Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Typing and Handwriting in “Two-Finger Typists”

Twelve subjects who are not touch typists, but have a median of ten years experience using computer keyboards performed two writing tasks: writing a short memorized passage and copying a four paragraph passage. Subjects performed each task once using a pen and paper and once using a display oriented text-editor. Typing speed was over five words per minute (wpm) faster than handwriting for both memorized and copied passages. Typing and writing were each about ten words per minute faster from memory than from copy. The number of errors was greater when typing from copy than in any other condition. These results suggest that for experienced two-finger typists, typing from a display-oriented document processor can be faster than handwriting.
Efficient Tumor Clearance and Diversified Immunity through Neoepitope Vaccines and Combinatorial Immunotherapy

A multifaceted approach utilizing a neoepitope vaccine in combination with an IL15 superagonist, PD-L1 blockade, and a tumor-targeting IL12 molecule promoted the expansion of antitumor T cell responses and efficient tumor clearance in a colon carcinoma mouse model. Progressive tumor growth is associated with deficits in the immunity generated against tumor antigens. Vaccines targeting tumor neoepitopes have the potential to address qualitative defects; however, additional mechanisms of immune failure may underlie tumor progression. In such cases, patients would benefit from additional immune-oncology agents targeting potential mechanisms of immune failure. This study explores the identification of neoepitopes in the MC38 colon carcinoma model by comparison of tumor to normal DNA and tumor RNA sequencing technology, as well as neoepitope delivery by both peptide- and adenovirus-based vaccination strategies. To improve antitumor efficacies, we combined the vaccine with a group of rationally selected immune-oncology agents. We utilized an IL15 superagonist to enhance the development of antigen-specific immunity initiated by the neoepitope vaccine, PD-L1 blockade to reduce tumor immunosuppression, and a tumor-targeted IL12 molecule to facilitate T-cell function within the tumor microenvironment. Analysis of tumor-infiltrating leukocytes demonstrated this multifaceted treatment regimen was required to promote the influx of CD8+ T cells and enhance the expression of transcripts relating to T-cell activation/effector function. Tumor-targeted IL12 resulted in a marked increase in clonality of T-cell repertoire infiltrating the tumor, which when sculpted with the addition of either a peptide or adenoviral neoepitope vaccine promoted efficient tumor clearance. In addition, the neoepitope vaccine induced the spread of immunity to neoepitopes expressed by the tumor but not contained within the vaccine. These results demonstrate the importance of combining neoepitope-targeting vaccines with a multifaceted treatment regimen to generate effective antitumor immunity.
MCF-7 as a Model for Functional Analysis of Breast Cancer Risk Variants

Background: Breast cancer genetic predisposition is governed by more than 142 loci as revealed by genome-wide association studies (GWAS). The functional contribution of these risk loci to breast cancer remains unclear, and additional post-GWAS analyses are required. Methods: We identified active regulatory elements (enhancers, promoters, and chromatin organizing elements) by histone H3K27 acetylation and CTCF occupancy and determined the enrichment of risk variants at these sites. We compared these results with previously published data and for other cell lines, including human mammary epithelial cells, and related these data to gene expression. Results: In terms of mapping accuracy and resolution, our data augment previous annotations of the MCF-7 epigenome. After intersection with GWAS risk variants, we found 39 enhancers and 15 CTCF occupancy sites that, between them, overlapped 96 breast cancer credible risk variants at 42 loci. These risk enhancers likely regulate the expression of dozens of genes, which are enriched for GO categories, including estrogen and prolactin signaling. Conclusions: Ten (of 142) breast cancer risk loci likely function via enhancers that are active in MCF-7 and are well suited to targeted manipulation in this system. In contrast, risk loci cannot be mapped to specific CTCF-binding sites, and the genes linked to risk CTCF sites did not show functional enrichment. The identity of risk enhancers and their associated genes suggests that some risk may function during later processes in cancer progression. Impact: Here, we report how the ER+ cell line MCF-7 can be used to dissect risk mechanisms for breast cancer.
Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles

Owing to the increasing application of engineered nanoparticles (NPs), besides the workplace, human beings are also exposed to NPs from nanoproducts through the skin, respiratory tract, digestive tract and vein injection. This review states pathways of cellular uptake, subcellular distribution and excretion of NPs. The uptake pathways commonly include phagocytosis, micropinocytosis, clathrin‐ and caveolae‐mediated endocytosis, scavenger receptor‐related pathway, clathrin‐ or caveolae‐independent pathway, and direct penetration or insertion. Then the ability of NPs to decrease cell viability and metabolic activity, change cell morphology, and destroy cell membrane, cytoskeleton and cell function was presented. In addition, the lowest dose decreasing cell metabolic viability compared with the control or IC50 of silver, titanium dioxide, zinc oxide, carbon black, carbon nanotubes, silica, silicon NPs and cadmium telluride quantum dots to some cell lines was gathered. Next, this review attempts to increase our understanding of NP‐caused adverse effects on organelles, which have implications in mitochondrial dysfunction, endoplasmic reticulum stress and lysosomal rupture. In particular, the disturbance of mitochondrial biogenesis and mitochondrial dynamic fusion‐fission, mitophagy and cytochrome c‐dependent apoptosis are involved. In addition, prolonged endoplasmic reticulum stress will result in apoptosis. Rupture of the lysosomal membrane was associated with inflammation, and both induction of autophagy and blockade of autophagic flow can result in cytotoxicity. Finally, the network mechanism of the combined action of multiple organelle dysfunction, apoptosis, autophagy and oxidative stress was discussed.
Probing broad timescale and heterogeneous conformational dynamics in the catalytic core of the Arf-GAP ASAP1 via methyl adiabatic relaxation dispersion.

Methyl-TROSY is one of the most powerful NMR spectroscopic tools for studying structures and conformational dynamics of large protein complexes in solution. In studying conformational dynamics, side-chains usually display heterogeneous dynamics, including col-lective and local motions, that can be difficult to detect and analyze by conventional relaxation dispersion (RD) approaches. The combi-nation of NH-based adiabatic relaxation dispersion experiments and geometric approximation (geoHARD) has been shown to have sev-eral advantages over conventional RD to reveal conformational dynamics over a broad timescale. Here, we demonstrate a new technique developed to detect both heterogeneous and wide timescale conformational dynamics in the hydrophobic interior of large macro-molecules utilizing methyl-geoHARD. It is shown that methyl-geoHARD will be feasible at ultra-high magnetic fields (> 1 GHz), when this technology becomes available. For the ZA domain of the Arf-GAP ASAP1, with a global correlational time of 24 ns at 15 ˚C, a wide range of conformational dynamics (exhibiting chemical exchange (kex) values between 0.1~100 k s-1) is observed in the methyl groups of isoleucine, leucine, and valine. The dynamics include collective and independent local motions. Furthermore, portions of the collective motions have been confirmed by single-quantum Carr-Purcell-Meiboom-Gill (SQ-CPMG) RD experiments; however, motions outside of the detectable CPMG window (400-8000 s-1) cannot be accurately determined by SQ-CPMG experiments. The methyl-geoHARD experiment allows dissection of heterogeneous conformational dynamics and pinpoints important motions that, potentially, can be correlated with important biological functions and recognition.
Research on the influences of five food-borne polyphenols on invitro slow starch digestion and the mechanism of action.

Inhibiting starch digestion can effectively control postprandial blood sugar level. In this study, the in vitro digestion differences among the mixtures of five polyphenols (i.e., procyanidins [PAs], catechin [CA], tannic acid [TA], rutin [RU], and quercetin [QU]) and starch were analyzed through an in vitro simulation test of starch digestion. The interaction characteristics of these five polyphenols with α-amylase and α-glucosidase were investigated in terms of the inhibition effect, dynamics, fluorescence quenching, and circular dichroism (CD). The results revealed that the rapidly digestible starch (RDS) contents decreased, while the resistant starch (RS) contents increased. All five polyphenols inhibited the α-amylase activity through the noncompetitive approach but inhibited the α-glucosidase activity through the competitive approach. Five polyphenols combined with α-amylase spontaneously by using hydrophobic effect. The interaction of PAs and QU with α-glucosidase were recognized as van der Waals force and H bond, whereas CA and TA interacted with α-glucosidase through the hydrophobic effect. All five polyphenols can cause conformational change in enzymes.
Plant facilitation through mycorrhizal symbiosis is stronger between distantly related plant species.

•The tendency of closely related plant species to share natural enemies has been suggested to limit their co-occurrence and performance, but we lack a deep understanding on how mutualistic interactions such as the mycorrhizal symbiosis affect plant-plant interactions depending on the phylogenetic relatedness of the interacting plants. We hypothesize that the effect of the mycorrhizal symbiosis on plant-plant facilitative interactions depends on the phylogenetic distance between the nurse and facilitated plants. •A recently published meta-analysis compiled the strength of plant facilitative interactions in the presence or absence (or reduced abundance) of mycorrhizal fungi. We use phylogenetically informed Bayesian linear models to test whether the effect size is influenced by the phylogenetic distance between the plant species involved in each plant facilitative interaction. •Conspecific facilitative interactions are more strongly enhanced by mycorrhizal fungi than interactions between closely related species. In heterospecific interactions, the effect of the mycorrhizal symbiosis on plant facilitation increases with the phylogenetic distance between the nurse and facilitated plant species. •Our result showing that the effect of mycorrhizal symbiosis on the facilitation interactions between plants depends on their phylogenetic relatedness provides new mechanisms to understand how facilitation is assembling ecological communities. This article is protected by copyright. All rights reserved.
Senataxin homologue Sen1 is required for efficient termination of RNA polymerase III transcription

R‐loop disassembly by the human helicase Senataxin contributes to genome integrity and to proper transcription termination at a subset of RNA polymerase II genes. Whether Senataxin also contributes to transcription termination at other classes of genes has remained unclear. Here, we show that Sen1, one of two fission yeast homologues of Senataxin, promotes efficient termination of RNA polymerase III (RNAP3) transcription in vivo. In the absence of Sen1, RNAP3 accumulates downstream of RNAP3‐transcribed genes and produces long exosome‐sensitive 3′‐extended transcripts. Importantly, neither of these defects was affected by the removal of R‐loops. The finding that Sen1 acts as an ancillary factor for RNAP3 transcription termination in vivo challenges the pre‐existing view that RNAP3 terminates transcription autonomously. We propose that Sen1 is a cofactor for transcription termination that has been co‐opted by different RNA polymerases in the course of evolution.
Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial

Introduction Thiamine (vitamin B1) deficiency remains a concern in Cambodia where women with low thiamine intake produce thiamine-poor milk, putting their breastfed infants at risk of impaired cognitive development and potentially fatal infantile beriberi. Thiamine fortification of salt is a potentially low-cost, passive means of combating thiamine deficiency; however, both the dose of thiamine required to optimise milk thiamine concentrations as well as usual salt intake of lactating women are unknown. Methods and analysis In this community-based randomised controlled trial, 320 lactating women from Kampong Thom, Cambodia will be randomised to one of four groups to consume one capsule daily containing 0, 1.2, 2.4 or 10 mg thiamine as thiamine hydrochloride, between 2 and 24 weeks postnatal. The primary objective is to estimate the dose where additional maternal intake of thiamine no longer meaningfully increases infant thiamine diphosphate concentrations 24 weeks postnatally. At 2, 12 and 24 weeks, we will collect sociodemographic, nutrition and health information, a battery of cognitive assessments, maternal (2 and 24 weeks) and infant (24 weeks only) venous blood samples (biomarkers: ThDP and transketolase activity) and human milk samples (also at 4 weeks; biomarker: milk thiamine concentrations). All participants and their families will consume study-provided salt ad libitum throughout the trial, and we will measure salt disappearance each fortnight. Repeat weighed salt intakes and urinary sodium concentrations will be measured among a subset of 100 participants. Parameters of Emax dose–response curves will be estimated using non-linear least squares models with both ‘intention to treat’ and a secondary ‘per-protocol’ (capsule compliance ≥80%) analyses. Ethics and dissemination Ethical approval was obtained in Cambodia (National Ethics Committee for Health Research 112/250NECHR), Canada (Mount Saint Vincent University Research Ethics Board 2017–141) and the USA (University of Oregon Institutional Review Board 07052018.008). Results will be shared with participants’ communities, as well as relevant government and scientific stakeholders via presentations, academic manuscripts and consultations. Trial registration number NCT03616288.
Load Balancing Techniques for Efficient Traffic Management in Cloud Environment

Cloud computing is an internet based computing. This computing paradigm has enhanced the use of network where the capability of one node can be utilized by other node. Cloud service provides access on demand to distributive resources such as database, servers, software, infrastructure etc. in pay as you go basis. Load balancing is one of the vexing issues in distributed environment. Resources of service provider need to balance the load of client request. Load balancing is adapted in order to increase the resource consumption in Data centers that leads to enhance the overall performance of system achieving client satisfaction.
Role of Big Data in Cardiovascular Research

B ig Data resemble people: interrogate them just so, and they will tell you whatever you want to hear. Perhaps you, gentle reader, have noticed that there seems to be an awful lot more data in recent years, but perhaps not a lot more knowledge. Welcome to the world of Big Data. Just what is Big Data, and how is it changing the world of cardiovascular medicine? Big Data may be defined as large sets of data that are given to analytic approaches that may reveal underlying patterns, associations, or trends. Big Data has also been characterized by the 4 Vs of volume (a lot of data), variety (data from different sources and in different forms), velocity (data are accumulated rapidly), and veracity (uncertainty as to whether the data are correct). However, these characteristics do not adequately define Big Data; one might say that if you have seen one set of Big Data you have seen one set of Big Data. It is perhaps more useful to think about Big Data as it relates to sources, repositories, and use (Figure 1, Table). Where do such data come from? How are they stored? How can they be analyzed and visualized? What can we learn from Big Data?
Fatiguing stimulation increases curvature of the force–velocity relationship in isolated fast-twitch and slow-twitch rat muscles

ABSTRACT In skeletal muscles, the ability to generate power is reduced during fatigue. In isolated muscles, maximal power can be calculated from the force–velocity relationship. This relationship is well described by the Hill equation, which contains three parameters: (1) maximal isometric force, (2) maximum contraction velocity and (3) curvature. Here, we investigated the hypothesis that a fatigue-induced loss of power is associated with changes in curvature of the force–velocity curve in slow-twitch muscles but not in fast-twitch muscles during the development of fatigue. Isolated rat soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles were incubated in Krebs–Ringer solution at 30°C and stimulated electrically at 60 Hz (soleus) and 150 Hz (EDL) to perform a series of concentric contractions to fatigue. Force–velocity data were fitted to the Hill equation, and curvature was determined as the ratio of the curve parameters a/F0 (inversely related to curvature). At the end of the fatiguing protocol, maximal power decreased by 58±5% in the soleus and 69±4% in the EDL compared with initial values in non-fatigued muscles. At the end of the fatiguing sequence, curvature increased as judged from the decrease in a/F0 by 81±20% in the soleus and by 31±12% in the EDL. However, during the initial phases of fatiguing stimulation, we observed a small decrease in curvature in the EDL, but not in the soleus, which may be a result of post-activation potentiation. In conclusion, fatigue-induced loss of power is strongly associated with an increased curvature of the force–velocity relationship, particularly in slow-twitch muscles. Summary: In rat fast-twitch and slow-twitch skeletal muscles, fatigue-induced loss of maximal power is associated with an increase in the curvature of the force–velocity relationship.
Factors related to privacy of Somali refugees in health care

Background: Privacy is one of the key principles in health care and requires understanding of the cultural aspects of patients’ privacy. In Western cultures privacy is focused on the individual, however, in some non-Western cultures, privacy is linked to the collectivism of the community or religion. Objectives: The objective of this study is to describe the factors related to the realisation of privacy of Somali refugees in health care by describing the factors related to the patient, healthcare professional and interpreter. Research design: The data were collected from Somali refugees (N = 29) using a qualitative questionnaire and were analysed by deductive content analysis based on factors related to the patient, healthcare professional and interpreter. Ethical consideration: Ethical approval was obtained from the University of Turku, and research permissions were obtained from all participating institutions. Findings: Factors related to the patient were as follows: privacy was realised when the patient had self-determination; was able to act according to Somali culture; had knowledge and understanding of treatment; and trusted the healthcare professional. Factors related to the healthcare professional were as follows: the healthcare professional was expected to be of the same gender as the patient, act professionally, focus on the health issues, and to have knowledge and understanding of the Somali culture. Factors related to the interpreter were as follows: the presence and Somali background of the interpreter decreased privacy; the interpreter was expected to be of the same gender as the patient; to have competence and to behave professionally. Discussion: Gender congruence, professionalism and caring attitude and common understanding between the Somali patient and Finnish provider increase the privacy of Somali patients. Conclusion: Somali patients’ privacy can be improved by increasing healthcare professionals’ understanding of Somali culture, acknowledging the importance of gender concordance in relation to healthcare professionals and interpreters, and the effect of the presence of the interpreter on patients’ privacy.
Assessing the Energy Consumption of 5G Wireless Edge Caching

Multi-access edge computing and caching (MEC) is regarded as one of the key technologies in fifth generation (5G) radio access networks to reduce network congestion and to improve user experience by bringing computing and storage resources closer to the end-users. However, deploying a large number of distributed MEC servers will consume a significant amount of network energy. Therefore, here we focus on the energy consumption of edge caching in 5G. We first introduce our proposed proactive caching (PC) algorithm for edge caching with Zipf request pattern, which could potentially improve the hit rate of user requests under the common deployment architectures of the edge caching in 5G. We then assess the energy consumption of the PC algorithm under different key factors and compare the energy consumption of the PC algorithm with that of traditional algorithms. The simulation results show that the trade-off of improving the hit rates using PC comes at the expense of additional energy consumption for network transmission.
Energy Aware Dynamic Workflow Application Partitioning and Task Scheduling in Heterogeneous Mobile Cloud Network

Mobile Edge Cloud Computing Architecture (MEC-CA) presents key opportunities in performance improvement and energy saving for resource constrained mobile device. The mobile applications such as healthcare application, Augmented Reality can be modeled by task graphs. This work investigates the problem of dynamic application and scheduling tasks (which belong to the same or possibly different applications) in the MCCA environment. Nevertheless, the existing offloading system algorithms did not consider network failure and cloud resource in their MCCA paradigm. More specilically, we suggest the dynamic application partitioning and task scheduling (DAPTS) algorithm such that the application completion time constraint are satisfied while the total energy dissipation of the mobile device and cloud resources is minimized. Performance evaluations result demonstrates that proposed DAPTS outperform minimize the objective function in context of completion time and energy use as compared to the baseline approaches.