Miracle-dz/UniFAR-FTUs huggingface dataset:
AUC Versus Peak–Trough Dosing of Vancomycin: Applying New Pharmacokinetic Paradigms to an Old Drug

Objectives: To compare and contrast the pharmacokinetic/pharmacodynamic foundations of traditional “peak–trough” vancomycin dosing methods versus newer “area under the curve” (AUC) strategies. To propose a new AUC-based dosing chart for empirically determining an initial vancomycin dosing regimen designed to achieve a desired AUC24 using the minimum inhibitory concentration (MIC), creatinine clearance (CrCl), and vancomycin clearance (ClVanco). Review of vancomycin dosing: Peak–trough vancomycin dosing is designed to achieve a Cpeak of 20–40 mg/L and a Ctrough of 10–15 or 15–20 mg/L, depending on the severity of the infection and the nature of the pathogen. New treatment guidelines for vancomycin suggest that therapy should achieve an AUC24/MIC of ≥400. AUC-based vancomycin dosing derives the daily dose from ClVanco, MIC, and the desired AUC24/MIC, without consideration of the patient’s weight. New AUC dosing chart: A vancomycin dosing chart is proposed that estimates ClVanco using the following formula developed by Matzke et al: ClVanco in L/h = [(CrClmL/min × 0.689) + 3.66] × 0.06, which simplifies to (CrClmL/min × 0.41) + 0.22. Two levels of dosing are included—high dose (Ctrough: 15–20 mg/L) and moderate dose (Ctrough: 10–15 mg/L). Although the chart has not been validated clinically, it represents the product of standard dosing equations that are used to determine a starting dosing regimen based on well-established vancomycin pharmacokinetic parameters. Conclusions: An understanding of pharmacokinetic and pharmacodynamic principles, including the relevance of AUC in relation to MIC, enables clinicians to make the best use of vancomycin dosing options. The proposed dosing chart is pharmacokinetically valid but has yet to be applied clinically. It provides a foundation for further study of how clinicians can determine an optimal AUC-based starting vancomycin dosing regimen without having to derive ClVanco or AUC24.
Multiple subspace matching pursuit for spectrum sensing

Spectrum sensing is used to perceive the spectral environment over a wide frequency band. The multiple measurement vector (MMV) model can be applied to the spectrum sensing scenario since it enables jointly sparse signal recovery. In this paper, a novel spectrum sensing algorithm, referred to as multiple subspace matching pursuit (MSMP), is proposed to reduce the miss detection and false alarm events in the spectrum sensing. Numerical simulations demonstrate that the proposed algorithm shows the outstanding recovery performance with the reduction of the incorrect spectrum decisions.
Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice

Liver regeneration stimulated by a loss of liver mass leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Mice with targeted disruption of the interleukin-6 (IL-6) gene had impaired liver regeneration characterized by liver necrosis and failure. There was a blunted DNA synthetic response in hepatocytes of these mice but not in nonparenchymal liver cells. Furthermore, there were discrete G1 phase (prereplicative stage in the cell cycle) abnormalities including absence of STAT3 (signal transducer and activator of transcription protein 3) activation and depressed AP-1, Myc, and cyclin D1 expression. Treatment of IL-6-deficient mice with a single preoperative dose of IL-6 returned STAT3 binding, gene expression, and hepatocyte proliferation to near normal and prevented liver damage, establishing that IL-6 is a critical component of the regenerative response.
Real-time visual analytics for event data streams

Real-time analysis of data streams has become an important factor for success in many domains such as server and system administration, news analysis and finance to name just a few. Introducing real-time visual analytics into such application areas promises a lot of benefits since the rate of new incoming information often exceeds human perceptual limits when displayed linearly in raw formats such as textual lines and automatic aggregation often hides important details. This paper presents a system to tackle some of the visualization challenges when analyzing such dynamic event data streams. In particular, we introduce the Event Visualizer, which is a loosely coupled modular system for collecting, processing, analyzing and visualizing dynamic real-time event data streams. Due to the variety of different analysis tasks the system provides an extensible framework with several interactive linked visualizations to focus on different aspects of the event data stream. Data streams with logging data from a computer network are used as a case study to demonstrate the advantages of visual exploration.
Knockout of Apolipoprotein E in rabbit promotes premature intervertebral disc degeneration: A new in vivo model for therapeutic approaches of spinal disc disorders

Intervertebral disc (IVD) degeneration that accelerates the loss of disc structural and functional integrities is recognized as one of the major factors of chronic back pain. Cardiovascular risk factors, such as deficits of apolipoproteins that elevate the levels of cholesterol and triglycerides, are considered critical for the progress of atherosclerosis; notably in the abdominal aorta and its lumbar branching arteries that supply lumbar vertebrae and IVDs. Obstruction of the lumbar arteries by atherosclerosis is presumed to promote lumbar disc degeneration and low back pain. APOE-knockout rabbits have recently been shown to generate hyperlipidemia with increased levels of cholesterol and triglycerides that mimic the symptoms of atherosclerosis in humans. Here, we analysed IVD degeneration in the lumbar spines of ten homozygous APOE-knockout and four wild-type New Zealand White rabbits of matching age to prove accelerated IVD degeneration in APOE-knockout rabbits, since APOE-knockout rabbits could be a beneficial model for therapeutic approaches of degenerative IVD disorders. Experiments were performed using T1/T2-weighted magnetic resonance imaging, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, glucose-oxidase assay, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot. APOE-knockout lumbar spines showed more advanced IVD degeneration, obstructed lumbar arteries and lower enhancement of contrast agent in IVDs. Moreover, lower concentration of glucose, lower number of viable cells and lower concentrations of aggrecan, collagen II and higher concentration of collagen I were detected in APOE-knockout IVDs (p < 0.0001). APOE-knockout in rabbits could induce structurally deteriorating premature IVD degeneration that mimics the symptoms of accelerated IVD degeneration in humans. APOE-knockout rabbits could be used as beneficial model, as they can bypass the standard surgical interventions that are commonly applied in research animals for the induction of enhanced IVD degeneration. Their parallel use in therapeutic approaches of IVD disorders and atherosclerosis could reduce the number of research animals to be used and contribute to the principles of 3Rs (Replacement, Reduction and Refinement).
Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors

Thrombospondin is a 420,000-D glycoprotein that has recently been shown to have several properties in common with the members of a class of adhesive proteins. To characterize further the adhesive properties of thrombospondin, we have studied its ability to support cell attachment. Thrombospondin adsorbed to plastic dishes supports the attachment of human endothelial and smooth muscle cells and the monocyte-like cell line (U937) as well as normal rat kidney cells. The majority of attached cells do not spread on the solid-phase thrombospondin. The attachment of all four cell types to thrombospondin is abolished if the assay is performed in the presence of EGTA, although the cells still attach to fibronectin. If thrombospondin is adsorbed to the dishes in the presence of EGTA and then washed with buffer containing calcium before addition of the cells, attachment is still markedly inhibited, indicating that calcium affects the conformation and function of thrombospondin. Attachment of all four cell types is also markedly inhibited by the synthetic peptides gly-arg-gly-asp-ser-pro (GRG-DSP) and gly-arg-gly-asp-ala-cys (GRGDAC) but not by the control peptide gly- arg-gly-glu-ser-pro (GRG-ESP). Affinity chromatography of n- octylglucoside extracts of surface-labeled endothelial cells or smooth muscle cells on thrombospondin-Sepharose and GRG-DSP-Affigel columns was used to identify an integrin complex related to glycoprotein IIb- IIIa as an RGD-dependent receptor for thrombospondin. In addition, a monoclonal antibody (LM609) that blocks attachment of endothelial cells to vitronectin, fibrinogen, and von Willebrand factor also inhibits attachment of endothelial cells to thrombospondin. These data indicate that the attachment of cells to thrombospondin is mediated by RGD and calcium-dependent mechanisms and is consistent with the hypothesis that the GRGDAC sequence in thrombospondin is a site for interaction with an integrin receptor of the beta 3 subclass.
Young People's Experiences Of Loss And Bereavement: Towards An Interdisciplinary Approach

Evidence shows that bereavement is an issue that touches the lives of the majority of young people, and yet it is often left to the province of specialists. This timely book provides the first in-depth, interdisciplinary overview of our knowledge and theorizing of bereavement and young people including the voices of young people, as well as major statistical studies of cohorts of young people followed over many years. Taking a broad sweep across a great range of relevant literatures, this book breaks new ground in spanning theoretical issues and empirical research to examine critically what we know about this important ' but often neglected ' issue. It also features in-depth original case studies of young people who have experienced bereavement and uses these as a basis for exploring how loss and bereavement impact upon young people's lives. Young People's Experiences of Loss and Bereavement provides essential reading on issues of loss, change and bereavement for students, researchers and professionals across a wide range of health and social care disciplines, especially those involving family and youth work. * case studies and other evidence of how young people discuss their experiences of bereavement * the theoretical history of research into bereavement and young people * the empirical evidence of bereavement as a 'risk factor' in the lives of young people * the social and cultural contexts of bereavement, and approaches to education and intervention * the implications for policy makers and practitioners developing best procedures and practice for working with bereavement young people.
Singleton, Union and Intersection Types for Program Extraction

Two type theories, ATT and ATTT, are introduced. ATT is an impredicative type theory closely related to the polymorphic type theory of implicit typing of MacQueen et al. [MPS86]. ATTT is another version of ATT that extends the Girard-Reynolds second order lambda calculus. ATT has notions of intersection, union and singleton types. ATTT has a notion of refinement types as in the type system for ML by Freeman and Pfenning [FP91], plus intersection and union of refinement types and singleton refinement types. We will show how singleton, union and intersection types serve for development of programs without unnecessary codes via a variant of the Curry-Howard isomorphism. More exactly, they give a way to write types as specifications of programs without unnecessary codes which is inevitable in the usual Curry-Howard isomorphism.
The relationship between selected independent variables and the level of job satisfaction of school counselors: implications for administors and policy makers

EDUCATIONAL LEADERSHIP MCFARLANE. RENEE ADENIKE B.A. SPELMAN COLLEGE, 2002 M.A. CLARK ATLANTA UNIVERSITY, 2004 THE RELATIONSHIP BETWEEN SELECTED INDEPENDENT VARIABLES AND THE LEVEL OF JOB SATISFACTION_QESCHOOL COUNSELORS IMPLICATIONS FOR ADMINISTRATORS AND POLICY MAKERS Advisor: Dr. Trevor Turner Dissertation dated July 2010 Many school counselors have not utilized their leadership opportunities because of role ambiguity in their position which leads to job dissatisfaction. The researcher believes that until school counselors can become more satisfied in their positions they will not operate as educational leaders. The primary purpose of the study was to identify if there was significant relationship between selected independent variables (school counselor demographics, school demographics, school counselor leadership attributes, principal leadership style. teacher-school counselor relationship, parent-school counselor relationship, school counselor recognition, and school counselor role responsibilities) and the level ofjob satisfaction of school counselors in a metropolitan Atlanta school district and to further reveal how administrators and policy makers can guide school counselors 1 in contributing to and improving the legitimacy of the profession. The statistical test that was used to test the relationships as expressed in the research questions is the correlation analysis. The results of the study were analyzed to explain which independent variables have the greatest impact on school counselors’ job satisfaction. Findings from this study suggest that there is a statistically signification relationship between selected independent variables (school counselor leadership attributes, principal leadership style, teacherschool counselor relationship, parent-school counselor relationship, school counselor recognition, and school counselor role responsibilities) and job satisfaction. THE RELATIONSHIP BETWEEN SELECTED INDEPENDENT VARIABLES AND THE LEVEL OF JOB SATISFACTION OF SCHOOL COUNSELORS IMPLICATIONS FOR ADMINISTRATORS AND POLICY MAKERS
Efficient Downlink Channel Probing and Uplink Feedback in FDD Massive MIMO Systems

Massive Multiple-Input Multiple-Output (massive MIMO) is a variant of multi-user MIMO in which the number of antennas at each Base Station (BS) is very large and typically much larger than the number of users simultaneously served. Massive MIMO can be implemented with Time Division Duplexing (TDD) or Frequency Division Duplexing (FDD) operation. FDD massive MIMO systems are particularly desirable due to their implementation in current wireless networks and their efficiency in situations with symmetric traffic and delay-sensitive applications. However, implementing FDD massive MIMO systems is known to be challenging since it imposes a large feedback overhead in the Uplink (UL) to obtain channel state information for the Downlink (DL). In recent years, a considerable amount of research is dedicated to developing methods to reduce the feedback overhead in such systems. In this paper, we use the sparse spatial scattering properties of the environment to achieve this goal. The idea is to estimate the support of the continuous, frequency-invariant scattering function from UL channel observations and use this estimate to obtain the support of the DL channel vector via appropriate interpolation. We use the resulting support estimate to design an efficient DL probing and UL feedback scheme in which the feedback dimension scales proportionally with the sparsity order of DL channel vectors. Since the sparsity order is much less than the number of BS antennas in almost all practically relevant scenarios, our method incurs much less feedback overhead compared with the currently proposed methods in the literature, such as those based on compressed-sensing. We use numerical simulations to assess the performance of our probing-feedback algorithm and compare it with these methods.
Testing an autoregressive structure in binary time series models

This paper introduces a Lagrange Multiplier (LM) test for testing an autoregressive structure in a binary time series model proposed by Kauppi and Saikkonen (2008). Simulation results indicate that the two versions of the proposed LM test have reasonable size and power properties when the sample size is large. A parametric bootstrap method is suggested to obtain approximately correct sizes also in small samples. The use of the test is illustrated by an application to recession forecasting models using monthly U.S. data.
Visualization of Binding and Transcytosis of Botulinum Toxin by Human Intestinal Epithelial Cells

Botulinum toxin is an unusually potent oral poison, which means that the toxin must have an efficient mechanism for escaping the lumen of the gut to reach the general circulation. Previous work involving iodination of toxin and analysis of its movement demonstrated a specific process of transepithelial transport. In the present study, botulinum toxin labeled with Alexa Fluor 488 was used to visualize the discrete steps of binding, internalization, transcytosis, and release. The data revealed that binding sites for the toxin were distributed across the apical surface of epithelial cells, and there was no evidence of significant clustering. The amount of toxin bound to receptors at saturation was too large to be accommodated in a single wave of endocytosis. Toxin that entered epithelial cells did not remain in the vicinity of the endocytosing membrane, which is in striking contrast to events in neuronal cells. Instead, the toxin began to spread across the length of cells, eventually being released on the basolateral surface. Migration of toxin through epithelial cells required redistribution to the cell periphery. This migration pattern could be attributed to the large and centrally located nucleus, which physically displaced transport vesicles. Transcytosed toxin began to reach the contralateral surface within ca. 5 min, and transcytosis was essentially complete within 20 to 30 min.
Permeability Characteristics of Calu-3 Human Bronchial Epithelial Cells: In Vitro - In Vivo Correlation to Predict Lung Absorption in Rats

The goal of this study was to evaluate the permeability characteristics of Calu-3, human bronchial epithelial cells to passive and actively transported drugs and to correlate the data with other in vitro models and rat lung absorption in vivo. Air-interface cultured Calu-3 cells grown on collagen-coated permeable filter supports formed "tight" polarized and well differentiated cell monolayers with apical microvilli and tight-junctional complexes. Within 8-10 days, cell monolayers developed transepithelial electrical resistance (TEER)>1000 ohm cm 2 and potential difference about 11-16 mV. Solute permeability was dependent on lipophilicity, and inversely related to molecular size. Calu-3 cells actively transported amino acids, nucleosides and dipeptide analogs, but not organic anions, organic cations or efflux pump substrates. The permeability characteristics of Calu-3 cells correlated well with primary cultured rabbit tracheal epithelial cells in vitro (r 2 =0.91), and the rate of drug absorption from the rat lung in vivo (r 2 =0.94). The absorption predicted from the regression equation correlated well with observed values. In conclusion, in vitro - in vivo correlation studies indicate that the Calu-3 cell culture model is a potentially useful model to predict absorption of inhalation delivery drug candidates.
flp‐1, the first representative of a new pilin gene subfamily, is required for non‐specific adherence of Actinobacillus actinomycetemcomitans

Actinobacillus actinomycetemcomitans, a Gram‐negative bacterium responsible for localized juvenile periodontitis and other infections such as endocarditis, produces long fibrils of bundled pili that are believed to mediate non‐specific, tenacious adherence to surfaces. Previous investigations have implicated an abundant, small (≈ 6.5 kDa), fibril‐associated protein (Flp/Fap) as the primary fibril subunit. Here, we report studies on fibril structure and on the function and evolution of Flp. High‐resolution electron microscopy of adherent clinical strain CU1000N revealed long bundles of 5‐ to 7‐nm‐diameter pili, whose subunits appear to be arranged in a helical array similar to that observed for type IV pili in other bacteria. Fibrils were found to be associated with the bacterial cell surface and smaller structures thought to be membrane vesicles. A modified version of the CU1000N Flp1 polypeptide with the T7‐TAG epitope fused to its C‐terminus was expressed in the wild‐type strain, and the presence of the modified Flp1 in fibrils was confirmed by immunogold electron microscopy with monoclonal antibody to T7‐TAG. To determine the importance of Flp1 in fibril formation and cell adherence, we used transposon IS903φkan to isolate insertion mutations in the flp‐1 gene (formerly designated flp). Mutants with insertions early in flp‐1 fail to produce fibrils and do not adhere to surfaces. Both fibril production and adherence were restored by cloned flp‐1 in trans, thus providing the first evidence that flp‐1 is required for fibril formation and tight, non‐specific adherence. One mutant was found to have an insertion near the 3′ end of flp‐1 that results in the expression of a truncated and altered C‐terminus of Flp1. This mutant produced short, unbundled pili, and its adherence to surfaces was significantly less than that of wild‐type bacteria. These findings and related observations with the Flp1‐T7‐TAG protein indicate that the C‐terminus of Flp1 is important for the bundling and adherence properties of pili. Extensive sequence comparisons and phylogenetic analysis of 61 predicted prepilin genes of bacteria revealed flp‐1 to be a member of a novel and widespread subfamily of type IV prepilin genes. Thus, Flp pili are likely to be expressed by diverse bacterial species. Furthermore, we found that it is common for bacterial genomes to contain multiple alleles of flp‐like genes, including the open reading frame (flp‐2, previously designated orfA) immediately downstream of flp‐1 in A. actinomycetemcomitans. The duplication and divergence of flp genes in bacteria may be important to the diversification of the colonization properties of these organisms.