Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors.

PURPOSE Topotecan is a specific inhibitor of topoisomerase I. Recently bioavailability of an oral formulation of approximately 30% with limited variability was reported. We conducted a phase I and pharmacokinetic study of the oral formulation of topotecan to characterize the maximum-tolerated dose (MTD), toxicities, pharmacokinetics, and antitumor effects in patients with refractory malignancies. PATIENTS AND METHODS Patients were treated with oral topotecan given twice daily for 21 days, with cycles repeated every 28 days. In subsequent cohorts, the dose was escalated from 0.15 to 0.6 mg/m2 twice daily. Pharmacokinetics were performed on day 1 and 8 of the first course using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. RESULTS Thirty-one patients entered the study; one patient was not assessable for toxicity and response as therapy was prematurely interrupted on request of the patient who had not experienced toxicity. Thirty patients received a total of 59 courses. The dose-limiting toxicity (DLT) was reached at a dose of 0.6 mg/m2 twice daily and consisted of diarrhea, which started subacutely at a median onset on day 15 (range, 12 to 20) and resolved after a median of 8 days (range, 7 to 16). Other toxicities were mild, including leukocytopenia, thrombocytopenia, nausea, and vomiting. The MTD was 0.5 mg/m2 twice daily. No responses were observed. Pharmacokinetics showed a substantial variation of the area under the plasma concentration-time curve at time point "t" [AUC(t)] of topotecan and ring-opened product hydroxyacid. A significant correlation was observed between the percentage of decrease in WBC count versus the AUC(t) of topotecan (r = .75), which was modeled by a sigmoidal maximal effect concentration (Emax) function. CONCLUSION The DLT in this phase I study for chronic oral topotecan for 21 days was diarrhea. The recommended dose for phase II studies is 0.5 mg/m2 twice daily.
Improving Application Migration to Serverless Computing Platforms: Latency Mitigation with Keep-Alive Workloads

Serverless computing platforms provide Function(s)-as-a-Service (FaaS) to end users while promising reduced hosting costs, high availability, fault tolerance, and dynamic elasticity for hosting individual functions known as microservices. Serverless Computing environments abstract infrastructure management including creation of virtual machines (VMs), containers, and load balancing from users. To conserve cloud server capacity and energy, cloud providers allow serverless computing infrastructure to go COLD, deprovisioning hosting infrastructure when demand falls, freeing capacity to be harnessed by others. In this paper, we present on a case study migration of the Precipitation Runoff Modeling System (PRMS), a Java-based environmental modeling application to the AWS Lambda serverless platform. We investigate performance and cost implications of memory reservation size, and evaluate scaling performance for increasing concurrent workloads. We then investigate the use of Keep-Alive workloads to preserve serverless infrastructure to minimize cold starts and ensure fast performance after idle periods for up to 100 concurrent client requests. We show how Keep-Alive workloads can be generated using cloud-based scheduled event triggers, enabling minimization of costs, to provide VM-like performance for applications hosted on serverless platforms for a fraction of the cost.
Real-time functional near infrared spectroscopy based brain activation strength estimation

Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that recently has been used for brain imaging applications. To date, there is no standard method for analyzing fNIRS data, especially for real-time applications. In this work, a novel real-time fNIRS data analysis framework based on the general linear model (GLM) and the Kalman estimator was devised. A pilot study was conducted by applying the proposed framework to a set of data recorded in a finger tapping experiment. The results so obtained suggested that the method can effectively estimate the brain activity strength of the detected areas in real-time, thereby demonstrating its potential for real-time fNIRS-based brain imaging applications.
Conflicts and Convergence in the Southwestern–European Border: Spain, South-Spain and the Maghreb (1995–2010)

Purpose – The main aim of this chapter is to analyze Spanish internal and external territorial conflicts, mostly associated with the border effect between two continents with different economic and cultural systems. We assess the impact that the emergence of the new economy, represented by new technologies, R&D, privatizations, and foreign direct investment, has had in South-Spain, particularly in Andalusia, throughout the period 1995–2010. Special attention has been paid to the dynamics of convergence–divergence processes in terms of per capita income with respect to its neighboring different economic and cultural areas: Europe and the Maghreb. Methodology – For the aforementioned purposes, we suggest applying the game theory approach to solve domestic secessionist conflicts, and the method followed by Mankiw, Romer, and Weil (1992) to address economic conflicts by means of promoting convergence with Europe. We propose economic competition between cities as a way to deal with external territorial conflicts concerning neighboring countries. Findings – The main results obtained from econometric applications indicate that privatization processes, foreign direct investment, research and investment, and investment in new technologies allow for the real convergence of Spain and Southern Spain with European economies. Research limitations – This chapter does not address smaller conflicts. Social implications – Conflicts resolutions promote peace in both continental borders. Originality – This chapter analyzes the most relevant domestic and external Spanish conflicts. The most important domestic conflicts are the linguistic and cultural conflicts in bilingual regions. The major external Spanish conflicts analyzed herein are both territorial conflicts between Spain and Morocco and Muslim immigration.
A Discriminative Feature-Based Mean-shift Algorithm for Object Tracking

The mean-shift algorithm has been proved to be efficient for object tracking. Traditional mean-shift algorithm uses global color histogram features, regardless the features belong to the object or to the background, which will cause localization drift. In this paper, we propose a new algorithm which can overcome this disadvantage. Our hypothesis is that the features that best discriminate between object and background are also the best for tracking, and our tracking is based on these discriminative features. Features are chosen by separating the object from the background, using a voting strategy. Experimental results show that the proposed algorithm in this paper is more robust than the traditional mean-shift algorithm.
Induction of Vascular Endothelial Growth Factor Gene Expression by Interleukin-1 in Rat Aortic Smooth Muscle Cells (*)

Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1β (IL-1β), which is present in atherosclerotic lesions, induces VEGF gene expression in vascular smooth muscle cells, we performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1β increased VEGF mRNA levels in RASMC in a time- and dose-dependent manner. As little as 0.1 ng/ml IL-1β increased VEGF mRNA levels by 2-fold and 10 ng/ml IL-1β increased VEGF mRNA by 4-fold. We also measured the half-life of VEGF mRNA and performed nuclear run-on experiments before and after addition of IL-1β to see if IL-1β increased VEGF mRNA levels by stabilizing the mRNA or by increasing its rate of transcription. The normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1β, and IL-1β increased the rate of VEGF gene transcription by 2.1-fold. In immunoblot experiments with an antibody specific for VEGF, we found that IL-1β increased VEGF protein levels in RASMC by 3.3-fold. Together these data indicate that IL-1β induces VEGF gene expression in smooth muscle cells. This IL-1β-induced expression of VEGF may accelerate the progression of atherosclerotic lesions by promoting the development of new blood vessels.
Bioluminescent Imaging Demonstrates That Transplanted Human Embryonic Stem Cell‐Derived CD34+ Cells Preferentially Develop into Endothelial Cells

Human embryonic stem cells (hESCs) provide an important resource for novel regenerative medicine therapies and have been used to derive diverse cell populations, including hematopoietic and endothelial cells. However, it remains a challenge to achieve significant engraftment of hESC‐derived blood cells when transplanted into animal models. To better understand mechanisms that enhance or limit the in vivo developmental potential of hESC‐derived cells, we utilized hESCs that express firefly luciferase (luc) to allow noninvasive, real‐time bioluminescent imaging of hESC‐derived CD34+ cells transplanted into the liver of neonatal immunodeficient mice. Serial imaging demonstrated stable engraftment and expansion of the luc+ hESC‐derived cells in vivo over several months. While we found that these hESC‐derived CD34+ cells have bipotential ability to generate both hematopoietic and endothelial lineages in vitro, these studies demonstrate preferential differentiation into endothelial cells in vivo, with only low levels of hematopoietic cell engraftment. Therefore, these studies reveal key differences in the developmental potential of hESC‐derived cells using in vitro and in vivo analyses. Although transplanted hESC‐derived CD34+ cells are well‐suited for revascularization therapies, additional measures are needed to provide higher levels of long‐term hematopoietic engraftment. STEM CELLS 2009;27:2675–2685
Physiological types and histochemical profiles in motor units of the cat gastrocnemius

1. A variety of physiological properties of single motor units have been studied in the gastrocnemius muscle (primarily in the medial head) of pentobarbitone‐anaesthetized cats. Intracellular stimulation of individual motoneurones ensured functional isolation of the muscle units innervated by them.
Bone Health and Human Immunodeficiency Virus Infection

Low bone mineral density is common among persons with human immunodeficiency virus (HIV) infection, and studies reporting increased fracture rates in this patient population are emerging. The causes of low bone mineral density, osteoporosis, and fractures in persons with HIV are likely multifactorial, involving traditional risk factors, HIV infection, and exposure to antiretroviral treatment. Specific antiretrovirals such as tenofovir may cause a greater loss of bone mineral density compared with other agents and have recently been linked to an increased risk for fracture. As a result, recent treatment guidelines suggest that clinicians consider avoiding tenofovir as initial therapy in postmenopausal women. Evaluating bone mineral density and vitamin D status in persons with HIV may be important steps in identifying those requiring pharmacotherapy; however, the appropriate timing for bone mineral density and vitamin D screening is uncertain, as is the appropriate method of replacing vitamin D in HIV‐positive patients who are deficient. Further study is necessary to definitively determine the approach to evaluating bone health and managing low bone mineral density and vitamin D deficiency in patients with HIV infection.
Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation

abstract Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. However, the role of N-glycans in the conducting function of T-type channels remains elusive. In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states.
Fiscal policies in EMU countries: strategies and empirical evidence

Purpose The aim of the paper is to evaluate fiscal adjustments that have occurred in the Economic and Monetary Union (EMU) countries in the last 35 years, and their consequences on the economic growth process by using the mean group (MG) estimators. Design/methodology/approach Our emphasis is on the effects of different composition of fiscal stimuli and consolidations. We compare the effects on the economic growth rate of different compositions of major fiscal changes. We use a cyclically adjusted value of the fiscal variables to leave aside variations of the fiscal variables induced by business cycle fluctuations. Findings Our empirical research of the effects of large changes in fiscal policy, both in case of a fiscal consolidation and of fiscal stimulus in the 18 EMU countries from 1980 to 2015, shows that adjustments by cutting current expenditures, rather than by tax increases are more likely to boost economic growth. It also shows that cuts of investment expenditures may reduce GDP growth. During fiscal stimulus episodes, tax cuts and public investments are more likely to increase growth than current public expenditure. Originality/value This is the first study devoted to the EMU countries. It should be underlined that the results obtained as for EMU countries are not necessarily applicable to other countries, as the different government size as well as different market institutions may influence the results.
Inhibition of cathelicidin activity by bacterial exopolysaccharides

The interaction of bacterial exopolysaccharides, produced by opportunistic lung pathogens, with antimicrobial peptides of the innate primate immune system was investigated. The exopolysaccharides were produced by Pseudomonas aeruginosa, Inquilinus limosus and clinical isolates of the Burkholderia cepacia complex, bacteria that are all involved in lung infections of cystic fibrosis patients. The effects of the biological activities of three orthologous cathelicidins from Homo sapiens sapiens, Pongo pygmaeus (orangutan) and Presbitys obscurus (dusky leaf monkey) were examined. Inhibition of the antimicrobial activity of peptides was assessed using minimum inhibitory concentration assays on a reference Escherichia coli strain in the presence and absence of exopolysaccharides, whereas complex formation between peptides and exopolysaccharides was investigated by means of circular dichroism, fluorescence spectroscopy and atomic force microscopy. Biological assays revealed that the higher the negative charge of exopolysaccharides the stronger was their inhibiting effect. Spectroscopic studies indicated the formation of molecular complexes of varying stability between peptides and exopolysaccharides, explaining the inhibition. Atomic force microscopy provided a direct visualization of the molecular complexes. A model is proposed where peptides with an α‐helical conformation interact with exopolysaccharides through electrostatic and other non‐covalent interactions.
Determination of ReQuest™-Based Symptom Thresholds to Define Symptom Relief in GERD Clinical Studies

Background/Aims: The growing importance of symptom assessment is evident from the numerous clinical studies on gastroesophageal reflux disease (GERD) assessing treatment-induced symptom relief. However, to date, the a priori selection of criteria defining symptom relief has been arbitrary. The present study was designed to prospectively identify GERD symptom thresholds for the broad spectrum of GERD-related symptoms assessed by the validated reflux questionnaire (ReQuest™) and its subscales, ReQuest™-GI (gastrointestinal symptoms) and ReQuest™-WSO (general well-being, sleep disturbances, other complaints), in individuals without evidence of GERD. Methods: In this 4-day evaluation in Germany, 385 individuals without evidence of GERD were included. On the first day, participants completed the ReQuest™, the Gastrointestinal Symptom Rating Scale, and the Psychological General Well-Being scale. On the other days, participants filled in the ReQuest™ only. GERD symptom thresholds were calculated for ReQuest™ and its subscales, based on the respective 90th percentiles. Results: GERD symptom thresholds were 3.37 for ReQuest™, 0.95 for ReQuest™-GI, and 2.46 for ReQuest™-WSO. Conclusion: Even individuals without evidence of GERD may experience some mild symptoms that are commonly ascribed to GERD. GERD symptom thresholds derived in this study can be used to define the global symptom relief in patients with GERD.
Experimental validation of a simple multiphysics model for drum roller driven by induction motor

This paper presents an efficient multiphysics analysis (electromechanics coupled with thermal) of a drum roller that is driven by a 3-phase induction motor. The drum roller performance at variable load can be accurately predicted using a simple non-linear equivalent electric circuit coupled with a customized load profile and a reduced thermal network. The multiphysics analysis is focused on the main problems related to the drum roller operation: stator current variation when a random load level is present and heat extraction via the drum shell and conveyor belt.
A prospective study examining balance confidence among individuals with lower limb amputation

Purpose: In this study we assessed whether balance confidence scores changed over a 2-year follow up period, and identified predictors of balance confidence and predictors of change in balance confidence among lower limb amputees. Method: A prospective follow-up survey of 245 community living adults with unilateral below and above knee lower limb amputation who used their prosthetic limb daily was conducted. Balance confidence, assessed using the 16-item Activity-specific Balance Confidence (ABC) Scale, socio-demographic, health and amputation related variables were collected at baseline and 2 years later. Results: ABC scores were similar at baseline (mean = 67.6; SD = 25.7) and follow up (mean = 68.0; SD = 25.8). Lower balance confidence scores at follow up were predicted by older age, being female, use of a mobility device, poor perceived health, increased symptoms of depression, having to concentrate while walking, and fear of falling (all p < 0.05). Predictors of change in balance confidence included gender and perceived health (all p < 0.05). Conclusion: Balance confidence appears to be a persistent problem in the amputee population. Health professionals are encouraged to consider balance confidence as a potentially important variable that may influence function in this clinically unique group of individuals. The identified predictor variables may be useful to clinicians in targeting individuals who require attention to improve balance confidence.
Dimensional representations of DSM-IV cluster B personality disorders in a population-based sample of Norwegian twins: a multivariate study

Background The personality disorders (PDs) in the ‘dramatic’ cluster B [antisocial (ASPD), histrionic (HPD), narcissistic (NPD) and borderline (BPD)] demonstrate co-morbidity. However, the degree to which genetic and/or environmental factors influence their co-occurrence is not known and, with the exception of ASPD, the relative impact of genetic and environmental risk factors on liability to the cluster B PDs has not been conclusively established. Method PD traits were assessed in 1386 Norwegian twin pairs between the age of 19 and 35 years using the Structured Interview for DSM-IV Personality Disorders (SIDP-IV). Using the statistical package Mx, multivariate twin models were fitted to dimensional representations of the PDs. Results The best-fitting model, which did not include sex or shared family environment effects, included common genetic and environmental factors influencing all four dramatic PD traits, and factors influencing only ASPD and BPD. Heritability was estimated at 38% for ASPD traits, 31% for HPD traits, 24% for NPD traits and 35% for BPD traits. BPD traits had the lowest and ASPD traits the highest disorder-specific genetic variance. Conclusion The frequently observed co-morbidity between cluster B PDs results from both common genetic and environmental influences. Etiologically, cluster B has a ‘substructure’ in which ASPD and BPD are more closely related to each other than to the other cluster B disorders.
Influence of Iterative relaxed median filter over FCM clustering in MR images

Image segmentation plays an important role in the analysis and applications of medical image processing and Impulse noise removal is a complex procedure in MR images. Hence in this paper, Iterative relaxed median filter is proposed to improve Peak signal to noise ratio of the filtered image and influence of Iterative relaxed median filter over Fuzzy C-Means clustering (FCM) in MR images is carried out using Cluster Error Index (CEI). For comparative analysis, median filtering methods such as standard median filter (SMF), adaptive median filter (AMF), hybrid median filter (HMF) and relaxed median filter (RMF) are used. Analysis of noise influence of these median filtering methods over FCM Clustering is done based on two validity measures.