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A membrane-based approach to pulsatile delivery, termed here as Barrier-Mediated Pulsatile Release (BMPR), sequesters each chemical dose into its own stimuli-sensitive reservoir film, each covered by a stimulant barrier membrane to delay triggering for a prescribed period time. These barrier/depot pairs are then stacked sequentially, with the delay time for the next barrier commencing with the stimulation of the previous depot, assuring a controlled period between each pulse. This paper introduces the first generalized BMPR system, using hydrogel depots that can be adapted to a variety of stimulants, coupled with barriers that rely on sacrificial stimulant scavengers to provide controlled delay times spanning orders of magnitude. Poly(methyl methacrylate-co-dimethylamino ethyl methacrylate) hydrogels are used to demonstrate pulsatile release of multiple solutes triggered by buffered citric acid. Zinc oxide nanoparticles loaded in poly(vinyl alcohol) hydrogel barriers delay acid permeation to each depot. Depot thickness, pH, and buffer strength are each shown to affect the stimulant permeation, swelling, and solute diffusion rates from the depots, with different processes becoming rate-limiting under different conditions. The delay time for each barrier varies linearly with ZnO scavenger loading, scavenger center-of-mass, and the square of the barrier thickness, providing multiple pathways for tuning delay time over a wide range. BMPR devices releasing up to 10 pulses are demonstrated, with no inherent limit on the number of pulses possible.
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Cervical cancer is the second most common form of cancer among women. There are over 100 different types of human papillomavirus (HPV), 40 of which are frequently detected in anogenital mucosa. HPV is the primary etiological agent of cervical cancer and is present predominantly in cervical cancers. Thirteen commonly recognized high-risk genotypes have oncogenic potential. The most common high-risk HPV (hrHPV) genotypes in cervical cancer are HPV16 and HPV18, which have the greatest malignancies. The objective of this study was to determine the distribution of hrHPV types in patient samples received at the Mount Sinai Medical Center for routine cytology and HPV testing. In addition, the study compared the sensitivity of the Hybrid Capture 2 (HC2) and Roche Linear Array HPV Genotyping assays.
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Generalized pustular psoriasis is a severe skin disease characterized by epidermal hyperplasia, neutrophil-rich abscesses within the epidermis, and a mixed inflammatory infiltrate in the dermis. The disease may be caused by missense mutations in the IL-36 receptor antagonist, IL-36Ra. Curiously, the related IL-1Ra has therapeutic effects in some of these latter patients. Here, using an experimental mouse model of psoriasiform skin inflammation, we demonstrate in vivo connections between IL-36 and IL-1 expression. After disease initiation, IL-36α-deficient mice exhibited dramatically diminished skin pathology, including absence of epidermal neutrophils, reduced keratinocyte acanthosis, and less dermal edema. In contrast, IL-36β and IL-36γ knockout mice developed disease indistinguishable from that of wild-type mice. The endogenous IL-36α was not processed through proteolysis. Although IL-36α expression was strongly induced in an IL-1 signaling-dependent manner during disease, expression of IL-1α was also dependent upon IL-36α. Hence, after being upregulated by IL-1α, IL-36α acts through a feedback mechanism to boost IL-1α levels. Analyses of double knockout mice further revealed that IL-36α and IL-1α cooperate to promote psoriasis-like disease. In conclusion, IL-1α and IL-36α form a self-amplifying inflammatory loop in vivo that in patients with insufficient counter regulatory mechanisms may become hyper-engaged and/or chronic.
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In this work, we propose a method to interactively deform high-resolution volumetric datasets, such as those obtained through medical imaging. Interactive deformation enables the visualization of these datasets in full detail using state-of-the-art volume rendering techniques as they are dynamically modified. Our approach relies on resampling the original dataset to a target regular grid, following a 3D rasterization technique. We employ an implicit auxiliary mesh to execute resampling, which allows us to decouple mapping of the deformation field to the volume from actual resampling. In this way, our method is practically independent of the deformation method of choice, as well as of the resolution of the deformation meshes. We show how our method lends itself nicely to an efficient, massively parallel implementation on GPUs, and we demonstrate its application on several high-resolution datasets and deformation models.
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Blood lost at exsanguination during the Halal slaughter of lambs was compared between the slaughter methods of Traditional Religious Slaughter without stunning (TRS), Electric Head-Only Stunning (EHOS) and Post-Cut Electric Head-Only Stunning (PCEHOS). Two protocols were examined, Experimental (80 lambs) and Commercial (360 lambs), assessing varying periods of animal orientation during the 4min bleeding process (upright orientation before vertical hanging). Live-weight, blood weight (Experimental only), carcass weights and by-product weights were recorded. The Experimental protocol highlighted an increase in blood loss at 60s in EHOS and PCEHOS compared to TRS (P0.05) in final blood loss between treatments. This research was undertaken to inform discussion on the merits of different slaughter methods compatible with Halal requirements.
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Levees have historically been a dominant approach to riverine flood control in the United States. Recent investigations have found many levees around the country are in substandard condition, however, and some communities are moving to upgrade and repair their levee systems. Little empirical work has examined how increasing flood protection from levees is valued. We present estimates of the capitalization of upgraded levee protection into commercial property prices in St. Louis County, Missouri. By using controls for surrounding land cover and coarsened exact matching to ensure close distribution between treatment and control on surrounding land cover, we attempt to isolate the price effect of the levee from agglomeration effects that may also be operating. We find that commercial properties protected by a 500-year levee do not have a statistically significant price discount as compared with properties not in a floodplain. We find the selling price of properties with levee protection to be higher (although also insignificant in many specifications) than those in a floodplain without levee protection.
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Programmed cell death (PCD) is crucial in plant organogenesis and survival. In this review the involvement of mitochondria and chloroplasts in PCD execution is critically assessed. Recent findings support a central role for mitochondria in PCD, with newly identified components of the mitochondrial electron transport chain (mETC), FOF1 ATP synthase, cardiolipins, and ATPase AtOM66. While chloroplasts received less attention, their contribution to PCD is well supported, suggesting that they possibly contribute by producing reactive oxygen species (ROS) in the presence of light or even contribute through cytochrome f release. Finally we discuss two working models where mitochondria and chloroplasts could cooperatively execute PCD: mitochondria initiate the commitment steps and recruit chloroplasts for swift execution or, alternatively, mitochondria and chloroplasts could operate in parallel.
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Anarchic hand syndrome (AHS) is a rare neurological condition characterized by seemingly purposeful, goal-directed hand movements which the person afflicted by the syndrome is not, however, in control of. By extensively examining a patient with AHS we provide novel neuropsychological and lesion mapping data that shed new light on the possibility of modulating specific symptoms associated with AHS, in particular unilateral apraxia and magnetic apraxia. Moreover, we compared lesion mapping data with an in depth analysis of previous studies in order to explore the neural network responsible for the complex symptomatology associated with this syndrome. We found that non-primarily motor variables (e.g. the nature of the object to be grasped and integration of visuo-spatial feedback in action) play an important role in determining AHS symptomatology. Moreover, we found that lesions involving various different parts of the motor control network (the corpus callosum, the anterior cingulate cortex and the supplementary motor area, the parietal areas and thalamus) are closely linked to partially differing AHS symptoms. The comparison of our data with those reported in previous studies indicate that AHS is a multifaceted and complex syndrome in which the influence of non-primarily motor, emotional and higher-order components may be largely underestimated.
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Increased concern with the impacts that changing coastal environments can have on coastal fishing communities led to a recent effort by NOAA Fisheries social scientists to develop a set of indicators of social vulnerability and resilience for the U.S. Southeast and Northeast coastal communities. A goal of the NOAA Fisheries social vulnerability and resilience indicator program is to support time and cost effective use of readily available data in furtherance of both social impact assessments of proposed changes to fishery management regulations and climate change adaptation planning. The use of the indicators to predict the response to change in coastal communities would be enhanced if community level analyses could be grouped effectively. This study examines the usefulness of combining 1130 communities into 35 relevant subgroups by comparing results of a numerical taxonomy with data collected by interview methods, a process herein referred to as “ground-truthing.” The validation of the taxonomic method by the method of ground-truthing indicates that the clusters are adequate to be used to select communities for in-depth research.
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The determination of the required seawall height is usually based on the combination of wind speed (or wave height) and still water level according to a specified return period, e.g., 50-year return period wind speed and 50- year return period still water level. In reality, the two variables are be partially correlated. This may be lead to overdesign (costs) of seawall structures. The above-mentioned return period for the design of a seawall depends on economy, society and natural environment in the region. This means a specified risk level of overtopping or damage of a seawall structure is usually allowed. The aim of this paper is to present a conditional risk probability-based seawall height design method which incorporates the correlation of the two variables. For purposes of demonstration, the wind speeds and water levels collected from Jiangsu of China are analyzed. The results show this method can improve seawall height design accuracy.
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