experimental animal studies have demonstrated that increasing concentrations of selenium throughout the normal dietary range increasingly counteracts methylmercury toxicity. Dietary concentrations of selenium that are slightly less than the average amount present in ocean fish have been shown to completely prevent the onset of toxic symptoms of mercury toxicity, while animals fed lesser amounts of selenium rapidly sickened and died. Dietary selenium from a variety of sources including ocean fish such as tuna, swordfish, menhaden, and rockfish has been shown to counteract mercury toxicity. Since ocean fish are among the richest sources of dietary selenium, it is important to include selenium concentration measurements in future mercury risk assessments and seafood safety criteria. Mercury:selenium molar ratios in blood provide far more consistent and physiologically meaningful risk assessments. Comprehensive seafood safety criteria such as the Selenium Health Benefit Value enable clear differentiation between seafoods that are safe and those that are hazardous for human consumption. Use of parameters that integrate mercury–selenium relationships also make it easy to understand the differences between the findings of maternal mercury exposure studies that have been performed in New Zealand, the Faroes, the Seychelles, and the United Kingdom. Development of criteria for evaluating mercury–selenium interactions will enhance environmental protection and improve public safety.
Educational outreach to mammography facility staff to assist with compliance with the mammography quality standards act in rural North Carolina

Rationale and Objectives. The purpose of this project was to develop and evaluate an educational program targeted at mammography facilities in rural areas of North Carolina that were having difficulty complying with the 1992 Mammography Quality Standards Act (MQSA). Materials and Methods. Fourteen facilities deemed at risk for closure under MQSA were identified by state inspection personnel. Problems at the facilities were evaluated by a radiologist, a physicist-educator, and a radiation physicist through a written survey, review of phantom and clinical images, and a site visit. Individual advice and instruction were provided on-site by the physicist-educator, with written materials provided in follow-up. A repeat site visit was made 4–6 months after the initial visit. Results. Of 51 problems identified at the 12 institutions that completed the program, 35 (69%) were corrected. All facilities that had failing phantom scores at the inspection prior to the intervention had passing scores at the inspection after the intervention. There was a statistically significant increase in the sum of the phantom scores for the facilities offered this interention compared with those not offered it ( P = .03). Conclusion. This educational program improved mammography quality at participating facilities.
The synthesis of herpes simplex virus proteins in the absence of virus DNA synthesis.

Summary When herpes simplex virus infected cells were blocked from synthesizing DNA, alterations in the production of certain classes of herpes simplex virus specific proteins were detected. Some proteins were made in excess, some in normal amounts, some in reduced amounts and some were not made. An example of each type was chosen, and its kinetics of synthesis studied. Possible explanations of the phenomena are discussed.
Effect of regional slope on drainage networks

Drainage networks that develop under conditions of no structural control and homogeneous lithology are generally dendritic, depending upon the shape and inclination of the surface on which they form. An experimental study was designed to investigate the effect of an increase of slope on the evolution and development of dendritic drainage patterns. As slope steepens, the pattern changes from dendritic at 1% slope, to subdendritic at 2%, to subparallel at 3%, to parallel at 5% and higher. The change from a dendritic-type pattern to a parallel-type pattern occurs at a low slope, between 2% and 3%, and primary channel junction angles decrease abruptly from about 60° to 43°.
Dual-pore glass chips for cell-attached single-channel recordings

While high-throughput planar patch-clamp instruments are now established to perform whole-cell recordings for drug screening, the conventional micropipette-based approach remains the gold standard for performing cell-attached single-channel recordings. Generally, planar platforms are not well-suited for such studies due to excess noise resulting from low seal resistances and the use of substrates with poor dielectric properties. Since these platforms tend to use the same pore to position a cell by suction and establish a seal, biological debris from the cell suspension can contaminate the pore surface prior to seal formation, reducing the seal resistance. Here, femtosecond laser ablation was used to fabricate dual-pore glass chips optimized for use in cell-attached single-channel recordings that circumvent this problem by using different pores to position a cell and to establish a seal. This dual-pore design also permitted the use of a relatively small patch aperture (D ~ 150 to 300 nm) that is better-suited for establishing high-resistance seals than the micropores used typically in planar patch-clamp setups (D ~ 1 to 2 μm) without compromising the ability of the device to position a cell. Taking advantage of the high seal resistances and low capacitive and dielectric noise realized using glass substrates, patch-clamp experiments with these dual-pore chips consistently achieved high seal resistances (rate of gigaseal formation = 61%, mean seal resistance = 53 GΩ), maintained gigaseals for prolonged durations (up to 6 hours), achieved RMS noise values as low as 0.46 pA at 5 kHz bandwidth, and enabled single-channel recordings in the cell-attached configuration that are comparable to those obtained by conventional patch-clamp.
Sagittal balance of the mandible

Sagittal balance of the mandible in­ volves, simultaneously, the anteropos­ terior and vertical relations of the man­ dible in the sagittal plane. Such balance exists when the teeth, the neuromuscular mechanism and the temporomandibular articulation are functioning in harmony. Either structural or functional dishar­ mony of these structures may give rise to sagittal imbalance, and serious harmful results may ensue. The dentist has a grave responsibility to the patient to es­ tablish and maintain the balance of the mandible.
Interaction between GFR and Risk Factors for Morbidity and Mortality in African Americans with CKD

Design, setting, participants, & measurements Enrollment in the African American Study of Kidney Disease Trial occurred between June of 1995 and September of 2001, with median follow-up of 48.6 months. Among 1094 patients with hypertensive kidney disease in the trial, this study tested whether the association between six previously identified risk factors for CKD progression (or death) and a composite clinical outcome (progression of CKD, ESRD, or death) depends on level of GFR. Multivariate Cox regression was used to control for other baseline risk factors. Results After controlling for baseline risk factors, only proteinuria was more closely associated with the composite clinical outcome at lower levels of GFR (P value for interaction term=0.002); increased hazards of the clinical composite outcome associated with a doubling of proteinuria ranged from 30% (95% confidence interval=21%–39%) with a GFR of 50 to 55% (95% confidence interval=40%–72%) with a GFR of 25. Conclusions The magnitude of the association between proteinuria and CKD progression, ESRD, or death in the African American Study of Kidney Disease Trial cohort depends on the level of GFR; proteinuria is a stronger independent predictor of the composite clinical outcome at lower levels of GFR. This finding reinforces that African Americans with proteinuria and lower GFR represent a population at particularly high risk for adverse outcomes.
Flash Fire Propensity of Some Upholstery Fabrics With and Without Backcoating

Evaluation of eighteen upholstery fabrics provided by the California Bureau of Home Furnishings, using the USF flash fire screening test method, indicated that these materials as a group did not exhibit greater flash fire propensity than other materials which could be found in the home.
Evidence for a Common Intermediate in Insulin Deamidation and Covalent Dimer Formation: Effects of pH and Aniline Trapping in Dilute Acidic Solutions

The effects of pH and aniline trapping on the partitioning of the A-21 cyclic anhydride intermediate of human insulin into deamidated insulin and covalent dimer were investigated at low pH and 35 degrees C. Characterization of the covalent dimer was achieved by proteolytic cleavage and electrospray mass spectrometry and indicated that the deamidated A-21 asparagine of one insulin molecule and the B-1 phenylalanine residue of another are involved. Anhydride trapping with aniline at pH 4.0 provided evidence that the rate-limiting generation of a cyclic anhydride intermediate is involved in the formation of both deamidated and dimeric insulin. In the presence of aniline at pH 4.0 insulin formed two anilide products, A-21 N delta 2-phenylasparagine and N delta 2-phenylasparagine and N gamma 2-phenylaspartic acid human insulin at the expense of both desamido A-21 and covalent dimer formation, consistent with the formation of a common intermediate. At 35 degrees C and under conditions where the insulin monomer predominates, the fraction of insulin reacting to form [desamidoA-21] insulin decreased with a concurrent increase in formation of [desamidoA-21-PheB-1] dimer with an increase in pH from 2.0 to 5.0. The pH dependence of insulin product distribution could not be quantitatively rationalized solely in terms of the fraction of the PheB-1 amine group in un-ionized form. Rather, consideration of the charge states of ionizable residues near the reacting groups was necessary to fully account for the observed pH effects on product formation.
Characterization of waste rock associated with acid drainage at the Penn Mine, California, by ground-based visible to short-wave infrared reflectance spectroscopy assisted by digital mapping

Prior to remediation at the abandoned Cu–Zn Penn Mine in the Foothills massive sulfide belt of the Sierra Nevada, CA, acid mine drainage (AMD) was created, in part, by the subaerial oxidation of sulfides exposed on several waste piles. To support remediation efforts, a mineralogical study of the waste piles was undertaken by acquiring reflectance spectra (measured in the visible to short-wave infrared range of light (0.35–2.5 Am) using a portable, digitally integrated pen tablet PC mapping system with differential global positioning system and laser rangefinder support. Analysis of the spectral data made use of a continuum removal and band-shape comparison method, and of reference spectral libraries of end-member minerals and mineral mixtures. Identification of secondary Fe-bearing minerals focused on band matching in the region between 0.43 and 1.3 Am. Identification of sheet and other silicates was based on band-shape analysis in the region between 1.9 and 2.4 Am. Analysis of reflectance spectra of characterized rock samples from the mine helped in gauging the spectral response to particle size and mixtures. The resulting mineral maps delineated a pattern of accumulation of secondary Fe minerals, wherein centers of copiapite and jarosite that formed at low pH (b3) were surrounded successively by goethite and hematite, which mark progressive increases in pH. This pattern represents the evolution of acid solutions discharged from the pyritic waste piles and the subsequent accumulation of secondary precipitates by hydrolysis reactions. The results highlight the high capacity of the pyritic waste to release further acid mine drainage into the environment, as well as the effectiveness of the mapping method to detect subtle changes in surface mineralogy and to produce maps useful to agencies responsible for remediating the site. D 2004 Elsevier B.V. All rights reserved.
The AProS Project: Strategic Thinking & Computational Logic

The paper discusses tools for teaching logic used in Logic & Proofs, a web-based introduction to modern logic that has been taken by more than 1,300 students since the fall of 2003. The tools include a wide array of interactive learning environments or cognitive mini-tutors; most important among them is the Carnegie Proof Lab. The Proof Lab is a sophisticated interface for constructing natural deduction proofs and is central, as strategically guided discovery of proofs is the distinctive focus of the course. My discussion makes explicit the broader intellectual context, but also the pursuit of pedagogical goals and their experimental examination. The intellectual context includes i) the theoretical background for the proof search algorithm AProS and its use for a dynamic Proof Tutor, and ii) the programmatic expansion of the course to Computational Logic. (I recommend that the reader enter the virtual classroom of Logic & Proofs: the interactive components just cannot be properly reflected in a narrative. It is also very easy to download AProS and observe its ways of searching for proofs.) 1
Associations between infectious bovine keratoconjunctivitis at weaning and ultrasongraphically measured body composition traits in yearling cattle

Objective—To assess associations between infectious bovine keratoconjunctivitis (IBK) diagnosed at weaning and production traits in yearling beef calves. Design—Retrospective population-based cohort study. Animals—1,882 Angus calves. Procedures—Angus calves from 1 farm were evaluated over 7 years. The association between yearling body production traits and detection of IBK lesions at weaning was evaluated. Results—Yearlings that had evidence of IBK at weaning had less 12th rib fat depth, ribeye area, and body weight than did cohorts without evidence of IBK. Average daily gain was greater in cattle that had IBK lesions at weaning, but this did not offset lower body weight at weaning. Conclusions and Clinical Relevance—The associations between IBK at weaning and production variables persisted well into the postweaning period, and there appeared to be a relationship between decreased body composition traits at yearling evaluation and IBK infection before weaning.
Does Photosensitivity Predict Photococarcinogenicity

Assessment of short-term and long-term effects of light (pho—totesting) is part of the safety evaluation of drugs. Results are incorporated into drug package inserts to advise patients and health care providers about the use of drug products on sun—exposed skin. We undertook an exhaustive literature search and a search of archived studies at the Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), in order to evaluate the potential of short—term photoassays to predict long—term effects of drugs used in sunlight (280–700 nm). The correlation between the findings from the photococarcinogenicity assays in mice that used exposure to simulated sunlight and those from photogenotoxicity and photosensitivity studies was examined. Results indicated that photosensitivity and photogenotoxicity assays did not necessarily predict effects in photococarcinogenicity studies in mice. Effects of drugs on skin that are not due to photoactivation of drug can be important factors in enhancement ...
Attribution Theory: A Fit with Substance Abuse Problems

How substance-abusing individuals early and late in treatment explain the problem behavior of other substance abusers is analyzed in attributional terms. Alcoholism was chosen as the problem of interest. Subjects were 42 male alcoholics newly enrolled in a treatment program, 41 male alcoholics nearing the completion of the program, and 46 male nonalcoholic controls. All subjects viewed a videotape interview with an actor who was identified as an alcoholic or not identified. As predicted, early-treatment alcoholics made greater situational attributions to the "alcoholic" and greater dispositional attributions to the "nonalcoholic" actor in comparison to the late-treatment alcoholics and controls. Early-treatment alcoholics, more than late-treatment alcoholics or controls, rated the actor labeled as alcoholic to be more similar to themselves. Discussion focuses on the applicability of attribution theory to problems of substance abuse.