cssi/SciSciGPT-SciSciNet huggingface dataset:
Cell division cycle in mammalian cells: VIII. Mapping of G1 into six segments using temperature-sensitive cell cycle mutants

The G1 blocks in three temperature-sensitive (ts) Syrian hamster cell-cycle mutants have been mapped in relation to other G1 landmarks. Two mutants reported here, ts-559 and ts-694, show defective progression only in G1. When shifted from the permissive temperature of 33 degrees C to the non-permissive temperature of 39 degrees C, G1 cells of these two mutants show no further cell cycle progression, while cells in S, G2 and mitosis progress through the cell cycle but become blocked after entering G1. The two mutants complement each other, and also complement the previously reported mutant ts-550C with blocks in both G1 and G2 of the cell cycle. The locations of the G1 blocks in both ts-559 and ts-694 are before the hydroxyurea arrest point. The G1 ts point in ts-694 is prior to the isoleucine deprivation and serum starvation points, while the G1 block in ts-559 is after the serum starvation point but before the isoleucine block. Other G1 block points which have been reported are in mutants of different species and isolated in different laboratories, causing difficulties for relative positioning of the blocks in G1. The mutants for mapping in this study have been isolated from the same cell line. The G1 ts arrest points of ts-559 and ts-694, and that found in ts-550C, together with nutritional deprivations and metabolic inhibitors, provide seven reference points which divide G1 into six segments, each of which is bracketed by two adjacent points: mitosis, ts-694 block, serum starvation arrest point, ts-559 block, isoleucine deprivation arrest point, ts-550C block, hydroxyurea or excess-thymidine arrest segment.
Controls on major solutes within the drainage network of a rapidly weathering tropical watershed

[1] Surface water chemistry in the main stem and source points of the Rio Icacos basin (Luquillo Experimental Forest, Puerto Rico) was studied to investigate the factors regulating spatial variability in major solutes in a rapidly weathering landscape. We sampled along the main stem as well as at small source points at high elevation where fresh bedrock is frequently exposed, and at low elevation in the floodplain/colluvial plain of the main stem. Concentrations of silicon, alkalinity, and the sum of base cations were lower at the source points than in the main stem, and were lowest in low-elevation source points. Calcium and sodium were the dominant cations at all sampling points after sea-salt correction, reflecting the weathering of plagioclase feldspar throughout the basin. The partial pressure of carbon dioxide (pCO2) tended to be higher, and HCO3− concentrations were lower, in the low-elevation source points than at other positions in the landscape. When coupled with the relatively low concentrations of Si and base cations, this suggests that the availability of primary reactive minerals, rather than carbonic acid concentrations, limits weathering in these low-elevation sources. Mechanical denudation appears to enhance chemical weathering rates not only by refreshing reactive mineral surfaces but also by contributing carbon dioxide from the decomposition of organic-rich material in landslides, which occur frequently. The spatial variability of major solutes appears to depend primarily on the availability of fresh primary reactive minerals, carbon dioxide concentrations, and hydrolysis conditions.
Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury

Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood-brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug-treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis.
Communication unbound: How facilitated communication is challenging traditional views of autism and ability/disability.

Facilitated communication is the means by which thousands of people who cannot speak or whose speech is highly disordered, and who were previously believed to be severely retarded, are revealing unexpected literacy abilities. This book describes how it works.
American chooser options

Abstract This paper examines the valuation of American chooser options, i.e., American-style contracts written on the maximum of an American put and an American call. The structure of the immediate exercise region is examined. The early exercise premium representation of the chooser's price is derived and used to construct a system of coupled recursive integral equations for a pair of boundary components. Numerical implementations of the model based on this system are carried out and used to examine the boundary properties and the price behavior.
The University of Chicago Institute for Translational Medicine

In an effort to speed the pace at which new biomedical knowledge gets put to practical and effective use to improve the health and health care of our nation’s people, the U.S. National Institutes of Health (NIH) initiated a series of CTSA Awards. In 2007, the University of Chicago (UC) received this prestigious award, and with it has established a broad series of research support and research training programs to accomplish this noble objective. The clinical and translational research support programs are housed in a new Institute for Translational Medicine (ITM), and the research training programs are organized through a new Committee on Clinical and Translational Science (CCTS).* The goals of our CTSA program are to train scientists and health care providers at the University of Chicago and in our community to determine the molecular underpinnings of disease and disease predisposition in any individual patient; to develop, test, implement, and make readily available to residents in our community personalized therapies; and to do this in a way that is rigorous, valid, efficient, ethical, and respectful of our community’s needs and values. The translation of biomedical discovery into effective, deliverable, and personalized therapies for diverse populations with common, complex disorders is a daunting but tremendously important task. Few cures for common health problems have been developed using strategies that ignore personalized needs. Undoubtedly, this reflects both the complexity and the heterogeneity of pathological disease processes among individual patients. Situated on the South Side of Chicago, an area in which more than a million community residents collectively suffer markedly poorer health status than the rest of Chicago, Illinois, or the nation, the University of Chicago faces a special obligation to meet this challenge. We and our partners, the Illinois Institute of Technology, Argonne National Laboratories, NorthShore University HealthSystem, ACCESS HealthCare Network, and Advocate Health System, are proud of our achievements. We have, therefore, put together the following list of lessons we’ve learned while establishing our CTSA program. We hope that future applicants might benefit from our experience.
Luminous arcs in clusters of galaxies

Observations are reported of what appears to be a new class of spatially coherent extragalactic features having, in the two most compelling known examples, the following joint properties: location in clusters of galaxies, narrow arclike shape, enormous apparent length, and situation of center of curvature toward both a cD galaxy and the apparent center of gravity of the cluster. The principal available facts concerning the arcs are presented and a variety of interpretations are briefly discussed. The weight of evidence seems to favor the interpretation that these features are images of more distant objects produced by the gravitational field of the intervening clusters.
Replication Protein A Stimulates Long Patch DNA Base Excision Repair

Two pathways for completion of DNA base excision repair (BER) have recently emerged. In one, called short patch BER, only the damaged nucleotide is replaced, whereas in the second, known as long patch BER, the monobasic lesion is removed along with additional downstream nucleotides. Flap endonuclease 1, which preferentially cleaves unannealed 5′-flap structures in DNA, has been shown to play a crucial role in the long patch mode of repair. This nuclease will efficiently release 5′-terminal abasic lesions as part of an intact oligonucleotide when cleavage is combined with strand displacement synthesis. Further gap filling and ligation complete repair. We reconstituted the final steps of long patch base excision repair in vitro using calf DNA polymerase e to provide strand displacement synthesis, human flap endonuclease 1, and human DNA ligase I. Replication protein A is an important constituent of the DNA replication machinery. It also has been shown to interact with an early component of base excision repair: uracil glycosylase. Here we show that human replication protein A greatly stimulates long patch base excision repair.
Mechanical and swelling behaviour of well characterized polybutadiene networks

Endlinking of hydroxyl-terminated polybutadiene with the appropriate isocyanate has been used to prepare well characterized networks. Two networks have been studied with molecular weights of the prepolymers being 6100 and 2400 g/mole by g.p.c. Cylindrical specimens were prepared and the derivatives of the stored energy function with respect to the stretch invariants were determined by torque and normal force measurements in torsion. From these data the Valanis-Landel (1967) stored energy function derivatives w-prime(lambda) were determined for both networks. The stored energy function for the junction constraint model of Flory (1953, 1977, 1979, 1985) which is a special form of the Valanis-Landel function, has been fitted to that determined from the experiments. The contributions to the stored energy function from the phantom network and from the junction constraints respectively do not agree with predictions from the topologies of the networks. In spite of this, the form of w-prime(lambda) for the junction constraint model gives an excellent 'curve fit' to the data. Comparison is also made with equilibrium swelling.
Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow

Embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) have been studied for years as primary cell sources for regenerative biology and medicine. MSCs have been derived from cell and tissue sources, such as bone marrow (BM), and more recently from ESCs. This study investigated MSCs derived from BM, H1- and H9-ESC lines in terms of morphology, surface marker and growth factor receptor expression, proliferative capability, modulation of immune cell growth and multipotency, in order to evaluate ESC-MSCs as a cell source for potential regenerative applications. The results showed that ESC-MSCs exhibited spindle-shaped morphology similar to BM-MSCs but of various sizes, and flow cytometric immunophenotyping revealed expression of characteristic MSC surface markers on all tested cell lines except H9-derived MSCs. Differences in growth factor receptor expression were also shown between cell lines. In addition, ESC-MSCs showed greater capabilities for cell proliferation, and suppression of leukocyte growth compared to BM-MSCs. Using standard protocols, induction of ESC-MSC differentiation along the adipogenic, osteogenic, or chondrogenic lineages was less effective compared to that of BM-MSCs. By adding bone morphogenetic protein 7 (BMP7) into transforming growth factor beta 1 (TGFβ1)-supplemented induction medium, chondrogenesis of ESC-MSCs was significantly enhanced. Our findings suggest that ESC-MSCs and BM-MSCs show differences in their surface marker profiles and the capacities of proliferation, immunomodulation, and most importantly multi-lineage differentiation. Using modified chondrogenic medium with BMP7 and TGFβ1, H1-MSCs can be effectively induced as BM-MSCs for chondrogenesis.
Observations of spray density effects on multicomponent chlorinated hydrocarbon vaporization and thermal destruction

Lean post-flame thermal destruction data are presented for polydisperse variable density solid cone sprays composed of 75/25 mixtures of 1.1.1-trichloroethane (TCA) with heptane and TCA with hexadecane. Our goal is to explore the effects of spray density-induced droplet interactions on waste stream blending methods aimed at improving chlorinated hydrocarbon incinerability. Atomization is accomplished through the use of a novel prefilming double-annular airblast atomizer, allowing independent variation of mean spray density and Sauter mean droplet diameter (SMD). Parametric flow reactor studies reveal no effect of spray density or composition on the vaporization of pure TCA and TCA-alkane sprays and no impact on the gas-phase decomposition of TCA within the limits of experimental error. However, dichloroethylene (DCE), the primary product of TCA decomposition, exhibits increased peak concentrations at lower temperatures for denser spray conditions and increased destruction rates at higher temperatures associated with both alkane addition and denser spray conditions. The data suggest that radical pool concentrations are responsible for density- and composition-induced variations in by-product formation and destruction.
The Orbital Search for Altered Materials on Mars

The Martian surface is dominated by primary igneous minerals common in basaltic rocks. Limited chemical alteration exists in fine-grained dust, and is likely in sands and rocks at high latitudes and in the northern lowland plains where materials have interacted with ice and snow. Evidence for extensive production of secondary phases is revealed at higher spatial resolutions, where alteration effects of unique, and perhaps time-limited, aqueous environments are observed. The distribution of ice on Mars thus appears to have a global influence on the production of alteration materials, whereas the effects of water are discovered in unique and locally diverse geological settings.
Progesterone and 20α-Hydroxypregn-4-en-3-one in Plasma, Ovaries and Uteri During Pregnancy in the Rat1

Progesterone and 20α-OH-P levels were measured by double isotope assay in pregnant rat peripheral plasma, ovaries, uteri and placentae at selected times extending from the 2nd day of pregnancy until term. Evidence is presented which supports the conclusion that uterine tissue is capable of concentrating pro-gesterone above peripheral blood levels throughout early and midpregnancy. High intrauterine concentrations of progesterone relate quantita-tively to biological events associated with hormon al function, e.g., nidation, decidua formation and myometrial quiescence. Increased uterine motility, resulting eventually in parturition, apparently follows a reduction in uterine proges-terone concentration. These correlations cannot be made with the closely related progesterone metabolite, 20α-OH-P. This is likely due, in part at least, to its more rapid clearance from systemic compartments. (Endocrinology 87: 43, 1970)
The reduction of the inhibitory effect of aluminum on Na+ efflux in barnacle muscles fibers by preinjecting phosphate.

Abstract The object of the present study was to test the hypothesis that the pre-enrichment of single muscle fibers from the barnacle Balanus nubilus with inorganic phosphate may protect the basal Na efflux from the inhibitory effect of Al injection. This approach was adopted in the light of evidence that the preinjection of ATP fails to stop the Na efflux in unpoisoned fibers from falling following the injection of Al. The results of the experiments are as follows: (i) Preinjection of K 2 HPO 4 into unpoisoned fibers reduces the magnitude of the inhibitory effect on the basal Na efflux of injected Al in a dose-dependent manner but fails to completely stop it from occuring. (ii) Injection of K 2 HPO 4 following Al into unpoisoned fibers fails to arrest or reverse the inhibitory effect of injected Al. (iii) Injection of K 2 HPO 4 in a concentration as high as 0.5 M is without effect on the course of the basal Na efflux. (iv) Injection of K 2 HPO 4 into ouabain-poisoned fibers fails to stop Al from stimulating the ouabain-insensitive Na efflux. Injection of K 2 HPO 4 following peak stimulation by injecting Al is also without effect. (v) Injection of K 2 HPO 4 in a concentration as high as 0.5 M is without effect on the course of the ouabain-insensitive Na efflux. Collectively, the results obtained with unpoisoned ‘hypersensitive’ fibers are consistent with the view that a significant fraction of the injected inorganic phosphate binds Al 3+ , and hence protects the basal Na efflux from the untoward action of Al 3+ .
A gut-heart connection in cardiometabolic regulation

A new study establishes a link between glucagon-like peptide-1 (GLP-1) release from the gut and the cardiac hormone atrial natriuretic peptide, which lowers blood pressure. As GLP-1 receptor agonists are used to control glycemia in patients with type 2 diabetes, this new gut-heart axis suggests a role of these agents in overall cardiovascular homeostasis (pages 567–575).
The rapid component of electron paramagnetic resonance signal II: a candidate for the physiological donor to photosystem II in spinach chloroplasts.

Rapid light-induced transients in EPR Signal IIf (F-+) are observed in 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-treated, Tris-washed chloroplasts until the state F P680 Q minus is reached. In the absence of exogenous redox mediators several flashes are required to saturate this photoinactive state. However, the Signal IIf transient is observed on only the first flash following DCMU addition if an efficient donor to Signal IIf, phenylenediamine or hydroquinone, is present. Complementary polarographic measurements show that under these conditions oxidized phenylenediamine is produced only on the first flash of a series. The DCMU inhibition of Signal IIf can be completely relieved by oxidative titration of a one-electron reductant with E'Os.o equals to + 480 mV. At high reduction potentials the decay time of Signal IIf is constant at about 300 ms, whereas in the absence of DCMU the decay time is longer and increases with increasing reduction potential. A model is proposed in which Q minus, the reduced Photosystem II primary acceptor, and D, a one-electron 480 mV donor endogenous to the chloroplast suspension, compete in the reduction of Signal IIf (F-+). At high potentials D is oxidized in the dark, and the (Q-+F-+) back reaction regenerates the photoactive F P680 Q state. The electrochemical and kinetic evidence is consistent with the hypothesis that the Signal IIf species, F, is identical with Z, the physiological donor to P680.
Visual Control of Altitude in Flying Drosophila

Unlike creatures that walk, flying animals need to control their horizontal motion as well as their height above the ground. Research on insects, the first animals to evolve flight, has revealed several visual reflexes that are used to govern horizontal course. For example, insects orient toward prominent vertical features in their environment [1], [2], [3], [4] and [5] and generate compensatory reactions to both rotations [6] and [7] and translations [1], [8], [9], [10] and [11] of the visual world. Insects also avoid impending collisions by veering away from visual expansion [9], [12], [13] and [14]. In contrast to this extensive understanding of the visual reflexes that regulate horizontal course, the sensory-motor mechanisms that animals use to control altitude are poorly understood. Using a 3D virtual reality environment, we found that Drosophila utilize three reflexes—edge tracking, wide-field stabilization, and expansion avoidance—to control altitude. By implementing a dynamic visual clamp, we found that flies do not regulate altitude by maintaining a fixed value of optic flow beneath them, as suggested by a recent model [15]. The results identify a means by which insects determine their absolute height above the ground and uncover a remarkable correspondence between the sensory-motor algorithms used to regulate motion in the horizontal and vertical domains.
6-Benzylthioinosine analogues: promising anti-toxoplasmic agents as inhibitors of the mammalian nucleoside transporter ENT1 (es).

Abstract Certain 6-benzylthioinosine analogues have been identified as potential chemotherapeutic agents against Toxoplasma gondii in cell culture and animal models. These compounds are selectively transported and metabolized by toxoplasma infected, but not uninfected, cells. In sharp contrast to mammalian nucleoside transporters, the toxoplasma adenosine/purine transporter (TgAT) allows the transport of these 6-benzylthioinosine analogues into infected cells. After entering the infected cell, these compounds act as subversive substrates for toxoplasma, but not the host, adenosine kinase (EC.2.7.1.20). Hence, 6-benzylthioinosine analogues become toxic to toxoplasma infected cells, but not uninfected host cells or animals. The basis for the lack of uptake of the anti-toxoplasmic 6-benzylthioinosines by uninfected host cells is currently unknown. These anti-toxoplasmic 6-benzylthioinosines may not be substrates for the mammalian nucleoside transporters or they may act as inhibitors of these transporters. Previous studies have shown that some 6-benzylthioinosines are inhibitors of the mammalian nucleoside transporter ENT1 ( es ). Therefore, we examined the efficacy of promising anti-toxoplasmic 6-benzylthioinosines as inhibitors of ENT1 ( es ) in an effort to elucidate the basis for the lack of uptake of anti-toxoplasmic 6-benzylthioinosines by uninfected host cells. The results showed that these compounds are inhibitors of ENT1 ( es ). In general, electron-withdrawing substituents at the ortho , meta or para positions of the benzyl ring improved binding. The most potent inhibitors identified were m - and p -nitro-6-benzylthioinosine, which had K i values in the subnanomolar range. Therefore, anti-toxoplasmic 6-benzylthioinosines are not only selectively toxic to parasites and parasite infected cells, they are also inhibitors of nucleoside transport in host cells. This inhibition of the host nucleoside transport is an added advantage for these 6-benzylthioinosine analogues as anti-toxoplasmic agents. Inhibitors of nucleoside transport in mammalian cells can selectively protect the host from the toxicity of toxic purine nucleosides that may be used in future combination therapy against toxoplasmosis or from metabolites of the 6-benzylthioinosine analogues that may be released by the destruction of infected cells. These findings further advance the rationale for developing 6-benzylthioinosine analogues as selective therapeutic agents for the treatment of toxoplasmosis.
Characterization of radiolabeled components of human sperm surface and seminal plasma.

Externally oriented components on the human sperm cell surface and components in human seminal plasma were labeled by enzymatic iodination with lactoperoxidase and [125I] NaI. SDS-7.5% PAGE of labeled sperm surface resolved one minor and four major components with approximate molecular weights of 92, 72, 46, 30, and 20K daltons, respectively. SDS-7.5% PAGE of labeled seminal plasma resolved five components with approximate molecular weights of 74, 51, 43, 28, and 20K daltons. Three of the five moieties seen on the sperm surface and in seminal plasma were similar in molecular weight. This suggested that these surface components were adsorbed from seminal secretions. Because the iodination procedure used labels both proteins and lipids, labeled sperm surface and labeled seminal plasma were subjected to isopycnic density gradient centrifugation to identify the chemical composition of the radioiodinated components. With human sperm surface, two areas of radioactivity were resolved in CsCl gradients, one corresponding to protein and the other to lipid. With human seminal plasma, only one area of radioactivity, corresponding to protein, was identified. Electrophoretic analysis of each peak of radioactivity obtained from the gradients demonstrated that all of the sperm surface and four of five seminal plasma components were in the protein fractions. All three of the seminal plasma components which correspond to sperm surface components were recovered in the protein fraction. This observation supports our hypothesis that some of the proteins labeled on the human sperm cell surface are adsorbed from seminal secretions.
Development of Eucalyptus clones for a summer rainfall environment with periodic severe frosts

Eucalyptus grandis, E. grandis hybrid, and E. saligna hybrid trees, developed through as many as four generations of selection in southern Florida, were naturally exposed to exceptionally low winter temperatures. In a genetic base population and related field studies, 100 phenotypically superior cloning candidates were selected after an 8-h freeze with a low of −11 °C. Following propagation as rooted cuttings, 55 clones (typically 11–42 ramets per clone) were outplanted in a single-tree plot design and evaluated for 3.8 years which included two additional severe freezes. Significant clonal variation was observed in frost resilience, vigor, and quality. After composite evaluation for frost resilience, size, and form, only three clones were considered suitable for operational planting. Selection of further clones for outplanting requires major commitments to locate candidates and to test them. Field testing for frost resilience requires considerable investment, much beyond the requirements for developing fast-growing clones alone. Clones identified by testing will not be resistant to freezing conditions but will be resilient and greatly reduce the risks now associated with plantation culture in southern Florida.
Multilevel continuation techniques for nonlinear boundary value problems with parameter dependence

A new technique is described to continue along solution branches of parameter- dependent nonlinear boundary value problems in order to obtain accurate multigrid solutions at specified points. In particular, the implementation for a general class of second order equations in divergence form in the program PLTMG is described and analyzed. This method has proven to be very robust and efficient, as is illustrated by several examples.
Road-runoff metal concentrations in Toledo, Ohio, and their relation to average daily traffic and age of pavement overlay.

Road runoff can contain metal concentrations and sampling of it can be expensive if auto-samplers are used. In this study, an inexpensive storm water sampling apparatus was developed and used for collecting the road runoff at eleven different sites in Toledo area. Sites were selected with the purpose of evaluating the effects of average daily traffic (ADT) and the age of pavement overlay on road runoff metal concentrations. Ag, As, Cd, and Mo concentrations were primarily below detection limit. Ba, Mn, Ni, Cu, Pb, and Zn were observed in higher concentrations but lower than < 800 μg/L. Mg, Al, Fe, K, Na, and Ca were observed in mg/L levels, much higher concentrations. ADT was positively correlated with runoff concentrations of K, Mn, Pb and Zn. The source of Ca, Mg, and Mn appeared to be the asphalt pavement surface; with time, as the pavement aged, these sources appeared to be depleted as observed by lower runoff concentrations in older pavements.
License plate reader (LPR) police patrols in crime hot spots: an experimental evaluation in two adjacent jurisdictions

Objectives This randomized controlled experiment tests whether license plate readers (LPR) deter crime generally, and automobile crime more specifically in crime hot spots. The limited intervention tested here reflects one current likely use of LPR at the time of this publication.
Evidence for antigen presentation to sensitized T cells by thyroid peroxidase (TPO)-specific B cells in mice injected with fibroblasts co-expressing TPO and MHC class II

Injection of AKR/N mice with fibroblasts co-expressing MHC class II and TPO in the absence of adjuvant induces IgG-class TPO antibodies that resemble spontaneously arising human thyroid autoantibodies. We have used this model to examine the effect of iodide on TPO antibody induction as well as to analyse the interaction between T and B cells. Despite its importance as a major environmental factor in thyroid autoimmunity, variable iodide intake had no detectable effects on TPO antibody levels, lymphocytic infiltration of the thyroid or thyroid hormone levels. In terms of T cell responsiveness, splenocytes from TPO fibroblast-injected mice, but not from control mice, proliferated in response to TPO. Intriguingly, B cell-depleted splenocytes (mainly T cells without reduction of macrophages) proliferated in response to TPO only when co-cultured with irradiated autologous splenocytes from TPO fibroblast-injected mice but not from control mice. These data suggest that TPO-specific B cells are involved in antigen presentation to sensitized T cells and are supported by the ability of spleen cells from TPO cell-injected (but not control) mice to secrete TPO antibodies spontaneously in culture. In conclusion, we provide the first evidence for the presence of thyroid autoantigen-specific B cells and their ability to present their autoantigen to sensitized T cells in mice induced to develop TPO antibodies resembling autoantibodies in humans.
A comparison of modeling nonlinear systems with artificial neural networks and partial least squares

Abstract Artificial neural networks (ANN) can be used to model nonlinear and noisy calibration systems. Models of such systems can also be made by partial least squares (PLS) regression after linearization of the data. These different models and their predictive properties have been tested. The data used are measurements of inorganic and organic air pollutants, solar light intensity, temperature, and corresponding ozone (O3) concentrations. The total data set sizes are: 710×57 and 710×10 for X and 710×1 for y. The large number of objects permits splitting the data into calibration and test sets. The orthogonality properties of the derived linear and nonlinear functional basis sets are investigated. This investigation shows that certain aspects of latent variable based linear modeling can be transferred to the ANN models. Nonlinear neurons can be linearized after the training iterations have been completed. The use of this mixed approach permits the development of additional understanding of the nature of the basis set expansion that is used in the typical neural network (NN). This approach also avoids overfitting and appreciably improves the predicted results.
A continuous, quantitative fluorescent assay for plant caffeic acid O-methyltransferases.

Plant caffeic acid O-methyltransferases (COMTs) use S-adenosylmethionine (ado-met), as a methyl donor to transmethylate their preferred (phenolic) substrates in vivo, and will generally utilize a range of phenolic compounds in vitro. Collazo et al. (Anal. Biochem. 2005, 342, 86−92) have published a discrete, end-point fluorescence assay to detect histone methyltransferases using S-adenosyl homocysteine hydrolase and adeonsine deaminase as coupling enzymes and a thiol-specific fluorophore, Thioglo1, as the detecting reagent. Using this previous assay as a guide, we have developed and validated a facile, sensitive and real-time fluorescence assay for characterizing plant COMTs and in the process simplified the original assay as well by obviating the need for adenosine deaminase in the assay, and simultaneously converting an end-point assay into a continuous one. Our assay has been used to kinetically characterize recombinant sorghum COMT (Bmr-12) a key enzyme involved in cell wall lignification, and analyze...
A fluorometric procedure for the determination of ammonia in blood

Abstract A new fluorometric method for the determination of ammonia in blood and plasma is described. The procedure involves the separation of ammonia from the sample by the Seligson's microdiffusion technique. The ammonia is then converted to 3,5 diacetyl-1,4 dihydrolutidine by the Hantzsch reaction in which acetyl acetone, formaldehyde and ammonia are the reactants. Satisfactory recoveries have been obtained by this method in which standard ammonia is added to blood or plasma. From the standpoint of sensitivity and time required, this technique is believed to be an improvement over previously described procedures for ammonia determination.
Preparation and photocatalytic studies on a novel Ti-substituted polyoxometalate

Abstract The crystal structure of a Ti-substituted Dawson-type polyoxotungstate K 19 H 9 [P 4 W 32 Ti 6 O 132 ] has been determined in the presence of coordinated oxalate anions. The K + salt is water soluble and the [ n -Bu 4 N] + salt is soluble in acetonitrile and acetone. The anion exists as a dimer of two [P 2 W 16 Ti 2 O 62 ] 10− units connected via two external TiO 6 octahedra. The photocatalytic activity of the [ n -Bu 4 N] + salt toward the oxidation of cyclohexanol, 1-hexanol, and 2-hexanol gave pseudo first-order rate constants of 0.03 h −1 , 0.01 h −1 , and 0.01 h −1 , respectively. The relative photocatalytic activities for the oxidation of cyclohexanol by ( n -Bu 4 N) 9 H 19 [P 4 W 32 Ti 6 O 132 ] and various polyoxotungstates of similar structure are compared.
Genetic Modifiers of Neurofibromatosis Type 1-Associated Café-au-Lait Macule Count Identified Using Multi-platform Analysis

Neurofibromatosis type 1 (NF1) is an autosomal dominant, monogenic disorder of dysregulated neurocutaneous tissue growth. Pleiotropy, variable expressivity and few NF1 genotype-phenotype correlates limit clinical prognostication in NF1. Phenotype complexity in NF1 is hypothesized to derive in part from genetic modifiers unlinked to the NF1 locus. In this study, we hypothesized that normal variation in germline gene expression confers risk for certain phenotypes in NF1. In a set of 79 individuals with NF1, we examined the association between gene expression in lymphoblastoid cell lines with NF1-associated phenotypes and sequenced select genes with significant phenotype/expression correlations. In a discovery cohort of 89 self-reported European-Americans with NF1 we examined the association between germline sequence variants of these genes with cafe-au-lait macule (CALM) count, a tractable, tumor-like phenotype in NF1. Two correlated, common SNPs (rs4660761 and rs7161) between DPH2 and ATP6V0B were significantly associated with the CALM count. Analysis with tiled regression also identified SNP rs4660761 as significantly associated with CALM count. SNP rs1800934 and 12 rare variants in the mismatch repair gene MSH6 were also associated with CALM count. Both SNPs rs7161 and rs4660761 (DPH2 and ATP6V0B) were highly significant in a mega-analysis in a combined cohort of 180 self-reported European-Americans; SNP rs1800934 (MSH6) was near-significant in a meta-analysis assuming dominant effect of the minor allele. SNP rs4660761 is predicted to regulate ATP6V0B, a gene associated with melanosome biology. Individuals with homozygous mutations in MSH6 can develop an NF1-like phenotype, including multiple CALMs. Through a multi-platform approach, we identified variants that influence NF1 CALM count.
Plasma Renin Activity Enzyme-Kinetic Assay: Protection of Angiotensin I from Bacterial Degradation

To the Editor: Bystrom et al. (1) recently reported substantial peptidase activity in human plasma that had been incubated at 37 °C to generate angiotensin I (Ang I)1 during the clinical plasma renin activity (PRA) assay. If this result is correct, it would call into question many of the PRA results previously reported by our laboratory and by Quest Diagnostics, especially those with low PRA (<0.65 μg · L− · h−). We believe, however, this observation is most likely an artifact caused by a failure to follow published protocols (2, 3). Several features of the Ang I degradation reported by …
On neglecting chemical exchange effects when correcting in vivo (31)P MRS data for partial saturation.

Abstract Signal acquisition in most MRS experiments requires a correction for partial saturation that is commonly based on a single exponential model for T 1 that ignores effects of chemical exchange. We evaluated the errors in 31 P MRS measurements introduced by this approximation in two-, three-, and four-site chemical exchange models under a range of flip-angles and pulse sequence repetition times ( T R ) that provide near-optimum signal-to-noise ratio (SNR). In two-site exchange, such as the creatine-kinase reaction involving phosphocreatine (PCr) and γ-ATP in human skeletal and cardiac muscle, errors in saturation factors were determined for the progressive saturation method and the dual-angle method of measuring T 1 . The analysis shows that these errors are negligible for the progressive saturation method if the observed T 1 is derived from a three-parameter fit of the data. When T 1 is measured with the dual-angle method, errors in saturation factors are less than 5% for all conceivable values of the chemical exchange rate and flip-angles that deliver useful SNR per unit time over the range T 1 /5 ≤ T R ≤ 2 T 1 . Errors are also less than 5% for three- and four-site exchange when T R ≥ T 1 * /2, the so-called “intrinsic” T 1 's of the metabolites. The effect of changing metabolite concentrations and chemical exchange rates on observed T 1 's and saturation corrections was also examined with a three-site chemical exchange model involving ATP, PCr, and inorganic phosphate in skeletal muscle undergoing up to 95% PCr depletion. Although the observed T 1 's were dependent on metabolite concentrations, errors in saturation corrections for T R = 2 s could be kept within 5% for all exchanging metabolites using a simple interpolation of two dual-angle T 1 measurements performed at the start and end of the experiment. Thus, the single-exponential model appears to be reasonably accurate for correcting 31 P MRS data for partial saturation in the presence of chemical exchange. Even in systems where metabolite concentrations change, accurate saturation corrections are possible without much loss in SNR.
Carbamate Insecticides: The Cross-Resistance Spectra of Four Carbamate-Resistant Strains of the House Fly After Protracted Selection Pressure

House fly ( Musca domestica L.) strains maximally resistant to m -isopropylphenyl N -methylcarbamate and Isolan® (1-isopropyl-3-methyl-5-pyrazolyl dimethylcarbamate) were further selected routinely with these compounds to maintain resistance. Selection pressure over M generations resulted in maximal or near-maximal cross-resistance to DDT and methoxychlor, and in various levels of cross-tolerance or cross-resistance to organo-phosphorus compounds. A second strain selected with m -isopropylphenyl N -methylcarbamate showed a cross-resistance pectrum similar to those of the previous strains and demonstrated the induction of cross-resistance to lindane and dieldrin through selection with carbamate. The cross-resistance spectra of the carbamate-selected strains showed greater resemblance to the spectra of organophosphorus-than of chlorinated hydrocarbon-selected strains, thus suggesting relationships in esterases responsible for organophosphorus and carbamate detoxication.
Intraoperative Urokinase Infusion for Embolic Stroke during Carotid Endarterectomy

Embolic stroke is an infrequent complication of carotid endarterectomy. Somatosensory evoked potential monitoring detected delayed acute neurological deterioration during endarterectomy performed on a 71-year-old woman. Intraoperative arteriography performed via an indwelling shunt revealed thrombus within the middle cerebral artery and distal branches. A microcatheter was placed into the internal carotid artery via the arteriotomy and advanced into the middle cerebral artery. Urokinase was infused into and around the thrombus until almost complete thrombolysis had been achieved. The patient recovered quickly and was discharged without neurological deficit.
Studies on the reaction of proteins and peptides with methyl isothiocyanate and identification of the methylthuohydantoins by gas-liquid chrormatography

Abstract A procedure for the N-terminal analysis of proteins and sequencing of small peptides is reported. The protein or peptide is coupled with methyl isothiocyanate and the N-terminal amino acid is split off as its thiazolinone, which is extracted with ethyl acetate and converted to its methylthiohydantoin. The methylthiohydantoins are analyzed as their trimethylsilyl derivatives by gas-liquid chromatography. It is possible to continue the degradation of a protein and obtain an N-terminal sequence. An additive approach to sequencing small peptides is described which is faster and simpler than existing methods. Analysis of the methylthiohydantoins by gas-liquid chromatography of the trimethylsilyl derivatives is possible for all of the common protein amino acids except arginine, Most of the methylthiohydantoins are resolved on an OV-17 column; an OV-1 column is required to differentiate the trimethylsilyl derivatives of MTH glycine and MTH valine. The identities of the gas chromatographic peaks were confirmed by gas chromatography-mass spectrometry.
Synthesis and radioiodination of ten aryl‐carbohydrate compounds for labeling monoclonal antibodies

Ten aryl-carbohydrate ligands have been synthesized that potentially increase the tumor retention and decrease the deiodination of iodinated monoclonal antibodies used in the imaging and treatment of cancer. The compounds were synthesized via reductive amination reactions, purified with cation exchange chromatography, and characterized using 1H and 13C NMR. These compounds were then radioiodinated to assess their iodination characteristics, for subsequent experiments involving attachment to monoclonal antibodies.
Physical Determinants of Fibrinolysis in Single Fibrin Fibers

Fibrin fibers form the structural backbone of blood clots; fibrinolysis is the process in which plasmin digests fibrin fibers, effectively regulating the size and duration of a clot. To understand blood clot dissolution, the influence of clot structure and fiber properties must be separated from the effects of enzyme kinetics and perfusion rates into clots. Using an inverted optical microscope and fluorescently-labeled fibers suspended between micropatterned ridges, we have directly measured the lysis of individual fibrin fibers. We found that during lysis 64 ± 6% of fibers were transected at one point, but 29 ± 3% of fibers increase in length rather than dissolving or being transected. Thrombin and plasmin dose-response experiments showed that the elongation behavior was independent of plasmin concentration, but was instead dependent on the concentration of thrombin used during fiber polymerization, which correlated inversely with fiber diameter. Thinner fibers were more likely to lyse, while fibers greater than 200 ± 30 nm in diameter were more likely to elongate. Because lysis rates were greatly reduced in elongated fibers, we hypothesize that plasmin activity depends on fiber strain. Using polymer physics- and continuum mechanics-based mathematical models, we show that fibers polymerize in a strained state and that thicker fibers lose their prestrain more rapidly than thinner fibers during lysis, which may explain why thick fibers elongate and thin fibers lyse. These results highlight how subtle differences in the diameter and prestrain of fibers could lead to dramatically different lytic susceptibilities.
Peer review for biomedical publications: we can improve the system

The lack of formal training programs for peer reviewers places the scientific quality of biomedical publications at risk, as the introduction of `hidden’ bias may not be easily recognized by the reader. The exponential increase in the number of manuscripts submitted for publication worldwide, estimated in the millions annually, overburdens the capability of available qualified referees. Indeed, the workload imposed on individual reviewers appears to be reaching a `breaking point’ that may no longer be sustainable. Some journals have made efforts to improve peer review via structured guidelines, courses for referees, and employing biostatisticians to ensure appropriate study design and analyses. Further strategies designed to incentivize and reward peer review work include journals providing continuing medical education (CME) credits to individual referees by defined criteria for timely and high-quality evaluations. Alternative options to supplement the current peer review process consist of `post-publication peer review,’ `decoupled peer review,’ `collaborative peer review,’ and `portable peer review’. This article outlines the shortcomings and flaws in the current peer review system and discusses new innovative options on the horizon. See related article: http://www.biomedcentral.com/content/pdf/s12916-014-0128-z.pdf .
Optimized intensity thresholds for volumetric analysis of magnetic-resonance imaging data (Proceedings Only)

A technique is presented for computing optimal threshold values for volumetric analysis of MRI data, in the presence of partial volume effects and noise. Thresholds are computed from nominal structure intensities, detected from intensity histograms. Histogram modification methods are described to improve the detectability of these intensities. The implementation of the technique is discussed for detection of contours of the brain and the ventricular system. Results are presented of validation experiments using simulated data, generated from MRI scans of a phantom of the ventricular system in the brain, and of six whole-brain MRI scans.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.