Miracle-dz/UniFAR-FTUs huggingface dataset:
FIH‐Dependent Asparaginyl Hydroxylation of Ankyrin Repeat Domain‐Containing Proteins

Studies on hypoxia‐sensitive pathways have identified a series of Fe(II)‐dependent dioxygenases that regulate hypoxia‐inducible factor (HIF) by prolyl and asparaginyl hydroxylation. The asparaginyl hydroxylase factor inhibiting HIF (FIH) targets a conserved asparaginyl residue in the C‐terminal transactivation domain of HIF‐α. This modification suppresses HIF transcriptional activity by inhibiting co‐activator recruitment. Recent work has demonstrated that FIH targets an alternative class of substrate. Proteins containing a common interaction motif known as the ankyrin repeat domain (ARD) have been shown to be efficiently hydroxylated by FIH. This review aims to summarize what is currently known regarding ARD hydroxylation, including the kinetics and determinants of FIH‐mediated ARD hydroxylation, the structural and functional consequences of ARD hydroxylation, and the potential for cross‐talk between ARD proteins and HIF signaling.
Prediction of Response to Treatment by Gene Expression Profiling of Peripheral Blood in Patients with Microscopic Polyangiitis

The JMAAV study was an open-labeled prospective clinical trial, which proposed severity-based treatment protocols for patients with microscopic polyangiitis (MPA). The results suggest that the proposed protocols are useful (remission rate: 89.4%), but are also indicative of relapse or patient demise regardless of the treatment (recurrence rate: 19.0%; mortality rate: 10.6%). The aim of this study is to develop the method to predict response to the treatment in patients with MPA. In the present study, transcriptome analysis was performed using peripheral blood from patients enrolled in the JMAAV study before and 1-week after the beginning of treatment. The gene expression profile before treatment was not directly related to the response to the treatment. However, when the samples from 9 patients with good response (persistent remission for 18 months) were examined, the expression of 88 genes was significantly altered by the treatment. Thirty statistically reliable genes were selected, and then the alteration of expression by the treatment was examined among 22 patients, including 17 with good response, which was defined as persistent remission for 18 months and 5 with poor response, which was defined as relapse after remission or no remission. Discrimination analysis between the alteration of expression of the 30 genes by the treatment and the response identified a combination of 16 genes as the most valuable gene set to predict the response to the treatment. This preliminary study identified IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2 as the important genes that can predict the response to the treatment in patients with MPA at an early point during the therapy.
Optical generation of linearly chirped microwave pulses using fiber Bragg gratings

We demonstrate a new method to generate broad spectrum chirped microwave pulses using an electrooptical system. Two fiber Bragg gratings and a mode-locked fiber laser were used to generate pulses with a linear frequency chirp. The bandwidth of the microwave pulses can be significantly broader than the bandwidth that can be obtained using electronic systems. The parameters of the chirp can be easily controlled by adjusting the parameters of the optical system. The same method can be used to generate microwave pulses with a complex frequency modulation.
Can Information Costs Explain the Equity Premium and Stock Market Participation Puzzles ?

Unlikely. Rational delay models argue that costs of acquiring and processing information will result in delays in consumption adjustments, which could potentially explain the low contemporaneous covariation between stock returns and consumption growth. However, information costs are likely to be small. In order to explain the equity premium puzzle with such costs, it is important that small costs can generate significant delays in adjustments. This condition holds when returns are i.i. d. However, return predictability implies large benefit for market timing, which makes agents plan more frequently. The inattentive investors rebalance their portfolios infrequently, and follow a unique strategy mixing the buy-and-hold and hedging demands. Major events draw immediate attention to the market ex post, but they actually make investors plan less frequently ex ante. Fixed information costs lead to big variations for stock holdings across households, but they have limited effects on stock market participation. This is because infrequent planning helps investors “dilute” the fixed costs. ∗I thank Snehal Banerjee, Frederico Belo, George Constantinides, Lars Hansen, John Heaton, Nick Roussanov, Martin Schneider, Pietro Veronesi, participants of the GSB Asset Pricing Brownbag and the 5th Transatlantic Doctoral Conference at London Business School, and especially John Cochrane and Monika Piazzesi for helpful comments. All errors are my own. Correspondence to hchen5@ChicagoGSB.edu.
The Role of Feature Tracking in the Furrow Illusion

In the furrow illusion (Anstis, 2012), the perceived path of a moving target follows the veridical path orientation when viewed foveally, but follows the orientation of the texture when viewed peripherally. These radically different motion percepts depending on whether the stimulus is viewed foveally or peripherally has led Anstis to conclude that the furrow illusion reveals “profound differences in the way that the periphery and fovea process visual motion. ” In the current study, we rather argue that the different percepts can be explained by reduced position acuity with eccentricity and therefore do not imply different ways of processing motion per se. If feature tracking, which is position-based, is involved in the perception of the veridical motion direction, then impairing the feature tracking motion system should strengthen the illusion. To reduce contribution of the feature tracking motion system, we used a crowding paradigm consisting in presenting many nearby targets. We found that under crowding conditions, the furrow illusion was stronger. We conclude that feature tracking was involved in the perception of the veridical motion direction, which is compatible with the hypothesis that the different motion percepts at fixation and in the periphery are due to a reduced position acuity with eccentricity affecting feature tracking, not to different ways of processing motion per se.
Diastolic dysfunction and mortality in severe sepsis and septic shock.

AIMS Systolic dysfunction in septic shock is well recognized and, paradoxically, predicts better outcome. In contrast, diastolic dysfunction is often ignored and its role in determining early mortality from sepsis has not been adequately investigated. METHODS AND RESULTS A cohort of 262 intensive care unit patients with severe sepsis or septic shock underwent two echocardiography examinations early in the course of their disease. All clinical, laboratory, and survival data were prospectively collected. Ninety-five (36%) patients died in the hospital. Reduced mitral annular e'-wave was the strongest predictor of mortality, even after adjusting for the APACHE-II score, low urine output, low left ventricular stroke volume index, and lowest oxygen saturation, the other independent predictors of mortality (Cox's proportional hazards: Wald = 21.5, 16.3, 9.91, 7.0 and 6.6, P< 0.0001, <0.0001, 0.002, 0.008, and 0.010, respectively). Patients with systolic dysfunction only (left ventricular ejection fraction ≤50%), diastolic dysfunction only (e'-wave <8 cm/s), or combined systolic and diastolic dysfunction (9.1, 40.4, and 14.1% of the patients, respectively) had higher mortality than those with no diastolic or systolic dysfunction (hazard ratio = 2.9, 6.0, 6.2, P= 0.035, <0.0001, <0.0001, respectively) and had significantly higher serum levels of high-sensitivity troponin-T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). High-sensitivity troponin-T was only minimally elevated, whereas serum levels of NT-proBNP were markedly elevated [median (inter-quartile range): 0.07 (0.02-0.17) ng/mL and 5762 (1001-15 962) pg/mL, respectively], though both predicted mortality even after adjusting for highest creatinine levels (Wald = 5.8, 21.4 and 2.3, P= 0.015, <0.001 and 0.13). CONCLUSION Diastolic dysfunction is common and is a major predictor of mortality in severe sepsis and septic shock.
Blood pressure estimation using video plethysmography

Remote sensing of vital physiological signs allows for unobtrusive, nonrestrictive and non-contact assessment of individual's health. By using video plethysmogram obtained by digital camera recordings of patient's face or hands, health parameters such as heart rate, respiratory rate and heart rate variability have already been investigated. In this paper, time-domain video plethysmogram from forehead was used for calculation of pulse transit time, which is related to blood pressure. Synchronous measurements of non-contact video plethysmogram, 12-channel electrocardiogram and invasive blood pressure were performed on three subjects. Our results demonstrate that pulse transit time method can be equally efficient with non-contact VPG signal, with error mean and standard deviation of 9.48 ± 7.13 mmHg and 4.48 ± 3.29 mmHg, for systolic and mean arterial pressure, respectively. Additionally our findings show that delay in pulse transit time, calculated from two different VPG signals from forehead and palm, could provide clinically useful measure of changes in systolic blood pressure.
Research Statement Ongoing Federally Funded Research at Unr Multi-transceiver Free-space-optical Modules

My research interests are in computer, networked, and wireless systems with a recent focus on big-data networking, UAV networks, optical wireless, cyber-security and network economics, online network management, cloud-assisted routing, and network architectures. Major application areas include datacenter management, multi-owner distributed systems (e.g., smart grid), cyber-physical systems, cloud computing, policy sciences, and data-intensive collaborative computations. My work spans both theoretical and experimental aspects of networked systems research. I strongly believe in the power of analytical understanding in research. However, research problems are not always analytically approachable and necessitate hands-on and experimental evaluation. I, therefore, use prototypes and simulations to experimentally evaluate the ideas at hand, and apply analytical modeling methods as long as it is possible. I am a strong believer in inter-disciplinary research and much of my work is collaborative with experts from fields other than networking. Below, I cover some of my current research at University of Nevada, Reno (UNR) and outline future directions. In addition to the followings, my research included wireless routing [1][2], peer-topeer overlay design [3][8], cross-layer multicast for backbone video delivery [7] (funded by AT&T’s VURI Program) and network modeling of thin film growth patterns [10]. For a detailed coverage of my current and past (pre-UNR) research please see my website.
Dynamic Response Due to Behind Helmet Blunt Trauma Measured with a Human Head Surrogate

A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies.
Transformative art: art as means for long-term neurocognitive change

Every artwork leads to a unique experience by the observer or participant, may it be sensory, emotional, cognitive, interactive, or spiritual experience. At the neurobiological level, such experiences are manifested as activation of the corresponding neural networks. Neuroscience has demonstrated that experience, in particular repeated experience, can cause a long-term change in the involved brain circuits (experience-dependent plasticity). This review will discuss the molding and transformative aspect of arts, examining how repeated and on-going experience of arts may alter cognitive, emotional, and behavioral patterns as well as their underlying neural circuits. The application of this approach to cognitive training and neuropsychological rehabilitation methods will be addressed as well. In addition, it will be suggested that this approach to art, as a long-term transformative medium, may lead to a novel viewpoint on art and a different approach to its creation. Artists can design artworks that aspire to form, in addition to one-shot influencing experience, on-going experiences which gradually create a lasting change, possibly improving audiences' neuropsychological functions.
Alpha oscillations control cortical gain by modulating excitatory-inhibitory background activity

The first recordings of human brain activity in 1929 revealed a striking 8-12 Hz oscillation in the visual cortex. During the intervening 90 years, these alpha oscillations have been linked to numerous physiological and cognitive processes. However, because of the vast and seemingly contradictory cognitive and physiological processes to which it has been related, the physiological function of alpha remains unclear. We identify a novel neural circuit mechanism—the modulation of both excitatory and inhibitory neurons in a balanced configuration—by which alpha can modulate gain. We find that this model naturally unifies the prior, highly diverse reports on alpha dynamics, while making the novel prediction that alpha rhythms have two functional roles: a sustained high-power mode that suppresses scortical gain and a weak, bursting mode that enhances gain.
CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells

In rhesus macaques (RMs), experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i) set-point viral load two-logs higher than controls; (ii) macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii) substantial expansion of pro-inflammatory monocytes; (iv) aberrant activation and infection of microglial cells; and (v) lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies.
Anticancer Activity of a Novel Selective CYP17A1 Inhibitor in Preclinical Models of Castrate-Resistant Prostate Cancer

VT-464 is a novel, nonsteroidal, small-molecule CYP17A1 inhibitor with 17,20-lyase selectivity. This study evaluates the anticancer activity of VT-464 compared with abiraterone (ABI) in castrate-resistant prostate cancer cell lines and xenograft models that are enzalutamide (ENZ)-responsive (C4-2) or ENZ-resistant (MR49C, MR49F). In vitro, androgen receptor (AR) transactivation was assessed by probasin luciferase reporter, whereas AR and AR-regulated genes and steroidogenic pathway enzymes were assessed by Western blot and/or qRT-PCR. The MR49F xenograft model was used to compare effects of oral VT-464 treatment to vehicle and abiraterone acetate (AA). Steroid concentrations were measured using LC-MS chromatography. VT-464 demonstrated a greater decrease in AR transactivation compared with ABI in C4-2 and both ENZ-resistant cell lines. At the gene and protein level, VT-464 suppressed the AR axis to a greater extent compared with ABI. Gene transcripts StAR, CYP17A1, HSD17B3, and SRD5A1 increased following treatment with ABI and to a greater extent with VT-464. In vivo, intratumoral androgen levels were significantly lower after VT-464 or AA treatment compared with vehicle, with the greatest decrease seen with VT-464. Similarly, tumor growth inhibition and PSA decrease trends were greater with VT-464 than with AA. Finally, an AR-antagonist effect of VT-464 independent of CYP17A1 inhibition was observed using luciferase reporter assays, and a direct interaction was confirmed using an AR ligand binding domain biolayer interferometry. These preclinical results suggest greater suppression of the AR axis with VT-464 than ABI that is likely due to both superior selective suppression of androgen synthesis and AR antagonism. Mol Cancer Ther; 14(1); 59–69. ©2014 AACR.
MA-LEACH: Energy Efficient Routing Protocol for WSNs using Particle Swarm Optimization and Mobile Aggregator

Routing protocols for wireless sensor networks pay a great attention to the limited resources of the nodes. In this paper, we study LEACH routing protocol and its performance and propose a new protocol, MA-LEACH. We introduce a mobile aggregator which is a gadget adopted to mitigate the overhead on the cluster heads(CHs). In addition, we optimize the trajectory using particle swarm optimization (PSO). Hence, we adapt the TSP problem to our protocol to determine the optimal trajectory that a mobile aggregator could travel to visit every cluster head in the network. We simulate the proposed protocol in MATLAB and the results reveal that it outperforms LEACH in network lifetime and energy consumption. Also, we compare our findings with a recent extension to the LEACH called LEACH with fuzzy descriptors. The simulation results show that MA-LEACH surpasses LEACH with fuzzy descriptor.
Measuring missing heritability: Inferring the contribution of common variants

Significance Studies have identified thousands of common genetic variants associated with hundreds of diseases. Yet, these common variants typically account for a minority of the heritability, a problem known as “missing heritability. ” Geneticists recently proposed indirect methods for estimating the total heritability attributable to common variants, including those whose effects are too small to allow identification in current studies. Here, we show that these methods seriously underestimate the true heritability when applied to case–control studies of disease. We describe a method that provides unbiased estimates. Applying it to six diseases, we estimate that common variants explain an average of 60% of the heritability for these diseases. The framework also may be applied to case–control studies, extreme-phenotype studies, and other settings. Genome-wide association studies (GWASs), also called common variant association studies (CVASs), have uncovered thousands of genetic variants associated with hundreds of diseases. However, the variants that reach statistical significance typically explain only a small fraction of the heritability. One explanation for the “missing heritability” is that there are many additional disease-associated common variants whose effects are too small to detect with current sample sizes. It therefore is useful to have methods to quantify the heritability due to common variation, without having to identify all causal variants. Recent studies applied restricted maximum likelihood (REML) estimation to case–control studies for diseases. Here, we show that REML considerably underestimates the fraction of heritability due to common variation in this setting. The degree of underestimation increases with the rarity of disease, the heritability of the disease, and the size of the sample. Instead, we develop a general framework for heritability estimation, called phenotype correlation–genotype correlation (PCGC) regression, which generalizes the well-known Haseman–Elston regression method. We show that PCGC regression yields unbiased estimates. Applying PCGC regression to six diseases, we estimate the proportion of the phenotypic variance due to common variants to range from 25% to 56% and the proportion of heritability due to common variants from 41% to 68% (mean 60%). These results suggest that common variants may explain at least half the heritability for many diseases. PCGC regression also is readily applicable to other settings, including analyzing extreme-phenotype studies and adjusting for covariates such as sex, age, and population structure.
Posttraumatic growth in post-surgical coronary artery bypass graft patients

Recent research in posttraumatic growth has been applied to people with life-threatening illnesses to optimise recovery. There is a lack of research exploring posttraumatic growth in coronary artery bypass graft patients. This article describes the recovery experience of 14 coronary artery bypass graft patients (13 males and 1 female) at their first outpatient review post-surgery. Grounded theory analysis was used to develop a model of distinct and shared pathways to growth depending on whether patients were symptomatic or asymptomatic pre-coronary artery bypass graft. Outcomes of posttraumatic growth in this sample included action-based healthy lifestyle growth and two forms of cognitive growth: appreciation of life and new possibilities. The model of posttraumatic growth developed in this study may be helpful in guiding future research into promoting posttraumatic growth and behaviour change in coronary artery bypass graft patients.
Numerical implementation of a cohesive zone model for time and history dependent materials

A cohesive zone model approach is used in order to study the behaviour of cracks in elasto-plastic materials. The cohesive zone model being studied is time-dependent, unlike standard cohesive zone models in elasto-plasticity. The stress distribution over the cohesive zone is related to the normalised equivalent stress functional, and is expressed in the form of an Abel-type integral equation. During the stationary crack stage as well as the propagating crack stage, the aim is to study the behaviour of the cohesive zone length with respect to time as well as the crack tip opening. To aid accomplishing this aim, the stress intensity factor was set to zero at the cohesive zone tip. As well as other material parameters, the external applied load participates in the model equations. We will consider two cases for the external load, namely the case when this load is constant in time, and the case when this load behaves linearly with time. We will implement numerical schemes to obtain the crack growth as well as the cohesive zone growth with respect to time for both the elastic case and the visco-elastic case while considering different sets of parameters. The numerical convergence rates are obtained for each of the problems solved. This justifies the suitability of the numerical schemes used.