Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved Vancomycin Dosing in Children Using Area Under the Curve Exposure

Background: Our objectives were to (1) determine the pharmacokinetic indices of vancomycin in pediatric patients; and (2) compare attainment of 2 target exposures: area under curve (AUC) / minimum inhibitory concentration (MIC) ≥400 and trough concentration ≥15 mcg/mL. Methods: The population-based pharmacokinetic modeling was performed using NONMEM 7.2 for children ≥3 months old who received vancomycin for ≥48 hours from 2003 to 2011. A 1-compartment model with first-order kinetics was used to estimate clearance, volume of distribution and AUC. Empiric Bayesian post hoc individual parameters and Monte Carlo simulations (N = 11,000) were performed. Results: Analysis included 702 patients with 1660 vancomycin serum concentrations. Median age was 6.6 (interquartile range 2.2–13.4) years, weight 22.7 (12.6–46) kg and baseline serum creatinine 0.40 (0.30–0.60) mg/dL. Final model pharmacokinetic indices were clearance (L/h) = 0.248 * Wt0.75 * (0.48/serum creatinine)0.361 * (ln(age)/7.8)0.995 and volume of distribution (L) = 0.636 * Wt. Using these parameters and the observed MIC distribution, Monte Carlo simulation indicated that the initial median dose of 44 (39–52) mg/kg/day was inadequate in most subjects. Regimens of 60 mg/kg/day for subjects ≥12 years old and 70 mg/kg/day for those <12 years old achieved target AUC/MIC in ~75% and trough concentrations ≥15 in ~45% of virtual subjects. An AUC/MIC ~400 corresponded to trough concentration ~8 to 9 mcg/mL. Conclusions: Targeted exposure using vancomycin AUC/MIC, compared with trough concentrations, is a more realistic target in children. Depending on age, serum creatinine and MIC distribution, vancomycin in a dosage of 60 to 70 mg/kg/day was necessary to achieve AUC/MIC ≥ 400 in 75% of patients.
The gene encoding the capsid protein P82 of the Choristoneura fumiferana multicapsid nucleopolyhedrovirus: sequencing, transcription and characterization by immunoblot analysis.

A gene encoding a capsid-associated viral structural protein has been identified and sequenced in the genome of the Choristoneura fumiferana multicapsid nucleopolyhedrovirus (CfMNPV). The gene has a 1872 nucleotide open reading frame (ORF) encoding 624 amino acids with a predicted molecular mass of 71.4 kDa. Transcription, which appeared to be initiated from a conserved GTAAG motif of baculovirus late genes, was detected at 12 h, reached a maximum at 48 h and declined at 72 h post-infection (p.i.). Part of the ORF was cloned in frame into a prokaryotic expression vector, pMAL-c2, and the fusion protein was used to generate antibodies in rabbits. It was shown, with the aid of the polyclonal antiserum, that this viral protein was detectable at 24 h p.i. in infected cells. The protein appeared as an 82 kDa band in occlusion-derived virus and as an 82 kDa band and a 72 kDa band in budded virus. Amino acid sequence comparisons revealed that this ORF had high homology with the ORF p87 (77% similarity) of Orgyia pseudotsugata (Op) MNPV and the ORF p80 (60% similarity) of Autographa californica (Ac) MNPV. Immunoblots confirmed that the CfMNPV protein had antigenic similarities to the P87 protein of OpMNPV, but not to the P80 of AcMNPV.
A system for MEA-based multisite stimulation

The capability for multisite stimulation is one of the biggest potential advantages of microelectrode arrays (MEAs). There remain, however, several technical problems which have hindered the development of a practical stimulation system. An important design goal is to allow programmable multisite stimulation, which produces minimal interference with simultaneous extracellular and patch or whole cell clamp recording. Here, we describe a multisite stimulation and recording system with novel interface circuit modules, in which preamplifiers and transistor transistor logic-driven solid-state switching devices are integrated. This integration permits PC-controlled remote switching of each substrate electrode. This allows not only flexible selection of stimulation sites, but also rapid switching of the selected sites between stimulation and recording, within 1.2 ms. This allowed almost continuous monitoring of extracellular signals at all the substrate-embedded electrodes, including those used for stimulation. In addition, the vibration-free solid-state switching made it possible to record whole-cell synaptic currents in one neuron, evoked from multiple sites in the network. We have used this system to visualize spatial propagation patterns of evoked responses in cultured networks of cortical neurons. This MEA-based stimulation system is a useful tool for studying neuronal signal processing in biological neuronal networks, as well as the process of synaptic integration within single neurons.
Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis.

BACKGROUND Partial deletions of the AZFc region of the Y chromosome were reported to be a significant risk factor for oligo-/azoospermia. In this study, we assessed the occurrence and frequency of partial AZFc microdeletions in patients with spermatogenic failure and in controls with normal spermatogenesis. METHODS In a retrospective study design, gr/gr, b1/b3 and b2/b3 deletions were analysed by multiplex PCR in 170 men with normal spermatogenesis and 348 men with non-obstructive oligo-/azoospermia. RESULTS gr/gr deletions were found in 14 men with oligozoospermia or azoospermia (4.0%) and in three normozoospermic men (1.8%) (NS). b1/b3 deletions were found both in controls (n=1) and in patients (n=1). b2/b3 deletions were significantly more frequent in the normozoospermic (five out of 170) than in the oligo-/azoospermic men (two out of 348). Three novel partial AZFc deletion patterns were found in four oligo-/azoospermic men. No correlation with semen or other clinical parameters was found. CONCLUSIONS The frequency of gr/gr deletions is not significantly increased in men with oligo-/azoospermia, indicating that they are not sufficient per se to cause spermatogenetic impairment and infertility. b1/b3 and b2/b3 deletions are probably irrelevant for spermatogenesis. Novel deletion patterns found exclusively in infertile men suggest that other, still unexplored partial deletions might contribute to spermatogenic failure.
Executive functioning in individuals with a history of ASDs who have achieved optimal outcomes

Executive functioning (EF) is examined among children and adolescents once diagnosed with an autism spectrum disorder (ASD), but who no longer meet diagnostic criteria. These individuals have average social and language skills, receive minimal school support and are considered to have achieved “optimal outcomes” (OOs). Since residual impairments in these individuals might be expected in deficits central to autism, and in developmentally advanced skills, EF was examined in 34 individuals who achieved OOs, 43 individuals with high-functioning autism (HFA), and 34 typically developing (TD) peers. Groups were matched on age (M = 13.49), gender, and nonverbal IQ (NVIQ) but differed on verbal IQ (VIQ; HFA < TD, OO). On direct assessment, all three groups demonstrated average EF; however, the OO and HFA groups exhibited more impulsivity and less efficient planning and problem-solving than the TD group, and more HFA participants exhibited below average inhibition than did OO and TD participants. Parent-report measures revealed average EF among the OO and TD groups; however, the OO group exhibited more difficulty than the TD group on set-shifting and working memory. HFA participants demonstrated more difficulty on all parent-reported EF domains, with a clinical impairment in attention-shifting. Results suggest that EF in OO appears to be within the average range, even for functions that were impaired among individuals with HFA. Despite their average performance, however, the OO and TD groups differed on measures of impulsivity, set-shifting, problem-solving, working memory, and planning, suggesting that the OO group does not have the above-average EF scores of the TD group despite their high-average IQs.
Influence of Additional Ankle Weights on Kinematic Variables of Late Preterm Infants Aged 3–4 Months

ABSTRACT The authors analyzed and compared the effect of additional weight on the spatiotemporal parameters of the kicking movement of late preterm and full-term infants. The experiment was divided into 4 conditions: training, baseline, weight, and postweight. In the W condition, a weight of one third the lower limb mass was added to the infant's ankle. During the baseline and postweight conditions, the ankle weight was removed. Late preterm infants do not differ from full-term infants in relation to spatiotemporal variables at 3 and 4 months. However, during the weight condition, the straightness index and the hip-ankle and knee-ankle correlations decreased in the preterm infants at both ages. In contrast, the straightness index increased in the postweight condition compared to the baseline values at both ages.
Detecting Terrorism Evidence in Text Documents

The paper presents a model to detect terrorism evi- dence in textual documents. The model pre-processes domain spe- cific documents to extract the general patterns of text associated with the domain. The model then incorporates the Conditional Random Field (CRF) model for detection of sentences containing patterns of terrorism evidence. For incorporation of CRF model, the features are selected from generalized patterns rather than the text itself. We prepared a small data set of manually tagged instances of terrorism evidence for training and testing the model. We found that the proposed model achieves better results than other models such as Hidden Markov Model or conventional CRF which are directly applied to text. The proposed model can be applied for improvement of terrorism event extraction and ontology creation systems, especially with the focus towards their effective role in Open Source Intelligence. We describe briefly the existing systems along with possible improvements with incorporation of the presented model at different levels. Index Terms—Open Source Intelligence, Terrorism Evidence Detection, Conditional Random Fields, Terrorism Ontology, Ter- rorism Event Extraction
Functional hierarchy and phenotypic suppression among Drosophila homeotic genes: the labial and empty spiracles genes.

The Drosophila homeotic cluster (HOM‐C) is made up of eight genes, which specify the identity of cephalic, thoracic and abdominal segments. These genes can be ordered in a hierarchy which correlates with their position along the 5′‐3′ transcriptional direction. When they are absent, thoracic and abdominal body segments develop the same ‘ground’ pattern, which is thoracic‐like but also includes cephalic structures (sclerotic plates). We find that these plates are specified by the homeobox gene empty spiracles (ems) which is not a member of the HOM‐C and which is expressed in all body segments. ems mutations, however, only produce defects in anterior head structures and the posterior spiracles. The ems product has the potential to induce sclerotic plates but this potential is suppressed by any of the HOM‐C genes, including the labial gene, which we show to be the lowest ranking of the HOM‐C hierarchy. This suppression does not occur at the transcriptional or translational level because the ems function is suppressed in cells containing the ems product. Thus, this appears to be the first case of phenotypic suppression operating in normal development. We propose that ems was originally a member of the HOM‐C which escaped from the complex and has also acquired new functions during evolution.
Survey of trainee attitudes to preparation for and participation in the FCEM examination

Introduction and aims In the UK, specialist trainees in emergency medicine are required to pass the Fellowship of the College of Emergency Medicine (FCEM). This examination assesses clinical knowledge, attitudes and skills, management principles, critical appraisal, and the ability to search medical literature and synthesise information. The aims of this study were to ascertain what resources trainees felt were most valuable in preparation for the FCEM and to obtain trainee feedback on the running of the FCEM. Methods A questionnaire was developed in conjunction with the TSC into nine parts covering all aspects of preparation for and experience of sitting the FCEM. Email addresses of those trainees who had sat the FCEM examination in 2006 and 2007 were provided by the CEM and questionnaires were sent electronically to recipients. Responses were collated and analysed using Microsoft Excel. Results There was a response rate of 42% (86/203), of whom about three-quarters felt well prepared for the FCEM. The most highly valued resources for exam preparation were practice questions, private study and small group work. A yearly mock FCEM examination was felt to be important by those who had such access and local trainer involvement in exam preparation was perceived significant for success. Conclusions Training programmes should make sure that facilities and expertise are available at a local level to allow trainees to have access to everything that is considered important in order to pass the FCEM.
Using redundant internal coordinates to optimize equilibrium geometries and transition states

A redundant internal coordinate system for optimizing molecular geometries is constructed from all bonds, all valence angles between bonded atoms, and all dihedral angles between bonded atoms. Redundancies are removed by using the generalized inverse of the G matrix; constraints can be added by using an appropriate projector. For minimizations, redundant internal coordinates provide substantial improvements in optimization efficiency over Cartesian and nonredundant internal coordinates, especially for flexible and polycyclic systems. Transition structure searches are also improved when redundant coordinates are used and when the initial steps are guided by the quadratic synchronous transit approach. © 1996 by John Wiley & Sons, Inc.
Broadening the mission of an RNA enzyme

The “RNA World” hypothesis suggests that life developed from RNA enzymes termed ribozymes, which carry out reactions without assistance from proteins. Ribonuclease (RNase) P is one ribozyme that appears to have adapted these origins to modern cellular life by adding protein to the RNA core in order to broaden the potential functions. This RNA‐protein complex plays diverse roles in processing RNA, but its best‐understood reaction is pre‐tRNA maturation, resulting in mature 5' ends of tRNAs. The core catalytic activity resides in the RNA subunit of almost all RNase P enzymes but broader substrate tolerance is required for recognizing not only the diverse sequences of tRNAs, but also additional cellular RNA substrates. This broader substrate tolerance is provided by the addition of protein to the RNA core and allows RNase P to selectively recognize different RNAs, and possibly ribonucleoprotein (RNP) substrates. Thus, increased protein content correlated with evolution from bacteria to eukaryotes has further enhanced substrate potential enabling the enzyme to function in a complex cellular environment. J. Cell. Biochem. 108: 1244–1251, 2009. © 2009 Wiley‐Liss, Inc.
Perinatal Hypoxia‐Ischemia Disrupts Striatal High‐Affinity [3H]Glutamate Uptake into Synaptosomes

Abstract We examined the impact of hypoxia‐ischemia on high‐affinity [3H]glutamate uptake into a synaptosomal fraction prepared from immature rat corpus striatum. In 7‐day‐old pups the right carotid artery was ligated, and pups were exposed to 8% oxygen for 0, 0.5, 1, or 2.5 h, and allowed to recover for up to 24 h before they were killed. High‐affinity glutamate uptakes in striatal synaptosomes derived from tissue ipsilateral and contralateral to ligation were compared. After 1 h of hypoxia plus ischemia, high‐affinity glutamate uptake in the striatum was reduced by 54 ± 13% compared with values from the opposite (nonischemic) side of the brain (p < 0.01, t test versus ligates not exposed to hypoxia). There were similar declines after 2.5 h of hypoxiaischemia. Activity remained low after a 1 h recovery period in room air, but after 24 h of recovery, high‐affinity glutamate uptake was equal bilaterally. Kinetic analysis revealed that loss of activity could be attributed primarily to a 40% reduction in the number of uptake sites. Hypoxia alone had no effect on high‐affinity glutamate uptake although it reduced synaptosomal uptake of [3H]3,4‐dihydroxyphenyl‐ethylamine. Addition of 1 mg/ml of bovine serum albumin to the incubation medium preferentia'ly stimulated high‐affinity glutamate uptake in hypoxic‐ischemic brain compared with its effects in normal tissue. These studies demonstrate that hypoxia‐ischemia reversibly inhibits high‐affinity glutamate uptake and this occurs earlier than the time required to produce neuronal damage in the model.
MULTITHREADED PARALLEL IMPLEMENTATION OF HMMPFAM ON EARTH by Weirong Zhu

Hmmpfam [1] is a widely used bioinformatics software for sequence classification provided by Sean Eddy’s Lab at the Washington University in St.Louis. In real situations, this program may need a few months to finish processing large amounts of sequence data. Thus parallelization of the Hmmpfam is an urgent demand from bioinformatics researchers. HMMer 2.2g provides a parallel hmmpfam program based on PVM (Parallel Virtual Machine) [2]. However, this PVM version does not have good scalability and can not fully take advantage of the current advanced supercomputing clusters. Using state-of-the-art multi-threading computing concept, we implement a new parallel version of hmmpfam on EARTH (Efficient Architecture for Running Threads), an event-driven fine-grain multithreaded programming execution model, which supports fine-grain, non-preemptive fibers. In its current implementations, the EARTH multithreaded execution model is built with off-the-shelf microprocessors in a distributed memory environment. The EARTH runtime system (version 2.5) performs fiber scheduling, inter-node communication, inter-fiber synchronization, global memory management, dynamic load balancing and SMP node support. Compared with the original PVM implementation, our implementation based on EARTH shows notable improvements on absolute speed-up, better scalability and robust performance. Experiments on the Chiba City supercomputing clusters at Argonne National Laboratory (ANL) achieve an absolute speedup of 222.8 on 128 dual-CPU nodes for a representative data set, which means that the total execution time is reduced from 15.9 hours (sequential program) to only 4.3 minutes. Our
3D image-guided robotic needle positioning system for small animal interventions.

PURPOSE This paper presents the design of a micro-CT guided small animal robotic needle positioning system. In order to simplify the robotic design and maintain a small targeting error, a novel implementation of the remote center of motion is used in the system. The system has been developed with the objective of achieving a mean targeting error of <200 μm while maintaining a high degree of user friendliness. METHODS The robot is compact enough to operate within a 25 cm diameter micro-CT bore. Small animals can be imaged and an intervention performed without the need to transport the animal from one workspace to another. Not requiring transport of the animal reduces opportunities for targets to shift from their localized position in the image and simplifies the workflow of interventions. An improved method of needle calibration is presented that better characterizes the calibration using the position of the needle tip in photographs rather than the needle axis. A calibration fixture was also introduced, which dramatically reduces the time requirements of calibration while maintaining calibration accuracy. Two registration modes have been developed to correspond the robot coordinate system with the coordinate system of the micro-CT scanner. The two registration modes offer a balance between the time required to complete a registration and the overall registration accuracy. The development of slow high accuracy and fast low accuracy registration modes provides users with a degree of flexibility in selecting a registration mode best suited for their application. RESULTS The target registration error (TRE) of the higher accuracy primary registration was TRE(primary) = 31 ± 12 μm. The error in the lower accuracy combined registration was TRE(combined) = 139 ± 63 μm. Both registration modes are therefore suitable for small-animal needle interventions. The targeting accuracy of the robotic system was characterized using targeting experiments in tissue-mimicking gelatin phantoms. The results of the targeting experiments were combined with the known calibration and needle deflection errors to provide a more meaningful measure of the needle positioning accuracy of the system. The combined targeting errors of the system were 149 ± 41 μm and 218 ± 38 μm using the primary and combined registrations, respectively. Finally, pilot in vivo experiments were successfully completed to demonstrate the performance of the system in a biomedical application. CONCLUSIONS The device was able to achieve the desired performance with an error of <200 μm and improved repeatability when compared to other designs. The device expands the capabilities of image-guided interventions for preclinical biomedical applications.
Home Boxes support for an efficient Video on Demand distribution

Video-on-Demand (VoD) streaming services have already acquired high popularity, which places hard requirements on Future Internet in terms of server and network bandwidth. Service scalability becomes then a crucial issue for which the server replication is the commonly used solution. However, this technique brings new challenges such as the server placement or the server selection. This paper presents an enhanced service oriented architecture with a new Home-Box layer that aims to provide a platform for efficient VoD streaming service. A popularity-based video contents placement in Home-Boxes and a two-steps end-users' requests redirection are also proposed and evaluated through simulation. The results confirm the promising aspects that motivate the considering of the Home-Box node in the video delivery chain.
Detection of traffic volume anomalies by evolution of negative classifiers in Artificial Immune Systems

Traffic volume anomalies can take a wide range of different forms, each characterized in principle by a different traffic profile, but all the forms having in common the overall surge in traffic at a particular site. Often anomalies, at the onset, appear up as innovations, an unprecedented experience for the network system. For this reason it is appropriate to face them with a negative selection approach that can detect foreign patterns in the complement space. In this work we propose to detect the onset of traffic anomalies within the paradigmatic approach of evolutionary artificial immune systems, through the use of classifiers evolved on the basis of normal traffic profile (the complementary space corresponds to the immune system non-self): the overall architecture can provide robustness and adaptability. The approach discussed here could apply not only to volume anomalies but to traffic anomalies in general.