Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct and Allosteric Inhibition of the FGF2/HSPGs/FGFR1 Ternary Complex Formation by an Antiangiogenic, Thrombospondin-1-Mimic Small Molecule

Fibroblast growth factors (FGFs) are recognized targets for the development of therapies against angiogenesis-driven diseases, including cancer. The formation of a ternary complex with the transmembrane tyrosine kinase receptors (FGFRs), and heparan sulphate proteoglycans (HSPGs) is required for FGF2 pro-angiogenic activity. Here by using a combination of techniques including Nuclear Magnetic Resonance, Molecular Dynamics, Surface Plasmon Resonance and cell-based binding assays we clarify the molecular mechanism of inhibition of an angiostatic small molecule, sm27, mimicking the endogenous inhibitor of angiogenesis, thrombospondin-1. NMR and MD data demonstrate that sm27 engages the heparin-binding site of FGF2 and induces long-range dynamics perturbations along FGF2/FGFR1 interface regions. The functional consequence of the inhibitor binding is an impaired FGF2 interaction with both its receptors, as demonstrated by SPR and cell-based binding assays. We propose that sm27 antiangiogenic activity is based on a twofold–direct and allosteric–mechanism, inhibiting FGF2 binding to both its receptors.
A Quad Router design for next-generation CMPs

This paper presents a router structure for Network-on-Chips called Quad Router which benefits from communication locality. The router can be shared among more than one Processing Element (PE), so the average hop count of a packet is decreased. This structure consists of eight input buffers and eight output ports by which two different topologies are introduced called Double-Link Mesh (DLM) and Crossbar Mesh (CM). In DLM topology, each Quad Router is connected to four immediate neighbors just like regular mesh topology, but with double links. In CM topology, each Quad Router is connected to eight neighbors in eight different directions. The main advantage of this architecture is reduction in packet latency because the PEs sharing a single Quad Router can connect directly to each other. Other advantages are drop in power and area overhead of the router. The experimental results show the effectiveness of the proposed topologies.
Data dissemination for delay tolerant vehicular networks: using historical mobility patterns

We propose a message dissemination algorithm for location-aware services in vehicular networks. The objective is to reduce information delivery time in intermittently connected urban vehicular networks by using historical mobility information of vehicles. Roads are divided based on observed traffic density into dense and sparse paths and vehicles share their current knowledge about fastest possible message delivery time to contouring dense roads. We use a Dijkstra based shortest path calculation with link weights set to packet dissemination time based on observed traffic and available relays in the vicinity. To simplify the shortest path calculation we calculate delay under two strategies. The first strategy is to relay information to closest dense road and use relaying. The second strategy is to try carry and forward towards the destination. Historical mobility information is used to find the best carrier candidate. On dense roads, information will be broadcast towards the destination without the carrying phase, while on sparse roads knowledge about the historical mobility patterns improves the next relay selection efficiency. Using simulations we show the superiority of our proposed method in delay and reliability of packet delivery compared to conventional data dissemination methods such as VADD in city traffic scenarios.
A compound interest approach to HIV cure

In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of integrated virus to persist within memory CD4+T cells in a transcriptionally quiescent state and reactivate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART would result in functional cure within 2-10 years rather than many decades on ART alone.
Bioinformatics Original Paper Recovering Metabolic Pathways via Optimization

Motivation: A metabolic pathway is a coherent set of enzyme catalysed biochemical reactions by which a living organism transforms an initial (source) compound into a final (target) compound. Some of the different metabolic pathways adopted within organisms have been experimentally determined. In this paper, we show that a number of experimentally determined metabolic pathways can be recovered by a mathematical optimization model.
The FOXG1/FOXO/SMAD network balances proliferation and differentiation of cortical progenitors and activates Kcnh3 expression in mature neurons

Transforming growth factor β (TGFβ)-mediated anti-proliferative and differentiating effects promote neuronal differentiation during embryonic central nervous system development. TGFβ downstream signals, composed of activated SMAD2/3, SMAD4 and a FOXO family member, promote the expression of cyclin-dependent kinase inhibitor Cdkn1a. In early CNS development, IGF1/PI3K signaling and the transcription factor FOXG1 inhibit FOXO- and TGFβ-mediated Cdkn1a transcription. FOXG1 prevents cell cycle exit by binding to the SMAD/FOXO-protein complex. In this study we provide further details on the FOXG1/FOXO/SMAD transcription factor network. We identified ligands of the TGFβ- and IGF-family, Foxo1, Foxo3 and Kcnh3 as novel FOXG1-target genes during telencephalic development and showed that FOXG1 interferes with Foxo1 and Tgfβ transcription. Our data specify that FOXO1 activates Cdkn1a transcription. This process is under control of the IGF1-pathway, as Cdkn1a transcription increases when IGF1-signaling is pharmacologically inhibited. However, overexpression of CDKN1A and knockdown of Foxo1 and Foxo3 is not sufficient for neuronal differentiation, which is probably instructed by TGFβ-signaling. In mature neurons, FOXG1 activates transcription of the seizure-related Kcnh3, which might be a FOXG1-target gene involved in the FOXG1 syndrome pathology.
Comparison of the potency of 10 different brands of Serenoa repens extracts.

BACKGROUND The extract of Serenoa repens is the phytopharmaceutical product most often used for the treatment of urological symptoms associated with benign prostatic hyperplasia (BPH). Several extracts are commercially available but extraction processes vary between manufacturers and thus not all these products are equivalent in terms of active ingredient content and composition of preparations. AIM As there is a paucity of comparative studies, we compared the activity of different extracts of Serenoa repens widely available on the world market. MATERIALS AND METHODS Beltrax Uno, Permicaps, Permixon, Prostadyn, Prostagutt, Prostamen, Prostamol Uno, ProstaX, Urocaps and Urogutt were assayed for 5-alpha-reductase activity on 10 day fibroblasts and epithelial cells cocultures. Human fibroblast growth factor (hFGF)-induced-proliferation inhibition was also assayed. RESULTS As to extract activity, differences were observed between the tested extracts, but all were able to inhibit 5-a-reductase types I and II isoenzymes (5alphaR-I and 5alphaR-II) as well as fibroblast proliferation. CONCLUSIONS Extract potency differs between products and so does proliferation inhibition potency. Quantitative and qualitative variations in the active ingredient are likely to account for these differences.
The Relationship of Serum 25-Hydroxyvitamin D and Insulin Resistance among Nondiabetic Canadians: A Longitudinal Analysis of Participants of a Preventive Health Program

Observational and intervention studies have revealed inconsistent findings with respect to the relationship between vitamin D and insulin resistance. No intervention studies have been conducted in community samples whereas this may be particularly relevant to the primary prevention of type 2 diabetes (T2D) and cardiovascular disease (CVD). In the present study we examined whether temporal improvements in vitamin D status, measured as serum 25-hydroxyvitamin D [25(OH)D], reduce the risk of insulin resistance among individuals without T2D. We accessed and analyzed data from 5730 nondiabetic participants with repeated measures of serum 25(OH)D who enrolled in a preventive health program. We used the homeostatic model assessment for insulin resistance (HOMA-IR) and applied logistic regression to quantify the independent contribution of baseline serum 25(OH)D and temporal increases in 25(OH)D on HOMA-IR. The median time between baseline and follow up was 1.1 year. On average serum 25(OH)D concentrations increased from 89 nanomoles per liter (nmol/L) at baseline to 122 nmol/L at follow up. Univariate analyses showed that relative to participants with baseline serum 25(OH)D less than 50 nmol/L, participants with baseline concentrations of “50-<75”, “75-<100”, “100-<125”, and ≥125 nmol/L were 0.76 (95% confidence intervals: 0.61–0.95), 0.54 (0.43–0.69), 0.48 (0.36–0.64) and 0.36 (0.27–0.49) times as likely to have insulin resistance at follow up, respectively. More importantly, relative to participants without temporal increases in 25(OH)D, those with increases in serum 25(OH)D of “<25”, “25-<50”, “50-<75”, “≥75” nmol/L were 0.92 (0.72–1.17), 0.86 (0.65–1.13), 0.66 (0.47–0.93), and 0.74 (0.55–0.99) times as likely to have insulin resistance at follow up, respectively. In the subgroup of participants without insulin resistance at baseline, this was 0.96 (0.72–1.27), 0.78 (0.56–1.10), 0.66 (0.44–0.99), and 0.67 (0.48–0.94), respectively. These observations suggest that improvements in vitamin D status reduce the risk for insulin resistance and herewith may contribute to the primary prevention of T2D and CVD.
Design on a unipolar and unidirectional stepper motor circuit

A unidirectional and unipolar stepper motor driver has been designed, for the purpose of effectively solving many existed pressing problems in the stepper motor such as high costs, poor universality, complex circuitry, and inconvenient manipulation and so forth. The unidirectional and unipolar stepper motor will become outstanding as the result of its low costs, stable performance, suitable for computer control and could be driven by unipolar stepper motor. The circuit employs CD4017 to distribute pulse, and applies 74LS02 TTL to converse the single-pass four circulations into dual-pass four circulations, and utilizes the integrated Darlington pairs (Darlington transistors) to amplify the power, and then activates the stepper motor by the amplified power. It has been verified in the experiment that the circuit operates stably and pertains high control accuracy. KeywordsUnipolar; Stepper Motor; CD4017; Circuit
Marine hydrocarbonoclastic bacteria as whole-cell biosensors for n-alkanes

Whole‐cell biosensors offer potentially useful, cost‐effective systems for the in‐situ monitoring of seawater for hydrocarbons derived from accidental spills. The present work compares the performance of a biosensor system for the detection of alkanes in seawater, hosted in either Escherichia coli (commonly employed in whole‐cell biosensors but not optimized for alkane assimilation) or different marine bacteria specialized in assimilating alkanes. The sensor system was based on the Pseudomonas putida AlkS regulatory protein and the PalkB promoter fused to a gene encoding the green fluorescent protein. While the E. coli sensor provided the fastest response to pure alkanes (25‐fold induction after 2 h under the conditions used), a sensor based on Alcanivorax borkumensis was slower, requiring 3–4 h to reach similar induction values. However, the A. borkumensis sensor showed a fourfold lower detection threshold for octane (0.5 μM), and was also better at sensing the alkanes present in petrol. At petrol concentrations of 0.0125%, the A. borkumensis sensor rendered a sevenfold induction, while E. coli sensor showed no response. We discuss possible explanations to this behaviour in terms of the cellular adaptations to alkane uptake and the basal fluorescence produced by each bacterial strain, which was lowest for A. borkumensis.
A retrospective view of software maintenance and reengineering research – a selection of papers from European Conference on Software Maintenance and Reengineering 2010

As a summary of past, current, and future trends in software maintenance and reengineering research, we give in this editorial a retrospective look from the past 14 years to now. We provide insight on how software maintenance has evolved and on the most important research topics presented in the series of the European Conference on Software Maintenance and Reengineering. Copyright © 2011 John Wiley & Sons, Ltd.
Suicidal Thoughts and Behaviors in Children of Immigrants: The Experience of Korean-American Women

ABSTRACT This qualitative study examines the experience of Korean-American women who had suicidal thoughts and/or used nonsuicidal self-injury (NSSI) during adolescence. This study aims to understand the etiology, help-seeking behaviors, and recovery of these young women. Eleven Korean-American women (mean age 26.7) were recruited and interviewed using in-depth semi-structured interviews. Transcripts were coded using a grounded theoretical framework. Themes indicate that participants experienced poor relationships with a parent, an inability to process their difficulties, and academic success despite their behaviors. Participants also indicated feelings of perfectionism and did not seek help, resulting in a theme called the paradox of perfection.
A not quite as quick but much cleaner alternative to the Expanded Programme on Immunization (EPI) Cluster Survey design.

BACKGROUND Although the Expanded Programme on Immunization (EPI) cluster survey methodology has been successfully used for assessing levels of immunization programme coverage in developing country settings, certain features of the methodology, as it is usually carried out, make it less-than-optimal choice for large, national surveys and/or surveys with multiple measurement objectives. What is needed is a 'middle ground' between rigorous cluster sampling methods, which are seen as unfeasible for routine use in many developing country settings, and the EPI cluster survey approach. METHODS This article suggests some fairly straightforward modifications to the basic EPI cluster survey design that put it on a solid probability footing and render it easily adaptable to differing and/or multiple measurement objectives, without incurring prohibitive costs or adding appreciably to the complexity of survey operations. The proposed modifications concern primarily the manner in which households are chosen at the second stage of sample selection. CONCLUSIONS Because the modified sampling strategy maintains the scientific rigor of conventional cluster sampling methods while retaining many of the desirable features of the EPI survey methodology, the methodology is likely to be a preferred 'middle ground' survey design, relevant for many applications, particularly surveys designed to monitor multiple health indicators over time. The fieldwork burden in the modified design is only marginally higher than in EPI cluster surveys, and considerably lower than in conventional cluster surveys.
The Strongly Polarized Afterglow of GRB 020405

We report polarization measurements and photometry for the optical afterglow of the gamma-ray burst GRB 020405. We measured a highly significant 9.9% polarization (in V band) 1.3 days after the burst and argue that it is intrinsic to the GRB. The light-curve decay is well fitted by a t-1.72 power law; we do not see any evidence for a break between 1.24 and 4.3 days after the burst. We discuss these measurements in the light of several models of GRB afterglows.
Priming in Macaque Frontal Cortex during Popout Visual Search: Feature-Based Facilitation and Location-Based Inhibition of Return

In popout search, humans and monkeys are affected by trial-to-trial changes in stimulus features and target location. The neuronal mechanisms underlying such sequential effects have not been examined. Single neurons were recorded in the frontal eye field (FEF) of monkeys performing a popout search during which stimulus features and target position changed unpredictably across trials. Like previous studies, repetition of stimulus features improved performance. This feature-based facilitation of return was manifested in the target discrimination process in FEF: neurons discriminated the target from distractors earlier and better with repetition of stimulus features, corresponding to improvements in saccade latency and accuracy, respectively. The neuronal target selection was mediated by both target enhancement and distractor suppression. In contrast to the repetition of features, repetition of target position increased saccade latency. This location-based inhibition of return was reflected in the neuronal discrimination process but not in the baseline activity in FEF. These results show adjustments of the target selection process in FEF corresponding to and therefore possibly contributing to changes in performance across trials caused by sequential regularities in display properties.
Using a vibro-tactile display for enhanced collision perception and presence

One of the goals and means of realizing virtual reality is through multimodal interfaces, leveraging on the many sensory organs that humans possess. Among them, the tactile sense is important and useful for close range interaction and manipulation tasks. In this paper, we explore this possibility using a vibro-tactile device on the whole body for simulating collision between the user and virtual environment. We first experimentally verify the effect of enhanced user felt presence by employing localized vibration feedback alone on collision, and further investigate how to effectively provide the sense of collision using the vibro-tactile display in different ways. In particular, we test the effects of using a vibration feedback model (for simulating collision with different object materials), saltation, and simultaneous use of 3D sound toward spatial presence and perceptual realism. The results have shown that employing the proposed vibro-tactile interface did enhance the sense of presence, especially when combined with 3D sound. Furthermore, the use of saltation also helped the user detect and localize the point of contact more correctly. The use of the vibration feedback model was not found to be significantly effective, and sometimes even hindered the correct sense of collision primarily due to the limitation of the vibrotactile display device.
k -means clustering

The sets Sj are the sets of points to which μj is the closest center. In each step of the algorithm the potential function is reduced. Let’s examine that. First, if the set of centers μj are fixed, the best assignment is clearly the one which assigns each data point to its closest center. Also, assume that μ is the center of a set of points S. Then, if we move μ to 1 |S| ∑ i∈S xi then we only reduce the potential. This is because 1 |S| ∑ i∈S xi is the best possible value for μ (can easily be seen by derivation of the cost function).
Locus heterogeneity disease genes encode proteins with high interconnectivity in the human protein interaction network

Mutations in genes potentially lead to a number of genetic diseases with differing severity. These disease genes have been the focus of research in recent years showing that the disease gene population as a whole is not homogeneous, and can be categorized according to their interactions. Locus heterogeneity describes a single disorder caused by mutations in different genes each acting individually to cause the same disease. Using datasets of experimentally derived human disease genes and protein interactions, we created a protein interaction network to investigate the relationships between the products of genes associated with a disease displaying locus heterogeneity, and use network parameters to suggest properties that distinguish these disease genes from the overall disease gene population. Through the manual curation of known causative genes of 100 diseases displaying locus heterogeneity and 397 single-gene Mendelian disorders, we use network parameters to show that our locus heterogeneity network displays distinct properties from the global disease network and a Mendelian network. Using the global human proteome, through random simulation of the network we show that heterogeneous genes display significant interconnectivity. Further topological analysis of this network revealed clustering of locus heterogeneity genes that cause identical disorders, indicating that these disease genes are involved in similar biological processes. We then use this information to suggest additional genes that may contribute to diseases with locus heterogeneity.
Learning SQL with a computerized tutor

SQL, the dominant database language, is a simple and highly structured language; yet, students have many difficulties learning it. This paper presents SQL-Tutor, an Intelligent Teaching System designed as a guided discovery learning environment, which helps students in overcoming these difficulties. We present design issues and the current state in the implementation of the system, with special focus on individualization of instruction towards a particular student.
Group Profiling in E-Service Portals

- Nowadays Service activities are social and involve different types of individuals that should be considered. Thus, group profiling can be used to connect similar customers together and recommend providers based on group evaluation. Accordingly, this paper proposes a new approach that recommends providers, based on group profiling and ranking, to be used in e-service portals. This approach focuses on group profiling and cluster users based on Ant Colony Clustering (ACC) method. In addition, the approach has been tested and three measures have been recorded including speed, aggregation precision, and result accuracy. The result of such test has shown that this approach is promising and has a high quality result.