cssi/SciSciGPT-SciSciNet huggingface dataset:
Reforming Off-Label Promotion to Enhance Orphan Disease Treatment

Once the U.S. Food and Drug Administration (FDA) approves uses for new drugs, physicians are free to prescribe them for any clinical condition they see fit ( 1 ). Promotion (by manufacturers) and patient use (guided by clinicians) for any indication, population, dosage, administration, or treatment duration other than that approved by a country's regulatory authority is deemed “off-label” ( 2 ). Such use is highly prevalent; 21% of all prescription drug use, and up to 83% for certain diseases and drugs, are off-label ( 3 ).
An Analytic Form for the Interresponse Time Analysis of Shull, Gaynor, and Grimes with Applications and Extensions.

Shull, Gaynor and Grimes advanced a model for interresponse time distribution using probabilistic cycling between a higher-rate and a lower-rate response process. Both response processes are assumed to be random in time with a constant rate. The cycling between the two processes is assumed to have a constant transition probability that is independent of bout length. This report develops an analytic form of the model which has a natural parametrization for a higher-rate within-bout responding and a lower-rate visit-initiation responding. The analytic form provides a convenient basis for both a nonlinear least-squares data reduction technique to estimate the model's parameters and Monte Carlo simulations of the model. In addition, the analytic formulation is extended to both a refractory period for the rats' behavior and, separately, the strongly-banded behavior seen with pigeons.
Titivated for Destruction: The Methyl Degron

In this issue, Lee et al. (2012) demonstrate that the degradation of RORα is regulated by the EZH2-DCAF1/DDB1/CUL4 proteasome axis, thus identifying protein methylation as a posttranslational modification that can orchestrate protein destruction through a motif termed the "methyl degron."
Inhaled nitric oxide, oxygen, and alkalosis: dose-response interactions in a lamb model of pulmonary hypertension.

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose-dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose-response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1–6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady-state pulmonary hypertension induced by U46619 (a thromboxane A2 mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO2) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose-dependent decreases in mean pulmonary arterial pressures (P 5 ppm, alkalosis induced further dose-independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose-dependent pulmonary vasodilation. However, when combined, a systemic arterial pH >7.40 augmented inhaled NO-induced pulmonary vasodilation, while an FiO2 >0.5 did not. Therefore, weaning high FiO2 during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies. Pediatr Pulmonol. 1999; 28:3–11. © 1999 Wiley-Liss, Inc.
Spruce budworm (Lepidoptera: Tortricidae) field fecundity: new insights into its estimation and use

Abstract Relationships between female spruce budworm, Choristoneura fumiferana (Clem.), pupal width and live weight, with realized field fecundity were determined in cages on branches of black spruce, Picea mariana (Mill.) B.S.P., in northern Maine. These are the first such determinations made on individual spruce budworms under field conditions. Fecundity varied from maximum levels similar to previously published findings in laboratory studies, to zero, independent of pupal size. Results suggest that previous laboratory studies of the pupal size–fecundity relationship have overestimated actual egg laying under field conditions, and therefore reduced the accuracy of some population studies.
The effect of column age on system suitability parameters for an HPLC assay of bitolterol mesylate aerosols

A reversed-phase ion-pairing HPLC method is developed for bitolterol mesylate (Tornalate, Winthrop-Breon) in aerosol dosage forms. Using data acquired by this method during a two-year period, the effect of ODS-3 column age on system suitability parameters is assessed. A BASIC program is used to calculate the resolution factor between bitolterol and colterol triester, capacity factors, number of theoretical plates, and tailing factors in studies that followed the performance of one column during this time period and five columns of different ages under normal usage. A 15 to 30% reduction in column performance per year is found.
Dislocation of the hip after reimplantation for infection: an analysis of risk factors.

Dislocation is a well documented complication after a two-stage revision arthroplasty for a deep periprosthetic hip infection. We are aware of no reports specifically evaluating the risk factors for dislocation after reimplantation for infection. We hypothesized greater age, increase in the number of operations on the hip, increase in the length of time from resection to reimplantation, greater limb length discrepancy, smaller femoral offset, and using smaller femoral heads would increase the risk of dislocation. We retrospectively reviewed 34 patients who had a two-stage hip revision for periprosthetic infection with a minimum followup of 2 years. Risk factors for dislocation were evaluated. We compared the rate of dislocation in this group to those patients having revision for aseptic failure. Sixteen dislocations occurred in five (14.7%) of 34 patients. Dislocation occurred in three (1.7%) of 171 patients having revision for aseptic failure. In this small series, age at reimplantation, number of previous operations on the hip, length of time from resection to reimplantation, limb length discrepancy, femoral offset, and femoral head size did not seem to be risk factors for dislocation. Level of Evidence: Therapeutic study, level III (case-control study). See Guidelines for Authors for a complete description of levels of evidence.
Importance of heat capacity effects in the association of hydrocarbon moieties in aqueous solution

Values are reported for changes in heat capacity that accompany the formation of hydrocarbon-hydrocarbon dimers and hydrocarbon-polar hydrocarbon derivative dimers in dilute aqueous solution. Highly negative ΔCpo are obtained; the enthalpy changes, endothermic at room temperature, tend to decrease to zero in the range 50 to 80°C. A discussion is given of the importance of heat capacity effects in relation to the stability of hydrophobic association complexes.
Effect of the illuminant on color appearance

The spectral power distribution of the light that reflects from a surface to the eye depends both on the reflectance function of the surface and on the spectral power distribution of the illuminant The human visual system actively adjusts to reduce the dependence of surface color appearance on the illumination. We use a matching paradigm to measure the change in the cone coordinates of a color signal necessary to maintain constant color appearance across an illuminant change. If the visual system made no adjustment, the measured cone coordinate change would be zero. If the visual system were perfectly color constant, the measured change would compensate exactly for the physical change in cone coordinates due to the change in illuminant It is not possible to measure the visual system’s adjustment to all combinations of illuminant changes and surfaces. Therefore we develop and test a model of this adjustment. In our laboratory experiments two variables govern the adjustment: the cone coordinates of the reflected color signal and the change in the spectral power distribution of the illuminant We model the visual system’s adjustment using a bilinear function. We determine the parameters of the bilinear function from a small number of measurements. We show that the bilinear model predicts the visual system’s adjustment to many other surface and illuminant combinations.
Bioassay for EDRF/NO by accumulation of cyclic GMP in RFL-6 fetal rat lung fibroblasts

Abstract We describe the use of fetal rat lung fibroblasts (RFL-6 cells) as a bioassay for endothelium-derived relaxing factor or nitric oxide (EDRF/NO). In these cells grown to confluency in 6-well plates, authentic NO, at concentrations as low as 2 nM, or EDRF/NO, basally released from as few as 1–2 × 10 6 endothelial cells, causes accumulation of guanosine 3′,5′-cyclic monophosphate. If cells are grown in 48-well plates (well area 1 10 that of 6-well plates) this gives a detection limit of 100–200 fmol NO and the possibility of detecting the basal EDRF/NO release from 1–2 × 10 5 endothelial cells. Thus, this method is more sensitive than any other currently available. In addition, RFL-6 cells may be used to detect the activity of EDRF/NO synthase in cell homogenates and column fractions during purification, making them an invaluable aid in purification and characterization of EDRF/NO synthase from brain and neuronal cells.
Site-specific platinum(II) cross-linking in a ribozyme active site.

The function of RNA depends on its ability to adopt complex and dynamic structures, and the incorporation of site-specific cross-linking probes is a powerful method for providing distance constraints that are valuable in RNA structural biology. Here we describe a new RNA-RNA cross-linking strategy based on Pt(II) targeting of specific phosphorothioate substitutions. In this strategy cis-diammine Pt(II) complexes are kinetically recruited and anchored to a phosphorothioate substitution embedded within a structured RNA. Substitution of the remaining exchangeable Pt(II) ligand with a nucleophile supplied by a nearby RNA nucleobase results in metal-mediated cross-links that are stable during isolation. This type of cross-linking strategy was explored within the catalytic core of the Hammerhead ribozyme (HHRz). When a phosphorothioate substitution is installed at the scissile bond normally cleaved by the HHRz, Pt(II) cross-linking takes place to nucleotides G8 and G10 in the ribozyme active site. Both of these positions are predicted to be within ~8 A of a phosphorothioate-bound Pt(II) metal center. Cross-linking depends on Mg(2+) ion concentration, reaching yields as high as 30%, with rates that indicate cation competition within the RNA three-helix junction. Cross-linking efficiency depends on accurate formation of the HHRz tertiary structure, and cross-links are not observed for RNA helices. Combined, these results show promise for using kinetically inert Pt(II) complexes as new site-specific cross-linking tools for exploring RNA structure and dynamics.
A novel method for induction of salt appetite in rats.

Abstract A number of procedures exist for the experimental induction of sodium appetite. With the exception of a low sodium diet, nearly all of these methods are invasive, requiring injections, surgery, or both. In addition to stimulating intake of concentrated salt, some of them produce substantial side-effects like reduced food intake and weight gain. The present experiment was designed to evaluate the efficacy of a novel non-invasive method to induce a salt appetite. We investigated the effects of ingesting 100 μM amiloride, a diuretic and natriuretic compound, on urine quantity, electrolyte balance, 0.51 M sodium chloride (NaCl) intake, water intake, and Na + -free chow intake, and weight gain in rats. A water ingestion only group served as control. Consumption of amiloride in mixture with water produced greater loss of urinary Na + and intake of 0.51 M NaCl compared with controls. This treatment was without effect on food intake and only modestly influenced weight gain. These results demonstrate a rapid and non-invasive method for the induction of salt appetite free of unwanted side-effects.
Quasiharmonic elastic constants corrected for deviatoric thermal stresses

The quasiharmonic approximation QHA, in its simplest form also called the statically constrained SC QHA, has been shown to be a straightforward method to compute thermoelastic properties of crystals. Recently we showed that for noncubic solids SC-QHA calculations develop deviatoric thermal stresses at high temperatures. Relaxation of these stresses leads to a series of corrections to the free energy that may be taken to any desired order, up to self-consistency. Here we show how to correct the elastic constants obtained using the SC-QHA. We exemplify the procedure by correcting to first order the elastic constants of MgSiO3 perovskite and MgSiO3 postperovskite, the major phases of the Earth’s lower mantle. We show that this first-order correction is quite satisfactory for obtaining the aggregated elastic averages of these minerals and their velocities in the lower mantle. This type of correction is also shown to be applicable to experimental measurements of elastic constants in situations where deviatoric stresses can develop, such as in diamond-anvil cells.
Mitochondrial biogenesis and the development of diabetic retinopathy

Retinal mitochondria become dysfunctional and their DNA (mtDNA) is damaged in diabetes. The biogenesis of mitochondrial DNA is tightly controlled by nuclear-mitochondrial transcriptional factors, and translocation of transcription factor A (TFAM) to the mitochondria is essential for transcription and replication. Our aim is to investigate the effects of diabetes on nuclear-mitochondrial communication in the retina and its role in the development of retinopathy. Damage of mtDNA, copy number, and biogenesis (PGC1, NRF1, TFAM) were analyzed in the retinas from streptozotocin-diabetic wild-type (WT) and MnSOD transgenic (Tg) mice. Binding between TFAM and chaperone Hsp70 was quantified by coimmunoprecipitation. The key parameters were confirmed in isolated retinal endothelial cells and in the retinas from human donors with diabetic retinopathy. Diabetes in WT mice increased retinal mtDNA damage and decreased copy number. The gene transcripts of PGC1, NRF1, and TFAM were increased, but mitochondrial accumulation of TFAM was significantly decreased, and the binding of Hsp70 and TFAM was subnormal compared to WT nondiabetic mice. However, Tg diabetic mice were protected from retinal mtDNA damage and alterations in mitochondrial biogenesis. In retinal endothelial cells, high glucose decreased the number of mitochondria, as demonstrated by MitoTracker green staining and by electron microscopy, and impaired the transcriptional factors. Similar alterations in biogenesis were observed in the donors with diabetic retinopathy. Thus, retinal mitochondrial biogenesis is under the control of superoxide radicals and is impaired in diabetes, possibly by decreased transport of TFAM to the mitochondria. Modulation of biogenesis by pharmaceutical or molecular means may provide a potential strategy to retard the development/progression of diabetic retinopathy.
A Relative Ad hoc Localization Scheme using Optical Wireless

Directional communication (for example, using directional antennas or free-space optics) has the potential to dramatically increase capacity reuse in multi-hop wireless mesh and ad hoc networks. What is less appreciated is that directional communications can also simplify network layer functions. In this paper, we show how directionality (combined with ranging) can be used to construct a scalable, fully distributed localization system and assign "relative" coordinates to each node (without the need for GPS) that can be used by highly scalable geographic routing systems. We show that range and orientation-based localization schemes (ROL) scale better than range-only or orientation-only localization schemes (e.g., triangulation) for such applications. We present simulations studying scalability, effect of errors (both range and directionality) and compare performance with triangulation methods. Finally, we discuss how such an ROL scheme can be realized with optical wireless nodes, based upon our ongoing efforts to build ad hoc and meshed networks using both FSO and RF technologies.
Hard Disk Drive Servo System Based on Field-Programmable Gate Arrays

Servo systems are essential components of current magnetic storage hard disk drives (HDDs). In this paper, we demonstrate a novel servo scheme using a field-programmable gate array (FPGA). Adjacent magnetic tracks with two different frequencies are recorded on the magnetic disk and are used as servo tracks to encode the position information. A discrete Fourier transform is employed to decode the magnetic head position and to obtain the position error signal (PES). The PES is defined in terms of the difference of the magnitudes of the two frequencies. The relationship between the displacement and the PES is obtained by offline calibration. A real-time signal acquisition and processing system using a commercial FPGA, analog-to-digital converter chips, and digital-to-analog converter chips is built to do the high-speed spectrum analysis and generate the PES. The PES is transmitted to a laboratory virtual instrument engineering workbench (LabVIEW) real-time control target to implement the control algorithm. The computed control output from the real-time control target is amplified to drive a piezoelectric stage, which moves the magnetic head along the radial direction to compensate for the position error. A simple repetitive and proportional-integral-derivative control algorithm is implemented for head positioning and to verify this new servo scheme in this paper. With the controller, most of the major disturbances, such as the harmonics of the spindle runout, have been effectively attenuated compared with an open-loop control scheme.
Understanding change in teachers’ ways of being through collaborative action research: a cultural–historical activity theory analysis

Despite major efforts to change teachers’ practice through professional development activities, much remains as it always was. Our claim is that this rarely happens because significant change in how one teaches can only come about as a result of some realization about oneself as a teacher, and the resulting changes in identity. In recent years we have been studying the ways in which participation in collaborative action research (CAR) can result in changes in teachers’ ways of being. In this paper we report on a study of teachers engaged in CAR to improve their implementation of digital photography in their teaching. The whole group (n = 28) completed one cycle of action research as part of the evaluation of the program using empowerment evaluation methods. A subset (n = 5) chose to continue doing CAR. We used ethnographic methods including participant observation, interviews, and document analysis. In this paper we use cultural–historical activity theory to understand why our data suggest that there was ...
Determinants of colobine monkey abundance: the importance of food energy, protein and fibre content.

Summary 1 A fundamental ecological question is what determines the abundance of animals? Answering this question is vital in the formulation of effective management plans for endangered or threatened species. However, there are few general hypotheses proposed to account for variation in animal abundance. Studies of folivorous primates are a notable exception. In this group, the protein to fibre ratio of mature leaves is a significant predictor of biomass. However, Dasilva (1992) suggested that the availability of energy may play a critical role in colobine behaviour and ecology. 2 Here we evaluate the importance of food energy content for the red colobus (Procolobus badius) and black-and-white colobus (Colobus guereza) monkeys of Kibale National Park, Uganda. 3 Energy was found to be of little importance. None of the eight groups studied selected high-energy foods: there was no correlation between food energy content and foraging effort. For all groups, estimates of energy expenditure [daily energy expenditure (DEE) and average daily metabolic needs (ADMN)] were less than estimates of energy consumption. Finally, the average energy content of mature leaves from the 20 most abundant tree species at four sites was not related to colobine biomass. 4 In contrast, the protein and fibre content of foods was important to both colobine species. Seven of the eight groups selected foods with a high-protein, low-fibre content. The average protein to fibre ratio of mature leaves from the 20 most abundant tree species at four sites was correlated positively with colobine biomass. 5 This study provides further validation of the protein to fibre model, suggesting the importance of this model for conservation and management of colobus monkeys, with the potential application to other small mammalian herbivores.
Spectroscopic and Biochemical Studies of TRIP8b Regulation of HCN Channels

TRIP8b, an accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, alters both cell surface expression and cyclic nucleotide dependence of these channels. The mechanism through which TRIP8b exerts these dual effects is still poorly understood. Besides binding the terminal three residues of HCN channels, TRIP8b also binds directly to the cyclic nucleotide-binding domain (CNBD). A small central portion of TRIP8b, termed TRIP8bcore, is involved in this interaction. Binding of TRIP8bcore to the CNBD dramatically reduces the effects of cAMP on the channel. Using spectroscopic and biochemical techniques, we sought to understand how and where TRIP8b binds to the CNBD and how it reduces the cyclic nucleotide dependence of HCN channels. To closely examine the binding of TRIP8bcore to the CNBD, we used double electron-electron resonance (DEER) at Q-band frequencies to study conformational changes in the soluble CNBD of HCN2 in the presence of TRIP8b and cAMP. We show that the overall structure of the TRIP8b bound conformation of the CNBD closely resembles the apo state. In addition, we use DEER between the CNBD and TRIP8bcore and nuclear magnetic resonance (NMR) to localize the binding site for TRIP8b on the CNBD. Finally, to understand the mechanism of TRIP8b inhibition of cAMP regulation of HCN channels, we performed binding studies of cAMP and TRIP8b on the CNBD and developed a multi-state mathematical model to explore 1) whether cAMP and TRIP8b can bind simultaneously to HCN channels, 2) whether TRIP8b reduces the affinity for cAMP binding, and 3) whether TRIP8b reduces the effect of cAMP on HCN channels by preventing the structural rearrangements associated with channel opening.
Cutaneous malignant histiocytosis: A clinical and histopathologic study of eight cases, with immunohistochemical analysis

Eight cases of autopsy-proved malignant histiocytosis (MH) are reported, in which cutaneous involvement was a prominent finding at initial clinical presentation. In two patients, the disease remained confined to the skin for significant periods before systemic dissemination appeared. Immunohistochemical analysis of cutaneous infiltrates of MH showed uniform negativity of the atypical cells for lysozyme, immunoglobulin light chain, glycogen, and chloroacetate esterase content. In five cases, cytochemical stains for acid phosphatase, butyrate (nonspecific) esterase, chloroacetate esterase, and peroxidase activity were performed on bone marrow aspirates containing malignant cells; all demonstrated diffuse positivity for acid phosphatase and nonspecific esterase, and negativity for peroxidase and chloroacetate esterase. Touch-imprint preparations of cutaneous lesions in one of these cases yielded identical results. These findings indicate that cytochemical methods are preferable to immunohistochemical technics in identification of histiocytic malignancies and that foci of skin involvement may provide a useful source for such diagnostic evaluation.
Stability of Plant Defense Proteins in the Gut of Insect Herbivores

Plant defense against insect herbivores is mediated in part by enzymes that impair digestive processes in the insect gut. Little is known about the evolutionary origins of these enzymes, their distribution in the plant kingdom, or the mechanisms by which they act in the protease-rich environment of the animal digestive tract. One example of such an enzyme is threonine (Thr) deaminase (TD), which in tomato ( Solanum lycopersicum ) serves a dual role in isoleucine (Ile) biosynthesis in planta and Thr degradation in the insect midgut. Here, we report that tomato uses different TD isozymes to perform these functions. Whereas the constitutively expressed TD1 has a housekeeping role in Ile biosynthesis, expression of TD2 in leaves is activated by the jasmonate signaling pathway in response to herbivore attack. Ingestion of tomato foliage by specialist ( Manduca sexta ) and generalist ( Trichoplusia ni ) insect herbivores triggered proteolytic removal of TD29s C-terminal regulatory domain, resulting in an enzyme that degrades Thr without being inhibited through feedback by Ile. This processed form (pTD2) of TD2 accumulated to high levels in the insect midgut and feces (frass). Purified pTD2 exhibited biochemical properties that are consistent with a postingestive role in defense. Shotgun proteomic analysis of frass from tomato-reared M. sexta identified pTD2 as one of the most abundant proteins in the excrement. Among the other tomato proteins identified were several jasmonate-inducible proteins that have a known or proposed role in anti-insect defense. Subtilisin-like proteases and other pathogenesis-related proteins, as well as proteins of unknown function, were also cataloged. We conclude that proteomic analysis of frass from insect herbivores provides a robust experimental approach to identify hyperstable plant proteins that serve important roles in defense.
Heat shock stress initiates simultaneous transcriptional and translational changes in the dog heart

Abstract The acute response to heat shock was examined in the intact canine heart. Ventricular samples were removed before the dogs were heated. After heat treatment, the hearts were removed. Total RNA was extracted from pre and post heat shocked samples, translated in vitro with [35S]methionine and visualized by autoradiography. Polysome profiles from pre and post heat shocked hearts were then analyzed. Heat shocked hearts synthesized mRNAs for 71 kD stress proteins. The polysome profile after heat treatment showed a steady decline of the polysomal material toward the heavier polysome region when compared to myocardium before heat treatment. Stress protein synthesis and polysomal disaggregation are initial responses to stress that, in the mammalian heart, may be precursors to hypertrophy.
Race, Residence, Discrimination, and Economic Opportunity Modeling the Nexus of Urban Racial Phenomena

A cross-sectional simultaneous equation model is specified wherein metropolitan-wide levels of racial residential segregation, housing discrimination, interracial occupational dissimilarities, and ...
An avian vocalization detector

A simple circuit to detect avian vocalizations is described. Adjustments of five different controls (frequency, bandwidth, amplitude, duration and spacing) allow the circuit to accurately detect the vocalizations of different ages and species of birds. Analyses of over 4000 peeps and 500 inter-peep intervals from 40 chicks and 16 ducklings showed that the circuit and an experienced observer agreed closely in the timing and counting of vocalizations.
Clinical and evoked pain, personality traits, and emotional states: Can familial confounding explain the associations?

Objectives Pain is a complex phenomenon influenced by context and person-specific factors. Affective dimensions of pain involve both enduring personality traits and fleeting emotional states. We examined how personality traits and emotional states are linked with clinical and evoked pain in a twin sample.
Multiple mechanisms of adriamycin resistance in the human leukemia cell line CCRF-CEM.

Abstract CEM cells exhibiting a 25-fold (C25X) or 80-fold (C80X) increase in resistance to adriamycin were isolated and characterized. C25X cells were cross-resistant to daunomycin and etoposide (VP-16) but not to vincristine or colchicine. These cells were not defective in the cellular accumulation of drug and did not contain detectable levels of P-glycoprotein. Continued exposure of C25X cells to adriamycin resulted in increased levels of resistance and additional phenotypic changes. These cells (C80X) now contained high levels of P-glycoprotein and were cross-resistant to a variety of agents including vincristine and colchicine. A fluorometric assay for DNA unwinding was used to measure levels of drug-induced DNA breaks in sensitive and C25X resistant cells. Studies carried out with VP-16, 4′9-acridinylaminomethanesulfon-m-anisidide (m-AMSA), adriamycin, or daunomycin showed that the level of drug-induced DNA strand breakage in resistant cells was considerably less than that occurring in drug treated sensitive cells. These studies, therefore, show that treatment of CEM cells with adriamycin resulted in a nuclear alteration that contributed to drug resistance. They also demonstrate that prolonged treatment of cells with adriamycin resulted in membrane alterations that affect cellular drug accumulation. Adriamycin resistance in CEM cells can thus occur as a result of at least two distinct mechanisms.
Characterization of the nonvolatile minor constituents responsible for the objectionable taste of defatted soybean flour.

A scheme was developed for the separation of the nonvolatile minor constituents from soy flour which are responsible for the astringent an bitter tastes. The scheme involved solvent extraction, freeze drying, and fractional crystallization. Two fractions, collected by semipreparative HPLC, had the characteristic bitter and astringent tastes. Further fractionation by reverse phase HPLC produced three pure compounds which were identified by UV, NMR spectrometry and elemental analysis, as daidzein, glycitein 7-β-O glucoside, and genestin. Preliminary sensory evaluation showed that these isoflavones might contribute additively to the undesirable bitter and astringent tastes of soy protein products.
Synthesis and Reactivity of [(DMSC)Ti(η2-OCAr2)L2] Complexes (DMSC = Dimethylsilyl-Bridged p-tert-Butylcalix[4]arene Dianion, Ar = Aryl Group, and L2 = Delocalized Diimine)

Reactions of titanapinacolate complexes [(DMSC)Ti(OCAr2CAr2O)] (1, Ar = Ph; 2, Ar = p-MeC6H4; DMSC = 1,2-alternate dimethylsilyl-bridged p-tert-butylcalix[4]arene dianion) with 1 equiv of a delocalized diimine furnished titanium η2-ketone complexes [(DMSC)Ti(η2-OCAr2)L2)] 3−6 (L2 = bpy, dmbpy, or phen). The ketone is weakly bound in 3−6, and it is readily dissociated. The compounds dissolve in aromatic hydrocarbon solvents to give intense green solutions and undergo a photochemically assisted transformation into 1-aza-5-oxa-titanacyclopentene derivatives 8−11, in which C−H activation of the heterocyclic diimine ligand and hydride migration to a Ti-bound ketone to form an alkoxide group has occurred. The reaction of 3−6 with one or more equivalents of appropriate ketone gave 8−11 in high yield. The compounds were characterized by NMR (1H and13C) and microanalysis data, as well as by X-ray crystallography for [(DMSC)Ti{κ3-OC(p-MeC6H4)2C10H7N2}{OCH(p-MeC6H4)2}] (9). The ease of transformation of [(DMSC)Ti{η2...
Novel identification of Dermacentor variabilis Arp2/3 complex and its role in rickettsial infection of the arthropod vector.

Tick-borne spotted fever group (SFG) Rickettsia species must be able to infect both vertebrate and arthropod host cells. The host actin-related protein 2/3 (Arp2/3) complex is important in the invasion process and actin-based motility for several intracellular bacteria, including SFG Rickettsia in Drosophila and mammalian cells. To investigate the role of the tick Arp2/3 complex in tick-Rickettsia interactions, open reading frames of all subunits of the protein including Arp2, Arp3, ARPC1, ARPC2, ARPC3, ARPC4, and ARPC5 were identified from Dermacentor variabilis. Amino acid sequence analysis showed variation (ranging from 25–88%) in percent identity compared to the corresponding subunits of the complex from Drosophila melanogaster, Mus musculus, Homo sapiens, and Saccharomyces cerevisiae. Potential ATP binding sites were identified in D. variabilis (Dv) Arp2 and Arp3 subunits as well as five putative WD (Trp-Asp) motifs which were observed in DvARPC1. Transcriptional profiles of all subunits of the DvArp2/3 complex revealed greater mRNA expression in both Rickettsia-infected and -uninfected ovary compared to midgut and salivary glands. In response to R. montanensis infection of the tick ovary, the mRNA level of only DvARPC4 was significantly upregulated compared to uninfected tissues. Arp2/3 complex inhibition bioassays resulted in a decrease in the ability of R. montanensis to invade tick tissues with a significant difference in the tick ovary, indicating a role for the Arp2/3 complex in rickettsial invasion of tick cells. Characterization of tick-derived molecules associated with rickettsial infection is imperative in order to better comprehend the ecology of tick-borne rickettsial diseases.
Caries-Preventive Effects of Daily and Weekly Fluoride Mouthrinsing in a Fluoridated Community: Final Results after 30 Months

Two groups of children rinsed their mouths at school once a week with a 0.2% solution of neutral sodium fluoride or once a day with a 0.05% neutral sodium fluoride solution. After 30 months, results showed that both mouthrinse procedures effectively reduced the incidence of dental caries.
Race, weight, and correlates of binge eating in female college students

This study examined the correlates of race, weight status, and binge eating among 715 female undergraduate students (77% Caucasian; 13% African American) enrolled at an urban university. Approximately 21.7% of Caucasians and 36.8% of African-Americans (AA) were overweight/obese. Higher BMI was associated with BED, and severity of binge eating symptoms. After removing participants who endorsed compensatory behaviors ≥ 1×/week from the analyses, 8.4% of the sample met criteria for BED (2.4% of the AA and 9.9% of the Caucasian students) and 44% reported severe binge eating symptoms. AA students were less likely to have BED than Caucasian students and reported less severe binge eating symptomatology. For Caucasian students, mood, cognitive restraint, drive for thinness, and BMI all contributed significant individual variance in binge eating severity. For African Americans, mood, body image dissatisfaction, and drive for thinness were found to be unique contributors. For those meeting criteria for BED, retrospectively recalled predictors of binge eating included negative affect (e.g., self-anger, worry, guilt), but not hunger. Behavioral triggers for binge behavior differed by race, as well, with African American students retrospectively reporting lower levels of anxiety prior to bingeing. Results from this study suggest that there are racial differences in binge eating behaviors. Future studies are needed to examine differences in eating practices among racial groups (e.g., grazing, large portions, high fat food preparation) that may contribute to early onset weight gain and obesity. The results suggest the importance of sensitive tailored weight and disordered eating interventions for college women from diverse backgrounds.
MEASURE+: a measurement-based dependability analysis package

Most existing dependability modeling and evaluation tools are designed for building and solving commonly used models with emphasis on solution techniques, not for identifying realistic models from measurements. In this paper, a measurement-based dependability analysis package, MEASURE+, is introduced. Given measured data from real systems in a specified format MEASURE+ can generate appropriate dependability models and measures including Markov and semi-Markov models, k-out-of-n availability models, failure distribution and hazard functions, and correlation parameters. These models and measures obtained from data are valuable for understanding actual error/failure characteristics, identifying system bottlenecks, evaluating dependability for real systems, and verifying assumptions made in analytical models. The paper illustrates MEASURE+ by applying it to the data from a VAXcluster multicomputer system. Models of field failure behavior identified by MEASURE+ indicate that both traditional models assuming failure independence and those few taking correlation into account are not representative of the actual occurrence process of correlated failures.
A Rule-Based Decision Support System for Critical Infrastructure Management

ABSTRACT This article presents a new rule-based decision support system for critical infrastructure management based on the interdependencies among critical infrastructures. Unlike the conventional flood front prediction model, the new failure front prediction model consists of both physical parameters and interdependencies among infrastructures, which is represented by a multi-level complex network. This study employs advanced computation methods to build tools for better understanding emergent behavior of water security infrastructure systems for use in developing superior preparedness and response strategies. This study highlights the important role played by the interdependencies among the infrastructures in failure front prediction.
Analysis of Masonry Bridges: Discrete Finite Element Method

Masonry bridges are composed of a finite number of distinct interacting blocks that have a length scale relatively comparable to the structure of interest. Therefore, they are ideal candidates for modeling as discrete systems instead of modeling as continuum systems. The discrete finite element method (DFEM) developed by the author to model discontinuum media consisting of blocks of arbitrary shapes is adopted in the static and dynamic analyses of masonry bridges. The developed DFEM is based on the principles of the FEM that incorporate contact elements. DFEM considers blocks as subdomains and represents them by solid elements. Contact elements, which are far superior to joint or interface elements, are used to model the block interactions, such as sliding or separation. In this study, the DFEM is briefly reviewed. Through some typical illustrative examples, the applicability of the DFEM to analysis of masonry arch bridges is examined and discussed. It is shown that the DFEM has the potential to become a useful tool for researchers and practicing engineers in designing, analyzing, and studying behavior of masonry bridges under static and dynamic loading.
Deep vein thrombosis and pulmonary embolism prophylaxis in joint replacement surgery.

As the population over the age of 65 increases in this country, the frequency of joint replacement secondary to arthritis or fractures will reflect this trend. Unique to this surgical group will be the frequency of postoperative thromboembolic disease. The incidence of deep vein thrombosis (DVT) overall in unprophylaxed patients has been documented to be between 45% to 57% for total hip replacement (THR), 39,43,51,89 36% to 60% for hip fracture (HF), 1,2,10,33,46,66,74,80,81 and 40% to 84% for total knee replacement (TKR). 15,60,85,86 Fatal pulmonary embolism varies between 0.34% and 6% in THR, 18,31,64,90 0.2% and 0.7% for TKR, 4,48,64 and 3.6% and 12.9% in patients following HF. 31,88 This high incidence of thromboembolic disease mandates appropriate assessment and management by physicians providing medical consultative services. This article reviews the pathophysiology of thrombosis, risk stratification, regimens for prophylaxis, and current literature on extended prophylaxis 4 to 6 weeks following surgery.
Blindsight in normal observers

Some patients with lesions in visual cortex lack conscious visual experience but, when tested, exhibit a significant ability, termed 'blindsight', to discriminate visual stimuli. Here we report two different visual displays that induce blindsight in normal observers. Using an objective measure, we show that conscious experience remains defective at presentation times much longer (1 s) than the onset of visual sensitivity (˜60 ms). To obtain this effect, we generate a contrast between visual textures and then conceal the contrast by superimposing 'complementary' textures. Complementarity can involve either opposite motion or binocular rivalry and orthogonal orientation. In both cases, observers locate the texture contrast reliably but do not, by either subjective or objective measures, consciously experience it. Taken together with present knowledge of the visual cortical site(s) at which opposite motion and rivalrous orientation interact, this observation bears upon the functional anatomy of conscious visual experience.
Extruded Soybeans and Corn Gluten Meal as Supplemental Protein Sources for Lactating Dairy Cattle

Abstract Holstein cows in early lactation were used to compare three combinations of extruded whole soybeans and corn gluten meal to soybean meal. Treatments were (as a percentage of supplemental crude protein) 100% soybean meal; 75% whole soybeans extruded at 149°C, 25% corn gluten meal; 50% extruded soybeans, 50% corn gluten meal; and 25% extruded soybeans, 75% corn gluten meal. Diets were formulated to be 37.5% corn silage, 12.5% alfalfa cubes, and 50% concentrate (dry matter). Dietary crude protein was 15.7% of dry matter, and supplemental protein sources supplied 27% of total dietary protein. Diets were fed as total mixed rations and data were collected from 4 to 116 d postpartum. Milk and fat-corrected milk yields ranged from 31.0 to 34.3 and from 29.3 to 33.3 kg/d, respectively, and were greater for cows fed soybean meal than those cows fed 75 or 50% of their supplemental protein as extruded soybeans. Milk yield of cows consuming 75% of their supplemental protein from corn gluten meal was similar to all other treatments. Ruminal ammonia concentrations were lower in cows fed extruded soybeans and corn gluten meal compared with those fed soybean meal and ranged from 9.1 to 12.4mg/100 ml. Total volatile fatty acid concentration and pH did not differ among treatments. Combinations of extruded soybeans and corn gluten meal were not advantageous compared with soybean meal as a supplemental protein source for lactating cows in this experiment.
Degree of completion of 3'-terminus of transfer ribonucleic acids of Bacillus subtilis 168 at various developmental stages and asporogenous mutants.

Abstract Transfer ribonucleic acids from sporulating cells, spores, sporangia, or stationary-phase asporogenous mutants of Bacillus subtilis all showed a deficiency in the 3′-terminal adenosine moiety.
Algorithms for self-healing networks

Many modern networks are reconfigurable, in the sense that the topology of the network can be changed by the nodes in the network. For example, peer-to-peer, wireless and ad-hoc networks are reconfigurable. More generally, many social networks, such as a company’s organizational chart; infrastructure networks, such as an airline’s transportation network; and biological networks, such as the human brain, are also reconfigurable. Modern reconfigurable networks have a complexity unprecedented in the history of engineering, resembling more a dynamic and evolving living animal rather than a structure of steel designed from a blueprint. Unfortunately, our mathematical and algorithmic tools have not yet developed enough to handle this complexity and fully exploit the flexibility of these networks. We believe that it is no longer possible to build networks that are scalable and never have node failures. Instead, these networks should be able to admit small, and maybe, periodic failures and still recover like skin heals from a cut. This process, where the network can recover itself by maintaining key invariants in response to attack by a powerful adversary is what we call self-healing. Here, we present several fast and provably good distributed algorithms for self-healing in reconfigurable dynamic networks. Each of these algorithms have different properties, a different set of gaurantees and limitations. We also discuss future directions and theoretical questions we would like to answer.
On the competitive optimality of Huffman codes

Let X be a discrete random variable drawn according to a probability mass function p(x), and suppose p(x), is dyadic, i.e., log(1/p(x)) is an integer for each x. It is shown that the binary code length assignment l(x)=log(1/p(x)) dominates any other uniquely decodable assignment l'(x) in expected length in the sense that El(X) Pr(l (X)>l'(X)), which indicates l is also optimal in the short run. In general, if p is not dyadic then l=(log 1/p) dominates l'+1 in expected length and competitivity dominates l'+1, where l' is any other uniquely decodable code. >
Solving dots-and-boxes

Dots-And-Boxes is a well-known and widely-played combinatorial game. While the rules of play are very simple, the state space for even very small games is extremely large, and finding the outcome under optimal play is correspondingly hard. In this paper we introduce a Dots-And-Boxes solver which is significantly faster than the current state-of-the-art: over an order-of-magnitude faster on several large problems. Our approach uses Alpha-Beta search and applies a number of techniques--both problem-specific and general--that reduce the search space to a manageable size. Using these techniques, we have determined for the first time that Dots-And-Boxes on a board of 4 × 5 boxes is a tie given optimal play; this is the largest game solved to date.
RASC: Dynamic Rate Allocation for Distributed Stream Processing Applications

In today's world, stream processing systems have become important, as applications like media broadcasting, sensor network monitoring and on-line data analysis increasingly rely on real-time stream processing. In this paper, we propose a distributed stream processing system that composes stream processing applications dynamically, while meeting their rate demands. Our system consists of the following components: (1) a distributed component discovery algorithm that discovers components available at nodes on demand, (2) resource monitoring techniques to maintain current resource availability information, (3) a scheduling algorithm that schedules application execution, and (4) a minimum cost composition algorithm that composes applications dynamically based on component and resource availability and scheduling demands. Our detailed experimental results, over the PlanetLab testbed, demonstrate the performance and efficiency of our approach.