Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Changes Measured by X-ray Scattering from Human Flap Endonuclease-1 Complexed with Mg2+ and Flap DNA Substrate*

Human flap endonuclease-1 (FEN-1) is a member of the structure-specific endonuclease family and is essential in DNA replication and repair. FEN-1 has specific endonuclease activity for repairing nicked double-stranded DNA substrates that have the 5′-end of the nick expanded into a single-stranded tail, and it is involved in processing Okazaki fragments during DNA replication. Magnesium is a cofactor required for nuclease activity. We used small-angle x-ray scattering to obtain global structural information pertinent to nuclease activity from FEN-1, the D181A mutant, the wild-type FEN-1·34-mer DNA flap complex, and the D181A·34-mer DNA flap complex. The D181A mutant, which has Asp-181 replaced by Ala, selectively binds to the flap structure, but has lost its cleaving activity. Asp-181 is thought to be involved in Mg2+binding at the active site (Shen, B., Nolan, J. P., Sklar, L. A., and Park, M. S. (1996) J. Biol. Chem. 271, 9173–9176). Our data indicate that FEN-1 and the D181A mutant each have a radius of gyration of ∼26 Å, and the effect of Mg2+ on the scattering from the proteins alone is insignificant. The 34-mer DNA fragment was constructed such that it readily forms a 5′-flap structure. The formation of the flap conformation of the DNA substrate was evident by both the extrapolatedI o scattering and radius of gyration and was supported by NMR spectrum and nuclease assays. In the absence of magnesium, the FEN-1·34-mer DNA flap complex has anR g value of ∼34 Å, whereas the D181A·34-mer DNA flap complex self-associates, suggesting that a significant protein conformational change occurs by addition of the flap DNA substrate and that Asp-181 is crucial for proper binding of the protein to the DNA substrate. A time course change in the scattering profiles arising from magnesium activation of the FEN-1·34-mer DNA flap complex is consistent with the protein completely releasing the DNA substrate after cleavage.
CYTOMEGALOVIRUS INFECTION IN TRANSPLANT RECIPIENTS THE ROLE OF TUMOR NECROSIS FACTOR

Human cytomegalovirns (CMV) infection is an important cause of morbidity and mortality in transplant recipients. CMV infection commonly results from the reactivation of a latent infection. Using a set of monoclonal anti-CMV antibodies, we found CMV antigen expression in peripheral blood mononuclear cells (PBMNC), particularly in monocytes, in 312 of 816 samples from 190 allograft recipients. The detection of CMV-IE antigens and CMV-IE DNA in PBMNC indicates that positive cells may represent truly infected cells. The relation between increased cytokine plasma levels (particularly following treatment by pan-T cell antibodies) and the appearance of CMV antigens in PBMNC suggests that cytokines may play an important role in the reversal of CMV latency. This hypothesis is supported by our finding that tumor necrosis factor-alpha (TNF) is able to stimulate the activity of the CMV-IE enhancer/promoter region in the human monocytic cell line, HL-60. The interleukins 1,2,3,4,6,8 and 10; transforming growth factor-β: interferongamma; and granulocyte/macrophage colony-stimulating factor did not show any enhancing effect on the CMV promoter activity. Thus, TNF-alpha seems to play a key role in regulating the balance between latency and reactivation of CMV infection. Inhibition of TNF-alpha release or action may be an alternative strategy for preventing CMV-associated morbidity in allograft recipients.
Role of hematopoietic microenvironment in prolonged impairment of B cell regeneration in age‐related stromal‐cell‐impaired SAMP1 mouse: effects of a single dose of 5‐fluorouracil

In this study, we examined the age‐associated defect of stromal cells, which support B cell development, treated with 5‐fluorouracil (5‐FU) to induce severe perturbation of hematopoiesis, including B lymphocyte development, using SAMP1 mice exhibiting senescence‐mimicking stromal‐cell impairment after 30 weeks of age. Significant findings of this study are as follows: first, a marked and prolonged decrease in number of CFU‐preB cells in non‐SCI mice (58% of the steady‐state level) associated with more markedly depressed number of CFU‐preB cells in SCI mice (20% of the steady‐state level), despite the absence of difference in the number of CFU‐GMs during the period; second, in the non‐SCI mice, a significant and prolonged up‐regulation of GM‐CSF and IL‐6, positive regulators of myelopoiesis and suppressive factors of B lymphopoiesis, was observed. In SCI mice, greater and prolonged suppression of B lymphopoiesis was clearly demonstrated by the significant up‐regulation of the negative regulator TNF‐α associated with the concomitant marked down‐regulation of the positive regulator SDF‐1, although the increases of GM‐CSF and IL‐6 were limited. That is, ‘negative complementation’ makes preB recovery after 5‐FU treatment impaired and prolonged. Principal component analysis clearly showed differences in the cytokine expression patterns in both early and later phases and the time course of the expression pattern of each cytokine between SCI and non‐SCI mice without supervising information. An impaired regulation of the expressions of not only positive but also negative regulators after 5‐FU treatment was, in part, the cause of the impaired regeneration of CFU‐preB cells in SCI mice. Copyright © 2008 John Wiley & Sons, Ltd.
Cloud Gaming: Understanding the Support From Advanced Virtualization and Hardware

Existing cloud gaming platforms have mainly focused on private nonvirtualized environments with proprietary hardware. Modern public cloud platforms heavily rely on virtualization for efficient resource sharing, the potentials of which have yet to be explored. Migrating gaming to a public cloud is nontrivial, however, particularly considering the overhead for virtualization and that the graphics processing units (GPUs) for game rendering has long been an obstacle in virtualization. This paper takes a first step toward bridging the online gaming system and the public cloud platforms. We present the design and implementation of a fully virtualized cloud gaming platform with the latest hardware support for both remote servers and local clients. We explore many critical design issues inherent in cloud gaming, including the choice of hardware or software video encoding, and the configuration and the detailed power consumption of thin client. We demonstrate that with the latest hardware and virtualization support, gaming over virtualized cloud can be made possible with careful optimization and integration of the different modules. We also highlight critical challenges toward full-fledged deployment of gaming services over the public virtualized cloud.
Reclamation of information from degraded and damaged document images by image binarization method

Reclamation of information from severely degraded document images is a highly difficult job because of huge dissimilarity among the document contextual surface (background) and the forefront text, characters and shapes of the various document images. This paper proposes an eminent document image binarization method which focusses these problems with the aid of an adaptive map. This adaptive map is a combo of a contrast image and the gradient image, which is resist to the dissimilarity present among the document background and the forefront text/characters of various document images suffering from various degradation and damages such as irregular lighting, image contrast dissimilarity and ink bleeding-through. In this proposed method, initially an adaptive map is created for each and every input degraded document images. Then binarization takes place to that contrast map to determine the boundary edges of the text stroke pixels by fusing it with canny edge map. The forefront text present in the document is divided by means of local thresholding, which predicts the forefront text depending upon the detected text stroke edge pixels intensity value. Considerable tests were conducted on the degraded document images and the performance were evaluated based on parametric such as PSNR and MSE respectively. The performance analysis indicates that this system shows promising results against a wide variety of document degradations.
The side effects of the prostaglandin analogues

In the last decade topically applied prostaglandin F2α analogues (bimatoprost, latanoprost, travoprost and unoprostone) have become widely used as a means to reduce elevated intraocular pressure in patients with glaucoma and ocular hypertension. These molecules all have similar side-effect profiles, which include both side effects that occur frequently (e.g., conjunctiva hyperaemia, increase of iris pigmentation and eyelash changes) and rare adverse reactions (e.g., periocular pigmentation, damage to the blood–aqueous barrier and cystoid macular oedema). Conjunctiva hyperaemia, eyelash changes and cystoid macular oedema are reversible, but certain other side effects, such as increased iris pigmentation, are not. However, the systemic side-effect profile is favourable for all the prostaglandin analogues, and some of the local side effects are only of cosmetic significance. Numerous clinical studies suggest that discontinuing treatment with prostaglandin analogues on account of their side effects is rare in clinical practice.
A spatial theory for characterizing predator–multiprey interactions in heterogeneous landscapes

Trophic interactions in multiprey systems can be largely determined by prey distributions. Yet, classic predator–prey models assume spatially homogeneous interactions between predators and prey. We developed a spatially informed theory that predicts how habitat heterogeneity alters the landscape-scale distribution of mortality risk of prey from predation, and hence the nature of predator interactions in multiprey systems. The theoretical model is a spatially explicit, multiprey functional response in which species-specific advection–diffusion models account for the response of individual prey to habitat edges. The model demonstrates that distinct responses of alternative prey species can alter the consequences of conspecific aggregation, from increasing safety to increasing predation risk. Observations of threatened boreal caribou, moose and grey wolf interacting over 378 181 km2 of human-managed boreal forest support this principle. This empirically supported theory demonstrates how distinct responses of apparent competitors to landscape heterogeneity, including to human disturbances, can reverse density dependence in fitness correlates.
Adaptive Neural-based Fault Tolerant Control for Nonlinear Systems ⋆

A neural network based fault tolerant control for unknown nonlinear systems is proposed. The faultless system is controlled by a nonlinear Internal Model Controller (IMC), where both the direct and inverse models of the plant are carried out by neural networks. Using the residual signal generated from the fault detection path, an extra neural-network fault compensation loop is introduced. This neural network is a two layer perceptron and the weights and bias are updated on-line by the modified-gradient approach, which tries to minimize the control error induced by the fault. In this context, a fault tolerant control scheme is obtained. This scheme is tested in simulation in a pH plant with good results.
Clicks to Conversion: The Impact of Product and Price Information

This study seeks to examine how different types of information – product-related and price-related information provided by retailers – impact purchase-related outcomes for consumers belonging to different states of shopping. Using mixture-modeling techniques on clickstream data obtained from a large online durable goods retailer, we find that a three-state model comprised of directed shoppers, deliberating researchers and browsers, best describes the latent differences across customers. In examining the impacts of information on purchase outcomes, we find that product and price-related information impacts consumers in these three shopping states differently. While product information highlighting features of product alternatives in a category has the strongest impact on deliberating researchers, specific price information related to category-level discounts increases the likelihood of purchase for both directed shoppers as well as browsers. Price information relating to site-wide free shipping has a positive impact on purchase for all consumers. Surprisingly, category-level discounts have a negative impact on deliberating researchers, while rich product information hampers the purchase process of directed shoppers. We discuss the managerial implications of our findings and the role of clickstream analytics in designing dynamic targeting and information provisioning strategies for online retailers.
Integration of numeric and symbolic information for semantic image interpretation

Semantic image interpretation (SII) is the process of generating meaningful descriptions of the content of images. Background knowledge (BK), in the form of logical theories, is extremely useful for SII. State-of-the-art algorithms for SII mainly adopt a bottom-up approach, which generates semantic interpretations of images starting from their low-level features. In these approaches BK is used only at a late stage for both enriching the semantic descriptions and improving image retrieval. In this paper, we show how BK plays an important role also during the early phase of SII. To this aim, we propose: (i) a reference framework where a semantic image description is a partial model of the BK. The elements of the partial model are grounded (linked) to a (set of) image segment(s). (ii) A loss function that evaluates how well this partial model fits the picture; (iii) a clustering-based optimization process that searches the partial model that better fits a picture. BK is used to prune branches of the search space that correspond to partial models which are inconsistent with BK. To evaluate our approach, we built a gold standard dataset of 203 pictures annotated with complex objects and their parts. We also evaluated our method on a reference dataset in Computer Vision, namely, the PASCAL-Part dataset. The results are positive. The evaluation assumes a perfect detection of parts. To understand the impact of a realistic (and noisy) part detection on our algorithm, we did a preliminary evaluation by implementing the entire SII pipeline. Part detection is performed by a recent deep learning architecture trained for detecting parts. From a qualitative analysis, it emerges that recognizing complex objects starting from parts in some cases gets better results than detecting complex objects directly.
Age at first childbirth and later poverty.

A linear structural equation model is used in this research study in order to estimate the simultaneous effects of age at first birth on a woman's subsequent socioeconomic conditions and related outcomes after the age of 27 years. Estimation was accomplished with a variant of Amemiya's principle and a feasible generalized least squares estimator. Analysis involved examination of the bivariate relationship between age at first birth and poverty at age 27 years for Blacks, Hispanics, and Whites, followed by structural equation models for each racial group and then analysis of the total and indirect effects of age at first birth on poverty. Poverty is measured as the ratio of family income to the poverty threshold. Findings indicate that the association between early childbearing and poverty at the age of 27 years is very strong. Young women with educated parents and women with reading materials in their home before the age of 14 years achieved more schooling. When these effects were controlled, being raised by both parents and having more siblings were only associated with more schooling among Whites. Rural Blacks and Whites completed more schooling than rural Hispanics. Blacks in poor states had lower educational attainment. Age at first birth was only significant among Hispanics. First birth was delayed by 1.26 years among Blacks, 0.88 years among Whites, and 0.98 years among Hispanics for having an additional year of schooling. Delaying marriage had the strongest effect among Whites. Delayed childbearing among Blacks was predicted by having fewer siblings, being raised by both parents, and later menstruation. Earlier White childbearing was associated with women from larger families and women with larger ideal family sizes. Hispanic women raised by both parents was associated with delayed childbearing. Findings confirm that age at first birth was associated for all racial groups with poverty. Age at first birth affected educational attainment of Hispanics and age at first marriage among Whites. Age at first birth impacted on poverty through the number of children among Blacks and Whites, White and Hispanic women's earnings, and Hispanic earnings among other household members. Delaying first births had minimal impact on later poverty among Blacks and considerable impact among Whites and Hispanics.
Anti-Inflammatory Effect Of Different Propolis Extracts In Thioacetamide-Induced Hepatotoxicity In Male Rat

Propolis is a natural product has anti-inflammatory and antioxidant activities. The present study aimed to investigate the therapeutic and anti-inflammatory effects of both aqueous extract (AEP) and oil extract of propolis (OEP) against thioacetamide (TAA) induced hepatotoxicity in rats. Seventy male rats were divided into 7 groups and treated for successive 8 weeks. Group1was kept as control; Group 2 was ingested orally with sunflower oil; Group 3 was injected intraperitoneally (ip) twice a week with TAA (200 mg/kg b.wt.); Group 4 was treated orally with AEP (100 mg/kg b.wt./day); Group 5 was treated orally with OEP (100 mg/kg b.wt./day); Group 6 was injected ip with TAA (200 mg/kg b.wt.) twice a week plus oral ingestion of AEP (100 mg/kg b.wt./day); Group 7 was injected ip with TAA (200 mg/kg b.wt.) twice a week plus oral ingestion of OEP (100 mg/kg b.wt./day). Thioacetamide induced liver damage in rats manifested by the significant rise in serum levels of AST, ALT, ALP, GGT, bilirubin, total cholesterol, triglyceride and LDL with decrease in the levels of total proteins, albumin and HDL compared with control. Both AEP and OEP reduced the toxic effect of TAA indicated by a decrease in the levels of previously elevated liver parameters with an increase in the levels of total proteins, albumin and HDL. On the other hand, TAA significantly decreased the levels of IL-6 and TNF-α and increased CRP, however, AEP and OEP counteracted this effect of TAA. These results revealed the anti-inflammatory effects of the different propolis extracts. AEP was more potent than OEP as an anti-inflammatory and anti-hepatotoxic extract. The histopathologic results supported the biochemical and immunological results.
Feasibility and reliability of pocket-size ultrasound examinations of the pleural cavities and vena cava inferior performed by nurses in an outpatient heart failure clinic

Background: Routine assessment of volume state by ultrasound may improve follow-up of heart failure patients. Aims: We aimed to study the feasibility and reliability of focused pocket-size ultrasound examinations of the pleural cavities and the inferior vena cava performed by nurses to assess volume state at an outpatient heart failure clinic. Methods: Ultrasound examinations were performed in 62 included heart failure patients by specialized nurses with a pocket-size imaging device (PSID). Patients were then re-examined by a cardiologist with a high-end scanner for reference within 1 h. Specialized nurses were able to obtain and interpret images from both pleural cavities and the inferior vena cava and estimate the volume status in all patients. Results: Time consumption for focused ultrasound examination was median 5 min. In total 26 patients had any kind of pleural effusion (in 39 pleural cavities) by reference. The sensitivity, specificity, positive and negative predictive values were high, all ≥ 92%. The correlations with reference were high for all measurements, all r ≥ 0.79. Coefficients of variation for end-expiratory dimension of inferior vena cava and quantification of pleural effusion were 10.8% and 12.7%, respectively. Conclusions: Specialized nurses were, after a dedicated training protocol, able to obtain reliable recordings of both pleural cavities and the inferior vena cava by PSID and interpret the images in a reliable way. Implementing focused ultrasound examinations to assess volume status by nurses in an outpatient heart failure clinic may improve diagnostics, and thus improve therapy.
Quality and Audit Fees: Evidence from Pakistan

Audit quality has been in the limelight for researchers over the last two to three decades. Researchers have endeavored to find out the factors that impact the quality of audit conducted by the auditors. The recent financial crises and financial scandals have further enhanced the importance of this topic. Although it is an empirically established fact that auditor’s performance is impeded by a number of factors that curb its independence however sudden surge in the emoluments of auditors during the last decades has actuated the researchers to study audit quality in context of compensation fee paid to the auditors. The results of studies differ as some are of the view that audit quality improves with the payment of excess fee while the rest are of the opposite view. Unluckily, Pakistan has been less explored in this regard and not even a single study has addressed the issue of audit quality in Pakistan. This study has attempted to analyze audit quality in context of abnormal or extra fee paid to auditor. Audit conducted without independence of auditor is futile and results in impairment of audit quality. Independence of auditor is usually curbed by extra fee paid to him, and auditor in fear of losing a lucrative fee does not report the misrepresentations of financial statements in his audit report. This study uses discretionary accruals as surrogate of audit quality which are computed by Cross-sectional Modified Jones Model (1995). The results are fortunately good for Pakistan and study has observed that auditors in Pakistan do not compromise on their standards and honesty when paid extra fee. In Pakistan, the quality of audit is not impaired when auditors are paid extra fee and the auditors work with diligence and exert extra effort to improve the audit quality. Therefore, the assertion that audit quality is impaired when high fee is paid to auditors does not hold well in Pakistan. Keywords: Audit fee, Audit Quality
400 mhz PLL-based frequency synthesizer with built-in self-test

As the requirement of a wider operating range becomes increasingly important for contemporary system-on-chip designs, the designers are in need of synthesizers to produce an extensive range of clock frequencies. Signal quality characteristics such as jitter etc. have to be enhanced in order to maintain correct operation with popular double data rate speeds. PLL synthesizer control complexity during test procedures on produced chips when the synthesizer block is being controlled from digital hardware part is also challenging. This work presents the 400 MHz clock multiplier PLL-based synthesizer with a wide operating range simulated to be 100 MHz to 400 MHz capable of automatically performing the functional test, which significantly reduces overall test time. The functional structure of the synthesizer, the design and performance concepts of the component blocks are presented. The prototype IC layout is verified in a 0.25-um SOI 3.3V CMOS process.