Miracle-dz/UniFAR-FTUs huggingface dataset:
Drosophila DNase I footprint database: a systematic genome annotation of transcription factor binding sites in the fruitfly, Drosophila melanogaster

UNLABELLED Despite increasing numbers of computational tools developed to predict cis-regulatory sequences, the availability of high-quality datasets of transcription factor binding sites limits advances in the bioinformatics of gene regulation. Here we present such a dataset based on a systematic literature curation and genome annotation of DNase I footprints for the fruitfly, Drosophila melanogaster. Using the experimental results of 201 primary references, we annotated 1367 binding sites from 87 transcription factors and 101 target genes in the D.melanogaster genome sequence. These data will provide a rich resource for future bioinformatics analyses of transcriptional regulation in Drosophila such as constructing motif models, training cis-regulatory module detectors, benchmarking alignment tools and continued text mining of the extensive literature on transcriptional regulation in this important model organism. AVAILABILITY http://www.flyreg. org/ CONTACT cbergman@gen.cam. ac.uk.
NBER WORKING PAPER SERIES FINANCIAL INNOVATION AND ENDOGENOUS GROWTH

Is financial innovation necessary for sustaining economic growth? To address this question, we build a Schumpeterian model in which entrepreneurs earn profits by inventing better goods and profit-maximizing financiers arise to screen entrepreneurs. The model has two novel features. First, financiers engage in the costly but potentially profitable process of innovation: they can invent better methods for screening entrepreneurs. Second, every screening process becomes less effective as technology advances. The model predicts that technological innovation and economic growth eventually stop unless financiers innovate. Empirical evidence is consistent with this dynamic, synergistic model of financial and technological innovation. Stelios Michalopoulos Brown University Department of Economics 64 Waterman Street Providence, RI 02912 and NBER smichalo@brown.edu Luc Laeven Deputy Division Chief International Monetary Fund 700 19th Avenue, NW Washington, DC 20431 and CEPR Llaeven@imf.org Ross Levine Haas School of Business University of California at Berkeley 545 Student Services Building, #1900 (F685) Berkeley, CA 94720-1900 and NBER Ross_levine@haas.berkeley. edu
E2F-Dependent Histone Acetylation and Recruitment of the Tip60 Acetyltransferase Complex to Chromatin in Late G1

ABSTRACT E2F proteins can either activate or repress transcription. Following mitogenic stimulation, repressive E2F4-p130-histone deacetylase complexes dissociate from, while activating species (E2F1, -2, and -3) associate with, target promoters. Histones H3 and H4 simultaneously become hyperacetylated, but it remains unclear whether this is a prerequisite or a consequence of E2F binding. Here, we show that activating E2F species are required for hyperacetylation of target chromatin in human cells. Overexpression of a dominant-negative (DN) E2F1 mutant in serum-stimulated T98G cells blocked all E2F binding, H4 acetylation, and, albeit partially, H3 acetylation. Target gene activation and S-phase entry were also blocked by DN E2F1. Conversely, ectopic activation of E2F1 rapidly induced H3 and H4 acetylation, demonstrating a direct role for E2F in these events. E2F1 was previously shown to bind the histone acetyltransferases (HATs) p300/CBP and PCAF/GCN5. In our hands, ectopically expressed E2F1 also bound the unrelated HAT Tip60 and induced recruitment of five subunits of the Tip60 complex (Tip60, TRRAP, p400, Tip48, and Tip49) to target promoters in vivo. Moreover, E2F-dependent recruitment of Tip60 to chromatin occurred in late G1 following serum stimulation. We speculate that the activities of multiple HAT complexes account for E2F-dependent acetylation, transcription, and S-phase entry.
Duration of Menopausal Hot Flushes and Associated Risk Factors

OBJECTIVE: To estimate the duration of moderate-to-severe menopausal hot flushes and identify potential risk factors for hot flush duration. METHODS: The Penn Ovarian Aging Study cohort was monitored for 13 years. Hot flushes were evaluated at 9-month to 12-month intervals through in-person interviews. The primary outcome was the duration of moderate-to-severe hot flushes estimated by survival analysis (n=259). Potential risk factors included menopausal stage, age, race, reproductive hormone levels, body mass index (BMI), and current smoking. A secondary analysis included women who reported any hot flushes (n=349). RESULTS: The median duration of moderate-to-severe hot flushes was 10.2 years and was strongly associated with menopausal stage at onset. Hot flushes that started near entry into the menopause transition had a median duration greater than 11.57 years; onset in the early transition stage had a median duration of 7.35 years (95% confidence interval [CI] 4.94–8.89; P<.001); and onset in the late transition to postmenopausal stages had a median duration of 3.84 years (95% CI 1.77–5.52; P<.001). The most common ages at onset of moderate-to-severe hot flushes were 45–49 years (median duration, 8.1 years; 95% CI 5.12–9.28). African American women had a longer duration of hot flushes than white women in adjusted analysis. CONCLUSION: The median duration of hot flushes considerably exceeded the timeframe that is generally accepted in clinical practice. The identified risk factors, particularly menopausal stage, race, and BMI, are important to consider in individualizing treatment and evaluating the risk-to-benefit ratio of hormones and other therapies. LEVEL OF EVIDENCE: II
Phylogenetic signal in the community structure of host-specific microbiomes of tropical marine sponges

Sponges (Porifera) can host diverse and abundant communities of microbial symbionts that make crucial contributions to host metabolism. Although these communities are often host-specific and hypothesized to co-evolve with their hosts, correlations between host phylogeny and microbiome community structure are rarely tested. As part of the Earth Microbiome Project (EMP), we surveyed the microbiomes associated with 20 species of tropical marine sponges collected over a narrow geographic range. We tested whether (1) univariate metrics of microbiome diversity displayed significant phylogenetic signal across the host phylogeny; (2) host identity and host phylogeny were significant factors in multivariate analyses of taxonomic and phylogenetic dissimilarity; and (3) different minimum read thresholds impacted these results. We observed significant differences in univariate metrics of diversity among host species for all read thresholds, with strong phylogenetic signal in the inverse Simpson's index of diversity (D). We observed a surprisingly wide range of variability in community dissimilarity within host species (4–73%); this variability was not related to microbial abundance within a host species. Taxonomic and phylogenetic dissimilarity were significantly impacted by host identity and host phylogeny when these factors were considered individually; when tested together, the effect of host phylogeny was reduced, but remained significant. In our dataset, this outcome is largely due to closely related host sponges harboring distinct microbial taxa. Host identity maintained a strong statistical signal at all minimum read thresholds. Although the identity of specific microbial taxa varied substantially among host sponges, closely related hosts tended to harbor microbial communities with similar patterns of relative abundance. We hypothesize that microbiomes with low D might be structured by regulation of the microbial community by the host or by the presence of competitively dominant symbionts that are themselves under selection for host specificity.
Hierarchical Bayesian modeling of heterogeneous cluster‐ and subject‐level associations between continuous and binary outcomes in dairy production

The augmentation of categorical outcomes with underlying Gaussian variables in bivariate generalized mixed effects models has facilitated the joint modeling of continuous and binary response variables. These models typically assume that random effects and residual effects (co)variances are homogeneous across all clusters and subjects, respectively. Motivated by conflicting evidence about the association between performance outcomes in dairy production systems, we consider the situation where these (co)variance parameters may themselves be functions of systematic and/or random effects. We present a hierarchical Bayesian extension of bivariate generalized linear models whereby functions of the (co)variance matrices are specified as linear combinations of fixed and random effects following a square‐root‐free Cholesky reparameterization that ensures necessary positive semidefinite constraints. We test the proposed model by simulation and apply it to the analysis of a dairy cattle data set in which the random herd‐level and residual cow‐level effects (co)variances between a continuous production trait and binary reproduction trait are modeled as functions of fixed management effects and random cluster effects.
Statistical Analysis of a Jointly Optimized Beamformer-Assisted Acoustic Echo Canceler

This work presents a statistical analysis of a jointly optimized beamformer-assisted acoustic echo canceler (AEC). It is shown that the constrained joint optimization problem can be formulated so that it becomes equivalent to the linearly-constrained minimum variance problem. The new formulation leads to analytical models that can be used to predict the transient performance of adaptive wideband beamformers. A stochastic model is derived for the transient and steady-state behaviors of the residual echo power. A convergence analysis provides a stability bound for the adaptation step-size. Monte Carlo simulations illustrate the accuracy of the model, which is then used to provide design guidelines. Application of the new model confirms previous experimental findings that the same cancellation performance of a single-microphone AEC can be achieved with a shorter AEC when the possibility of spatial filtering is available.
Region Management by Finite-State Robots

Advancing technologies have enabled simple mobile robots that collaborate to perform complex tasks. Understanding how to achieve such collaboration with simpler robots leverages these advances, potentially allowing more robots for a given cost and/or decreasing the cost of deploying a fixed number of robots. This paper is a step toward understanding the algorithmic strengths and weaknesses of robots that are identical mobile finite-state machines (FSMs)—FSMs being the avatars of simple, yet non-trivial, discrete control structures.We study the ability of (teams of) FSMs to identify and search varied-size quadrants of square (i.e. n×n) meshes of tiles—such meshes being the avatars of simple tesselated geographically constrained environments. Each team must be able to accomplish its assigned tasks in arbitrarily large meshes—i.e. for arbitrarily large values of n. Partitions of a mesh into quadrants are specified via pairs of rational numbers 〈φ, ψ〉, where 0 < φ, ψ < 1, chosen from a fixed, finite repertoire of such pairs. The quadrants specified by a pair 〈φ, ψ〉 are delimited by a horizontal line and a vertical line that that cross at the anchor mesh-tile v = 〈 φ(n−1) , ψ(n−1) 〉. The following results are established.
cis-acting ompF mutations that result in OmpR-dependent constitutive expression

OmpR and EnvZ differentially control the transcription of the major outer membrane porin genes, ompF and ompC, in Escherichia coli in response to the osmolarity of the medium. We have previously provided evidence that OmpR works both positively and negatively at the ompF promoter to give the characteristic switch from OmpF to OmpC production with increasing osmolarity. Here, we describe the isolation of cis-acting ompF mutations that affect negative regulation by OmpR by affecting the three-dimensional structure of the promoter region as measured by agarose gel mobility. These results further clarify the mechanism by which OmpR negatively regulates ompF expression, suggesting a model in which OmpR forms a repressive loop in the ompF promoter region.
Evidence for a hierarchy of predictions and prediction errors in human cortex

According to hierarchical predictive coding models, the cortex constantly generates predictions of incoming stimuli at multiple levels of processing. Responses to auditory mismatches and omissions are interpreted as reflecting the prediction error when these predictions are violated. An alternative interpretation, however, is that neurons passively adapt to repeated stimuli. We separated these alternative interpretations by designing a hierarchical auditory novelty paradigm and recording human EEG and magnetoencephalographic (MEG) responses to mismatching or omitted stimuli. In the crucial condition, participants listened to frequent series of four identical tones followed by a fifth different tone, which generates a mismatch response. Because this response itself is frequent and expected, the hierarchical predictive coding hypothesis suggests that it should be cancelled out by a higher-order prediction. Three consequences ensue. First, the mismatch response should be larger when it is unexpected than when it is expected. Second, a perfectly monotonic sequence of five identical tones should now elicit a higher-order novelty response. Third, omitting the fifth tone should reveal the brain's hierarchical predictions. The rationale here is that, when a deviant tone is expected, its omission represents a violation of two expectations: a local prediction of a tone plus a hierarchically higher expectation of its deviancy. Thus, such an omission should induce a greater prediction error than when a standard tone is expected. Simultaneous EEE- magnetoencephalographic recordings verify those predictions and thus strongly support the predictive coding hypothesis. Higher-order predictions appear to be generated in multiple areas of frontal and associative cortices.
Detecting Zimbabwe's Decadal Economic Decline Using Nighttime Light Imagery

Zimbabwe’s economy declined between 2000 and 2009. This study detects the economic decline in different regions of Zimbabwe using nighttime light imagery from the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP-OLS). We found a good correlation (coefficient = 0.7361) between Zimbabwe’s total nighttime light (TNL) and Gross Domestic Product (GDP) for the period 1992 to 2009. Therefore, TNL was used as an indicator of regional economic conditions in Zimbabwe. Nighttime light imagery from 2000 and 2008 was compared at both national and regional scales for four types of regions. At the national scale, we found that nighttime light in more than half of the lit area decreased between 2000 and 2008. Moreover, within the four region types (inland mining towns, inland agricultural towns, border towns and cities) we determined that the mining and agricultural sectors experienced the most severe economic decline. Some of these findings were validated by economic survey data, proving that the nighttime light data is a potential data source for detecting the economic decline in Zimbabwe.
A study of severe domestic squalor: 173 cases referred to an old age psychiatry service

ABSTRACT Background: Although community psychiatric services commonly encounter cases where intervention is needed due to persons’ unclean or cluttered living conditions, evidence concerning the referral rate and prevalence of severe domestic squalor is sparse. Methods: Between 2000 and 2009, ratings of cleanliness and clutter have been made in all cases of people living in squalor who have been referred to an old age psychiatry service in Central Sydney. Where possible, one-year follow-up was arranged. Results: 173 persons aged 65 years or more were referred to the service during the ten years and assessed as living in squalor (120 moderate or severe, two thirds of whom showed a moderate or severe degree of hoarding/clutter). Of 157 followed up after one year, 47% were still at home, 32% were in long-term care homes, 12% had moved elsewhere, and 9% had died. The annual new referral rate was close to 1 per 1000 elderly people in the catchment area, and of moderate or severe squalor was 0.66 per 1000. Limiting follow-up to those in moderate or severe squalor, 41% were still at home one year later. Current findings suggest that the minimum prevalence in the community of older people living in moderate or severe squalor in Sydney is 1 per 1000. Conclusions: The costs of intervening in cases of severe domestic squalor are considerable. Increased attention and funding are warranted, as the incidence and prevalence are higher than had previously been estimated.
Haemolytic disease of the newborn.

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Rituximab treatment in patients with active Graves' orbitopathy: effects on proinflammatory and humoral immune reactions

In active Graves' orbitopathy (GO), proinflammatory cytokines predominate. Circulating thyroid stimulating hormone (TSH)‐receptor antibodies (TRAb) have been correlated with GO clinical activity and severity. In preliminary studies rituximab (RTX), an anti‐CD 20 monoclonal antibody, has induced clinical improvement of active GO without a change in serum anti‐thyroid antibodies. We have studied whether RTX in GO acts by affecting proinflammatory cytokines and thyroid and orbital‐directed antibodies. Ten patients with GO were treated with RTX, administered twice intravenously (i.v.) (1000 mg) at days 1 and 15, and 20 with methylprednisolone, administered weekly i.v. (500 mg), for 16 weeks. Patients were studied before treatment, at B cell depletion and at 4, 8, 16, 20, 30 and 50 weeks. Peripheral lymphocytes, serum interleukin (sIL)‐6, sIL‐6r, chemokine (C‐X‐C motif) ligand 10 (CXCL10), TRAb and stimulating antibodies (TSAb) and autoantibodies against orbital calsequestrin, collagen XIII and flavoprotein subunit of succinate dehydrogenase (FP‐SDH) were measured at baseline and after treatment. Serum IL‐6 and sIL‐6R concentrations did not change after RTX [P = not significant (n.s.)]. Serum CXCL10 increased after RTX at B cell depletion and at 30 weeks (P < 0·003). Serum TSAb did not change in relation to TRAb, nor did antibodies against orbital antigens (P = n.s.). In conclusion, this study shows that RTX in GO does not affect humoral reactions. The observed increase of serum CXCL10 concentrations at B cell depletion may result from cell lysis. We suggest that RTX may exert its effect in GO by inhibiting B cell antigen presentation.
Current and Emerging Pharmacological Treatment Options for Dementia

Treatments for the symptomatic relief of Alzheimer’s disease are available but despite advances in our ability to treat persons with various forms of dementia, more effective treatments are needed. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in improving cognition and global status and to a lesser extent, behavioral abnormalities relative to placebo in patients with mild-to-moderate Alzheimer’s disease. Rivastigmine has been shown to benefit patients with dementia with Lewy Bodies and with dementia associated with Parkinson's disease. Donepezil and galantamine have also been shown to be mildly effective in dementia due to cerebral ischemia. Memantine has a distinct mechanism of action and is effective in moderate-to-severe AD. The benefits from these drugs, however, are limited and their long-term effectiveness has not been well-demonstrated. Their clinical utility is controversial. Many novel approaches that promise to provide more effective treatments are currently being pursued.
Non-linear Real Exchange Rate Effects in the UK Labour Market

Using UK data over the 1973q1-2004q1 period, we find that the dynamics of the real exchange rate, real wages and unemployment vary both with large versus small real exchange rate disequilibria and rising versus falling unemployment regimes. The short-run real exchange rate adjusts only when large disequilibrium deviations occur. We report fast real exchange rate adjustment in periods of falling unemployment. This implies that prices and wages are more flexible when real output is high. When the real exchange rate is highly undervalued, workers respond to an improvement in domestic competitiveness by demanding and getting higher wages. Unemployment is reduced following gains in competitiveness when the real exchange rate is further away from equilibrium.
Amplification and Molecular Cloning of HTLV-I Sequences from DNA of Multiple Sclerosis Patients. Correction.

Techniques of gene amplification, molecular cloning, and sequence analysis were used to test for the presence of sequences related to human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells of six patients with multiple sclerosis (MS) and 20 normal individuals. HTLV-I sequences were detected in all six MS patients and in one individual from the control group by DNA blot analysis and molecular cloning of amplified DNAs. The viral sequence in MS patients were associated with adherent cell populations consisting predominantly of monocytes and macrophages. Molecular cloning and nucleotide sequence analysis indicated that these amplified viral sequences were related to the HTLV-I proviral genome.