Miracle-dz/UniFAR-FTUs huggingface dataset:
ONECUT transcription factors induce neuronal characteristics and remodel chromatin accessibility

Abstract Remodeling of chromatin accessibility is necessary for successful reprogramming of fibroblasts to neurons. However, it is still not fully known which transcription factors can induce a neuronal chromatin accessibility profile when overexpressed in fibroblasts. To identify such transcription factors, we used ATAC-sequencing to generate differential chromatin accessibility profiles between human fibroblasts and iNeurons, an in vitro neuronal model system obtained by overexpression of Neurog2 in induced pluripotent stem cells (iPSCs). We found that the ONECUT transcription factor sequence motif was strongly associated with differential chromatin accessibility between iNeurons and fibroblasts. All three ONECUT transcription factors associated with this motif (ONECUT1, ONECUT2 and ONECUT3) induced a neuron-like morphology and expression of neuronal genes within two days of overexpression in fibroblasts. We observed widespread remodeling of chromatin accessibility; in particular, we found that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. There was substantial overlap with iNeurons, still, many regions that gained accessibility following ONECUT overexpression were not accessible in iNeurons. Our study highlights both the potential and challenges of ONECUT-based direct neuronal reprogramming.
Chronic ethanol feeding increases activation of NADPH oxidase by lipopolysaccharide in rat Kupffer cells: role of increased reactive oxygen in LPS‐stimulated ERK1/2 activation and TNF‐α production

Reactive oxygen species (ROS) contribute to the development of chronic ethanol‐induced liver injury. Although ROS modulate the activity of many signal transduction pathways, the molecular targets of ROS during ethanol exposure are not well understood. Here, we investigated whether specific ROS‐sensitive signal transduction pathways contribute to increased tumor necrosis factor α (TNF‐α) production by Kupffer cells after chronic ethanol feeding to rats. Lipopolysaccharide (LPS) rapidly increased ROS production, measured by dihydrorhodamine fluorescence, in Kupffer cells from ethanol‐ and pair‐fed rats, and ROS production was 2.5‐fold greater in ethanol‐fed compared with pair‐fed. Pretreatment with diphenyleneiodonium (DPI), which inhibits reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, normalized ROS production in Kupffer cells from ethanol‐fed rats. LPS rapidly increased Rac1‐guanosinetriphosphatase (GTPase) activity and p67phox translocation to the plasma membrane in Kupffer cells from pair‐fed rats. After ethanol feeding, Rac1‐GTPase activity was already increased over pair‐fed at baseline and remained elevated over pair‐fed after LPS stimulation. Further, LPS‐stimulated p67phox translocation to the plasma membrane was enhanced after chronic ethanol feeding. LPS‐stimulated extracellular signal‐regulated kinase (ERK)1/2 and p38 phosphorylation, two signaling pathways regulated by ROS, were increased twofold in Kupffer cells from ethanol‐fed rats compared with pair‐fed controls. However, only LPS‐stimulated ERK1/2 phosphorylation was inhibited by DPI, which also reduced LPS‐stimulated TNF‐α production in Kupffer cells from pair‐ and ethanol‐fed rats. These results demonstrate that chronic ethanol feeding increases LPS‐stimulated NADPH oxidase‐dependent production of ROS in Kupffer cells. Further, ERK1/2 is an important target of NADPH oxidase‐derived ROS in Kupffer cells, contributing to enhanced LPS‐stimulated TNF‐α production by Kupffer cells after chronic ethanol feeding.
Voice Capacity of Cognitive Radio Networks

Providing multimedia services over cognitive radio (CR) networks has become an interesting research topic during past few years. As multimedia applications require specific quality of service (QoS) guarantees, supporting multimedia applications to secondary users over a CR network is a challenging task due to the random nature of resource availability. In this paper, we consider a secondary system operating over a timeslotted primary system with multiple channels and secondary users accessing the channels at the spectrum holes without interfering with primary users. We derive the voice capacity of the CR system based on the theories of effective bandwidth (EB) and effective capacity (EC). The capacity is represented in terms of the number of simultaneous independent voice calls that the system can support, providing stochastic delay guarantee. It is shown that (i) the analytical results match well with simulation results and stays slightly lower than the simulation results due to the conservative nature of the EB and EC theories, and (ii) the mean duration of channel being unavailable to secondary users has a significant impact on the system capacity. With proper medium access control, this analysis can help to develop a call admission control policy for QoS provisioning in CR networks.
High prevalence of cardiac hypertophy without detectable signs of fibrosis in patients with untreated active acromegaly: an in vivo study using magnetic resonance imaging

Objective Left ventricular (LV) hypertrophy and myocardial fibrosis are considered the main pathological features of acromegalic cardiomyopathy. The aim of the study was to evaluate the proportion of LV hypertrophy and the presence of fibrosis in acromegalic cardiomyopathy in vivo using cardiac magnetic resonance (CMR).
Employee reactions to a pay incentive plan.

The reaction of a work group to a pay incentive plan is studied. An analysis of the employees’ attitudes reveals that they trust management, understand the plan, and see a close relationship between their pay and their performance. Based upon expectancy theory, it is hypothesised that because these conditions exist, the workers will respond directly to the economic payoff structure of the plan. In order to test this hypothesis, a mathematical model is developed to predict the productivity of the work group. The data show a high degree of fit between the model’s predictions and the actual productivity of the group. The implications of this for future research and for the design of incentive systems are discussed.
Binding , gating , a nity and e cacy : The interpretation of structure-activity relationships for agonists and of the e ects of mutating receptors

The nature of the problem is illustrated by the curves in Figure 1. A mutation in a receptor is seen to produce 100 fold increase in the EC50 for an agonist (Figure 1a). A ligand binding experiment with the same agonist, on the same mutant receptor (Figure 1b) shows that the measured anity for the binding of the agonist has also been reduced by about 100 fold. Obviously the mutation has aected the agonist-binding site, and the mutated amino acid is likely to be part of that site? No! It is not in the least obvious. The example in Figure 1 was calculated on the basis that the anity for the binding step of the reaction was totally unaected by the mutation (the equilibrium constant for this step was 100 mM for both wild type and mutant). The only dierence between wild type and mutant receptor in this example is the ability of the receptor, once the agonist has bound, to change conformation to its active state. There is no reason at all why the amino acids that aect the ability to change conformation should be anywhere near the agonist binding site. Binding experiments do not measure affinity (in any sense that is useful for learning about the binding site), for any ligand that causes a conformation change. The term `apparent affinity' is often used to describe EC50 for the response but it is meaningless (unless you define what you mean by `apparent'). Making this distinction between eects on binding and eects on conformation change is arguably the fundamental problem of modern molecular studies of receptors. It is not an easy distinction to make, but unless it can be solved, the interpretation of structure-function studies is quite likely to be nonsense. It is not just a theoretical problem; this is how ion channels actually behave. Nevertheless, the very existence of the problem has not always been recognized. For example, statements like the following are not at all uncommon*. (a) `Simplistically, the ecacy of a full agonist can be set equal to 1, that of an antagonist to 0, and that of a partial agonist to a value between 0 and 1' (Ross, 1996, in Goodman & Gilman, 9th Edition). This statement obscures the point that is crucial, both for the interpretation of structureactivity relations and of mutant studies, that ecacy has no upper limit in principle, and that when it is large, changes in it are indistinguishable from changes in anity.
Perceptions and negotiations of the “business case” for flexible careers and the integration of part‐time work

Looks at the extent to which employers recognise and act on “business case” incentives for implementing working‐time flexibility for those wishing to develop career paths. Focuses, in particular, on women's flexibility following maternity and their ability to access part‐time management positions through accommodating a reduction in working hours, or the integration and promotion of women working part‐time to managerial status. The research was generated through 62 qualitative interviews with mothers currently working in the hospitality industry and a further ten interviews with male and female managers of these women. Findings reveal that while managers are aware of the benefits of retaining highly qualified women managers, these informal practices are not universally accessible. There is little evidence that managers recognise a “business case” for the integration of part‐time workers into higher occupational grades, despite the recent regulation of part‐time work in the UK.
Differential regulation of platelet aggregation and aminophospholipid exposure by calpain

Aggregation, exposure of procoagulant phospholipids and shedding of microparticles are platelet responses that depend on activating conditions. To determine how these different responses are interconnected, we simultaneously measured fibrinogen (Fg) binding and aminophospholipid exposure on activated platelets by means of flow cytometry. Low calcium ionophore (A23187) concentrations induced Fg binding but not annexin V binding. In contrast, high A23187 concentrations induced annexin V binding but not Fg binding. Collagen, both alone and in the presence of thrombin, induced both Fg and annexin V binding. Dual labelling was found on 38 ± 9% of platelets stimulated by thrombin plus collagen. The regulatory role of calpain in these platelet functions was investigated. When calpain was partially inhibited by 2 μg/ml calpeptin, Fg binding still occurred but aminophospholipid exposure was limited. By contrast, complete inhibition of calpain by 100 μg/ml calpeptin or E64d decreased Fg binding but enhanced aminophospholipid exposure. In these latter conditions, cytosolic calcium‐extruding systems were inhibited. The results suggest that (i) conditions that favour aminophospholipid exposure tend to decrease the aggregation process and (ii) calpain determines the switch to either aggregation or aminophospholipid exposure by controlling intracellular calcium.
Genotyping and Phylogenetic Analysis of Fasciola Spp. Isolated from Sheep and Cattle Using PCR-RFLP in Ardabil Province, Northwestern Iran

Abstract Background The aim of this study was to detect the genotype of Fasciola spp. in Meshkin-Shahr, Ardabil Province, northwestern Iran in different hosts using PCR-RFLP. Methods The parasite hosts included cattle, and sheep. Overall, 70 adult flukes from livers of slaughtered animals were collected from the abattoirs of aforementioned area. The included 35 samples from infected sheep and 35 samples from 35 infected cattle. PCR-RFLP and sequence analysis of the first nuclear ribosomal internal transcribed spacer (ITS 1) region from Fasciola species were used to conduct the study. Results The fragment of approximately 700bp in all of the Fasciola samples was amplified. PCR products of ITS 1 were subjected for digestion by restriction enzyme. RsaI restriction enzyme was selected for RFLP method that caused the separation specifically of Fasciola species. Amplicons with the sequences of F. hepatica had a pattern of about 360, 100, and 60 bp band size, whereas F. gigantica worms had a profile of 360, 170, and 60 bp in size, respectively. Results based on PCR-RFLP analysis were confirmed by sequence analysis of representative ITS 1 amplicons. No hybrid forms were detected in the present study. All sheep were infected with F. hepatica but cattle were infected with both species. Conclusion Both species of Fasciola are present in Ardabil. The method described here can be valuable for identification of Fasciola species in endemic parts for fasciolosis, regions with intermediate species and in that overlapping distribution area.
Metaplasia of smooth muscle cells into juxtaglomerular cells in the juxtaglomerular apparatus, arteries, and arterioles of the ischemic (endocrine) kidney. An ultrastructural-cytochemical and autoradiographic study.

Partial ligation of the aorta between the renal arteries induces marked atrophy of the cortical tubules of the left (endocrine) kidney with a remarkable increase in the number and granularity of hypersecretory juxtaglomerular cells (JGC), which are found not only at the glomerular pole of arterioles but also in the walls of arteries and arterioles far removed from the glomerulus. Typical vascular smooth muscle cells (SMC), in which secretory granules appear, show a concomitant development of their Golgi complex and rough endoplasmic reticulum, with a gradual decrease in the number of their filaments. Microtubules also appear in the Golgi area. Thiery's periodic acid-thiocarbohydrazide-silver proteinate technique demonstrates that in these "intermediate" cells, as in mature JGC, the amount of glycogen is greater than in SMC. The newly-developed secretory granules of intermediate cells are stained by phosphotungstic acid at a low pH, as are the mature granules of JGC, an indication that both types contain glycoproteins. Light and electron microscopic autoradiography reveal that both JGC and "intermediate" cells of the vascular wall do not incorporate radioactive thymidine (injected during the 10-day observation period). Thus, they develop by metaplasia of preexistent SMC. In control kidneys, radioactive thymidine is practically never incorporated into the nuclei of SMC but is found in a few glomerular and tubular cells of all zones except the papilla.The endocrine kidney shows virtually no reactive nuclei in vascular SMC, glomeruli, or tubular cells of the outer cortex. Thymidine is incorporated into practically all nuclei of the straight portion of proximal tubules and into about half the nuclei of all medullary tubular cells including the papilla.
Indexing Weblogs One Post at a Time

In order to perform analysis over weblogs, we must first identify the appropriate unit of a weblog that corresponds to a document. We argue in the paper that, for weblogs, the correct unit is the weblog post. A weblog post is a structured document with the following fields: date, timestamp, title, content, permalink and author. We present our approach for segmenting weblogs into posts, which breaks down into several steps: (1) automatic feed discovery; (2) feed-guided segmentation, using the weblog feed and HTML; and (3) modelbased weblog segementation.
On Dimension-independent Rates of Convergence for Function Approximation with Gaussian Kernels

This article studies the problem of approximating functions belonging to a Hilbert space $\mathcal{H}_d$ with an isotropic or anisotropic translation invariant (or stationary) reproducing kernel with special attention given to the Gaussian kernel $K_d(\boldsymbol{x},\boldsymbol{t}) = \exp\big(-\sum_{\ell=1}^d\gamma_\ell^2(x_\ell-t_\ell)^2\big)$ for all $\boldsymbol{x},\boldsymbol{t}\in\mathbb{R}^d. $ The isotropic (or radial) case corresponds to using the same shape parameters for all coordinates, i.e., $\gamma_\ell=\gamma>0$ for all $\ell$, whereas the anisotropic case corresponds to varying $\gamma_\ell$. The approximation error of the optimal approximation algorithm, called a meshfree or kriging method, is known to decay faster than any polynomial in $n^{-1}$, for fixed $d$, where $n$ is the number of data points. We are especially interested in moderate to large $d$, which in particular arise in the construction of surrogates for computer experiments. This article presents dimension-independent error bounds, i.e., the error is bounded by $Cn^{-p}$, where $C$ and $p$ are independent of both $d$ and $n$. This is equivalent to strong polynomial tractability. The pertinent error criterion is the worst case of such an algorithm over the unit ball in $\mathcal{H}_d$, with the error for a single function given by the ${\mathcal L}_2$ norm whose weight is also a Gaussian which is used to “localize” $\mathbb{R}^d$. We consider two classes of algorithms: (i) using data generated by finitely many arbitrary linear functionals, and (ii) using only finitely many function values. Provided that arbitrary linear functional data is available, we show $p=1/2$ is possible for any translation invariant positive definite kernel. We also consider the sequence of shape parameters $\gamma_d$ decaying to zero like $d^{-\omega}$ as $d$ tends to $\infty$. Note that for large $\omega$ this means that the function to be approximated is “essentially low-dimensional. ” Then the largest $p$ is roughly $\max(1/2,\omega)$. If only function values are available, dimension-independent convergence rates are somewhat worse. If the goal is to make the error smaller than $Cn^{-p}$ times the initial $(n=0)$ error, then the corresponding dimension-independent exponent $p$ is roughly $\omega$. In particular, for the isotropic case, when $\omega=0$, the error does not even decay polynomially with $n^{-1}$. In summary, excellent dimension-independent error decay rates are possible only when the sequence of shape parameters decays rapidly.
Progress in High-Amylose Cereal Crops through Inactivation of Starch Branching Enzymes

High-amylose cereal starches provide many health benefits for humans. The inhibition or mutation of starch branching enzyme (SBE) genes is an effective method to develop high-amylose cereal crops. This review summarizes the development of high-amylose cereal crops through the inactivation of one or more SBE isoforms or combination with other genes. This review also reveals the causes of increase in amylose content in high-amylose crops. A series of changes, including amylopectin structure, crystalline structure, thermal properties, and hydrolysis properties, occurs as amylose content increases. The different morphological starch granules nominated as heterogeneous starch granules or differently stained starch granules are detected in high-amylose cereal crops. Detailed studies on four heterogeneous starch granules in high-amylose rice, which is developed by antisense RNA inhibition of SBEI/IIb, indicate that granules with different morphologies possess various molecular structures and physicochemical and functional properties. This variation diversifies their applications in food and non-food industries. However, current knowledge regarding how these heterogeneous starch granules form and why they exhibit regional distribution in endosperm remain largely unknown.
Small Glandular Proliferations on Needle Biopsies: Most Common Benign Mimickers of Prostatic Adenocarcinoma Sent in for Expert Second Opinion

The current study aimed to determine the incidence of various benign mimickers of prostatic adenocarcinoma most commonly encountered in a busy consultation practice. All prostate needle biopsies from the consult service of one of the authors were prospectively evaluated over a 7-month period. Only cases with foci where the contributor questioned malignancy and which upon expert review the entire case was determined to be benign were included in this study. A total of 567 separate suspected atypical foci from 345 patients of a total of 4,046 patients (8.5%) received in consultation were identified. Of these, 281 foci (49.5%) had immunohistochemical (IHC) studies performed by the outside institution, which included high molecular weight cytokeratin (HMWCK) (n = 280), alpha-methylacyl-CoA racemase (AMACR) (P504s) (n = 45), and p63 (n = 34). The most common mimicker was partial atrophy (203 of 567; 35.8%). Technically adequate IHC for basal cells was performed in 117 cases of partial atrophy with patchy or patchy/negative staining seen in 102 of 117 (87%), with the remaining 13% of cases completely negative. A total of 15 of 19 (79%) cases of partial atrophy were positive with AMACR. Crowded benign glands, insufficiently crowded or numerous to warrant a diagnosis of adenosis, was the second most common mimicker (146 of 567; 25.7%). Crowded benign glands had patchy or patchy/negative IHC for basal cells in 66 of 81 (81%) cases with the remaining 19% of cases completely negative. A total of 7 of 11 (64%) cases of crowded glands were positive for AMACR. In the past, complete atrophy, adenosis, seminal vesicle, and granulomatous prostatitis were considered common mimickers of prostate cancer on prostatic needle biopsies. Our study shows that currently partial atrophy and crowded benign glands are the most common benign changes causing diagnostic difficulty and prompting consultation. Negative or patchy staining for basal cells and positive staining for AMACR may contribute to diagnostic difficulty in these entities.
A Multi-Dimensional Smart Community Discovery Scheme for IoT-Enriched Smart Homes

The proliferation of the Internet into every household has provided more opportunities for residents to become closer to each other than before. However, solid structural barrier is raised and social relationships within such neighborhoods are weak compared to those in traditional towns. Accordingly, activating communities and ultimately enhancing a sense of community through constructive participation and communal sharing of labor among residents has currently emerged as a challenging issue in a contemporary housing complex. In an effort to activate those communities, a notion of smart community is presented in which multiple smart homes are equipped with Internet of Things and interconnected with each other. Beyond the unadorned smart community composed by physical proximity, it is essential to discover a human-centric community that achieves communal benefits and enables residents to maximize individual economic gain by leveraging collective intelligence. In this article, we present a multi-dimensional smart community discovery scheme that enables householders to find human-centric community considering multi-dimensional factors in terms of physical, social, and economical aspects. We conduct experiments with 30 real households by applying a community-based energy saving scenario. Experiment results show that the proposed scheme performs better when compared to the physical proximity-based one in energy consumption and user satisfaction.
Thermal-mechanical reliability analysis of connection structure between redistribution layer and TSV for MEMS packaging

This paper proposes a combination of annular copper and cylindrical copper as the TSV conductor to decrease the effect of thermal mismatch between copper and silicon in MEMS packaging, which results in a reliability risk between redistribution layer (RDL) and TSV. There are three important factors which may have the most serious influence on the reliability being simulated and analyzed. They are the opening diameter of RDL in insulation layer, the thickness of cylindrical copper and the thickness of insulation layer at the bottom of TSV. It is significant to understand the effect of the three factors and get the optimum structure parameters which can reduce the effect of the risky connection structure on the package reliability obviously.