Miracle-dz/UniFAR-FTUs huggingface dataset:
Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

Pluripotency in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is regulated by three transcription factors—OCT3/4, SOX2, and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behavior of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11) and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.
Efficient 1-D and 2-D DOA Estimation for Non-Circular Sourceswith Hexagonal Shaped Espar Arrays

This contribution is focused on direction of arrival (DoA) estimation with a regular-hexagonal shaped ESPAR (electronically steerable parasitic antenna radiator) array that has received increased attention recently. It is shown how the estimation accuracy is improved by employing non-circular (NC) signal constellations that facilitate the application of the NC Unitary ESPRIT algorithm. It is demonstrated how this method allows the joint estimation of the azimuth and the elevation angles of up to eight uncorrelated sources with a 7-element ESPAR array. Moreover, the achievable benefits of using non-circular sources are assessed by studying deterministic Cramer-Rao bounds. It is shown that for special phase constellations between the impinging wavefronts the estimation accuracy is independent of the angular separation of the corresponding DoAs
Pit pattern classification using extended Local Binary Patterns

In this work we present a method for automated classification of endoscopic images according to the pit pattern classification scheme. Images taken during colonoscopy are transformed using a modified version of the local binary patterns operator (LBP). Then, two-dimensional histograms based on the LBP data from different color channels are created. Finally, the classification is carried out by employing the nearest-neighbors (1-NN) classifier in conjunction with the Bhattacharyya distance metric. The experimental results show that the extended LBP operator delivers superior results and an automated classification of endoscopic images based on the pit pattern classification scheme is feasible.
Which determinants predict tibiofemoral and patellofemoral osteoarthritis after anterior cruciate ligament injury? A systematic review

Background Anterior cruciate ligament (ACL) injury is an important risk factor for development of knee osteoarthritis (OA). To identify those ACL injured patients at increased risk for knee OA, it is necessary to understand risk factors for OA. Aim To summarise the evidence for determinants of (1) tibiofemoral OA and (2) patellofemoral OA in ACL injured patients. Methods MEDLINE, EMBASE, Web of Science and CINAHL databases were searched up to 20 December 2013. Additionally, reference lists of eligible studies were manually and independently screened by two reviewers. 2348 studies were assessed for the following main inclusion criteria: ≥20 patients; ACL injured patients treated operatively or non-operatively; reporting OA as outcome; description of relationship between OA outcome and determinants; and a follow-up period ≥2 years. Two reviewers extracted the data, assessed the risk of bias and performed a best-evidence synthesis. Results Sixty-four publications were included and assessed for quality. Two studies were classified as low risk of bias. Medial meniscal injury/meniscectomy showed moderate evidence for influencing OA development (tibiofemoral OA and compartment unspecified). Lateral meniscal injury/meniscectomy showed moderate evidence for no relationship (compartment unspecified), as did time between injury and reconstruction (tibiofemoral and patellofemoral OA). Conclusions Medial meniscal injury/meniscectomy after ACL rupture increased the risk of OA development. In contrast, it seems that lateral meniscal injury/meniscectomy has no relationship with OA development. Our results suggest that time between injury and reconstruction does not influence patellofemoral and tibiofemoral OA development. Many determinants showed conflicting and limited evidence and no determinant showed strong evidence.
Self-Rated Health and Long-Term Prognosis of Depression

PURPOSE Indicators of prognosis should be considered to fully inform clinical decision making in the treatment of depression. This study examines whether self-rated health predicts long-term depression outcomes in primary care. METHODS Our analysis was based on the first 5 years of a prospective 10-year cohort study underway since January 2005 conducted in 30 randomly selected Australian primary care practices. Participants were 789 adult patients with a history of depressive symptoms. Main outcome measures include risks, risk differences, and risk ratios of major depressive syndrome (MDS) on the Patient Health Questionnaire. RESULTS Retention rates during the 5 years were 660 (84%), 586 (74%), 560 (71%), 533 (68%), and 517 (66%). At baseline, MDS was present in 27% (95% CI, 23%–30%). Cross-sectional analysis of baseline data showed participants reporting poor or fair self-rated health had greater odds of chronic illness, MDS, and lower socioeconomic status than those reporting good to excellent self-rated health. For participants rating their health as poor to fair compared with those rating it good to excellent, risk ratios of MDS were 2.10 (95% CI, 1.60–2.76), 2.38 (95% CI, 1.77–3.20), 2.22 (95% CI, 1.70–2.89), 1.73 (95% CI, 1.30–2.28), and 2.15 (95% CI, 1.59–2.90) at 1, 2, 3, 4, and 5 years, after accounting for missing data using multiple imputation. After adjusting for age, sex, multimorbidity, and depression status and severity, self-rated health remained a predictor of MDS up to 5 years. CONCLUSIONS Self-rated health offers family physicians an efficient and simple way to identify patients at risk of poor long-term depression outcomes and to inform therapeutic decision making.
Genetic radiation risks: a neglected topic in the low dose debate

Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (Abomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down’s syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.
New frontiers in cell-based immunotherapy of cancer

Background: Cancer remains one of the leading causes of death. Over the past decade, discovery of tumor antigens, as well as new findings in basic immunology, have led to novel opportunities for developing active immunotherapeutical approaches for prevention and treatment of cancer. Objective/methods: This is a review of the literature and patents on the therapeutic potential of immune-based cell cancer therapies. Results/conclusion: In this article, we discuss the different approaches at present used for immune-based cell cancer therapies, and the results obtained both in preclinical models and in clinical trials of hematological malignancies and solid tumors.
Promoting physical activity: The role of neighbourhood safety and renewal of deprived areas

Even though physical inactivity is known to be detrimental for health, many adults remain inactive. Physical inactivity is particularly prevalent in deprived areas. It remains unclear to what extent physical activity is related to neighbourhood characteristics like neighbourhood safety. Moreover, there is scarce evidence on whether and how physical activity in deprived areas can be promoted by area-based initiatives that aim to improve the living conditions in deprived areas. The first objective of this thesis was to explore to what extent neighbourhood safety was associated with leisure-time physical activity among adults. The second objective of this thesis was to explore to what extent and how a Dutch area-based initiative called the District Approach was associated with changes in neighbourhood safety and leisure-time physical activity in 40 deprived target areas. This thesis provides evidence to suggest that safe neighbourhoods may promote leisure-time cycling and sports among adults. Good neighbourhood safety may also promote leisure-time walking, but only in deprived areas. In deprived areas, area-based initiatives like the Dutch District Approach appear to be able to promote leisure-time physical activity among adults. More specifically, they seem to promote leisure-time walking by making parks and trails less frightening, more convenient, and more relaxing. These results emphasize the need for large-scale and multidisciplinary approaches to solve neighbourhood problems and hence stimulate leisure-time physical activity in deprived areas.
Optimal energy beamforming and data routing for immortal wireless sensor networks

Wireless sensor networks (WSNs) consist of energy limited sensor nodes, which limits the network lifetime. Such a lifetime can be prolonged by employing the emerging technology of wireless energy transfer (WET). In WET systems, the sensor nodes can harvest wireless energy from wireless charger, which can use energy beamforming to improve the efficiency. In this paper, a scenario where dedicated wireless chargers with multiple antennas use energy beamforming to charge sensor nodes is considered. The energy beamforming is coupled with the energy consumption of sensor nodes in terms of data routing, which is one novelty of the paper. The energy beamforming and the data routing are jointly optimized by a non-convex optimization problem. This problem is transformed into a semidefinite optimization problem, for which strong duality is proved, and thus the optimal solution exists. It is shown that the optimal solution of the semi-definite programming problem allows to derive the optimal solution of the original problem. The analytical and numerical results show that optimal energy beamforming gives two times better monitoring performance than that of WET without using energy beamforming.
Experimental Study of the Seismic Behavior of Predamaged Reinforced-Concrete Columns Retrofitted with Basalt Fiber–Reinforced Polymer

AbstractReinforced concrete (RC) frame structures are widely used in earthquake regions, and damage to these structures has been reported after many earthquakes. Small parts of seriously damaged RC frames should be demolished and reconstructed, and a large number of earthquake-damaged RC frames can be retrofitted and used again. In this paper, the seismic behavior of predamaged reinforced concrete columns repaired using early-strength cement mortar and basalt fiber–reinforced polymer (BFRP) has been investigated through lateral reversed cyclic tests on seven large-sized RC columns. Two predamage levels [(1) moderate damage, and (2) severe damage] were assigned to the RC columns through cyclic loading. The axial load and residual displacement were kept constant during the retrofitting process, and the retrofitted columns were retested after 6 days of mortar and epoxy curing at room temperature. The ductility and energy dissipation capacities of the fiber-reinforced polymer (FRP)-retrofitted predamaged RC c.
Human infection with an avian influenza A (H9N2) virus in the middle region of China

During the epidemic period of the novel H7N9 viruses, an influenza A (H9N2) virus was isolated from a 7‐year‐old boy with influenza‐like illness in Yongzhou city of Hunan province in November 2013. To identify the possible source of infection, environmental specimens collected from local live poultry markets epidemiologically linked to the human case in Yongzhou city were tested for influenza type A and its subtypes H5, H7, and H9 using real‐time RT‐PCR methods as well as virus isolation, and four other H9N2 viruses were isolated. The real‐time RT‐PCR results showed that the environment was highly contaminated with avian influenza H9 subtype viruses (18.0%). Sequencing analyses revealed that the virus isolated from the patient, which was highly similar (98.5–99.8%) to one of isolates from environment in complete genome sequences, was of avian origin. Based on phylogenetic and antigenic analyses, it belonged to genotype S and Y280 lineage. In addition, the virus exhibited high homology (95.7–99.5%) of all six internal gene lineages with the novel H7N9 and H10N8 viruses which caused epidemic and endemic in China. Meanwhile, it carried several mammalian adapted molecular residues including Q226L in HA protein, L13P in PB1 protein, K356R, S409N in PA protein, V15I in M1 protein, I28V, L55F in M2 protein, and E227K in NS protein. These findings reinforce the significance of continuous surveillance of H9N2 influenza viruses. J. Med. Virol. 87:1641–1648, 2015. © 2015 Wiley Periodicals, Inc.
Shear Strength of Simply- or Rigidly-Supported RC Beams with Various Design Variables

An experimental study was performed to systematically investigate the variation of shear strength of simply- or rigidly-supported RC beams with various design variables. In this study, the tensile reinforcement ratio, load applying condition, end supporting condition, shear span to depth ratio, and prestressing force were selected as the main variables. Twenty RC beams without shear reinforcement were tested under monotonic loading, and the influences of the main variables on shear strength were analyzed with shear force-displacement relationships and failure modes. The test results indicated that the shear strength of RC beams increased as the tensile reinforcement ratio, the number of loading points, the compressive force, or the initial prestressing force increased. However, it decreased as the shear span to depth ratio increased. The influence of the end supporting condition on the shear strength of specimens was not significant. The test results were compared with the predicted values provided by design codes and existing model equations.
Effect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Outcome and Cardiac Function in Patients With Diabetes and Heart Failure　- Insights From the Ibaraki Cardiac Assessment Study-Heart Failure (ICAS-HF) Registry.

BACKGROUND Although experimental animal studies report many pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), their prognostic value has not been demonstrated in clinical trials.Methods and Results:Among 838 prospectively enrolled heart failure (HF) patients hospitalized for acute decompensated HF, 79 treated with DPP-4i were compared with 79 propensity score-matched non-DPP-4i diabetes mellitus (DM) patients. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of cardiovascular death and hospitalization. During follow-up (423±260 days), 8 patients (10.1%) in the DPP-4i group and 13 (16.5%) in the non-DPP-4i group died (log-rank, P=0.283). The DPP-4i group did not have a significantly higher rate of all-cause mortality (log-rank, P=0.283), or cardiovascular death or hospitalization (log-rank, P=0.425). In a subgroup analysis of HF with preserved ejection fraction (HFpEF; n=75), the DPP-4i group had a significantly better prognosis than the non-DPP-4i group regarding the primary endpoint (log-rank, P=0.021) and a tendency to have better prognosis regarding the secondary endpoint (log-rank, P=0.119). In patients with HF with reduced EF (n=83), DPP-4i did not result in better prognosis. CONCLUSIONS DPP-4i did not increase the risk of adverse clinical outcomes in patients with DM and HF. DPP-4i may be beneficial in HFpEF.
A Bijective String Sorting Transform

Given a string of characters, the Burrows-Wheeler Transform rearranges the characters in it so as to produce another string of the same length which is more amenable to compression techniques such as move to front, run-length encoding, and entropy encoders. We present a variant of the transform which gives rise to similar or better compression value, but, unlike the original, the transform we present is bijective, in that the inverse transformation exists for all strings. Our experiments indicate that using our variant of the transform gives rise to better compression ratio than the original Burrows-Wheeler transform. We also show that both the transform and its inverse can be computed in linear time and consuming linear storage.
Homoarginine and Cardiovascular Outcome in the Population-Based Dallas Heart Study

Objective—The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. Approach and Results—Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36–52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0–9.8) years. Median plasma homoarginine was 2.80 (2.14–3.54) &mgr;mol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75–0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73–0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (&bgr;-estimate, −0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. Conclusions—Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease.
In Vitro Reconstruction of Neuronal Networks Derived from Human iPS Cells Using Microfabricated Devices

Morphology and function of the nervous system is maintained via well-coordinated processes both in central and peripheral nervous tissues, which govern the homeostasis of organs/tissues. Impairments of the nervous system induce neuronal disorders such as peripheral neuropathy or cardiac arrhythmia. Although further investigation is warranted to reveal the molecular mechanisms of progression in such diseases, appropriate model systems mimicking the patient-specific communication between neurons and organs are not established yet. In this study, we reconstructed the neuronal network in vitro either between neurons of the human induced pluripotent stem (iPS) cell derived peripheral nervous system (PNS) and central nervous system (CNS), or between PNS neurons and cardiac cells in a morphologically and functionally compartmentalized manner. Networks were constructed in photolithographically microfabricated devices with two culture compartments connected by 20 microtunnels. We confirmed that PNS and CNS neurons connected via synapses and formed a network. Additionally, calcium-imaging experiments showed that the bundles originating from the PNS neurons were functionally active and responded reproducibly to external stimuli. Next, we confirmed that CNS neurons showed an increase in calcium activity during electrical stimulation of networked bundles from PNS neurons in order to demonstrate the formation of functional cell-cell interactions. We also confirmed the formation of synapses between PNS neurons and mature cardiac cells. These results indicate that compartmentalized culture devices are promising tools for reconstructing network-wide connections between PNS neurons and various organs, and might help to understand patient-specific molecular and functional mechanisms under normal and pathological conditions.