Miracle-dz/UniFAR-FTUs huggingface dataset:
Orthotopic hepatic cancer: radiofrequency hyperthermia-enhanced intratumoral herpes simplex virus-thymidine kinase gene therapy

Purpose To validate the feasibility of using interventional radiofrequency hyperthermia(RFH) to enhance herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV) gene therapy of rat orthotopic hepatic cancer. Material and Methods Rat hepatocellular carcinoma cells (MCA-RH-7777) were transduced with lentivirus/luciferase gene for optical imaging. In-vitro experiments with the luciferase cells and in-vivo experiments on rats with orthotopic hepatic tumors were divided into four treatment groups: (i) HSV-TK/GCV-mediated gene therapy combined with RFH; (ii) gene therapy alone; (iii) RFH alone; and (iv) phosphate buffered saline (PBS). Cell viability was evaluated by MTS assay and confocal microscopy, and HSV-TK gene expression in cells and tumors was quantified by western blotting. Bioluminescent optical imaging and ultrasound imaging were used to monitor and compare the photon signal and tumor size changes among different treatment groups overtime, respectively. The imaging findings were correlated with histology. Results For in-vitro experiments, the combination therapy group (gene therapy + RFH) demonstrated the lowest cell proliferation by MTS assay, compared to the gene therapy alone, RFH alone, and PBS (26.1±3.2% vs 50.4±4.6% vs 82.9±6.3% vs 100%, p<0.01). The combination therapy group also showed fewer survived cells by the confocal microscopy and the lowest bioluminescent signal by the optical imaging. For in-vivo experiments, the combination therapy group demonstrated a significantly decreased signal intensity on the bioluminescent optical imaging (0.57±0.09, 1.06±0.10 vs 3.43±0.27 vs 3.85±0.12, p<0.05) and smallest tumor volume by ultrasound imaging (0.28±0.11 vs 1.28±0.23vs 4.64±0.35 vs 6.37±0.36, p<0.05), compared to the other three groups. Additionally, these imaging findings correlated well with the histological confirmation. Conclusion It is feasible to use RFH to enhance HSV-TK/GCV gene therapy of hepatic tumors in in-vitro and in-vivo settings, as assessed by molecular imaging. This technical development may provide a novel opportunity for effective treatment of liver malignancies by employing simultaneous integration of radiofrequency technology, interventional oncology, and direct intratumoral gene therapy.
Stat3 phosphorylation is required for embryonic stem cells ground state maintenance in 2i culture media

Embryonic stem cells (ES cells) can be maintained its undifferentiated state with feeder cells or LIF, which can activate Jak/Stat3 pathway. Recently, it has been reported a new culture condition comprising serum-free medium with ERK and GSK3β inhibitors (2i) could drive ES cells into a state of pluripotency more like inner cell mass (ICM) in mouse blastocysts called ground state. However, although 2i could sustain ES cells self-renewal, LIF is routinely added. The roles of Stat3 activation are still unclear now. Here we investigated whether Jak/Stat3 might also contribute to the induction of ground state pluripotency. We introduced a lentiviral construct with 7-repeat Stat3-binding sequence to drive Renilla luciferase into ES cells, which can be used as a reporter to detect Stat3 activation by noninvasive bioluminescence imaging. Using this ES cells, we investigated the role of Stat3 activation in ground state maintenance. The results showed that Stat3 could be activated by 2i. Stattic, a chemical inhibitor of Stat3 phosphorylation, could effectively inhibit Stat3 activation in ES cells. When Stat3 activation was suppressed, ground state related genes were down regulated, and ES cells could not be maintained the ground state pluripotency even in 2i medium. All of these results indicate Stat3 activation is required in ground state maintenance.
Meta-strategy for cooperative tasks with learning of environments in multi-agent continuous tasks

With the development of robot technology, we can expect self-propelled robots working in large areas where cooperative and coordinated behaviors by multiple (hardware and software) robots are necessary. However, it is not trivial for agents, which are control programs running on robots, to determine the actions for their cooperative behaviors, because such strategies depend on the characteristics of the environment and the capabilities of individual agents. Therefore, using the example of continuous cleaning tasks by multiple agents, we propose a method of meta-strategy that decide the appropriate planning strategies for cooperation and coordination through with the learning of the performance of individual strategies and the environmental data in a multi-agent systems context, but without complex reasoning for deep coordination due to the limited CPU capability and battery capacity. We experimentally evaluated our method by comparing it with a conventional method that assumes that agents have knowledge on where agents visit frequently (since they are easy to become dirty). We found that agents with the proposed method could operate as effectively as and, in complex areas, outperformed those with the conventional method. Finally, we describe that the reasons for such a counterintuitive phenomenon is induced from splitting up in working by autonomous agents based on the local observations. We also discuss the limitation of the current method.
Circulating IGF-1, IGFB-3, GH and TSH levels in multiple sclerosis and their relationship with treatment

Abstract Objectives: Improving the proficiency of oligodendrocytes in their ability to repair myelin damage is one of the major goals of multiple sclerosis treatment. Insulin-like growth factor-1 (IGF-1) is one of several polypeptides that are considered to have potential benefits in that sense. In the present study, we aimed to determine serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3), thyroid stimulating hormone (TSH) and growth hormone (GH) among treated and non-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and a healthy control group. Methods: The study enrolled 100 RRMS patients and 100 age- and sex-matched control subjects diagnosed with definite multiple sclerosis (MS). Serum GH, IGF-1, IGFBP-3, and TSH levels were studied. Results: The number of relapses and Expanded Disability Status Scale were negatively correlated and IGFBP-3 and GH were positively correlated with IGF-1. A statistically significant difference was not observed when patients were divided into two subgroups as patients treated with a MS-specific therapy (n = 54) and non-treated patients (n = 46). TSH and IGFBP-3 values were significantly lower in patient group vs. control group. Conclusion: While no difference was determined with in IGF-1 levels, low levels of IGF-1 was in correlation with the least levels of IGFBP-3. To understand the relation between IGF-1 and IGFBP-3, the role of low levels of IGFBP-3 and TSH may be studied with clinic isolated syndrome patients and the evolution of these patients to definite MS.
The VFH1 (YLL056C) promoter is vanillin‐inducible and enables mRNA translation despite pronounced translation repression caused by severe vanillin stress in Saccharomyces cerevisiae

Vanillin, furfural and 5‐hydroxymethylfurfural (HMF) are representative fermentation inhibitors generated during the pretreatment process of lignocellulosic biomass in bioethanol production. These biomass conversion inhibitors, particularly vanillin, are known to repress translation activity in Saccharomyces cerevisiae. We have reported that the mRNAs of ADH7 and BDH2 were efficiently translated under severe vanillin stress despite marked repression of overall protein synthesis. In this study, we found that expression of VFH1 (YLL056C) was also significantly induced at the protein level by severe vanillin stress. Additionally, we demonstrated that the VFH1 promoter enabled the protein synthesis of other genes including GFP and ALD6 under severe vanillin stress. It is known that transcriptional activation of VFH1 is induced by furfural and HMF, and we verified that Vfh1 protein synthesis was also induced by furfural and HMF. The null mutant of VFH1 delayed growth in the presence of vanillin, furfural and HMF, indicating the importance of Vfh1 for sufficient tolerance against these inhibitors. The protein levels of Vfh1 induced by the inhibitors tested were markedly higher than those of Adh7 and Bdh2, suggesting the superior utility of the VFH1 promoter over the ADH7 or BDH2 promoter for breeding optimized yeast strains for bioethanol production from lignocellulosic biomass.
Therapeutic Applications of Rose Hips from Different Rosa Species

Rosa species, rose hips, are widespread wild plants that have been traditionally used as medicinal compounds for the treatment of a wide variety of diseases. The therapeutic potential of these plants is based on its antioxidant effects caused by or associated with its phytochemical composition, which includes ascorbic acid, phenolic compounds and healthy fatty acids among others. Over the last few years, medicinal interest in rose hips has increased as a consequence of recent research that has studied its potential application as a treatment for several diseases including skin disorders, hepatotoxicity, renal disturbances, diarrhoea, inflammatory disorders, arthritis, diabetes, hyperlipidaemia, obesity and cancer. In this review, the role of different species of Rosa in the prevention of treatment of various disorders related to oxidative stress, is examined, focusing on new therapeutic approaches from a molecular point of view.
Definitive Zygosity Scores in the Peas in the Pod Questionnaire is a Sensitive and Accurate Assessment of the Zygosity of Adult Twins

Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the ‘peas in the pod’ questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.
Semi-supervised entity relation extraction based on trigger word

Relation extraction is one of the most important tasks in the process of information extraction. This paper studies a semi-supervised entity relation extraction method, most of the existing semi-supervised relation extraction methods are based on the bootstrapping algorithm, the obvious drawback of this method is that it is prone to semantic drift, resulting in the lower recall rate. In order to solve this problem, this paper based on the traditional method of trigger words extraction, presents an advanced trigger words extraction method (ATW), it is more flexible and accurate, effectively alleviates the problem of semantic drift. The experimental result show that the method has a good performance, precision, recall rate and F value have been greatly improved.
Emerging Strategies of Cancer Therapy Based on Ferroptosis

Ferroptosis, a new form of regulated cell death that is iron‐ and reactive oxygen species dependent, has attracted much attention in the research communities of biochemistry, oncology, and especially material sciences. Since the first demonstration in 2012, a series of strategies have been developed to induce ferroptosis of cancer cells, including the use of nanomaterials, clinical drugs, experimental compounds, and genes. A plethora of research work has outlined the blueprint of ferroptosis as a new option for cancer therapy. However, the published ferroptosis‐related reviews have mainly focused on the mechanisms and pathways of ferroptosis, which motivated this contribution to bridge the gap between biological significance and material design. Therefore, it is timely to summarize the previous efforts on the emerging strategies for inducing ferroptosis and shed light on future directions for using such a tool to fight against cancer. Here, the current strategies of cancer therapy based on ferroptosis will be elaborated, the design considerations and the advantages and limitations are highlighted, and finally a future perspective on this emerging field is given.
Cyclic AMP and glycogen synthase kinase 3 form a regulatory loop in spermatozoa

The multifaceted glycogen synthase kinase (GSK3) has an essential role in sperm and male fertility. Since cyclic AMP (cAMP) plays an important role in sperm function, we investigated whether GSK3 and cAMP pathways may be interrelated. We used GSK3 and soluble adenylyl cyclase (sAC) knockout mice and pharmacological modulators to examine this relationship. Intracellular cAMP levels were found to be significantly lower in sperm lacking GSK3α or GSK3β. A similar outcome was observed when sperm cells were treated with SB216763, a GSK3 inhibitor. This reduction of cAMP levels was not due to an effect on sperm adenylyl cyclase but was caused by elevated phosphodiesterase (PDE) activity. The PDE4 inhibitor RS25344 or the general PDE inhibitor IBMX could restore cAMP levels in sperm lacking GSK3α or β‐isoform. PDE activity assay also showed that hyperactivated PDE4 contributes in lowering of cAMP levels in GSK3α null sperm suggesting that in wild‐type sperm PDE4 activity is kept in check by GSK3. Conversely, PKA being triggered by cAMP, affected GSK3 activity through increasing its phosphorylation. Increased GSK3 phosphorylation also occurred by inhibition of sperm specific protein phosphatase type 1, PP1γ2. The relationship between cAMP, GSK3, and PP1γ2 activities was also confirmed in sperm from sAC null mice. Pull‐down assay using recombinant PP1γ2 indicated that PKA, GSK3, and PP1γ2 could exist as a complex. Pharmacological inhibition of GSK3 in mature spermatozoa resulted in significantly reduced fertilization of eggs in vitro. Our results show that cAMP, PKA, and GSK3 are interrelated in regulation of sperm function.
A bottom-up kernel of pattern learning for relation extraction

Measuring the similarity of patterns is the key in pattern-based approaches in relation extraction. Most existing methods generally rely on inflexible pattern similarity measurements which often lead to low recall. In this work, a novel kernel-based model is proposed to address this problem. Depending on the pattern similarities produced by our bottom-up kernel, the most similar semantic shortest dependency patterns are selected to update seed patterns in each iteration of bootstrapping. To obtain insights of the reliability and applicability of our proposed method, we applied it to the task of English Slot Filling (ESF) in Knowledge Base Population (KBP) track at Text Analysis Conference (TAC). The experimental results validate our proposed method that importantly improves the recall which resulting in the improvement of F1 value. The effectiveness of the bottom-up kernel is also verified by further experimental results.
Dental Undergraduate Views of Objective Structured Clinical Examinations (OSCEs): A Literature Review

Objective Structured Clinical Examinations (OSCEs) are widely used in dental undergraduate assessment, often determining progression or graduation. Student evaluation of this assessment process is important, and this includes identifying the views of the student. The aim of this paper is to present a review of the current literature regarding dental student perceptions of OSCEs. A search of the PubMed database covering the period 1975 to 2015 identified 121 possible papers from which only six were suitable for review. The remaining papers were excluded due to them not reporting on dental undergraduate views. Students perceived the OSCE to be a valid assessment in three studies, but not in one. The educational benefit of an OSCE is well supported by these studies. OSCEs can induce high levels of anxiety compared to other forms of assessments, but this did not affect student performance. The majority of students would chose to have a similar format of assessment again, showing support for OSCEs. Further research using larger cohorts of students could be undertaken in order to support these finding which would give added evidence for the continuing use of OSCEs as a valid method of both dental undergraduate education and assessment.
Non-stationarities significantly distort short-term spectral, symbolic and entropy heart rate variability indices

The autonomic regulation is non-invasively estimated from heart rate variability (HRV). Many methods utilized to assess autonomic regulation require stationarity of HRV recordings. However, non-stationarities are frequently present even during well-controlled experiments, thus potentially biasing HRV indices. The aim of our study is to quantify the potential bias of spectral, symbolic and entropy HRV indices due to non-stationarities. We analyzed HRV series recorded in healthy subjects during uncontrolled daily life activities typical of 24 h Holter recordings and during predetermined levels of robotic-assisted treadmill-based physical exercise. A stationarity test checking the stability of the mean and variance over short HRV series (about 300 cardiac beats) was utilized to distinguish stationary periods from non-stationary ones. Spectral, symbolic and entropy indices evaluated solely over stationary periods were contrasted with those derived from all the HRV segments. When indices were calculated solely over stationary series, we found that (i) during both uncontrolled daily life activities and controlled physical exercise, the entropy-based complexity indices were significantly larger; (ii) during uncontrolled daily life activities, the spectral and symbolic indices linked to sympathetic modulation were significantly smaller and those associated with vagal modulation were significantly larger; (iii) while during uncontrolled daily life activities, the variance of spectral, symbolic and entropy rate indices was significantly larger, during controlled physical exercise, it was smaller. The study suggests that non-stationarities increase the likelihood to overestimate the contribution of sympathetic control and affect the power of statistical tests utilized to discriminate conditions and/or groups.
Content placement in heterogeneous end-to-end virtual networks

One of the distinctive features of the new virtualized ecosystem, is the multi-stakeholder participation in the way cloud services are designed, deployed and offered. In this work, we address the emerging content replication problem a Content Delivery Network (CDN) provider needs to consider, when deploying its network over multi-domain, heterogeneous environments, where virtual network operators utilize both the CDN services and the virtualized infrastructures. In our model, the benefit that the CDN provider enjoys may be different per network operator for the same request, while our model takes into account the replication cost to every domain, as well as the user mobility, besides physical storage limitations. Since the optimal placement of the objects at the caches of the various domains resembles the multiple knapsack problem, which is NP-complete, we provide two approximate solutions to the emerging content placement problem. We evaluate the proposed policies through extensive simulations and we compare them against a myopic method, where a domain is unaware of the caching strategy of the other domains that is connected to.
High dynamic stripe image enhancement for reliable center extraction in complex environment

High-precision laser vision sensors, as an important mean of 3D data acquisition, are being widely used for online high-speed measurement in complex environment. However, due to the complexity of the scene environment, the stripe images show high dynamic, low signal to noise ratio, which seriously affect the reliability and detection accuracy. In this paper, a high dynamic stripe image brightness enhancement method is proposed. The Retinex theory is adopted to enhance stripe brightness, which makes the gray value of stripe in cross-section is close to Gaussian distribution. Meanwhile, the stripe is segmented correctly based on the reflectivity, which ensures low quality stripes can be enhanced correctly. In that case, the central coordinate of stripe can be easily extracted. Finally, a multi-thread flow acceleration and serialized output program are used to meet the requirement of real-time measurement. The physical experiments indicate that this method can improve the system reliability greatly, which has important practical application value.
Generalization of task model using compliant movement primitives in a bimanual setting

Compliant Movement Primitives (CMPs) showed good performance for a desirable behavior of robots to maintain low trajectory error while being compliant without knowing the dynamic model of the task. This framework uses the integral representation of reference trajectories in a feedback loop together with driving joint torques that represent the feed-forward control term. To achieve CMPs generalization, refer-ence trajectories (represented in the form of task space position trajectories) are encoded as Dynamic Movement Primitives (DMPs) while the feed-forward torques are learned through the Gaussian Process Regression (GPR) and are represented as a combination of radial basis functions. This paper extends the existing framework through the generalization of CMPs in bimanual settings that can concurrently achieve low trajectory errors in relative task space and compliant behavior in absolute task space. To achieve this behavior of the bimanual robotic system, the control terms derived from CMP framework are extended with the symmetric control approach. We show how the task-specific bimanual task dynamics can be learned and generalized to different task parameters that influence the task space trajectory and to a different load. Real-world results on a bimanual Kuka LWR-4 robots configuration confirms the usability of the extended framework.