Miracle-dz/UniFAR-FTUs huggingface dataset:
Promoter Scanning for Transcription Inhibition with DNA-Binding Polyamides

ABSTRACT When targeted to sequences adjacent to a TATA element, pyrrole-imidazole (Py-Im) polyamides inhibit the DNA binding activity of TATA box binding protein (TBP) and basal transcription by RNA polymerase II. In the present study, we scanned the human immunodeficiency virus type 1 promoter for polyamide inhibition of TBP binding and transcription using a series of DNA constructs in which a polyamide binding site was placed at various distances from the TATA box. Polyamide interference with either TBP-DNA or TFIID-TFIIA-DNA contacts both upstream and downstream of the TATA element resulted in inhibition of transcription. Our results define important protein-DNA interactions outside of the TATA element and suggest that transcription inhibition of selected gene promoters can be achieved with polyamides that target unique sequences within these promoters at a distance from the TATA element. Our studies also demonstrate the utility of the Py-Im polyamides for discovery of functionally important protein-DNA contacts involved in transcription.
The Scandinavian Fantasy: The Sources of Intergenerational Mobility in Denmark and the US

Abstract This paper examines the sources of differences in social mobility between the US and Denmark. Measured by income mobility, Denmark is a more mobile society, but not when measured by educational mobility. There are pronounced non‐linearities in income and educational mobility in both countries. Greater Danish income mobility is largely a consequence of redistributional tax, transfer, and wage compression policies. While Danish social policies for children produce more favorable cognitive test scores for disadvantaged children, they do not translate into more favorable educational outcomes, partly because of disincentives to acquire education arising from the redistributional policies that increase income mobility.
Z-DNA-forming sites identified by ChIP-Seq are associated with actively transcribed regions in the human genome

Z-DNA, a left-handed double helical DNA is structurally different from the most abundant B-DNA. Z-DNA has been known to play a significant role in transcription and genome stability but the biological meaning and positions of Z-DNA-forming sites (ZFSs) in the human genome has not been fully explored. To obtain genome-wide map of ZFSs, Zaa with two Z-DNA-binding domains was used for ChIP-Seq analysis. A total of 391 ZFSs were found and their functions were examined in vivo. A large portion of ZFSs was enriched in the promoter regions and contain sequences with high potential to form Z-DNA. Genes containing ZFSs were occupied by RNA polymerase II at the promoters and showed high levels of expression. Moreover, ZFSs were significantly related to active histone marks such as H3K4me3 and H3K9ac. The association of Z-DNA with active transcription was confirmed by the reporter assay system. Overall, our results suggest that Z-DNA formation depends on chromatin structure as well as sequence composition, and is associated with active transcription in human cells. The global information about ZFSs positioning will provide a useful resource for further understanding of DNA structure-dependent transcriptional regulation.
Form-Focused Discovery Activities in English Classes.

Form-focused discovery activities allow language learners to grasp various aspects of a target language by contributing implicit knowledge by using discovered explicit knowledge. Moreover, such activities can assist learners to perceive and discover the features of their language input. In foreign language teaching environments, they can be used for various teaching purposes. This study investigates form-focused instruction in developing implicit knowledge of a language by a poetry-discovery process. Although most language learners avoid poetry due to its complex linguistic and semantic components, poetry holds implicit knowledge (and other qualities) that make it an excellent means by which language rules can be learned. This study was aimed at defeating learners’ prejudices about poetry by prompting their deep processing and creativity through the inquiries into the complexity of poetry’s structure.
Finland radar observations of the ionospheric signatures of ̄ ux transfer events and the resulting plasma ̄ ows

The CUTLASS Finland radar has been run in a two-beam special scan mode, which oered excellent temporal and spatial information on the ̄ows in the high-latitude ionosphere. A detailed study of one day of this data revealed a convection reversal boundary (CRB) in the CUTLASS ®eld of view (f.o.v) on the dayside, the direction of plasma ̄ow either side of the boundary being typical of a dawn-cell convection pattern. Poleward of the CRB a number of pulsed transients are observed, seemingly moving away from the radar. These transients are identi®ed here as the ionospheric signature of ̄ux transfer events (FTEs). Equatorward of the CRB continuous backscatter was observed, believed to be due to the return ̄ow on closed ®eld lines. The two-beam scan oered a new and innovative opportunity to determine the size and velocity of the ionospheric signatures associated with ̄ux transfer events and the related plasma ̄ow pattern. The transient signature was found to have an azimuthal extent of 1900  900 km and an poleward extent of 250 km. The motion of the transient features was in a predominantly westward azimuthal direction, at a velocity of 7.5  3 km.
String Theory and Pre-big bang Cosmology

Summary. In string theory, the traditional picture of a Universe that emerges from the inflation of a very small and highly curved space-time patch is a possibility, not a necessity: quite different initial conditions are possible, and not necessarily unlikely. In particular, the duality symmetries of string theory suggest scenarios in which the Universe starts inflating from an initial state characterized by very small curvature and interactions. Such a state, being gravitationally unstable, will evolve towards higher curvature and coupling, until string-size effects and loop corrections make the Universe “bounce” into a standard, decreasing-curvature regime. In such a context, the hot big bang of conventional cosmology is replaced by a “hot big bounce” in which the bouncing and heating mechanisms originate from the quantum production of particles in the high-curvature, large-coupling pre-bounce phase. Thanks to the strong coupling there is also an associate production of higher-dimensional branes, which could prepare (and provide the initial conditions for) a subsequent phase of brane-dominated inflation.
The Investment Behavior of Private Equity Fund Managers

Using a unique dataset of private equity funds over the last two decades, this paper analyzes the investment behavior of private equity fund managers. Based on recent theoretical advances, we link the timing of funds' investment and exit decisions, and the subsequent returns they earn on their portfolio companies, to changes in the demand for private equity in a setting where the supply of capital is 'sticky' in the short run. We show that existing funds accelerate their investment flows and earn higher returns when investment opportunities improve and the demand for capital increases. Increases in supply lead to tougher competition for deal flow, and private equity fund managers respond by cutting their investment spending. These findings provide complementary evidence to recent papers documenting the determinants of fund-level performance in private equity.
Benchmarking of the advanced hygrothermal model-hygIRC with mid scale experiments

Recent research in the field of assessment of hygrothermal response has focused on either laboratory experimentation or modelling, but less work has been reported in which both aspects are combined. Indeed, it is generally acknowledged that assessing the hygrothermal performance of building envelope systems is both expensive and time consuming. Such type of studies can potentially offer useful information regarding the benchmarking of models and related methods to assess hygrothermal performance of wall assemblies. This paper focuses on the use of an advanced hygrothermal model to assess the hygrothermal response of various components in woodframe wall assemblies when subjected to nominally steady-state environmental conditions. A comparison is made of results obtained from the computer model simulations to those derived from tests on mid scale specimens in controlled laboratory measurements. The experimental results were subsequently used to help benchmark the model. Specifically, hygIRC was implemented, in this series of simulations, to assess the drying rate of various combinations of sheathing membrane in close contact with wood-based sheathing. The overall agreement between experimental and simulated results is very good in terms of the shape of the drying curve and the time taken to reach equilibrium moisture content.
Measuring the cosmological parameters with the Ep,i–Eiso correlation of gamma-ray bursts

We have used the E p,i -E iso correlation of gamma-ray bursts (GRBs) to measure the cosmological parameter Ω M . By adopting a maximum likelihood approach which allows us to correctly quantify the extrinsic (i.e. non-Poissonian) scatter of the correlation, we constrain (for a flat universe) Ω M to 0.04-0.40 (68 per cent confidence level), with a best-fitting value of Ω M ∼ 0.15, and exclude Ω M = 1 at >99.9 per cent confidence level. If we release the assumption of a flat universe, we still find evidence for a low value of Ω M (0.04-0.50 at 68 per cent confidence level) and a weak dependence of the dispersion of the E p,i -E iso correlation on Ω Λ (with an upper limit of Ω Λ ∼ 1.15 at 90 per cent confidence level). Our approach makes no assumptions on the E p,i -E iso correlation and it does not use other calibrators to set the 'zero' point of the relation, therefore our treatment of the data is not affected by circularity and the results are independent of those derived via Type Ia supernovae (or other cosmological probes). Unlike other multi-parameters correlations, our analysis grounds on only two parameters, then including a larger number (a factor of ∼3) of GRBs and being less affected by systematics. Simulations based on realistic extrapolations of ongoing (and future) GRB experiments (e.g. Swift, Konus-Wind, GLAST) show that: (i) the uncertainties on cosmological parameters can be significantly decreased and (ii) future data will allow us to get clues on the 'dark energy' evolution.
The site of incorporation of sialic acid residues into glycoproteins and the subsequent fates of these molecules in various rat and mouse cell types as shown by radioautography after injection of [3H]N- acetylmannosamine. II. Observations in tissues other than liver

Biochemical evidence from the preceding paper indicated that [3H]N- acetylmannosamine may be used as a fairly specific precursor for the sialic acid residues of glycoproteins (and perhaps glycolipids) in radioautographs of rat liver and duodenum. In order to study the site of incorporation of this label in cell types of various tissues, we gave 40-g rats and 15-g Swiss albino mice a single intravenous injection of 8 mCi of [3H]N-acetylmannosamine and sacrificed them after 2 and 10 min. To trace the subsequent migration of the labeled glycoproteins, we injected 40-g rats with 4 mCi of [3H]N- acetylmannosamine and sacrificed them after 20 and 30 min, 1, 4, and 24 h, and 3 and 9 d. Light microscope radioautographic analysis revealed that in a great variety of cell types the label was initially localized to the Golgi region. Electron microscope radioautographic analysis of duodenal villous columnar and goblet cells, pancreatic acinar cells and Paneth cells, from rats and mice sacrificed 10 min after injection, showed that the silver grains were localized over Golgi saccules (and adjacent secretion granules). In kidney proximal and distal tubule cells reaction was initially localized to the Golgi apparatus in some areas of the kidney cortex whereas in other areas it was more diffuse. In all cells, the proportion of silver grains over the Golgi apparatus decreased with time after injection while an increasing number of grains appeared over secretion products in secretory cells or over the plasma membrane in other cell types. Lysosomes also became increasingly labeled at later time intervals. The above results suggest that in most cell types sialic acid residues are incorporated into glycoproteins (and perhaps glycolipids), primarily in the Golgi apparatus. With time, these newly synthesized molecules migrate to secretion products, to the plasma membrane, or to the lysosomes.
Binding of the Heterogeneous Ribonucleoprotein K (hnRNP K) to the Epstein-Barr Virus Nuclear Antigen 2 (EBNA2) Enhances Viral LMP2A Expression

The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA- antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV- infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties.
Why are the 2000s so Different from the 1970s? A Structural Interpretation of Changes in the Macroeconomic Effects of Oil Prices

In the 1970s, large increases in the price of oil were associated with sharp decreases in output and large increases in inflation. In the 2000s, even larger increases in the price of oil were associated with much milder movements in output and inflation. Using a structural VAR approach, Blanchard and Gali (2009) argued that this reflected a change in the causal relation from the price of oil to output and inflation. They then argued that this change could be due to a combination of three factors, namely, a smaller share of oil in production and consumption, lower real wage rigidity and better monetary policy. Their argument, based on simulations of a simple new-Keynesian model, was informal. Our purpose in this paper is to take the next step, and to estimate the explanatory power and contribution of each of these factors. To do so, we use a minimum distance estimator that minimizes, over the set of structural parameters and for each of two samples (pre- and post-1984), the distance between the empirical SVAR-based impulse response functions and those implied by a new-Keynesian model. Our empirical results point to an important role for all three factors.
Biosimilar medicines – their use in the treatment of inflammatory bowel diseases. Position statement of the Working Group of the Polish National Consultant in Gastroenterology

Biological medical products are drugs whose active components are produced only by living, genetically modified organisms or live cell cultures. Patents and exclusivity for most biopharmaceuticals has either expired or will expire soon, which enables biotechnological companies to introduce similar biological products. The problem of replacing a biological medicine with a biosimilar in the course of therapy remains open. In this statement, the Working Group of the Polish National Consultant in Gastroenterology, in the absence of data regarding bioequivalence in patients with inflammatory bowel disease, does not recommend switching from original biological medicine to its biosimilar analogue in the course of treatment in inflammatory disease patients; however, this may change after receiving the results of controlled studies regarding bioequivalence in this group.
Non-tame Mice from Tame Failures of the Unique Branch Hypothesis

Abstract In this paper, we show that the failure of the unique branch hypothesis $\left( \text{UBH} \right)$ for tame trees implies that in some homogenous generic extension of $V$ there is a transitive model $M$ containing Ord $\cup \mathbb{R}$ such that $M\,\vDash \,\text{A}{{\text{D}}^{+}}\,+\,\Theta \,>\,{{\theta }_{0}}$ . In particular, this implies the existence (in $V$ ) of a non-tame mouse. The results of this paper significantly extend J. R. Steel's earlier results for tame trees.
Ubiquitin specific protease 21 upregulation in breast cancer promotes cell tumorigenic capability and is associated with the NOD-like receptor signaling pathway

Ubiquitination and deubiquitination have emerged as critical regulators in cancer. In the present study, the expression pattern of 50 ubiquitin-specific proteases (USPs) was summarized in breast cancer using a bioinformatics approach, and USP21 was identified as the most altered gene in breast cancer. In particular, expression of USP21 in triple negative breast cancer (TNBC) cell lines was greater compared with other subtypes of breast cancer. Knockdown of USP21 in TNBC cells inhibited cell proliferation, migration and invasion. Microarray profiling of the USP21 knockdown cells revealed significant downregulation of multiple genes associated with the NOD-like receptor signaling pathway. The results of the present study suggest that USP21 has a significant role in TNBC progression, and therefore may represent a novel therapeutic target.
The Transitive Reduction of a Directed Graph

We consider economical representations for the path information in a directed graph. A directed graph $G^t $ is said to be a transitive reduction of the directed graph G provided that (i) $G^t $ has a directed path from vertex u to vertex v if and only if G has a directed path from vertex u to vertex v, and (ii) there is no graph with fewer arcs than $G^t $ satisfying condition (i). Though directed graphs with cycles may have more than one such representation, we select a natural canonical representative as the transitive reduction for such graphs. It is shown that the time complexity of the best algorithm for finding the transitive reduction of a graph is the same as the time to compute the transitive closure of a graph or to perform Boolean matrix multiplication.
RECONFIGURABLE CONTROL USING CONSTRAINED OPTIMIZATION

A conceptual scheme for reconfiguring control systems in the event of major failures is advocated. This addresses a 'big problem' which is understandable by the man in the street, delivers enormous benefits if it can be made to work, and requires interesting and challenging research from control and systems theorists and practitioners. The scheme relies on the convergence of several technologies which are currently emerging: Constrained predictive control, High-fidelity modelling of complex systems , Fault detection and identification, and Model approximation and simplification. Much work is needed, both theoretical and algorithmic, to get this scheme to work, but we believe that there is enough evidence, especially from existing industrial practice, for the scheme to be considered achievable. After outlining the problem and proposed solution, the paper briefly reviews constrained predictive control, object-oriented modelling , which is an essential ingredient for practical implementation, and the prospects for automatic model simplification. The paper emphasises some emerging trends in industrial practice, as regards modelling and control of complex systems. Examples from process control and flight control are used to illustrate some of the ideas.
Natural degradation rates of BTEX compounds and naphthalene in a sulphate reducing groundwater environment

Abstract Field and laboratory evidence show natural degradation of toluene, ethylbenzene, m-, p- and o-xylenes, 1,3,5-trimethylbenzene and naphthalene in sulphate reducing groundwater conditions of the Bassendean Sands in the Perth basin, Western Australia. Natural degradation rates were obtained from a groundwater tracer test with deuterated organic compounds injected into a dissolved hydrocarbon plume, down-gradient of a leaking underground storage tank at an urban service station. These were compared with similar data obtained from modelling of the whole contaminant plume itself and also with data obtained from large-scale laboratory column experiments with groundwater spiked with BTEX compounds. Toluene degradation rate was 200 to 500 times higher in the anaerobic laboratory columns than in the field. Degradation rates in the tracer test compared well with model-derived field estimates.
Complications and Outcomes of Lumbar Spine Surgery in Elderly People: A Review of the Literature

As the number of elderly persons in the United States continues to increase, there will be an associated increase in age‐related diseases, such as degenerative conditions of the lumbar spine. Elderly patients frequently present to their geriatrician or primary care provider with low back and leg pain. Spine surgery is one of several options the geriatric patient may consider for symptomatic relief, but the literature describing the safety and efficacy of spine surgery in older patients is inconclusive and at times confusing. The purpose of this article is to describe common degenerative conditions of the lumbar spine and to review the complications and outcomes of spine surgery in elderly patients, with particular attention to how they compare with those of younger patients. A better understanding of the risks and prognosis associated with these types of surgeries will enable more‐informed decision‐making by patients and physicians.
Clinical controlled abservation on generalized anxiety disorder treated by duloxetine and fluoxetine tablets

Objective:To evaluate the efficacy and safety of generalized anxiety disorde treated by duloxetine and fluoxetine.Methods:sixty cases with generalized anxiety disorde were divided randmonly into duloxetine group(30 cases) and fluoxetine group(30 cases). Course of treatment was 8 weeks.Hamilton anxiety scale(HAMA) and treatment emergent symptom scale(TESS) were used.Results: Both groups had significant efficacies and few side effects.Conclusions: generalized anxiety disorde treated with duloxetine had definite efficacy and good safety.