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(2000). Triumphalism and Reality in U.S. Cold War Policies. Peace Review: Vol. 12, No. 4, pp. 613-617.

In this article, we provide a systematic analysis of the extent to which political, economic, and cultural factors are associated with civil wars in the post-colonial states of Africa, Asia, and the Middle East. Results of logistic regression analyses corroborate previous findings that semi-democracy is associated with an increased likelihood of civil war, while greater economic development reduces the probability of civil war. We also found that militarized post-colonial states are more likely to experience civil war, as are Asian — more than Middle Eastern and African — states. Among the political, economic, and cultural factors, semi-democracy has the greatest impact on the probability of civil war, which suggests the greater role of political — more than economic or cultural — factors in post-colonial civil wars. All told, the findings suggest that a multifaceted strategy of full democratization, demilitarization, and development is required to reduce the likelihood of civil war in post-colonial states.

Everyone knows that war destroys and war kills. We also know that preparedness for war, despite all the protests of prudence, deterrence, self‐defense, and the like, often makes war more likely. Less self‐evident, however, are some of the consequences for our physical environment. Thanks to the work of Arthur H. Westing [Warfare in a Fragile World: Military Impact on the Human Environment (London: Taylor and Francis, 1980); Cultural Norms, War and the Environment (New York: Oxford University Press, 1988)] and a few others, we are increasingly aware of the damage that war itself inflicts on this environment, but outside of the effects of nuclear weapons production and testing, little attention has been given to the environmental effects of preparation for war. The purpose of this essay is to help rectify this unfortunate state of affairs. Thus, we present here a summary of what has been observed and reported in regard to the environmental effects of military preparedness programs in the more indus...

Seven years after the launching of the Correlates of War project there, Stuart Bremer joined the Department of Political Science at the University of Michigan and shortly thereafter began attending the project's weekly research seminar. At his death, thirty-two years later, Stuart had been Director of the project for 2 years and Chairman of the COW Council for 5 years; the Council was his invention and its leadership his enthusiastic self-selection. Such a history might suggest that from start to finish he was in full accord with the premises, research program, and overall trajectory of the enterprise. Never has a social science institution had so rigorous, dedicated, and capable a supporter, but rarely have we seen so constructive and lively a critic. As founder and director of the project from 1963 until my retirement in 2000, it is my pleasure to record this fascinating tale. As coordinator of the World Politics program in the Department of Political Science, I first learned about this Michigan State graduate student from his dissertation chairman Rufus Browning and then from Harold Guetzkow with whom Stuart was doing a post-doctoral stint at Northwestern. I invited him to visit with a few of my colleagues and several weeks later invited him to come back and give the standard academic “job talk.” We found his intelligence, breadth, and charm irresistible, and not long thereafter offered him a position in our department. Worth emphasizing is how different he was from the rest of the World Politics faculty; like me and no one else, he was clearly of a …

Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer’s disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau229-237[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B241-255 originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible.

Militarized interstate disputes are united historical cases of conflict in which the threat, display or use of military force short of war by one member state is explicitly directed towards the government, official representatives, official forces, property, or territory of another state. Disputes are composed of incidents that range in intensity from threats to use force to actual combat short of war. The new dispute data set generated by the Correlates of War project contains information on over 2,000 such disputes found to have occurred in the period 1816–1992. As in the earlier version of the data set, the participants, start and end dates, fatality totals, and hostility levels for each dispute are identified, but the newer version disaggregates this information for each participant and provides additional information about the revisionist state(s), type(s) of revision sought, outcome, and method of settlement for each dispute. A preliminary analysis of the data shows some interesting empircal patterns. Contagion and a slight upward trend are found in the frequency of disputes at the system level. The duration of disputes appears to be positively associated with the level of hostility reached and the number of states involved, and disputes appear to have a feud-like character. The single most important factor found to increase the fatality level of a dispute is the number of states that join after its onset. However, most disputes begin and end as one-on-one confrontations, and this tendency is stronger in the current period than in the past. An examination of dispute escalation reveals that many disputes begin with uses of force rather than less intense threats or displays of force and that states joining an ongoing dispute raise the likelihood that the dispute will reach higher levels of hostility. With respect to the settlement of disputes it was found that the longer a dispute continues, the higher the likelihood of some settlement, either negotiated or imposed, being achieved, althogh there is a discernable trend away from such settlements over the period studied. A related trend was found with respect to the outcome of disputes as stalemate has become a much more likely outcome in the present than in the past.

Alzheimer's disease is characterized by two pathological hallmarks, the intracellular deposition of hyperphosphorylated Tau protein and the extracellular deposition of Aβ1-40/42 , both being targets for immunotherapy. This study evaluates the immunogenic properties of three AD-specific B-cell epitopes (Tau229-237 [pT231/pS235], pyroGluAβ3-8 , and Aβ37/38-42/43 ) linked to five foreign T-cell epitopes (MVFP, TT, TBC Ag85B, PvT19, and PvT53) by immunizing inbred C57BL/6J (H-2(b) ), SJL/J (H-2(s2) ), and C3H/HeN (H-2(k) ) mice. Two promising candidates with respect to MHC II restriction were selected, and two transgenic mouse models of AD, P301S (H-2(b/) (k) ) and Tg2576 (H-2(b/) (s) ) animals, were immunized with one B-cell epitope in combination with two T-cell epitopes. Responders displayed an enhanced immune response compared with wild-type animals, which supports the vaccine design and the vaccination strategy. The immune response was also characterized by specific IgG subtype titers, which revealed a strong polarization toward the humoral pathway for immunization of phospho-Tau, whereas for both Aβ vaccines, a mixed cellular/humoral pathway response was observed. Despite the diversity and unpredictability of the immunogenicity of the peptide vaccines, all three peptide vaccine formulations appear to be promising constructs for future evaluation of their therapeutic properties.

Objective. To assess the multiple mini-interview (MMI) as an admission tool for a satellite campus. Methods. In 2013, the MMI was implemented as part of a new admissions model at the UNC Eshelman School of Pharmacy. From fall 2013 to spring 2015, 73 candidates were interviewed by 15 raters on the satellite campus in Asheville, North Carolina. A many-facet Rasch measurement (MFRM) with three facets was used to determine the variance in candidate ratings attributable to rater severity, candidate ability, and station difficulty. Candidates were surveyed to explore their perceptions of the MMI. Results. Rasch measures accounted for 48.3% of total variance in candidate scores. Rater severity accounted for 9.1% of the variance, and candidate ability accounted for 36.2% of the variance. Eighty percent of survey respondents (strongly) agreed that interviewers got to know them based on questions they answered.Conclusion. This study suggests that the MMI is a useful and valid tool for candidate selection at a satellite campus.

BACKGROUND: Organotypic brain slice cultures represent an excellent compromise between single cell cultures and complete animal studies, in this way replacing and reducing the number of animal experiments. Organotypic brain slices are widely applied to model neuronal development and regeneration as well as neuronal pathology concerning stroke, epilepsy and Alzheimer's disease (AD). AD is characterized by two protein alterations, namely tau hyperphosphorylation and excessive amyloid β deposition, both causing microglia and astrocyte activation. Deposits of hyperphosphorylated tau, called neurofibrillary tangles (NFTs), surrounded by activated glia are modeled in transgenic mice, e.g. the tauopathy model P301S. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explore the benefits and limitations of organotypic brain slice cultures made of mature adult transgenic mice as a potential model system for the multifactorial phenotype of AD. First, neonatal (P1) and adult organotypic brain slice cultures from 7- to 10-month-old transgenic P301S mice have been compared with regard to vitality, which was monitored with the lactate dehydrogenase (LDH)- and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays over 15 days. Neonatal slices displayed a constant high vitality level, while the vitality of adult slice cultures decreased significantly upon cultivation. Various preparation and cultivation conditions were tested to augment the vitality of adult slices and improvements were achieved with a reduced slice thickness, a mild hypothermic cultivation temperature and a cultivation CO(2) concentration of 5%. Furthermore, we present a substantial immunohistochemical characterization analyzing the morphology of neurons, astrocytes and microglia in comparison to neonatal tissue. CONCLUSION/SIGNIFICANCE: Until now only adolescent animals with a maximum age of two months have been used to prepare organotypic brain slices. The current study provides evidence that adult organotypic brain slice cultures from 7- to 10-month-old mice independently of the transgenic modification undergo slow programmed cell death, caused by a dysfunction of the neuronal repair systems.

An 11-mer peptide taken from a subsequence of the human protein ubiquitin was synthesized. The peptide has been fully characterized by NMR spectroscopy using chemical shift analysis and by NOE measurements. The conformation was calculated using state of the art MD methods of protein chemistry. A hairpin conformation was found which is to a large part identical with the structure of this peptide fragment within the human ubiquitin. The surprising result that already an 11-mer peptide adopts a hairpin conformation in aqueous solution is discussed in terms of initials sites for protein folding.

There seems to be three general orientations regarding the appropriate role for a major university in society. To simplify a bit, one orientation would have the university integrate into the society, accepting most mainstream values and servicing mainstream institutions. Thus, our mission would be to train people for business, government, education, and the military. Although the professional schools are most prominent in this mission, our typical “liberal arts” undergraduate programs still provide the bulk of the people trained for these roles. Similarly, under this orientation university research capabilities would be made available to the institutions and interest groups that not only provide the funding but also define the problems to be examined. As Dean Rosovsky's book The University: An Owner's Manual makes clear, many administrators are more than happy with such a state of affairs. A second orientation is that of the familiar, if mythical, ivory tower, in which we not only turn our backs on the pr...

Huntington’s disease (HD) is a neurodegenerative disorder that affects approximately 1 in 10 000 individuals. The underlying gene mutation was identified as a CAG-triplet repeat expansion in the genehuntingtin. The CAG sequence codes for glutamine, and in HD, an expansion of the polyglutamine (poly-Q) stretch above 35 glutamine residues results in pathogenicity. It has been demonstrated in various animal models that only the expression of exon 1 huntingtin, a 67-amino acid-long polypeptide plus a variable poly-Q stretch, is sufficient to cause full HD-like pathology. Therefore, a deeper understanding of exon 1 huntingtin, its structure, aggregation mechanism and interaction with other proteins is crucial for a better understanding of the disease. Here, we describe the synthesis of a 109-amino acid-long exon 1 huntingtin peptide including a poly-Q stretch of 42 glutamines. This microwave-assisted solid phase peptide synthesis resulted in milligram amounts of peptide with high purity. We also synthesized a nonpathogenic version of exon 1 huntingtin (90-amino acid long including a poly-Q stretch of 23 glutamine residues) using the same strategy. In circular dichroism spectroscopy, both polypeptides showed weak alpha-helical properties with the longer peptide showing a higher helical degree. These model peptides have great potential for further biomedical analyses, e.g. for large-scale pre-screenings for aggregation inhibitors, further structural analyses as well as protein – protein interaction studies. Copyright c � 2010 European Peptide Society and John Wiley & Sons, Ltd.

Most mammalian proteins are transiently phosphorylated on seryl, threonyl, or tyrosyl positions by kinases and dephosphorylated by phosphatases in response to specific intra- or extracellular signals. Many diseases, such as cancer, are caused by altered kinase and phosphatase activities or changed expression levels of either of these enzymes. Thus phosphopeptides are important and universal tools to study disease-specific changes, such as protein-protein/DNA interactions or hyperactive kinases, using phosphopeptides or the corresponding mimics. Here we describe two generally applicable techniques to synthesize multiply phosphorylated peptides as basic tools for drug development. The phosphopeptides were purified to homogeneity and characterized by mass spectrometry.

Several lines of evidence suggest that quantification of phosphorylated sites in the tau-protein (phospho-tau) might be favorable for early and specific Alzheimer's disease diagnosis. The typical setup to quantify phosphorylated tau-epitopes relies on a sandwich ELISA with a capture antibody (Ab) recognizing tau independent of its phosphorylation status and a detector Ab binding specifically to a certain phosphorylation site. Besides Ab specificities, major challenges arise from the very low tau-concentrations in cerebrospinal fluid (CSF) ranging from 100 to 2,000 pg/ml. Based on the phosphorylation degree of a given position, which can be below 10%, the corresponding phospho-tau-level might be much lower, especially for multiphosphorylated epitopes studied here. Thus, a novel, highly sensitive, and generally applicable immunoassay is described to quantify tau-versions, which are phosphorylated at pThr212/pSer214/pThr231/pSer235, down to tau-concentrations of 2 pg/ml in CSF.

Most mammalian proteins are transiently phosphorylated on seryl, threonyl, or tyrosyl positions by kinases and dephosphorylated by phosphatases in response to specific intra- or extracellular signals. Many diseases, such as cancer, are caused by altered kinase and phosphatase activities or changed expression levels of either of these enzymes. Thus phosphopeptides are important and universal tools to study disease-specific changes, such as protein-protein/DNA interactions or hyperactive kinases, using phosphopeptides or the corresponding mimics. Here we describe two generally applicable techniques to synthesize multiply phosphorylated peptides as basic tools for drug development. The phosphopeptides were purified to homogeneity and characterized by mass spectrometry.

The title of this article can be understood in three different ways. First, it is the name of a research project in quantitative history begun in 1964 at the University of Michigan, and still under way. Second, it means the extent to which a wide variety of factors rise and fall with fluctuations in the incidence of war: whether they correlate or covary with war, strongly or weakly, positively or negatively. And, third, it describes a research strategy by which we can make the transition from a stage in which the efforts to account for war were largely speculative and anecdotal to a stage in which well-articulated theoretical models can be subjected to the most rigorous scientific scrutinizing. Let me begin with a brief look at the intellectual history of the human effort to understand the ‘causes’ of war and thus to reduce its frequency or severity, or even perhaps to eliminate it entirely from the face of the earth.

Most mammalian proteins are transiently phosphorylated on seryl, threonyl, or tyrosyl positions by kinases and dephosphorylated by phosphatases in response to specific intra- or extracellular signals. Many diseases, such as cancer, are caused by altered kinase and phosphatase activities or changed expression levels of either of these enzymes. Thus phosphopeptides are important and universal tools to study disease-specific changes, such as protein-protein/DNA interactions or hyperactive kinases, using phosphopeptides or the corresponding mimics. Here we describe two generally applicable techniques to synthesize multiply phosphorylated peptides as basic tools for drug development. The phosphopeptides were purified to homogeneity and characterized by mass spectrometry.

In Alzheimer’s disease (AD) neurofibrillary tangles (NFT) are formed by hyperphosphorylated microtubule-associated tau protein. It is still a matter of controversy which phosphorylation sites are AD-specific and how these might be linked to the cause or progress of the disease. Whereas most research projects in this field rely on phosphorylation-dependent tau-specific monoclonal antibodies (mAbs), the phosphorylation patterns recognized by these mAbs are often not characterized in detail. Therefore, we synthesized unphosphorylated, two monophosphorylated (pThr231, pSer235), and the bisphosphorylated (pThr231 + pSer235) tau226-240 peptides. The phosphopeptides were ligated via an N-terminal cysteine to the thioester-activated C-terminus of human aldo/keto reductase AKR1A1. After purification by preparative gel electrophoresis, the ligation products were analyzed by Western blotting and probed with phosphorylation-dependent anti-tau mAbs HPT-101, HPT-103, HPT-104, and HPT-110. The obtained specificities were very similar to the data obtained by ELISA, showing that ELISA-based epitope mapping studies are also valid for immunoblot analyses.

Nonenzymatic glycosylation or glycation of amino groups in peptides and proteins by D-glucose is a universal reaction with important implications for the pathogenesis of many diseases including diabetes mellitus. Here a general approach is reported to synthesize site specifically glucose-derived N-glycated peptides. Therefore, model peptides H-AKASASFL-NH2, H-AKASADFL-NH2, H-ASKASKFL-NH2, and H-AKDSASFL-NH2 were synthesized on solid phase by Fmoc chemistry using Fmoc-Lys(4-methyltrityl)-OH in positions 2 or 3 to be glycated. After completion of the synthesis, the acid labile 4-methyltrityl-group was cleaved with 1% TFA in DCM and the free amino groups were glycated by the Lobry de Bruyn reaction using 2,3:4,5-di-O-isopropylidene-aldehydo-β-D-arabino-hexos-2-ulo-2,6-pyranose on solid phase. After TFA treatment, the crude peptides were obtained in high yields and purities above 80%. Minor by-products were well separated on reversed-phase HPLC. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.

This paper reports the latest developments for a wireless pen-based classroom interaction system, classroom learning partner (CLP), and two new variations - group learning partner (GLP) and elementary learning partner (ELP). CLP consists of a network of Tablet PCs and software for posing questions to students, interpreting their handwritten answers, and aggregating the answers into equivalence classes. Through controlled classroom experiments, we have demonstrated that use of CLP improves student learning, especially among students who might otherwise be left behind. GLP extends CLP to support student group work in the classroom by supporting the transmission of ink between students. ELP is a version of CLP developed for use in elementary school classrooms.

Post-mortem diagnosis of Alzheimer's disease relies on high numbers of senile plaques and neurofibrillary tangles (NFTs) stained in distinct brain areas. NFTs mostly consist of hyperphosphorylated versions of the microtubule attached tau protein (PHF-tau) with more than 30 serine and threonine phosphorylation sites identified so far. Characterization of hyperphosphorylated tau regions and the hope to develop robust assays for early AD diagnosis relies mostly on phosphorylation-dependent monoclonal antibodies (mAbs) recognizing only disease-specific phosphorylation patterns. Here, we report that anti-PHF-tau mAb AT8 recognizes an epitope doubly phosphorylated at serine 202 and threonine 205, which was not influenced by a third phosphate group at serine 199. But mAb AT8 was cross-reactive to two doubly phosphorylated motifs containing either serines 199 and 202 or serines 205 and 208 of the human tau sequence. The epitope of anti-tau mAb Tau5 was mapped to the human tau sequence 218-225, which is not phosphorylated in vivo.

Successful advanced Naval ship design must be based on integrating multiple cross-functional systems. Future Naval systems will require innovation and a systematic integration in order to achieve increasingly demanding mission profiles in a cost effective manner. Since a large amount of the design cost (up to 80%) is locked during the conceptual phase, it is important to include both the traditional Naval Architecture concerns and the specialized war fighting operational objectives within the conceptual design. Accurate assessment of proper specifications and design objectives using a "system of systems" cost conscious design environment will eliminate situations where cost becomes prohibiting because performance expectations were set at each system level without coordination and without a parallel interaction among systems performance and objectives. Developments are performed for developing a system for Tree-Multi-Disciplinary Optimization under Uncertainty (T-MDO-U) and including Fast Running Model (FRM) technology in the optimization process.

This paper describes two pilot studies, one completed and one ongoing, that evaluate the use of Tablet PCs and a Tablet-PC-based classroom presentation system in an introductory computer science class. The presentation system, Classroom Presenter [2, 3], supports student wireless submission of digital ink answers to in-class exercises. In these studies, we evaluate the hypothesis that the use of such a system increases student learning by: (1) increasing student focus and attentiveness in class, (2) providing immediate feedback to both students and instructor about student misunderstandings, (3) enabling the instructor to adjust course material in real-time based upon student answers to in-class exercises, (4) increasing student satisfaction. The studies evaluate each of the above four parameters by means of classroom observation, surveys, and interviews.