Miracle-dz/UniFAR-FTUs huggingface dataset:
Atrial Natriuretic Peptide-initiated cGMP Pathways Regulate Vasodilator-stimulated Phosphoprotein Phosphorylation and Angiogenesis in Vascular Endothelium*

Nitric oxide (NO)- and atrial natriuretic peptide (ANP)-initiated cGMP signaling cascades are important in the maintenance of cardiovascular homeostasis. The molecular signaling mechanisms downstream of cGMP are not well understood, however. We have used small interfering RNA (siRNA) approaches to specifically knock down a series of signaling proteins in bovine aortic endothelial cells, and we have combined biochemical analyses with physiological assays to investigate cGMP-mediated signal transduction pathways. Activation of particulate guanylate cyclase (GC-A) by ANP leads to a substantial, dose-dependent, rapid, and sustained increase in intracellular cGMP. In contrast, stimulation of soluble guanylate cyclase by NO yields only a weak and transient increase in cGMP. ANP-induced cGMP production is selectively suppressed by siRNA-mediated knockdown of GC-A. ANP greatly enhances the phosphorylation at Ser-239 of the vasodilator-stimulated phosphoprotein (VASP), a major substrate of cGMP-dependent protein kinase (PKG) that significantly influences actin dynamics. Moreover, the ANP-induced phosphorylation of VASP at Ser-239 is accompanied by increased actin stress fiber formation and enhanced endothelial tube formation. siRNA-mediated knockdown of GC-A, VASP, or PKG abolishes ANP-induced VASP Ser-239 phosphorylation, stress fiber formation, and endothelial tube formation. We have demonstrated similar findings in human umbilical vein endothelial cells, where ANP substantially enhances intracellular cGMP content, phosphorylation of VASP at Ser-239, and endothelial tube formation. Taken together, our findings suggest that ANP-mediated cGMP signal transduction pathways regulate PKG phosphorylation of VASP Ser-239 in endothelial cells, resulting in reorganization of the actin cytoskeleton and enhancement of angiogenesis.
Simple, Fast, and Scalable Reachability Oracle

A reachability oracle (or hop labeling) assigns each vertex v two sets of vertices: Lout(v) and Lin(v), such that u reaches v iff Lout(u) ∩ Lin(v) ≠ 0. Despite their simplicity and elegance, reachability oracles have failed to achieve efficiency in more than ten years since their introduction: The main problem is high construction cost, which stems from a set-cover framework and the need to materialize transitive closure. In this paper, we present two simple and efficient labeling algorithms, Hierarchical-Labeling and Distribution-Labeling, which can work onmassive real-world graphs: Their construction time is an order of magnitude faster than the set-cover based labeling approach, and transitive closure materialization is not needed. On large graphs, their index sizes and their query performance can now beat the state-of-the-art transitive closure compression and online search approaches.
TRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements

ABSTRACT Previous studies identified clones of the U937 promonocytic cell line that were either permissive or nonpermissive for human immunodeficiency virus type 1 (HIV-1) replication. These clones were investigated further in the search for host restriction factors that could explain their differential capacity to support HIV-1 replication. Among known HIV-1 restriction factors screened, tripartite motif-containing protein 22 (TRIM22) was the only factor constitutively expressed in nonpermissive and absent in permissive U937 cells. Stable TRIM22 knockdown (KD) rescued HIV-1 long-terminal-repeat (LTR)-driven transcription in KD-nonpermissive cells to the levels observed in permissive cells. Conversely, transduction-mediated expression of TRIM22 in permissive cells reduced LTR-driven luciferase expression by ∼7-fold, supporting a negative role of TRIM22 in HIV-1 transcription. This finding was further confirmed in the human T cell line A3.01 expressing TRIM22. Moreover, overexpression of TRIM22 in 293T cells significantly impaired basal and phorbol myristate acetate-ionomycin-induced HIV-1 LTR-driven gene expression, whereas inhibition of tumor necrosis factor alpha-induced viral transcription was a consequence of lower basal expression. In agreement, TRIM22 equally inhibited an LTR construct lacking the tandem NF-κB binding sites. In addition, TRIM22 did not affect Tat-mediated LTR transactivation. Finally, these effects were independent of TRIM22 E3 ubiquitin-ligase activity. In the context of replication-competent virus, significantly higher levels of HIV-1 production were observed in KD-nonpermissive versus control nonpermissive U937 cells after infection. In contrast, lower peak levels of HIV-1 replication characterized U937 and A3.01 cells expressing TRIM22 versus their control transduced counterpart. Thus, nuclear TRIM22 significantly impairs HIV-1 replication, likely by interfering with Tat- and NF-κB-independent LTR-driven transcription.
Sales Force Contracting Under Endogenous Risk ∗

for many helpful comments on earlier versions of this paper. The paper has also benefited from comments at the MIT Marketing Seminar and the Marketing Science Conference. Abstract Salespeople choose actions by trading off cost, return and risk. The literature does not consider the impact of risk on action choice. This tradeoff has important implications for the firm. First, the firm may provide no insurance in the salary. Since the agent's action choice will determine her risk, the salary cannot compensate her for it. Second, the firm may not be able to design an incentive scheme to implement particularly risky actions. Finally, a multi-product firm may not be able to design a scheme in which the agent splits her effort across two products that are technological substitutes. One solution is a sales force structured by product. Complements may be more costly to sell through a product structure. Thus, substitutes (complements) should be sold through a product (territory) structure. Scene from " My Little Chickadee " in which a group of men are playing cards: Cousin Zeb: (Walking by, surprised) Uh, is this a game of chance? Cuthbert J. Twillie: Not the way I play it, no.
Credit Market Imperfections and Persistent Unemployment

This paper develops the thesis that credit market frictions may be an important contributor to high unemployment in Europe. When a change in the technological regime necessitates the creation of new firms, this can happen relatively rapidly in the U.S. where credit markets function efficiently. In contrast, in Europe, job creation is constrained by credit market imperfections, so unemployment rises and remains high for an extended period. The data show that there has not been slower growth in the most credit dependent industries in Europe relative to the U.S., but the share of employment in these industries is lower than in the U.S. This suggests that although credit market imperfections are unlikely to have been the major cause of the increase in European unemployment, they may have played some role in limiting European employment growth.
Transformation from relative observability to observability

In order to operate discrete event systems, agents utilize information from observing event sequences. This information is often incomplete due to communication defects, sensor malfunction, etc. Thus, understanding partial observation is essential to operating these systems. We develop, in this paper, an algorithm that reduces relative observability problems to observability problems in the context of centralized systems. Our extended results are in the context of a general language-based dynamic observation setup in which event-based observation in literature is a special case.
Estimate of exponential convergence rate and exponential stability for neural networks

Estimate of exponential convergence rate and exponential stability are studied for a class of neural networks which includes the Hopfield neural networks and the cellular neural networks. Both local and global exponential convergence is discussed. Theorems for estimate of exponential convergence rate are established and the bounds on the rate of convergence are given. The domains of attraction in the case of local exponential convergence are obtained. Simple conditions are presented for checking exponential stability of the neural networks.
Post-Transcriptional Silencing of Flavonol Synthase mRNA in Tobacco Leads to Fruits with Arrested Seed Set

Flavonoids are synthesized by phenylpropanoid pathway. They are known to participate in large number of physiological and biochemical processes in plants. Parthenocarpy and male sterility has earlier been reported by silencing chalcone synthase (CHS) encoding gene. Silencing of CHS has blocked the synthesis of most of useful flavonoids including flavan-3-ols and flavonols. Also, these studies could not identify whether parthenocarpy/male sterility were due to lack of flavan-3-ols or flavonols or both. Flavonol synthase (FLS) is an important enzyme of flavonoid pathway that catalyzes the formation of flavonols. In this article, we propose a novel strategy towards the generation of seedless or less-seeded fruits by downregulation of flavonol biosynthesis in tobacco (Nicotiana tabacum cv Xanthi) through post-transcriptional gene silencing (PTGS) of FLS encoding mRNA. The FLS silenced lines were observed for 20-80% reduction in FLS encoding gene expression and 25–93% reduction in flavonol (quercetin) content. Interestingly, these FLS silenced tobacco lines also showed reduction in their anthocyanidins content. While the content of flavan-3-ols (catechin, epi-catechin and epi-gallocatechin) was found to be increased in FLS silenced lines. The delayed flowering in FLS silenced lines could be due to decrease in level of indole acetic acid (IAA) at apical region of their shoots. Furthermore, the pollen germination was hampered and pollens were unable to produce functional pollen tube in FLS silenced tobacco lines. Pods of FLS silenced lines contained significantly less number of seeds. The in vitro and in vivo studies where 1 µM quercetin was supplied to germination media, documented the restoration of normal pollen germination and pollen tube growth. This finding identified the role of flavonols particularly quercetin in pollen germination as well as in the regulation of plant fertility. Results also suggest a novel approach towards generation of seedless/less-seeded fruits via PTGS of FLS encoding gene in plants.
Unexpected persistence of platelet hyporeactivity beyond the neonatal period: a flow cytometric study in neonates, infants and older children

Summary Previous studies, using flow cytometry, have reported a lower platelet reactivity in neonates compared to adults. Only few studies were carried out in older children, and results were controversial in terms of age to reach adult platelet function. We studied a total of 125 healthy neonates, infants and older children, and 15 adults. αIIbβ3 expression on resting and activated platelets was lower in all children, with an impaired capability of αIIbβ3 activation (PAC1 and bound fibrinogen). This defect was observed until the age of fifteen with a gradual recovery with age. In neonates, we observed a defect of GPIbα internalization, and demonstrated that this defect persisted in older children as well. In contrast with αIIbβ3 integrin activation, we did not observe a gradual age-dependent recovery. These unexpected results point out the need for reference values in childhood.
Molecular dynamics and MesoDyn simulations for the miscibility of polyvinyl alcohol/polyvinyl pyrrolidone blends

The miscibility of polyvinyl alcohol (PVA)/polyvinyl pyrrolidone (PVP) blends is investigated by atomistic molecular dynamics (MD). Specific volumes of five PVA/PVP blends (with mass ratio (ω, ω = mPVA /mPVP) at 25%, 50%, 100%, 200% and 400%) as well as pure PVA and PVP are reviewed at the temperature of 298 K. The Flory–Huggins parameter determined from the cohesive energy densities and the radial distribution functions of the inter-molecular atoms suggest that PVA/PVP blends can be miscible at all sample. This is further supported by the morphologies of PVA/PVP blends. Then the phase separation kinetics of PVA/PVP blends was examined using density profiles calculated from the MesoDyn approach to examine mesoscopic morphology of the blends, and the result strengthening the view that the blends can be miscible with any sample mass fraction by the enthalpy contributions of H-bonds.
Distinguishing cognitive state with multifractal complexity of hippocampal interspike interval sequences

Fractality, represented as self-similar repeating patterns, is ubiquitous in nature and the brain. Dynamic patterns of hippocampal spike trains are known to exhibit multifractal properties during working memory processing; however, it is unclear whether the multifractal properties inherent to hippocampal spike trains reflect active cognitive processing. To examine this possibility, hippocampal neuronal ensembles were recorded from rats before, during and after a spatial working memory task following administration of tetrahydrocannabinol (THC), a memory-impairing component of cannabis. Multifractal detrended fluctuation analysis was performed on hippocampal interspike interval sequences to determine characteristics of monofractal long-range temporal correlations (LRTCs), quantified by the Hurst exponent, and the degree/magnitude of multifractal complexity, quantified by the width of the singularity spectrum. Our results demonstrate that multifractal firing patterns of hippocampal spike trains are a marker of functional memory processing, as they are more complex during the working memory task and significantly reduced following administration of memory impairing THC doses. Conversely, LRTCs are largest during resting state recordings, therefore reflecting different information compared to multifractality. In order to deepen conceptual understanding of multifractal complexity and LRTCs, these measures were compared to classical methods using hippocampal frequency content and firing variability measures. These results showed that LRTCs, multifractality, and theta rhythm represent independent processes, while delta rhythm correlated with multifractality. Taken together, these results provide a novel perspective on memory function by demonstrating that the multifractal nature of spike trains reflects hippocampal microcircuit activity that can be used to detect and quantify cognitive, physiological, and pathological states.
Recreational Scuba Diving In Caribbean Marine Protected Areas: Do The Users Pay?

Abstract There are more than 200 marine protected areas (MPAs) in the Caribbean and Central America that contain coral reefs and are therefore theoretically attractive to scuba divers. One fifth of dive operators in 30 countries were surveyed for their use of MPAs: the majority are located within 20 km of at least one MPA and 46% conduct at least 80% of their diving within a MPA. An estimated 15 million dives take place outside of Florida each year, half of these occurring inside MPAs. Only 25% of MPAs containing coral reefs charge divers an entry or user fee, which is most usually USD 2–3 levied per dive or per diver. The revenue generated by these fees is estimated at USD 1–2 million annually, but the potential for generating income has not been fully realized. A significant contribution to the cost of regional conservation could be achieved if higher fees were applied more widely than at present.
Multilevel decision method for band-limited digital FM with limiter-discriminator detection

A new decision method for band-limited digital FM that employs discriminator detection is presented. This new method adopts a multilevel decision scheme to soften the intersymbol interference effects caused by severe band limitation. It is shown that applying this method significantly improves bit error rate (BER) performance of digital FM using discriminator detection. Theoretical BER evaluation proves the superiority of this method, and establishes the optimum values for fundamental transmitter parameters. Experimental results are provided to support the superiority of this method.
Twentieth-century fire patterns on forest service lands

Maps of twentieth-century fires on Forest Service lands were analyzed. Time trends showed no overall trend in acreage, but humancaused fires decreased and lightning fires increased. The increase in lightning fire was dominated by two recent years (1987 and 1990), but more subtle trends prior to 1987 indicated that lightning fires were following a trajectory separate from that of human-caused fires. Landscape-level analysis indicated a strong and stable elevation gradient in burn frequency, and this allowed the development of an accurate descriptive model. An analysis relating fire frequency to vegetation type showed that certain types of vegetation burn more than expected given their elevation, but that burning within these types followed the general trend, with higher-elevation types burning less frequently. An analysis of reburn patterns showed that, given a particular risk zone, fire location is nearly random. Acreage that burned more than three times had a greater burn frequency than would be expected if the fires were random, but the total area with multiple burns was tiny. The location of multiple-burn sites indicated that they were associated with special features such as busy roads. Fire correlations with general weather indices were weak, but more area burned in hot, dry years. Perhaps more importantly, all of the extreme fire years occurred when it was hot and dry. Short-term (1979-89) analyses of drought patterns indicated that drought decreased with increasing elevation, paralleling the decrease in fire frequency. Periods of drought were highly synchronized between weather stations, increasing the window during which extreme fire events could occur at all elevations. The strong and stable elevation trends in fire frequency indicated that future risk could be inferred from twentieth-century fire patterns. The largely random location of fires within each risk zone indicated that a general zonal strategy for fire control would be most effective. The fire acreage patterns over time indicate that while suppression and possibly education can reduce human-caused fires, large lightning fires will continue to occur. Overall risk will vary with weather, but we can expect that large fires will occur during future droughts. If the weather in the twenty-first century is similar to weather in the twentieth century, we might reasonably expect 40% to 60% of the foothills zone to see fire at least once in the next 100 years.
AEGIS-X: DEEP CHANDRA IMAGING OF THE CENTRAL GROTH STRIP

We present the results of deep Chandra imaging of the central region of the Extended Groth Strip, the AEGIS-X Deep (AEGIS-XD) survey. When combined with previous Chandra observations of a wider area of the strip, AEGIS-X Wide (AEGIS-XW), these provide data to a nominal exposure depth of 800 ks in the three central ACIS-I fields, a region of approximately 0.29 deg2. This is currently the third deepest X-ray survey in existence; a factor ∼ 2 – 3 ? > shallower than the Chandra Deep Fields (CDFs), but over an area ∼3 times greater than each CDF. We present a catalog of 937 point sources detected in the deep Chandra observations, along with identifications of our X-ray sources from deep ground-based, Spitzer, GALEX, and Hubble Space Telescope imaging. Using a likelihood ratio analysis, we associate multiband counterparts for 929/937 of our X-ray sources, with an estimated 95% reliability, making the identification completeness approximately 94% in a statistical sense. Reliable spectroscopic redshifts for 353 of our X-ray sources are available predominantly from Keck (DEEP2/3) and MMT Hectospec, so the current spectroscopic completeness is ∼38%. For the remainder of the X-ray sources, we compute photometric redshifts based on multiband photometry in up to 35 bands from the UV to mid-IR. Particular attention is given to the fact that the vast majority the X-ray sources are active galactic nuclei and require hybrid templates. Our photometric redshifts have mean accuracy of &sgr; = 0.04 ? > and an outlier fraction of approximately 5%, reaching &sgr; = 0.03 ? > with less than 4% outliers in the area covered by CANDELS . The X-ray, multiwavelength photometry, and redshift catalogs are made publicly available.
Management of adult diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is a rare yet potentially fatal hyperglycemic crisis that can occur in patients with both type 1 and 2 diabetes mellitus. Due to its increasing incidence and economic impact related to the treatment and associated morbidity, effective management and prevention is key. Elements of management include making the appropriate diagnosis using current laboratory tools and clinical criteria and coordinating fluid resuscitation, insulin therapy, and electrolyte replacement through feedback obtained from timely patient monitoring and knowledge of resolution criteria. In addition, awareness of special populations such as patients with renal disease presenting with DKA is important. During the DKA therapy, complications may arise and appropriate strategies to prevent these complications are required. DKA prevention strategies including patient and provider education are important. This review aims to provide a brief overview of DKA from its pathophysiology to clinical presentation with in depth focus on up-to-date therapeutic management.
Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice

Insulin‐like growth factor 2 (IGF2) was recently found to play a critical role in memory consolidation in rats and mice, and hippocampal or systemic administration of recombinant IGF2 enhances memory. Here, using a gene therapy‐based approach with adeno‐associated virus (AAV), we show that IGF2 overexpression in the hippocampus of aged wild‐type mice enhances memory and promotes dendritic spine formation. Furthermore, we report that IGF2 expression decreases in the hippocampus of patients with Alzheimer's disease, and this leads us to hypothesize that increased IGF2 levels may be beneficial for treating the disease. Thus, we used the AAV system to deliver IGF2 or IGF1 into the hippocampus of the APP mouse model Tg2576 and demonstrate that IGF2 and insulin‐like growth factor 1 (IGF1) rescue behavioural deficits, promote dendritic spine formation and restore normal hippocampal excitatory synaptic transmission. The brains of Tg2576 mice that overexpress IGF2 but not IGF1 also show a significant reduction in amyloid levels. This reduction probably occurs through an interaction with the IGF2 receptor (IGF2R). Hence, IGF2 and, to a lesser extent, IGF1 may be effective treatments for Alzheimer's disease.