cssi/SciSciGPT-SciSciNet huggingface dataset:
Renal involvement in patients with chronic hepatitis C virus infection

There is an increasing recognition of the association between chronic hepatitis C virus (HCV) infection and glomerular diseases. Renal complications may be the presenting manifestation of HCV infection. Patients may present with systemic vasculitis secondary to cryoglobulinemia, or they may present with proteinuria, microscopic hematuria, acute renal failure, or nephrotic syndrome. The pathogenesis of HCV-associated renal disease remains incompletely understood; however, deposition of HCV-containing circulating immune complexes in the glomeruli (ie, subendothelial space and mesangium) seems to play an important role. The most common renal pathology associated with HCV infection is type I membranoproliferative glomerulonephritis with or without cryoglobulinemia. In patients who do not have significant renal impairment, combination therapy with interferon-a and ribavirin is the treatment of choice. The experience with this combination therapy is quite limited in patients with renal impairment. Prolonged courses of high-dose interferon-a therapy have been successfully used for these patients; however, relapse of HCV viremia and recurrence of renal disease is common after discontinuation of therapy.
A Handy Guide to Educate Physicians on Rational Use of Opioids for Chronic Pain

is not an overuse of figures, tables, or specialty jargon. Many of the most notable basic and clinical researchers who are on the forefront of work in these areas contributed chapters to this book. I was particularly taken by the chapter on opioids and the treatment of chronic pain written by Bennett, Squire, and Brookoff. In it, they raise important questions such as: What are clinicians trying to treat with opioids? What is it about opioids that makes them abusable? To what extent do opioids promote abuse behaviors? Given the rapidly evolving nature of these fields, some of the chapters are already dated. There are recently developed screening tools for risk of substance abuse that were not included in this volume. There is also some redundancy between chapters. Readers of this journal may be disappointed to find less attention to issues of cancer pain management than to noncancer pain. Overall, however, this is an extremely valuable book packed with practical information that will be consulted by pain clinicians, addiction specialists, and researchers. It is clearly intended as a reference book to enlighten the owner on specific topics of interest. It comes very highly recommended, and I have placed it within easy reach on my office bookshelf.
The vertical distribution of radon in the Bomex area

Measurements of the vertical distribution of222Rn in the Bomex area yield a number of important pieces of oceanographic information. They yield a gas exchange piston velocity of 700 m/yr (equivalent to a stagnant boundary layer thickness of 60 μ). They allow a limit of greater than 160 cm2/sec to be placed on the coefficient of vertical eddy diffusion in the 0 to 20 m depth zone and of less than 4 cm2/sec in the 30 to 40 m depth zone. They also provide a vertical profile of the226Ra concentration in sea water.
Retention of ellipticity between enzymatic states of the Ca2+-ATPase of sarcoplasmic reticulum

Circular dichroism spectra in the peptide region were obtained from the Ca2+-ATPase of sarcoplasmic reticulum, to establish whether transitions of intermediate states of the enzyme cycle are accompanied by large changes of secondary structure. Since membrane-bound ATPase was used to avoid denaturation, absolute estimates of secondary structural content could not be obtained, due to light scattering interference. Nevertheless, it was possible to demonstrate unambiguously that nearly constant ellipticity is retained by the enzyme following enzyme transitions produced by calcium binding or phosphorylation, even though conformational changes are revealed by other structural probes under the same conditions. We conclude that the conformational changes involved in the long-range reciprocal influence of calcium and phosphorylation sites are related to ligand-induced displacements of amino acid residues which in turn produce reorientation of whole peptide segments of the ATPase protein. This is contrasted by the behavior of calmodulin which undergoes a definite change in ellipticity upon calcium binding.
Theoretical zero‐temperature isotherm and structural phase stability of thorium dioxide

The static-lattice equation of state (EOS) and structural phase stability of Thorium Dioxide (ThO2) have been investigated for pressures up to 500 kbar using the relativistic linear combinations of Gaussian type orbitals-fitting function (LCGTO-FF) technique, within the generalized gradient approximation (GGA) to density functional theory (DFT). Two observed room temperature crystal structures for ThO2 have been considered here, the ambient fluorite structure and the high-pressure cotunnite structure. The EOS parameters calculated for the fluorite structure and the external cell parameters found for the cotunnite structure are consistent with experiment to within the known limitations of the GGA model. The internal lattice parameters obtained for the cotunnite phase differ greatly from the experimental values reported in the literature. There is strong theoretical evidence that the measured values of the internal parameters are in error. The predicted transition pressure (275 kbar) is in reasonable agreement with the measured value of 330 kbar, given the likelihood of strong metastability in this oxide. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
Role of experience and oscillations in transforming a rate code into a temporal code

In the vast majority of brain areas, the firing rates of neurons, averaged over several hundred milliseconds to several seconds, can be strongly modulated by, and provide accurate information about, properties of their inputs. This is referred to as the rate code. However, the biophysical laws of synaptic plasticity require precise timing of spikes over short timescales (<10 ms). Hence it is critical to understand the physiological mechanisms that can generate precise spike timing in vivo, and the relationship between such a temporal code and a rate code. Here we propose a mechanism by which a temporal code can be generated through an interaction between an asymmetric rate code and oscillatory inhibition. Consistent with the predictions of our model, the rate and temporal codes of hippocampal pyramidal neurons are highly correlated. Furthermore, the temporal code becomes more robust with experience. The resulting spike timing satisfies the temporal order constraints of hebbian learning. Thus, oscillations and receptive field asymmetry may have a critical role in temporal sequence learning.
Individual differences in servant leadership: the roles of values and personality

– The paper seeks to address the lack of empirical research on servant leadership by investigating relationships between servant leadership and four individual differences – values of empathy, integrity, and competence and the five‐factor model's personality factor of agreeableness., – Dennis and Winston's servant leadership scale (a revision of Page and Wong's servant leadership instrument), Braithwaite and Law's Goal and Mode Values Inventories, Mayer and Davis' integrity scale, and Costa and McCrae's NEO Five‐Factor Inventory were used with 288 followers and 126 leaders in three organizations in order to measure relationships between followers' ratings of leaders' servant leadership, followers' ratings of leaders' values of empathy, integrity, and competence and leaders' ratings of their own agreeableness., – Followers' ratings of leaders' servant leadership were positively related to followers' ratings of leaders' values of empathy, integrity, and competence. Followers' ratings of leaders' servant leadership were also positively related to leaders' ratings of their own agreeableness., – Common method bias is a potential limitation due to respondents' tendency toward consistency in responses., – Organizations embracing servant leadership may benefit from selecting leaders partly on the basis of certain personal attributes such as those investigated in the present study. Furthermore, in order to maintain a servant leadership culture and to retain leaders in a servant leadership organization, recruiters and trainers in servant leadership organizations would likely benefit from communicating accurate information about attributes valued in a servant leadership culture – e.g. attributes explored in the present research., – The study extends our understanding of servant leadership research by offering support for individual attributes related to the practice of servant leadership.
Resistance to purine and pyrimidine nucleoside and nucleobase analogs by the human MDR1 transfected murine leukemia cell line L1210/VMDRC.06

Overexpression of human MDR1 P-glycoprotein [Pgp] is associated with cellular resistance to bulky amphipathic drugs, such as taxol, anthracyclines, vinca alkaloids, and epipodophyllotoxins by actively effluxing drugs from cells. We have found that human MDR1 transfected murine L1210/VMDRC.06 leukemia cells exhibit relatively large amounts of Pgp and high levels of resistance to 6-mercaptopurine [6-MP] and other purine and pyrimidine nucleobase and nucleoside analogs. L1210/VMDRC.06 cells accumulated 6-MP as the nucleotide in vitro at only about one-third of that formed by parental L1210 cells in normal medium; however, under conditions of ATP-depletion, the amount of 6-MP nucleotide formed was essentially the same in both cell lines. The findings support active efflux of 6-MP in L1210 cells, suggesting involvement of Pgp in 6-MP resistance even though it is generally believed that Pgp does not transport such agents. The resistance pattern observed in L1210/VMDRC.06 cells was not duplicated in P388/VMDRC.04 leukemia cells transfected with the same MDR1 cDNA, even though a similar amount of Pgp was present in both cell lines. Immunofluorescent staining of surface membrane Pgp showed that L1210/VMDRC.06 cells contained at least three-fold more surface Pgp than P388/VMDRC.04, implying that P388/VMDRC.04 cells are unable to actively efflux 6-MP and other antimetabolites as effectively as L1210/VMDRC.06, because of significantly lower membrane Pgp. The findings suggest that the exceedingly large concentration of overexpressed Pgp in the surface membrane of L1210/MDRC.06 cells is responsible for resistance to 6-MP and other purine and pyrimidine analogs, even though these agents usually are not considered to be substrates for Pgp.
Insulin regulates retinol dehydrogenase expression and all-trans-retinoic acid biosynthesis through FoxO1

All-trans-retinoic acid (atRA), an autacoid derived from retinol (vitamin A), regulates energy balance and reduces adiposity. We show that energy status regulates atRA biosynthesis at the rate-limiting step, catalyzed by retinol dehydrogenases (RDH). Six h after re-feeding, Rdh1 expression decreased 80–90% in liver and brown adipose tissue and Rdh10 expression was decreased 45–63% in liver, pancreas, and kidney, all relative to mice fasted 16 h. atRA in the liver was decreased 44% 3 h after reduced Rdh expression. Oral gavage with glucose or injection with insulin decreased Rdh1 and Rdh10 mRNA 50% or greater in mouse liver. Removing serum from the medium of the human hepatoma cell line HepG2 increased Rdh10 and Rdh16 (human Rdh1 ortholog) mRNA expression 2–3-fold by 4 h, by increasing transcription and stabilizing mRNA. Insulin decreased Rdh10 and Rdh16 mRNA in HepG2 cells incubated in serum-free medium by inhibiting transcription and destabilizing mRNA. Insulin action required PI3K and Akt, which suppress FoxO1. Serum removal increased atRA biosynthesis 4-fold from retinol in HepG2 cells, whereas dominant-negative FoxO1 prevented the increase. Thus, energy status via insulin and FoxO1 regulate Rdh expression and atRA biosynthesis. These results reveal mechanisms for regulating atRA biosynthesis and the opposing effects of atRA and insulin on gluconeogenesis, and also suggest an interaction between atRA and insulin signaling related diseases, such as type II diabetes and cancer.
Sensitivity Theory and Its Application to a Large Energy-Economics Model

This paper discusses a nonlinear equation theory of sensitivity analysis and demonstrates its applicability to a large energy-economics model by applying it to a specific calculation carried out with the Long-Term Energy Analysis Program LEAP. It presents numerical results for calculating derivatives of two results of interest with respect to several values of the underlying data elements for which the derivatives are appreciable. In a number of cases, the accuracy of the derivative information obtained has been verified by direct calculations and these comparisons are also presented. The theory used here is, in principle, applicable to a variety of models. It is most useful when applied to models that contain a very large number of data elements.
Rectus sheath hematoma complicating low-molecular weight heparin therapy

Rectus sheath hematoma (RSH) is an uncommon but serious bleeding complication of anticoagulant therapy that has received little attention in the literature. Two cases of RSH among recent admissions to an inpatient medicine service and four archival cases were reviewed. All six patients were on low-molecular weight heparin (LMWH) therapy. Five of the six patients had a creatinine clearance of 40 ml/min or less, and five also had cough. Two patients with the most serious outcome were aged 90 and 92 years. RSH complicating LMWH therapy appears to constitute a clinical syndrome consisting of sudden onset of abdominal pain in the setting of renal insufficiency, advanced age and abdominal straining (e.g. cough). Risk of RSH may be reduced in patients receiving LMWH by assessing renal function, monitoring heparin levels (e.g. when the creatinine clearance is 40 ml/min or less) and adjusting the dose accordingly; by avoidance of abdominal strain (e.g. by treating cough); and by attention to technique when the abdominal wall is used as the injection site. Patients of advanced age may be at particular risk for RSH.
Interrogating Cultural Diversity: Inquiry and Action.

There are no monolithic solutions to the complex and often unique problems of understanding and responding to the increasing cultural diversity in schools and classrooms in the United States. Prese...
Development of a self-emulsifying formulation that reduces the food effect for torcetrapib.

Abstract Torcetrapib is a highly lipophilic ( C log P = 7.45) and water insoluble cholesteryl ester transfer protein (CETP) inhibitor developed for the treatment of atherosclerosis. Self-emulsifying drug delivery system (SEDDS) formulations have been developed to reduce the food effect observed in early clinical trials using medium chain triglyceride (MCT) softgels and to increase the dose per capsule. MCT/Triacetin/Polysorbate 80/Capmul MCM (20/30/20/30) (MTPC) increased fasted exposure and thus reduced the food effect from 5- to 3-fold in dogs at a dose of 90 mg. Self-emulsifying formulations also accelerated absorption and generally decreased variability. Use of the lipophilic, GRAS cosolvent triacetin allowed a 2-fold increase in the dose per capsule. For the three formulations evaluated in dogs that showed significant differences in absorption, emulsion droplet size did not appear to play a significant role. Absorption did increase with Cremophor RH40 content, and at 50% Cremophor RH40 there was no food effect (at 30 mg). High polar surfactant content also resulted in poor dose proportionality, while there was good dose proportionality for MTPC. Studies of in vitro lipolysis are being conducted to aid in understanding the in vitro/in vivo relationships for torcetrapib SEDDS absorption.
Staking out the successful student

With the performance of students, teachers, and schools defining success under current standards-based accountability policies (e.g. Chicago Public Schools (Note 1); No Child Left Behind Act, (United States Department of Education, 2002)), school districts are implementing various forms of intervention programs as a means to improve student performance. By examining a pilot summer school program that is transitioning from a ‘low-stakes’ to a ‘high -stakes’ intervention program, this article examines the possibilities that exist for students to author themselves as learners, and it questions whether opportunities for students to identify themselves as successful learners are lost when an intervention program, such as summer school, becomes mandatory. The implications of this analysis highlight questions and concerns that policymakers and school personnel need to address when formulating high-stakes standardsbased accountability policies and intervention programs.
Cognitive fusion analysis based on context

The standard fusion model includes active and passive user interaction in level 5 - “User Refinement”. User refinement is more than just details of passive automation partitioning - it is the active management of information. While a fusion system can explore many operational conditions over myopic changes, the user has the ability to reason about the hyperopic “big picture.” Blasch and Plano developed cognitive-fusion models that address user constraints including: intent, attention, trust, workload, and throughput to facilitate hyperopic analysis. To enhance user-fusion performance modeling (i.e. confidence, timeliness, and accuracy); we seek to explore the nature of context. Context, the interrelated conditions of which something exists, can be modeled in many ways including geographic, sensor, object, and environmental conditioning. This paper highlights user refinement actions based on context to constrain the fusion analysis for accurately representing the trade space in the real world. As an example, we explore a target identification task in which contextual information from the user’s cognitive model is imparted to a fusion belief filter.
Regulation of Gene Expression in Plants through miRNA Inactivation

Eukaryotic organisms possess a complex RNA-directed gene expression regulatory network allowing the production of unique gene expression patterns. A recent addition to the repertoire of RNA-based gene regulation is miRNA target decoys, endogenous RNA that can negatively regulate miRNA activity. miRNA decoys have been shown to be a valuable tool for understanding the function of several miRNA families in plants and invertebrates. Engineering and precise manipulation of an endogenous RNA regulatory network through modification of miRNA activity also affords a significant opportunity to achieve a desired outcome of enhanced plant development or response to environmental stresses. Here we report that expression of miRNA decoys as single or heteromeric non-cleavable microRNA (miRNA) sites embedded in either non-protein-coding or within the 3′ untranslated region of protein-coding transcripts can regulate the expression of one or more miRNA targets. By altering the sequence of the miRNA decoy sites, we were able to attenuate miRNA inactivation, which allowed for fine regulation of native miRNA targets and the production of a desirable range of plant phenotypes. Thus, our results demonstrate miRNA decoys are a flexible and robust tool, not only for studying miRNA function, but also for targeted engineering of gene expression in plants. Computational analysis of the Arabidopsis transcriptome revealed a number of potential miRNA decoys, suggesting that endogenous decoys may have an important role in natural modulation of expression in plants.
High-Resolution Gamma-Ray Spectrometers using Bulk Absorbers Coupled to Mo/Cu Multilayer Superconducting Transition-Edge Sensors

In x-ray and gamma-ray spectroscopy, it is desirable to have detectors with high energy resolution and high absorption efficiency. At LLNL, we have developed superconducting tunnel junction-based single photon x-ray detectors with thin film absorbers that have achieved these goals for photon energies up to 1 keV. However, for energies above 1 keV, the absorption efficiency of these thin-film detectors decreases drastically. We are developing the use of high-purity superconducting bulk materials as microcalorimeter absorbers for high-energy x-rays and gamma rays. The increase in absorber temperature due to incident photons is sensed by a superconducting transition-edge sensor (TES) composed of a Mo/Cu multilayer thin film. Films of Mo and Cu are mutually insoluble and therefore very stable and can be annealed. The multilayer structure allows scaling in thickness to optimize heat capacity and normal state resistance. We measured an energy resolution of 70 eV for 60 keV incident gamma-rays with a 1 x 1 x 0.25 mm{sup 3} Sn absorber. We present x-ray and gamma-ray results from this detector design with a Sn absorber. We also propose the use of an active negative feedback voltage bias to improve the performance of our detector and show preliminary results.
A hybrid Newton-type method for censored survival data using double weights in linear models

As an alternative to the Cox model, the rank-based estimating method for censored survival data has been studied extensively since it was proposed by Tsiatis [Tsiatis AA (1990) Ann Stat 18:354–372] among others. Due to the discontinuity feature of the estimating function, a significant amount of work in the literature has been focused on numerical issues. In this article, we consider the computational aspects of a family of doubly weighted rank-based estimating functions. This family is rich enough to include both estimating functions of Tsiatis (1990) for the randomly observed data and of Nan et al. [Nan B, Yu M, Kalbfleisch JD (2006) Biometrika (to appear)] for the case-cohort data as special examples. The latter belongs to the biased sampling problems. We show that the doubly weighted rank-based discontinuous estimating functions are monotone, a property established for the randomly observed data in the literature, when the generalized Gehan-type weights are used. Though the estimating problem can be formulated to a linear programming problem as that for the randomly observed data, due to its easily uncontrollable large scale even for a moderate sample size, we instead propose a Newton-type iterated method to search for an approximate solution of the (system of) discontinuous monotone estimating equation(s). Simulation results provide a good demonstration of the proposed method. We also apply our method to a real data example.
The digital production gap: The digital divide and Web 2.0 collide

Abstract How does class intersect with claims of digital democracy? Most digital inequality research focuses on digital consumption or participation, but this study uses a production lens to examine who is creating digital content for the public sphere. My results point to a class-based gap among producers of online content. A critical mechanism of this inequality is control of digital tools and an elite Internet-in-practice and information habitus to use the Internet. Using survey data of American adults, I apply a logit analysis of 10 production activities—from Web sites and blogs to discussion forums and social media sites. Even among people who are already online, a digital production gap challenges theories that the Internet creates an egalitarian public sphere. Instead, digital production inequality suggests that elite voices still dominate in the new digital commons.
Conformational Changes and Stabilization of Inosine 5′-Monophosphate Dehydrogenase Associated with Ligand Binding and Inhibition by Mycophenolic Acid

The effects of substrate, product, and inhibitor (mycophenolic acid) binding on the conformation and stability of hamster type II inosine 5'-monophosphate dehydrogenase (IMPDH) have been examined. The protein in various states of ligand occupancy was compared by analyzing susceptibility to in vitro proteolysis, the degree of binding of a hydrophobic fluorescent dye, secondary structure content as determined by far-UV circular dichroism spectra, and urea-induced denaturation curves. These analysis methods revealed consistent evidence that IMPDH undergoes a local reorganization when IMP or XMP bind. NAD+ produced no such effect. In fact, no evidence was found for NAD+ binding independently of IMP. It is proposed that IMPDH adopts an open conformation around its nucleotide binding sites in the absence of substrates and that binding of IMP stabilizes a closed conformation that has a higher affinity for NAD+. The data also suggest the enzyme remains in the closed configuration throughout the catalytic steps and then reverts to the open conformation with XMP release, thereby consummating the enzyme cycle. Mycophenolic acid inhibition appeared to impart even greater stability. We propose that localized conformational changes occur during the normal and mycophenolic acid-inhibited reaction sequences of IMPDH.
Initial study on the predictability of real power on the grid based on PMU data

Operations on the electric power grid provide highly reliable power to the end users. These operations involve hundreds of human operators and automated control schemes. However, the operations process can often take several minutes to complete. During these several minutes, the operations are often evaluated on a past state of the power system. Proper prediction methods could change this to make the operations evaluate the state of the power grid minutes in advance. Such information allows proactive, rather than reactive, actions on the power system and aids in improving the efficiency and reliability of the power grid as a whole. A successful demonstration of this prediction framework is necessary to evaluate the feasibility of utilizing such predicted states in grid operations.
A quantifiable biochemical marker for cold shock damage to porcine sperm

s / Theriogenology 578 10% FBS, 10% DMSO, and 0.07 M sucrose; (B) DMEM with 10% FBS and 10% DMSO; and (C) FBS with 10% DMSO. The vials were held at 80 8C for 24 h, and then transferred to liquid nitrogen ( 196 8C). After 3 weeks, cells were thawed in a water bath at 38 8C for 2 min. After adding 2 mL of DMEM with 10% FBS, cells were centrifuged and resuspended to 0.5 mL in DMEM with 1% BSA. Cell viability was assessed by Trypan blue exclusion immediately after isolation (L0), before adding the freezing medium (L1), and after freezing and thawing (L2). Survival rate (S) was defined as L2/L1 100. The effect of treatment on L2 or S was evaluated using one-way ANOVA. Cell viability after isolation, culture, and freezing and thawing (L0, L1 and L2) was compared using ANOVA for repeated measurements (SAS Institute Inc., Cary, NC). There was no effect of treatment on L2 or S. Overall mean values ( S.D.) of L0, L1 and L2 were 99.1 1.9, 78.5 14.9 and 67.8 20.5%, respectively (P < 0.05). Overall survival rate was 86.4 21.5%. We concluded that the three freezing media tested were equally suited for freezing equine testicular cells. Enzymatic digestion yielded a cell suspension with excellent viability, which decreased after incubation and cryopreservation. Freezing equine testicular cells immediately after isolation may result in better postthaw viability. However, functional assays are still required to positively identify SSCs among testicular cells, and to determine the ability of this cell population to survive freezing and thawing.
Detection of anomalous insiders in collaborative environments via relational analysis of access logs

Collaborative information systems (CIS) are deployed within a diverse array of environments, ranging from the Internet to intelligence agencies to healthcare. It is increasingly the case that such systems are applied to manage sensitive information, making them targets for malicious insiders. While sophisticated security mechanisms have been developed to detect insider threats in various file systems, they are neither designed to model nor to monitor collaborative environments in which users function in dynamic teams with complex behavior. In this paper, we introduce a community-based anomaly detection system (CADS), an unsupervised learning framework to detect insider threats based on information recorded in the access logs of collaborative environments. CADS is based on the observation that typical users tend to form community structures, such that users with low affinity to such communities are indicative of anomalous and potentially illicit behavior. The model consists of two primary components: relational pattern extraction and anomaly detection. For relational pattern extraction, CADS infers community structures from CIS access logs, and subsequently derives communities, which serve as the CADS pattern core. CADS then uses a formal statistical model to measure the deviation of users from the inferred communities to predict which users are anomalies. To empirically evaluate the threat detection model, we perform an analysis with six months of access logs from a real electronic health record system in a large medical center, as well as a publicly available dataset for replication purposes. The results illustrate that CADS can distinguish simulated anomalous users in the context of real user behavior with a high degree of certainty and with significant performance gains in comparison to several competing anomaly detection models.
A double-blind, randomized comparison of IV lorazepam versus midazolam for Sedation of ICU patients via a pharmacologic model

Background: Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients. Methods: With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12‐72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling. Results: A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > ss) 5 50%) values for midazolam (sedation score [SS] > n, where n 5 a Ramsay Sedation Score of 2, 3 ,...6 )were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS 5 3) and deep (SS 5 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively. Conclusions: The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.
From business reengineering to business process change management: a longitudinal study of trends and practices

Business process reengineering has been prominently discussed and implemented in a large number of firms around the world. While the notion of radical change is intuitively appealing to "fix" organizational woes, it has not always met with the degree of success originally claimed by its many proponents. This article studies the evolution of the reengineering concept and its evolution toward the broader notion of process change management. Reported here are the results of two studies that explore reengineering from a project implementation perspective and an organizational perspective at two different points in time. The results show remarkable consistency in the importance of nontechnology management issues concerning strategy, change and people. Further, the notion of continuous change seems to be becoming,more important. The study provides a foundation for identifying key variables that can be studied in order to effectively manage this multifaceted phenomenon.
The roles of turn formation and cross‐strand interactions in fibrillization of peptides derived from the OspA single‐layer β‐sheet

We previously demonstrated that a β-hairpin peptide, termed BH9–10, derived from a single-layer β-sheet of Borrelia OspA protein, formed a native-like β-turn in trifluoroethanol (TFE) solution, and it assembled into amyloid-like fibrils at higher TFE concentrations. This peptide is highly charged, and fibrillization of such a hydrophilic peptide is quite unusual. In this study, we designed a circularly permutated peptide of BH9–10, termed BH10–9. When folded into their respective β-hairpin structures found in OspA, these peptides would have identical cross-strand interactions but different turns connecting the strands. NMR study revealed that BH10–9 had little propensity to form a turn structure both in aqueous and TFE solutions. At higher TFE concentration, BH10–9 precipitated with a concomitant α-to-β conformational conversion, in a similar manner to the BH9–10 fibrillization. However, the BH10–9 precipitates were nonfibrillar aggregation. The precipitation kinetics of BH10–9 was exponential, consistent with a first-order molecular assembly reaction, while the fibrillization of BH9–10 showed sigmoidal kinetics, indicative of a two-step reaction consisting of nucleation and molecular assembly. The correlation between native-like turn formation and fibrillization of our peptide system strongly suggests that BH9–10 adopts a native-like β-hairpin conformation in the fibrils. Remarkably, seeding with the preformed BH10–9 precipitates changed the two-step BH9–10 fibrillization to a one-step molecular assembly reaction, and disrupted the BH9–10 fibril structure, indicating interactions between the BH10–9 aggregates and the BH9–10 peptide. Our results suggest that, in these peptides, cross-strand interactions are the driving force for molecular assembly, and turn formation limits modes of peptide assembly.
Dataflow anomaly detection

Beginning with the work of Forrest et al, several researchers have developed intrusion detection techniques based on modeling program behaviors in terms of system calls. A weakness of these techniques is that they focus on control flows involving system calls, but not their arguments. This weakness makes them susceptible to several classes of attacks, including attacks on security-critical data, race-condition and symbolic link attacks, and mimicry attacks. To address this weakness, we develop a new approach for learning dataflow behaviors of programs. The novelty in our approach, as compared to previous system-call argument learning techniques, is that it learns temporal properties involving the arguments of different system calls, thus capturing the flow of security-sensitive data through the program. An interesting aspect of our technique is that it can be uniformly layered on top of most existing control-flow models, and can leverage control-flow contexts to significantly increase the precision of dataflows captured by the model. This contrasts with previous system-call argument learning techniques that did not leverage control-flow information, and moreover, were focused on learning statistical properties of individual system call arguments. Through experiments, we show that temporal properties enable detection of many attacks that aren't detected by previous approaches. Moreover, they support formal reasoning about security assurances that can be provided when a program follows its dataflow behavior model, e.g., tar would read only files located within a directory specified as a command-line argument.
Central Neurofibromas in Two Dogs

Two dogs each had a fibrous tumor of the central nervous system. One tumor involved the spinal cord and ventral nerve root, and the other involved the midbrain and posterior brain stem. Both tumors had spindle-shaped cells arranged in rhythmic patterns. There was perivascular tumor cell infiltration in the adjacent parenchyma. The tumor cells strongly resembled fibroblasts and seemed to produce collagen. Because both tumors were near nerve roots and because their histological appearances were characteristic of nerve sheath tumors they were classified as central neurofibromas. Collagen producing tumors in the central nervous system mostly are confined to neoplasms of the meninges and associated structures (7, 231. True fibromas of the brain and spinal cord are rare. A recent review of the literature lists only 13 such cases in man, (13) and the existence of such tumors in animals is doubtful (7, 151. This paper reports two fibroblastic tumors that were confined mainly to the central nervous system in dogs. Case Histories Dog 1 A 3'h-year-old mixed breed dog had a 3-week history of progressive right forelimb lameness. The dog was bright and alert and walked with a crouched, hypometric gait in both front limbs. Postural reactions were depressed in both front limbs, especially the right. The segmental spinal myotatic reflexes were exaggerated in all limbs. The results of hematology, blood chemistry and cerebrospinal fluid examination were within normal limits. Myelogra- phy showed spinal cord enlargement between C6 and T1, which suggested there was an intradural space-occupying mass. At C7 the diameter of the cord was greatest and filling defects were noted dorsally and ventrally. The dog was killed and necropsied. Dog 2
Effects of dopamine and serotonin on concentrations of luteinizing hormone and estradiol-17 beta in plasma of cycling ewes.

Effects of 0, 0.66 and 6.6 micrograms/kg per min of dopamine (DA) and of 0, 0.06 and 0.66 micrograms/kg per min of serotonin (5-HT) on secretion of luteinizing hormone (LH), estradiol-17 beta and progesterone were examined in ewes during luteal regression and the follicular phase. Onset of luteolysis was synchronized with two injections of 7.5 mg prostaglandin F2 alpha (PGF2 alpha) (i.m.) given 3 h apart in ewes which were 12-14 days postestrus. Ewes were infused intravenously with DA, 5-HT or a combination of DA and 5-HT for a 60-h period beginning at the time of the first PGF2 alpha injection. Neither DA nor 5-HT influenced the decrease in plasma concentrations of progesterone following PGF2 alpha. Effects of DA and 5-HT on tonic secretion of LH changed during the infusion. During the first 12 h, increasing doses of DA depressed and increasing doses of 5-HT increased mean concentrations of LH in plasma in a linear manner (DA, P less than 0.01; 5-HT, P less than 0.05). Between 16 and 34 h, 6.6 micrograms/kg per min of DA continued to suppress LH, however, 5-HT was no longer stimulatory to secretion of LH. DA was unable to inhibit secretion of LH after 40 h. Also, between 0 and 34 h, concentrations of estradiol-17 beta in plasma were decreased by infusion of DA (P less than 0.01). Interval from PGF2 alpha to onset of the preovulatory surge of LH, magnitude of the surge and duration of the surge were not altered by infusion of either DA or 5-HT.
Microwave oven application in the extraction of fat from the subcutaneous tissue of Iberian pig ham

The fat from subcutaneous tissue samples of Iberian pigs was extracted by solvent (2:1 chloroform-methanol) and by the action of microwave energy. The samples of liquid fat obtained by both extraction techniques were analysed by gas chromatography. Paired comparisons showed no significant differences in fatty acids in suggesting that the fat obtained by the two techniques was the same and that the extraction of fatty acids by microwaves is suitable for quality classification of Iberian pig carcasses.
Digestive Tract Clearance of Broilers Cooped or Deprived of Water

Abstract Feed is withdrawn from broilers to facilitate digestive tract clearance before processing. This research examined the effects of cooping and water deprivation on contents of the digestive tract during feed withdrawal in two experiments. Broilers were reared to 48 days of age on litter in a windowless house. Corn-soybean meal diets and water were provided ad libitum. In the first experiment, broilers were continuously fed before feed withdrawal. In the second experiment, broilers were placed on a meal-feeding regimen of 1.5 h on feed and 4.5 h off feed for 42 h prior to feed withdrawal. Withdrawal began at the end of a 1.5-h feeding period. At the time of feed withdrawal, broilers were cooped, left on litter without water, or left on litter with water available. At 2, 4, 6, and 8 h after withdrawal, ten broilers from each treatment were killed and the crop, proventriculus plus gizzard, and small intestine were removed. The weight of the contents of each segment was determined. Water deprivation did not change the weight of contents in any segment. Cooped broilers retained digesta in the crop and proventriculus plus gizzard for a longer time than broilers on litter. The combination of meal feeding and cooping soon after feed withdrawal greatly increased the quantity of digesta in the crop 8 h after feed withdrawal. Cooping should be delayed until the crop is empty. Meal feeding increases the time required to accomplish this.
HTSMA: A Hybrid Temporal-Spatial Multi-Channel Assignment Scheme in Heterogeneous Wireless Mesh Networks

A number of multi-channel assignment schemes have recently been proposed to improve the throughput of IEEE 802.11-based multi-hop wireless mesh networks (WMNs). In these schemes, channel coordination is done either through time synchronization across all the hosts, or through the use of a dedicated channel for the transmission of necessary control messages. Either way, excessive system overhead and/or waste of bandwidth resource become unavoidable, undermining the overall network throughput. To maximize the network throughput, we propose a synchronization-free, hybrid temporal-spatial multi-channel assignment scheme in a random heterogeneous network requiring only a single radio interface per host. In this scheme, the gateway is allowed to use all the available channels sequentially in a round-robin fashion. This temporal channel assignment approach ensures that all the neighboring hosts that communicate with the gateway directly shall have a fair access to the gateway. The channel assignment for the remaining wireless hosts is based on the geographical location and channel availability (a spatial approach) to avoid the interference within the communication region of each sender host in its transmission time period. Compared with another multi-channel scheme MMAC, extensive simulation results demonstrate that our proposed scheme can improve the network throughput substantially with the acceptable collision ratio.
A recent drilling program to investigate radionuclide migration at the Nevada Test Site

Recent drilling affords new opportunities to investigate the occurrence, distribution and transport of radionuclides in the unsaturated and saturated zone at the Nevada Test Site (NTS), Nye County, Nevada. This program is unique becmise of the elevated activities of radionuclides encountered during drilling (> 3.7E+6 Bq/L 3H), extreme completion depths (> 950 m), the expense of constructing new wells (> $IE+6/borehole), and collaboration of government, academic, and industrial partners in the planning and execution of the program. The recent chilling is significant because it substantively augments earlier field of radionuclide migration at NTS, most notably the 1974 CAMBRIC RNM experiment Sites of five nuclear tests fired below or adjacent to the saturated zone have been drilled. Three of the events were fired in Yucca Flat which is a hydrologically closed basin and two were fired in fractured volcanics of Pahute Mesa. Results from Yucca Flat indicate that volatile and refractory radionuclides, fractionated at zero time, we not highly mobile under sawmted conditions. In contrast, borcholes completed on Pahute Mesa indicate Wgh concentrations of tritium (> 3.7E+6 Bq/L 3H) and other radionuclides may be rted more than 300 m from event cavities as dissolved species or as colloids.
A putative ATP-binding protein from the che/fla locus of Bacillus subtilis

A majority of the chemotaxis and flagellar genes of Bacillus subtilis are found in the major che/fla operon which spans over 26 kilobases of DNA and encodes at least 30 genes. In this operon, a single open reading frame, designated orf298, has been demonstrated to encode a 33,131 Dalton protein which shows no evidence of being involved in chemotaxis or motility. A strain disrupted in orf298 was assayed for motility and chemotaxis and always behaved as the wild-type strain. Inspection of the translated sequence revealed a consensus ATP-binding region. While the role of ORF298 has not yet been determined, ATP-binding and/or hydrolysis is a likely function.
A robust all-atom model for LCAT generated by homology modeling.

LCAT is activated by apoA-I to form cholesteryl ester. We combined two structures, phospholipase A2 (PLA2) that hydrolyzes the ester bond at the sn-2 position of oxidized (short) acyl chains of phospholipid, and bacteriophage tubulin PhuZ, as C- and N-terminal templates, respectively, to create a novel homology model for human LCAT. The juxtaposition of multiple structural motifs matching experimental data is compelling evidence for the general correctness of many features of the model: i) The N-terminal 10 residues of the model, required for LCAT activity, extend the hydrophobic binding trough for the sn-2 chain 15–20 A relative to PLA2. ii) The topography of the trough places the ester bond of the sn-2 chain less than 5 A from the hydroxyl of the catalytic nucleophile, S181. iii) A β-hairpin resembling a lipase lid separates S181 from solvent. iv) S181 interacts with three functionally critical residues: E149, that regulates sn-2 chain specificity, and K128 and R147, whose mutations cause LCAT deficiency. Because the model provides a novel explanation for the complicated thermodynamic problem of the transfer of hydrophobic substrates from HDL to the catalytic triad of LCAT, it is an important step toward understanding the antiatherogenic role of HDL in reverse cholesterol transport.
Time evolution of lubricant-slider dynamic interactions

This paper presents time evolution studies of slider dynamics as a result of lubricant-slider interaction. Lubricant moguls and ripples are observed to form and they change in frequency and amplitude, following the slider dynamics. The slider motion and lubricant thickness modulation appear to build on each other. Eventually when enough lubricant is lost, mogul and ripple amplitudes decrease and the slider dynamics stabilizes.