cssi/SciSciGPT-SciSciNet huggingface dataset:
Structure-activity relationships of bisphosphate nucleotide derivatives as P2Y1 receptor antagonists and partial agonists.

The P2Y1 receptor is present in the heart, in skeletal and various smooth muscles, and in platelets, where its activation is linked to aggregation. Adenosine 3',5'- and 2',5'-bisphosphates have been identified as selective antagonists at the P2Y1 receptor (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329) and have been modified structurally to increase receptor affinity (Camaioni et al. J. Med. Chem. 1998, 41, 183-190). We have extended the structure-activity relationships to a new series of deoxyadenosine bisphosphates with substitutions in the adenine base, ribose moiety, and phosphate groups. The activity of each analogue at P2Y1 receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-(methylthio)adenosine 5'-diphosphate (antagonist effect). 2'-Deoxyadenosine bisphosphate analogues containing halo, amino, and thioether groups at the 2-position of the adenine ring were more potent P2Y1 receptor antagonists than analogues containing various heteroatom substitutions at the 8-position. An N6-methyl-2-chloro analogue, 6, was a full antagonist and displayed an IC50 of 206 nM. Similarly, N6-methyl-2-alkylthio derivatives 10, 14, and 15 were nearly full antagonists of IC50 < 0.5 microM. On the ribose moiety, 2'-hydroxy, 4'-thio, carbocyclic, and six-membered anhydrohexitol ring modifications have been prepared and resulted in enhanced agonist properties. The 1,5-anhydrohexitol analogue 36 was a pure agonist with an EC50 of 3 microM, i.e., similar in potency to ATP. 5'-Phosphate groups have been modified in the form of triphosphate, methyl phosphate, and cyclic 3',5'-diphosphate derivatives. The carbocyclic analogue had enhanced agonist efficacy, and the 5'-O-phosphonylmethyl modification was tolerated, suggesting that deviations from the nucleotide structure may result in improved utility as pharmacological probes. The N6-methoxy modification eliminated receptor affinity. Pyrimidine nucleoside 3', 5'-bisphosphate derivatives were inactive as agonists or antagonists at P2Y receptor subtypes.
Assessment of right ventricular function in swine using sonomicrometry and conductance

Background. Assessment of right ventricular (RV) prssure-volume relations has been hampered by difficulty measuring instantaneous, absolute RV volume. Accordingly, several methods were tested for their ability to reflect relative RV volume and to determine changes in RV contractile state. Methods. Swine (46 to 54 kg; n=7) were anesthetized and instrumented to measure instantaneous RV pressure, septal-to-RV free wall diameter (SFWD), RV free wall segment length (FWSL), RV volume via conductance (CV), and pulmonary artery flow, the integral of which was used as the standard for stroke volume. Flow-derived stroke volume was correlated with the systolic change in CV, FWSL, and SFWD in the steady state after incremental volume loading and on a beat-to-beat basis during transient inferior vena caval occlusion. Contractility was altered by calcium and pentobarbital and assessed by preload recruitable stroke work (PRSW). Results. Mean (± standard error of the mean) correlations ( r ) versus stroke volume during steady state conditions were 0.85 ± 0.04 for FWSL, 0.83 ± 0.04 for CV, and −0.04 ± 0.24 for SFWD. Mean r values versus stroke volume during caval occlusions were 0.83 ± 0.03 for FWSL, 0.85 ± 0.04 for CV, and −0.03 ± 0.31 for SFWD. Calcium increased mean PRSW slope compared with control using CV (20.3 ± 2.6 versus 16.1 ± 1.9 mm Hg; p p p Conclusions. In the normal heart, both FWSL and CV, but not SFWD, accurately reflect relative instantaneous RV volume and are thus useful for determining RV contractility by pressure-volume (pressure-dimension) indices.
A numerical model for swirl flow cooling in high-heat-flux particle beam targets and the design of a swirl-flow-based plasma limiter

An unsteady, two-dimensional heat conduction code has been used to study the performance of swirl-flow-based neutral particle beam targets. The model includes the effects of two-phase heat transfer and asymmetric heating of tubular elements. The calorimeter installed in the Medium Energy Test Facility, which has been subjected to 30-s neutral beam pulses with incident heat flux intensities of greater than or equal to 5 kW/cm/sup 2/, has been modeled. The numerical results indicate that local heat fluxes in excess of 7 kW/cm/sup 2/ occur at the water-cooled surface on the side exposed to the beam. This exceeds critical heat flux limits for uniformly heated tubes wih straight flow by approximately a factor of 5. The design of a plasma limiter based on swirl flow heat transfer is presented.
Magnitude and implications of spontaneous hemodynamic variability in primary pulmonary hypertension

Abstract The pulmonary artery (PA) pressure and pulmonary resistance at rest have been noted to vary spontaneously in patients with primary pulmonary hypertension. To evaluate this variation, in 12 patients (8 women, 4 men, aged 43 ± 13 years), hourly measurements were made for 6 consecutive hours of heart rate, systemic and PA pressures, cardiac output, systemic and pulmonary resistance. After these baseline measurements the patients were tested with hydralazine and nifedipine therapy. Spontaneous variability in pulmonary pressures and resistances occurred in each patient, with the amount of variation (coefficient of variation) in PA pressure averaging 8% and in total pulmonary resistance 13% over the 6 hours. The patients with the most variability in mean PA pressure also had the most variability in cardiac output (r = 0.69, p = 0.02). Variability also correlated with the severity of the disease, as the patients with the highest total pulmonary resistances also had the most variation for that factor (r = 0.91, p
A Physiologically Relevant Pharmacokinetic Model of Xenobiotic Percutaneous Absorption Utilizing the Isolated Perfused Porcine Skin Flap

A physiologic pharmacokinetic model describing percutaneous absorption of topically applied compounds in the isolated perfused porcine skin flap (IPPSF) is presented. As an extension of a previously reported hybrid physiologically relevant compartmental model of uptake of intra-arterially administered drug in the IPPSF, this percutaneous model should allow experimental results obtained from an in vitro preparation to serve as quantitative input to an in vivo pharmacokinetic system. Model parameters estimated from 8–10-h IPPSF experiments were able to predict 6-day in vivo radiolabel absorptions in pigs for topically applied benzoic acid, caffeine, malathion, parathion, DFP, testosterone, and progesterone. These results compare favorably with those obtained previously using a classical compartmental modeling approach.
Remarkably Stable Titanium Complexes Containing Terminal Alkylidene, Phosphinidene, and Imide Functionalities

PNP pincer-type complexes of titanium(III) and -(IV) have been prepared, characterized, and proven to be remarkably stable, despite having terminal alkylidene, phosphinidene, and imide functionalities.
Fragmentation Pathway for Glutamine Identification: Loss of 73 Da from Dimethylformamidine Glutamine Isobutyl Ester

A fragmentation mechanism for the neutral loss of 73 Da from dimethylformamidine glutamine isobutyl ester is investigated. Understanding this mechanism will allow to improve the identification and quantification of 15N-labeled and unlabeled glutamine and the distinguishing of glutamine and glutamic acid by electrospray ionization (ESI)-tandem mass spectrometry. Before mass spectrometry analysis, glutamine and glutamic acid are derivatized with dimethylformamide dimethyl acetal and isobutanol to form dimethylformamidine isobutyl ester. Derivatization conditions are modified based on an existing method to ensure complete derivatization of glutamic acid and to prevent the hydrolysis of glutamine. The fragmentation mechanism of dimethylformamidine glutamine isobutyl ester is studied and possible fragmentation pathways are proposed. Based on the fragmentation mechanism, a quantification method is developed to quantify both 15N-labeled and unlabeled glutamine and glutamic acid at a series of different neutral losses by performing multiple-reaction monitoring (MRM) scans in a triple-quadrupole mass spectrometer. Labeled glutamine includes 15N-amide labeled, 15N-amine labeled glutamine and glutamine 15N-labeled at both amide and amine positions. Deuterium labeled glutamine and glutamic acid are used as internal standards. Isotope effects are characterized for 15N labeled and deuterium labeled glutamine. It is found that the same method can be used to distinguish aspartic acid from asparagine. This study will improve the application of MS/MS for amino acid quantification and stable isotope labeling metabolism studies.
Single-channel properties in endoplasmic reticulum membrane of recombinant type 3 inositol trisphosphate receptor.

The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular Ca2+-release channel localized in endoplasmic reticulum (ER) with a central role in complex Ca2+ signaling in most cell types. A family of InsP3Rs encoded by several genes has been identified with different primary sequences, subcellular locations, variable ratios of expression, and heteromultimer formation. This diversity suggests that cells require distinct InsP3Rs, but the functional correlates of this diversity are largely unknown. Lacking are single-channel recordings of the recombinant type 3 receptor (InsP3R-3), a widely expressed isoform also implicated in plasma membrane Ca2+ influx and apoptosis. Here, we describe functional expression and single-channel recording of recombinant rat InsP3R-3 in its native membrane environment. The approach we describe suggests a novel strategy for expression and recording of recombinant ER-localized ion channels in the ER membrane. Ion permeation and channel gating properties of the rat InsP3R-3 are strikingly similar to those of Xenopus type 1 InsP3R in the same membrane. Using two different two-electrode voltage clamp protocols to examine calcium store-operated calcium influx, no difference in the magnitude of calcium influx was observed in oocytes injected with rat InsP3R-3 cRNA compared with control oocytes. Our results suggest that if cellular expression of multiple InsP3R isoforms is a mechanism to modify the temporal and spatial features of [Ca2+]i signals, then it must be achieved by isoform-specific regulation or localization of various types of InsP3Rs that have relatively similar Ca2+ permeation properties.
Metabotropic glutamate 2/3 receptors as drug targets

Abstract Metabotropic glutamate receptors are a family of class III G-protein-coupled receptors comprising eight members (mGluR1–8), which are an attractive target in the central nervous system because of the widespread use of glutamate as the principal excitatory amino acid transmitter. The unique pharmacology of class III G-protein coupled receptors, their forebrain localization in key limbic-related cortical/thalamic/striatal/amygdaloid circuits, and the promise of subtle modulation of glutamatergic neurotransmission make these receptors intriguing targets for a wide variety of neuropsychiatric disorders.
The role of phosphofructokinase in metabolic regulation

Summary The kinetics of phosphofructokinase have been investigated with especial reference to possible physiological controls. ATP, citrate and Mg were found to be inhibitors for liver and brain PFK. The inhibition can be overcome wholly or in part by the presence of FDP, Pi, F6P, AMP, 3′,5′-AMP or ADP. In addition, the rate of PFK can be enhanced by these same substances, or by the addition of NH4+ or K+. The nature of the effects of various combinations of these materials has made it necessary to postulate two active substrate sites, two ATP inhibitor sites, two distinct enhancement sites, and a citrate inhibitory site. The role of PFK as a controlling step in metabolism is discussed.
Analysis of Cerro Prieto well logs: Some results and problems

Abstract The evaluation of well logs from the Cerro Prieto geothermal field is made difficult by the wellbore conditions existing during the logging runs and by the complex minerology of the hydrothermal reservoir. In order to obtain well logs at the Cerro Prieto geothermal field, the wellbore must be cooled to at least the maximum operational temperature of available well-logging equipment, normally 120°C. Since undisturbed formation temperatures are usually in excess of 250°C at Cerro Prieto, the cooling of the wellbore creates an acute thermal gradient between the wellbore and the undisturbed formations. An understanding of the influence of this gradient on logging responses is necessary to establish confidence in well log evaluations. Similarly, since the mineralogic characteristics of the formations affect the well-log responses, quantitative mineralogic studies of wellbore cuttings and core make an important contribution to log evaluation. This influence is pronounced in a hydrothermal reservoir where complex mineralogies occur. An appreciation of the effects of wellbore cooling and complex mineralogies on log responses should increase confidence in the evaluation of Cerro Prieto geothermal well logs.
Taxonomy of Begonia longifolia Blume (Begoniaceae) and related species

TheBegonia longifolia Blume complex is revised and seven species are recognized.Begonia crassirostris Irmsch.,B. inflata C. B. Clarke,B. tricornis Ridl., andB. trisulcata (A. DC.) Warb. are synonymized withBegonia longifolia Blume, making this the most widely distributedBegonia species within Asia.Begonia tetragona Irmsch. is synonymized withB. acetosella Craib. Descriptions are provided forBegonia longifolia, B. acetosella, and four closely related and also poorly known species with baccate fruit:B. cristata Warb. ex L. B. Sm. & Wassh.,B. renifolia Irmsch.,B. sarcocarpa Ridl., andB. turbinata Ridl.Begonia hayatae Gagnep. is also recognized as a member of this complex but is not described here. Evidence for a speciation mechanism within this group is discussed.Begonia acetosella andB. sarcocarpa are lectotypified.
Mass Spectrometry in Organic Geochemistry

Mass spectrometry does not represent a novel physical tool in geochemical research. Petroleum chemists have made use of mass spectrometry for many years in the analysis of the components of crude oil. Such applications were concerned primarily with quantitative analytical problems, with emphasis on the determination of compound types which constitute a given petroleum sample, and the number of papers on this subject is legion. In recent years — and the developments of recent years are primarily the subject of this review — the tremendous potential of mass spectrometry for the solution of structural problems has been recognized by the organic chemical community in general, and since then rather extensive and sophisticated use has been made of the technique for structural studies on organic compounds. The widespread application to problems of organic chemistry has in turn sparked intense interest in mechanistic studies on the fragmentation processes of ionized molecules in the vapor state. Practical applications and fundamental studies combined have thus within a few years produced a substantial body of information on the nature of mass spectra of organic compounds, information which makes feasible a fruitful exploitation of mass spectrometric data for the solution of structural problems. The considerable number of volumes [1–10] addressing themselves wholly or in part to the application of mass spectrometry to problems of organic and natural products chemistry reflects the pace of progress and the scope of this field; it is recommended that these works be consulted for a thorough initiation into all phases of organic mass spectrometric research and its ramifications.
OSCAR: An incentive-based collaborative bandwidth aggregation system

The explosive demand for mobile data, predicted to reach a 25 to 50 times increase by 2015, along with expensive data roaming charges, and user expectation to remain continuously connected, are all creating novel challenges for service providers and researchers. A potential approach for solving these problems, is exploiting all communication interfaces available on modern mobile devices in both solitary and collaborative forms. In the solitary form, the goal is to exploit any direct Internet connectivity on any of the available interfaces by distributing application data across them in order to achieve higher throughput, minimize energy consumption, and/or minimize cost. In the collaborative form, the goal is to enable and incentivize mobile devices to utilize their neighbors' under-utilized bandwidth in addition to their own direct Internet connections. Despite today's mobile devices being equipped with multiple interfaces, there has been a high deployment barrier for adopting collaborative multi-interfa...
Comparison of isoflurane and sevoflurane for anesthesia in beaver.

We compared the hemodynamic and respiratory effects, recovery time, and cost of two gas inhalants (isoflurane and sevoflurane) for anesthetic induction and maintenance of beaver (Castor canadensis) during surgery to implant radio transmitters in the peritoneal cavity. Heart rate, respiratory rate, relative hemoglobin saturation with oxygen (SpO2), and body temperature were measured every 5 min for the first 45 min, and arterial blood gas was measured once, 25 min into the anesthetic procedure. Induction for either agent was smooth and rapid. Heart rate and respiratory rate both decreased during the procedure though neither was lower than baseline values reported in the literature for beaver. Relative hemoglobin saturation with oxygen, body temperature, and blood gas variables did not differ between each anesthetic regime. Both inhalants caused slight respiratory acidosis. Recovery time from anesthesia was highly variable (1–178 min) but did not differ statistically between drugs. Sevoflurane costs ($22.30...
Compounding and molding of polyethylene composites reinforced with keratin feather fiber

Polyethylene-based composites are prepared using keratin feather fiber obtained from chicken feathers. Keratin fibers are mixed into high-density polyethylene (HDPE) at 20 wt% using a Brabender mixing head. This is the compounding step and the variables studied are compounding time, temperature, speed and state of fiber dispersion. Following compounding, the composites are compression molded at various times and temperatures and this is the molding step. The effects of compounding and molding are studied using tensile testing and scanning electron microscopy. It is found that keratin feather fiber provides a stiffness increase to HDPE but lowers tensile breaking stress. The fibers are thermally stable for long periods of time up to 200 °C, but the best composite properties are found at processing temperatures of 205 °C, where the fibers are only stable for a few minutes.
Acute liver failure due to drugs

Acetaminophen overdose and idiosyncratic drug-induced liver injury (DILI) are the most commonly identified causes of acute liver failure (ALF) in the United States. Suspected acetaminophen hepatotoxicity can be effectively treated with N-acetylcysteine but still an estimated 500 patients die each year. Product labeling changes, dispensing restrictions, and reformulation of acetaminophen containing narcotic analgesics have been proposed to reduce the rising incidence of this preventable form of dose-dependent liver injury. In contrast, idiosyncratic DILI is not preventable due to our lack of understanding of host susceptibility and outcome factors. Patients with ALF due to DILI are difficult to diagnose and have a low likelihood of spontaneous recovery. Patients with severe idiosyncratic DILI should be urgently referred to a transplant center as there are no established medical treatments beyond drug discontinuation. Investigation of host variability in metabolic, regeneration, and immunological pathways may provide insights into the molecular basis of DILI as well as improved diagnostic and prognostic biomarkers.
The clinical and biochemical implications of pyruvate carboxylase deficiency

A 10 month old female infant was evaluated for severe lactic acidosis. Clinically she was well nourished and had a substantial amount of adipose tissue despite recurrent episodes of acidosis. Her psychomotor development was retarded, her movements were dystonic and generalized seizures punctuated her course. Metabolic abnormalities included elevated blood concentrations of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, alanine, proline and glycine, decreased blood concentrations of glutamine, aspartate, valine and citrate, and intermittent elevations of serum cholesterol. A trial on a high-fat diet worsened the clinical condition and intensified the ketoacidosis and hyperalaninemia. Analysis of hepatic tissue obtained by open biopsy revealed increased concentrations of lactate, alanine, acetyl-CoA and other short-chain acyl-CoA esters, and decreased concentrations of oxaloacetate, citrate, alpha-ketoglutarate, malate and aspartate. The blood and tissue metabolic perturbations reflected a deficiency of hepatic pyruvate carboxylase. The apparent Km of hepatic citrate synthase for oxaloacetate was 4.6 micrometer. Calculated tissue oxaloacetate concentrations were 0.50--0.84 micrometer suggesting that tricarboxylic acid cycle activity was severely limited by the decreased availability of this substrate. An iv glucose tolerance test resulted in the paradoxical synthesis of ketone bodies. This observation, coupled with the intermittent hypercholesterolemia and the increased tissue acetyl-CoA concentrations, suggests that pyruvate carboxylase is important in modulating the fractional distribution of intracellular acetyl-CoA between the tricarboxylic acid cycle, the beta-hydroxy-beta-methyl-glutaryl-CoA cycle (and the synthesis of cholesterol and ketone bodies), and fatty acid synthesis. Treatment in future cases might be directed toward increasing tissue concentrations of oxaloacetate.
Sex-specific roost selection by adult red bats in a diverse forested landscape

Abstract The eastern red bat ( Lasiurus borealis ) is a common, widespread species that occurs throughout eastern North America; however, information on potential differences in roost selection between sexes is limited. We studied summer diurnal roosting of adult red bats in a diverse forested landscape to: (1) characterize roosts of adult males and females, (2) determine habitat relationships for both sexes, and (3) compare roost selection between the sexes. We radiotracked 21 male and 20 female red bats to 142 roost locations and quantified roost characteristics. Both sexes roosted mostly in overstory hardwoods (82% of male and 81% of female roosts), but males occasionally (8% of roosts) roosted in sapling ( Quercus alba ) and hickories ( Carya spp.) but avoided Pines ( Pinus spp.). Sex-specific habitat models created using an information-theoretic approach indicated males were more likely to roosts at sites with more midstory (5–10 cm dbh) and small overstory (10–25 cm dbh) hardwoods, taller hardwoods, shorter pines, and further from the nearest tree than random. Females were more likely to roost at sites with more midstory hardwoods, fewer small overstory pines (10–25 cm dbh), and fewer understory ( P 2 /ha of overstory hardwoods and retaining unharvested buffers along stream drains in harvested areas would likely provide adequate roosting habitat for both sexes of red bats in managed landscapes during summer.
One book fits all sizes

Fillers used in polymer composites range from nanosized particles to macroscale fibers, and a new volume aims to cover them all.
Vascular surgery and the Internet: a poor source of patient-oriented information.

Abstract Objective: Increasing numbers of patients use the Internet to obtain medical information. The Internet is easily accessible, but available information is under no guidelines or regulations. We sought to evaluate the type, quality, and focus of vascular disease information presented on the Internet and the role in patient education with simple search techniques. Methods: The arbitrarily chosen search phrases "abdominal aortic aneurysm (AAA)," "carotid surgery (CEA)," "claudication surgery," and "leg gangrene surgery" were entered into five common Internet search engines. No attempt was made to refine searches. As indicated by the search engines, the 50 most commonly encountered web sites for both AAA and CEA were reviewed. The first 25 claudication sites and the first 25 gangrene sites were combined for a total of 50 leg ischemia (LIS) sites. An information score (IS) was developed as a weighted score ranging from 0 (poor) to 100 (outstanding) and was designed to assess how well the web page educated the patient about the disease, the treatment options, and the medical and surgical complications. Each vascular surgery web site was classified according to the author, the referenced information source, and the therapeutic recommendations. This was followed by an evaluation of each web site with the IS independently scored by two observers. Results: Of the 150 web sites, 146 were accessible. Ninety-six sites (65.8%) had no useful patient-oriented information (IS P = .9). The mean IS of the 59 sites with scores of more than 10 were: AAA, 39.8 (n = 17); CEA, 44.8 (n = 19); and LIS, 24.8 (n = 23; P P = .9). Misleading or unconventional care recommendations were recognized in one AAA site (1 of 47, 2.1%), two CEA sites (2 of 49, 4.1%), and 13 LIS sites (13 of 50, 26.0%). The Joint Vascular Societies web page was identified only as a tertiary link. Conclusion: Patient-oriented vascular surgery information, for common vascular diseases, is difficult to find on the Internet. The overall quality is poor, and information is difficult to obtain in part because of the large number of irrelevant sites. Of the sites that were relevant to patient education (33%), one third presented information that was classified by the authors as misleading or unconventional. This was most apparent in the leg ischemia sites. The Internet is a poor overall source of patient-oriented vascular surgery information and education. Focused and refined searches and improvements in search engines and educational web sites may yield improved information. Public and medical community awareness needs to be improved regarding the severe limitations of the Internet as an information resource. (J Vasc Surg 1999;30:84-91.)
Chunking in Spatial Memory

In order to gain insight into the nature of human spatial representations, the current study examined how those representations are affected by blind rotation. Evidence was sought on the possibility that whereas certain environmental aspects may be updated independently of one another, other aspects may be grouped (or chunked) together and updated as a unit. Participants learned the locations of an array of objects around them in a room, then were blindfolded and underwent a succession of passive, whole-body rotations. After each rotation, participants pointed to remembered target locations. Targets were located more precisely relative to each other if they were (a) separated by smaller angular distances, (b) contained within the same regularly configured arrangement, or (c) corresponded to parts of a common object. A hypothesis is presented describing the roles played by egocentric and allocentric information within the spatial updating system. Results are interpreted in terms of an existing neural systems model, elaborating the model's conceptualization of how parietal (egocentric) and medial temporal (allocentric) representations interact.
Thermal expansion and elastic properties of Nb-Mo alloys

The linear thermal expansion coefficients alpha (T) of Nb and Nb-Mo alloys have been measured between 80 and 300 K. The results are shown graphically and polymomial expressions for alpha (T) are tabulated. A minimum of alpha (T) occurs near the critical composition of 40% Mo in Nb. Features of the temperatures and composition dependence of alpha (T) are analysed in terms of the known elastic properties of the alloys. It is shown that the temperature dependence of the shear elastic constant c44 consists of an intrinsic component and a volume-dependent extrinsic component. An estimate is made of the electronic contribution to c44 in the alloys.
Preparation, biodistribution, and micropet imaging of 45Ti-transferrin

Several titanium complexes are currently being investigated for their ability to exhibit antitumor activity both in vitro and in vivo (1). Sun et al. recently showed the first specific Ti(IV)-protein complex through binding experiments with transferrin (2). This suggests that transferrin could be the mode of transport for titanium anticancer drugs since tumor cells show high levels of transferrin receptors on the cell surface (3). Transferrin has a molecular weight of 80 kDa and is only 30% saturated with iron, leaving available binding sites for other metal ions (4). Titanium-45 has a half-life of 3.09 hours and a positron branching ratio of 85% with an Eβ+max of 1.04 MeV. The work of Ishiwata et al. investigated 45Ti as a potential metal for labeling pharmaceuticals for PET imaging (5). In the current study, the biodistribution of 45Ti-transferrin was examined to investigate the mode of transport of titanium compounds to tumors.
The advent of twenty‐first century library services

Purpose – This column aims to examine the issue of modular library technology infrastructure, and how it can help libraries to offer more flexible services to patrons.Design/methodology/approach – This column is exploratory, and looks at the pros and cons of various technology approaches to digital library services.Findings – In order to remain flexible with regard to the evolving needs of patrons, libraries should seriously consider a technology model which would allow the digital library to offer more responsive services to patrons. It is suggested that a deeper look at service‐oriented architecture (SOA) design principles as opposed to the standard model of large monolithic systems be examined and adopted.Originality/value – This column offers alternatives in the area of digital library services, and focuses primarily on the possibilities rendered by service‐oriented architectures and robust web services.
Stable expression of adenylyl cyclase 2 leads to the functional rescue of human 5-HT6 receptor in a CHODUKX cell line

Abstract Introduction The generation and selection of recombinant cell lines specifically designed to express high picomolar levels of heterologous G-protein-coupled receptors can lead to loss of ligand-dependent functional activity. As a result, the clonal selection of a suitable host model and/or lower receptor expression levels within the same cell system becomes important especially when a functional assay is necessary to evaluate the pharmacological potencies of ligands at the receptor site. To address this question, we examined the utility of various signal transducers to restore the functional capacity of a high expressing human 5-HT 6 receptor CHODUKX system. Methods The plasmids for human 5-HT 6 receptor and full-length human G s , G olf and rat adenylyl cyclase isoforms 2 (rAC2) and 5 were obtained by PCR. The h5-HT 6 receptor pHTop plasmid was stably transfected into a CHODUKX cell line to generate an h5-HT 6 expressing clone. h5-HT 6 CHODUKX cells were transfected with signaling components and functional cAMP responses measured. rAC2 was selected to generate a double stable h5-HT 6 receptor/rAC2 pHTop CHODUKX line. Results The h5-HT 6 receptor CHODUKX line was a high receptor expressor (> 2 pmol/mg protein) but an extremely poor ligand-dependent functional responder, failing to produce the appropriate cAMP signal upon addition of selective agonists. We found that stable co-expression of rAC2 with h5-HT 6 receptor in the CHODUKX cell line displayed dose-dependent cAMP accumulation following agonist treatment. The pharmacological profile of several agonists in the h5-HT 6 receptor/rAC2 cell line was consistent with an h5-HT 6 -like receptor-mediated event. Discussion We provide evidence for restoration of functional capacity in a heterologous G s -coupled 5-HT 6 /AC2 CHODUKX expression system. We discuss the broader value of a stable AC2-expressing CHODUKX cell line in which the generation of high expressing GPCR receptor/AC2 lines can retain their functional responsiveness and provide pharmacological drug comparisons between the same host line for screening purposes and measurement of multiple cellular parameters.
Combinatorics and Applications to Experimental Designs

We present an overview of the developments in combinatorial mathematics starting from the fundamental early contributions made by Professor Bose and some of the applications to experimental designs. We discuss in particular the impact of Bose's contributions in research on orthogonal latin squares, orthogonal arrays, incomplete block designs, and factorial experiments.
Magnesium-DNA interactions from interpretation of 25Mg-nmr relaxation rates: field and coion dependence.

We have used 25Mg-nmr to investigate the binding of magnesium ions to double-stranded DNA. We have measured line shapes for 25Mg in the presence of monodisperse calf thymus DNA (160 base pairs; b.p.) (magnesium : phosphate = 2.0) at two different field strengths, 11.75 T and 7.05 T, and used the isotropic model of two-site exchange developed by Westlund and Wennerstrom to simultaneously fit the line shapes at both field strengths. This model does not reproduce the observed field dependence. This is in contrast to a previous study [E. Berggren, L. Nordenskiold, and W. H. Braunlin (1992), Biopolymers, Vol. 32, pp. 1339–1350] in which a similar model of isotropic two-site exchange qualitatively reproduced the temperature dependence of the line widths. Relaxation rates were also measured as a function of magnesium : phosphate ratio and colon type. These measurements were used to assess the sensitivity of magnesium relaxation measurements to small changes in DNA structure induced by changes in the solvent environment. The temperature dependence of the line shape varies with the type of coion (chloride or sulfate) present. This coion dependence of the line shape is consistent with the coion dependence of the aggregation midpoint temperature reported by Bloomfield and co-workers [O. A. Knoll, M. G. Fried, and V. A. Bloomfield (1988) in Structure and Expres-sion, Vol. 2, R. H. Sarma and M. H. Sarma, Eds., Adenine Press, New York] and attributed to a lyotropic effect. These results suggest that even at low magnesium : phosphate ratios, relaxation parameters are specific to each magnesium–coion–DNA system. © 1994 John Wiley & Sons, Inc.
A Nine-Year Follow-up of People Diagnosed With Multiple Chemical Sensitivities

The authors assessed self-reported health status and clinical symptoms in people reporting multiple chemical sensitivities (MCS) at a 9-year follow-up interview using structured and semistructured instruments and self-report questionnaires. Of the original sample, 18 people (69%) consented to an interview. By use of the best estimate diagnostic method, 15 subjects (83%) met DSM-IV criteria for a lifetime mood disorder, 10 (56%) for a lifetime anxiety disorder, and 10 (56%) for a lifetime somatoform disorder. None of the subjects met the criteria for a substance use disorder (current or lifetime). The Illness Behavior Questionnaire and the Symptom Checklist-90-Revised results showed little change from 1988 and remained significantly different from the control group on many subscales. The authors conclude that the subjects remain strongly committed to the diagnosis of MCS, and although improved since their original interview, many remain symptomatic and continue to report ongoing lifestyle changes.
Speech recognition system evaluation.

his is a feature that is important articularly for larger practices in hich there may be several servers nd the workload is balanced mong them. In addition for mision critical roles such as speech ecognition, the ability to have reundant hardware may be of vital mportance to the practice. Those ractices that could revert to traitional transcription methods learly may not use this feature. i oes the System Alert upport Personnel of ailure?
Pedogenic Carbonates in Texas: Stable-Isotope Distributions and Their Implications for Reconstructing Region-Wide Paleoenvironments

Abstract Pedogenic carbonates are ubiquitous in paleosols through geologic history, and have been widely used to speculate on paleoclimatic conditions during their formation. They are widespread and well developed in large areas of Texas. A majority are of late Quaternary age and have formed across a range of climatic conditions on various types of substrates. To evaluate the usefulness of pedogenic carbonates as environmental indicators, this study investigates regional-scale trends in stable-isotope compositions of pedogenic carbonates across approximately 900 km of Texas. The δ13C values of 49 pedogenic carbonate profiles (182 analyses) on various host strata (e.g., limestone, igneous rocks), range from −10.6‰ to +0.7‰ V-PDB. Most δ13C values are evenly distributed between −9‰ and −1‰, and the δ18O values range from −9.1‰ to +0.2‰ V-PDB, mainly between −6‰ and −2‰. There is no correlation between carbon and oxygen isotopic values (R2 = 0.0002). Pedogenic carbonates in the Texas Gulf Coastal Plains, Southern High Plains, and west Texas exhibit higher δ13C values than those in south and central Texas, which corresponds to the spatial change in vegetation between C4-dominated and C3-dominated plants. The marked increase in δ13C values of the pedogenic carbonates from the Tertiary strata into the overlying Quaternary strata confirms the invasion of a C4 biomass into the Southern High Plains since the early Pliocene. From east to west, the δ18O values of late Quaternary pedogenic carbonates decrease gradually, a trend that mimics the spatial variation of δ18O values of modern meteoric water primarily due to the increased distance from the Gulf of Mexico (source of most of the meteoric water). In contrast to the regional trends, the stable-isotope values of some pedogenic carbonates developed on marine limestone and calcareous alluvium in central Texas and south Texas have isotopic signatures inherited from the host strata. In addition, some of the δ13C values of pedogenic carbonate nodules in the Gulf Coastal Plains have been affected by saline groundwater. Soil carbonates formed in the shallow parts of the profile, such as petrocalcic horizons, may have also been influenced by the atmospheric CO2. Nevertheless, climatic trends are readily apparent in the isotopic data, thus demonstrating their potential value in region-wide paleoclimatic analyses.
Sequence-selective nonmacrocyclic two-armed receptors for peptides

Tweezer-like receptor molecules have proven their potential for molecular recognition on several occasions. We decided to make twofold use of this receptor design: firstly to learn whether simple molecular forceps consisting of two peptide chains linked by a spacer are able to selectively bind to small peptides, and secondly to investigate the importance of structural preorganization for the characteristics of the receptors. We prepared two encoded combinatorial libraries based on this design, featuring two combinatorial tripeptide chains held by different scaffolds: the use of chenodeoxycholic acid as spacer provided a rigid scaffold for the forceps, whereas linking the peptide chains by a pentamethylene chain yielded a very flexible forceps structure. Molecules from the cholic acid library recognize and discriminate various enkephalins with micromolar affinities. Molecules from the flexible library show distinct interactions with the enkephalins as well, but the specificity and affinity are clearly diminished. Thus, although the interactions of molecular forceps with peptides are not crucially dependent on structural preorganization, receptors with a rigid design are clearly superior to flexible molecular forceps.
Distal emboli protection in patients undergoing percutaneous coronary intervention after a recent myocardial infarction.

Devices to prevent distal atheroembolization are an important addition to the armamentarium of an interventional cardiologist. We report the use of PercuSurge, a distal balloon occlusion device, in two patients with recent myocardial infarction of differing etiologies. The first case is a patient with an old degenerated vein graft with thrombotic occlusion of greater than 48-hr duration and the second case is a patient with an embolic myocardial infarction in a native coronary artery. In both cases, significant thromboembolic debris was aspirated with technical success and no complications. These cases illustrate use of the PercuSurge device in patients after a recent myocardial infarction for preserving distal myocardial perfusion and microvascular integrity.
Assuring consistency and increasing reliability in group communication mechanisms in computational resiliency

The computational resiliency library (CRLib) provides distributed systems with the ability to sustain operation and dynamically restore the level of assurance in system function during attacks or failures. In the presence of arbitrary faults, replicated threads need to agree on the values received in order to achieve consistency, when doing group communication in CRLib. To guarantee data integrity and increase reliability, we have implemented a variant of the Lamport-Shostak-Pease oral message algorithm for the Byzantine Generals problem, which provides fuzzy agreement as well as a reduction of the expected communication overhead. Instead of agreeing on the original messages, which could be extremely large, agreement is performed over the 160-bit hashes of normalized messages computed using SHA-1. Performance measurements of applications using CRLib supporting both fail-stop and arbitrary failure models indicate that a reasonable overhead in execution time is worth paying in cases when Byzantine failures are expected.
Yeast HAP1 activator binds to two upstream activation sites of different sequence.

Abstract We show that the HAP1 protein binds in vitro to the upstream activation site (UAS) of the yeast CYC7 gene. Strikingly, this sequence bears no obvious similarity to the sequence bound by HAP1 at UAS1 of the CYC1 gene. The CYC1 and CYC7 sites compete for binding to HAP1 and have comparable affinities for the protein. The gross features of the interaction of HAP1 with the two sites are similar: multiple major and minor groove contacts, spanning 23 bp, on one helical face, with a back-side major groove contact toward one end. The precise positions of the contacts differ, however. A mutant form of HAP1, HAP1–18 , abolishes the ability of the protein to bind to UAS1 but not CYC7 DNA. Possible mechanisms for how a single protein recognizes two sequences are discussed.
A Preliminary Assessment of Chlamydia and Gonnorhea Infections in the U.S.A. Communities Neighboring Military Installations

Sexually transmitted infections (STIs) among U.S. military personnel and neighboring communities prior, during, and after deployment are a threat to military readiness and community health. This pilot study used data from the Virginia Department of Health. Geographic and spatial pattern analysis of two STIs, Chlamydia trachomatis and Neisseria gonorrhoeae, were conducted. Of special interest was the STI spread patterns correlated with locations of military staging bases, in the aftermath of September 11, 2001. Higher prevalence rates of STIs were found in the counties contiguous to military installations.
Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

The hypothalamic-pituitary-adrenal (HPA) axis is activated during many bacterial and viral infections, resulting in an increase in circulating glucocorticoid levels. This HPA axis activation and glucocorticoid response are critical for the survival of the host, as demonstrated by the fact that removal of the HPA axis (by adrenalectomy or hypophysectomy) or glucocorticoid receptor (GR) blockade enhances the severity of the infection and in some cases enhances the mortality rate. Replacement with a synthetic glucocorticoid reverses these effects by reducing the severity of the infection and provides protection against lethal effects. In addition, some bacteria and viral infections have been shown to affect the GR directly. These have been described and the implications of such an effect discussed.
Comparisons of air traffic control implementations on an associative processor with a MIMD and consequences for parallel computing

This paper has two complementary focuses. The first is the system design and algorithmic development for air traffic control (ATC) using an associative SIMD processor (AP). The second is the comparison of this implementation with a multiprocessor implementation and the implications of these comparisons. This paper demonstrates how one application, ATC, can more easily, more simply, and more efficiently be implemented on an AP than is generally possible on other types of traditional hardware. The AP implementation of ATC will take advantage of its deterministic hardware to use static scheduling. The software will be dramatically smaller and cheaper to create and maintain. Likewise, a large AP system will be considerably simpler and cheaper than the MIMD hardware currently used. While APs were used for ATC-type applications earlier, these are no longer available. We use a ClearSpeed CSX600 accelerator to emulate the AP solutions of ATC on an ATC prototype consisting of eight data-intensive ATC real-time tasks. Its performance is compared with an 8-core multiprocessor (MP) using OpenMP. Our extensive experiments show that the AP implementation meets all deadlines while the MP will regularly miss a large number of deadlines. The AP code will be similar in size to sequential code for the same tasks and will avoid all of the additional support software needed with an MP to handle dynamic scheduling, load balancing, shared resource management, race conditions, false sharing, etc. At this point, essentially only MIMD systems are built. Many of the advantages of using an AP to solve an ATC problem would carry over to other applications. AP solutions for a wide variety of applications will be cited in this paper. Applications that involve a high degree of data parallelism such as database management, text processing, image processing, graph processing, bioinformatics, weather modeling, managing UAS (Unmanned Aircraft Systems or drones) etc., are good candidates for AP solutions. This raises the issue of whether we should routinely consider using non-multiprocessor hardware like the AP for applications where substantially simpler software solutions will normally exist. It also raises the question of whether the use of both AP and MIMD hardware in a single hetergeneous system could provide more versatility and efficiency. Either the AP or MIMD could serve as the primary system, but could hand off jobs it could not handle efficiently to the other system.