Miracle-dz/UniFAR-FTUs huggingface dataset:
Once-daily Gentamicin in Infants and Children: A Prospective Cohort Study Evaluating Safety and the Role of Therapeutic Drug Monitoring in Minimizing Toxicity

Background: The clinical evidence base for ototoxicity and nephrotoxicity outcomes with once-daily dosing (ODD) of gentamicin in children is suboptimal. Therapeutic drug monitoring (TDM) in once-daily gentamicin regimens is variable and its role in predicting or preventing clinical toxicity is unclear. We aimed to assess the safety of ODD of gentamicin and the usefulness of TDM in a pediatric cohort. Methods: Children with suspected sepsis were prospectively enrolled to receive ODD of gentamicin at 7 mg/kg/day. Hearing and renal function were objectively assessed at baseline, during therapy, and after therapy. TDM was performed using an interval-adjusted graphical method (Hartford nomogram). Results: A total of 79 children (median age: 5.6 years; range: 1 month–16 years) received 106 episodes of therapy. In all, 61% of these episodes were for febrile neutropenia. Evaluation was complete in 88% for ototoxicity and 92% for nephrotoxicity. Two patients (1.88%, 95% confidence interval: 0.10%–7.13%) experienced permanent hearing loss. One patient (0.94%, 95% confidence interval: <0.10%–5.73%) experienced transient nephrotoxicity. No abnormal serum gentamicin values were detected, even in those experiencing toxicity. Children experiencing toxicity were undergoing treatment for malignancies and had received nephrotoxic or ototoxic medicines before gentamicin. Conclusions: In this pediatric cohort receiving ODD of gentamicin, nephrotoxicity was uncommon and reversible, but irreversible ototoxicity occurred more frequently. TDM using a nomogram neither predicted nor prevented toxicity, which was only observed in those with risk factors.
Evaluation of PCR‐DGGE methodology to monitor fungal communities on grapes

Aims: Some fungi present on the surface of grapes may have a negative effect on the quality of wine. The aim of this study was to evaluate PCR‐denaturing gradient gel electrophoresis (PCR‐DGGE), for the establishment of fungal community profiles from grapes, in order to monitor fungi potentially involved in wine defects.
Research article IN VITRO FLOWERING AND PLANTLETS ELONGATION IN "SUNDEW" DROSERA CAPILLARIS

Experimental data pertaining to the possible participation of mineral nutrients, plant growth regulators, particularly gibberellic acid, carbohydrates and vernalization, in flowers or inflorescence initiation and plantlets elongation in "sundew" Drosera capillaris (a long-day plant) were obtained. The plantlets were cultivated in MS medium supplemented with 0.01 mg/L NAA, 0.01 mg/L GA3, 2% sucrose and 0.18% Phytagel under 12/12, 16/8 and 20/4 h (light/dark) photoperiodic conditions at 24-26°C for 90 days. Under very long day conditions (20/4 h) the flowering process was significantly increased (40-60%) when plantlets of D. capillaries were cultured on medium MS 1/10 and with addition of gibberellic acid (0.1 and 1.0 mg/L) and sucrose (4-6%). These factors not replace the effect of long days to induce flowering. Both foliar development and root formation was much greater on MS media supplemented with 0.5 mg/L IAA in all photoperiodic conditions.
Industrial Strength Ontology Management

Ontologies are becoming increasingly prevalent and important in a wide range of e-commerce applications. E-commerce applications are using ontologies to support parametric searches, enhanced navigation and browsing, interoperable heterogeneous information systems, supplier enablement, configuration management, and transaction discovery. Applications such as information and service discovery and autonomous agents that are built on top of the emerging Semantic Web for the WWW also require extensive use of ontologies. Ontology-enhanced commercial applications, such as these and others require ontology management that is scalable (supporting thousands of simultaneous distributed users), available (running 365×24×7), fast, and reliable. This level of ontology management is necessary not only for the initial development and maintenance of ontologies, but is essential during deployment, when scalability, availability, reliability and performance are absolutely critical. VerticalNet's Ontology Builder and Ontology Server products are specifically designed to provide the ontology management infrastructure needed for e-commerce applications. These tools bring the best ontology and knowledge representation practices together with the best enterprise solutions architecture to provide a robust and scalable ontology management solution.
A New Hypothesis for Sleep: Tuning for Criticality

We propose that the critical function of sleep is to prevent uncontrolled neuronal feedback while allowing rapid responses and prolonged retention of short-term memories. Through learning, the brain is tuned to react optimally to environmental challenges. Optimal behavior often requires rapid responses and the prolonged retention of short-term memories. At a neuronal level, these correspond to recurrent activity in local networks. Unfortunately, when a network exhibits recurrent activity, small changes in the parameters or conditions can lead to runaway oscillations. Thus, the very changes that improve the processing performance of the network can put it at risk of runaway oscillation. To prevent this, stimulus-dependent network changes should be permitted only when there is a margin of safety around the current network parameters. We propose that the essential role of sleep is to establish this margin by exposing the network to a variety of inputs, monitoring for erratic behavior, and adjusting the parameters. When sleep is not possible, an emergency mechanism must come into play, preventing runaway behavior at the expense of processing efficiency. This is tiredness.
Response to Intervention and the Pyramid Model

Response to Intervention (RtI) is a systematic decision-making process that has gained widespread popularity as a problem-solving framework for organizing hierarchies of evidence-based interventions in the context of ongoing progress monitoring. Initially applied to literacy instruction, RtI is being incorporated into an expanding breadth of domains, including early intervention and the prevention of social-emotional delays and the occurrence of challenging behaviors. In this article, we describe RtI and its relationship to the “Pyramid Model” (L. Fox, G. Dunlap, M. L. Hemmeter, G. Joseph, & P. Strain, 2003) for promoting social, emotional, and behavioral development of young children. The 2 approaches have close parallels and are considered to be highly compatible. The discussion examines this congruence, identifies challenges in need of resolution, and emphasizes the exciting promise offered by the emergence and implementation of the 2 problem-solving and decision-making frameworks.
The primary cilium

The primary cilium is an antenna-like organelle that plays a vital role in organ generation and maintenance. It protrudes from the cell surface where it receives signals from the surrounding environment and relays them into the cell. These signals are then integrated to give the required outputs in terms of proliferation, differentiation, migration and polarization that ultimately lead to organ development and homeostasis. Defects in cilia function underlie a wide range of diverse but related human developmental or degenerative diseases. Collectively known as ciliopathies, these disorders present with varying severity and multiple organ involvement. The appreciation of the medical importance of the primary cilium has stimulated a huge effort into studies of the underlying cellular mechanisms. These in turn have revealed that ciliopathies result not only from defective assembly or organization of the primary cilium, but also from impaired ciliary signaling. This special edition of Organogenesis contains a set of review articles that highlight the role of the primary cilium in organ development and homeostasis, much of which has been learnt from studies of the associated human diseases. Here, we provide an introductory overview of our current understanding of the structure and function of the cilium, with a focus on the signaling pathways that are coordinated by primary cilia to ensure proper organ generation and maintenance.
Caenorhabditis elegans Contains Two Distinct Acid Sphingomyelinases*

Mounting evidence supports a role for acid sphingomyelinase (ASM) in cellular stress signaling. Only murine and human sphingomyelinases have been defined at the molecular level. These enzymes are the products of a conserved gene and at the amino acid level share 82% identity. In this study, we show that the nematodeCaenorhabditis elegans possesses two ASMs, termed ASM-1 and ASM-2 encoded by two distinct genes, but lacks detectable neutral sphingomyelinase activity. The C. elegans ASMs are about 30% identical with each other and with the human and murine enzymes. The conserved regions include a saposin-like domain, proline-rich domain, and a putative signal peptide. In addition, 16 cysteines distributed throughout the molecules, and selected glycosylation sites, are conserved. The expression of these genes in C. elegansis regulated during development. Asm-1 is preferentially expressed in the embryo, whereas asm-2 is predominantly expressed in postembryonic stages. When transfected as Flag-tagged proteins into COS-7 cells, ASM-1 is found almost entirely in a secreted form whereas only 20% of ASM-2 is secreted. Only the secreted forms display enzymatic activity. Furthermore, ASM-2 requires addition of Zn2+ to be fully active, whereas ASM-1 is active in the absence of cation. C. elegans is the first organism to display two ASMs. This finding suggests the existence of an ASM gene family.
The impact of pre-transplant valganciclovir on early cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Cytomegalovirus reactivation is a common complication of allogeneic hematopoietic stem cell transplant. The use of pre-transplant valganciclovir during the conditioning regimen followed by preemptive therapy has been used in an attempt to reduce the rate of early cytomegalovirus reactivation, but efficacy data are lacking. In this retrospective study, we evaluated the impact of pre-transplant valganciclovir during the conditioning regimen followed by a preemptive approach on the rate of early cytomegalovirus reactivation through day 100. The rate of cytomegalovirus reactivation through day 100 was 41% in the no-valganciclovir group compared to 46% in the valganciclovir group (p = 0.4). Interestingly, median time to cytomegalovirus reactivation was earlier in the no-valganciclovir group compared to the valganciclovir group (26 vs. 34 days; p = 0.008) and there was a trend toward a higher rate of cytomegalovirus disease through day 100 in the no-valganciclovir group (0.7% valganciclovir vs. 4% no-valganciclovir; p = 0.1). Day 100 survival was similar between the groups (90% valganciclovir vs. 91% no-valganciclovir; p = 0.8). Although the time to cytomegalovirus reactivation is significantly longer in the valganciclovir group, this did not impact the rate of cytomegalovirus reactivation or survival by day 100 suggesting that other strategies need to be explored.
Towards a new generation of security requirements definition methodology using ontologies

In recent years, security in Information Systems (IS) has become an important issue, and needs to be taken into account in all stages of IS development, including the early phase of Requirement Engineering (RE). Recent studies proposed some useful approaches for security requirements definition but analysts still suffer from a considerable lack of knowledge about security and domain field. Ontologies are known to be wide sources of knowledge. We propose in this research to include ontologies into the requirements engineering process. Ontologies are factors in achieving success in requirements elicitation of high quality.
Discovery of photospheric Ca X emission lines in the far-UV spectrum of the hottest known white dwarf (KPD 0005+5106)

For the first time, we have identified photospheric emission lines in the far-UV spectrum of a white dwarf. They were discovered in the Far Ultraviolet Spectroscopic Explorer spectrum of the hot (Teff ≈ 200 000 K) DO white dwarf KPD 0005+5106 and they stem from extremely highly ionized calcium (Ca x λλ 1137, 1159 A). Their photospheric origin is confirmed by non-LTE line-formation calculations. This is the highest ionisation stage of any element ever observed in a stellar photosphere. Calcium has never been detected before in any hot white dwarf or central star of planetary nebula. The calcium abundance determination for KPD 0005+5106 (1–10 times solar) is difficult, because the line strengths are rather sensitive to current uncertainties in the knowledge of effective temperature and surface gravity. We discuss the possibility that the calcium abundance is much lower than expected from diffusion/levitation equilibrium theory. The same emission lines are exhibited by the [WCE]-type central star NGC 2371. Another Ca x line pair (λλ 1461, 1504 A) is probably present in a Hubble Space Telescope spectrum of the PG 1159-type central star NGC 246.
Involutions of SL ( n , k ) , ( n > 2 )

Abstract. A first characterization of the isomorphism classes of k-involutions for any reductive algebraic groups defined over a perfect field was given in [7] using 3 invariants. In this paper we give a simple characterization of the isomorphism classes of involutions of SL (n, k) with k any field of characteristic not 2. We classify the isomorphism classes of involutions for k algebraically closed, the real numbers, the p-adic numbers and finite fields. We also determine in which cases the corresponding fixed point group H is k-anisotropic. In those cases the corresponding symmetric k-variety consists of semisimple elements.
Real-Time Optimization for Adaptive Traffic Signal Control Using Genetic Algorithms

Control methodologies of traffic signals have significantly improved during the recent past along with advancements in technology. Adaptive traffic signal control is the most recent and advanced control type of traffic signals. Adaptive control is able to efficiently relieve traffic congestion by continuously adjusting signal timings according to real-time traffic conditions. Conventional optimization methods such as integer programming, hill climbing, or descent gradient searching have been gradually overshadowed by genetic algorithms in many areas including traffic signal operation. The research presented in this article is distinct from previous studies in that it focuses on real-time adaptive signal optimization using genetic algorithms. The proposed adaptive signal system provides acyclic signal operation based on a rolling horizon real-time control approach. The algorithm was tested using microsimulation for on-line evaluation and comparison to fixed-time plans generated from the latest TRANSYT-7F version 9.7, which has a genetic optimization feature. The developed signal system consists of three major components including a genetic algorithm optimization module, an internal traffic simulation module, and a database management system all working in cooperation to optimize signal timings in real time. Using the pseudo on-line simulation platform, three testing scenarios for high, medium, and low level of traffic demands were conducted focusing on evaluating several important features of the proposed adaptive signal control system. The test results indicated that real-time genetic control outperformed fixed-signal timing plan in all scenarios based on total vehicle delay.
Changing patterns of teenage pregnancy: population based study of small areas

Abstract Objectives: To measure the impact of socioeconomic deprivation on rates of teenage pregnancy and the extent of local variation in pregnancy rates in Scotland, and to examine how both have changed over time. Design: Population study using routine data from hospital records, aggregated for small areas. Subjects: Female teenagers resident in Scotland who were treated for pregnancy in an NHS hospital in either 1981-5 (62 338 teenagers) or 1991-5 (48 514) and who were aged 13-19 at the time of conception. Main outcome measures: Pregnancy rates per 1000 in age group and the proportions of pregnancies resulting in a maternity (live birth or stillbirth) in teenagers aged 13-15, 16-17, and 18-19. Results: From the 1980s to the 1990s pregnancy rates increased differentially according to levels of local deprivation, as measured by the Carstairs index. Among teenagers aged less than 18 the annual pregnancy rate increased in the most deprived areas (from 7.0 to 12.5 pregnancies per 1000 13-15 year olds and from 67.6 to 84.6 per 1000 16-17 year olds), but there was no change, on average, among teenagers in the most affluent areas (3.8 per 1000 13-15 year olds and 28.9 per 1000 16-17 year olds). Among 18-19 year olds the pregnancy rate decreased in the most affluent areas (from 60.0 to 46.3 per 1000) and increased in the most deprived areas (from 112.4 to 116.0 per 1000). The amount of local variation explained by deprivation more than doubled from the 1980s to the 1990s. The proportion of pregnancies resulting in a maternity was positively associated with level of deprivation, but the effect remained similar over time. Conclusion: From the 1980s to the 1990s the difference in rates of teenage pregnancy between more affluent and more deprived areas widened. This has implications for allocating resources to achieve government targets and points to important social processes behind the general increase in the number of teenage pregnancies in Scotland. What is already known on this topic Rates of teenage pregnancy are considerably higher in the United Kingdom than in other western European countries In the United Kingdom rates of teenage pregnancy are known to be higher in areas of greater socioeconomic deprivation, although local variation may also reflect differential access to family planning services What this study adds From 1981-5 to 1991-5 rates of teenage pregnancy in Scotland increased more rapidly in areas of greater socioeconomic deprivation In the 1990s socioeconomic deprivation explained more than 50% of local variation in rates of teenage pregnancy, more than double the amount explained by it in the 1980s
One-Pot, Mix-and-Read Peptide-MHC Tetramers

Background Cytotoxic T Lymphocytes (CTL) recognize complexes of peptide ligands and Major Histocompatibility Complex (MHC) class I molecules presented at the surface of Antigen Presenting Cells (APC). Detection and isolation of CTL's are of importance for research on CTL immunity, and development of vaccines and adoptive immune therapy. Peptide-MHC tetramers have become important reagents for detection and enumeration of specific CTL's. Conventional peptide-MHC-tetramer production involves recombinant MHC production, in vitro refolding, biotinylation and tetramerization; each step followed by various biochemical steps such as chromatographic purification, concentration etc. Such cumbersome production protocols have limited dissemination and restricted availability of peptide-MHC tetramers effectively precluding large-scale screening strategies involving many different peptide-MHC tetramers. Methodology/Principal Findings We have developed an approach whereby any given tetramer specificity can be produced within 2 days with very limited effort and hands-on time. The strategy is based on the isolation of correctly oxidized, in vivo biotinylated recombinant MHC I heavy chain (HC). Such biotinylated MHC I HC molecules can be refolded in vitro, tetramerized with streptavidin, and used for specific T cell staining-all in a one-pot reaction without any intervening purification steps. Conclusions/Significance We have developed an efficient “one-pot, mix-and-read” strategy for peptide-MHC tetramer generation, and demonstrated specific T cell straining comparable to a commercially available MHC-tetramer. Here, seven peptide-MHC tetramers representing four different human MHC (HLA) class I proteins have been generated. The technique should be readily extendable to any binding peptide and pre-biotinylated MHC (at this time we have over 40 different pre-biotinylated HLA proteins). It is simple, robust, and versatile technique with a very broad application potential as it can be adapted both to small- and large-scale production of one or many different peptide-MHC tetramers for T cell isolation, or epitope screening.
Influence of flow velocity on biofilm growth in a tubular heat exchanger-condenser cooled by seawater

The influence of flow velocity (FV) on the heat transfer process in tubes made from AISI 316L stainless steel in a heat exchanger-condenser cooled by seawater was evaluated based on the characteristics of the resulting biofilm that adhered to the internal surface of the tubes at velocities of 1, 1.2, 1.6, and 3 m s−1. The results demonstrated that at a higher FV, despite being more compact and consistent, the biofilm was thinner with a lower concentration of solids, and smoother, which favoured the heat transfer process within the equipment. However, higher velocities increase the initial cost of the refrigerating water-pumping equipment and its energy consumption cost to compensate for the greater pressure drops produced in the tube. The velocity of 1.6 m s−1 represented the equilibrium between the advantages and disadvantages of the variables analysed for the test conditions in this study.
Potential beneficial effects of sacubitril-valsartan in renal disease: a new field for a new drug

ABSTRACT Introduction: Patients with renal dysfunction are at a higher risk of cardiovascular disease (CVD), which often shares manifestations with heart failure (HF). Last year, the FDA approved the use of sacubitril-valsartan in patients with HF. This dual-acting agent enhances the functions of natriuretic peptides and inhibits the renin-angiotensin system. Areas covered: This review summarizes the existing preclinical and clinical studies carried out with sacubitril-valsartan (and other drugs with similar pharmacological mechanisms) in HF and hypertensive patients. We put the focus on the renal data provided by these studies. Data were obtained from English peer-reviewed articles on PubMed and clinical trials registered in ClinicalTrials.gov. Expert opinion: Overall, sacubitril-valsartan might be a promising therapeutic approach in patients with renal dysfunction. Renal conditions with marked CV risk, such as arterionephrosclerosis, could constitute a particular setting where to evaluate the impact of the drug. Nevertheless, large, randomized trials are needed to confirm the beneficial effects and safety profile of the drug in renal patients, as well as to elucidate some concerns observed in HF trials, such as the slight increase in proteinuria.
A unified approach to detecting crosstalk faults of interconnects in deep sub-micron VLSI

The crosstalk fault effects in deep sub-micron VLSI, namely, glitches and the crosstalk-induced delay, are investigated. The origin of their occurrence, relationship and importance in circuit operation are elucidated. It is shown that the crosstalk-induced delay is only superposition of the induced glitch with the original signal delay on the affected victim line; and crosstalk-induced delay is more important in affecting the circuit performance, and should be considered in more details for testing. A scheme which is to detect both types of faults in a unified way by just detecting glitches is proposed and studied, considering the manufacture process variation. In this way, detection of crosstalk-induced faults becomes much easier.