Miracle-dz/UniFAR-FTUs huggingface dataset:
RecQ helicases in the malaria parasite Plasmodium falciparum affect genome stability, gene expression patterns and DNA replication dynamics

The malaria parasite Plasmodium falciparum has evolved an unusual genome structure. The majority of the genome is relatively stable, with mutation rates similar to most eukaryotic species. However, some regions are very unstable with high recombination rates, driving the generation of new immune evasion-associated var genes. The molecular factors controlling the inconsistent stability of this genome are not known. Here we studied the roles of the two putative RecQ helicases in P. falciparum, PfBLM and PfWRN. When PfWRN was knocked down, recombination rates increased four-fold, generating chromosomal abnormalities, a high rate of chimeric var genes and many microindels, particularly in known ‘fragile sites’. This is the first identification of a gene involved in suppressing recombination and maintaining genome stability in Plasmodium. By contrast, no change in mutation rate appeared when the second RecQ helicase, PfBLM, was mutated. At the transcriptional level, however, both helicases evidently modulate the transcription of large cohorts of genes, with several hundred genes—including a large proportion of vars—showing deregulated expression in each RecQ mutant. Aberrant processing of stalled replication forks is a possible mechanism underlying elevated mutation rates and this was assessed by measuring DNA replication dynamics in the RecQ mutant lines. Replication forks moved slowly and stalled at elevated rates in both mutants, confirming that RecQ helicases are required for efficient DNA replication. Overall, this work identifies the Plasmodium RecQ helicases as major players in DNA replication, antigenic diversification and genome stability in the most lethal human malaria parasite, with important implications for genome evolution in this pathogen.
Evaluation of a commercial enzyme-linked immunosorbent assay (ELISA) for detecting antibodies against Toxoplasma gondii from naturally and experimentally infected pigs

Abstract Background: Toxoplasmosis is one of the most frequent parasitic infections in animals causing reproductive disorders and thus notable economic losses in productivity. Among food animals, pigs along with sheep and goats possess the highest incidence of Toxoplasma gondii cysts in meat, and play a role as a source of human infection. Methods: The commercial ELISA kit (PrioCHECK® Toxoplasma Ab SR, Prionics Schlieren-Zurich, Switzerland) for the detection of specific antibodies against T. gondii in swine serum was compared with a commercial IFAT (indirect fluorescent antibody test) (Toxo-Spot IF, bioMérieux, France), used as the reference test. Results: The kappa value obtained comparing the results performed on sera by ELISA with the by IFAT was 1. By a receiver operating characteristics curve analysis, the commercial ELISA had a relative sensitivity of 100%, and a relative specificity of 100% respect to IFAT. Conclusions: The commercial ELISA showed a very good agreement with the commercial IFAT in the detection of serum antibodies to Toxoplasma in pigs. Our study confirmed the usefulness of the commercial ELISA kit for the detection of antibodies against T. gondii in pigs, representing a valuable tool to improve the diagnostic activity for T. gondii in swine populations at the farm level or at the slaughterhouse, contributing to the control of this widespread infection.
The Availability of Quantitative Assessment of Pain Perception in Patients With Diabetic Polyneuropathy

Objective To evaluate the usefulness of the quantitative assessment of pain perception (QAPP) in diabetic polyneuropathy (DPN) patients. Methods Thirty-two subjects with DPN were enrolled in this study. The subjects’ pain perception was assessed quantitatively. Current perception threshold (CPT) and pain equivalent current (PEC) were recorded. All patients were tested with a nerve conduction study (NCS) for evaluation of DPN and pain-related evoked potential (PREP) for evaluation of small fiber neuropathy (SFN) on bilateral upper and lower limbs. All patients were asked to participate in tests such as visual analogue scale (VAS) and SF-36 Health Survey Version 2 to evaluate their subjective pain and quality of life, respectively. Results The PEC of QAPP showed significant correlations with VAS (p=0.002) and physical function surveyed with SF-36 Health Survey Version 2 (p=0.035). The results of QAPP had no correlation with NCS, but there was a significant relationship between the CPT of QAPP and PREP (p=0.003). Conclusion The QAPP may be useful not only in providing objective evaluations of subjective pain in patients with DPN but also in the assessment of diabetic SFN.
Concurrent renal dysfunction with ischemic heart disease is an important determinant for cardiac and cerebrovascular mortality in patients on chronic digoxin therapy for atrial fibrillation

Background Major adverse cardiac and cerebrovascular events (MACCEs) are main concerns in patients with atrial fibrillation (AF); however, factors affecting MACCEs remain inconclusive in AF patients chronically treated with digoxin. We investigated the major clinical determinants for fatal MACCEs in AF patients treated with digoxin over a 10-year follow-up period. Methods We analyzed a retrospective cohort of 1,480 AF patients at Eulji University Hospital, Daejeon, South Korea from March 2004 to August 2015. Among this population, 402 consecutive patients receiving chronic digoxin therapy were selected for the study. Data for electrocardiography, medication history, laboratory values including the serum digoxin concentration (SDC) and fatal MACCEs were collected. All data were divided and compared between groups based on the occurrence of MACCEs. Results The overall incidence of fatal MACCEs among the 402 digoxin-treated AF patients (age, 68 ± 11 years; male, 40.3%) was 12.1%. These fatalities resulted from heart failure (46.1%), fatal stroke (26.9%), fatal myocardial infarction (15.3%) and sudden cardiac death (5.7%). A higher prevalence of diabetes, pre-existing ischemic heart disease (IHD), lower estimated glomerular filtration rate (eGFR), higher SDC, and junctional bradycardia were more frequently observed in patients with MACCEs compared to those without MACCEs. Multivariable analysis showed that an eGFR of ≤ 60 mL/min/1.73 m2 and pre-existing IHD had a hazard ratio of 3.35 and a confidence interval of 1.64–6.87 (P < 0.001) for fatal MACCEs. Conclusion Chronic kidney disease stage III–V with pre-existing IHD is significantly associated with increased cardiac and cerebrovascular mortality in AF patients with chronic digoxin use.
When Control Exacerbates Distress: A Qualitative Study Exploring the Experiences of Hong Kong Chinese Parents in Caring for a Child with Asthma

Background: Many parents have difficulty managing childhood asthma. In Hong Kong (HK), while medication is the primary form of treatment, traditional Chinese medicine is another favored option. In addition, HK follows a dual-track healthcare system, which may pose unique experiences for Chinese parents in managing childhood asthma. This qualitative descriptive study aimed to explore the experiences of HK Chinese parents in caring for their children with asthma. Methods: Fourteen HK Chinese mothers of children (aged 3–10) suffering from asthma were purposively sampled to participate in individual, semi-structured interviews. A realist approach following conventional content analysis was used to interpret the interviews. Results: The mothers expressed feelings of uncertainty, fear of asthma crises, and searched for ways to cope. As long as their child’s asthma symptoms recurred, the mothers’ distress continued. Their distress was sometimes exacerbated by self-doubt and worries over whether they would receive adequate support from their family and healthcare professionals. Conclusions: Helping parents to understand their limits may help them be more open to varied aspects of their caregiving experiences, and thus to cope better. Psychological interventions together with traditional educational training may help to alleviate the psychological difficulties of parents.
BK channel inhibition by strong extracellular acidification

BK-type voltage- and Ca2+-dependent K+ channels are found in a wide range of cells and intracellular organelles. Among different loci, the composition of the extracellular microenvironment, including pH, may differ substantially. For example, it has been reported that BK channels are expressed in lysosomes with their extracellular side facing the strongly acidified lysosomal lumen (pH ~ 4.5). Here we show that BK activation is strongly and reversibly inhibited by extracellular H+, with its conductance-voltage relationship shifted by more than +100 mV at pHO 4. Our results reveal that this inhibition is mainly caused by H+ inhibition of BK voltage-sensor (VSD) activation through three acidic residues on the extracellular side of BK VSD. Given that these key residues (D133, D147, D153) are highly conserved among members in the voltage-dependent cation channel superfamily, the mechanism underlying BK inhibition by extracellular acidification might also be applicable to other members in the family.
The Role of Norepinephrine and &agr;-Adrenergic Receptors in Acute Stress-Induced Changes in Granulocytes and Monocytes

Objective Acute stress induces redistribution of circulating leucocytes in humans. Although effects on lymphocytes as adaptive immune cells are well understood, the mechanisms underlying stress effects on granulocytes and monocytes as innate immune blood cells are still elusive. We investigated whether the stress hormone norepinephrine (NE) and &agr;-adrenergic receptors (&agr;-ADRs) may play a mediating role. Methods In a stress study, we cross-sectionally tested 44 healthy men for associations between stress-induced NE increases and simultaneous granulocyte and monocyte cell count increases, as measured immediately before and several times after the Trier Social Stress Test. In a subsequent infusion study, 21 healthy men participated in three different experimental trials with sequential infusions of 1- and 15-minute duration with varying substances (saline as placebo, the nonspecific &agr;-ADR blocker phentolamine [2.5 mg/min], and NE [5 &mgr;g/min]): trial 1 = saline+saline, trial 2 = saline+NE, trial 3 = phentolamine+NE. Granulocyte and monocyte cell numbers were assessed before, immediately after, 10 minutes, and 30 minutes after infusion procedures. Results In the stress study, higher NE related to higher neutrophil stress changes (&bgr; = .31, p = .045, R2 change = .09), but not epinephrine stress changes. In the infusion study, saline+NE induced significant increases in neutrophil (F(3/60) = 43.50, p < . 001, &eegr;2 = . 69) and monocyte (F(3/60) = 18.56, p < . 001, &eegr;2 = . 48) numbers compared with saline+saline. With phentolamine+NE, neutrophil (F(3/60) = 14.41, p < . 001, &eegr;2 = . 42) and monocyte counts (F(2.23/44.6) = 4.32, p = . 016, &eegr;2 = . 18) remained increased compared with saline+saline but were lower compared with saline+NE (neutrophils: F(3/60) = 19.55, p < . 001, &eegr;2 = . 494, monocytes: F(3/60) = 2.54, p = . 065, &eegr;2 = . 11) indicating partial mediation by &agr;-ADRs. Trials did not differ in eosinophil and basophil count reactivity. Conclusions Our findings suggest that NE-induced immediate increases in neutrophil and monocyte numbers resemble psychosocial stress effects and can be reduced by blockade of &agr;-ADRs.
A proposal for innovation in the teaching of analysis and modeling of business process: Case UCM

The reaccreditation of the career informatic engineering of the Universidad Católica del Maule left several lessons learned and challenges to improve the strategies and learning outcomes of the students, among them is the innovation in the methodologies teaching and the elaboration of resource, both employees to improve student learning outcomes. In particular, the paper presents a methodology of business process modeling that has been developed and updated, from the year 2015 through different uses. The methodology emphasizes the analysis of information, instead of focusing on the BPMN notation. The article presents a process that guides the application of the methodology and shows a case study.
Micro-Blog Friend-Recommendation Based on Topic Analysis and Circle Found

Because of the increasing popularity of Sina micro-blog, its data volume gets larger and larger. Friend recommendation gets harder. Users' behavior on Sina micro-blog reflects their value and interests. People who have similar interests are more likely to become friends. In view of the above-mentioned facts, we build micro-blog topic model based on users' operations and the concept of time slices. Then calculate the user similarity based on topic probability distribution that we get through the topic model. After that, clustering the users and getting social circles. Recalculating the user similarity based on circle structure and calculates user's trust degree of other users. In the end we can finish the friend recommendation based on user similarity and trust degree. Experimental results show this algorithm is better than traditional methods.
Learning models for visual 3D localization with implicit mapping

We propose a formulation of visual localization that does not require construction of explicit maps in the form of point clouds or voxels. The goal is to learn an implicit representation of the environment at a higher, more abstract level, for instance that of objects. To study this approach we consider procedurally generated Minecraft worlds, for which we can generate visually rich images along with camera pose coordinates. We first show that Generative Query Networks (GQNs) enhanced with a novel attention mechanism can capture the visual structure of 3D scenes in Minecraft, as evidenced by their samples. We then apply the models to the localization problem, investigating both generative and discriminative approaches, and compare the different ways in which they each capture task uncertainty. Our results show that models with implicit mapping are able to capture the underlying 3D structure of visually complex scenes, and use this to accurately localize new observations, paving the way towards future applications in sequential localization. Supplementary video available at this https URL
Dynamic future knowledge maximum transmission unit (DFK-MTU) for optic wireless networks

Optic Wireless Networks (OWN) is the emerging field of interest because of its monumental bandwidth, energy efficiency, inherent security, low capital, and operating expenditure. Nevertheless, the OWN field is still in infancy and it is confronted with many challenges. Existing Medium Access Control (MAC) protocols do not take into consideration the physical properties of the OWN, hence they are deemed not suitable for OWN. The current Visible Light Communication (VLC) allows data transmission in contention and non-contention modes. The non-contention mode performs better in terms of packet loss and channel utilization. However, several issues such as Maximum Transmission Unit (MTU), and beacon duration need to be resolved in order to exploit potential benefits of non-contention mode. MTU size affects the performance of the network significantly. In this study, we present the Dynamic Future Knowledge Maximum Transmission Unit (DFK-MTU) algorithm for OWN. The proposed algorithm dynamically estimates the MTU size depending on the current content of the polling table and assigns each requesting node transmission slot by considering the requesting transmission size and the current MTU. Numerical results from our study show that the DFK-MTU enhances system utilization, and fairness.
okuhashi score and other prognostic factors in 260 patients with urgery for vertebral metastases

Background: Metastatic disease of the spine is an increasingly common public health problem. Surgery should be an integral component of the overall cancer treatment plan and, importantly, must neither delay not jeopardize any of the other components. The prognosis governs the choice of the surgical strategy. Tokuhashi et al. developed a prognostic score in 1990, then revised it in 2000 and 2005. Here, our objective was to evaluate the performance of the Tokuhashi score in a cohort of 260 patients and to look for other variables that might improve preoperative outcome prediction. Material and method: We retrospectively established a single-centre cohort of 260 patients who underwent spinal metastasis surgery between 1998 and 2008. For each patient, the following data were collected prospectively: socio-demographic features, history of the malignancy, variables needed to determine the Tokuhashi score, and treatments used. SAS 9.0 software was chosen for the statistical analysis. Variables were described as mean ± SD, overall survival was estimated using the Kaplan–Meier method, and survivals in subgroups were compared by the log-rank test. To assess agreement between survival predicted by the Tokuhashi score and observed survival, we computed Cohen’s kappa and interpreted the results according to Landis and Koch. Results: There were 143 females and 117 males with a mean age of 59 years and overall median survival of 10 months. Median observed survivals in the three Tokuhashi score categories (< 6, 6–12, and > 12 months predicted survival) were 5, 10, and 36 months, respectively. These survival times differed significantly (P < 0.0001). Cohen’s kappa indicated moderate agreement between predicted and observed survivals. Other factors associated with significant survival differences were time from cancer diagnosis to metastasis diagnosis (synchronous, < 2 years, 2–5 years, or > 5 years; P < 0.0001) and age (< 70 years or ≥ 70 years, P = 0.0053). Conclusion: Our cohort study supports the validity and reproducibility of the Tokuhashi score. Our finding that shorter time to metastasis diagnosis and age ≥ 70 years were also significantly associated with survival in our population invites further efforts to improve and update the Tokuhashi score. Level of evidence: IV, retrospective study. © 2015 Elsevier Masson SAS. All rights reserved.
Clone-and-Own software product derivation based on developer preferences and cost estimation

Clone-and-own is a common reuse practice that is widely adopted for evolving a family of software systems. However, this practice loses its effectiveness if not supported with valuable indicators that guide the derivation of new products. In this paper, we propose an approach to support the derivation of new product variants based on clone-and-own, by providing the possible scenarios in terms of operations to perform to accomplish the derivation. We generate a constraints system prior to a product derivation, to facilitate the software engineer selection of the suitable scenario and operations based on his preferences. In addition, we propose a cost estimation for each operation and respectively for each scenario, thus, a software engineer can rely on it as an additional parameter to achieve the derivation. The proposed scenarios and cost estimation are based on indicators retrieved after an automated identification of the mappings between the features implemented by the family of software products and the assets in which they are implemented. We preliminarily validate our approach on a case study where results show that the provided support can considerably reduce the amount of time and efforts that can be required to achieve a product derivation.
Fault estimation for time varying delay nonlinear systems with actuator fault and external disturbance

Aiming at a class of time varying delay nonlinear systems subjected to actuator fault, sensor fault and external disturbance, an improved unknown input observer is proposed. Concretely, first of all, an argument system is constructed and a descriptor system is designed. Then, a simultaneous state and fault estimation technique is developed. Furthermore, the stability of the error dynamitic system is proved. For the feasibility of the observer, the H-infinite performance is taken into consideration. Finally, the effectiveness of the proposed method is verified by the two-stage chemical reactor example.
Reducing variance in MCTS using bootstrap method

Monte Carlo Tree Search (MCTS) is a heuristic search algorithm for some kinds of decision processes, it has many important applications to computer game domain. The most important thing in theory for MCTS is to reduce vari­ance of the estimate values of the tree nodes under the limited search scope due to the constraints of computing resource and time consumption. The original MCTS algorithm uses a random policy which usually does not converge. Some optimizations, like the UCT and the RAVE, can reduce variances partly through the use of episode information. In this paper, we introduce a new algorithm, which could produce low-variance estimate of node values via a statistical method called bootstrap. Experimental results show that the new algorithm significantly improves the theoretical performance of MCTS.
MACHINE LEARNING FOR RELIABLE MMWAVE SYSTEMS: BLOCKAGE PREDICTION AND PROACTIVE HANDOFF

The sensitivity of millimeter wave (mmWave) signals to blockages is a fundamental challenge for mobile mmWave communication systems. The sudden blockage of the line-of-sight (LOS) link between the base station and the mobile user normally leads to disconnecting the communication session, which highly impacts the system reliability. Further, reconnecting the user to another LOS base station incurs high beam training overhead and critical latency problem. In this paper, we leverage machine learning tools and propose a novel solution for these reliability and latency challenges in mmWave MIMO systems. In the developed solution, the base stations learn how to predict that a certain link will experience blockage in the next few time frames using their observations of adopted beamforming vectors. This allows the serving base station to proactively hand-over the user to another base station with highly probable LOS link. Simulation results show that the developed deep learning based strategy successfully predicts blockage/hand-off in close to 95% of the times. This reduces the probability of communication session disconnection, which ensures high reliability and low latency in mobile mmWave systems.
Potential Applications of Nanotechnology in Urological Cancer

Nowadays, the potential scope of nanotechnology in uro-oncology (cancers of the prostate, bladder, and kidney) is broad, ranging from drug delivery, prevention, and diagnosis to treatment. Novel drug delivery methods using magnetic nanoparticles, gold nanoparticles, and polymeric nanoparticles have been investigated in prostate cancer. Additionally, renal cancer treatment may be profoundly influenced by applications of nanotechnology principles. Various nanoparticle-based strategies for kidney cancer therapy have been proposed. Partly due to the dilution of drug concentrations by urine production, causing inadequate drug delivery to tumor cells in the treatment of bladder cancer, various multifunctional bladder-targeted nanoparticles have been developed to enhance therapeutic efficiency. In each of these cancer research fields, nanotechnology has shown several advantages over widely used traditional methods. Different types of nanoparticles improve the solubility of poorly soluble drugs, and multifunctional nanoparticles have good specificity toward prostate, renal, and bladder cancer. Moreover, nanotechnology can also combine with other novel technologies to further enhance effectivity. As our understanding of nanotechnologies grows, additional opportunities to improve the diagnosis and treatment of urological cancer are excepted to arise. In this review, we focus on nanotechnologies with potential applications in urological cancer therapy and highlight clinical areas that would benefit from nanoparticle therapy.