Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Kidney Function on Amikacin Pharmacokinetics on Hospitalized Patients: Knowledge to Improve Therapy

Despite the narrow therapeutic window characteristic of amikacin, this amino glycoside remains one of the most frequently prescribed particularly against multiple drug-resistant pathogens. In order to achieve an effective antibiotic therapeutic effect with minimal toxicity and, simultaneously avoid bacterial resistance development, the pharmacokinetics drug monitoring is recommended for amikacin. Since amikacin is almost 100% eliminated by glomerular filtration and it is nephroand ototoxic, its exposure and availability in renal patients is expected to be altered in relation to patients with normal organ function. In this context, the present study aimed at assessing the correlation between demographical/biochemical data and the pharmacokinetic parameters of amikacin in an attempt of developing dosage recommendations to renal patients. The present retrospective study included 628 patients undergoing therapy with amikacin and admitted in Coimbra University Hospital pole of the Hospital and University Centre of Coimbra, EPE, in Portugal, between 2008 and 2015. Blood samples were collected 1 h after the end of amikacin infusion and 30 min before the following administration to attain the peak concentration (Cmax) and the trough concentration (Cmin). Demographic data, dose and frequency of administration of amikacin and creatinemia were also collected for each patient, whose pharmacokinetic parameters were then calculated using equations Sawchuk and Zaske. The population was divided regarding the age of each patient (18-34; 35-49; 50-64; 65-79 and ≥80 years old) and regarding the glomerular filtration rate: <60, 60120 and ≥120 mL/min/1.73m. After checking the normality and homogeneity of variances test, ANOVA was used to determine statistical differences among those distinct sub-populations. Statistically significant differences were found between the 5 age groups Research Article
Does Accounting for Mitochondrial Genetic Variation Improve the Fit of Genetic Models?

We describe a simple variance component model for estimating the effect of mitochondrial DNA (mtDNA) inheritance on quantitative trait variation. The model is applied to quantitative trait Q5 in the simulated general population data from Genetic Analysis Workshop (GAW) 12. Although the mitochondrial effect on Q5 is small (5.3%) and the power of the method to detect the effect is correspondingly low, analysis over the available population replicates demonstrates that the effect of maternal relatedness can be detected and estimated accurately. © 2001 Wiley‐Liss, Inc.
Five ADNFLE mutations reduce the Ca2+ dependence of the mammalian alpha4beta2 acetylcholine response.

Five nicotinic acetylcholine receptor (nAChR) mutations are currently linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The similarity of their clinical symptoms suggests that a common functional anomaly of the mutations underlies ADNFLE seizures. To identify this anomaly, we constructed rat orthologues (S252F, +L264, S256L, V262L, V262M) of the human ADNFLE mutations, expressed them in Xenopus oocytes with the appropriate wild-type (WT) subunit (alpha4 or beta2), and studied the Ca2+ dependence of their ACh responses. All the mutations significantly reduced 2 mM Ca2+-induced increases in the 30 microM ACh response (P < 0.05). Consistent with a dominant mode of inheritance, this reduction persisted in oocytes injected with a 1:1 mixture of mutant and WT cRNA. BAPTA injections showed that the reduction was not due to a decrease in the secondary activation of Ca2+-activated Cl- currents. The S256L mutation also abolished 2 mM Ba2+ potentiation of the ACh response. The S256L, V262L and V262M mutations had complex effects on the ACh concentration-response relationship but all three mutations shifted the concentration-response relationship to the left at [ACh] >= 30 microM. Co-expression of the V262M mutation with a mutation (E180Q) that abolished Ca2+ potentiation resulted in 2 mM Ca2+ block, rather than potentiation, of the 30 microM ACh response, suggesting that the ADNFLE mutations reduce Ca2+ potentiation by enhancing Ca2+ block of the alpha4beta2 nAChR. Ca2+ modulation may prevent presynaptic alpha4beta2 nAChRs from overstimulating glutamate release at central excitatory synapses during bouts of synchronous, repetitive activity. Reducing the Ca2+ dependence of the ACh response could trigger seizures by increasing alpha4beta2-mediated glutamate release during such bouts.
A Knowledge-based System to Support Legal Case Construction

We have designed a system to support collaborative case reasoning and building in corporate litigation cases, that is, processes of bringing and pursuing lawsuits. The design is based on our understanding of the domain acquired through analysis of the literature, interviews of various parties involved in corporate litigation processes, and studies of the commercial tools already available. In this paper we illustrate the designed system and in particular the interaction modes that it supports that we believe address a number of the requirements that emerged through our analysis. We also describe its main components and their integration, including a knowledge model that represents the domain, and a natural language processing component for extracting semantic information. A description of a prototype system is also provided.
Research on UWB indoor positioning based on TDOA technique

Ultra wideband (UWB) wireless communication technology has been regarded as a very important way of indoor short distance, high speed transition at present. In this paper the system structures and working principles of indoor positioning using UWB are introduced. The basic location principles and realization ways based on TDOA (Time-Difference-Of Arrival) are discussed and a new method to estimate the value of TDOA is proposed. In the indoor positioning system, the content being transmitted are simple, the system complexity is low, and it is prone to link with other outdoor positioning system such as GPS to realize accurate positioning.
Reader Engagement

This is a work-in-progressproject.The purpose of this research is to help increasing the readers’ level of engagement using a multimedia approach. Previous studies have shown that active reading engage readers to keep reading as an interactiveway of learning. However, reading is a very personal experience for each reader due to readers’ understanding and different points of views. This project focuses in giving the reader the best reading experience even when the reading is not interesting or in this case boring. This project propose an interactive multimedia reading approach in order to increase the reading engagement level of the subjects using the Brain-Computer Interfaces as a measurement of the engagement level among the participantsto trigger a video to pop out when readers' the engagement level has reached a low engagement.
Specific regulation of intestinal nutrient transporters by their dietary substrates.

Studies of bacteria provide most information on the regulation of protein synthesis. Since bacteria are unicellular organisms living in media whose' composition they cannot control, they are exposed to wide variations in substrate levels. Thus, it makes sense that levels of many bacterial enzymes and transporters are regulated by levels of their substrates or products. Cells of multicellular organisms, on the other hand, are bathed in an internal milieu whose composition is maintained constant by the organism itself. Hence, levels of most eukaryotic enzymes are not regulated by sub­ strate levels. The few exceptions mainly involve enzymes of the gastrointes­ tinal (01) tract, which are exposed to a luminal milieu that varies with diet, or of liver, pancreas, and adipocytes, which are exposed to plasma nutrient levels that also vary with diet. Examples of adaptive enzymes in the OJ tract have long been known; in fact, pancreatic amylase and chymotrypsin, which are regulated by dietary carbohydrate and protein, were among the first adaptive enzymes discovered in any organism. Yet little attention has been paid to the regulation of intestinal nutrient transporters despite the vast literature on the transport mechanisms themselves. This chapter summarizes the evidence that levels of most intestinal nutrient transporters are regulated by their substrates. This phenomenon is interesting for at least four reasons: It is physiologically
Future prospects for cannabinoids and endogenous cannabinoid system in the epileptic brain - A short overview of the latest scientific reports

SUMMARY Effective treatment of epilepsy has been the main therapeutic challenge for the past several years. The biggest problem is refractory epilepsy. Despite the fact that the problem of seizure resistance to monotherapy affects approximately 30% of epileptic patients, clear algorithms of drug selection have not been yet fully developed. Considering the treatment with two or more antiepileptic drugs (AEDs), it is of particular importance that the AEDs should be selected based on their high anticonvulsant properties, as well as a high level of neuroprotection and minimal side effects. For the last several years many researchers focused their efforts on looking for new potent natu ral and synthetic anticonvulsants. Results from studies of some natu ral cannabinoid compounds as well as synthetic cannabinoids clearly prove the anticonvulsive properties of these substances in various in vitro and in vivo models of epilepsy. This review summarizes the latest experimental data concerning the potential significance of the endoge nous cannabinoid system and cannabinoids in the treatment of epilepsy.
Root type and soil phosphate determine the taxonomic landscape of colonizing fungi and the transcriptome of field-grown maize roots

Our data illustrates for the first time that root type identity and phosphate availability determine the community composition of colonizing fungi and shape the transcriptomic response of the maize root system. Summary Plant root systems consist of different root types colonized by a myriad of soil microorganisms including fungi, which influence plant health and performance. The distinct functional and metabolic characteristics of these root types may influence root type inhabiting fungal communities. We performed internal transcribed spacer (ITS) DNA profiling to determine the composition of fungal communities in field-grown axial and lateral roots of maize (Zea mays L.) and in response to two different soil phosphate (P) regimes. In parallel, these root types were subjected to transcriptome profiling by RNA-Seq. We demonstrated that fungal communities were influenced by soil P levels in a root type-specific manner. Moreover, maize transcriptome sequencing revealed root type-specific shifts in cell wall metabolism and defense gene expression in response to high phosphate. Furthermore, lateral roots specifically accumulated defense related transcripts at high P levels. This observation was correlated with a shift in fungal community composition including a reduction of colonization by arbuscular mycorrhiza fungi as observed in ITS sequence data and microscopic evaluation of root colonization. Our findings point towards a diversity of functional niches within root systems, which dynamically change in response to soil nutrients. Our study provides new insights for understanding root-microbiota interactions of individual root types to environmental stimuli aiming to improve plant growth and fitness.
Wide-Angle Scanning Phased Array Using an Efficient Decoupling Network

The active impedance of each element in a phased array changes substantially with scan angle due to mutual coupling. Therefore, a key challenge in the design of wide-angle scanning phased array is to achieve wide-angle impedance matching (WAIM). In this communication, an efficient decoupling network is developed to reduce the mutual coupling between adjacent elements for this purpose. A complete scattering matrix analysis of the decoupling network is given and the design procedure is summarized. A 1 × 16 linear microstrip phased array has been designed and fabricated for experimental verification. Good agreement is obtained between measured and simulated results. The measured mutual coupling between adjacent elements is reduced to lower than -35 dB at the center frequency. Due to the reduced mutual coupling, the array can experimentally scan to 66° with a gain reduction of only 3.04 dB.
The pathway to clinical use of a cancer biomarker

Abstract Biomarkers play a key role in the diagnosis and management of patients with cancer, and are important for fulfilling the promise of precision medicine in oncology. However, although numerous biomarkers have been shown to have clinical validity, many have not undergone rigorous testing to demonstrate clinical utility so that they can be appropriately incorporated into clinical care. This review article highlights the characteristics of a good biomarker and the steps required to demonstrate clinical utility, and gives examples of both successful established biomarkers and promising new tissue-based and circulating biomarkers on the horizon.
The prion protein and New World primate phylogeny

The PrPC prion protein contains 250 amino acids with some variation among species and is expressed in several cell types. PrPC is converted to PrPSc by a post-translational process in which it acquires amino acid sequences of three-dimensional conformation of b-sheets. Variations in the prion protein gene were observed among 16 genera of New World primates (Platyrrhini), and resulted in amino acid substitutions when compared with the human sequence. Seven substitutions not yet described in the literature were found: W ® R at position 31 in Cebuella, T ® A at position 95 in Cacajao and Chiropotes, N® S at position 100 in Brachyteles, L ® Q at position 130 in Leontopithecus (in the sequence responsible for generating the b-sheet 1), D ® E at position 144 in Lagothrix (in the sequence responsible for the a-helix 1), D® G at position 147 in Saguinus (also located in the a-helix 1 region), and M ® I at position 232 in Alouatta. The phylogenetic trees generated by parsimony, neighbor-joining and Bayesian analyses strongly support the monophyletic status of the platyrrhines, but did not resolve relationships among families. However, the results do corroborate previous findings, which indicate that the three platyrrhine families radiated rapidly from an ancient split.
Optimal Power Flow in the Smart Grid Using Direct Load Control Program

This paper proposes an Optimal Power Flow (OPF) algorithm by Direct Load Control (DLC) programs to optimize the operational cost of smart grids considering various scenarios based on different constraints. The cost function includes active power production cost of available power sources and a novel flexible load curtailment cost associated with DLC programs. The load curtailment cost is based on a virtual generator for each load (which participates in DLC program). To implement the load curtailment in the objective function, we consider incentive payments for participants and a load shedding priority list in some events. The proposed OPF methodology is applied to IEEE 14, 30-bus, and 13-node industrial power systems as three examples of the smart grids, respectively. The numerical results of the proposed algorithm are compared with the results obtained by applying MATPOWER to the nominal case by using the DLC programs. It is shown that the suggested approach converges to a better quality solution in an acceptable computation time.
Validation platform implementation description – D5.2

This deliverable describes different test-beds for the validation of the architecture, algorithms and protocols for the operator governed opportunistic networking as defined in the OneFIT Project. Further on, this deliverable provides a description of the implementation of the OneFIT cognitive management systems CSCI and CMON as well as the C4MS protocol. Also, implementation of the blocks supporting the OneFIT system (JRRM, CCM, DSONPM, and DSM) is described. This document also describes the implementation of the OneFIT scenarios for opportunistic coverage extension, opportunistic capacity extension, infrastructure supported ad-hoc networking and device-to-device communication as well as opportunistic resource aggregation in the backhaul network.
Usability evaluation of Augmented Reality systems

Augmented Reality is a technological area that has met with significant growth in our times and its applications cover an ever increasing range of everyday life activities. Despite the rapid development of Augmented Reality technology, not much attention has been given to the important aspect of system's interface usability. To date, some of the methods used in the assessment of common software applications are also employed in the limited number of studies regarding the usability assessment of Augmented Reality systems. In this paper, we investigate the issue of usability evaluation of Augmented Reality systems and we discuss the use of the assessment methods currently employed for traditional applications. Furthermore, we present and discuss issues that arise from their employment in the assessment of Augmented Reality systems and possible ways to overcome these issues.
Translational control of synthesis of simian virus 40 late proteins from polycistronic 19S late mRNA

The simian virus 40 (SV40) 19S late mRNA is polycistronic, encoding multiple late proteins: agnoprotein, VP2, and VP3. We constructed a chloramphenicol acetyltransferase (CAT) transient expression vector in which the SV40 sequences between nucleotides 5171 and 1046 (via the SV40 origin of replication and including the late promoter) were inserted 5' to the cat gene; therefore, the AUG for CAT expression occurs after the AUGs for agnoprotein, VP2, and VP3. CAT enzyme activity assayed after transfection of these constructions indicates the level of CAT AUG utilization and, therefore, can be used as a measure of the ability of prior AUGs to intercept scanning ribosomes. Specifically, deletions and point mutations of the viral AUGs resulted in increased CAT enzyme activity owing to increased utilization of the downstream CAT AUG. To compare a variety of mutants, we used the levels of increase to calculate the translational efficiency of the viral AUGs. Some of our data agree with predictions of the modified scanning model (MSM). Little variation in downstream CAT AUG utilization was noted regardless of whether the VP2 AUG (in a weak MSM sequence context) was intact or removed. Hence, a scanning ribosome may easily bypass it. Similar analysis of the VP3 AUG (in a favorable MSM sequence context) demonstrated that it could efficiently intercept ribosomes prior to the downstream AUG. Overall, these data indicate that the structure of the 19S late mRNA and the relative efficiency of translational start codon utilization can account for the VP3/VP2 ratio found in infected cells. The agnoprotein reading frame, depending on how the mRNA precursor is spliced, is either not contained in the mRNA or is terminated near the VP2 AUG. Under these conditions, the ability of the agnoprotein AUG to block downstream CAT AUG utilization was found to be minimal in our assay. However, we directly tested the blocking ability of the agnoprotein AUG under conditions in which the reading frame terminated well after the CAT AUG. Although the agnoprotein AUG lies in a very good sequence context, this direct analysis showed that it interfered minimally with utilization of the CAT AUG when under the control of the SV40 late promoter. However, expected high levels of interference were regained when the late promoter was replaced with the Rous sarcoma virus long terminal repeat. (ABSTRACT TRUNCATED AT 400 WORDS)
Skeletal Muscle Plasticity After Hemorrhagic Stroke in Rats: Influence of Spontaneous Physical Activity

ObjectiveThe aim of this study was to determine the contribution of spontaneous post-stroke physical activity to skeletal muscle plasticity after stroke. DesignA randomized controlled study was conducted of 24 young adult male Sprague-Dawley rats assigned to three experimental groups: (1) STR—hemorrhagic stroke in the right caudoputamen; (2) SHAM—procedural control; and (3) CONT—no intervention (n = 8/group). Neurologic testing was performed before and 2 wks after stroke. Spontaneous physical activity was monitored five nights per week for 1 wk preoperatively and 2 wks postoperatively. Two weeks after stroke induction, bilateral soleus and tibialis anterior muscles were harvested. Myofiber cross-sectional areas were determined, and fiber typing was performed with immunohistochemistry. ResultsSTR animals demonstrated neurologic deficit in the contralesional hindlimb 2 wks after stroke. Quantity of spontaneous physical activity did not differ between groups within each of the week-long study intervals. No significant difference was found in fiber types or cross-sectional areas in the soleus muscle of STR vs. CONT groups. However, the tibialis anterior muscle of the contralesional hindlimbs of the STR animals showed atrophy in 2x and 1 + 2x myofibers, as well as type 1 hypertrophy. ConclusionsSkeletal muscle adaptation occurs by 2 wks post-stroke in this model. It is muscle specific and appears to be influenced by factors other than spontaneous post-stroke physical activity.
PGD for glycogen storage disease type IV: Birth of healthy twins following successful clinical application of a mutation‐specific protocol

Glycogen storage disease type IV (GSD-IV OMIM 232 500) is a rare autosomal recessive disorder with an estimated frequency of 2.3 children of 100 000 births. It is caused by a deficiency of amylo-1, 4 to 1, 6-transglucosidase [glycogen branching enzyme (EC 2.4.1.18) GBE] leading to the accumulation of amylopectin-like glycogens in various cell types including hepatocytes and myocytes (Tay et al., 2004). The GBE 1 gene codes for a 702aa protein and it is expressed in all tissues. Reported mutations span the gene and correlate with various phenotypes, including the neonatal form of GSD-IV which leads to neonatal death (L’Hermine-Coulomb et al., 2005; Bruno et al. 2007). Although prenatal diagnosis for GSD-IV is available (either by molecular analysis, or by measuring enzyme activity in amniocytes), the decision of terminating a pregnancy is emotionally stressful especially for couples who have previously experienced a neonate loss. Preimplantation genetic diagnosis (PGD) is now an established alternative to couples who are at risk of transmitting a known genetic disease as it offers the advantage of avoiding the termination of affected pregnancies by the identification and selective transfer of unaffected in vitro-fertilized (IVF) embryos. The positive outcome of a clinical PGD cycle (i.e. unaffected fullterm baby) depends upon the success of both the assisted reproductive treatment and the genetic diagnosis. In this article, we report the development, optimization of a case-dependent genotyping protocol for PGD of GSD-IV and its successful clinical application, in collaboration with a centre of assisted reproductive treatment in Athens. PGD for GSD-IV was offered to a Greek carrier couple who had the experience of a GSD-IV affected neonate that had died at 19 days postpartum. The diagnosis of the neonate was based on postmortem histological examination and confirmed molecular analysis