Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice.

Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes

Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala

Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM) test. The open-arm preference (ratio of open arm entries to the total number of entries) was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914) or vehicle was administered systemically (i.p.) or into the central nucleus of the amygdala (CeA, by microdialysis). The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala

Analogy Mining for Specific Design Needs

Finding analogical inspirations in distant domains is a powerful way of solving problems. However, as the number of inspirations that could be matched and the dimensions on which that matching could occur grow, it becomes challenging for designers to find inspirations relevant to their needs. Furthermore, designers are often interested in exploring specific aspects of a product-- for example, one designer might be interested in improving the brewing capability of an outdoor coffee maker, while another might wish to optimize for portability. In this paper we introduce a novel system for targeting analogical search for specific needs. Specifically, we contribute a novel analogical search engine for expressing and abstracting specific design needs that returns more distant yet relevant inspirations than alternate approaches

The inverse relationship between solar-induced fluorescence yield and photosynthetic capacity: Benefits for field phenotyping

Improving photosynthesis is considered a promising way to increase crop yield to feed a growing population. Realizing this goal requires non-destructive techniques to quantify photosynthetic variation among crop cultivars. Despite existing remote sensing-based approaches, it remains a question whether solar-induced fluorescence (SIF) can facilitate screening crop cultivars of improved photosynthetic capacity in plant breeding trials. Here we tested a hypothesis that SIF yield rather than SIF had a better relationship with the maximum electron transport rate (Jmax). Time-synchronized hyperspectral images and irradiance spectra of sunlight under clear-sky conditions were combined to estimate SIF and SIF yield, which were then correlated with ground-truth Vcmax and Jmax. With observations binned over time (i.e. group 1: 6, 7, and 12 July 2017; group 2: 31 July and 18 August 2017; and group 3: 24 and 25 July 2018), SIF yield showed a stronger negative relationship, compared with SIF, with photosynthetic variables. Using SIF yield for Jmax (Vcmax) predictions, the regression analysis exhibited an R2 of 0.62 (0.71) and root mean square error (RMSE) of 11.88 (46.86) μmol m-2 s-1 for group 1, an R2 of 0.85 (0.72) and RMSE of 13.51 (49.32) μmol m-2 s-1 for group 2, and an R2 of 0.92 (0.87) and RMSE of 15.23 (30.29) μmol m-2 s-1 for group 3. The combined use of hyperspectral images and irradiance measurements provides an alternative yet promising approach to characterization of photosynthetic parameters at plot level

Design-by-analogy: experimental evaluation of a functional analogy search methodology for concept generation improvement

Design-by-analogy is a growing field of study and practice, due to its power to augment and extend traditional concept generation methods by expanding the set of generated ideas using similarity relationships from solutions to analogous problems. This paper presents the results of experimentally testing a new method for extracting functional analogies from general data sources, such as patent databases, to assist designers in systematically seeking and identifying analogies. In summary, the approach produces significantly improved results on the novelty of solutions generated and no significant change in the total quantity of solutions generated. Computationally, this design-by-analogy facilitation methodology uses a novel functional vector space representation to quantify the functional similarity between represented design problems and, in this case, patent descriptions of products. The mapping of the patents into the functional analogous words enables the generation of functionally relevant novel ideas that can be customized in various ways. Overall, this approach provides functionally relevant novel sources of design-by-analogy inspiration to designers and design teams.SUTD-MIT International Design Centre (IDC)National Science Foundation (U.S.) (Grant Numbers CMMI-0855326, CMMI-0855510, and CMMI-08552930

Function Based Design-by-Analogy: A Functional Vector Approach to Analogical Search

Design-by-analogy is a powerful approach to augment traditional concept generation methods by expanding the set of generated ideas using similarity relationships from solutions to analogous problems. While the concept of design-by-analogy has been known for some time, few actual methods and tools exist to assist designers in systematically seeking and identifying analogies from general data sources, databases, or repositories, such as patent databases. A new method for extracting functional analogies from data sources has been developed to provide this capability, here based on a functional basis rather than form or conflict descriptions. Building on past research, we utilize a functional vector space model (VSM) to quantify analogous similarity of an idea's functionality. We quantitatively evaluate the functional similarity between represented design problems and, in this case, patent descriptions of products. We also develop document parsing algorithms to reduce text descriptions of the data sources down to the key functions, for use in the functional similarity analysis and functional vector space modeling. To do this, we apply Zipf's law on word count order reduction to reduce the words within the documents down to the applicable functionally critical terms, thus providing a mapping process for function based search. The reduction of a document into functional analogous words enables the matching to novel ideas that are functionally similar, which can be customized various ways. This approach thereby provides relevant sources of design-by-analogy inspiration. As a verification of the approach, two original design problem case studies illustrate the distance range of analogical solutions that can be extracted. This range extends from very near-field, literal solutions to far-field cross-domain analogies.National Science Foundation (U.S.) (Grant CMMI-0855326)National Science Foundation (U.S.) (Grant CMMI-0855510)National Science Foundation (U.S.) (Grant CMMI-0855293)SUTD-MIT International Design Centre (IDC

Mathematically Modeling Spillover Dynamics of Emerging Zoonoses with Intermediate Hosts

The World Health Organization describes zoonotic diseases as a major pandemic threat, and modeling the behavior of such diseases is a key component of their control. Many emerging zoonoses, such as SARS, Nipah, and Hendra, mutated from their wild type while circulating in an intermediate host population, usually a domestic species, to become more transmissible among humans, and moreover, this transmission route will only become more likely as agriculture and trade intensifies around the world. Passage through an intermediate host enables many otherwise rare diseases to become better adapted to humans, and so understanding this process with mathematical epidemiological models is necessary to prevent epidemics of emerging zoonoses, guide policy interventions in public health, and predict the behavior of an epidemic. In this paper, we account for spillovers of a zoonotic disease mutating in an intermediate host by means of modeling transmission dynamics within and between three host species, namely, wild reservoir, intermediate domestic animals, and humans. We calculate the basic reproductive number of the pathogen, present critical conditions for the emergence dynamics of zoonosis, and perform stability analysis of admissible disease equilibria. Our analytical results agree well with long-term simulations of the system. We find that in the presence of biologically realistic interspecies transmission parameters, a zoonotic disease can establish itself in humans even if it fails to persist in its reservoir and intermediate host species. Our model and results can be used to understand the dynamic behavior of any zoonosis with intermediate hosts and assist efforts to protect public health.Comment: Comments are welcom

Facilitating Design-by-Analogy: Development of a Complete Functional Vocabulary and Functional Vector Approach to Analogical Search

Design-by-analogy is an effective approach to innovative concept generation, but can be elusive at times due to the fact that few methods and tools exist to assist designers in systematically seeking and identifying analogies from general data sources, databases, or repositories, such as patent databases. A new method for extracting analogies from data sources has been developed to provide this capability. Building on past research, we utilize a functional vector space model to quantify analogous similarity between a design problem and the data source of potential analogies. We quantitatively evaluate the functional similarity between represented design problems and, in this case, patent descriptions of products. We develop a complete functional vocabulary to map the patent database to applicable functionally critical terms, using document parsing algorithms to reduce text descriptions of the data sources down to the key functions, and applying Zipf’s law on word count order reduction to reduce the words within the documents. The reduction of a document (in this case a patent) into functional analogous words enables the matching to novel ideas that are functionally similar, which can be customized in various ways. This approach thereby provides relevant sources of design-by-analogy inspiration. Although our implementation of the technique focuses on functional descriptions of patents and the mapping of these functions to those of the design problem, resulting in a set of analogies, we believe that this technique is applicable to other analogy data sources as well. As a verification of the approach, an original design problem for an automated window washer illustrates the distance range of analogical solutions that can be extracted, extending from very near-field, literal solutions to far-field cross-domain analogies. Finally, a comparison with a current patent search tool is performed to draw a contrast to the status quo and evaluate the effectiveness of this work.National Science Foundation (U.S.) (grant number CMMI-0855510)National Science Foundation (U.S.) (grant number CMMI-0855326)National Science Foundation (U.S.) (grant number CMMI-0855293)SUTD-MIT International Design Centre (IDC