Crystal structure of the catalytic domain of Pseudomonas exotoxin A complexed with a nicotinamide adenine dinucleotide analog: implications for the activation process and for ADP ribosylation.

The catalytic, or third domain of Pseudomonas exotoxin A (PEIII) catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, inhibiting protein synthesis. We have determined the structure of PEIII crystallized in the presence of NAD to define the site of binding and mechanism of activation. However, NAD undergoes a slow hydrolysis and the crystal structure revealed only the hydrolysis products, AMP and nicotinamide, bound to the enzyme. To better define the site of NAD binding, we have now crystallized PEIII in the presence of a less hydrolyzable NAD analog, beta-methylene-thiazole-4-carboxamide adenine dinucleotide (beta-TAD), and refined the complex structure at 2.3 angstroms resolution. There are two independent molecules of PEIII in the crystal, and the conformations of beta-TAD show some differences in the two binding sites. The beta-TAD attached to molecule 2 appears to have been hydrolyzed between the pyrophosphate and the nicotinamide ribose. However molecule 1 binds to an intact beta-TAD and has no crystal packing contacts in the vicinity of the binding site, so that the observed conformation and interaction with the PEIII most likely resembles that of NAD bound to PEIII in solution. We have compared this complex with the catalytic domains of diphtheria toxin, heat labile enterotoxin, and pertussis toxin, all three of which it closely resembles.

D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release.

Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D-serine immunoreactivity correlate closely with those of D-serine binding to the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor as visualized by autoradiography and are inversely correlated to the presence of D-amino acid oxidase. D-Serine is enriched in process-bearing glial cells in neuropil with the morphology of protoplasmic astrocytes. In glial cultures of rat cerebral cortex, D-serine is enriched in type 2 astrocytes. The release of D-serine from these cultures is stimulated by agonists of non-NMDA glutamate receptors, suggesting a mechanism by which astrocyte-derived D-serine could modulate neurotransmission. D-Serine appears to be the endogenous ligand for the glycine site of NMDA receptors.

Infrared microspectroscopy of inflammatory process and colon tumors.

According to the last global burden of disease published by the World Health Organization, tumors were the third leading cause of death worldwide in 2004. Among the different types of tumors, colorectal cancer ranks as the fourth most lethal. To date, tumor diagnosis is based mainly on the identification of morphological changes in tissues. Considering that these changes appears after many biochemical reactions, the development of vibrational techniques may contribute to the early detection of tumors, since they are able to detect such reactions. The present study aimed to develop a methodology based on infrared microspectroscopy to characterize colon samples, providing complementary information to the pathologist and facilitating the early diagnosis of tumors. The study groups were composed by human colon samples obtained from paraffin-embedded biopsies. The groups are divided in normal (n=20), inflammation (n=17) and tumor (n=18). Two adjacent slices were acquired from each block. The first one was subjected to chemical dewaxing and H&E staining. The infrared imaging was performed on the second slice, which was not dewaxed or stained. A computational preprocessing methodology was employed to identify the paraffin in the images and to perform spectral baseline correction. Such methodology was adapted to include two types of spectral quality control. Afterwards the preprocessing step, spectra belonging to the same image were analyzed and grouped according to their biochemical similarities. One pathologist associated each obtained group with some histological structure based on the H&E stained slice. Such analysis highlighted the biochemical differences between the three studied groups. Results showed that severe inflammation presents biochemical features similar to the tumors ones, indicating that tumors can develop from inflammatory process. A spectral database was constructed containing the biochemical information identified in the previous step. Spectra obtained from new samples were confronted with the database information, leading to their classification into one of the three groups: normal, inflammation or tumor. Internal and external validation were performed based on the classification sensitivity, specificity and accuracy. Comparison between the classification results and H&E stained sections revealed some discrepancies. Some regions histologically normal were identified as inflammation by the classification algorithm. Similarly, some regions presenting inflammatory lesions in the stained section were classified into the tumor group. Such differences were considered as misclassification, but they may actually evidence that biochemical changes are in course in the analyzed sample. In the latter case, the method developed throughout this thesis would have proved able to identify early stages of inflammatory and tumor lesions. It is necessary to perform additional experiments to elucidate this discrepancy between the classification results and the morphological features. One solution would be the use of immunohistochemistry techniques with specific markers for tumor and inflammation. Another option includes the recovering of the medical records of patients who participated in this study in order to check, in later times to the biopsy collection, whether they actually developed the lesions supposedly detected in this research.

Accounts related to maps and pamphlets, 1809-1823

This folder contains eight handwritten account statements and notes primarily related to the collection of subscriptions for Croswell's maps and pamphlets, as well as the disbursement and storage of his printed maps and pamphlets.

Comparative regional perspectives: the Bologna process and higher education attainment. Jean Monnet/Robert Schumann Paper Series Vol 13 No. 11, August 2013

Since 1999, countries have voluntarily chosen to reform their higher education systems to join the European Higher Education Area. This paper compares Bologna Process implementation across four regions within the European Union. While there are 47 countries participating in the Bologna Process, this paper uses statistical analysis to consider 25 of the 28 EU Member States. The time period of analysis is 2000-2011, prior to Croatia’s accession to the EU on 1 July 2013. Across Europe there are inter-regional differences in how the Bologna Process has been implemented and in the political economy contexts that influence higher education reform for policy convergence. There are three explanatory variables in the political economy context: 1. competitive economic pressures and globalization 2. domestic politics at the national level 3. leadership from the supranational European Union that socially constructs regional norms Tertiary education attainment is the dependent variable of interest in this research. The objective of 40%, for 30-34 year olds, is Europe 2020 benchmark target. There are additional higher education reform criteria encompassed in the Bologna Process. These criteria concern Credit and Degree Structure, Quality Assurance, and Recognition of academic degrees among countries in the EHEA. This tertiary education attainment variable, which is of interest in this paper, does not capture the entire implementation process. Nevertheless, it is a measure of one important indicator of success in providing higher education access to populations within the context of democratic governance. This research finds that statistically GDP Per Capita is the most significant variable in relationship to tertiary education attainment across four regional areas in the European Union.

The Potential Evolution of the European Energy System to 2020 and 2050. CEPS Working Document No. 392, 26 March 2014

This paper assesses the impact of decarbonisation of the energy sector on employment in Europe. Setting the stage for such an assessment, the paper provides an analysis of possible pathways to decarbonise Europe’s energy system, taking into account EU greenhouse gas emissions reduction targets for 2020 and 2050. It pays particular attention to various low-carbon technologies that could be deployed in different regions of the EU. It concludes that efficiency and renewables play a major role in any decarbonisation scenario and that the power sector is the main enabler for the transition to a low-carbon economy in Europe, despite rising electricity demand. The extent of the decline in the share of fossil fuels will largely depend on the existence of carbon capture and storage (CCS), which remains a major source of uncertainty.

Hegemony Without Stability: The fiscal and political vulnerabilities of monetary union. ACES Cases No. 2011.2

The crisis has forced the Euro area to establish an emergency fund that supports member states experiencing a sovereign debt crisis. The difficulties of coming up with such a fund for Greece and other Euro area members stands in marked contrast to the balance of payments support that non-Euro members like Hungary received, swiftly and quietly. In order to solve this puzzle, we first establish the difference between EU interventions and IMF programs and, second, trace the evolution of crisis management with France and Germany in the lead. The lens of hegemonic stability theory suggests that the Franco-German leadership is too weak to provide stability and the extensive use of conditionality is one symptom of this weakness. Providing incentives for cooperation "after hegemony" (Keohane) is the unresolved issues troubling the monetary union. Its dominant powers must acknowledge that markets perceive monetary union to be already politically more integrated than its lack of fiscal integration suggests.

Creating Stability: National Preferences and the Origins of European Monetary System. CES Germany & Europe Working Papers, No. 00.9, December 2000

This essay compares the preferences of France, Italy, and Britain on the creation of the European Monetary System in 1978-1979, especially the Exchange Rate Mechanism, which stabilised nominal exchange rates. My claim is that the different conclusions reached by the governments (France and Italy in, Britain out) cannot be explained by economic circumstances or by interests, and I elaborate an intervening institutional variable which helps explain preferences. Deducing from spatial theory that where decisionmakers `sit' on the left-right spectrum matters to their position on the EMS, I argue that domestic constitutional power-. sharing mechanisms privilege certain actors over others in a predictable and consistent way. Where centrists were in power, the government's decision was to join. Where left or right extremists were privileged, the government's decision was negative. The article measures the centrism of the governments in place at the time, and also reviews the positions taken by the national political parties in and out of government. It is intended to contribute to the growing comparativist literature on the European Union, and to the burgeoning literature on EU-member-state relations.

Industrial process and space heat from nuclear reactors : a literature search /

"October 1959."

Shipping and storage of radioactive materials : a literature search /

"Health and Safety."

Shipping, handling and storage of radioactive materials : a literature search /

"Distributed according to TID-4500 (16th Ed.) ; Health and Safety."

Shipping, handling and storage of radioactive materials : A literature search /

"Distributed according to TID-4500 (16th Ed.) ; Health and Safety."

WALSHSTORE : the application of burst processing to fail-soft storage systems using Walsh transforms /

"UILU-ENG 77 1753."

Antirecession fiscal assistance to state and local governments.

Describes the antirecession fiscal assistance allocation process and lists each recipient government individually, showing the allocation and payment for each quarter with the unemployment rate data upon which the allocation is based.

An introduction to leaking underground storage tanks in Illinois.

"Fall 1994."