Optimized routing of unmanned aerial systems for the interdiction of improvised explosive devices

As of September 2007, improvised explosive devices (IED) account for 43% of U.S. casualties in Iraq - the largest single cause of death. One reason for their high rate of effectiveness is that they are extremely difficult to detect. This research develops a tool for selecting routes that will best employ unmanned aerial systems (UAS) for the purpose of detecting IED or related activity. We refer to this tool as IED Search Optimization Model (ISOM). ISOM - which uses prediction model results as an underpinning - accounts for factors such as winds, sensor sweep-width, and aircraft deconfliction. We formulate the problem as an Integer Program and optimally solve it to select the best routes. Initial evaluation of ISOM through field experiments with actual UAS suggest that the tool produces realistic routes which can be flown in the expected amount of time. Furthermore, these routes result in a 42% increase in the likelihood of achieving a detection opportunity over searching nodes in a random manner. ISOM could be implemented as a "reach-back" capability with an analyst providing daily routes for tactical operators.http://archive.org/details/optimizedrouting109453242Outstanding ThesisUS Marine Corps (USMC) author.Approved for public release; distribution is unlimited

Characterization of Brown Adipose Tissue in a Diabetic Mouse Model with Spiral Volumetric Optoacoustic Tomography

PURPOSE Diabetes is associated with a deterioration of the microvasculature in brown adipose tissue (BAT) and with a decrease in its metabolic activity. Multispectral optoacoustic tomography has been recently proposed as a new tool capable of differentiating healthy and diabetic BAT by observing hemoglobin gradients and microvasculature density in cross-sectional (2D) views. We report on the use of spiral volumetric optoacoustic tomography (SVOT) for an improved characterization of BAT. PROCEDURES A streptozotocin-induced diabetes model and control mice were scanned with SVOT. Volumetric oxygen saturation (sO) as well as total blood volume (TBV) in the subcutaneous interscapular BAT (iBAT) was quantified. Segmentation further enabled separating feeding and draining vessels from the BAT anatomical structure. RESULTS Scanning revealed a 46 % decrease in TBV and a 25 % decrease in sO in the diabetic iBAT with respect to the healthy control. CONCLUSIONS These results suggest that SVOT may serve as an effective tool for studying the effects of diabetes on BAT. The volumetric optoacoustic imaging probe used for the SVOT scans can be operated in a handheld mode, thus potentially providing a clinical translation route for BAT-related studies with this imaging technology

À propos de The Practice of Liberal Pluralism de William Galston : un dialogue avec l’auteur

Document de travailLa publication de The Practice of Liberal Pluralism est apparue comme un événement de première importance dans la réflexion contemporaine sur l’apport du pluralisme au libéralisme. La pensée de William Galston a connu une évolution : dans Liberal Purposes, l’accent est mis sur la critique du neutralisme et la position d’un libéralisme perfectionniste, tandis que Liberal Pluralism s’intéresse au contraire aux limites de l’intervention étatique. Cette évolution fait l’objet de nombreuses questions dans la discussion qui suit. The Practice of Liberal Pluralism opère une synthèse intéressante sur ce point. Galston se définit comme un libéral pluraliste dans la lignée de Berlin. Bien qu’il insiste sur le conflit tragique des valeurs, il minimise cet aspect dans les discussions qui suivent, et pose la possibilité consécutive d’avoir des devoirs prima facie (cf. la discussion sur sa négation du particularisme moral). Un des arguments centraux pour justifier le pluralisme des valeurs est qu’il rend le mieux compte de la complexité de notre univers moral (cf. la discussion sur le pluralisme et le sentiment de regret). Galston endosse également un pluralisme politique, lequel signifie que les sources d’autorité sont multiples. Le libéralisme de Galston est très tolérant à l’égard des pratiques communautaires non libérales. Cette tolérance est cependant assortie de la défense du « droit de sortie », notion qui apparaît donc comme fondamentale. Dans les discussions qui suivent, Galston propose la manière adéquate de comprendre l’exercice de ce droit de sortie (cf. les discussions sur les rapports entre liberté expressive, droit de sortie et autonomie).The publication of The Practice of Liberal Pluralism has appeared as an event of first importance regarding contemporary theory about the relation between pluralism and liberalism. William Galston’s theory has had a visible evolution: in Liberal Purposes, the main object is a critique of neutralism and a defence of perfectionist liberalism, whereas Liberal Pluralism main concern was to draw the limits of state intervention. This evolution is the object of numerous questions in the following discussion. The Practice of Liberal Pluralism operates an interesting synthesis on this point. Galston defines himself as a liberal pluralist such as Berlin, but although he acknowledges that conflict between values can be tragic, he minimizes this aspect in the following discussions, and considers the possibility of having prima facie duties (cf. the discussion on his rejection of moral particularism). One of the main arguments for the defence of value pluralism is its capacity to explain the complexity of the moral universe (cf. the discussion on pluralism and regret). Galston endorses a political pluralism, which means that the sources of authority are multiple. Galston’s liberalism is very tolerant regarding non-liberal communitarian practices, although this tolerance is based on the defence of an exit right, which is a fundamental notion in his theory. In the following discussion Galston proposes how to understand this right of exit in an adequate manner (cf. the questions regarding expressive liberty, exit rights and autonomy)

A Smartphone-Based Tool for Rapid, Portable, and Automated Wide-Field Retinal Imaging.

Purpose:High-quality, wide-field retinal imaging is a valuable method for screening preventable, vision-threatening diseases of the retina. Smartphone-based retinal cameras hold promise for increasing access to retinal imaging, but variable image quality and restricted field of view can limit their utility. We developed and clinically tested a smartphone-based system that addresses these challenges with automation-assisted imaging. Methods:The system was designed to improve smartphone retinal imaging by combining automated fixation guidance, photomontage, and multicolored illumination with optimized optics, user-tested ergonomics, and touch-screen interface. System performance was evaluated from images of ophthalmic patients taken by nonophthalmic personnel. Two masked ophthalmologists evaluated images for abnormalities and disease severity. Results:The system automatically generated 100° retinal photomontages from five overlapping images in under 1 minute at full resolution (52.3 pixels per retinal degree) fully on-phone, revealing numerous retinal abnormalities. Feasibility of the system for diabetic retinopathy (DR) screening using the retinal photomontages was performed in 71 diabetics by masked graders. DR grade matched perfectly with dilated clinical examination in 55.1% of eyes and within 1 severity level for 85.2% of eyes. For referral-warranted DR, average sensitivity was 93.3% and specificity 56.8%. Conclusions:Automation-assisted imaging produced high-quality, wide-field retinal images that demonstrate the potential of smartphone-based retinal cameras to be used for retinal disease screening. Translational Relevance:Enhancement of smartphone-based retinal imaging through automation and software intelligence holds great promise for increasing the accessibility of retinal screening

FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors

Replication-dependent histone genes are up-regulated during the G1/S phase transition to meet the requirement for histones to package the newly synthesized DNA. In mammalian cells, this increment is achieved by enhanced transcription and 3′ end processing. The non-polyadenylated histone mRNA 3′ ends are generated by a unique mechanism involving the U7 small ribonucleoprotein (U7 snRNP). By using affinity purification methods to enrich U7 snRNA, we identified FUS/TLS as a novel U7 snRNP interacting protein. Both U7 snRNA and histone transcripts can be precipitated by FUS antibodies predominantly in the S phase of the cell cycle. Moreover, FUS depletion leads to decreased levels of correctly processed histone mRNAs and increased levels of extended transcripts. Interestingly, FUS antibodies also co-immunoprecipitate histone transcriptional activator NPAT and transcriptional repressor hnRNP UL1 in different phases of the cell cycle. We further show that FUS binds to histone genes in S phase, promotes the recruitment of RNA polymerase II and is important for the activity of histone gene promoters. Thus, FUS may serve as a linking factor that positively regulates histone gene transcription and 3′ end processing by interacting with the U7 snRNP and other factors involved in replication-dependent histone gene expressio

Multicellular Architecture of Malignant Breast Epithelia Influences Mechanics

Cell–matrix and cell–cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the “perceived stiffness” of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing

The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid–liquid phase separation

Liquid–liquid phase separation (LLPS) of proteins and RNAs has emerged as the driving force underlying the formation of membrane-less organelles. Such biomolecular condensates have various biological functions and have been linked to disease. The protein Fused in Sarcoma (FUS) undergoes LLPS and mutations in FUS have been causally linked to the motor neuron disease Amyotrophic Lateral Sclerosis (ALS-FUS). LLPS followed by aggregation of cytoplasmic FUS has been proposed to be a crucial disease mechanism. However, it is currently unclear how LLPS impacts the behaviour of FUS in cells, e.g. its interactome. Hence, we developed a method allowing for the purification of LLPS FUS-containing droplets from cell lysates. We observe substantial alterations in the interactome, depending on its biophysical state. While non-LLPS FUS interacts mainly with factors involved in pre-mRNA processing, LLPS FUS predominantly binds to proteins involved in chromatin remodelling and DNA damage repair. Interestingly, also mitochondrial factors are strongly enriched with LLPS FUS, providing a potential explanation for the observed changes in mitochondrial gene expression in mouse models of ALS-FUS. In summary, we present a methodology to investigate the interactomes of phase separating proteins and provide evidence that LLPS shapes the FUS interactome with implications for function and disease

Sales and sincerity: The role of relational framing in word-of-mouth marketing

In word-of-mouth marketing, marketers often provide financial rewards for referrals. These rewards introduce a financial motive into an interaction among friends or acquaintances, which may harm the perceived sincerity of the referring customer. We show that this negative effect can be mitigated by disclosing the presence of financial motives, but also by the activation of a market pricing (‘sales’) relationship norm. However, such a norm has a negative effect on compliance with the referral. The effects of relationship norms are strongest when cognitive capacity is impaired, which suggests that the influence of relationship norms occurs outside the awareness of consumers. Conversely, the impact of disclosures is stronger when consumers have full cognitive capacity available