204 research outputs found
Unintended Architectures: Terrorism's Role in Shaping Post-War France, the European Union, and the Muslim Presence in the West
This article argues that the Algerian FLN (Front de libération nationale) played a major role in shaping the character of post-Second World War Europe. A sub-state terrorist organization dedicated to ending colonial domination of Algeria in the 1950s, the FLN effectively dashed France's dreams of resuming its position as a global power, which in turn promoted greater commitment on the part of France to the nascent European Community. The FLN may also be said to have inadvertently contributed to the first large-scale immigration of Muslims into Europe during the modern era, while also severely complicating the relationship between France and its Muslims for decades. While the FLN's use of political terror shaped national liberation movements across the developing world, the primary focus of this articler will instead be on the ways in which the FLN's victory in Algeria served to promote French participation in the European experiment and how the exodus of France's Arab and Berber allies at the conclusion of the conflict added to the extant piedmont of Muslim Europeans reshaping the ethnography of Western Europe
Critical Success Factors for Software Reuse Projects
Systematic reuse is becoming an increasingly popular way to improve software development productivity and quality. The implementation of a software reuse methodology requires substantial investments for the company. The factors that contribute to the overall success of reuse for an organization have been examined in prior research. However, even in organizations that are successful in employing reuse, some projects may fail to achieve the targeted amounts of reuse. This suggests that there are other factors beyond the overall organizational factors affecting the success of software reuse in projects. This research explores the factors contributing to reuse success of individual projects in organizations that practice systematic software reuse methodologies. Structured interviews are conducted with software developers to identify the factors and project data is scrutinized to assess the impact of these factors. Reuse success is measured by the reuse percentage achieved. A large scale survey of software development firms will be used to empirically tests the relevance of the identified factors to systematic reuse in general. We believe that an organization that can identify the factors affecting potential software reuse will be able to better target investments in the improve- ment of reuse methodology and thus influence the software productivity and quality
Recommended from our members
Engineering a Repeats-in-Toxin Scaffold for Stimulus-Responsive Biotechnology Applications
Protein scaffolds are described as polypeptide frameworks with well-defined tertiary structures that are tolerable to mutagenesis or insertions. These scaffolds have gained significant interest from researchers and clinicians as they have challenged immunoglobulin domains as the preferred protein to address critical problems in biomedical engineering and biotechnology. While engineered antibodies and antibody fragments have been immensely successful, their complex structure, costly production and purification requirements, and large size preclude them from a host of applications. Small, stable proteins devoid of disulfide bond networks that express well recombinantly in prokaryotic systems offer viable alternatives to immunoglobulins.
Repeat proteins are characterized structurally by tandem repeats of a consensus motif. These proteins are used in nature to mediate a variety of protein-protein interactions and are appealing scaffolds to bioengineers because of their predictable secondary structures. Several repeat scaffolds have been identified and successfully engineered for in vivo imaging and therapeutic applications. We have identified the repeats-in-toxin (RTX) protein as a potential antibody mimetic and interesting scaffold for protein engineering studies. RTX domains are commonly associated with extracellular proteins secreted through the type 1 secretion system in Gram-negative bacteria. They are composed of tandem repeats of a nonamer calcium binding sequence capped by N and C-termianl flanking regions. These proteins are conformationally dynamic and will fold from an intrinsically disordered state to a compact β-roll secondary structure in response to increasing calcium concentration. We aim to explore the RTX domain as an alternative protein scaffold and exploit the intrinsic conformational response to calcium as a mechanism to mediate molecular interactions.
In our first study, we rationally engineer the RTX domain as a calcium-responsive physical cross-linker for hydrogel formation. Protein based materials are favorable for may biomedical applications because of their biocompatibility, tunable mechanical properties, and predictable erosion rates. We have designed a hydrophobic interface on the surface of the RTX domain that is present only in the calcium-bound β-roll conformation. In the absence of calcium, the peptide returns to its disordered state, delocalizing the hydrophobic patch and in turn mitigating the driving force for self-assembly. We show that these mutant RTX domains, with the aid of additional protein cross-linkers, self-assemble into cross-linked macromolecular hydrogel networks, only in the presence of calcium.
To expand on this study, we further engineered the RTX domain to contain hydrophobic surfaces on both sides of the folded β-roll simultaneously. By doing this, we doubled the cross-linking capacity of the mutant RTX. This translates to a higher oligomerization state and lower protein concentration required for self-assembly. We also show the double mutant can function as a stand-alone cross-linking domain, eliminating the need for extraneous self-assembling proteins. This designed RTX mutant provides a new platform for stimulus-responsive cross-linking and self-assembly.
In our next line of work, we created several synthetic RTX peptides based on a consensus design approach. Such an approach relies on identifying the minimal requirements for a single repeating unit, and concatenating the unit to achieve a desired protein interface. We identified the consensus nonameric unit for the RTX domain and generated several constructs of varying lengths using this sequence. However, it was discovered that these designed RTX peptides undergo a reversible phase change in response to calcium. Rather than abandon these synthetic peptides, we looked to use them as calcium-responsive protein purification tags. By appending a consensus RTX domain to a protein of interest, we were able rapidly and efficiently purify fusions out of cell lysate by precipitation cycling. We were also able to separate the tag from the protein of interest by including a protease recognition site between the two. This system offers an alternative to time consuming and expensive chromatographic techniques for recombinant protein purification.
In our final study, we evaluated the RTX domain as a scaffold for evolving molecular recognition. We planned to use the calcium-responsive structural rearrangement as a switch to turn an evolved binding interface "on" and "off". One face of the folded β-roll structure was randomized on the genetic level and the resultant protein constructs were selected against a target protein using ribosome display technology. A consensus binding sequence emerged after several rounds of biopanning and was thoroughly characterized. The evolved β-roll bound the target protein with low micromolar affinity. Although this weak attraction was not suitable for efficiently capturing the target protein in a packed column application, this work provides a platform for evolving the RTX protein for molecular recognition. Several strategies are discussed to achieve higher affinity binders.
Overall, this dissertation explores the RTX domain as an alternative stimulus-responsive scaffold for use in a variety of biotechnology applications. We have successfully developed new protein based platforms based on rationally designed or combinatorailly selected RTX proteins for calcium-responsive biomaterials, non-chromatographic protein purification, and calcium-dependent molecular recognition
Value Sinks: A Process Theory of Corruption Risk during Complex Organizing
Theories and studies of corruption typically focus on individual ethics and agency problems in organizations. In this paper, we use concepts from complexity science to propose a process theory that describes how corruption risk emerges from conditions of uncertainty that are intrinsic in social systems and social interactions. We posit that our theory is valid across multiple levels of scale in social systems. We theorize that corruption involves dynamics that emerge when agents in a system take actions that exploit disequilibrium conditions of uncertainty and ethical ambiguity. Further, systemic corruption emerges when agent interactions are amplified locally in ways that create a hidden value sink which we define as a structure that extracts, or ‘drains’, resources from the system for the exclusive use of certain agents. For those participating in corruption, the presence of a value sink reduces local uncertainties about access to resources. This dynamic can attract others to join the value sink, allowing it to persist and grow as a dynamical system attractor, eventually challenging broader norms. We close by identifying four distinct types of corruption risk and suggest policy interventions to manage them. Finally, we discuss ways in which our theoretical approach could motivate future research
Mindfulness-based cognitive therapy for residual depressive symptoms
Objectives. Mindfulness-based cognitive therapy (MBCT) is a new group-based intervention for prevention of relapse in recurrent depression which has not been scientifically evaluated regarding its clinical effectiveness for ameliorating residual depressive symptoms following a depressive episode. The aim of this study was to assess the efficacy of MBCT in reducing residual depressive symptoms in psychiatric outpatients with recurrent depression, and to particularly explore the effects of mindfulness techniques on rumination. Design. The design of this study was a mixed model complex design. Design 1 consisted of a consecutive series of patients. They were assigned to either MBCT or TAU. The independent variables were time and group allocation, and dependent variables were Beck Depression Inventory (BDI) and Rumination Scale. In Design 2, the TAU group proceeded to complete an MBCT group, and the BDI and Rumination Scale results of the two groups were collapsed. Method. Nineteen patients with residual depressive symptoms following a depressive episode, and who were attending outpatient clinic, were assigned to either MBCT or treatment as usual (TAU), with the TAU group then proceeding to complete an MBCT group. Depressive and ruminative symptoms were assessed before, during, and after treatment, and at one-month follow-up. Results. A significant reduction in depressive symptoms was found at the end of MBCT, with a further reduction at one-month follow-up. A trend towards a reduction in rumination scores was also observed. Conclusions. Group MBCT has a marked effect on residual depressive symptoms, which may be mediated through the mindfulness-based cognitive approach toward
No. 4 - Agriculture and the WTO: Subsidies in the Cross Hairs
September 2003 saw trade talks pursuing the Doha Development Agenda at the Cancún WTO Ministerial Meeting collapse, primarily over the disagreements between rich and developing countries regarding agriculture. Despite the great pessimism that ensued, on August 1, 2004, WTO negotiators from 147 countries announced a breakthrough in negotiations to liberalize trade in agricultural products. The most striking aspect of this new framework agreement is the proposed elimination of agricultural subsidies by rich countries in return for developing countries opening up their markets to more imports. At the same time, WTO dispute resolution panels have delivered stunning decisions against the U.S. cotton subsidy program and the European Union\u27s sugar subsidies. Clearly agriculture trade policy will be a pivotal issue determining the failure or success of the Doha round. This conference featured noted experts from senior levels of government, the private sector, and the legal profession addressing current developments in multilateral negotiations and the WTO cases on agriculture and analyzing their impact on the future of the world agricultural market. It was presented on November 16, 2004, at the University of Georgia School of Law by the Dean Rusk Center–International, Comparative, and Graduate Legal Studies and the College of Agricultural and Environmental Sciences
Absolute Pitch and Tone Language: Two New Studies
ABSTRACT Two new studies provide evidence in favor of the hypothesis that absolute pitch is strongly influenced by a speech-related critical period. The first study examined the prevalence of absolute pitch among students in at the University of Southern California's Thornton School of Music, as a function of age of onset of musical training, ethnicity, fluency in speaking a tone language, and country of early music education. Among those of East Asian ethnicity, performance on a test of absolute pitch was strongly correlated with fluency in speaking a tone language. The advantage of early onset of musical training did not interact statistically with the effects of tone language fluency, and further analyses showed that the results could not be explained by country of early music education. The second study investigated the pitch ranges of female speech in two relatively isolated villages in China. These pitch ranges clustered within each village, but differed significantly across the villages, indicating that, at least for speakers of tone language, the pitch range of speech is heavily influenced by an absolute pitch template that is developed through long term exposure to speech in the environment. Implications of these findings are discussed
Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy
Abstract Background To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms. Methods Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods. Results For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D50 = 64.2Gy, m = 0.50, n = 1.0; 2) D50 = 95.0Gy, m = 0.45, n = 0.50; 3) D50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3. Conclusions Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes
2011 Report of NSF Workshop Series on Scientific Software Security Innovation Institute
Over the period of 2010-2011, a series of two workshops were held in response to NSF Dear Colleague Letter NSF 10-050 calling for exploratory workshops to consider requirements for Scientific Software Innovation Institutes (S2I2s). The specific topic of the workshop series was the potential benefits of a security-focused software institute that would serve the entire NSF research and development community.
The first workshop was held on August 6th, 2010 in Arlington, VA and represented an initial exploration of the topic. The second workshop was held on October 26th, 2011 in Chicago, IL and its goals were to 1) Extend our understanding of relevant needs of MREFC and large NSF Projects, 2) refine outcome from first workshop with broader community input, and 3) vet concepts for a trusted cyberinfrastructure institute. Towards those goals, the participants other 2011workshop included greater representation from MREFC and large NSF projects, and, for the most part, did not overlap with the participants from the 2010 workshop.
A highlight of the second workshop was, at the invitation of the organizers, a presentation by Scott Koranda of the LIGO project on the history of LIGO’s identity management activities and how those could have benefited from a security institute. A key analysis he presented is that, by his estimation, LIGO could have saved 2 senior FTE-years of effort by following suitable expert guidance had it existed.
The overarching finding from the workshops is that security is a critical crosscutting issue for the NSF software infrastructure and recommended a security focused activity to address this issue broadly, for example a security software institute (S2I2) under the SI2 program. Additionally, the 2010 workshop participants agreed to 15 key additional findings, which the 2011 workshop confirmed, with some refinement as discussed in this report.NSF Grant # 1043843Ope
Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts
We outline the scientific motivation behind a search for gravitational waves
associated with short gamma ray bursts detected by the InterPlanetary Network
(IPN) during LIGO's fifth science run and Virgo's first science run. The IPN
localisation of short gamma ray bursts is limited to extended error boxes of
different shapes and sizes and a search on these error boxes poses a series of
challenges for data analysis. We will discuss these challenges and outline the
methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on
Gravitational Waves, July 2011, Cardiff, U
- …