Integrating Events Across Levels of Consciousness

Our knowledge grows as we integrate events experienced at different points in time. We may or may not become aware of events, their integration, and their impact on our knowledge and decisions. But can we mentally integrate two events, if they are experienced at different time points and at different levels of consciousness? In this study, an event consisted of the presentation of two unrelated words. In the stream of events, half of events shared one component ("tree desk" … "desk fish") to facilitate event integration. We manipulated the amount of time and trials that separated two corresponding events. The contents of one event were presented subliminally (invisible) and the contents of the corresponding overlapping event supraliminally (visible). Hence, event integration required the binding of contents between consciousness levels and between time points. At the final test of integration, participants judged whether two supraliminal test words ("tree fish") fit together semantically or not. Unbeknown to participants, half of test words were episodically related through an overlap ("desk"; experimental condition) and half were not (control condition). Participants judged episodically related test words to be closer semantically than unrelated test words. This subjective decrease in the semantic distance between test words was both independent of whether the invisible event was encoded first or second in order and independent of the number of trials and the time that separated two corresponding events. Hence, conscious and unconscious memories were mentally integrated into a linked mnemonic representation.

Sizing up your enemy: individual predation vulnerability predicts migratory probability

Partial migration, in which a fraction of a population migrate and the rest remain resident, occurs in an extensive range of species and can have powerful ecological consequences. The question of what drives differences in individual migratory tendency is a contentious one. It has been shown that the timing of partial migration is based upon a trade-off between seasonal fluctuations in predation risk and growth potential. Phenotypic variation in either individual predation risk or growth potential should thus mediate the strength of the trade-off and ultimately predict patterns of partial migration at the individual level (i.e. which individuals migrate and which remain resident). We provide cross-population empirical support for the importance of one component of this model—individual predation risk—in predicting partial migration in wild populations of bream Abramis brama, a freshwater fish. Smaller, high-risk individuals migrate with a higher probability than larger, low-risk individuals, and we suggest that predation risk maintains size-dependent partial migration in this system.

An 'Ideal' Decomposition of Industry Dynamics: An Application to the Nationwide and State Level U.S. Banking Industry

This paper considers the aggregate performance of the banking industry, applying a modified and extended dynamic decomposition of bank return on equity. The aggregate performance of any industry depends on the underlying microeconomic dynamics within that industry . adjustments within banks, reallocations between banks, entry of new banks, and exit of existing banks. Bailey, Hulten, and Campbell (1992) and Haltiwanger (1997) develop dynamic decompositions of industry performance. We extend those analyses to derive an ideal decomposition that includes their decomposition as one component. We also extend the decomposition, consider geography, and implement decomposition on a state-by-state basis, linking that geographic decomposition back to the national level. We then consider how deregulation of geographic restrictions on bank activity affects the components of the state-level dynamic decomposition, controlling for competition and the state of the economy within each state and employing fixed- and random-effects estimation for a panel database across the fifty states and the District of Columbia from 1976 to 2000.

An 'Ideal' Deconposition of Industry Dynamics: An Application to the Nationwide and State Level U.S. Banking Industry

This paper considers the aggregate performance of the banking industry, applying a modified and extended dynamic decomposition of bank return on equity. The aggregate performance of any industry depends on the underlying microeconomic dynamics within that industry --- adjustments within banks, reallocations between banks, entry of new banks, and exit of existing banks. Bailey, Hulten, and Campbell (1992) and Haltiwanger (1997) develop dynamic decompositions of industry performance. We extend those analyses to derive an ideal dynamic decomposition that includes their dynamic decomposition as one component. We also extend the decomposition, consider geography, and implement decomposition on a state-by-state basis, linking that geographic decomposition back to the national level. We then consider how deregulation of geographic restrictions on bank activity affects the components of the state-level dynamic decomposition, controlling for competition and the state of the economy within each state and employing fixed- and random-effects estimation for a panel database across the fifty states and the District of Columbia from 1976 to 2000.

Role of telomere dysfunction, DNA damage response and p53 mutations in tumorigenesis and aging

The ends of eukaryotic chromosomes are protected by specialized ribonucleoprotein structures termed telomeres. Telomeres protect chromosomes from end-to-end fusions, inappropriate repair and degradation. Disruption of this complex activates an ATM/ATR DNA damage response (DDR) pathway. One component of the complex is the Protection Of Telomeres 1 (POT1) protein, an evolutionarily conserved protein which binds single-stranded 3' overhang and is required for both chromosomal end protection and telomere length regulation. The mouse contains two POT1 orthologs, Pot1a and Pot1b. Here we show that both proteins colocalize with telomeres through interaction with the adapter protein TPP1. In addition, compared to Pot1a, the OB-folds of Pot1b possess less sequence specificity for telomeres. Disruption of POT1 proteins result in telomere dysfunction and activation of an ATR-dependent DDR at telomeres, suggesting that this response is normally suppressed by POT1 binding to the single-stranded G-overhang. ^ Telomeres are maintained by telomerase, and its absence in somatic cells results in telomere progressive loss that triggers the activation of p53. Telomere dysfunction initiates genomic instability and induces both p53-dependent replicative senescence and apoptosis to suppress tumorigenesis. In the absence of functional p53, this genomic instability promotes cancer. It was previously not known which aspect of the p53 dependent DNA damage response is important to suppress tumorigenesis initiated by dysfunctional telomeres. The p53R172P knock-in mouse, which is unable to induce apoptosis but retains intact cell cycle arrest/cellular senescence pathways, allowed us to examine whether p53-dependent apoptosis is a major tumor suppression pathway initiated in the setting of telomere dysfunction. Spontaneous tumorigenesis remains potently suppressed in late generation telomerase null mice possessing the p53P/P mutation. These results suggest that suppression of spontaneous tumorigenesis initiated by dysfunctional telomeres requires activation of a p53-dependent senescence pathway. In addition, we used another knock-in mouse model with a p53R172H (p53H) point mutation to test the hypothesis that telomere dysfunction promotes chromosomal instability and accelerates the onset of tumorigenesis in vivo in the setting of this most common gain-of-function mutation in the human Li Fraumeni cancer syndrome. We unexpectedly observed that telomerase null mice possessing dysfunctional telomeres in the setting of the p53H/+ mutation develop significantly fewer tumors, die prematurely and exhibit higher level of cellular senescence, apoptosis and elevated genomic instability compared to telomerase intact p53H/+ and telomerase null p53+/+ mice. These contrasting results thus link cancer and aging to the functional status of telomeres and the integrity of the p53 pathway. ^

A review of the Malaria Chemoprophylaxis Compliance Program at ExxonMobil Corporation

ExxonMobil, a Fortune 500 oil and gas corporation, has a global workforce with employees assigned to projects in areas at risk for infectious diseases, particularly malaria. As such, the corporation has put in place a program to protect the health of workers and ensure their safety in malaria endemic zones. This program is called the Malaria Control Program (MCP). One component of this program is the more specific Malaria Chemoprophylaxis Compliance Program (MCCP), in which employees enroll following consent to random drug testing for compliance with the company's chemoprophylaxis requirements. Each year, data is gathered on the number of employees working in these locations and are selected randomly and tested for chemoprophylaxis compliance. The selection strives to test each eligible worker once per year. Test results that come back positive for the chemoprophylaxis drug are considered "detects" and tests that are negative for the drug and therefore show the worker is non-compliant at risk for severe malaria infection are considered "non-detect". ^ The current practice report used aggregate data to calculate statistics on test results to reflect compliance among both employees and contractors in various malaria-endemic areas. This aggregate, non-individualized data has been compiled and reflects the effectiveness and reach of ExxonMobil's Malaria Chemoprophylaxis Compliance Program. In order to assess compliance, information on the number of non-detect test results was compared to the number of tests completed per year. The data shows that over time, non-detect results have declined in both employee and contractor populations, and vary somewhat by location due to size and scope of the MCCP implemented in-country. Although the data indicate a positive trend for the corporation, some recommendations have been made for future implementation of the program.^

Geochemistry and isotopic ratios of boninites and related rocks of the Izu-Bonin Forearc

Twenty-six samples representing the wide range of lithologies (low- and intermediate-Ca boninites and bronzite andesites, high-Ca boninites, basaltic andesites-rhyolites) drilled during Leg 125 at Sites 782 and 786 on the Izu-Bonin outer-arc high have been analyzed for Sr, Nd, and Pb isotopes. Nd-Sr isotope covariations show that most samples follow a trend parallel to a line from Pacific MORB mantle (PMM) to Pacific Volcanogenic sediment (PVS) but displaced slightly toward more radiogenic Sr. Pb isotope covariations show that all the Eocene-Oligocene samples plot along the Northern Hemisphere Reference Line, indicating little or no Pb derived from subducted pelagic sediment in their source. Two young basaltic andesite clasts within sediment do have a pelagic sediment signature but this may have been gained by alteration rather than subduction. In all isotopic projections, the samples form consistent groupings: the tholeiites from Site 782 and Hole 786A plot closest to PMM, the boninites and related rocks from Sites 786B plot closest to PVS, and the boninite lavas from Hole 786A and late boninitic dikes from Hole 786B occupy an intermediate position. Isotope-trace element covariations indicate that these isotopic variations can be explained by a three-component mixing model. One component (A) has the isotopic signature of PMM but is depleted in the more incompatible elements. It is interpreted as representing suboceanic mantle lithosphere. A second component (B) is relatively radiogenic (epsilon-Nd = ca 4-6; 206Pb/204Pb = ca 19.0-19.3; epsilon-Sr = ca -10 to -6)). Its trace element pattern has, among other characteristics, a high Zr/Sm ratio, which distinguishes it from the ìnormalî fluid components associated with subduction and hotspot activity. There are insufficient data at present to tie down its origin: probably it was either derived from subducted lithosphere or volcanogenic sediment fused in amphibolite facies; or it represents an asthenospheric melt component that has been fractionated by interaction with amphibole-bearing mantle. The third component (C) is characterized by high contents of Sr and high epsilon-Sr values and is interpreted as a subducted fluid component. The mixing line on a diagram of Zr/Sr against epsilon-Sr suggests that component C may have enriched the lithosphere (component A) before component B. These components may also be present on a regional basis but, if so, may not have had uniform compositions. Only the boninitic series from nearby Chichijima would require an additional, pelagic sediment component. In general, these results are consistent with models of subduction of ridges and young lithosphere during the change from a ridge-transform to subduction geometry at the initiation of subduction in the Western Pacific.

Predicting academic performance with learning analytics in virtual learning environments: A comparative study of three interaction classifications

Learning analytics is the analysis of static and dynamic data extracted from virtual learning environments, in order to understand and optimize the learning process. Generally, this dynamic data is generated by the interactions which take place in the virtual learning environment. At the present time, many implementations for grouping of data have been proposed, but there is no consensus yet on which interactions and groups must be measured and analyzed. There is also no agreement on what is the influence of these interactions, if any, on learning outcomes, academic performance or student success. This study presents three different extant interaction typologies in e-learning and analyzes the relation of their components with students? academic performance. The three different classifications are based on the agents involved in the learning process, the frequency of use and the participation mode, respectively. The main findings from the research are: a) that agent-based classifications offer a better explanation of student academic performance; b) that at least one component in each typology predicts academic performance; and c) that student-teacher and student-student, evaluating students, and active interactions, respectively, have a significant impact on academic performance, while the other interaction types are not significantly related to academic performance.

Sostenibilidad en el sector de la construcción. Sostenibilidad en estructuras y puentes ferroviarios

La escasez de recursos, el cambio climático, la pobreza y el subdesarrollo, los desastres naturales, son solo algunos de los grandes retos a que se enfrenta la humanidad y a los que la economía verde y el desarrollo sostenible tienen que dar respuesta. El concepto sostenible surge a raíz de la necesidad de lograr en todas las actividades humanas un nuevo equilibrio con el medioambiente, la sociedad y la economía, es decir un desarrollo más sostenible. La construcción supone en este nuevo concepto un sector básico, con grandes impactos en los recursos, los residuos, las emisiones, la biodiversidad, el paisaje, las necesidades sociales, la integración, el desarrollo económico del entorno, etc. Es por ello, que la construcción sostenible tiene una importancia esencial como demuestra su amplia aplicación teórica y práctica ya en proyectos de planificación urbana y de edificación. En la ingeniería civil estas aproximaciones son todavía mínimas, aunque ya se están considerando ciertos criterios de sostenibilidad en proyectos de construcción. La construcción consume muchos recursos naturales, económicos y tiene gran incidencia social. En la actualidad su actividad consume un 30% de los recursos extraídos de la tierra y la energía, y en consecuencia genera el 30% de los gases de efecto invernadero y residuos sólidos del mundo (EEA, 2014). Este impacto debería suponer una gran responsabilidad para los profesionales y gobiernos que toman cada día las decisiones de diseño e inversión en la construcción, y su máxima eficiencia debería estar muy presente entre los objetivos. En esta tesis doctoral se plantea un nuevo modelo para la evaluación de la sostenibilidad en los proyectos mediante un sistema de indicadores, basados en las áreas de estudio de las certificaciones de sostenibilidad existentes y en un análisis multi-criterio de cada uno de los axiomas de la sostenibilidad. Como reto principal se marca la propuesta de una metodología que permita identificar, priorizar y seleccionar los indicadores y las variables más importantes de lo que es considerado como una construcción sostenible en el caso de infraestructuras ferroviarias, más concretamente en puentes ferroviarios, y que además sirva para priorizar nuevos proyectos que se adapten a los nuevos objetivos del desarrollo sostenible: el respeto al medioambiente, la integración social y la económica. El objetivo es la aplicación de estos indicadores desde las etapas más tempranas del proyecto: planificación, diseño de alternativas y selección de alternativas. Para ello, en primer lugar, se ha realizado un análisis en profundidad de los distintas organizaciones de certificación de la sostenibilidad mundiales y se ha desarrollado una comparativa entre ellas, detallando el funcionamiento de las más extendidas (BREEAM, LEED, VERDE, DGNB). Tras esto, se ha analizado la herramienta matemática MIVES de análisis multi-criterio para su aplicación, en la tesis, a las infraestructuras ferroviarias. En la segunda parte se desarrolla para las estructuras ferroviarias un nuevo modelo de indicadores, un sistema de ayuda a la decisión multi-criterio basado en los tres axiomas de las sostenibilidad (sociedad, medioambiente y economía), articulados en un árbol de requerimientos inspirado en el método MIVES, que propone una metodología para el caso de las infraestructuras ferroviarias. La metodología MIVES estructura el proceso de decisión en tres ramas: Requisitos, componentes y ciclo de vida. Estas ramas definen los límites de los sistemas. El eje de los requisitos del árbol de los requisitos o se estructura en tres niveles que corresponden al requisito específico: criterios e indicadores. Además, es necesario definen la función del valor para cada indicador, definen el peso de importancia de cada elemento del árbol y finalmente con el calcular el valor de cada alternativa selecciona el mejor de él. La generación de este árbol de requerimientos en estructuras ferroviarias y la medición de los parámetro es original para este tipo de estructuras. Por último, tras el desarrollo de la metodología, se ha aplicado la propuesta metodológica mediante la implementación práctica, utilizando el método propuesto con 2 puentes ferroviarios existentes. Los resultados han mostrado que la herramienta es capaz de establecer una ordenación de las actuaciones coherente y suficientemente discriminante como para que el decisor no tenga dudas cuando deba tomar la decisión. Esta fase, es una de las grandes aportaciones de la tesis, ya que permite diferenciar los pesos obtenidos en cada una de las áreas de estudio y donde la toma de decisión puede variar dependiendo de las necesidades del decisor, la ubicación del puente de estudio etc. ABSTRACT Scarce resources, climate change, poverty and underdevelopment, natural disasters are just some of the great challenges facing humanity and to which the green economy will have to respond. The sustainable concept arises from the need for all human activities in a new equilibrium with the environment, society and the economy, which is known as sustainable development. The construction industry is part of this concept, because of its major impacts on resources, waste, emissions, biodiversity, landscape, social needs, integration, economical development, environment, etc. Therefore, sustainable construction has a critical importance as already demonstrated by its wide application and theoretical practice in urban planning and building projects. In civil engineering, these approaches are still minimal, although some criteria are already taken into account for sustainability in infrastructure projects. The construction industry requires a lot of natural resources, has a real economic relevance and a huge social impact. Currently, it consumes 40% of produced power as well as natural resources extracted from the earth and thus leads to an environmental impact of 40% regarding greenhouse gas emissions and solid wastes (EEA 2014). These repercussions should highly concern our governments and professional of this industry on the decisions they take regarding investments and designs. They must be inflexible in order to ensure that the main concern has to be a maximum efficiency. Major events like the COP21 held in Paris in December 2015 are a concrete signal of the worldwide awareness of the huge impact of each industry on climate. In this doctoral thesis a new model for the evaluation of the sustainability in the projects by means of a system of indicators, based on the areas of study of the existing certifications of sustainability and on an analysis considers multi-criterion of each one of the axioms of the sustainability. The primary aim of this thesis is to study the mode of application of sustainability in projects through a system of indicators. . The main challenge consists of create a methodology suitable to identify, prioritize and select the most important indicators which define if a building is sustainable in the specific case of railway infrastructures. The methodology will help to adapt future projects to the new goals of sustainable development which are respect of nature, social integration and economic relevance. A crucial point is the consideration of these indicators from the very beginning steps of the projects: planning, design and alternatives reflections. First of all, a complete inventory of all world energy certification organizations has been made in order to compare the most representative ones regarding their way of functioning (BREEAM, LEED, VERDE, DGNB). After this, mathematical tool MIVES of analysis has been analyzed multi-criterion for its application, in the thesis, to railway infrastructures. The second part of the thesis is aimed to develop a new model of indicators, inspired by the MIVES method, consisting in a decision-making system based on the 3 foundations of sustainability: nature impact, social concerns, and economic relevance. The methodology MIVES structures the decision process in three axes: Requirements, components and life cycle. These axes define the boundaries of the systems. The axis of requirements o tree requirements is structured in three levels corresponding to specific requirement: criteria and indicators. In addition, is necessary define the value function for each indicator, define the weight of importance of each element of the tree and finally with the calculate the value of each alternative select the best of them. The generation of this tree requirements in railway structures and measuring the parameter is original for this type of structures. Finally, after the development of the methodology, it has validated the methodology through practical implementation, applying the proposed method 2 existing railway bridges. The results showed that the tool is able to establish a coherent management of performances and discriminating enough so that the decision maker should not have doubts when making the decision. This phase, is one of the great contributions of the thesis, since it allows to differentiate the weights obtained in each one from the study areas and where the decision making can vary depending on the necessities of the decisor, the location of the bridge of study etc.

Pro-phenol oxidase activating proteinase from an insect, Manduca sexta: A bacteria-inducible protein similar to Drosophila easter

Activation of pro-phenol oxidase (proPO) in insects and crustaceans is important in defense against wounding and infection. The proPO zymogen is activated by a specific proteolytic cleavage. PO oxidizes phenolic compounds to produce quinones, which may help to kill pathogens and can also be used for synthesis of melanin to seal wounds and encapsulate parasites. We have isolated from the tobacco hornworm, Manduca sexta, a serine proteinase that activates proPO, and have cloned its cDNA. The isolated proPO activating proteinase (PAP) hydrolyzed artificial substrates but required other protein factors for proPO activation, suggesting that proPO-activating enzyme may exist as a protein complex, one component of which is PAP. PAP (44 kDa) is composed of two disulfide-linked polypeptide chains (31 kDa and 13 kDa). A cDNA for PAP was isolated from a hemocyte library, by using a PCR-generated probe based on the amino-terminal amino acid sequence of the 31-kDa catalytic domain. PAP belongs to a family of arthropod serine proteinases containing a carboxyl-terminal proteinase domain and an amino-terminal “clip” domain. The member of this family most similar in sequence to PAP is the product of the easter gene from Drosophila melanogaster. PAP mRNA was present at a low level in larval hemocytes and fat body, but became much more abundant in fat body after insects were injected with Escherichia coli. Sequence data and 3H-diisopropyl fluorphosphate labeling results suggest that the same PAP exists in hemolymph and cuticle.

A repressible female-specific lethal genetic system for making transgenic insect strains suitable for a sterile-release program

We have developed a tetracycline-repressible female-specific lethal genetic system in the vinegar fly Drosophila melanogaster. One component of the system is the tetracycline-controlled transactivator gene under the control of the fat body and female-specific transcription enhancer from the yolk protein 1 gene. The other component consists of the proapoptotic gene hid under the control of a tetracycline-responsive element. Males and females of a strain carrying both components are viable on medium supplemented with tetracycline, but only males survive on normal medium. A strain with such properties would be ideal for a sterile-insect release program, which is most effective when only males are released in the field.

The Arp2/3 complex mediates actin polymerization induced by the small GTP-binding protein Cdc42

The small GTP-binding protein Cdc42 is thought to induce filopodium formation by regulating actin polymerization at the cell cortex. Although several Cdc42-binding proteins have been identified and some of them have been implicated in filopodium formation, the precise role of Cdc42 in modulating actin polymerization has not been defined. To understand the biochemical pathways that link Cdc42 to the actin cytoskeleton, we have reconstituted Cdc42-induced actin polymerization in Xenopus egg extracts. Using this cell-free system, we have developed a rapid and specific assay that has allowed us to fractionate the extract and isolate factors involved in this activity. We report here that at least two biochemically distinct components are required, based on their chromatographic behavior and affinity for Cdc42. One component is purified to homogeneity and is identified as the Arp2/3 complex, a protein complex that has been shown to nucleate actin polymerization. However, the purified complex alone is not sufficient to mediate the activity; a second component that binds Cdc42 directly and mediates the interaction between Cdc42 and the complex also is required. These results establish an important link between a signaling molecule, Cdc42, and a complex that can directly modulate actin networks in vitro. We propose that activation of the Arp2/3 complex by Cdc42 and other signaling molecules plays a central role in stimulating actin polymerization at the cell surface.

Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia

Ischemic stroke is the most common life-threatening neurological disease and has limited therapeutic options. One component of ischemic neuronal death is inflammation. Here we show that doxycycline and minocycline, which are broad-spectrum antibiotics and have antiinflammatory effects independent of their antimicrobial activity, protect hippocampal neurons against global ischemia in gerbils. Minocycline increased the survival of CA1 pyramidal neurons from 10.5% to 77% when the treatment was started 12 h before ischemia and to 71% when the treatment was started 30 min after ischemia. The survival with corresponding pre- and posttreatment with doxycycline was 57% and 47%, respectively. Minocycline prevented completely the ischemia-induced activation of microglia and the appearance of NADPH-diaphorase reactive cells, but did not affect induction of glial acidic fibrillary protein, a marker of astrogliosis. Minocycline treatment for 4 days resulted in a 70% reduction in mRNA induction of interleukin-1β-converting enzyme, a caspase that is induced in microglia after ischemia. Likewise, expression of inducible nitric oxide synthase mRNA was attenuated by 30% in minocycline-treated animals. Our results suggest that lipid-soluble tetracyclines, doxycycline and minocycline, inhibit inflammation and are neuroprotective against ischemic stroke, even when administered after the insult. Tetracycline derivatives may have a potential use also as antiischemic compounds in humans.

Suppression of ras-mediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways

Lethal factor is a protease, one component of Bacillus anthracis exotoxin, which cleaves many of the mitogen-activated protein kinase kinases (MEKs). Given the importance of MEK signaling in tumorigenesis, we assessed the effects of anthrax lethal toxin (LeTx) on tumor cells. LeTx was very effective in inhibiting mitogen-activated protein kinase activation in V12 H-ras-transformed NIH 3T3 cells. In vitro, treatment of transformed cells with LeTx caused them to revert to a nontransformed morphology, and inhibited their abilities to form colonies in soft agar and to invade Matrigel without markedly affecting cell proliferation. In vivo, LeTx inhibited growth of ras-transformed cells implanted in athymic nude mice (in some cases causing tumor regression) at concentrations that caused no apparent animal toxicity. Unexpectedly, LeTx also greatly decreased tumor neovascularization. These results demonstrate that LeTx potently inhibits ras-mediated tumor growth and is a potential antitumor therapeutic.

Components of verbal working memory: Evidence from neuroimaging

We review research on the neural bases of verbal working memory, focusing on human neuroimaging studies. We first consider experiments that indicate that verbal working memory is composed of multiple components. One component involves the subvocal rehearsal of phonological information and is neurally implemented by left-hemisphere speech areas, including Broca’s area, the premotor area, and the supplementary motor area. Other components of verbal working memory may be devoted to pure storage and to executive processing of the contents of memory. These studies rest on a subtraction logic, in which two tasks are imaged, differing only in that one task presumably has an extra process, and the difference image is taken to reflect that process. We then review studies that show that the previous results can be obtained with experimental methods other than subtraction. We focus on the method of parametric variation, in which a parameter that presumably reflects a single process is varied. In the last section, we consider the distinction between working memory tasks that require only storage of information vs. those that require that the stored items be processed in some way. These experiments provide some support for the hypothesis that, when a task requires processing the contents of working memory, the dorsolateral prefrontal cortex is disproportionately activated.