Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating candidate agents of selective pressure for cystic fibrosis

Cystic fibrosis is the most common lethal single-gene mutation in people of European descent, with a carrier frequency upwards of 2%. Based upon molecular research, resistances in the heterozygote to cholera and typhoid fever have been proposed to explain the persistence of the mutation. Using a population genetic model parameterized with historical demographic and epidemiological data, we show that neither cholera nor typhoid fever provided enough historical selective pressure to produce the modern incidence of cystic fibrosis. However, we demonstrate that the European tuberculosis pandemic beginning in the seventeenth century would have provided sufficient historical, geographically appropriate selective pressure under conservative assumptions. Tuberculosis has been underappreciated as a possible selective agent in producing cystic fibrosis but has clinical, molecular and now historical, geographical and epidemiological support. Implications for the future trajectory of cystic fibrosis are discussed. Our result supports the importance of novel investigations into the role of arylsulphatase B deficiency in cystic fibrosis and tuberculosis.
Cerebellar Motor Learning: When Is Cortical Plasticity Not Enough?

Classical Marr-Albus theories of cerebellar learning employ only cortical sites of plasticity. However, tests of these theories using adaptive calibration of the vestibulo–ocular reflex (VOR) have indicated plasticity in both cerebellar cortex and the brainstem. To resolve this long-standing conflict, we attempted to identify the computational role of the brainstem site, by using an adaptive filter version of the cerebellar microcircuit to model VOR calibration for changes in the oculomotor plant. With only cortical plasticity, introducing a realistic delay in the retinal-slip error signal of 100 ms prevented learning at frequencies higher than 2.5 Hz, although the VOR itself is accurate up to at least 25 Hz. However, the introduction of an additional brainstem site of plasticity, driven by the correlation between cerebellar and vestibular inputs, overcame the 2.5 Hz limitation and allowed learning of accurate high-frequency gains. This “cortex-first” learning mechanism is consistent with a wide variety of evidence concerning the role of the flocculus in VOR calibration, and complements rather than replaces the previously proposed “brainstem-first” mechanism that operates when ocular tracking mechanisms are effective. These results (i) describe a process whereby information originally learnt in one area of the brain (cerebellar cortex) can be transferred and expressed in another (brainstem), and (ii) indicate for the first time why a brainstem site of plasticity is actually required by Marr-Albus type models when high-frequency gains must be learned in the presence of error delay.
Eﬄux in the Oral Metagenome: The Discovery of a Novel Tetracycline and Tigecycline ABC Transporter

Antibiotic resistance in human bacterial pathogens and commensals is threatening our ability to treat infections and conduct common medical procedures. As novel antibiotics are discovered and marketed it is important that we understand how resistance to them may arise and know what environments may act as reservoirs for such resistance genes. In this study a tetracycline and tigecycline resistant clone was identified by screening a human saliva metagenomic library in Escherichia coli EPI300 on agar containing 5 μg/ml tetracycline. Sequencing of the DNA insert present within the tetracycline resistant clone revealed it to contain a 7,765 bp fragment harboring novel ABC half transporter genes, tetAB(60). Mutagenesis studies performed on these genes confirmed that they were responsible for the tetracycline and tigecycline resistance phenotypes. Growth studies performed using E. coli EPI300 clones that harbored either the wild type, the mutated, or none of these genes indicated that there was a fitness cost associated with presence of these genes, with the isolate harboring both genes exhibiting a significantly slower growth than control strains. Given the emergence of E. coli strains that are sensitive only to tigecycline and doxycycline it is concerning that such a resistance mechanism has been identified in the human oral cavity.
Epicardial Colour-Doppler Scanning of Coronary Artery Stenoses and Graft Anastomoses

Objective : Epicardial ultrasound scanning was applied during coronary surgery to assess coronary artery stenoses and quality of distal graft anastomoses, with special emphasis to the left anterior descending artery (LAD). Design : Twenty-three patients with coronary artery disease (M:F 19:4, mean age 65.0 - 9.5 years) had coronary artery bypass grafting (CABG) on cardiopulmonary bypass. Intraoperative scanning of coronary artery stenoses and graft anastomoses was performed with a new 10 MHz linear array Vingmed transducer connected to a GE Vingmed System FiVe echocardiography unit. Coronary stenoses detected by ultrasound were compared with preoperative angiograms. Intraoperatively, coronary graft flow was assessed with a Medi-Stim transit-time flowmeter. Results : Twenty LADs were investigated. In 17 LADs (85%) stenoses were clearly identified. In three LADs (15%) stenoses were not identified because LADs were deeply intramyocardial or the stenosis was very proximal. There was a significant correlation between LAD stenoses detected by ultrasound and angiogram ( R = 0.7; p < 0.01). Mean number of grafts was 3.8 - 0.9. Of 26 LAD anastomoses assessed, good images were obtained in 22 cases (84.4%); the mean LAD diameter measured 1 cm below the anastomosis was 1.6 - 0.2 mm. In two LADs images were rated fair and in two LADs images were poor because of intramyocardial LAD. No technical error of the anastomoses was detected. All grafts had good flows as ascertained by flow measurements. Conclusion : Epicardial ultrasound scanning with the new 10 MHz transducer allowed satisfactory imaging of coronary stenoses and graft anastomoses. Factors limiting the quality of imaging are proximal lesions, intramyocardial vessel, vessel tortuosity, and extensive calcifications. Epicardial ultrasound scanning with updated technology should become a further advancement to graft assessment during off-pump coronary surgery.
Freeman–Sheldon Syndrome: First Molecularly Confirmed Case from Sub-Saharan Africa

We report a case of a male baby who has characteristic signs of Freeman–Sheldon syndrome, a rare but recognizable, severe autosomal dominant form of distal arthrogryposis. Diagnosis was based on the distinctive clinical characteristics of the syndrome and confirmed by genetic analysis that showed a de novo missense mutation c.2015G>A (p.Arg672His) of the MYH3 gene. We highlight the different features present in our patient and describe the etiology of the Freeman–Sheldon phenotype and how its clinical complications can be dealt with. To the best of our knowledge, this is the first molecularly confirmed case of Freeman–Sheldon syndrome in sub-Saharan Africa.
Anger, Interpersonal Relationships, and Health-Related Quality of Life in Bullying Boys Who Are Treated With Outpatient Family Therapy: A Randomized, Prospective, Controlled Trial With 1 Year of Follow-up

Objective. Ten to 30% of students engage in bullying behavior. Bullies stand out on account of increased anger, poor interpersonal relationships, and poor quality of life. Our aim was to determine the effectiveness of outpatient family psychotherapy as a monotherapy for anger reduction and improvement of behavior and interpersonal relationships and of health-related quality of life in male youths with bullying behavior. Methods. Twenty-two boys with bullying behavior took part in a family therapy program for 6 months. The control group was also composed of 22 youths and took part in a placebo intervention program. Every 2 weeks, results were checked with the Adolescents Risky-Behavior Scale (ARBS), the State-Trait Anger Expression Inventory (STAXI), the Inventory of Interpersonal Problems (IIP-D), and the SF-36 Health Survey (SF-36). Follow-up testing took place 12 months after treatment. Results. In comparison with the control group (according to the intention-to-treat principle), bullying behavior was reduced (family therapy group: from n = 22 to n = 6; control group: from n = 22 to n = 20). Significant changes on all ARBS scales and on the STAXI scales State-Anger, Trait-Anger, Anger-Out, and Anger-Control were observed after 6 months. In the IIP-D, significant differences were found on the scales for overly autocratic, overly competitive, overly introverted, overly expressive, and exploitable/compliant. In the SF-36, significant differences were observed in general health perceptions, vitality, social functioning, role-emotional, and mental health. The reduction in expression of anger correlated with a reduction in several scales of the ARBS, IIP-D, and SF-36. Follow-up after 1 year showed relatively stable, lasting treatment effects. Conclusion. The results of this study show that outpatient family therapy seems to be an effective method of reducing anger and improving interpersonal relationships and health-related quality of life in male youths with bullying behavior.
Sampling from Discrete Distributions and Computing Frechet Distances

In the first part of this dissertation, we study the fundamental problem of sampling from a discrete probability distribution. Specifically, given non-negative numbers p1, . , pn the task is to draw i with probability proportional to pi. We extend the classic solution to this problem, Walker’s alias method, in various directions: 1. We improve upon its space requirements by presenting optimal succinct sampling data structures. 2. We present improved trade-offs between preprocessing and query time for sorted inputs, and generalize this from proportional sampling to sampling subsets. 3. For Bernoulli, geometric, and binomial random variates we present optimal sampling algorithms on a bounded precision machine. 4. As an application, we speed up sampling of internal diffusion limited aggregation. The second part of this dissertation belongs to the area of computational geometry and deals with algorithms for the Frechet distance, which is a popular measure of similarity of two curves and can be computed in quadratic time (ignoring logarithmic factors). We provide the first conditional lower bound for this problem: No polynomial factor improvement over the quadratic running time is possible unless the Strong Exponential Time Hypothesis fails. Our various extensions of this main result include conditional lower bounds under realistic input assumptions, which do not match the known algorithms. We close this gap by presenting an improved approximation algorithm for the Frechet distance.
Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer

ABSTRACT Objective: We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. Materials and Methods: Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2) and 40 healthy control group (Group 1) were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. Results: Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021). Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. Conclusions: Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.
Optimal placement and parameter settings of unified power flow controller device using a perturbed particle swarm optimization

This paper presents the application of a perturbed particle swarm optimization (PPSO) technique to find optimal location and parameter setting of unified power flow controller (UPFC) for enhancing power system security under single line contingencies. A contingency analysis is first outlined to identify the most severe line outage contingencies, considering lines overload and bus voltage limit violations as a performance index. Then, the proposed algorithm is applied to find out the optimal location and parameter setting of UPFC under the determined contingency scenario. Simulations are performed on IEEE 14 bus system. The results indicate that PPSO is a powerful optimization technique and enhance the convergence of the standard PSO. Installing UPFC in the optimal location determined by the proposed approach can significantly enhance the security of power system by eliminating or minimizing the number of overloaded lines and the bus voltage limit violations.
Laser Acupuncture Therapy in Patients with Treatment-Resistant Temporomandibular Disorders

Objective To investigate the clinical effects of laser acupuncture therapy for temporomandibular disorders (TMD) after ineffective previous treatments. Methods A retrospective observational study was conducted in 29 treatment-resistant TMD patients (25 women, 4 men; age range, 17–67 years). Subjects were treated 3 times per week for 4 weeks with the Handylaser Trion (GaAlAs laser diode, 810 nm, 150 mW, pulsed waves), which delivered 0.375 J of energy (5 s) to ST7, ST6, and LI4 and 3 J (40 s) to each Ashi point, 7.5–26.25 J/cm2 in total. The visual analog scale (VAS) and maximal mouth opening (MMO) were evaluated before and after treatment. Results VAS analysis showed that the patients were free of pain at rest (endpoint) after 5.90±6.08 sessions of laser acupuncture for acute TMD and after 16.21±17.98 sessions for chronic TMD. The VAS score on palpation of the temporomandibular joint reduced to 0.30±0.67 for patients with acute TMD (p = 0.005) and to 0.47±0.84 for those with chronic TMD (p<0.001). The MMO significantly increased in patients with acute TMD (7.80±5.43 mm, p = 0.008) and in patients with chronic TMD (15.58±7.87 mm, p<0.001). Conclusions Our study shows that laser acupuncture therapy improves the symptoms of treatment-resistant TMD. Further studies with a more appropriate design, involving long-term follow-up examinations in a larger patient sample, are needed to evaluate its efficacy.
The SDF-1α/CXCR4 Axis is Required for Proliferation and Maturation of Human Fetal Pancreatic Endocrine Progenitor Cells

The chemokine receptor CXCR4 and ligand SDF-1α are expressed in fetal and adult mouse islets. Neutralization of CXCR4 has previously been shown to diminish ductal cell proliferation and increase apoptosis in the IFNγ transgenic mouse model in which the adult mouse pancreas displays islet regeneration. Here, we demonstrate that CXCR4 and SDF-1α are expressed in the human fetal pancreas and that during early gestation, CXCR4 colocalizes with neurogenin 3 (ngn3), a key transcription factor for endocrine specification in the pancreas. Treatment of islet like clusters (ICCs) derived from human fetal pancreas with SDF-1α resulted in increased proliferation of epithelial cells in ICCs without a concomitant increase in total insulin expression. Exposure of ICCs in vitro to AMD3100, a pharmacological inhibitor of CXCR4, did not alter expression of endocrine hormones insulin and glucagon, or the pancreatic endocrine transcription factors PDX1, Nkx6.1, Ngn3 and PAX4. However, a strong inhibition of β cell genesis was observed when in vitro AMD3100 treatment of ICCs was followed by two weeks of in vivo treatment with AMD3100 after ICC transplantation into mice. Analysis of the grafts for human C-peptide found that inhibition of CXCR4 activity profoundly inhibits islet development. Subsequently, a model pancreatic epithelial cell system (CFPAC-1) was employed to study the signals that regulate proliferation and apoptosis by the SDF-1α/CXCR4 axis. From a selected panel of inhibitors tested, both the PI 3-kinase and MAPK pathways were identified as critical regulators of CFPAC-1 proliferation. SDF-1α stimulated Akt phosphorylation, but failed to increase phosphorylation of Erk above the high basal levels observed. Taken together, these results indicate that SDF-1α/CXCR4 axis plays a critical regulatory role in the genesis of human islets.
Monetary Policy Rules in the Open Economy: Effects on Welfare and Business Cycles

This Paper computes welfare maximizing Taylor-style interest rate rules, in a business cycle model of a small open economy. The model assumes staggered price setting and shocks to domestic productivity, to the world interest rate, to world inflation and to the uncovered interest rate parity condition. Optimized policy rules have a pronounced anti-inflation stance and entail significant nominal and real exchange rate volatility. The country responds to an increase in external volatility by holding more foreign assets. The policy rule affects the variance and the mean of consumption. The effect on the mean matters significantly for welfare.
The value of remotely sensed surface soil moisture for model calibration using SWAT

Remotely sensed (RS) data can add value to a hydrological model calibration. Among this, RS soil moisture (SM) data have mostly been assimilated into conceptual hydrological models using various transformed variable or indices. In this study, raw RS surface SM is used as a calibration variable in the Soil and Water Assessment Tool model. This means the SM values were not transformed into another variable (e.g., soil water index and root zone SM index). Using a nested catchment, calibration based only on RS SM and optimizing model parameters sensitive to SM using particle swarm optimization improved variations in streamflow predictions at some of the gauging stations compared to the uncalibrated model. This highlighted part of the catchments where the SM signal directly influenced the flow distribution. Additionally, highlighted high and low flow signals were mostly influenced. The seasonal breakdown indicates that the SM signal is more useful for calibrating in wetter seasons and in areas with higher variations in elevation. The results identified that calibration only on RS SM improved the general rainfall–runoff response simulation by introducing delays but cannot correct the overall routing effect. Furthermore, catchment characteristics (e.g., land use, elevation, soil types, and precipitation) regulating SM variation in different seasons highlighted by the model calibration are identified. This provides further opportunities to improve model parameterization.
Data Imputation Using Least Squares Support Vector Machines in Urban Arterial Streets

Some traffic data from loop detectors settled in urban arterial streets are incomplete. The importance of effectively imputing the missing values emerges. The letter introduces least squares support vector machines (LS-SVMs) to missing traffic flow prediction based on spatio-temporal analysis. It is the first time to apply the technique to missing data imputation. A baseline imputation technique, expectation maximization/data augmentation (EM/DA), is selected for comparison because of its proved effectiveness. Experimental results demonstrate that our method is more applicable and performs better at relatively high missing data rates. This reveals that it is a promising approach in the field.
Biomimetic Approach for Root Caries Prevention Using a Proanthocyanidin-Rich Agent

The aim of this study was to evaluate the effects of a proanthocyanidin-rich grape seed extract (GSE) on the in vitro demineralization of root dentine. Root fragments were obtained from sound human teeth. The fragments were randomly assigned to different treatments solutions: GSE, fluoride (F), GSE+F and distilled water (control). Samples were treated daily for 30 min and subjected to a pH cycling artificial caries protocol using demineralization cycles (2.2 mM CaCl2×H2O, 2.2 mM KH2PO4, 50 mM acetic acid, pH 4.3) for 6 h and remineralization cycles (20 mM HEPES, 2.25 mM CaCl2×H2O, 1.35 mM KH2PO4, 130 mM KCl, pH 7.0) for 17.5 h. Mineral loss (ΔZ) and lesion depth (LD) were determined after 18 days of treatment/pH cycling, by transverse microradiography. GSE was able to minimize ΔZ and LD compared with the control group (p < 0.0001). The GSE+F and F groups showed the lowest values of ΔZ and LD (p < 0.05), with no statistically significant differences between them (p = 0.554 and p = 0.726, respectively). A biomimetic approach to strengthen root dentine using GSE results in decreased rates of root demineralization and may be used in conjunction with F to prevent root caries.
LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation

Germinal centers (GCs) are microanatomical structures critical for the development of high-affinity Abs and B cell memory. They are organized into two zones, light and dark, with coordinated roles, controlled by local signaling. The innate lectin-like transcript 1 (LLT1) is known to be expressed on B cells, but its functional role in the GC reaction has not been explored. In this study, we report high expression of LLT1 on GC-associated B cells, early plasmablasts, and GC-derived lymphomas. LLT1 expression was readily induced via BCR, CD40, and CpG stimulation on B cells. Unexpectedly, we found high expression of the LLT1 ligand, CD161, on follicular dendritic cells. Triggering of LLT1 supported B cell activation, CD83 upregulation, and CXCR4 downregulation. Overall, these data suggest that LLT1–CD161 interactions play a novel and important role in B cell maturation within the GC in humans.
Minimizing Euclidian State Estimation Error for Linear Uncertain Dynamic Systems Based on Multisensor and Multi-Algorithm Fusion

In this paper, a multisensor linear dynamic system with model uncertainty and bounded noises is considered. Based on previously developed set-valued estimation methods in terms of convex optimization, we propose several efficient algorithms of centralized sensor fusion, distributed sensor fusion, and multi-algorithm fusion to minimize the Euclidian estimation error of the state vector. Obviously, an ellipsoid/box with a larger “size” cannot be in general guaranteed to contain another ellipsoid/box with a smaller “size” since centers and shapes of the two ellipsoids/boxes may be different from each other. This fact and the complementary advantages of multiple sensors and multiple algorithms motivate us to construct multiple estimation ellipsoids/boxes squashed along each entry of the state vector as much as possible respectively by using the technique of multiple differently weighted objectives. Then intersection fusion of these estimation ellipsoids/boxes yields a final Euclidian-error-minimized state estimate. Numerical examples show that the new method with multi-algorithm at both the sensors and the fusion center can significantly reduce the Euclidian estimation error of the state.