cssi/SciSciGPT-SciSciNet huggingface dataset:
Multicentric Castleman’s Disease of the Central Nervous System

Castleman’s disease (CD) is defined as a non-neoplastic reactive proliferation of lymphoid tissue, also known as angiofollicular lymph node hyperplasia and giant lymph node hyperplasia. Initial identification of this eponymous disease dates back to 1956 [1]. Two distinct histological classifications are described extensively in the literature: hyaline-vascular and plasma cell types [2]. However, remarkable advances have been made in the characterization of CD, including the most recent elaboration of human herpes virus-8 (HHV-8)-related CD [3]. Hyaline-vascular CD is more common than the plasma cell type and usually presents as localized or unicentric disease involving one or several lymph node aggregates. Perhaps the most well recognized manifestation of localized CD presents with avidly enhancing mediastinal adenopathy. Despite what the histology implies, extranodal CD has been documented in multiple locations. In rare instances, extranodal disease may affect the central nervous system (CNS) and bears a remarkably similar appearance to meningioma, both clinically and using various imaging methods (e.g. magnetic resonance imaging and arteriography, [4–10]). In this article a follow-up discourse of a case of intracranial CD is presented which will be a unique addition to the literature [11]. This is the first case of intracranial CD which has been evaluated using an advanced imaging technique, dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI). The goals are two-fold: first to chronicle the initial surgical resection of localized CD of the CNS and to remark on what was strongly felt to represented recurrent perineural spread of the disease in a separate, noncontiguous location; second it is hoped that the role that perfusion MRI may play in characterizing intracranial CD will be illuminated, as the inherent limitations of conventional imaging prevent adequate differentiation between CD of the CNS and more commonly encountered extra-axial lesions (e.g. meningioma).
Abstract P100: Kidney Health and Sudden Death Risk: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort

Objective: Chronic kidney disease (CKD) is a known risk factor for sudden death (SD). Recent improvements in the detection and classification of kidney disease using creatinine and cystatin C-based estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) have identified individuals with mild forms of kidney dysfunction who are at risk for adverse events. A comprehensive assessment of SD incidence across the spectrum of kidney health in a racially diverse population has not been performed. Methods: The study was a prospective, longitudinal analysis among 27,296 participants ≥ 45 years (54% women, 40% Black) from across the continental US enrolled in the REGARDS study. Serum cystatin C and creatinine and urine albumin and creatinine were measured at baseline. SD was defined as sudden pulselessness from a presumed cardiac origin that occurred out of hospital or in the emergency room in a previously stable individual without other clear precipitating cause. Associations between estimated glomerular filtration rate (eGFR), derived from serum creatinine-cystatin C CKD-EPI, and urine albumin to creatinine ratio (UACR) and SD were estimated. RESULTS: Over a mean follow-up of 5.8 ± 1.9 years, there were 335 SD. The annual incidence of SD increased across eGFR and ACR categories (from 1.2 to 5.2 per 1000-person years). Both eGFR and ACR were independently and additively associated with graded increases in SD risk after adjustment for sociodemographics, total cholesterol, HDL, statin use, blood pressure, anti-hypertensive medication, smoking, and heart failure (Table). Participants with mild decreases in eGFR (60-90 ml/min/1.73m2) combined with mild elevations in UACR (15-30 mg/g) were at significantly increased SD risk, and UACR Conclusion: Sensitive measures of eGFR and ACR provide a gradient of SD risk across the spectrum of kidney health.
A human IgM signals axon outgrowth: coupling lipid raft to microtubules

Mouse and human IgMs support neurite extension from primary cerebellar granule neurons. In this study using primary hippocampal and cortical neurons, we demonstrate that a recombinant human IgM, rHIgM12, promotes axon outgrowth by coupling membrane domains (lipid rafts) to microtubules. rHIgM12 binds to the surface of neuron and induces clustering of cholesterol and ganglioside GM1. After cell binding and membrane fractionation, rHIgM12 gets segregated into two pools, one associated with lipid raft fractions and the other with the detergent-insoluble cytoskeleton-containing pellet. Membrane-bound rHIgM12 co-localized with microtubules and co-immuno precipitated with β3-tubulin. rHIgM12-membrane interaction also enhanced the tyrosination of α-tubulin indicating a stabilization of new neurites. When presented as a substrate, rHIgM12 induced axon outgrowth from primary neurons. We now demonstrate that a recombinant human mAb can induce signals in neurons that regulate membrane lipids and microtubule dynamics required for axon extension. We propose that the pentameric structure of the IgM is critical to cross-link membrane lipids and proteins resulting in signaling cascades.
Temporal Broadening Of Femtosecond High Harmonic Radiation

Measurement of femtosecond high harmonic radiation indicates that significant pulse shortening can be accomplished by limiting the transverse intensity variation of the generating laser pulse.
Profiling alternatively spliced mRNA isoforms for prostate cancer classification

Prostate cancer is one of the leading causes of cancer illness and death among men in the United States and world wide. There is an urgent need to discover good biomarkers for early clinical diagnosis and treatment. Previously, we developed an exon-junction microarray-based assay and profiled 1532 mRNA splice isoforms from 364 potential prostate cancer related genes in 38 prostate tissues. Here, we investigate the advantage of using splice isoforms, which couple transcriptional and splicing regulation, for cancer classification. As many as 464 splice isoforms from more than 200 genes are differentially regulated in tumors at a false discovery rate (FDR) of 0.05. Remarkably, about 30% of genes have isoforms that are called significant but do not exhibit differential expression at the overall mRNA level. A support vector machine (SVM) classifier trained on 128 signature isoforms can correctly predict 92% of the cases, which outperforms the classifier using overall mRNA abundance by about 5%. It is also observed that the classification performance can be improved using multivariate variable selection methods, which take correlation among variables into account. These results demonstrate that profiling of splice isoforms is able to provide unique and important information which cannot be detected by conventional microarrays.
Arsenic speciation, and arsenic and phosphate distribution in arsenic hyperaccumulator Pteris vittata L. and non-hyperaccumulator Pteris ensiformis L.

This study examined the roles of arsenic translocation and reduction, and P distribution in arsenic detoxification of Pteris vittata L. (Chinese Brake fern), an arsenic hyperaccumulator and Pteris ensiformis L. (Slender Brake fern), a non-arsenic hyperaccumulator. After growing in 20% Hoagland solution containing 0, 133 or 267 μM of sodium arsenate for 1, 5 or 10 d, the plants were separated into fronds, rhizomes, and roots. They were analyzed for biomass, and concentrations of arsenate (AsV), arsenite (AsIII) and phosphorus. Arsenic in the fronds of P. vittata was up to 20 times greater than that of P. ensiformis, yet showing no toxicity symptoms as did in P. ensiformis. While arsenic was concentrated primarily in the fronds of P. vittata as arsenite it was mainly concentrated in the roots of P. ensiformis as arsenate. Arsenic reduction in the plants took longer than 1-d. P. vittata maintained greater P in the roots while P. ensiformis in the fronds. The high arsenic tolerance of the hyperaccumulator P. vittata may be attributed to its ability to effectively reduce arsenate to arsenite in the fronds, translocate arsenic from the roots to fronds, and maintain a greater ratio of P/As in the roots.
Visualizing brand associations from web community photos

Brand Associations, one of central concepts in marketing, describe customers' top-of-mind attitudes or feelings toward a brand. Thus, this consumer-driven brand equity often attains the grounds for purchasing products or services of the brand. Traditionally, brand associations are measured by analyzing the text data from consumers' responses to the survey or their online conversation logs. In this paper, we propose to go beyond text data and leverage large-scale online photo collections contributed by the general public, which have not been explored so far. As a first technical step toward the study of photo-based brand associations, we aim to jointly achieve the following two visualization tasks in a mutually-rewarding way: (i) detecting and visualizing core visual concepts associated with brands, and (ii) localizing the regions of brand in the images. With experiments on about five millions of images of 48 brands crawled from five popular online photo sharing sites, we demonstrate that our approach can discover complementary views on the brand associations that are hardly mined from the text data. We also quantitatively show that our approach outperforms other candidate methods on the both visualization tasks.
Dendritic cell function in HIV infection

Dendritic cells (DCs) are antigen-presenting cells that serve as critical links between innate and adaptive immunity. Recent advances have revealed that DC interactions with HIV are pleiotropic. As direct antimicrobial effector cells, DCs may play a role in whether HIV infection is established upon mucosal exposure. As potent antigen-presenting cells, DCs probably modulate control of chronic HIV disease through the priming of adaptive immune responses. By contrast, DCs may contribute to HIV pathogenesis through the enhancement of T-cell infection, production of inflammatory cytokines that lead to chronic immune activation (and a proapoptotic state) and the formation of suppressive T-regulatory cells. In this article, recent progress in the field of HIV–DC interactions, including mucosal infection and HIV transmission to T cells, DC infection and activation, DC number and function in acute and chronic HIV infection, and DC immunoregulatory effects are discussed.
INTRA-INDUSTRY TRADE UNDER PERFECT MONOPOLISTIC COMPETITION*

Abstract This paper applies the analysis of perfect monopolistic competition, developed earlier by the author, to the problem of intra-industry trade. It is shown that a high volume of intra-industry trade can be expected even between economies which are identical in all respects and thus between which no trade would be predicted on the basis of comparative advantage. It is shown that similar economies may generate more mutual trade than dissimilar ones, and that tariffs may sometimes increase intra-industry trade.
Sequence Ontology Annotation Guide

This Sequence Ontology (SO) [13] aims to unify the way in which we describe sequence annotations, by providing a controlled vocabulary of terms and the relationships between them. Using SO terms to label the parts of sequence annotations greatly facilitates downstream analyses of their contents, as it ensures that annotations produced by different groups conform to a single standard. This greatly facilitates analyses of annotation contents and characteristics, e.g. comparisons of UTRs, alternative splicing, etc. Because SO also specifies the relationships between features, e.g. part_of, kind_of, annotations described with SO terms are also better substrates for validation and visualization software.This document provides a step-by-step guide to producing a SO compliant file describing a sequence annotation. We illustrate this by using an annotated gene as an example. First we show where the terms needed to describe the gene's features are located in SO and their relationships to one another. We then show line by line how to format the file to construct a SO compliant annotation of this gene.
How to Tangle with a Nested Radical

Like many an intriguing question in algebraic manipulation, the problem of denesting nested radicals had its origins with Ramanujan. That is not to say that no one had ever considered the problem of denesting radicals before he did. Certainly the fact that q _____(____ ( __ ( __ 5 + 2 6 = 2 + 3 is simple enough that it must have been known several centuries ago. Ramanujan [?] upped the ante. For each of the formulae below, he took the doubly nested radical on the left and simplified it to a combination of singly nested radicals on the right: q3(3_______ q3 _____ 3q_____ 3q_____ 2 - 1 = 1/9 - 2/9 + 4/9 q (3____3(___ (3__ 3(___ 3(___ 5 - 4 = 1/3( 2 + 20 - 25 ) q6_(3__________ q3 _____ 3q_____ 7 20 - 19 = 5/3 - 2/3 v _____(4____ 4(__ u43 + 2 5 5 + 1 u _____(4___ = (4_______ t 3 - 2 5 5 - 1 q (3______3(____ (3___ 3(___ 28 - 27 = 1/3( 98 - 28 - 1) 3rq5________5q_______ q5 ______ 5q______ 5q______ 32/5 - 27/5 = 1/25 + 3/25 - 9/25 . What Ramanujan neglected to do was provide a theory for simplifying nested radicals. When computers came along, symbolic computation became important. There was a practical reason to find an algorithm for denesting nested radicals. A machine has no problem with: q _____(____ ( __ ( __ 3/2 1, 5 + 2 6 , 5 + 2 6 , (5 + 2 6 ) q _____(____ as a basis for Q( 5 + 2 6 ) over Q. Most human beings seem to prefer the basis: ( __ ( __ ( __ 1, 2, 3, 6. The difficulty is that there was no general method to go from the complex form of a nested radical to a simplified version. If Ramanujan had one, he never wrote it down. Necessity has often been the mother of invention, and so it proved to be in this case. Although the general problem remains open, there are now solutions to a number of sub- problems: for denesting real nested square roots [?], for radicals of a special form [?], [?], for radicals using roots of unity [?], [?]. We are interested in three questions: When does a simplification exist? Is there a technique for finding it? How long does it take? In this article, we will briefly present some recent theorems for radical simplification, and the algo- rithms they lead to. For proofs, and complete presentations, the reader is urged to read the original papers.
Ion exchange reaction of silver and sodium β″-alumina in molten mercury salts

Abstract Single and polycrystalline samples of Ag and Na β″-alumina were treated in molten HgCl2 and HgI2 and then examined by energy dispersive X-ray analysis. A measurable exchange of Hg2+ ions for the mobile ions in the β″ lattice was obtained only from the single crystal Ag β″-alumina samples. Treating these crystals in HgI2 gave the largest fraction of ion exchange. Our results indicate that the mercury exchange is limited by unfavorable thermodynamics. Estimates of the equilibrium distribution of Hg2+ and Ag+ cations in the crystal and molten salt suggest that multiple exchange treatments with a large excess of the mercury salt are necessary to approach complete Hg2+ ion exchange by this technique.
Numerical solution of a continuum equation for interface growth in 2+1 dimensions

We present the results of extensive large-scale numerical integrations of the Kardar-Parisi-Zhang equation for stochastic interface growth in 1+1 and 2+1 dimensions as a function of the nonlinearity parameter \ensuremath{\epsilon}. We find results for the growth exponents \ensuremath{\alpha} and \ensuremath{\beta} close to those obtained for discrete models. In particular, we find that for large values of \ensuremath{\epsilon}, the values of the exponents are close to the conjecture of Kim and Kosterlitz, indicating that the smaller values obtained previously are due to crossover effects. In contrast to recent studies of discrete models, our results do not show evidence of a phase transition in 2+1 dimensions for \ensuremath{\epsilon}\ensuremath{\ge}1.
EFFECT OF ALUMINA ON DEVITRIFICATION OF SODA-LIME-SILICA GLASSES*

The effect of the substitution of Al2O3 for the oxides of sodium, calcium, and silicon on the liquidus temperatures and phase relations has been determined for glasses lying within the composition range Na2O 11 to 19%, CaO 6 to 18%, SiO2 59 to 79%, and Al2O3 0 to 8%. The results on 137 individual determinations show that the substitution of Al2O3 for CaO permits wollastonite to be the primary phase in glasses of relatively low CaO content. As the Al2O3 content increases, the Na2O-3CaO-6SiO2—CaO·SiO2 boundary shifts to lower CaO contents, and the decomposition of Na2O·3CaO·6SiO2 to CaO·-SiO2 takes place at lower temperatures. In compositions with tridymite as a primary phase, the substitution of Al2O3 for SiO2 is effective in lowering the liquidus temperature. For the composition range investigated, the SiO2-CaO-SiO2 and Na2O·3CaO·6SiO2-SiO2 boundary remains at essentially the same SiO2 content for all glasses containing not more than 4% Al2O3.
Burn Injury Pain: The Continuing Challenge

Abstract The development of more effective methods of relieving pain associated with burn injury is a major unmet medical need. Not only is acute burn injury pain a source of immense suffering, but it has been linked to debilitating chronic pain and stress-related disorders. Although pain management guidelines and protocols have been developed and implemented, unrelieved moderate-to-severe pain continues to be reported after burn injury. One reason for this is that the intensity of pain associated with wound care and rehabilitation therapy, the major source of severe pain in this patient population, varies widely over the 3 phases of burn recovery, making it difficult to estimate analgesic requirements. The effects of opioids, the most commonly administered analgesics for burn injury procedural pain, are difficult to gauge over the course of burn recovery because the need for an opioid may change rapidly, resulting in the overmedication or undermedication of burn-injured patients. Understanding the mechanisms that contribute to the intensity and variability of burn injury pain over time is crucial to its proper management. We provide an overview of the types of pain associated with a burn injury, describe how these different types of pain interfere with the phases of burn recovery, and summarize pharmacologic pain management strategies across the continuum of burn care. We conclude with a discussion and suggestions for improvement. Rational management, based on the underlying mechanisms that contribute to the intensity and variability of burn injury pain, is in its infancy. The paucity of information highlights the need for research that explores and advances the identification of mechanisms of acute and chronic burn injury pain. Perspective Researchers continue to report that burn pain is undertreated. This review examines burn injury pain management across the phases of burn recovery, emphasizing 3 types of pain that require separate assessment and management. It provides insights and suggestions for future research directions to address this significant clinical problem.
A laser Raman spectroscopic investigation of phospholipid and protein configurations in hemoglobin-free erythrocyte ghosts.

Abstract Configurations of both the protein and lipid components of human red blood cell ghosts are examined by laser Raman spectroscopy. Protein configuration is estimated from bands observed in the Amide III region at 1240–1267 cm −1 in water and the Amide I' region at 1630–1670 cm −1 observed in 2 H 2 O. The protein fraction appears to contain 40–55% α-helix with little β-configuration. The hydrophobic side chains of the phospholipid component, as interpreted from the 1060–1130 cm −1 C-C stretching region, are estimated to contain 55–65% all- trans rigid configuration. These estimates are within the limits set by other physical techniques.
Starting School at Four: The Effect of Universal Pre-Kindergarten on Children's Academic Achievement

Universal Pre-Kindergarten (Pre-K) programs differ from widely known and extensively evaluated programs like Head Start and Perry Preschool because access is open to all children of the appropriate age. To estimate the intent-to-treat effects of these programs on the long term educational achievement of children, I use a differences-in-differences framework and individual-level data from the National Assessment of Educational Progress. For disadvantaged children residing in small towns and rural areas, Universal Pre-K availability increases both reading and mathematics test scores at fourth grade as well as the probability of students being on-grade for their age. Increases in some measures of achievement also were seen among other groups, though the patterns were less uniform across outcome measures. The results correspond with other work showing children living in less densely populated areas are those most likely to enroll in preschool because of the program's availability.
A method for separation of X-Ray diffraction patterns from Co-ZSM-5 catalysts

Abstract A Fourier method to unfold an X-ray diffraction pattern from a mixture to obtain the X-ray pattern from one component in the mixture is developed. The method is applied to the X-ray pattern from the catalyst mixture of 9.5% Co on a ZSM-5 support to obtain the diffraction pattern from metallic cobalt. Analysis of the details of the cobalt pattern shows the cobalt to be hexagonal in structure and dispersed with an average particle size of 220 A. The shapes of the profiles indicate that the cobalt particles are heavily faulted on the basal plane.
The standard deviation as an informative measure of variability in reporting interobserver agreement means

The range is the measure of variability typically presented with the means of interobserver agreement scores of behavioral data. However, the range by itself yields little information about the individual interobserver agreement scores before they were averaged. The standard deviation, on the other hand, is a measure of variability that provides the researcher and reader with information regarding the dispersion of scores, allowing a more thorough interpretation of the interobserver agreement mean. The case is presented for the adoption of the standard deviation as an adjunct to the range in reporting the mean of interobserver agreement scores.
Interactions in associative thickener/220 nm methyl methacrylate latex dispersions

Abstract The rheology of commercial associative thickener dispersions containing 220 nm ‘model’ methyl methacrylate (MMA) latices have been examined. These high Tg MMA latices were synthesized by a semicontinuous process with variable percentages of methacrylic acid (MAA). The latex surface without monomer acid segments was only 70% saturated. The latices stabilized with neutralized methacrylic acid segments provided surfactant-saturated surfaces and uniform dispersions when thickened. With the acid-monomer-free latex, the addition of surfactant to saturate the surface of the latex and to increase the free surfactant concentration in the aqueous phase to the level needed to optimize viscosity by intermicellar participation did not effect viscosities equivalent to those noted in associative thickener dispersions containing acid-stabilized latices. These observations support the ion—dipole associative thickener mechanism previously proposed. The viscoelastic behavior of associative thickener dispersions containing stabilized MMA/MAA latices neutralized with ammonium and alkali metal hydroxides has also been examined. The viscosities of all dispersions containing associative thickeners were highest with NH4OH-neutralized latices. These results are interpreted in terms of the greater solubilizing power and lower pKa value of the ammonium salt. The viscosity of hydroxy-ethylcellulose (HEC) thickened dispersions was found to be insensitive to the free surfactant concentration and the nature of the base cation, with only minimal changes in low shear rate viscosities (LSVs) being observed with increasing latex surface acids. These variables notably influence the LSV of the associative thickeners (AT), the magnitude of the latter variations being specific to the AT employed. In oscillatory experiments, dispersions containing commercial associative thickeners, used predominately with acrylic latices in the U.S. and Australian markets, were observed to exhibit large viscous components. A large elastic component, reflecting thickening via network formation, was noted with commercial associative thickener used largely with commercial vinyl/acrylic latices.
Intrahippocampal NMDA Administration Alters Fos, Fos-Related Antigens, and Opioid Peptide Immunoreactivity and mRNA in Rats

In this study, the glutamate receptor agonist, NMDA, was used to induce epileptic seizures in order to compare the expression of the immediate early gene (IEG) products, Fos and Fos-related antigens (Fras), with the opioid peptides, dynorphin (DYN) and leu(5)-enkephalin (LE), in the rat hippocampus. Fos-ir and Fra-ir were observed in the dentate granule cells and nonpyramidal cells within the hippocampal formation at 1 h, and in all hippocampal cells and fields, 3 h following injection of NMDA into the ventral hippocampus. A detailed time-course analysis revealed a differential expression of Fos-ir and Fra-ir. In adjacent sections, a substantial decrease in DYN-ir and LE-ir in the mossy fibers occurred 1, 3, and 6 h after NMDA which was followed by a normalization or an elevation of the opioid peptides at later time points. Quantitative in situ hybridization histochemistry revealed that the hybridization signal representing c-fos mRNA was induced rapidly and transiently in hippocampal neurons. An increase in preproenkephalin (PPE) mRNA in the dentate granule cells was observed 1, 3, and 6 h after NMDA, with a peak at 6 h. Twenty-four and 48 h after NMDA, hybridization signals for PPE and preprodynorphin (PPD) were barely detectable. At 72 h, the level of PPD mRNA was not significantly different from control values. There is a different time course of expression for the Fos and Fra family of genes after in vivo NMDA. The significance of the results is discussed with regard to IEG regulation of opioid peptide gene expression.
Analytical mass spectrometry of herbicides

Herbicides are chemical substances that are applied to agricultural soils, gardens, lawns, or plants to destroy or to prevent the growth of undesirable vegetation. The herbicides included in this review are generally synthetic organic compounds that are ingredients in commercial herbicide products that were designated active during late 2002 in the U.S. Environmental Protection Agency's database of registered and canceled pesticide products. The compounds are organized into 21 categories according to their general chemical structures or a common structural group. The herbicides in each category are discussed in terms of their structures, their database electron ionization mass spectra, and their amenability to separation and measurement with gas chromatography, reversed-phase liquid chromatography, and capillary electrophoresis combined with mass spectrometry. Ionization techniques that are considered here are mainly electron ionization, electrospray, and atmospheric pressure chemical ionization. Sixty-six references are provided to herbicide reviews, and to the recent herbicide analytical chemistry and mass spectrometry research literature.
Optimization of Embedded Sensor Placement for Structural Health Monitoring of Composite Airframes

Thisstudy develops anoptimization methodspecifically for embeddedsensors forstructural health monitoring of a composite laminated aircraft structure. The chosen cost function is the component lifetime, balancing both the positive benefits of the condition-based monitoring enabled by the sensor information with the negative costs of the structural-performance degradation.Theoptical-fiberspacingisoptimized,ratherthantheplacement ofindividual sensors. Sensor interaction with damage and sensor-feature extraction are included into the optimization problem through experimentally derived probabilistic models. The resulting sensor-placement optimization has regions of decreasing laminate lifetime and regions of increasing laminate lifetime as a function of sensor spacing. A critical sensor spacing is also calculated, below which sensors are not recommended to be embedded.
Efficient rents 1 rent-seeking behavior in the long-run

We have analyzed long-run behavior in rent-seeking under several conditions and behavioral hypotheses. The question of interest is whether or not the long-run expenditures will exactly equal the value of the rents. Our results depend on the type of competitive response which is assumed to exist in the long-run and on the r-value governing the probability of winning.
Procaine isothiocyanate: an irreversible inhibitor of the specific binding of [3H]batrachotoxinin-A benzoate to sodium channels.

[3H]Batrachotoxinin-A benzoate ([3H]BTX-B) binds with high affinity to sites on voltage sensitive sodium channels in synaptoneurosomes from guinea pig cerebral cortex. Local anesthetics competitively antagonize the binding of [3H]BTX-B. An irreversible local anesthetic, procaine isothiocyanate (PRIT) and a tritiated derivative ([3H]PRIT) have been prepared. PRIT inhibits the binding of [3H]BTX-B in a noncompetitive, irreversible manner (apparent Ki=13 μM) whereas the parent compound, procaine, inhibits in a competitive, reversible manner (Ki=40 μM). The dissociation rate of [3H]BTX-B from sites on the sodium channel is greatly accelerated in a concentration dependent manner in the presence of PRIT. A 50% increase in the dissociation rate of [3H]BTX-B is achieved in the presence of 0.98 μM PRIT. [3H]PRIT binds irreversibly to three proteins in synaptoneurosomes with apparent molecular weights of 20, 42, and 68 kDa. Protection studies with procaine and other local anesthetics suggest that only the 68 kDa species was related to local anesthetic binding.
Effect of vitamin E on carbon tetrachloride-induced lipid peroxidation as demonstrated by in vivo pentane production

Abstract Pentane production by rats fed a stock diet exhibited a dose-dependent relationship with carbon tetrachloride (CCl4) administered intraperitoneally. Total pentane produced during a 2-h test period following administration of a single dose of 30 μl CCl4/100 g body wt. was greater by rats fed a vitamin Edeficient diet than by rats fed a diet supplemented with vitamin E. Vitamin Esupplemented rats pretreated with 30 μl CCl4 daily for 4 days produced less pentane following administration of 60 μl CCl4 on day 5 than did rats not pretreated with CCl4; conversely, rats fed a vitamin E-deficient diet and similarly treated produced more pentane than did non-pretreated rats. This study confirmed that CCl4 toxicity involves lipid peroxidation and that protection is provided by vitamin E. The usefulness in toxicological studies of monitoring pentane as an index of lipid peroxidation in vivo was shown.
Broad-band high-order frequency multiplication

It is shown that considerable simplification of high-order frequency multiplier systems is possible using a tunable YIG filter.
Average-case analysis of off-line and on-line knapsack problems

We consider the average-case behavior of the Zero?One Knapsack problem, as well as an on-line version studied by Marchetti-Spaccamela and Vercellis. We allow the capacity of the knapsack to grow proportionally to the number of items, so that the optimum solution tends to be ?(n). Under fairly general conditions on the distribution, we obtain a description of the expected value of the optimum offline solution which is accurate up to terms which areo(1). We then consider a simple greedy method for the on-line problem, which is calledOnLineGreedyand is allowed to use knowledge of the distribution, and we show that the solution obtained by this algorithm differs from the true optimum by an average of ?(logn); in fact, we can determine the multiplicative constant hidden by the ?-notation. Thus on average the cost of being forced to give answers on-line is quite small compared to the optimum solution. We also show that no on-line algorithm can improve overOnLineGreedyby more thano(logn). Our results hold, under fairly general conditions on the input distribution, for either the Zero?One Knapsack problem or its linear programming relaxation.
Crystal Structure at 2.4 Å Resolution of the Complex of Transducin βγ and Its Regulator, Phosducin

Abstract The crystal structure of transducin's βγ subunits complexed with phosducin, which regulates G t βγ activity, has been solved to 2.4 A resolution. Phosducin has two domains that wrap around G t βγ to form an extensive interface. The N-terminal domain binds loops on the "top" G t β surface, overlapping the G t α binding surface, explaining how phosducin blocks G t βγ's interaction with G t α. The C-terminal domain shows structural homology to thioredoxin and binds the outer strands of G t β's seventh and first blades in a manner likely to disrupt G t βγ's normal orientation relative to the membrane and receptor. Phosducin's Ser-73, which when phosphorylated inhibits phosducin's function, points away from G t βγ, toward a large flexible loop. Thus phosphorylation is not likely to affect the interface directly, but rather indirectly through an induced conformational change.
Response of the overturning circulation to high-latitude fresh-water perturbations in the North Atlantic

Studies have suggested that sea-ice cover east and west of Greenland fluctuates out-of phase as a part of the Atlantic decadal climate variability, and greater changes are possible under global warming conditions. In this study, the response of the Atlantic meridional overturning circulation (MOC) to the distribution of surface fresh-water flux is explored using a global isopycnal ocean model. An Arctic ice related fresh-water flux of 0.1 Sv entering the Nordic Seas is shown to reduce the maximum overturning by 1 to 2 Sv (106 m3 s–1). A further decrease of 3 to 5 Sv in the MOC is observed when the fresh-water flux is shifted from the Fram Strait to the southern Baffin Bay area. Surprisingly, the salinity in much of the upper Nordic Seas actually increases when the Arctic fresh-water source is the strongest there, as a result of enhanced global overturning. It reflects the great influence of Labrador Sea convection on this model’s MOC. By applying a weaker surface fresh-water transport perturbation (0.02 Sv) on the Baffin Bay area and therefore perturbing the Labrador Sea Water (LSW) formation, we have also investigated the interaction between the overflows across the Greenland–Scotland Ridge and the LSW and find that, with the same surface forcing conditions in the Nordic Seas, volume transport of the overflows weakens when the LSW formation intensifies.
Optimizing Drug Therapy in Patients with Cardiovascular Disease: The Impact of Pharmacist‐Managed Pharmacotherapy Clinics in a Primary Care Setting

We evaluated the effectiveness of pharmacist-managed pharmacotherapy clinics in implementing and maximizing therapy with agents known to reduce the morbidity and mortality associated with cardiovascular disease. This was a retrospective chart review of 150 patients who were treated for coronary artery disease in primary care clinics. Appropriate treatment of hypercholesterolemia occurred in 96% of patients referred to a clinical pharmacy specialist, compared with 68% of those followed by primary care providers alone (p<0.0001). Eighty-five percent and 50%, respectively, achieved goal low-density lipoprotein (LDL) values below 105 mg/dl (p<0.0001). Appropriate therapy with aspirin or other antiplatelet or anticoagulant drugs was prescribed in 97% and 92%, respectively (p=0.146). As appropriate therapy with these agents was high in both groups, the ability to detect a difference between groups was limited Among patients with an ejection fraction below 40%, appropriate therapy with an angiotensin-converting enzyme inhibitor or acceptable alternative was 89% and 69%, respectively (p<0.05). Twenty-seven cardiac events were documented in the clinical pharmacy group, versus 22 in the primary care group (p=0.475). Despite the relatively high percentage of patients reaching goal LDL in the primary care group, referral to clinical pharmacy specialists resulted in statistically significant increases in the number of patients appropriately treated for hypercholesterolemia and achieving goal LDL.
Histologic Findings of Silastic Medialization in the Canine Model

Objectives: Examine the long-term histological effects of Silastic medialization using a canine model. Study Design: Prospective study evaluating the effects of Silastic medialization in six canine larynges. Methods: Two subject groups were evaluated. The first group of four dogs underwent recurrent laryngeal section followed by Silastic medialization on the paralyzed side and placement of a smaller implant on the mobile side. Two of the dogs were sacrificed at 9 months and two at 2 years. The second subject group consisted of two additional dogs who underwent Silastic medialization followed by removal of the implants at 7 months and were sacrificed 18 months later. The larynges were then processed, sectioned in the axial plane, and examined microscopically. Results : Histological findings of both the mobile and paralyzed sides showed a thin (<0.5 mm) fibrous capsule surrounding the implant and minimal inflammatory response. Vocal fold mobility was maintained in all cases in which the recurrent laryngeal nerve was left intact. Capsule formation and inflammatory response were similar in all cases. Conclusions: Minimal tissue reactivity over a prolonged period of time suggests that long-term results of Silastic medialization remain stable in paralyzed and mobile vocal folds for up to 2 years. Similar tissue response in the subjects in which the Silastic block was removed also suggests that Silastic medialization is a reversible procedure.
Regulation of hepatic lipogenesis by the transcription factor XBP1

Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.
Neutrophil function in septic dogs.

Background: Leukocytes appear to enter a hypo-inflammatory state in human patients with a severe bacterial infection, whereas, in swine, intra-abdominal sepsis produces an initial increase and subsequent decrease in neutrophil Fc receptor-mediated phagocytosis. Hypothesis: Impaired neutrophil function (hypo-inflammatory state) develops in dogs with sepsis. Animals: Thirteen adult client-owned dogs that developed clinical signs consistent with sepsis were assessed for evidence of neutrophil dysfunction. These results were compared with those of 12 healthy dogs. Methods: Flow cytometry combined with the appropriate fluorescent markers allowed for quantification of the phagolysosomal oxidative burst after Fc receptor-mediated phagocytosis of immune complexes, neutrophil phagocytosis of opsonized Escherichia coli, and the intracellular concentration of reduced glutathione as a measure of oxidative stress. Results: The phagolysosomal oxidative burst after Fc receptor-mediated phagocytosis was significantly lower in neutrophils from septic dogs (mean fluorescence intensity ± standard deviation; 118 ± 13 and 165 ± 27 for septic and control dogs, respectively, p = 0.001), although the phagocytosis of opsonized E coli was significantly increased (155 ± 74 and 77 ± 44 for septic and control dogs, respectively, p = 0.004). Intracellular reduced glutathione was not significantly different in neutrophils from septic and healthy control dogs. Conclusions: An important component of neutrophil function is decreased in septic dogs. The diminished oxidative burst after Fc receptor-mediated phagocytosis in neutrophils from septic dogs could hinder the ability of the innate immune system to clear bacterial infections or it might help protect these patients from the systemic consequences of infection.
(+)-N-3-Benzyl-nirvanol and (-)-N-3-benzyl-phenobarbital: new potent and selective in vitro inhibitors of CYP2C19.

Highly potent and selective CYP2C19 inhibitors are not currently available. In the present study, N -3-benzyl derivatives of nirvanol and phenobarbital were synthesized, their respective (+)- and (−)-enantiomers resolved chromatographically, and inhibitor potencies determined for these compounds toward CYP2C19 and other human liver cytochromes P450 (P450s). (−)- N -3-Benzyl-phenobarbital and (+)- N -3-benzyl-nirvanol were found to be highly potent, competitive inhibitors of recombinant CYP2C19, exhibiting K i values of 79 and 250 nM, respectively, whereas their antipodes were 20- to 60-fold less potent. In human liver preparations, (−)- N -3-benzyl-phenobarbital and (+)- N -3-benzyl-nirvanol inhibited ( S )-mephenytoin 4′-hydroxylase activity, a marker for native microsomal CYP2C19, with K i values ranging from 71 to 94 nM and 210 to 280 nM, respectively. At single substrate concentrations of 0.3 μM [(−)- N -3-benzyl-phenobarbital] and 1 μM [(+)- N -3-benzyl-nirvanol] that were used to examine inhibition of a panel of cDNA-expressed P450 isoforms, neither CYP1A2, 2A6, 2C8, 2C9, 2D6, 2E1, nor 3A4 activities were decreased by greater than 16%. In contrast, CYP2C19 activity was inhibited ∼80% under these conditions. Therefore, (+)- N -3-benzyl-nirvanol and (−)- N -3-benzyl-phenobarbital represent new, highly potent and selective inhibitors of CYP2C19 that are likely to prove generally useful for screening purposes during early phases of drug metabolism studies with new chemical entities.
Changing pattern of surgical revascularization for critical limb ischemia over 12 years: endovascular vs. open bypass surgery.

Objective This study is a review and evaluation of our 12-year experience of revascularization for critical limb ischemia (CLI) with angioplasty/stenting and bypass surgery to identify specific trends of procedure volume and outcomes in this particular group. Methods Endovascular and open bypass procedures done for CLI by a single surgeon between 1993 and 2004 were evaluated retrospectively. Thrombolysis and thrombectomy procedures done as the only revascularization procedure were excluded from analysis. The data were divided into three groups by time periods: the first period, 1993 to 1996; the second period, 1997 to 2000; and the third period, 2001 to 2004. Outcomes were defined according to the reporting standards of the Society for Vascular Surgery/International Society for Cardiovascular Surgery. The study included 416 procedures done in 237 limbs in 192 patients. The mean follow-up was 23 months (range, 1 to 122 months). Results Primary revascularization procedures for CLI were angioplasty in 153 limbs (65%) and bypass surgery in 84 (35%). Subsequent procedures were angioplasty in 102 limbs (57%) and open surgery (bypass and/or patch angioplasty) in 77 limbs (43%). The rates for technical and clinical success and complications in the entire group were 99%, 95%, and 4%, respectively. One patient died perioperatively (0.5%). Among the three periods, TransAtlantic Inter-Society Consensus lesion types were significantly more severe in patients in the first period (P Conclusions In our experience, open surgical procedures for the treatment of CLI have been largely replaced by angioplasty procedures without compromising outcomes. Angioplasty is a feasible, safe, and effective procedure and can be the procedure of choice for the primary and secondary treatment of CLI. Open surgical procedures can be reserved for lesions technically unsuitable for endovascular procedures and patients who do not demonstrate clinical improvement after angioplasty.
Nostalgia for the Future: Remembrance of Things to Come in Doris Lessing's Martha Quest

Historically, nostalgia has a bad name. But what might an oppositional, regenerative nostalgia look like? In this article, it takes the form of a "nostalgia for the future," a temporally-misoriented concept that is both a nostalgia for that which has yet to happen but feels as though it already has, and a nostalgia utilized for future revolutionary gain, a phenomenon best exemplified by Doris Lessing's Martha Quest (1952). Nostalgia is often thought to begin at home, with a deep longing to return to that originary plenitude, but for white African settlers like the Quests, where is home? With only a provisional dwelling, living in self-exile, what is nostalgia's object? Martha, unsettled by waves of nostalgia, uses her nostalgia to literally envision a homeland for black and white alike, a utopic golden cityon the horizon that both may have been and may yet still be. Lessing returns to nostalgia's past and remedicalizes it, producing a "home-sickness," those waves of nostalgia that create melancholy and despondency that rob one of presence and selfhood, disaggregated from their traditional referents. In order to achieve her vision, Martha must overcome her home-sickness and wield her nostalgia as a weapon, overpowering racism and anti-Semitism.
Infusion of apomorphine into the dorsocentral striatum produces acute drug-induced recovery from neglect produced by unilateral medial agranular cortex lesions in rats.

Previous studies have shown that systemic administration of apomorphine is effective in producing acute drug-induced recovery from neglect induced by unilateral medial agranular cortex (AGm) lesions. More recent studies have demonstrated that recovery from neglect may be due to plastic changes occurring in the dorsal central striatum (DCS). Further, lesions of the DCS produce neglect that does not respond to systemic administration of apomorphine, suggesting that this area may be crucial for the therapeutic effects of apomorphine. In the present study, the behavioral effects of apomorphine infused into the DCS of animals with AGm lesion-induced neglect were examined to determine whether the DCS is a site of drug action. An infusion of 0.375 μg of apomorphine into the DCS, but not a lateral striatal control area, was effective in producing acute recovery from neglect. The results of this study support the crucial role of the DCS in recovery from neglect induced by unilateral AGm lesions and suggest that the DCS may be an important site of action for the therapeutic effects of apomorphine. Because dopamine agonist therapy has been shown to be effective in humans with neglect, the results of the current study may represent an important step in the development of future pharmacotherapies.