Miracle-dz/UniFAR-FTUs huggingface dataset:
More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature

Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at .
High prevalence of mouse mammary tumor virus-like gene sequences in breast cancer samples of Iranian women

ABSTRACT Mouse mammary tumor virus (MMTV) is considered to be responsible for breast tumor development in mice. In several instances sequences homologous to the genome of this virus have been reported in human breast cancer samples. Here we aimed to evaluate MMTV involvement in human breast cancer development. DNA was extracted from 118 formalin fixed and paraffin embedded malignant (n = 59) and benign (n = 59) breast lesions. Using two sets of outer and inner MMTV-like envelope specific primers, in a nested PCR setup, MMTV genome was detected in 19 samples out of 59 (%32.2) cases of breast carcinomas, while in non-malignant breast tissue samples, only 3 samples out of 59 (%5) were positive. The difference was statistically highly significant (p < 0.001). Alignment of PCR amplified sequences with BR6, GR and C3H mouse mammary tumor virus strains emerged to be around 99% identical which is indicative of tumor tissue infection by an exogenous mouse MMTV genome.
Toward a modern theory of adaptive networks: expectation and prediction.

Many adaptive neural network theories are based on neuronlike adaptive elements that can behave as single unit analogs of associative conditioning. In this article we develop a similar adaptive element, but one which is more closely in accord with the facts of animal learning theory than elements commonly studied in adaptive network research. We suggest that an essential feature of classical conditioning that has been largely overlooked by adaptive network theorists is its predictive nature. The adaptive element we present learns to increase its response rate in anticipation of increased stimulation, producing a conditioned response before the occurrence of the unconditioned stimulus. The element also is in strong agreement with the behavioral data regarding the effects of stimulus context, since it is a temporally refined extension of the Rescorla-Wagner model. We show by computer simulation that the element becomes sensitive to the most reliable, nonredundant, and earliest predictors of reinforcement . We also point out that the model solves many of the stability and saturation problems encountered in network simulations. Finally, we discuss our model in light of recent advances in the physiology and biochemistry of synaptic mechanisms.
Assessment of cell proliferation in knitting scaffolds with respect to pore‐size heterogeneity, surface wettability, and surface roughness

In this study, various types of poly(e-caprolactone) (PCL) knitting scaffolds were fabricated and analyzed to assess the cell-culturing characteristics of knitting scaffolds with respect to pore-size heterogeneity, surface wettability, and surface roughness. First, control knitting scaffolds were fabricated using 150-µm-diameter PCL monofilaments. Using chloroform and NaOH, PCL knitting scaffolds with varying roughness, pore-size heterogeneity, and surface wettability were fabricated. Cell-culture assessments were performed on these six types of PCL knitting scaffolds. Saos-2 cells were used for cell assessments and cultured for 14 days on each scaffold. Consequently, heterogeneous pore-size distribution and high surface wettability were found to enhance cell proliferation in knitting scaffolds. In addition, for highly hydrophobic knitting scaffolds exhibiting water contact angles greater than 110 degrees, smaller surface roughness was found to enhance cell proliferation. According to this study, in the case of knitting scaffold, NaOH-treated knitting scaffold, without any control for the pore-size homogenization, could be a candidate as the optimal knitting scaffold. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42566.
An FPGA-based key-store for improving the dependability of security services

A key-store is a facility for storing sensitive information, most typically the keys of a cryptographic application which provides a security service. In this paper, we present a hardware implemented key-store, which allows secure storage and high performance retrieval of RSA keys. Since RSA is the most widely adopted standard for cryptographic keys, our key-store can be effectively used to improve the dependability of a wide class of security services. Tfie device is implemented on top of a commercial off the shelf (COTS) programmable hardware board, namely a Celoxica RCWOO mounting a Xilinx Virtex-E 2000 FPGA part. We describe the architecture of the hardware device, illustrate the organization of the associated device driver, and evaluate the security and performance gain which can be achieved by integrating our device in real-world applications.
Nasogastric feeding for stroke patients: practice and education.

BACKGROUND AND AIMS Dysphagia is common after stroke, so feeding through a nasogastric (NG) tube may be necessary. These tubes are frequently dislodged, causing interruption to feeding and hydration, and potential aspiration of feed or fluids into the lungs. Interventions to prevent this may include taping tubes to the face; the application of hand mittens or bandaging patients' hands; inserting the NG tube into the nostril on the stroke-affected side; and nasal bridles. The aims of this survey were to investigate the management of NG feeding for stroke patients, including current tube confirmation and securing techniques, and associated nurse education. This was part of a three-phased sequential mixed-methods study. This paper reports on the second quantitative phase. METHODS A quantitative postal survey, based on initial qualitative findings, was sent to registered nurses (n=528) from the National Stroke Nurses Forum and Scottish Stroke Nurses Forum, in addition to registered nurses working on stroke units within the local health board. RESULTS The overall response rate was 59% (n=314/528). Tape was the most commonly used method for securing tube position, followed by inserting the tube on the stroke-affected side. Hand mittens were used more frequently than the nasal bridle; bandaging hands was reported once. Taping was considered to be more acceptable and safer than hand mittens or the nasal bridle, but less effective. Training in inserting NG feeding tubes was received by 56% (n=176/314). Methods used for confirming tube position included aspiration and X-ray. Provision of training in confirmation techniques varied. CONCLUSIONS This study shows that the management of NG feeding for dysphagic stroke patients requires standardisation, as does the education for nurses to ensure that this intervention is carried out safely, effectively and acceptably.
Protein Lysine Acetylated/Deacetylated Enzymes and the Metabolism-Related Diseases

Lysine acetylation is a reversible posttranslational modifcation, an epigenetic phenomenon, referred to as transfer of an acetyl group from acetyl CoA to lysine e- amino group of targeted protein, which is modulated by acetyltransferases (histone/ lysine (K) acetyltransferases, HATs/KATs) and deacetylases (histone/lysine (K) deacetylases, HDACs/KDACs). Lysine acetylation regulates various metabolic processes, such as fatty acid oxidation, Krebs cycle, oxidative phosphorylation, angiogenesis and so on. Thus disorders of lysine acetylation may be correlated with obesity, diabetes and cardiovascular disease, which are termed as the metabolic complication. With accumulating studies on proteomic acetylation, lysine acetylation also involves in cell immune status and degenerative diseases, for example, Alzheimer’s disease and Huntington’s disease. This review primarily summarizes the current studies of lysine acetylation in metabolism modulation and in metabolism-related diseases, such as cardiovascular disease and fat metabolism disorder.
Extracting flexible, replayable models from large block traces

I/O traces are good sources of information about realworld workloads; replaying such traces is often used to reproduce the most realistic system behavior possible. But traces tend to be large, hard to use and share, and inflexible in representing more than the exact system conditions at the point the traces were captured. Often, however, researchers are not interested in the precise details stored in a bulky trace, but rather in some statistical properties found in the traces--properties that affect their system's behavior under load. We designed and built a system that (1) extracts many desired properties from a large block I/O trace, (2) builds a statistical model of the trace's salient characteristics, (3) converts the model into a concise description in the language of one or more synthetic load generators, and (4) can accurately replay the models in these load generators. Our system is modular and extensible. We experimented with several traces of varying types and sizes. Our concise models are 4-6% of the original trace size, and our modeling and replay accuracy are over 90%.
Prospective comparison of severity scores for predicting clinically relevant outcomes for patients hospitalized with community-acquired pneumonia.

BACKGROUND The comparative accuracy and discriminatory power of three validated rules for predicting clinically relevant outcomes other than mortality in patients hospitalized with community-acquired pneumonia (CAP) are unknown. METHODS We prospectively compared the newly developed severe community-acquired pneumonia (SCAP) score, pneumonia severity index (PSI), and the British Thoracic Society confusion, urea > 7 mmol/L, respiratory rate > or = 30 breaths/min, BP < 90 mm Hg systolic or < 60 mm Hg diastolic, age > or = 65 years (CURB-65) rule in an internal validation cohort of 1,189 consecutive adult inpatients with CAP from one hospital and an external validation cohort of 671 consecutive adult inpatients from three other hospitals. Major adverse outcomes were admission to ICU, need for mechanical ventilation, progression to severe sepsis, or treatment failure. Mean hospital length of stay (LOS) was also evaluated. The rules were compared based on sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic. RESULTS The rate of all adverse outcomes and hospital LOS increased directly with increasing SCAP, PSI, or CURB-65 scores (p < 0.001) in both cohorts. Patients classified as high risk by the SCAP score showed higher rates of adverse outcomes (ICU admission, 35.8%; mechanical ventilation, 16.4%; severe sepsis, 98.5%; treatment failure, 22.4%) than PSI and CURB-65 high-risk classes. The discriminatory power of SCAP, as measured by AUC, was 0.75 for ICU admission, 0.76 for mechanical ventilation, 0.79 for severe sepsis, and 0.61 for treatment failure in the external validation cohort. AUC differences with PSI or CURB-65 were found. CONCLUSIONS The SCAP score is as accurate or better than other current scoring systems in predicting adverse outcomes in patients hospitalized with CAP while helping classify patients into different categories of increasing risk for potentially closer monitoring.
Characterization of Trapped Lignin-Degrading Microbes in Tropical Forest Soil

Lignin is often the most difficult portion of plant biomass to degrade, with fungi generally thought to dominate during late stage decomposition. Lignin in feedstock plant material represents a barrier to more efficient plant biomass conversion and can also hinder enzymatic access to cellulose, which is critical for biofuels production. Tropical rain forest soils in Puerto Rico are characterized by frequent anoxic conditions and fluctuating redox, suggesting the presence of lignin-degrading organisms and mechanisms that are different from known fungal decomposers and oxygen-dependent enzyme activities. We explored microbial lignin-degraders by burying bio-traps containing lignin-amended and unamended biosep beads in the soil for 1, 4, 13 and 30 weeks. At each time point, phenol oxidase and peroxidase enzyme activity was found to be elevated in the lignin-amended versus the unamended beads, while cellulolytic enzyme activities were significantly depressed in lignin-amended beads. Quantitative PCR of bacterial communities showed more bacterial colonization in the lignin-amended compared to the unamended beads after one and four weeks, suggesting that the lignin supported increased bacterial abundance. The microbial community was analyzed by small subunit 16S ribosomal RNA genes using microarray (PhyloChip) and by high-throughput amplicon pyrosequencing based on universal primers targeting bacterial, archaeal, and eukaryotic communities. Community trends were significantly affected by time and the presence of lignin on the beads. Lignin-amended beads have higher relative abundances of representatives from the phyla Actinobacteria, Firmicutes, Acidobacteria and Proteobacteria compared to unamended beads. This study suggests that in low and fluctuating redox soils, bacteria could play a role in anaerobic lignin decomposition.
Exploring the Use of Thermal Infrared Imaging in Human Stress Research

High resolution thermal infrared imaging is a pioneering method giving indices of sympathetic activity via the contact-free recording of facial tissues (thermal imprints). Compared to established stress markers, the great advantage of this method is its non-invasiveness. The goal of our study was to pilot the use of thermal infrared imaging in the classical setting of human stress research. Thermal imprints were compared to established stress markers (heart rate, heart rate variability, finger temperature, alpha-amylase and cortisol) in 15 participants undergoing anticipation, stress and recovery phases of two laboratory stress tests, the Cold Pressor Test and the Trier Social Stress Test. The majority of the thermal imprints proved to be change-sensitive in both tests. While correlations between the thermal imprints and established stress markers were mostly non-significant, the thermal imprints (but not the established stress makers) did correlate with stress-induced mood changes. Multivariate pattern analysis revealed that in contrast to the established stress markers the thermal imprints could not disambiguate anticipation, stress and recovery phases of both tests. Overall, these results suggest that thermal infrared imaging is a valuable method for the estimation of sympathetic activity in the stress laboratory setting. The use of this non-invasive method may be particularly beneficial for covert recordings, in the study of special populations showing difficulties in complying with the standard instruments of data collection and in the domain of psychophysiological covariance research. Meanwhile, the established stress markers seem to be superior when it comes to the characterization of complex physiological states during the different phases of the stress cycle.
Broadband Spectral Analysis of PKS 0528+134: A Report on Six Years of EGRET Observations

The multiwavelength spectra of PKS 0528+134 during 6 yr of observations by EGRET have been analyzed using synchrotron self-Compton (SSC) and external radiation Compton (ERC) models. We find that a two-component model, in which the target photons are produced externally to the gamma-ray-emitting region, but also including an SSC component, is required to reproduce suitably the spectral energy distributions of the source. Our analysis indicates that there is a trend in the observed properties of PKS 0528+134, as the source goes from a gamma-ray low state to a flaring state. We observe that during the higher gamma-ray states, the bulk Lorentz factor of the jet increases and the ERC component dominates the high-energy emission. Our model calculations indicate the trend that the energies of the electrons giving rise to the synchrotron peak decrease, and the power-ratio of the gamma-ray and low-energy spectral components increases, as the source goes from a low to a high gamma-ray state.
Plant expression systems for early stage discovery and development of lead therapeutic antibodies.

BACKGROUND Antibodies for human clinical applications are predominantly produced in mammalian expression systems, with Chinese hamster ovary (CHO) cells being the gold standard. CHO cells are ideal for the manufacturing of the IgG class of antibodies, but not for the production of complex antibodies like secretory IgAs (SIgAs) and IgMs, which remain unavailable for clinical use. In contrast, plant seeds and leaves hold the promise to produce SIgAs, IgMs and similar complex antibody formats to scalable amounts. Using transient transformation of Nicotiana benthamiana leaves, complex antibody formats can be produced up to milligram amounts in less than a month. OBJECTIVE Based on these merits, we propose a model for early-phase exploration and designing of innovative antibody formats for therapeutic application. Further in this essay, we elaborate how the model was followed during the selection of novel antibodies for seed-based production. RESULT This exploratory model led to the engineering of novel light-chain devoid porcinized-llama antibodies (VHH-Fc) of the IgG (VHH-IgG) and IgA (VHH-IgA) isotypes and also tetravalent dimeric and SIgAs. CONCLUSION The proposed strategy may lead to plant-based rapid engineering of innovative antibodies more apt and efficacious for therapy, and in the coarse also add to the understanding of their mode of action.
Fluticasone or Montelukast in Preschool Wheeze

Introduction. Approximately 30% of children younger than 3 years experience at least 1 episode of wheezing. Antiasthmatic medication is routinely prescribed, but its effectiveness remains unclear. Our study was aimed to evaluate the effect of anti-inflammatory treatment on frequency and severity of preschool wheeze episodes (PWEs). Methods. Children aged 6 to 36 months with the first up to the third PWE were randomly assigned to receive montelukast, fluticasone, or no treatment for 12 weeks. The outcome measures were the number of PWEs, the number of hospitalizations due to PWE, and the severity of respiratory symptoms. Results. There were no significant differences in outcome measures between the groups. However, tobacco-exposed children treated with fluticasone had significantly fewer PWEs (P = .01). Conclusion. Neither montelukast nor fluticasone has proven effective in the prevention of PWE recurrence. Children of smoking parents may benefit from fluticasone treatment after PWE. This observation requires confirmation in larger studies.
Induction of matrix metalloproteinase gene expression in an endothelial cell line by direct interaction with malignant cells

Mouse endothelial TKD2 cells in monolayers were cocultured with various human cell lines for 24 h, and the expression of several secreted matrix metalloproteinases (MMP) and cell adhesion molecules was examined by real‐time reverse transcription–polymerase chain reaction using mouse‐specific primers. Coculture with normal fibroblasts did not elicit the expression of these molecules, but coculture with cancer cells induced the expression of MMP‐3, MMP‐9 and MMP‐10 mRNA in endothelial cells, and in normal mouse embryonic fibroblasts. The induction of MMP mRNA was dependent on direct cell adhesion, as separate culture of A549 cells in Boyden chambers did not induce MMP mRNA, and neutralizing antibody against VLA‐4 abolished the induction. An inhibitor of phosphatidylinositol‐3‐phosphate kinase strongly suppressed the induction of MMP‐3, MMP‐9 and MMP‐10 mRNA, and expression of the dominant‐negative mutant of phosphatidylinositol‐3‐phosphate kinase also decreased the induction. It was suggested that intracellular reactive oxygen species (ROS) levels were increased in TKD2 cells following adhesion to cancer cells. ROS scavengers decreased the levels of MMP induction, and roterone, an inhibitor of mitochondrial complex I, strongly suppressed the induction of MMP‐3, MMP‐9 and MMP‐10. The depletion of mitochondria in TKD2 cells decreased the induction of MMP‐9, but the induction of MMP‐3 and MMP‐10 was not affected. These results indicate that the adhesion of cancer cells to endothelial cells activates several distinct signaling pathways to induce MMP gene expression, and the pathways for MMP‐3, MMP‐9 and MMP‐10 are partly different. For the induction of MMP‐9, mitochondria participate in induction, possibly through the production of ROS. (Cancer Sci 2007; 98: 58–67)
Territorial and Microvascular Perfusion Impairment in Brain Arteriovenous Malformations

BACKGROUND AND PURPOSE: Both the existence and clinical relevance of a steal phenomenon in brain arteriovenous malformations (AVMs) remains a matter of debate. This study aimed to assess perfusion in the brain adjacent to brain AVMs and to relate these to macrovascular blood flow in a single measurement. MATERIALS AND METHODS: Twenty consecutive patients with AVMs with a median age of 37 years were evaluated by 3T MR imaging by using 3D time-resolved MR angiography to determine blood flow and perfusion patterns. Cerebral perfusion was estimated by using an arterial spin-labeling technique in vascular territories around the nidus and in symmetric regions of interest in the ipsilateral and contralateral hemispheres. Mapping of concentric shells around the nidus was used to define the immediate and adjacent brain and relative perfusion reductions >20% of baseline, termed perinidal dip (PND). RESULTS: A significant reduction in perfusion ratios between ipsilateral and contralateral hemispheres remote to the AVMs was demonstrated in the middle and posterior cerebral artery territories. PND was detected in 5 patients, and 17 patients overall showed reduced perfusion in the perinidal region on visual inspection. There was a negative correlation of the hemispheric territorial perfusion with the affected/nonaffected inflow time ratio (R = −0.402, P = .015). CONCLUSIONS: The perfusion impairment in vascular territories adjacent to brain AVMs that we identified as PND may reflect the existence of 2 levels of perfusion impairment: a territorial and a microvascular perfusion disturbance. Although the hemispheric asymmetry in territorial perfusion seems the result of arterioarterial redistribution, the PND was inhomogeneously distributed within a single vascular territory and thus might result from low perfusion pressure in small arteries and arterioles.