cssi/SciSciGPT-SciSciNet huggingface dataset:
Polymer-drug conjugates: Progress in polymeric prodrugs

Abstract Polymers are used as carriers for the delivery of drugs, proteins, targeting moieties, and imaging agents. Several polymers, poly(ethylene glycol) (PEG), N -(2-hydroxypropyl)methacrylamide (HPMA), and poly(lactide- co -glycolide) (PLGA) copolymers have been successfully utilized in clinical research. Recently, interest in polymer conjugation with biologically active components has increased remarkably as such conjugates are preferably accumulated in solid tumors and can reduce systemic toxicity. Based on the site and the mode of action, polymer conjugates possess either ‘tuned’ degradable or non-degradable bonds. In order to obtain such bonds, most of the strategies involve incorporation of amino acids, peptides or small chains as spacer molecules through multiple steps to include protections and deprotections. There is a need to design efficient synthetic methods to obtain polymeric conjugates with drugs and other bioactive components. Designs should aim to decrease the steric hindrance exhibited by polymers and the biocomponents. In addition, the reactivity of polymer and drug must be enhanced. This is especially true for the use of high molecular weight linear polymers and bulkier unstable drugs such as steroids and chemotherapeutic agents. Further, it is essential to elucidate the structure activity relationship (SAR) of a drug when it is conjugated with a polymer using different conjugation sites, as this can vary the efficacy and mechanism of action when compared with its free form. This review will discuss the current synthetic advances in polymer-conjugation with different bioactive components of clinical importance. In addition, the review will describe the strategies for reduction of steric hindrance and increase in reactivity of the polymers, drugs and bioactive agents and highlight the requisite structure activity relationship in polymer–drug bioconjugates. Finally, we will focus on passive and active targeting of polymeric drug delivery systems to specific site of drug action.
Retention of Inhibitory Potency of an ACE Inhibitor Conjugated with Rh(III) and Pd(II) (Iminophosphorano)phosphines. Synthesis and X-ray Structural Investigations

Succinimido, amido, and ester functionalized tetrafluoroaryl azides selectively oxidize bisdiphenylphosphinomethane at one of the P(III) centers giving (iminophosphorano)phosphines 6, 7, and 8 respectively in high yields. Succinimido functionalized perfluoroaryl azido (iminophosphorano)phosphine is attached to angiotensin converting enzyme (ACE) inhibitor, lisinopril at one end, leaving the other end for chelation to Rh(III) and Pd(II) precursors including radioactive analogues establishing the hetero-bifunctionality for potential in vivo tracking of the radiotracer. The measurement of inhibitory potency of lisinopril−metal conjugates (Rh and Pd), modified through the primary amine reveals an increase in inhibitory potency, although small, retaining the target potential of native lisinopril toward specific biological sites. However, direct complexation utilizing the carboxylic groups of lisinopril with a Cu precursor resulted in the reduction of inhibitory potency from nM to μM levels rendering it less us...
Optimal temperature policy for reversible reactions with deactivation: Applied to enzyme reactors

The optimal temperature policy which will maximize the final catalyst activity that gives a fixed conversion of reactants in a specified time for batch operation was determined by the formulation of a calculus of variations problem following the technique of Szepe and Levenspiel (1968). The method was applied to the general case of first-order reversible reactions which occur in the presence of catalysts deactivating by an irreversible first-order mechanism. To reduce trial and error estimations and circumvent numerical instabilities, the two-point boundary value variational problem was reformulated in terms of an initial value problem with a parameter which includes the initial value of temperature. This initial value problem was solved by a regression technique. These techniques were applied to the industrially important enzymatic reaction of the isomerization of D-glucose to D-fructose catalyzed by glucose isomerase in solution. Kinetic and deactivation data are available for this endothermic reaction which obeys first-order reversible kinetics and for the isomerase denaturation which appears to be first order. The optimal temperature operational policy as stated above maximized final enzyme activity such that 10% less denaturation of glucose isomerase occurred when compared to final isomerase activity yielding the same conversion for the same reaction time when the reactor is operated at the optimal isothermal temperature.
Mecamylamine acutely increases human intravenous nicotine self-administration.

Previous studies of human cigarette smoking have shown that administration of the nicotinic acetylcholine receptor antagonist mecamylamine produces acute increases in smoking behavior. In contrast, studies of intravenous nicotine self-administration in animals typically show an immediate decrease in self-administration behavior following mecamylamine administration. To investigate whether this discrepancy might be due in part to the mode of nicotine self-administration (intravenous vs. cigarette smoke), we measured the rate of intravenous nicotine self-administration in tobacco-dependent human smokers. After being trained in a preliminary session to self-administer puff-sized bolus doses of nicotine, 16 subjects were exposed to two sessions (4 h duration) in which they could self-administer intravenous nicotine ad lib. Two hours prior to one session, subjects swallowed a capsule containing 10 mg mecamylamine, and before the other session they took a placebo capsule. Rates of responding for nicotine were assessed, as were subjective reports of withdrawal symptoms and plasma nicotine levels. There was a significantly higher rate of nicotine self-administration in the mecamylamine condition, and mecamylamine attenuated the reduction in craving over the session that occurred during nicotine self-administration. These results indicate that route of administration is not likely the major source of the discrepancy between findings from animal and human studies of nicotine administration. Instead, it is likely that the higher rates of nicotine self-administration induced by mecamylamine were due to an attenuation of the effects of nicotine (e.g., alleviation of withdrawal symptoms) in nicotine-dependent subjects. Thus, animal models of nicotine dependence may need to be employed in conjunction with self-administration procedures in order to duplicate the effects of mecamylamine observed in studies of human smokers.
Effects of exposure to diethyl phthalate, 4-(tert)-octylphenol, and 2,4,5-trichlorobiphenyl on activity of chitobiase in the epidermis and hepatopancreas of the fiddler crab, Uca pugilator

Abstract Seven-day exposure of fiddler crabs, Uca pugilator , to diethyl phthalate at 50.0 mg l −1 significantly inhibited the activity of chitobiase (also known as N -acetyl- β -glucosaminidase) in the epidermis and hepatopancreas. Epidermal chitobiase activity of crabs exposed to 10.0 mg l −1 4-( tert )-octylphenol for 7 days significantly decreased. PCB29 at 0.5 and 2.0 mg l −1 significantly inhibited chitobiase activity in the epidermis and hepatopancreas of crabs exposed for 3 days. The inhibitory effects rendered by diethyl phthalate and PCB29 can at least partly account for the delayed molting they cause because chitobiase is needed to break down the old exoskeleton of crustaceans prior to ecdysis. Since chitinolytic enzymes are apparently the products of ecdysteroid regulated genes in arthropods, the decline in chitobiase activity after exposure to diethyl phthalate, 4-( tert )-octylphenol, and PCB29 along with the delayed molting they cause strongly suggests that these xenobiotics disturb the Y-organ–ecdysteroid receptor axis. Such disturbance may involve an interaction between ecdysteroid receptors and steroid mimics where the steroid mimics act as antagonists of endogenous steroid molting hormones, and/or arise from the interference with synthesis and excretion of ecdysteroids by these compounds.
Hospitality Education 2005: Curricular and Programmatic Trends

The hospitality higher education paradigm needs to change. The general business and trade press report that the current work force in the United States is not adequately skilled or educated to meet the technological needs of the next decade. There is reason to question the content and delivery of hospitality education in institutions of higher education.
A strategic approach to the product life cycle

Abstract This paper analyzes the steady state open-loop Nash equilibrium of a game in which a Northern monopolist devotes resources to new product development and a Southern planner diverts resources into reverse engineering to learn the technology to produce these. A steady state equilibrium technology gap exists, showing that a constant technology gap over time may be explained by optimal strategic behavior of decision-makers in a product cycle model. Given resource costs, neither the Northern monopolist nor the Southern planner wants to alter the gap. Finally, analysis of comparative steady states shows the importance of strategic versus non-strategic behavior.
Expression of Angiopoietin-2 by Human Endometrial Endothelial Cells: Regulation by Hypoxia and Inflammation

The functional endometrial layer receives the implanting blastocyst, but is sloughed off during menstruation. Angiogenesis regulates growth and repair of cycling human endometrium. While vascular endothelial growth factor initiates angiogenesis, the angiopoietins (Angs) acting via the Tie2 receptor, are key regulators of subsequent angiogenic steps. This study is the first to localize Ang-2 and Tie2 in human endometrium and to study Ang-2 regulation in cultured human endometrial endothelial cells (HEECs). Immunohistochemistry revealed that expression of Ang-2 and Tie2 was absent from the glands, low in stromal cells, and intense in the endothelial cells. In contrast, only weak expression of Ang-1 was detected. The phase of the menstrual cycle did not appear to affect the expression of Ang-2 or Tie2. In vitro studies were carried out utilizing isolated HEECs, the most relevant model for endometrial microvascular biology studies. Both hypoxia and phorbol-myristate-acetate enhanced Ang-2 mRNA levels in HEECs. These results suggest that Ang-2 plays a role in endometrial pathologies complicated by impaired blood flow and inflammation.
Lock-free Hash Table on Graphics Processors

Lock-free data structures guarantee higher throughput than lock-based implementations in parallel architectures. This paper presents the first CAS-based lock-free hash table that is based on chaining on GPUs. We achieve an improvement of about 2-8X over lock-free OpenMP implementation. We also achieve over 2-25X speed up over GPU lock-based implementation. We achieve 1.3X to 3.5X increase on throughput with combined Insert and Search workloads over the counterpart OpenMP implementation.
Surface Polarity Induced Domains in Liquid Crystals

Abstract Observations that the free surface of liquid crystals sometimes break up into a pattern of regularly spaced domains are explained as originating from surface polarity. Linear coupling to the surface polarity demands some splay deformation and under appropriate conditions, this will require disclinations. Similar effects may occur with biological membranes.
Development of an Ionization Chamber for the SPIDER Fission Fragment Detector

Abstract The ionization chamber component of the SPIDER detector has been designed to measure energy loss and kinetic energy of fragments produced through neutron-induced fission with energy resolutions of
Metabolite–P450 Complex Formation by Methylenedioxyphenyl HIV Protease Inhibitors in Rat and Human Liver Microsomes

Abstract P450 complex formation and the unusual pharmacokinetics of methylenedioxyphenyl HIV protease inhibitors were examined by in vitro studies using human and rat liver microsomes and by in vivo oral dosing studies. In vitro spectral studies indicated that the formation of a P450 complex having absorbance maxima at 425 and 456 nm was time and concentration dependent; 27–60% of the total P450 was complexed in dexamethasone-induced rat liver microsomes after a 30-min incubation with 100 μM HIV protease inhibitors. Methoxy substitution on the phenyl ring of the methylenedioxyphenyl moiety increased formation of the P450 complex, whereas chlorine substitution markedly decreased the P450 complexation. Kinetic studies on the P450 complex formation indicated that both methoxy and chlorine substitution affected the maximum complex formation rate ( V max ), while it had little effect on K m values (∼10 μM). This complexation in human liver microsomes was inhibited markedly by an anti-CYP3A1 antibody. Furthermore, the P450 complex formation resulted in a time-dependent loss of CYP3A-catalyzed marker activities (testosterone 2β/6β-hydroxylase) in both rat and human liver microsomes. Collectively, these results point to the involvement of CYP3A isoforms in P450 complexation by methylenedioxyphenyl HIV protease inhibitors. Additionally, after oral administration to rats, one of these HIV protease inhibitors (Compound I ), which complexed P450 to the greatest extent, showed no elimination over a period of 500 min after administration of the highest dose. It is suggested that formation of a quasi-irreversible metabolite–CYP3A complex with methylenedioxyphenyl HIV protease inhibitors was responsible for the CYP3A-selective time-dependent loss of catalytic function and the unusual dose-dependent pharmacokinetics after oral administration.
A geometric projection-space reconstruction algorithm

Abstract We present a method to reconstruct images from finite sets of noisy projections that may be available only over limited or sparse angles. The algorithm calculates the maximum a posteriori (MAP) estimate of the full sinogram (which is an image of the 2-D Radon transform of the object) from the available data. It is implemented using a primal-dual constrained optimization procedure that solves a partial differential equation in the primal phase with an efficient local relaxation algorithm and uses a simple Lagrange-multiplier update in the dual phase. The sinogram prior probability is given by a Markov random field (MRF) that includes information about the mass, center of mass, and convex hull of the object, and about the smoothness, fundamental constraints, and periodicity of the 2-D Radon transform. The object is reconstructed using convolution backprojection applied to the estimated sinogram. We show several reconstructed objects which are obtained from simulated limited- and sparse-angle data using the described algorithm, and compare these results with images obtained using convolution backprojection directly.
Whither the Common Good

Since the administrative reform period of the 1880s, American reformers have periodically drawn on the British civil service for ideas. With the 1883 Civil Service Reform Act that created the modern civil service, reformers adapted, to use a phrase from Paul Van Riper, "a British political inven tion to American needs" (1978, 309). Later, some of the elements of the British administrative class in
Seismic Source Summary for All U.S. Below-Surface Nuclear Explosions

A summary of information is presented for all U.S. nuclear tests detonated below the Earth's surface. The data include explosion times, locations, yields, and depths of burial, as well as geophysical information about working-point media, and, for the underground explosions, data about surface collapse (subsidence) phenomena. This summary is intended to furnish available and up-to-date data useful for studies of seismic and hydroacoustic sources, as well as for studies of the seismic and hydroacoustic transmission characteristics of the Earth. Manuscript received 2 July 2001.
Walking speed and peak plantar pressure distribution during barefoot walking in persons with diabetes.

Background. The impact of walking speed has not been evaluated as a feasible outcome measure associated with peak plantar pressure (PPP) distribution, which may result in tissue damage in persons with diabetic foot complications. The objective of this pilot study was to determine the walking speed and PPP distribution during barefoot walking in persons with diabetes. Methods. Nine individuals with diabetes and nine age–gender matched individuals without diabetes participated in this study. Each individual was marked at 10 anatomical landmarks for vibration and tactile pressure sensation tests to determine the severity of sensory deficits on the plantar surface of the dominant limb foot. A steady state walking speed, PPP, the fore and rear foot (F/R) PPP ratio and gait variables were measured during barefoot walking. Results. Persons with diabetes had a significantly slower walking speed than the age–gender matched group resulting in a significant reduction of PPP at the F/R foot during barefoot walking (p 0.05). There was a significant difference between the diabetic and non-diabetic groups for cadence, step time, toe out angle and the anterior–posterior excursion (APE) for centre of force (p < 0.05). Conclusion. Walking speed may be a potential indicator for persons with diabetes to identify PPP distribution during barefoot walking in a diabetic foot. However, the diabetic group demonstrated a more cautious walking pattern than the age–gender matched group by decreasing cadence, step length and APE, and increasing step time and toe in/out angle. People with diabetes may reduce the risk of foot ulcerations as long as they are able to prevent severe foot deformities such as callus, hammer toe or charcot foot. Copyright © 2011 John Wiley & Sons, Ltd.
Characterization and Design of a Non Ported Conventional Speaker for Acoustic Control

A loud speaker has been widely used as a major actuator in the field of active noise control (ANC). In this paper, the design procedures for a non-ported conventional speaker that must meet restrictive size constraint as well as required sound pressure level at a targeted frequency for an acoustic control was presented. Dynamic model of a speaker that includes linear and nonlinear effects such as radiation resistance on speaker damping, voice coil electrical resistance has been developed and its responses were compared to measured data. The effects of speaker design parameter variations on a sound pressure and power consumption were also assessed experimentally and through simulation. It was found that the simulation results are well collated with experimental data and the desired objective has been met.Copyright © 2005 by ASME
Some aspects of environment-enhanced fatigue-crack growth

Abstract Metal fatigue as an engineering problem has been well recognized. Many experiments have been carried out in recent years to assess the effects of load amplitude, mean load, load range and test frequency on the rate of fatigue-crack growth to characterize material response to different load profiles and to develop methods for estimating the service behavior of structural components. Recent studies have shown that fatigue-crack growth can be influenced strongly by the test environment; the effect being dependent on the particular material-environment involved. These results suggest that careful reassessments of the data of previous studies and of the proper direction for future fatigue research will be required. Hence, a critical review and analysis of existing fatigue-crack-growth data on high-strength aluminum and titanium alloys and high-strength steels has been made. The influences of load profile, test frequency, temperature, test environment and state-of-stress on fatigue-crack growth are discussed. Correlation with environment-enhanced crack growth under sustained loads and the associated changes in material response are examined. Possible mechanisms, synergistic effects and implications regarding methods for service-life estimation are considered.
Termination: Analytic Reflections on Client Contact after Counselor Relocation.

Client post-termination contact with counselors who have relocated has been neglected as a training and practice issue. The client may attempt to re-open the therapeutic relationship, even though the counselor has moved to a different geographical location and is not available to continue service delivery. In this article, analytic reflections are used to explore counselor, client, and process variables relative to counselors' response to “following” clients.
Androgen Receptor and Vasopressin Receptor (AVPR1a) Genetic Polymorphisms are not associated with Marital Status or Fertility among Ariaal Men of Northern Kenya

A growing body of scholarship implicates testosterone and vasopressin in male reproductive behavior, including in humans. Since hormones exert their effects through their respective receptors, an open question has been whether genetic polymorphisms in the androgen receptor and vasopressin 1a receptor (AVPR1a) impact human male social behavior. Here, we sought to test for associations between polymorphisms in the coding region of the androgen receptor and promoter region of AVPR1a in relation to marital status and fertility among pastoralist Ariaal men of northern Kenya. None of the three polymorphisms were related to marital status (single, monogamously married, polygynously married) or fertility (number of current living children). We discuss these null findings in light of existing data.
DNA immunization of infants: potential and limitations

DNA immunization is a relatively new and efficacious approach to vaccination. Only recently have we begun to test the efficacy of DNA vaccines in infants. DNA vaccines for a retrovirus, hepatitis B, influenza, rabies, measles, tetanus toxoid, and sendai virus, have now been proven to induce cellular and humoral immune responses in infant animals. Here we review the field of DNA immunization of newborn animals, some new promising immunization strategies, and the rapid progress obtained in this field.
Threonine production by dihydrodipicolinate synthase-defective mutants of Brevibacterium flavum.

Threonine-producing mutants of Brevibacterium flavum that lacked dihydrodipicolinate synthase (DPS) activity but had wild-type homoserine dehydrogenase (HD) sensitive to feedback inhibition by threonine were isolated as strains resistant to α-amino-β-bydroxyvaleric acid (AHV). The growth of a mutant, DK131, derived from an aspartate-producing strain was slow and markedly enhanced by diaminopimelic acid (DAP), but not by L-lysine alone. In a medium containing 10% glucose and the optimum concentration of DAP, strain DK131 produced 13.7 g/l of threonine, which was comparable to that by the previously reported mutant, BB69, with a feedback-resistant HD (HDR). The production was more strongly inhibited by lysine in strain DK131 than in strain BB69. DPS-defective mutants derived from a lysine producer with feedback-insensitive aspartokinase were selected as those which were resistant to AHV and which produced more threonine than lysine. A representative strain, DA105, produced 10.3 g/l of threonine and 3.5 g/l of lysine•HC1, while AHV-resistant mutant, BA68, with an HDR, derived from the same parent, produced 9.7 g/l of threonine and 12.2 g/l of lysine•HC1. Strain DA105 grew well in the absence of DAP.
Temperature measurements near the contact line of an evaporating meniscus V-groove

Abstract Evaporation from a meniscus of heptane liquid in a V-groove geometry is experimentally investigated. A thin layer of titanium coated on the backside of the fused quartz groove is electrically heated to provide a constant heat flux. The temperature profile in the evaporating thin film region of the extended meniscus is measured using high-resolution infrared thermography and the temperature suppression in this region is obtained as a function of liquid feeding rate. The meniscus shape is captured using a goniometer. A temperature suppression of ∼0.2 K in the 150 μm region surrounding the contact line on each side indicates the efficacy of evaporation in the extended meniscus. At a given axial location, the fraction of total meniscus heat transfer which takes place in a 50 μm sub-region measured from the contact line is estimated by an approximate heat balance analysis to be ∼45% for the range of liquid feeding rates explored.
Moving Grief : Exploring Dance/Movement Therapists’ Experiences and Applications with Grieving Children

Current studies in children’s grief and bereavement illuminate that creative arts therapies may support children in the sharing and healing of their experiences with a death loss. However, theories or models suggesting the specific role of dance/movement therapy as a possible creative intervention for this population have not yet been published. This qualitative study is designed to explore the experiences of dance/movement therapists who have worked with children grieving a death loss. Second, this research seeks to elucidate how dance/movement therapists’ experiences with this population may inform their choices to use specific clinical interventions. The results of this study highlight themes that may be relevant in dance/movement therapy applications with grieving children, and is meant to provoke further discussion and continued research that may allow for the development of new dance/movement therapy models within grief studies.
Spoof surface plasmon polariton switches for GHz ∼ THz system

Below the THz spectrum, the textured surfaces on a subwavelength scale generate surface bound modes and henceforth are called spoof surface plasmon polariton (SSPP) modes similar to surface plasmon polariton modes in the visible spectrum. Specifically, when SSPP architectures are combined with electro-optical and nonlinear materials, dynamic SSPP devices could be feasible.
SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmission

Most new emerging viruses are derived from strains circulating in zoonotic reservoirs. Coronaviruses, which had an established potential for cross-species transmission within domesticated animals, suddenly became relevant with the unexpected emergence of the highly pathogenic human SARS-CoV strain from zoonotic reservoirs in 2002. SARS-CoV infected approximately 8000 people worldwide before public health measures halted the epidemic. Supported by robust time-ordered sequence variation, structural biology, well-characterized patient pools, and biological data, the emergence of SARS-CoV represents one of the best-studied natural models of viral disease emergence from zoonotic sources. This review article summarizes previous and more recent advances into the molecular and structural characteristics, with particular emphasis on host–receptor interactions, that drove this remarkable virus disease outbreak in human populations.
Sequence analysis of 515 kinase genes in chronic lymphocytic leukemia

The pathogenesis of chronic lymphocytic leukemia (CLL) remains incompletely understood.1 Although acquired chromosomal aberrations have been demonstrated to influence CLL biology and clinical behavior, it remains unclear what single gene defects other than p53 or ATM mutations cause or contribute to the CLL phenotype.2 In particular, recurrent gene mutations that are increasingly found in other hematological malignancies have not yet been identified in CLL. One recent CLL gene re-sequencing study reported the analysis of selected exons of 70 tyrosine kinase genes in 95 CLL patients and reported no somatically acquired mutations.3 Given the frequent identification of stereotypical immunoglobulin receptor genes in CLL, it has been suggested that antigen engagement of the B-cell receptor on CLL cells serves a critical role in CLL cell survival and CLL disease etiology. Further, the reduced expression of del(13q)(14)-resident microRNAs has been implicated in early CLL pathogenesis in a subset of cases.4 It is unknown whether CLL is driven by high-frequency recurrent gene mutations in one or a few genes.
Model predictive control of parabolic PDE systems with dirichlet boundary conditions via Galerkin model reduction

We propose a framework to solve a closed-loop, optimal tracking control problem for a parabolic partial differential equation (PDE) via diffusivity, interior, and boundary actuation. The approach is based on model reduction via proper orthogonal decomposition (POD) and Galerkin projection methods. A conventional integration-by-parts approach during the Galerkin projection fails to effectively incorporate the considered Dirichlet boundary control into the reducedorder model (ROM). To overcome this limitation we use a spatial discretization of the interior product during the Galerkin projection. The obtained low dimensional dynamical model is bilinear as the result of the presence of the diffusivity control term in the nonlinear parabolic PDE system. We design a closed-loop optimal controller based on a nonlinear model predictive control (MPC) scheme aimed at bating the effect of disturbances with the ultimate goal of tracking a nominal trajectory. A quasi-linear approximation approach is used to solve on-line the quadratic optimal control problem subject to the bilinear reduced-order model. Based on the convergence properties of the quasi-linear approximation algorithm, the asymptotical stability of the closed-loop nonlinear MPC scheme is discussed. Finally, the proposed approach is applied to the current profile control problem in tokamak plasmas and its effectiveness is demonstrated in simulations.
Psychosocial factors and hematopoietic stem cell transplantation: Potential biobehavioral pathways

While psychosocial factors are known to affect cancer progression via biobehavioral pathways in many patient populations, these relationships remain largely unexplored in hematopoietic stem cell transplant (HCT) patients. The purpose of this paper is to critically review the literature regarding psychosocial and endocrine/immune aspects of HCT, with an emphasis on exploring pathways that may mediate the associations between psychosocial factors and disease outcomes. These include the roles of catecholamines, glucocorticoids, inflammation, vascular endothelial growth factor (VEGF), immune reconstitution and infectious susceptibility, as well as the new opportunities available in genomics research. We also discuss the implications for potential immunomodulating psychosocial interventions. Elucidating the biological pathways that account for the associations between psychosocial factors and clinical course could ultimately lead to improved outcomes for this psychologically and immunologically vulnerable population.
LU 51198, A HIGHLY SULFATED, LOW-MOLECULAR-WEIGHT HEPARIN DERIVATIVE, PREVENTS COMPLEMENT-MEDIATED MYOCARDIAL INJURY IN THE PERFUSED RABBIT HEART

Evidence is presented that treatment with a highly sulfated low-molecular-weight heparin fraction, LU 51198, protects the ex vivo perfused rabbit heart from human complement-mediated injury. Hearts from male New Zealand White rabbits were perfused under constant flow in the Langendorff mode. After equilibration, normal human plasma was added to the perfusate as a source of complement. Either control ( n = 8) or LU 51198 (0.6 mg/ml; n = 7) was added to the perfusion medium 10 min before the addition of human plasma. Hemodynamic variables were obtained for both groups before treatment of human plasma. Hemodynamic variables were obtained for both groups before treatment (baseline), 10 min after treatment (zero) and after the addition of human plasma. Compared to control-treated hearts, variables recorded during perfusion with human plasma, including coronary perfusion pressure, left ventricular developed pressure, and left ventricular end-diastolic pressure, along with a reduction of creatine kinase and potassium efflux, were significantly improved in hearts treated with LU 51198 ( P < .05). ELISA assays were used to analyze lymphatic effluent for the presence of iC3b, Bb and SC5b-9 proteins derived from the activation of human complement. The increased presence of the Bb fragment in the effluent obtained from LU 51198-perfused hearts suggests an accelerated dissociation of the convertases responsible for complement amplification, an observation that coincided with protection from complement-mediated damage in the presence of the glycosaminoglycan. The lysis of rabbit red blood cells upon exposure to human plasma was inhibited by LU 51198, which is evidence of the drug’s ability to modulate complement reactivity. The results of this study indicate that a highly sulfated heparin fraction, LU 51198, can reduce tissue injury and preserve discordant organ function that otherwise would be compromised during activation of the human complement cascade.
Some requirements of a colliding comet source of gamma ray bursts

Colliding comets in the Solar System may be an important source of gamma ray bursts. The spherical gamma ray comet cloud required by the results of the Venera Satellites (Mazets and Golenetskii, 1987) and the BATSE detector on the Compton Satellite (Meeganet al., 1992a, b) is neither the Oort Cloud nor the Kuiper Belt. To satisfy observations ofN(>Pmax) vsPmax for the maximum gamma ray fluxes,Pmax > 10−5 erg cm−2 s−1 (about 30 bursts yr−1), the comet density,n, should increase asn ∼a1 from about 40 to 100 AU wherea is the comet heliocentric distance. The turnover above 100 AU requiresn ∼a−1/2 to 200 AU to fit the Venera results andn ∼a1/4 to 400 AU to fit the BATSE data. Then the masses of comets in the 3 regions are from: 40–100 AU, about 9 earth masses,mE; 100–200 AU about 25mE; and 100–400 AU, about 900mE. The flux of 10−5 erg cm−2 s−1 corresponds to a luminosity at 100 AU of 3 × 1026 erg s−1. Two colliding spherical comets at a distance of 100 AU, each with nucleus of radiusR of 5 km, density of 0.5 g cm−3 and Keplerian velocity 3 km s−1 have a combined kinetic energy of 3 × 1028 erg, a factor of about 100 greater than required by the burst maximum fluxes that last for one second. Betatron acceleration in the compressed magnetic fields between the colliding comets could accelerate electrons to energies sufficient to produce the observed high energy gamma rays. Many of the additional observed features of gamma ray bursts can be explained by the solar comet collision source.
Juries and Medical Malpractice Claims: Empirical Facts versus Myths

Juries in medical malpractice trials are viewed as incompetent, antidoctor, irresponsible in awarding damages to patients, and casting a threatening shadow over the settlement process. Several decades of systematic empirical research yields little support for these claims. This article summarizes those findings. Doctors win about three cases of four that go to trial. Juries are skeptical about inflated claims. Jury verdicts on negligence are roughly similar to assessments made by medical experts and judges. Damage awards tend to correlate positively with the severity of injury. There are defensible reasons for large damage awards. Moreover, the largest awards are typically settled for much less than the verdicts.
Commissureless endocytosis is correlated with initiation of neuromuscular synaptogenesis

We show that the Commissureless (COMM) transmembrane protein is required at neuromuscular synaptogenesis. All muscles in the Drosophila embryo express COMM during the period of motoneuron-muscle interaction. It is endocytosed into muscles before synaptogenesis. In comm loss-of-function mutants, motoneuron growth cones fail to initiate synaptogenesis at target muscles. This stall phenotype is rescued by supplying wild-type COMM to the muscles. Cytoplasmically truncated COMM protein fails to internalize. Expressing this mutant protein in muscles phenocopies the synaptogenesis defects of comm mutants. Thus, synaptogenesis initiation is positively correlated with endocytosis of COMM in postsynaptic muscle cells. We propose that COMM is an essential part of the dynamic cell surface remodeling needed by postsynaptic cells in coordinating synaptogenesis initiation.
Superconducting Microresonators: Physics and Applications

Interest in superconducting microresonators has grown dramatically over the past decade. Resonator performance has improved substantially through the use of improved geometries and materials as well as a better understanding of the underlying physics. These advances have led to the adoption of superconducting microresonators in a large number of low-temperature experiments and applications. This review outlines these developments, with particular attention given to the use of superconducting microresonators as detectors.
Point: hyperbaric oxygen is beneficial for diabetic foot wounds.

Background. Diabetic foot ulceration is common, affecting 1.0%-4.1% of diabetic persons per year and up to 25% in a lifetime. Diabetic foot ulcers are multifactorial in origin, and many are slow to heal and/or are complicated by infection, frequently leading to amputation. Hyperbaric oxygen therapy has been suggested for numerous indications, and it is recognized by funding agencies for a smaller number including diabetic foot wounds. Methods. I reviewed the literature about the history and practice of hyperbaric oxygen therapy and key issues relevant to efficacy, effectiveness, and cost-effectiveness. Results. Although recognized for reimbursement by Medicare and major insurers, the evidence base for hyperbaric oxygen therapy for diabetic foot care remains weak. A systematic review for the Cochrane Collaboration concluded that hyperbaric oxygen therapy may have value in treating diabetic wounds, but the studies reviewed all had methodological weaknesses, and the positive effect of treatment was not seen in the single reviewed randomized trial to include a sham treatment arm. Hyperbaric oxygen therapy consumes very substantial resources-and has the potential to consume far more-that could be better spent on other aspects of management or prevention of diabetic foot ulceration. Conclusions. Hyperbaric oxygen therapy should not be offered for diabetic foot wounds until large-scale, adequately blinded, controlled, and powered randomized studies have clearly demonstrated efficacy and cost effectiveness in the healing of ulcers and the prevention of major amputation.
Cost-effectiveness of diagnostic approaches to suspected appendicitis in children.

Background Our group recently published a clinical pathway (Le Bonheur Clinical Pathway [LeB-P]) that used the Samuel Pediatric Appendicitis Score with selective use of ultrasonography (USG) for diagnosis of children at risk for appendicitis. The objective of this study was to model the cost-effectiveness of implementing the LeB-P compared with usual care. Study Design We constructed a decision analytic model comparing hospital costs for the following diagnostic strategies for suspected appendicitis: emergency department clinician judgment alone, USG on all patients, CT on all patients, overnight observation with surgical evaluation without studies, and the LeB-P. Prevalence of disease, outcomes probabilities, and hospital and professional costs for each option were derived from published literature, national cost data, and our previous study results. Cost-effectiveness was calculated using these 3 sets of parameters. Results In the base case model, USG was the preferred strategy over LeB-P and overnight observation with surgical evaluation without studies. Emergency department clinician judgment alone and CT were dominated by the other pathways, based on either lower diagnostic accuracy or increased costs. Compared with LeB-P, USG costs $337 less per patient evaluated, but increased the diagnostic error rate by 2%. Using LeB-P rather than USG would cost an institution an additional $17,206 to eliminate one misdiagnosis, which is known as the incremental cost-effectiveness ratio. Conclusions Although performing USG on all children with suspected appendicitis was determined to be the most cost-effective strategy, using the Pediatric Appendicitis Score with selective use of USG (LeB-P) improved diagnostic accuracy at a moderate increase in cost and decreased CT use.
Application of a discontinuous Galerkin time domain method to simulation of optical properties of dielectric particles

We applied a discontinuous Galerkin time domain (DGTD) method, using a fourth-order Runga-Kutta time stepping of the Maxwell equations, to the simulation of the optical properties of dielectric particles in two-dimensional (2D) geometry. As examples of the numerical implementation of this method, the single-scattering properties of 2D circular and hexagonal particles are presented. In the case of circular particles, the scattering phase matrix was computed using the DGTD method and compared with the exact solution. For hexagonal particles, the DGTD method was used to compute single-scattering properties of randomly oriented 2D hexagonal ice crystals, and results were compared with those calculated using a geometric optics method. We consider both shortwave (visible) and longwave (infrared) cases, with particle size parameters 50 and 100. In the hexagonal case, scattering results are also presented as a function of both incident and scattering angles, revealing a structure apparently not reported before. Using the geometric optics method, we are able to interpret this structure in terms of contributions from varying numbers of internal reflections within the crystal.
Ribosomal RNA and Translation

BIOCHEMICAL EVIDENCE.. """'''''''' ''''' ''' .... ' " ' ' '' ' Activity of Protein-Depleted RNA . Affinity Labeling and Cross-Linking . . Protection from Chemical and Enzymatic Probes . Binding of IRNA to the A, P, and E Sites . Intermediale States in Translocation: Hybrid Sites . Interactions of Antibiotics with Ribosomal RNA . Elongation Factors and Ribosomal RNA . Initiation Factors and Ribosomal RNA . Subunit Association . RNA-Direcled Biochemical Inactivation .
Modeling of air operations for course-of-action determination

This paper introduces the concept of using simulation for both plan tracking and state estimation and prediction. Given some set of objectives the military commander must devise a sequence of actions that transform the current state to the desired one. The desire to do this in faster than real-time so that many courses of action can be considered motivates us to investigate modeling techniques that explicitly produce such courses of action. This class of problem can be modeled as a Markov decision process (MDP) whose principal solution is stochastic dynamic programming. In this paper we consider the extension of a MDP model of air operations to the partially observed case.
Development and formative evaluation of a foot self-care program for African Americans with diabetes

African Americans with diabetes have a higher rate of lower-extremity amputation due to diabetic foot complications than the general public. Education about proper foot care can help prevent serious diabetic foot complications and assist in early detection of problems. The purpose of this project was to develop, formatively evaluate, and pilot test a self-care, take-home program for the prevention of foot problems in African Americans with diabetes. The program included a brief one-on-one orientation session and a take-home foot self-care packet. Through telephone follow-up subjects reported the following: good to excellent overall rating of the program, favorable reactions to the patient instruction booklet, an overwhelming positive response to the large hand mirror, and a positive effect on their daily foot-care practices. The Afrocentricity of the patient education materials was preferred by younger subjects; older subjects found this approach too restrictive.
Identification of SV40 in brain, kidney and urine of healthy and SIV-infected rhesus monkeys

Recent reports of simian virus 40 (SV40) sequences in human tumors have prompted investigations into the poorly understood association of this polyomavirus with its primate host, the rhesus monkey (Macaca mulatta). In the present study we have used PCR to analyze tissues from 20 monkeys for the presence of SV40. Five of the animals, which were infected with simian immunodeficiency virus (SIV), were found to exhibit SV40-induced lesions and to have SV40 sequences present in their kidney and brain. Lesions associated with SV40 were not observed in 15 SIV monkeys, and SV40 DNA was detected in kidney and urine of only one of these animals. Three regions of SV40 DNA were examined in each tissue: the non-coding transcriptional control region (TCR), the sequences encoding the host range domain (HRD) within the carboxy-terminus of T antigen (TAg), and a portion of the VP1 gene. Each region contained nucleotide alterations compared to the SV40 reference strain 776. In all six animals, the TCR had an archetype structure containing a single 72 bp enhancer element. In addition, the TCR amplified from two animals lacked one of three copies of a GC-rich 21 bp repeat which is part of the promoter in strain 776. Multiple clones of unique HRD sequences were derived from different animals, and in some instances from the same animal. No correlation was found between a particular HRD sequence and its presence in a specific tissue type. Nucleotide changes identified within the VP1 gene indicate that this region, as with the closely-related human polyomavirus JCV, may permit the typing of the virus into individual strains. This study is the first to characterize SV40 sequences present in both healthy and SIV-infected animals and supports the suggestion that strain 776 is not the predominant type of SV40 circulating in its natural host.
Macular Ganglion Cell/Inner Plexiform Layer Measurements by Spectral Domain Optical Coherence Tomography for Detection of Early Glaucoma and Comparison to Retinal Nerve Fiber Layer Measurements

Purpose To evaluate the performance of ganglion cell layer/inner plexiform layer (GCL/IPL) measurements with spectral-domain optical coherence tomography (Cirrus HD-OCT) for detection of early glaucoma and to compare results to retinal nerve fiber layer (RNFL) measurements. Design Cross-sectional prospective diagnostic study. Methods We enrolled 99 subjects, including 59 eyes with glaucoma (47 subjects) (mean deviation >−6.0 dB) and 91 normal eyes (52 subjects). Patients underwent biometry and peripapillary and macular OCT imaging. Performance of the GCL/IPL and RNFL algorithms was evaluated with area under receiver operating characteristic curves (AUC), likelihood ratios, and sensitivities/specificities adjusting for covariates. Combination of best parameters was explored. Results Average (SD) mean deviation in the glaucoma group was −2.5 (1.9) dB. On multivariate analyses, age ( P P = 0.03) predicted GC/IPL measurements in normal subjects. No significant correlation was found between average or regional GC/IPL thickness and respective outer retina (OR) thickness measurements ( P > 0.05). Average RNFL thickness performed better than average GCL/IPL measurements for detection of glaucoma (AUC = 0.964 vs 0.937; P = 0.04). The best regional measures from each algorithm (inferior quadrant RNFL vs minimum GCL/IPL) had comparable performances ( P = 0.78). Entering the GC/IPL to OR ratio into prediction models did not enhance the performance of the GCL/IPL measures. Combining the best parameters from each algorithm improved detection of glaucoma ( P = 0.04). Conclusions Regional GCL/IPL measures derived from Cirrus HD-OCT performed as well as regional RNFL outcomes for detection of early glaucoma. Using the GC/IPL to OR ratio did not enhance the performance of GCL/IPL parameters. Combining the best measures from the 2 algorithms improved detection of glaucoma.