cssi/SciSciGPT-SciSciNet huggingface dataset:
Cross-reactivity between cockroach allergens and arthropod, nematode and mammalian allergens

Summary Cockroaches (CRs) are major indoor allergens that can pose a serious risk for respiratory allergies in sensitized subjects. Recent evidence suggests that CR allergens cross-react with allergens present in insect and other invertebrates. IgE antibodies of insect-allergic subjects were shown to react with silverfish, CR and chironomid extracts. Cross-reactivity between house dust mites, silverfish, CR and chironomids and between cockroach and the reduviid, German CR and chironomids, and CRs crustacea species was established by RAST inhibition. There is some evidence that CR cross-reacts with the nematodes Anisakis and Ascaris. No cross-reactivity has been demonstrated between CR and mammalian allergens. The protein implicated in the cross-reactivity of CR with invertebrate allergens is tropomyosin. Tropomyosin has been identified as a major allergen in shrimp and other crustacea, CR, dust mites, and squid ; these tropomyosins show substantial amino acid homology as well as immunological cross-reactivity. Clinical relevance of these cross-reactivities is suggested.
De Novo Formal Synthesis of (−)-Apicularen A via an Iterative Asymmetric Hydration Sequence

A de novo approach to the formal total synthesis of the macrolide natural product (−)-apicularen A has been achieved in 18 steps from achiral starting materials. Both the absolute and relative stereochemistries of apicularen A were introduced by a Sharpless asymmetric dihydroxylation, a π-allyl-palladium catalyzed reduction, a stereoselective reduction, and a base-promoted transannulation to install the C-9 stereocenter.
Identification of genetic loci associated with fire blight resistance in Malus through combined use of QTL and association mapping

Fire blight, incited by the enterobacterium Erwinia amylovora, is a destructive disease of Rosaceae, particularly of apples and pears. There are reports on the molecular mechanisms underlying E. amylovora pathogenesis and how the host activates its resistance mechanism. The host's resistance mechanism is quantitatively controlled, although some major genes might also be involved. Thus far, quantitative trait loci (QTL) mapping and differential expression studies have been used to elucidate those genes and/or genomic regions underlying quantitative resistance present in the apple genome. In this study, an effort is undertaken to dissect the genetic basis of fire blight resistance in apple using both QTL and genome-wide association mapping. On the basis of an F1 pedigree of ‘Coop 16’ × ‘Coop 17’ and a genome-wide association study (GWAS) mapping population of Malus accessions (species, old and new cultivars and selections), new QTLs and associations have been identified. A total of three QTLs for resistance to fire blight, with above 95% significant logarithm of odds threshold value of 2.5, have been identified on linkage groups (LGs) 02, 06, and 15 of the apple genome with phenotypic variation explained values of 14.7, 20.1 and 17.4, respectively. Although elevated P-values with signals for marker-trait associations are observed for some LGs, these are not found to be significant. However, a total of 34 significant associations, with P-values ≥0.02, have been detected including 8 for lesion length at 7 days following inoculation (PL1), 14 for lesion length at 14 days following inoculation (PL2), and 12 for shoot length.
Fast reversible wavelet image compressor

We present a unified image compressor with spline biorthogonal wavelets and dyadic rational filter coefficients which gives high computational speed and excellent compression performance. Convolutions with these filters can be preformed by using only arithmetic shifting and addition operations. Wavelet coefficients can be encoded with an arithmetic coder which also uses arithmetic shifting and addition operations. Therefore, from the beginning to the end, the while encoding/decoding process can be done within a short period of time. The proposed method naturally extends form the lossless compression to the lossy but high compression range and can be easily adapted to the progressive reconstruction.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Predictors of survival in patients with spinal ependymoma

AbstractObjectives:We aimed to examine the impact of demographic and treatment factors on overall survival among spinal ependymoma patients.Methods:Using data from Surveillance, Epidemiology, and End Results (SEER) from 1990–2008, we evaluated subjects with histologically confirmed spinal cord ependymoma.Results:We identified 1,353 patients with spinal ependymoma (mean age 43.5 years). Among these, 26 had anaplastic ependymoma (AE), 374 had myxopapillary ependymoma (MPE), and 953 had other low-grade ependymoma (non-MPE). Median follow-up was 61 months. Overall survival at 5 years was 97% for MPE, 92% for low-grade non-MPE, and 73% for AE. Gross total resection (GTR) was achieved in 58% of subjects with MPE, 51% with low-grade non-MPE, and 50% with AE. Radiation occurred more often after subtotal resection (STR) than after GTR, and more often among those with anaplastic histology. Histology and extent of surgical resection were significant prognostic factors in multivariate analyses. Compared to MPE, subje...
Second-trimester loss and subsequent pregnancy outcomes: What is the real risk?

Objective This study was performed to determine whether second-trimester pregnancy loss was associated with an increased risk for spontaneous preterm birth or recurrent second-trimester loss in a subsequent pregnancy. Study Design A retrospective cohort study was conducted. Patients with a second-trimester pregnancy loss (n = 38), a spontaneous preterm birth (n = 76), and a full term delivery (n = 76) were identified from 2002 to 2005 (index pregnancy). Computerized medical records were used to obtain demographic and obstetrical histories. Results Frequencies of subsequent second-trimester loss were 27%, 3%, and 1% in the second-trimester loss, spontaneous preterm birth, and full-term delivery cohorts, respectively. Frequencies of subsequent spontaneous preterm birth were 33%, 39.5%, and 9% in the same 3 cohorts. Patients with a prior second-trimester loss were 10.8 times more likely to have recurrent second-trimester loss or spontaneous preterm birth, compared with those with prior full-term delivery (confidence interval 3.6 to 32.1, P Conclusion Patients with a prior second-trimester loss are at significantly increased risk for spontaneous preterm birth and recurrent second-trimester loss in their next pregnancy.
An open study of methylphenidate in bipolar depression.

Background The treatment of bipolar depression is problematic. Mood stabilizing agents are often inadequate, while antidepressants may induce mania or mood destabilization. Methylphenidate has been advocated as an effective antidepressant agent in unipolar depression, and depression secondary to medical illness. Amphetamine administration has been shown to reduce manic behavior. These independent observations suggest that methylphenidate may be a safe and effective agent in bipolar depression. Methods Fourteen depressed subjects with DSM-IV bipolar illness and a Hamilton-depression (HAM-D) scale score of at least 15 had methylphenidate added to a stable mood stabilizer regiment. Patients were followed weekly for 4 weeks and then biweekly for an additional 8 weeks. Results HAM-D scores dropped from 16.9 +/- 1.79 SD at baseline to 9.4 +/- 9.73 on week 12 (p = 0.12, t = 1.84, df= 6) and 9.8 +/- 7.56 on last observation carried forward (LOCF) (p = 0.019, t = 2.8, df = 10). Psychiatric symptom assessment scale (PSAS) scores dropped from 17.9 +/- 5.63 at baseline to 4.8 +/- 7.47 at week 12 (p = 0.016, t = 4.02, df= 4) and 6.3 +/- 6.75 on LOCF (p = 0.007, t = 3.74, df = 7). Three individuals stopped secondary to anxiety, agitation, and hypomania, respectively. Conclusion In this brief, open study, methylphenidate was effective and relatively safe in depressed bipolar subjects.
Relief of Carbon Dioxide Narcosis by Simple Intermittent Positive Pressure Therapy

The history of a patient is presented in which severe carbon dioxide narcosis and right heart failure resulted from long standing pulmonary emphysema. The usual cardiac regime was ineffective and relief was obtained by the use of simple intermittent positive pressure therapy on compressed air. It is suggested that pulmonary hypertension from the hypercapnia may be the controlling factor in patients of this type.
Polyribosomes and control of protein synthesis: Effects of sodium fluoride and temperature in reticulocytes

Reticulocytes from phenylhydrazine-treated rabbits were pre-incubated with 0·01 M -sodium fluoride to inhibit protein synthesis and dissociate polyribosomes to 80 s ribosomes. Upon incubation of these cells without fluoride, protein synthesis is restored and reaches rates comparable to control cells (not pre-incubated with fluoride) within three minutes at 37°C when only a fraction of the polyribosomes have re-formed. In these cells, polyribosome content and polyribosome size may continue to increase for 60 to 120 minutes at 37°C without a change in rate of protein synthesis. As polyribosome content increases, the specific activity of the polyribosomes remains constant. These data indicate that in these cells polyribosome content is not the factor which limits the rate of protein synthesis. An estimate of the time for globin chain synthesis indicates that it increases progressively as polyribosome content increases. The protein synthesized during polyribosome formation in fluoride pre-incubated cells is predominantly globin and, by sedimentation and chromatographic characteristics, indistinguishable from the protein synthesized in control cells. The effect of the temperature of incubation on protein synthesis by reticulocytes was examined. In contrast to the alterations in polyribosomes with a constant rate of protein synthesis during recovery from the “fluoride effect”, increasing the temperature of incubation of reticulocytes between 17 and 37°C is associated with no change in polyribosome size or content, but an increase in polyribosome specific activity and in rate of protein synthesis. The data are interpreted in terms of mechanisms which might alter polyribosome size, content and/or function in reticulocytes which synthesize no RNA.
On the coupling of respiration to cation transport in slices of rat liver.

Abstract 1. 1. Rat-liver slices utilizing endogenous substrate respired at a rate of 9.2 μl O 2 per mg fat-free dry wt. per h, in a medium containing 5 mM K + and 161 mM Na + . Inhibition of the active transport of Na + and K + by ouabain, reduced the rate of respiration of these slices by 2.4 μl O 2 per mg per h (26% inhibition). 2. 2. In a medium containing 75 mM K + and 91 mM Na + , the control rate of respiration was 10.1 μl O 2 per mg fat-free dry wt. per h; ouabain lowered this by only 0.8 μl per mg per h (8% inhibition). It is suggested that the latter portion of the total O 2 uptake is coupled to the energy requirements of ion transport (‘transport-coupled respiration’). The additional inhibition caused by ouabain in the 5 mM K + medium appears to be due to changes in the oxidative metabolism resulting from the altered cation composition of the intracellular environment (‘cation-sensitive respiration’). 3. 3. Malonate and ethanol, at concentrations which are known to inhibit citric acid cycle activity, have little effect on ion transport. 4. 4. In the presence of ethanol or malonate, inhibition of ion transport (by ouabain, or K + -free medium) inhibits respiration only by an amount similar to the transport-coupled respiration (0.65–1.16 μl per mg per h). The cation-sensitive portion of the respiration appears to be due to the provision of reducing equivalents by the citric acid cycle. 5. 5. Approximate calculations are made of the amount of energy made available by the transport-coupled respiration, and this is compared to an estimate of the minimal energy requirement of the Na + transport.
Drug utilization and cost in a Medicaid population: A simulation study of community vs. mail order pharmacy

Outpatient drugs are dispensed through both community and mail order pharmacies. There is no empirical evidence that substitution of community pharmacy with mail order reduces overall drug expenditures. The need for evaluating the potential effects on utilization and costs of the possible extension of mail order services in Medicaid provides the rationale for conducting this study. This study compares drug utilization and drug product cost in community vs. mail order pharmacy dispensing services in a Medicaid population. This study is a retrospective cohort study comparing utilization and cost patterns in community vs. mail order pharmacy. A simulation model was employed to assess drug utilization and cost in mail order pharmacy using community pharmacy claim data. The model assumed that courses of drug therapy (CDT) in mail order pharmacy would have utilization patterns similar to those found in community pharmacy. A 95% confidence interval surrounding changes in average utilization and average cost were estimated using bootstrap analysis. A sensitivity analysis was performed by varying drug selection criteria and supply, fill point, and medication possession ratio (MPR). Sub-analyses were performed to address differences between mail order and community pharmacy related to therapeutic class and dual-eligible patients. Data for the study derived from pharmacy claims database of Ohio Medicaid State program for the period January 2000-September 2004. Drug claims were aggregated to obtain a set of CDTs representing unique patient IDs and unique drug products. Drug product cost estimates excluded dispensing fees and were used to estimate the cost reduction required in mail order to become cost neutral in comparison with community pharmacy. The baseline model revealed that the use of mail order vs. community pharmacy would result in a 5.5% increase in drug utilization and a 5.4% cost reduction required in mail order to become cost neutral. Results from Ohio Medicaid drugs for chronic use revealed a 5.1% increase in utilization and a 4.9% cost reduction required to become cost neutral in comparison with community pharmacy. The results of the simulation model indicate that mail order pharmacy increases drug utilization and can also increase drug product cost if the cost per unit is not reduced accordingly. Prior consideration should be given to the patient population, day-supply, disease, therapy, and insurance characteristics to ensure the appropriate use of mail order pharmacy services.
Quantitative analysis of, the principle soy isoflavones genistein, daidzein and glycitein, and their primary conjugated metabolites in human plasma and urine using reversed-phase high-performance liquid chromatography with ultraviolet detection

Soy isoflavones are becoming of increasing interest as nutritional agents which can be used to combat osteoporosis and hyperlipidemia, and are also being considered as potential cancer chemopreventive compounds. However, prior to their formulation and distribution as therapeutic agents, thorough pharmacokinetic and toxicological assessment needs to be completed in men and women in a variety of health conditions in order to ensure their therapeutic efficacy and safety. At this time, studies of purified soy isoflavones are possible, and are being designed to fully evaluate the pharmacological utility of these preparations. In support of these studies, quantitative analysis of soy isoflavones in biological fluids can be accomplished with a wide variety of methods and analytical instrumentation. However, the relatively ubiquitous presence of high-performance liquid chromatography with ultraviolet detection (HPLC-UV) in most analytical laboratories, the relative ease of its operation, and the lesser expense of this instrumentation as compared to more sophisticated techniques such as liquid chromatography-mass spectrometry, offers some distinct advantages for its use in pharmacokinetic studies. In this manuscript, the development and validation of an HPLC-UV method for the quantitation of the principal soy isoflavones, genistein, daidzein, and glycitein, and their primary metabolites, in human plasma and urine is described. This analytical approach allows for pharmacologically relevant concentrations of the analytes and their principle metabolites to be detected, and has been validated in close agreement with the US Food and Drug Administration's guidelines for the validation of methods to be used in support of pharmacokinetic studies.
Infants' perceptual differentiation of amodal and modality-specific audio-visual relations.

Abstract Ninety-six infants of 3 1 2 months were tested in an infant-control habituation procedure to determine whether they could detect three types of audio-visual relations in the same events. The events portrayed two amodal invariant relations, temporal synchrony and temporal microstructure specifying the composition of the objects, and one modality-specific relation, that between the pitch of the sound and the color/shape of the objects. Subjects were habituated to two events accompanied by their natural, synchronous, and appropriate sounds and then received test trials in which the relation between the visual and the acoustic information was changed. Consistent with Gibson's increasing specificity hypothesis, it was expected that infants would differentiate amodal invariant relations prior to detecting arbitrary, modality-specific relations. Results were consistent with this prediction, demonstrating significant visual recovery to a change in temporal synchrony and temporal microstructure, but not to a change in the pitch-color/shape relations. Two subsequent discrimination studies demonstrated that infants' failure to detect the changes in pitch-color/shape relations could not be attributed to an inability to discriminate the pitch or the color/shape changes used in Experiment 1. Infants showed robust discrimination of the contrasts used.
Infrared Faraday rotation of n-type InSb.

The Faraday rotation of n-type InSb has been measured for wavelengths between 8.0 and 13.0 \ensuremath{\mu}m at 9 K, using magnetic fields up to 150 kG. Measurements were made on samples with nominal carrier concentration of 1\ifmmode\times\else\texttimes\fi{}${10}^{14}$, 6\ifmmode\times\else\texttimes\fi{}${10}^{14}$, 1\ifmmode\times\else\texttimes\fi{}${10}^{15}$, and 5\ifmmode\times\else\texttimes\fi{}${10}^{15}$ ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}3}$. The experimental results have been successfully analyzed in terms of interband and intraband transitions at the \ensuremath{\Gamma} point in the Brillouin zone, using a quantum-mechanical treatment. The four-band k\ensuremath{\cdot}p Pidgeon and Brown model was used to calculate the energy levels and the matrix elements for these transitions.
Photoionization of neon between 100 and 2000 eV: Single and multiple processes, angular distributions, and subshell cross sections

All aspects of photoionization in the soft-x-ray region are taken into account, and a complete partitioning of the photoionization cross section of neon is given in terms of single-electron processes in $2p$, $2s$, and $1s$ subshells and multiple-electron processes involving these subshells. The various processes, including their angular dependences, are identified and studied by the technique of photoelectron spectrometry. The partition relies solely on experimental evidence. Absolute subshell cross sections for the emission of a single electron are compared with current theoretical predictions: The single-particle, frozen-structure model (Cooper, 1962) that uses the Herman-Skillman potential overestimated ${\ensuremath{\sigma}}_{2p}$ by up to 15%, ${\ensuremath{\sigma}}_{2s}$ by (25-35)%, and ${\ensuremath{\sigma}}_{1s}$ by about 20%; the random-phase-approximation-with-exchange model (Amusia, 1972) that includes multielectron correlation and uses Hartree-Fock wave functions predictions correctly ${\ensuremath{\sigma}}_{2s}$ at $110lh\ensuremath{\nu}l220$ eV, where comparative data exist. The absolute cross section for double ionization in the $L$ shell is 5 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}20}$ ${\mathrm{cm}}^{2}$ at $h\ensuremath{\nu}=278$ eV as compared with the theoretical value of 4 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}20}$ ${\mathrm{cm}}^{2}$. The energy dependence of simultaneous excitation and ionization processes in the $L$ shell is reported. A finite threshold value is observed and a plateau at higher energy is indicated. For $h\ensuremath{\nu}g130$ eV, $\ensuremath{\epsilon}l,{n}^{\ensuremath{'}}{l}^{\ensuremath{'}}$ transitions are found to be most probable in which the continuum electron changes its angular momentum, $\ensuremath{\Delta}l=\ifmmode\pm\else\textpm\fi{}1$, and the excited electron retains its momentum, $\ensuremath{\Delta}l=0$, namely $2{p}^{6}\ensuremath{\rightarrow}2{p}^{4}\ensuremath{\epsilon}d,np$. Anisotropy parameters $\ensuremath{\beta}$ for $2p$ electrons agree well with theoretical results; however an unexplained maximum near $\ensuremath{\theta}={0}^{\ensuremath{\circ}}$ at $h\ensuremath{\nu}g1$ keV is found for the angular distributions of $2p$ photoelectrons.
Arthropod natural enemies of the Colorado potato beetle.

Abstract Mites, phalangids, spiders and insects have been studied as potential biological control agents of the Colorado potato beetle, Leptinotarsa decemlineata (Say). Insects include lacewings (Neuroptera: Chrysopidae), predatory stink bugs (Hemiptera: Pentatomidae, subfamily Asopinae), parasitic flies (Diptera: Tachinidae), predatory beetles (Coleoptera: Coccinelidae, Cicinilidae, Staphylinidae and Carabidae) and parasitic and predatory Hymenoptera. Both augmentative release and conservation of natural enemies are likely to increase in importance in Colorado potato beetle management, as broad-spectrum insecticides are replaced by more selective materials.
Development of a model to predict air contaminant concentrations following indoor spills of volatile liquids

A personal computer spreadsheet model which predicts air contaminant concentrations following indoor spills of volatile liquids has been developed. Three mass transfer models are compared for predicting evaporative flux in the model, the flat plate mass transfer theory, Penetration Theory, and Mackay and Matsugu models. Two methods of predicting spill temperature during evaporation are presented, the isothermal method, which assumes spill temperature remains at ambient throughout evaporation, and the spill temperature method, which predicts spill temperature using equations developed from a heat balance over the spill pool. Dispersion is approximated in the model as a well-mixed room with short-circuiting. Model equations are programmed into a Lotus 1,2,3 spreadsheet. Calculations of room concentration, spill pool surface temperature, and spill area are made at consecutive 20-s intervals following the spill. Model predictions are compared with concentration measurements made after two test spills in a laboratory. The model gives a good first estimate of room concentration, performing best when the spill is assumed to be isothermal and the Penetration Theory or Mackay and Matsugu methods are used to predict evaporation rate.
RF System Design for the Slac Storage Ring

In the proposed SLAC electron-positron storage ring, two one-ampere, 3-GeV beams will radiate energy at the rate of 1.13 megawatts with 880-kV peak voltage required for storage. This energy is restored through a six-cavity rf system operating at 50 MHz, the 36th harmonic of the rotation frequency. Of the total power over 90% will be delivered to the beams with the remaining part to the cavities and their associated networks. An experimental ultra-high vacuum cavity designed to operate at 200 kV peak across its accelerating gap and capable of dissipating 20 kilowatts in wall losses is described. The requirements of an automatic tuning and coupling system which will match continuously the cavity and the beam to the amplifier output are discussed.
Disparity estimation window size

Disparity estimation plays a crucial role in many stereo image compression techniques. To reduce computational complexity most methods limit the estimation search area to a limited window. The performance of the disparityestimation depends on the choice of the limited search window. Most techniques use a predetermined value for the window size, which is not optimal over a wide range of images. We show how the choice of the window size affects the performance of the stereo image compression algorithm and propose a method to obtain a better search window size. Our simulation results indicate an improvement of up to 1.81 dB over rigid window size selection and with performance very close to the optimal selection.
A quadratic nonconforming vector finite element for H(curl; Ω) ∩ H(div; Ω)

Abstract We present a quadratic nonconforming vector finite element for problems posed on the space H ( curl ; Ω ) ∩ H ( div ; Ω ) , where Ω ⊂ R 2 . Generalizations to higher order and higher dimension are also discussed.
A comparison of three combinations of injectable anesthetics in miniature donkeys

Abstract Objective To compare three combinations of injectable anesthetics in miniature donkeys for quality of induction, recovery, muscle relaxation, cardiopulmonary changes during anesthesia and duration of recumbency. Design Prospective, randomized experimental study. Animals Six miniature donkeys ( Materials and methods The drug combinations were: xylazine−butorphanol−ketamine (XBK), xylazine−butorphanol−tiletamine−zolazepam (XBT) and xylazine−propofol (XP). Each miniature donkey was anesthetized with each combination at 1–week intervals in random order. Heart and respiratory rates, indirect blood pressure and temperature were measured before and at 5–minute intervals during recumbency. Arterial blood samples were drawn for blood–gas analysis before and at 5, 15 and 30 minutes of anesthesia when samples could be collected. Recumbency time to sternal and time to standing were recorded and a subjective evaluation of induction, muscle relaxation and recovery were made. Results Mean recumbency time ± SD was 14.7 ± 9.4, 33.8 ± 6.3 and 14.6 ± 1.9 minutes with XBK, XBT and XP, respectively. Mean time to standing ± SD was 28.4 ± 11.3, 43.7 ± 7.2 and 26.3 ± 2.9 minutes with XBK, XBT and XP, respectively. Heart and respiratory rates and blood pressures varied from baseline but were always within normal ranges. Hemoglobin saturation, pH and PaO 2 tended to be lower with these doses of XBT and XP. Conclusions and clinical relevance Overall quality of anesthesia was poor with XBK. At the doses used this combination did not provide sufficient anesthesia compared with the combinations of XBT and XP, which appeared to provide acceptable anesthesia of short duration in miniature donkeys.
The impelling function method applied to global optimization

A new global optimization method, the impeller function method (IFM), is proposed in this paper. Both the theory and the algorithm are presented. This new approach is analogous to a classical achievement in the local optimization research: the penalty function method (PFM). Therefore, the significance of the IFM for global optimization is expected to be similar to that of the PFM for local optimization.
Electron transfer reactions relevant to atom transfer radical polymerization

The continuous development of more active and stable catalysts in atom transfer radical polymerization (ATRP) has increasingly required a thorough knowledge of concurrent electron transfer reactions that can affect catalyst performance. Special attention is provided in this short review to such processes, including disproportionation, most pronounced in Cu-mediated ATRP, the reduction of radicals to carbanions or oxidation to carbocations, and radical coordination to the metal catalyst resulting in the interplay of controlled radical polymerization mechanisms.
Recent developments in oral chemotherapy options for gastric carcinoma.

The incidence of carcinoma of the stomach is low in the United States, Canada, and Australia but is a significant health problem in Asia, South America, Eastern Europe, and countries of the previous Soviet Union. For patients with advanced disease, chemotherapy remains palliative. With the increasing emphasis on patients’ quality of life, convenience, and cost containment, oral chemotherapy has come into increasing focus. We review oral chemotherapy agents for use in patients with advanced gastric carcinoma.
The application of micro-coil NMR probe technology to metabolomics of urine and serum

Increasing the sensitivity and throughput of NMR-based metabolomics is critical for the continued growth of this field. In this paper the application of micro-coil NMR probe technology was evaluated for this purpose. The most commonly used biofluids in metabolomics are urine and serum. In this study we examine different sample limited conditions and compare the detection sensitivity of the micro-coil with a standard 5 mm NMR probe. Sample concentration is evaluated as a means to leverage the greatly improved mass sensitivity of the micro-coil probes. With very small sample volumes, the sensitivity of the micro-coil probe does indeed provide a significant advantage over the standard probe. Concentrating the samples does improve the signal detection, but the benefits do not follow the expected linear increase and are both matrix and metabolite specific. Absolute quantitation will be affected by concentration, but an analysis of relative concentrations is still possible. The choice of the micro-coil probe over a standard tube based probe will depend upon a number of factors including number of samples and initial volume but this study demonstrates the feasibility of high-throughput metabolomics with the micro-probe platform.
Associations of N-terminal pro–B-type natriuretic peptide with kidney function decline in persons without clinical heart failure in the Heart and Soul Study

Background Subclinical volume overload in the absence of diagnosed heart failure (HF) may be an underrecognized contributor to kidney function decline in coronary artery disease (CAD) patients. We evaluated associations of circulating N-terminal pro–B-type natriuretic peptide (NT-proBNP), a marker of ventricular stretch, with change in estimated glomerular filtration rate (eGFR). Methods We evaluated 535 patients with stable CAD and no history of HF, who were enrolled in the Heart and Soul Study and followed for 5 years. N-terminal pro–B-type natriuretic peptide was measured at baseline. We evaluated the associations of NT-proBNP with change in kidney function over 5 years: ( a ) annual percent change in eGFR, ( b ) rapid kidney function loss (>3% per year for 5 years), and ( c ) incident eGFR 2 . In multivariable models, we adjusted for demographics, comorbid conditions, echocardiographic parameters, medications, and baseline kidney function. Results Among 535 participants, median NT-proBNP was 130.6 (interquartile range 61.8-280.9) pg/mL, and median B-type natriuretic peptide (BNP) was 32.5 (14.4-75.9) pg/mL. Individuals with NT-proBNP levels in the highest quartile (>280.9 pg/mL) had a greater odds of rapid kidney function loss after full adjustment (odds ratio 2.95; 95% CI 1-8.65; P = .0492). Associations with incident eGFR 2 were also significant (adjusted odds ratio 4.23; 95% CI 1.05-16.98; P = .0422). Results were similar when analyzed using BNP as the predictor. Conclusions N-terminal pro–B-type natriuretic peptide and BNP are strongly and independently associated with accelerated kidney function loss, even in the absence of clinical HF. These findings suggest that subclinical cardiovascular dysfunction may contribute to elevated kidney disease risk in persons with CAD.
Loss of Plasma Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) After Lipoprotein Apheresis

Rationale: Lipoprotein apheresis (LA) reduces low-density lipoprotein (LDL) levels in patients with severe familial hypercholesterolemia (FH). We have recently reported that >30% of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) is bound to LDL, thus we predicted that LA would also reduce plasma PCSK9 levels by removing LDL. Objective: Pre- and post-apheresis plasma from 6 patients with familial hypercholesterolemia on 3 consecutive treatment cycles was used to determine changes in PCSK9 levels. Methods and Results: LA drastically reduced plasma LDL (by 77±4%). Concomitantly, PCSK9 levels fell by 52±5%, strongly correlating with the LDL drop ( P =0.0322; r 2=0.26), but not with decreases in triglyceride (49±13%) or high-density lipoprotein levels (18±2%). Levels of albumin, creatinine, and CK-MB did not show significant changes after LA. Similar to LDL, PCSK9 levels returned to pretreatment values between cycles (2-week intervals). Fractionation of pre- and post-apheresis plasma showed that 81±11% of LDL-bound PCSK9 and 48±14% of apolipoprotein B–free PCSK9 were removed. Separation of whole plasma, purified LDL, or the apolipoprotein B–free fraction through a scaled-down, experimental dextran sulfate cellulose beads column produced similar results. Conclusions: Our results show, for the first time, that modulation of LDL levels by LA directly affects plasma PCSK9 levels, and suggest that PCSK9 reduction is an additional benefit of LA. Because the loss of PCSK9 could contribute to the LDL-lowering effect of LA, then (1) anti-PCSK9 therapies may reduce frequency of LA in patients currently approved for therapy, and (2) LA and anti-PCSK9 therapies may be used synergistically to reduce treatment burden. # Novelty and Significance {#article-title-32}
Therapy for and Prevention of Traveler's Diarrhea

Acute diarrhea associated with international travel is commonly caused by enterotoxigenic Escherichia coli, enteroaggregative E. coli, or noroviruses. Early studies to define these enteropathogens took place at the University of Maryland during the Theodore E. Woodward years. Although a reduction in the rate of diarrhea may be possible through avoidance of foods and beverages likely to be contaminated, a more effective preventive strategy is to administer nonabsorbed (<0.4%) rifaximin each day during trips to areas where the risk of traveler's diarrhea is high (i.e., high-risk areas). For the self-treatment of diarrhea that occurs during travel, all persons planning trips to high-risk areas should take with them medication with expected activity against the prevalent bacterial enteropathogens: rifaximin (for the treatment of common afebrile, nondysenteric diarrhea), a fluoroquinolone, or azithromycin. Further study is needed to determine whether it is possible to avoid important morbidity associated with diarrhea and the development of postinfectious irritable bowel syndrome with chemoprophylaxis and/or early effective treatment.
Cloning of the Rhesus Lymphocryptovirus Viral Capsid Antigen and Epstein-Barr Virus-Encoded Small RNA Homologues and Use in Diagnosis of Acute and Persistent Infections

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with the development of several human malignancies. A closely related herpesvirus in the same lymphocryptovirus (LCV) genera as EBV naturally infects rhesus monkeys and provides an important animal model for studying EBV pathogenesis. We cloned the small viral capsid antigen (sVCA) homologue from the rhesus LCV and developed a peptide enzyme-linked immunosorbent assay (ELISA) to determine whether epitopes in the rhesus LCV sVCA are a reliable indicator of rhesus LCV infection. In order to define a “gold standard” for rhesus LCV infection, we also cloned the EBV-encoded small RNA 1 (EBER1) and EBER2 homologues from rhesus LCV and developed a reverse transcription (RT)-PCR assay to detect persistent LCV infection in rhesus monkey peripheral blood lymphocytes. Animals from a conventional and a hand-reared colony were studied to compare the prevalence of rhesus LCV infection in the two groups. There was a 100% correlation between the peptide ELISA and EBER RT-PCR results for rhesus LCV infection. In addition, specificity for LCV infection and exclusion of potential cross-reactivity to the rhesus rhadinovirus sVCA homologue could be demonstrated using sera from experimentally infected animals. These studies establish two novel assays for reliable diagnosis of acute and persistent rhesus LCV infections. The rhesus LCV sVCA peptide ELISA provides a sensitive and reliable assay for routine screening, and these studies of the hand-reared colony confirm the feasibility of raising rhesus LCV-naive animals.
Carotid Plaque MRI and Stroke Risk A Systematic Review and Meta-analysis

Background and Purpose— MRI characterization of carotid plaque has been studied recently as a potential tool to predict stroke caused by carotid atherosclerosis. We performed a systematic review and meta-analysis to summarize the association of MRI-determined intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap with subsequent ischemic events. Methods— We performed a comprehensive literature search evaluating the association of carotid plaque composition on MRI with ischemic outcomes. We included cohort studies examining intraplaque hemorrhage, lipid-rich necrotic core, or thinning/rupture of the fibrous cap with mean follow-up of ≥1 month and an outcome measure of ipsilateral stroke or transient ischemic attack. A meta-analysis using a random-effects model with assessment of study heterogeneity and publication bias was performed. Results— Of the 3436 articles screened, 9 studies with a total of 779 subjects met eligibility for systematic review. The hazard ratios for intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap as predictors of subsequent stroke/transient ischemic attack were 4.59 (95% confidence interval, 2.91–7.24), 3.00 (95% confidence interval, 1.51–5.95), and 5.93 (95% confidence interval, 2.65–13.20), respectively. No statistically significant heterogeneity or publication bias was present in the 3 main meta-analyses performed. Conclusions— The presence of intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap on MRI of carotid plaque is associated with increased risk of future stroke or transient ischemic attack in patients with carotid atherosclerotic disease. Dedicated MRI of plaque composition offers stroke risk information beyond measurement of luminal stenosis in carotid atherosclerotic disease.
The Walking Impairment Questionnaire stair-climbing score predicts mortality in men and women with peripheral arterial disease.

Objective The Walking Impairment Questionnaire (WIQ) measures self-reported walking distance, walking speed, and stair-climbing ability in men and women with lower extremity peripheral arterial disease (PAD). We determined whether poorer WIQ scores are associated with higher all-cause and cardiovascular disease (CVD) mortality in individuals with and without PAD. Methods We identified 1048 men and women with and without PAD from Chicago-area medical centers. Participants completed the WIQ at baseline and were monitored for a median of 4.5 years. Cox proportional hazards models were used to relate baseline WIQ scores with death, adjusting for age, sex, race, the ankle-brachial index (ABI), comorbidities, and other covariates. Results During follow-up, 461 participants (44.0%) died, including 158 deaths from CVD. PAD participants in the lowest baseline quartile of the WIQ stair-climbing scores had higher all-cause mortality (hazard ratio, 1.70; 95% confidence interval, 1.08-2.66, P = .02) and higher CVD mortality (hazard ratio, 3.11; 95% confidence interval, 1.30-7.47, P = .01) compared with those with the highest baseline WIQ stair-climbing score. Among PAD participants, there were no significant associations of lower baseline WIQ distance or speed scores with rates of all-cause mortality (P = .20 and P = .07 for trend, respectively) or CVD mortality (P = .51 and P = .33 for trend, respectively). Among non-PAD participants there were no significant associations of lower baseline WIQ stair-climbing, distance, or speed score with rates of all-cause mortality (P = .94, P = .69, and P = .26, for trend, respectively) or CVD mortality (P = .28, P = .68, and P = .78, for trend, respectively). Conclusions Among participants with PAD, lower WIQ stair-climbing scores are associated with higher all-cause and CVD mortality, independently of the ABI and other covariates.
A Rich Heritage Lost: Observations on the Effects of the Bhuj Earthquake, India

In March of 2001 I flew into Bhuj, the city in Gujarat, India that was the center of the area devastated by the earthquake of January 26, 2001. From the air the view of Bhuj belied its true condition. From that distance the city seemed quite normal, with many tall blocks of apartments standing seemingly unharmed. On the ground, however, the scene was quite different. The first close-up view of those same large apartment blocks showed them to be leaning at crazy angles, with their first floors collapsed and their upper walls laced with cracks like a crazed china pot. While the city now contains many modern reinforced concrete buildings, Bhuj was originally an ancient walled city and still has both part of its original fortifications and many historic buildings within the city core. Some of the fort walls had survived the vicissitudes of time, only to be heavily damaged by the earthquake. They looked as if they were cheese nibbled by a giant mouse. The battlements had fallen. Large areas of the facing stone had come off. In some places only the inner rubble stone core remained standing. [O]ne was confronted with a view of total devastation. As far as one could see, everything within view had either totally or partially collapsed. The first view of the inner precincts of the walled city of Bhuj was shocking. In the area immediately inside the city gate, the buildings had almost totally disappeared into rubble piles that lay along either side of the road like great waves. Riding on these waves were the still-whole pieces of the upper floors of broken newer concrete buildings, leaning at crazy angles as if they were riding in surf. These “waves” of rubble were the result of the first phase of plowing to clear the …
Counting chickens before the eggs hatch: Associating new product development portfolios with shareholder expectations in the pharmaceutical sector

article i nfo Drug development is the lifeblood of pharmaceutical firms and a critical source of innovation in the healthcare industry. Pharmaceutical firms maintain their competitiveness by continuously developing and introducing new drugs, which requires an efficient new drug portfolio management process. However, the current literature does not elaborate on strategies pertaining to these new drug (product) portfolios (i.e., portfolios of drugs under development), nor does it provide the means with which to understand the future cash flow-generating potential of these portfolio strategies. To address this problem, we propose a set of generic descriptors of new drug portfolio strategies (i.e., portfolio breadth, portfolio depth, blockbuster strategy, and stages of the drug development process) and relate these descriptors to Tobin's q, a forward- looking measure of shareholder expectations. The results of a latent class regression analysis show that shareholder expectations of firms with broad new drug portfolios and potential blockbusters are positive. For most firms, shareholders focus on the final stage of the drug development process and deemphasize portfolio depth. In contrast, for a minority of mostly small firms, shareholders seem to value the earlier stages of the drug development process and stress portfolio depth.
Safety of Nighttime 2-Hour Suspension of Basal Insulin in Pump-Treated Type 1 Diabetes Even in the Absence of Low Glucose

Objective An integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2-hrs if patients fail to respond to low glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low sensor glucose levels could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2-hrs in the overnight period would not lead to clinically important increases in blood β-hydroxybutyrate (BHB) levels despite widely varying glucose values prior to the suspension. Research Design and Methods Subjects measured meter blood glucose (BG) and BHB levels each night at 9PM and fasting the next morning. On control nights, usual basal rates were continued; on experimental nights, the basal insulin infusion was re-programmed for a 2-hr zero basal rate at random times after 11:30PM. Results In seventeen type 1 diabetes subjects (age 24±9yr, duration 14±11yr, A1c 7.3±0.5 [56mmol/mol]) BG and BHB levels were similar at 9PM on suspend (144±63mg/dL and 0.09±0.07mmol/L) and non-suspend (151±65mg/dL and 0.08±0.06mmol/L) nights (p=0.39 and p=0.47, respectively). Fasting morning BG increased following suspend nights compared to non-suspend nights (191±68mg/dL vs. 141±75mg/dL, p Conclusions Systems that suspend basal insulin for 2-hrs are safe and do not lead to clinically significant ketonemia even if BG is elevated at the time of the suspension.
A Local Oscillator for Chip-Scale Atomic Clocks at NIST

We describe the first local oscillator (LO) that demonstrates viability in terms of performance, size, and power, for chip-scale atomic clocks (CSAC) and has been integrated with the physics package at the National Institute of Standards and Technology (NIST) in Boulder, CO. This voltage-controlled oscillator (VCO) achieves the lowest combined size, DC power consumption, phase noise, and thermal frequency drift among those previously reported, while achieving a tuning range large enough to compensate for part tolerances but small enough to permit precision locking to an atomic resonance. We discuss the design of the LO and the integration with the NIST physics package.
Beyond the printed page: physiology education without a textbook?

Pedagogical innovations, ideas, and outcomes designed to enhance student learning in physiology courses are encouraged by our professional organizations and are actively discussed at conferences an...
State-dependent block of CNG channels by dequalinium.

Cyclic nucleotide–gated (CNG) ion channels are nonselective cation channels with a high permeability for Ca2+. Not surprisingly, they are blocked by a number of Ca2+ channel blockers including tetracaine, pimozide, and diltiazem. We studied the effects of dequalinium, an extracellular blocker of the small conductance Ca2+-activated K+ channel. We previously noted that dequalinium is a high-affinity blocker of CNGA1 channels from the intracellular side, with little or no state dependence at 0 mV. Here we examined block by dequalinium at a broad range of voltages in both CNGA1 and CNGA2 channels. We found that dequalinium block was mildly state dependent for both channels, with the affinity for closed channels 3–5 times higher than that for open channels. Mutations in the S4-S5 linker did not alter the affinity of open channels for dequalinium, but increased the affinity of closed channels by 10–20-fold. The state-specific effect of these mutations raises the question of whether/how the S4-S5 linker alters the binding of a blocker within the ion permeation pathway.