Arguing for the Philosophy of Political Science

While there are many working scientists who engage in things like theory building and empirical testing, there has also been a group of scientists who sought to better understand the philosophy behind science. This philosophical study of science as a project is referred to as the philosophy of science and there are different sub-fields for each of the natural and social sciences, except for political science. This lack of an explicit sub-field dedicated to reflecting on our philosophy of science, i.e., our beliefs, values, methods, etc., has caused this knowledge to become tacit within our community. Because the knowledge of our philosophy of science is now tacit, we as a community are hindered in our capacity to engage in critical self-reflection which is an important part of any scientific endeavor. However, what has been is not what need be moving forward, we can still turn this tacit knowledge into formal knowledge which will then allow us to grow as a community. This thesis will demonstrate a few of the ways in which our knowledge of the philosophy of our science has become tacit, and why this is indeed a bad thing. The specific topic areas addressed are the misunderstandings of the natural sciences in our community, the process of categorization, and our goals as a scientific tradition. This is in service of the true goal of this thesis project, which is to give a proper augment for the creation of the philosophy of political science as an explicit sub-field

The carbene/carbenoid chemistry of lithium and tin cyclopropylidenoids

In Chapter I of this dissertation, the Skattebol-type rearrangement (in THF solution at -78(DEGREES)) of anti-7-bromo-syn-7-lithiobicyclo4.1.0hept-2-ene (34-anti) and its C(\u277)-epimer (34-syn) is investigated. The following discoveries demonstrate that, in solution, this rearrangement proceeds through a carbenoid: (a) carbenoid 34-anti undergoes 1,3-rearrangement and generates the carbenoid coupling products 42-syn and 42-anti 17 times faster than does 34-syn, (b) the coupling products 42-syn and 42-anti are formed in a much different ratio from 34-anti (7.5 to 1) than from 34-syn (1.5 to 1), (c) no carbene trapping products were formed in the presence of a large excess of isobutylene, cyclohexene, or triethylsilane, and (d) the saturated analogs of 34-anti and 34-syn (i.e., 89-anti and 89-syn, respectively) do not generate the corresponding free cyclopropylidene under the same reaction conditions (or under a variety of other reaction conditions which are investigated in Chapter II);In Chapter III, the pyrolysis reactions of anti-7-bromo-syn-7-trimethylstannylbicyclo4.1.0hept-2-ene (35-anti) and its C(\u277)-epimer (35-syn) are studied, in hopes of observing the Skattebol rearrangement of the corresponding cyclopropylidene. The results of the gas-phase pyrolysis studies are not easily understood. In the solution phase, however, the pyrolysis reactions of 35-anti and 35-syn have both been discovered to involve initial C-Br bond heterolysis, with no carbene involvement. The reaction of 35-anti involves an ionic 1,3-rearrangement (through double bond participation), and that of 35-syn involves an ionic opening of the cyclopropyl ring (favored by the stereochemistry of the bromine group);Chapter IV describes the solution-phase pyrolysis reactions of the saturated analogs of 35-anti and 35-syn (205-anti and 205-syn, respectively). Both reactions again involve initial C-Br bond heterolysis. The major reaction pathway of 205-anti is C-Br bond heterolysis, leading to a cyclopropyl ion pair, which, in the absence of cation traps, loses trimethyltin bromide, to generate the corresponding cyclopropylidene. The major reaction pathway of 205-syn is ionic opening of the cyclopropyl ring (again favored by the stereochemistry of the bromine group)

Marines vs. Contractors: an analysis of a supply outsourcing initiative and its impact on cost and efficiency

Since 2001, the Marine Corps has outsourced the management of all individual issue combat gear. This contracted outsourcing, called the Consolidated Issue Facility (CIF) and then the Individual Issue Facility (IIF) under the direction of local Marine Expeditionary Force Headquarters (MEF HQ) and Marine Corps Logistics Command (LOGCOM), are responsible for the distribution, management, and collection of every Marine's individual combat issue of gear; a task previously accomplished by each unit's individual organic supply section. By removing this burden on the supply sections, the Marine Corps was theoretically able to free-up Marines to fill billets in warfighting roles. The Marine Corps has touted the ability to save money and create efficiencies that did not exist previously with organic Marine Corps led supply operations. The Marine Corps is looking to increase the amount of assets managed by an outside vendor, by outsourcing management of unit assets such as Soft Walled Shelters and Camouflage netting to a Unit Issue Facility (UIF) using the same model as the CIF/IIF. This paper will explore if the CIF/IIF program saved the Marine Corps money from 2001 thru 2010, allowed for transfer of personnel to other roles, and if the program is an effective model for future outsourcing endeavors.http://archive.org/details/marinesvscontrac1094510592US Marine Corps (USMC) author

Efficient computation of absent words in genomic sequences

Herold J, Kurtz S, Giegerich R. Efficient computation of absent words in genomic sequences. BMC Bioinformatics. 2008;9(1): 167.Background: Analysis of sequence composition is a routine task in genome research. Organisms are characterized by their base composition, dinucleotide relative abundance, codon usage, and so on. Unique subsequences are markers of special interest in genome comparison, expression profiling, and genetic engineering. Relative to a random sequence of the same length, unique subsequences are overrepresented in real genomes. Shortest words absent from a genome have been addressed in two recent studies. Results: We describe a new algorithm and software for the computation of absent words. It is more efficient than previous algorithms and easier to use. It directly computes unwords without the need to specify a length estimate. Moreover, it avoids the space requirements of index structures such as suffix trees and suffix arrays. Our implementation is available as an open source package. We compute unwords of human and mouse as well as some other organisms, covering a genome size range from 109 down to 105 bp. Conclusion: The new algorithm computes absent words for the human genome in 10 minutes on standard hardware, using only 2.5 Mb of space. This enables us to perform this type of analysis not only for the largest genomes available so far, but also for the emerging pan- and meta-genome data

Analyse und Visualisierung der Siedlungsentwicklung mit SEMENTA®-CHANGE

In diesem Beitrag werden Methoden der gebäudebasierten Erfassung der Siedlungsstruktur, deren Veränderung und Visualisierung vorgestellt. Die Analyse der Siedlungsentwicklung mit SEMENTA®-CHANGE basiert auf der automatisierten Auswertung topographischer Kartenwerke verschiedenster Zeitstände im Maßstab 1:25 000. Der Verfahrensansatz leistet einen wichtigen Beitrag für die Planung, da er für große Flächen eine Verortung der Gebäude-, Siedlungsflächen- und Siedlungsstrukturentwicklung der vergangenen Jahrzehnte erlaubt und sich daraus auch wertvolle Aussagen über die Wirksamkeit von raumplanerischen Instrumenten (z. B. Verhältnis der Innen- zur Außenentwicklung) ableiten lassen. Beispielhaft werden an ausgewählten Projektergebnissen das Anwendungspotenzial sowie die Grenzen des Verfahrens diskutiert

CTCF genomic binding sites in Drosophila and the organisation of the bithorax complex.

Insulator or enhancer-blocking elements are proposed to play an important role in the regulation of transcription by preventing inappropriate enhancer/promoter interaction. The zinc-finger protein CTCF is well studied in vertebrates as an enhancer blocking factor, but Drosophila CTCF has only been characterised recently. To date only one endogenous binding location for CTCF has been identified in the Drosophila genome, the Fab-8 insulator in the Abdominal-B locus in the Bithorax complex (BX-C). We carried out chromatin immunopurification coupled with genomic microarray analysis to identify CTCF binding sites within representative regions of the Drosophila genome, including the 3-Mb Adh region, the BX-C, and the Antennapedia complex. Location of in vivo CTCF binding within these regions enabled us to construct a robust CTCF binding-site consensus sequence. CTCF binding sites identified in the BX-C map precisely to the known insulator elements Mcp, Fab-6, and Fab-8. Other CTCF binding sites correlate with boundaries of regulatory domains allowing us to locate three additional presumptive insulator elements; "Fab-2," "Fab-3," and "Fab-4." With the exception of Fab-7, our data indicate that CTCF is directly associated with all known or predicted insulators in the BX-C, suggesting that the functioning of these insulators involves a common CTCF-dependent mechanism. Comparison of the locations of the CTCF sites with characterised Polycomb target sites and histone modification provides support for the domain model of BX-C regulation

Bundesweites Monitoring von Innenentwicklungspotenzialen – Ausgangslage und Perspektive

Der Beitrag zeigt mögliche Wege eines bundesweiten Monitorings von Innenentwicklungspotenzialen auf. Die Erfassung und das Monitoring von Innenentwicklungspotenzialen, das heißt von Baulücken, Brachflächen und Leerständen, bilden eine wichtige Grundlage für eine flächensparende Siedlungsentwicklung, einen besseren Schutz von Außenbereichen sowie Planungs- und Entscheidungsprozesse im Sinne einer „Innen-vor-Außen“-Politik. Ausgehend von einem Überblick der aktuellen Erfassungsaktivitäten in Deutschland, werden verschiedene Varianten einer bundesweiten Erfassung vorgestellt, diskutiert und ein Ansatz entwickelt, der perspektivisch ein kontinuierliches Monitoring der Innenentwicklung ermöglichen könnte. Damit würde ein entscheidendes informatorisches Instrument zur dauerhaften nachhaltigen Flächenentwicklung geschaffen

Application of high throughput in vitro metabolomics for hepatotoxicity mode of action characterization and mechanistic-anchored point of departure derivation: a case study with nitrofurantoin

Omics techniques have been increasingly recognized as promising tools for Next Generation Risk Assessment. Targeted metabolomics offer the advantage of providing readily interpretable mechanistic information about perturbed biological pathways. In this study, a high-throughput LC–MS/MS-based broad targeted metabolomics system was applied to study nitrofurantoin metabolic dynamics over time and concentration and to provide a mechanistic-anchored approach for point of departure (PoD) derivation. Upon nitrofurantoin exposure at five concentrations (7.5 µM, 15 µM, 20 µM, 30 µM and 120 µM) and four time points (3, 6, 24 and 48 h), the intracellular metabolome of HepG2 cells was evaluated. In total, 256 uniquely identified metabolites were measured, annotated, and allocated in 13 different metabolite classes. Principal component analysis (PCA) and univariate statistical analysis showed clear metabolome-based time and concentration effects. Mechanistic information evidenced the differential activation of cellular pathways indicative of early adaptive and hepatotoxic response. At low concentrations, effects were seen mainly in the energy and lipid metabolism, in the mid concentration range, the activation of the antioxidant cellular response was evidenced by increased levels of glutathione (GSH) and metabolites from the de novo GSH synthesis pathway. At the highest concentrations, the depletion of GSH, together with alternations reflective of mitochondrial impairments, were indicative of a hepatotoxic response. Finally, a metabolomics-based PoD was derived by multivariate PCA using the whole set of measured metabolites. This approach allows using the entire dataset and derive PoD that can be mechanistically anchored to established key events. Our results show the suitability of high throughput targeted metabolomics to investigate mechanisms of hepatoxicity and derive point of departures that can be linked to existing adverse outcome pathways and contribute to the development of new ones

Immunochemotherapy and Maintenance With Obinutuzumab or Rituximab in Patients With Previously Untreated Marginal Zone Lymphoma in the Randomized GALLIUM Trial

The aim of this study was to explore the efficacy and safety of obinutuzumab (G)- versus rituximab (R)-chemotherapy in a subgroup of patients with previously untreated marginal zone lymphoma (MZL) in the phase III GALLIUM trial (NCT01332968). Patients had stage III/IV (or stage II with bulky disease), splenic, nodal, or extranodal MZL requiring treatment. Patients were randomized 1:1 to receive G- or R-chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; cyclophosphamide, vincristine, and prednisone; or bendamustine, allocated at patient level). Patients with complete/partial response at the end of induction (EOI) received G/R maintenance. Investigator-assessed progression-free survival (PFS), other time-to-event endpoints, response, and safety were assessed. Overall, 195 patients with MZL were included in this analysis: G-chemotherapy (n = 99), R-chemotherapy (n = 96). Median observation time: 59.3 months. No meaningful difference was observed between arms for PFS (4-y PFS rates: G-chemotherapy, 72.6%; R-chemotherapy, 64.1%), other time-to-event endpoints, or EOI response rates (by computed tomography [CT; G-chemotherapy, 81.8%; R-chemotherapy, 81.3%] and positron emission tomography CT [G-chemotherapy, 79.2%; R-chemotherapy, 87.5%]). All patients experienced ≥1 adverse event (AE). G-chemotherapy was associated with a higher incidence of grade 3–5 (86.1% versus 77.4%), grade 5 (14.9% versus 9.7%), and serious (66.3% versus 51.6%) AEs versus R-chemotherapy. Both arms had a higher incidence of grade 3–5 and serious AEs than patients with follicular lymphoma (GALLIUM), with G-chemotherapy being less tolerable than R-chemotherapy. Based on the observed tolerability of G-chemotherapy versus R-chemotherapy, and the comparable efficacy of G-chemotherapy and R-chemotherapy in this analysis, G-chemotherapy cannot be recommended as first-line treatment for MZL