cssi/SciSciGPT-SciSciNet huggingface dataset:
Alpha and Omega of Carotenoid Cleavage

In early 1900s, based on indirect evidence, Steenbock and Morton independently predicted that beta-carotene could be the biological precursor of vitamin A, although this notion was contested by others. In the 1930s, Thomas Moore showed the in vivo formation of vitamin A from beta-carotene. But it was not until Jim Olson and DeWitt Goodman independently showed in 1965 the formation of retinal, the aldehyde form of vitamin A from beta-carotene in cell-free extracts of liver and intestine, that this vital pathway of beta-carotene was recognized. Despite compelling evidence in several experimental systems for the central cleavage of beta-carotene to retinal by many investigators, there were some careful independent studies by Glover et al., Ganguly et al., Hansen and Meret and Krinsky et al. showing the eccentric cleavage of beta-carotene resulting in the formation of apocarotenoids both in vivo and in vitro. In an attempt to resolve this controversial issue, we revisited this problem in 1989 and showed beyond doubt the formation of retinal as the sole enzymatic product of a cytosolic enzyme from rabbit and rat intestinal mucosa by mass spectrometry and tracer analysis of the crystallized product. This was confirmed in 1996 by Nagao using the pig intestinal extract. Yeum et al. confirmed in 2000 that retinal is the sole product of beta-carotene cleavage in the presence of alpha-tocopherol, and that the observed formation of apocarotenoids occurs only in the absence of an antioxidant like alpha-tocopherol. In the same year, Barua and Olson also concluded from their in vivo studies in rats that central cleavage is by far the major pathway for the formation of vitamin A from beta-carotene. Beta, beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) is the key enzyme that cleaves beta-carotene into two molecules of retinal. It is a cytosolic enzyme primarily localized in the duodenal mucosa although it has been found in liver. It is a 66 kDa sulfhydryl protein, requires molecular oxygen and is activated by ferrous ions. It is highly specific for 15:15' ethylenic bond of carotenoids although it has fairly broad specificity towards a number of carotenoids with at least one intact beta-ionone ring. The dioxygenase was recently cloned from Drosophila melanogaster and from the chicken intestine. The recombinant protein was found to form retinal as the sole cleavage product of beta-carotene. No apo-carotenoids were formed. Therefore, it is unequivocally proven that the major, if not the sole, pathway of beta-carotene cleavage to vitamin A is by oxidative cleavage of the central ethylenic bond of beta-carotene to yield two molecules of retinal. Most recently, human dioxygenase has also been cloned. Thus, the wisdom, vision and epoch-making mission of Jim Olson in the science of beta-carotene metabolism have been accomplished. I have no doubt that the impact of his original discovery of the dioxygenase and its importance in vitamin A nutriture should be forthcoming in the near future.
The persistence of object file representations.

Coherent visual experience of dynamic scenes requires not only that the visual system segment scenes into component objects but that these object representations persist, so that an object can be identified as the same object from an earlier time. Object files (OFs) are visual representations thought to mediate such abilities: OFs lie between lower level sensory processing and higher level recognition, and they track salient objects over time and motion. OFs have traditionally been studied viaobjectspecific preview benefits (OSPBs), in which discriminations of an object’s features are speeded when an earlier preview of those features occurred on the same object, as opposed to on a different object, beyond general displaywide priming. Despite its popularity, many fundamental aspects of the OF framework remain unexplored. For example, although OFs are thought to be involved primarily in online visual processing, we do not know how long such representations persist; previous studies found OSPBs for up to 1,500msec but did not test for longer durations. We explored this issue using a modifiedobject reviewing paradigm and found that robust OSPBs persist for more than five times longer than has previously been tested—for at least 8 sec, and possibly for much longer. Object files may be the “glue” that makes visual experience coherent not just in online moment-by-moment processing, but on the scale of seconds that characterizes our everyday perceptual experiences. These findings also bear on research in infant cognition, where OFs are thought to explain infants’ abilities to track and enumerate small sets of objects over longer durations.
Identification and quantification of a guanine-thymine intrastrand cross-link lesion induced by Cu(II)/H2O2/ascorbate.

Reactive oxygen species (ROS) can be induced by both endogenous and exogenous processes, and they can damage biological molecules including nucleic acids. It was shown that X- or γ-ray irradiation of aqueous solutions of DNA, during which •OH is one of the major ROS, can lead to the formation of intrastrand cross-link lesions where the neighboring nucleobases in the same DNA strand are covalently bonded. Previous 32P-postlabeling studies suggested that the intrastrand cross-link lesions may arise from Fenton reaction, which also induces the formation of •OH; the structures of the proposed intrastrand cross-link lesions, however, have not been determined. Here, we showed for the first time that the treatment of calf thymus DNA with Cu(II)/H2O2/ascorbate could lead to the formation of an intrastrand cross-link lesion, i.e., G∧T, where the C8 of guanine is covalently bonded to the neighboring 3‘-thymine through its methyl carbon. LC-MS/MS quantification results showed dose−responsive formation of G∧T. In add...
Quantitative Analysis of the DNA Adduct N2,3- Ethenoguanine Using Liquid Chromatography/ Electrospray Ionization Mass Spectrometry

The need for specificity and sensitivity in the analysis of DNA adducts has led the development of GC/MS methods. Such methods require chemical derivatization (i.e. silylation, electrophore labelling), which can also bring its own sets of problems, including the production of artifacts, interferences and sample to sample variability in derivatization. To obviate such problems, a liquid chromatographic/electrospray ionization mass spectrometric (LC/ESI-MS) method was developed to quantify N2,3-ethenoguanine (epsilon Gua), a promutagenic DNA adduct of vinyl chloride exposure. The response of epsilon Gua to isotopically labelled internal standard [13C4]epsilon Gua was linear (r2 = 0.999) and reproducible from 0.027 to 0.538 pmol microliter-1. We obtained an accuracy of 86 +/- 14% by analyzing chloroethylene oxide (CEO)-treated calf thymus DNA enriched with authentic epsilon Gua. The analysis of CEO-treated calf thymus DNA samples not enriched with authentic epsilon Gua provided a precision of 15%. The detection limits with a signal-to-noise ratio (S/N) 2.5:1 were obtained in the determination of authentic epsilon Gua at 5 fmol per injection. The detection limit obtained in the routine analysis of the biological samples was 50 fmol epsilon Gua with S/N = 3:1. The applicability of the method was established by determining epsilon Gua in rats treated with CEO by portal vein injection and an unexposed human liver. It was observed that the concentration of epsilon Gua in the rat livers increased with increase in dose and was inversely related to the time after, CEO exposure. This trend suggests rapid repair of the adduct in rat livers. In the human liver DNA sample, epsilon Gua was quantitated at 0.06 +/- 0.01 pmol mg-1 DNA.
Silver ion solid‐phase extraction chromatography for the analysis of trans fatty acids

Summary This article describes the application of silver ion solid-phase extraction (Ag + -SPE) to the separation of the fatty acid methyl esters (FAMEs)prepared from a partially hydrogenated fish oil (PHFO) with a trans fatty acid (FA) content of 41%. The complex FAME mixture wasresolved into the following FAME fractions: saturated FA, trans-monounsaturated FA (trans-MUFA), cis-MUFA, and several polyunsatu-rated FA (PUFA) fractions with mixed geometric and positional isomers. Fractions were analyzed by gas chromatography (GC) using a 100 mcyanopropyl polysiloxane (CPS) coated capillary column. The GC analysis of the Ag + -SPE fractions allowed for the identification of the trans-andcis-MUFAandotherFAMEpreparedfromPHFO. Introduction As early as 1966 Morris [1] had concluded that argentation chroma-tography was third in importance to GC and thin-layer chromato-graphy (TLC) for the analysis of lipids. This optimistic predictionwas largely based on separations achieved by using Ag + -TLC toresolve FAMEs with different numbers and geometric configura-tions of double bonds. These results were essential to complementGC separations of FAMEs on packed columns that provided reso-lution determined by chain length and number of double bonds, butcould not resolve geometric isomers. One might have thought thatthe subsequent development of the very long, highly polar GC ca-pillary columns that now make it possible to resolve most geo-metric and positional isomers and PUFAs would have phased outthe need for silver ion (Ag
Cervical electromyographic activity during low-speed rear impact.

Whiplash motion of the neck is characterized by having an extension-flexion motion of the neck. It has been previously assumed that muscles do not play a role in the injury. Eight healthy males were seated in a car seat mounted on a sled. The sled was accelerated by a spring mechanism. Muscle electromyographic (EMG) activity was measured by wire electrodes in semispinalis capitis, splenius capitis, and levator scapulae. Surface EMG activity was measured over trapezius and sternocleidomastoideus. Wavelet analysis was used to establish the onset of muscle activity with respect to sled movement. Shorter reaction times were found to be as low as 13.2 ms from head acceleration and 65.6 ms from sled acceleration. Thus the muscles could influence the injury pattern. It is of interest that clinical symptoms are often attributed to muscle tendon injuries.
Inhibition of catechol-o-methyl transferase by catechols and polyphenols☆

Abstract The effects of the polyphenolic decarboxylase inhibitor, N1-(d,l-seryl)-N2-(2,3,4-Trihydroxybenzyl)-hydrazine (RO4-4602), were compared with the effects of dopa and pyrogallol as inhibitors of catechol-o-methyl transferase (COMT). The apparent Km, for [3H]norepinephrine as the substrate was 0.36 mM. The catechol amino acid, l -dihydroxyphenylalanine ( l -dopa), a substrate of COMT, was a weak inhibitor of COMT (Ki = 0.42 mM) and appeared to be competitive with norepinephrine; D-dopa was slightly less potent. In contrast, the polyphenol pyrogallol exhibited partially noncompetitive inhibition of COMT with respect to the substrate (Ki = 30 μM). RO4-4602 exhibited similar noncompetitive inhibitory kinetics (Ki = 60 μM). In contrast to dopa and pyrogallol, RO4-4602 appears to be a relatively poor substrate for COMT. In vivo, RO4-4602 led to markedly increased recovery from brain of labeled catechol products of peripherally administered [3H] l -dopa, probably partly due to inhibition of decarboxylation as well as methylation. Furthermore, R04-4602 led to increased recovery of catechol products of [3H]norepinephrine in the heart for as long as 3–5 hr. RO4-4602 was found to be a weak inhibitor of monoamine oxidase in vitro ( ic 50 about 1 mM) and inactive in vivo (up to 100 mg/kg, i.p.). Thus, RO4-4602, an analog of pyrogallol, has similar COMT-inhibitory characteristics to the latter compound in vitro and appears to inhibit COMT in vivo. This property may be partly responsible for its beneficial effects in patients treated with l -dopa.
The Influence of Format and Questions on Candidates' Strategic Argument Choices in the 2000 Presidential Debates

Building on past content analyses of presidential debates to determine how format affects the levels of clash and candidates' strategies, this study answers three questions about the 2000 presidential debates: (a) Do candidates differ in their use of clash and nonclash argument strategies? (b) Does format affect candidates' strategic choices? and (c) Does the structure of questions explain strategic choices? Results of the content analysis suggest that format and question content affect candidates' strategic choices; however, other factors including the larger campaign strategy, polling data, and performance in previous debates also influence strategies.
Uncertainty Analysis of the Remote Exploration and Experimentation System

DOI: 10.2514/1.51380 This paper discusses a method for computing the uncertainty in output metrics of stochastic models due to epistemic uncertainties in the model-input parameters. The method is illustrated by applying it to compute the distribution and confidence interval of the reliability of the Remote Exploration and Experimentation system. This method makes use of Monte Carlo sampling and propagates the epistemic uncertainty in the model parameters through the system reliability model. It acts as a wrapper to already-existing models as well as their solution tools/ techniquesandhasawiderangeofapplicability.Althoughitisasampling-basedmethod,nosimulationiscarriedout whenperforminguncertaintypropagationthroughanalyticmodels,butanalyticoranalytic–numericsolutionofthe underlying stochastic model is performed for each set of input-parameter values, sampled from their distributions. Using the input epistemic uncertainty, in the form of 95% confidence intervals of input parameters of the stochastic model, the two-sided 95% confidence interval of reliability of the Remote Exploration and Experimentation system at a time t 5 years is computed to be (0.949485, 0.981994).
Influence of exchange transfusion on the development of serum immunoglobulins

Thirteen neonates with severe jaundice of various etiologies were followed after exchange transfusion fora period of one year. Blood levels of IgG, IgA, and IgM were measured before and after exchange transfusion, four and ten days later, and at 1, 3, 6, 9, and 12 months of age. Normal and jaundiced but not exchange-transfused infants, matched for age, were used as control subjects. It was concluded that exchange transfusion suppresses the production of autologous IgG and IgA, whereas it provokes IgM synthesis.
The Role of Free Tissue Transfer in Merkel Cell Carcinoma of the Head and Neck

Merkel cell carcinoma (MCC) is an uncommon neuroendocrine malignancy with a propensity for the head and neck. It typically presents asymptomatically in elderly Caucasians and is characterized by early local and regional spread. There is currently limited data on the appropriate algorithm for treatment of MCC. However, multimodal therapy with wide surgical excision with or without radiation therapy has become standard of care. The location of the primary tumor and intensive adjuvant therapy is often required, provides a challenge to the reconstructive head and neck surgeon. Occasionally, free tissue transfer reconstructive techniques are employed in the reconstruction of MCC defects. This paper will discuss the role of free tissue transfer as a reconstructive option after surgery for advanced head and neck MCC.
Bendway weirs: Could they create habitat for the endangered Rio Grande silvery minnow

Rehabilitation of the Middle Rio Grande in central New Mexico has become necessary to mitigate the effects of over a century of water and land development. The primary driving force behind rehabilitation efforts is the federally endangered Rio Grande silvery minnow (Hybognathus amarus). Bendway weirs, erosion control and channel-stabilization structures placed transverse to the channel flow, have been used to prevent river migration while enhancing aquatic habitat. Habitat improvement plans on the Middle Rio Grande include the installation of bendway weirs, but the potential benefits of these structures for Rio Grande silvery minnow are unknown. We conducted a theoretical study on the flow conditions created by bendway weirs to determine if it is possible to create physical habitat for Rio Grande silvery minnow while simultaneously protecting the riverbank. Our study suggested that bendway weir installation could lead to the reduction of downstream displacement of Rio Grande silvery minnow eggs, the creation of Rio Grande silvery minnow feeding and refugia habitat, and the creation of drought or low flow habitat through scour hole formation. We also noted that the weirs could also serve as potential habitat for predators, and suggest further studies to better quantify the possible role of bendway weir installation. Copyright © 2009 John Wiley & Sons, Ltd.
Liquid crystal lens with large focal length tunability and low operating voltage.

We demonstrate a tunable focus liquid crystal (LC) lens by sandwiching a homogeneous LC layer between a planar electrode and a curved electrode. The curved electrode which is made of conductive polymer has parabolic shape with a large apex distance. Such design dramatically reduces the phase loss which leads to a short focal length (~15 cm). By using a thin top glass substrate on the curved electrode side, the operating voltage of the lens cell for achieving the shortest focal length is reduced to ~23 Vrms. This LC lens has advantages in large focal length tunability, low operating voltage, and good mechanical stability.
Microwave synthesis of zeolites: effect of power delivery.

The effect of microwave power magnitude and pulsing frequency on the synthesis enhancement of zeolites, silicoaluminophosphate SAPO-11, silicalite, and NaY, was studied. Pulsing the microwave power compared to continuous delivery at the same averaged fed microwave power showed no effect on the nucleation and crystallization rates of SAPO-11, silicalite, or NaY. However, SAPO-11 synthesized with continuous microwave power delivery produced larger particles compared to pulsed microwave power with the same reaction time (3.77 μm for continuous versus 2.49 μm for pulsed 1 s on; 3 s off). Further, pulsed microwave power delivery used lower steady state power to maintain the same reaction temperature compared to continuous power delivery (55 W compared to 65 W, respectively). The microwave power used to heat the reaction precursors of SAPO-11 and silicalite was varied by applying cooling gas at various rates while maintaining the reaction temperatures. Significant enhancement of the crystallization rate for SAP...
Non-hazardous synthesis of isocephosphorin intermediates via α-vinylamino-β-lactams

Abstract The reaction of a Schiff Base derived from veratrylamine and cinnamaldehyde with (α-methyl-β-alkoxycarbonyl)-vinylamino acetic acid (from glycine and an acetoacetate ester) in presence of a chloroformate ester and triethylamine constitutes a safe synthesis of α-vinylamino β-lactams that can be converted by literature methods to known intermediates for the synthesis of isocephalosporins and analogs.
Extending structure, type, and expression in APL2

The two principal directions of APL today are discussed in the light of recent standards committee meetings. The approach often taken to an extended standard was to place features of both dialects into a work space and force them to work; this might be called a top down approach with hammer. Herein APL2, considered as a representative of nested array systems, is assumed as a base. A growth path is described toward a system which includes features similar to some found in boxed array systems. A parallel discussion beginning with a boxed system and extending toward nested arrays would be welcome. Perhaps working toward a common goal could provide more inspiration than striving to preserve pieces of the past.
Plaque distribution on bonded brackets: a scanning microscope study.

N ew and often extensive patterns of plaque accumulation can develop in association with resin-bonded orthodontic brackets in addition to a subject’s already established plaque pattern.’ Weitman and Eames5 showed that plaque covers the surface of resin restorations within 24 hours of placement and concluded that the resin surface was rough and, therefore, predisposed to the rapid attachment and growth of oral microorganisms. Waerhaug4 demonstrated, histologically, the presence of both supragingival and subgingival plaque on acrylic and other restorations. He also concluded that rough surfaces are likely to encourage the rapid attachment of bacteria and the ultimate promotion of gingival and periodontal disease. Weitman and Eames used erythrocin dye to disclose the plaque but did not correlate their clinical observations with those derived by other methods. However, Jordan and his co-workers,” using the scanning electron microscope, photographed microorganisms on surfaces of composite (filled) restorations as well as acrylic (unfilled) restorations. Their observations supported the Weitman and Eames conclusion and confirmed Waerhaug’s findings. Since filled and unfilled resins are used to bond orthodontic brackets, it was postulated that they may be among the factors contributing to the plaque patterns recorded by ultraviolet photography.’ Because a large number of bonded brackets were available from our study subjects, with significant amounts of resin still attached to them, we undertook their detailed examination for plaque with the scanning electron microscope. The objective of the study was to determine the sites of plaque accumulation and the extent to which plaque accumulated on mesh-back and perforated types of brackets and the resin associated with them.
Role of CD73 and extracellular adenosine in disease

An erratum to this article can be found at http://dx.doi.org/10.1007/s11302-011-9287-y About the authors Moritz Schmelzle, M.D. is a research associate at the Transplant Institute, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA. His research focuses on purinergic mechanisms in stem and immune cell responses in inflammation and organ restoration. Elliot Tapper, M.D is a resident physician and research associate at Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA. His research focuses on purinergic mechanisms of nonalcoholic fatty liver disease and quality care in clinical hepatology. Holger K. Eltzschig, M.D., Ph.D. is a physician scientist at the University of Colorado, Aurora, CO. Simon C. Robson, M.D., Ph.D. is a physician scientist at Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
Topological dynamics and ergodic theory

It is shown that when viewed properly some concepts in topological dynamics and ergodic theory are not merely analogous but equivalent. Also the Mackey-Halmos-von Neumann theorem on ergodic processes with discrete spectrum is generalized and an account of the Mackey-Zimmer theory of minimal cocycles is given in a more general setting.
5-Hydroxytryptamine and thromboxane in platelets from rats treated with monocrotaline pyrrole.

Abstract Monocrotaline pyrrole (MCTP), a metabolite of the plant toxin monocrotaline, produces pulmonary vascular injury, pulmonary hypertension, and right ventricular enlargement (RVE) in rats by an unknown mechanism. A role for platelets has been suggested by the observation that antibody-induced thrombocytopenia reduces the RVE caused by MCTP. The platelet can release a number of vasoconstrictive agents, such as 5-hydroxytryptamine (5HT) and thromboxane A 2 (TxA 2 ), that could possibly contribute to pulmonary hypertension. It was of interest to determine whether treatment with MCTP alters platelet 5HT content or alters the release of TxA 2 in platelet-rich plasma (PRP) in response to aggregation. Fourteen days following treatment with MCTP when pulmonary hypertension is well-established and RVE is present, the concentration of 5HT in washed platelets or in platelet-poor plasma was not different in treated and control rats. One day following treatment with MCTP, before lung injury is evident, the concentration of TxB 2 , a stable metabolite of TxA 2 , was higher in unstimulated PRP from treated rats than in control rats. The concentration of TxB 2 was also examined in PRP at 4 days (when lung injury first appears), 7 days (when pulmonary arterial pressure first increases), and 14 days after treatment with MCTP (when RVE is evident). At 4, 7, or 14 days following treatment there was no difference in the concentration of TxB 2 in unstimulated PRP from MCTP-treated and control rats. Following stimulation with arachidonic acid, the release of TxB 2 at maximal aggregation was not different in PRP from MCTP-treated and control rats at any time after treatment. The rate of release of TxB 2 was lower in PRP from rats treated with MCTP 7 days earlier, but was not different at any other time following treatment. At concentrations up to 250 μg/ml, MCTP added in vitro to PRP from untreated rats did not affect the concentration of TxB 2 released during aggregation induced by arachidonic acid. Only at very high concentrations (1 mg/ml) did MCTP abolish the aggregation response and depress TxB 2 release in PRP. These results indicate that MCTP treatment does not affect platelet 5HT content and does not affect basal TxB 2 production or TxB 2 release by platelets stimulated in vitro .
Cardiovascular disease management: the need for better diagnostics

Current diagnostic testing for cardiovascular pathology usually rests on either physiological or anatomic measurement. Multiple tests must then be combined to arrive at a conclusion regarding treatment of a specific pathology. Much of the diagnostic decisions currently made are based on rough estimates of outcomes, often derived from gross anatomic observations or extrapolation of physical laws. Thus, intervention for carotid and coronary disease is based on estimates of diameter stenosis, despite data to suggest that plaque character and lesion anatomy are important determinants of outcome. Similarly, abdominal aortic aneurysm (AAA) intervention is based on maximal aneurysm diameter without regard for arterial wall composition or individual aneurysm geometry. In other words, our current diagnostic tests do not reflect the sophistication of our current knowledge of vascular disease. Using a multimodal approach, computer modeling has the potential to predict clinical outcomes based on a variety of factors including arterial wall composition, surface anatomy and hemodynamic forces. We term this more sophisticated approach “patient specific diagnostics”, in which the computer models are reconstructed from patient specific clinical visualizing modalities, and material properties are extracted from experimental measurements of specimens and incorporated into the modeling using advanced material models (including nonlinear anisotropic models) and performed as dynamic simulations using the FSI (fluid structure interaction) approach. Such an approach is sorely needed to improve the effectiveness of interventions. This article will review ongoing work in “patient specific diagnostics” in the areas of carotid, coronary and aneurismal disease. We will also suggest how this approach may be applicable to management of aortic dissection. New diagnostic methods should allow better patient selection, targeted intervention and modeling of the results of different therapies.
Exponential bounds for discrete-time singularly perturbed Markov chains

Abstract This paper develops exponential type upper bounds for scaled occupation measures of singularly perturbed Markov chains in discrete time. By considering two-time scale in the Markov chains, asymptotic analysis is carried out. The cases of the fast changing transition probability matrix is irreducible and that are divisible into l ergodic classes are examined first; the upper bounds of a sequence of scaled occupation measures are derived. Then extensions to Markov chains involving transient states and/or nonhomogeneous transition probabilities are dealt with. The results enable us to further our understanding of the underlying Markov chains and related dynamic systems, which is essential for solving many control and optimization problems.
An ab initio study of the electronic and geometric structures of Si m C n + cationic nanoclusters

The theoretical formalism of local density approximation (LDA) to density functional theory (DFT) has been used to study the electronic and geometric structures of SimCn + (1≤m, n ≤4) cationic clusters. An all electron 6-311++G** basis set has been used and complete geometry optimizations of different possible structures for a specific cluster have been carried out. Binding energies, relative energies, fragmentation energies, vibrational frequencies, and adiabatic ionization potentials of the optimized clusters have been investigated and reported in detail. Results have been compared with other experimental and theoretical results available in the literature.
Optimal Treatment Strategies for Anal Cancer

Squamous cell carcinoma (SCCA) of the anal canal is an underrecognized malignancy that is growing in annual incidence. Over the years, combined chemoradiation has been the mainstay of treatment for locally advanced SCCA of the anal canal. Currently, the human papilloma virus (HPV) vaccine is recommended to prevent the development of HPV and its associated precancerous lesion(s). Patients diagnosed with the human immunodeficiency virus (HIV+) are prone to develop anal cancer due to their high risk of contracting HPV infection. We will focus on the development and management of SCCA of the anal canal (both localized and metastatic), including special details on HIV-positive patients. Highlights will include the role of targeted therapy based on available literature. Our objective is to aid practicing physicians in formulating a treatment plan for both locally advanced and metastatic patients.
Comparative analysis of the expressed genome of the infective juvenile entomopathogenic nematode, Heterorhabditis bacteriophora.

We report the first cDNA-sequencing project of the entomopathogenic nematode, Heterorhabditis bacteriophora. A total of 1246 expressed sequence tags (ESTs) were generated by random sequencing of clones from a cDNA library of the infective juvenile stage. The ESTs were annotated resulting in 1072 useful ESTs that were categorized into functional categories according to Kyoto Encyclopedia of Genes and Genomes. Approximately 459 of 1072 ESTs (43%) had significant similarities to annotated sequences in GenBank. Of these, 417 had significant similarities to the free-living nematode Caenorhanditis elegans proteins. Most ESTs (18%) belonged to the genetic information processing category followed by metabolism (15% ESTs) and environmental information processing (15%) pathways. Several interesting ESTs were found that may have roles in the infectivity and survival of infective juveniles. These included proteases, dauer pathway genes ( akt-1, pdk-1 & daf-7) and aging and stress resistance genes such as superoxide dismutase (sod-4), heat shock genes (hsp-4 & hsp-6), and eat genes, and signaling proteins like G-protein coupled receptors, regulators of G-protein signaling ( rgs), and serine/threonine kinases. Other interesting ESTs include systemic RNAi defective protein (sid-1), ribonuclease III family members (rnh-2 & rnc) and transposase gene (Tc3A). About 67% of the ESTs did not find matches in any of the searched databases suggesting potentially novel genes in this enomopathogenic nematode. © 2006 Published by Elsevier B.V.
TH‐E‐218‐08: In‐Vivo Dosimetric Verification of Hypo‐Fractionated Proton Radiation Therapy of the Liver with Hepatocyte‐Specific Functional MRI

Purpose: To investigate if MRI of the liver can be used for in‐vivo dose verification in proton therapy. Recently it was shown that irradiated healthy livertissue shows a strong systematic decrease in uptake of a hepatobiliary‐directed contrast agent (Gd‐EOB‐DTPA) six weeks after brachytherapy. In this study it is investigated, if the radiation‐related effect is also detectable for hypo‐fractionated proton therapy. Methods: For patients who receive liver lesion directed hypo‐fractionated proton therapy (5 fractions within 2 weeks) Gd‐EOB‐DTPA enhanced MRI is performed 10–12 weeks after treatment. MR images are registered to the planning CT and the planned dose map by non‐rigid image registration. The reviewer contours the border of hypointensity on T1‐w images that indicates the hepatocyte function loss. The threshold dose for this function loss is evaluated as the D90, the dose achieved in at least 90% of the pseudolesion volume. Moreover, irradiated‐ to‐non‐irradiated livercontrast and the correlation of detected signal change in MRI with the planned dose map are analyzed. Results: Gd‐EOB‐DTPA enhanced T1‐w MR images taken after hypo‐fractionated proton therapy show a hypo‐intense area that is correlated to the area of high dose deposition in shape and volume with small deviations in location (up to 5–6 mm) giving information on the actual distal edge position. With Gd‐EOB‐DTPA enhanced MRI, irradiated‐to‐non‐irradiated contrast is superior to MRI enhanced with extracellular, nonspecific contrast agents used in a previous study. Conclusions: A biomarker for radiation induced changes in livertissue was identified and promising post‐treatment MRI data have been acquired and are currently evaluated. For the next step, a pilot patient study has been set up to investigate, if radiation‐induced changes using Gd‐EOB‐DTPA enhanced MRI can be detected prospectively during fractionated proton therapy and therefore would allow for an immediate assessment of the proton therapy with direct impact on patient safety. The work was partly supported by the German Federal Ministry of Education and Research (BMBF) under contract no. 03ZIK445.
Efecto del endoparásito Prosorhynchoides sp. (Trematoda: Bucephalidae) en la capacidad de nado sostenido del baunco Girella laevifrons (Osteichthyes: Kyphosidae)

This study analyzed whether the trematode Prosorhynchoides sp., at metacercaria stage, affects the sustained swimming capacity of the intertidal juvenile sea chub Girella laevifrons. Fifteen non-parasitized and 15 experimentally infested fish were used in this study. Wild fish were infested under laboratory conditions by cercaria from an infected mussel Perumytilus purpuratus. The parasite mainly infested the tail muscles of the fish. The maximum time of sustained swimming of each fish was measured through a swimming camera. Parasitized fish showed less time of sustained swimming and traveled less distance estimated than non-parasitized fish. This result was independent of fish body size, condition factor and trematode abundance. Therefore, Prosorhynchoides sp. affects the swimming capacity of juvenile G. laevifrons that might influence the migration and distribution of the fish.
The Kinetics of Haemolysis in Cell-Taurocholate-Serum Systems

It is well known that the serum and plasma proteins usually produce inhibition of haemolysis by saponin, the bile salts, the soaps, and other related lysins. As early as 1908, however, Sachs described an acceleration of haemolysis as occurring when serum or plasma is added to systems containing sodium oleate, after the oleate had been in contact with the cells for some time. The same effect was later observed, under certain conditions, by Ponder for sodium glycocholate (1922), for sodium taurocholate (1923), and for stearates and oleates (1924), and also by Sen and Mitra (1928) in systems containing taurocholate, although Sen and Sen (1928) had previously failed to obtain it. It is known from these investigations that the concentration of taurocholate, etc., used, the quantity of serum or plasma added, and the time for which the lysin is allowed to react with the cells determine whether, and how great, an acceleration replaces the more usual inhibition, but otherwise the kinetics of haemolysis in these systems is obscure. They are of interest, however, because of their resemblance to colloidal silicic acid-complement and brilliant green-serum systems, in which the cells react with the lysin only after being acted on by a sensitizing agent, and in which, as in these systems, the order of addition of the various components largely determines the final result (see Ponder, 1928, 1932, a , 1933). It has been already suggested, indeed, that the taurocholate acts by sensitizing the cells to the lytic action of the subsequently added serum, as well as by producing lysis itself, just as brilliant green brings about a similar sensitization, and is, in sufficient concentration, a lysin per se (Ponder, 1934, a ). The only other suggestion which has been put forward is that of Sen and Roy (1930-31), who observe that either an inhibition or an acceleration can be obtained by adding various amines to systems containing sodium taurocholate, the result depending on whether the addition is made before or after the taurocholate has come into contact with the cells. Since the addition of the amines makes the systems containing cells and taurocholate more alkaline (the p H of such systems usually being between 5·0 and 6·0), Sen and Roy suggest that the similar accelerating effect of serum may be due, in part at least, to its alkali content.
Index of a family of Dirac operators on loop space

We use methods of constructive field theory to generalize index theory to an infinite-dimensional setting. We study a family of Dirac operatorsQ on loop space. These operators arise in the context of supersymmetric nonlinear quantum field models with HamiltoniansH=Q2. In these modelsQ is self-adjoint and Fredholm. A natural grading operator Γ exists such that ΓQ+QΓ=0. We studyQ+=P−QP+, whereP±=1/2 (1±Γ) are the orthogonal projections onto the eigenspaces of Γ. We calculate the indexi(Q+) for Wess-Zumino models defined by a superpotentialV(ω). HereV is a polynomial of degreen≧2. We establish thati(Q+)=n−1=degδV. In particular, the field theory models have unbroken supersymmetry, and (forn≧3) they have degenerate vacua. We believe that this is the first index theorem for a Dirac operator that couples infinitely many degrees of freedom.
Spectroscopic characterization of processing-induced property changes in doped ZnO films

Abstract The optical response and electronic conductivity of neat and trivalent cation doped ZnO films are dependent upon film deposition parameters and subsequent post-deposition processing. As-deposited films which show high resistivity can be made conducting through gas phase reduction with hydrogen at elevated temperatures or by electrochemical reduction at room temperature using both aqueous and non-aqueous solvents. Resistive sputter and solution deposited films which exhibit c-axis or random crystallite orientation respectively, become conducting after these treatments and show increased infrared reflectivity owing to free carrier absorption. Raman measurements are used to confirm the wurtzite crystalline phase and dopant incorporation into the lattice. Optical properties of selected films are determined from transmission and spectroscopic ellipsometry measurements using models parameterized with previously determined microstructural information. Based upon the electrochemical results, a mechanism is proposed to describe the reduction process which requires the generation of atomic hydrogen as a reducing species.
Disulphide bond reduction of a therapeutic monoclonal antibody during cell culture manufacturing operations

BackgroundDisulphide bonding is critical to maintaining immuno-globulin (IgG) tertiary and quaternary structure for ther-apeutic monoclonal antibodies (MAb). Both inter- andintra-chain disulphide bonds are formed intracellularlyin the expression host prior to secretion and purificationduring MAb production processes. Disulphide bondshuffling has previously been reported for IgG
Spatial Variability Analysis of Soil Physical Properties of Alluvial Soils

ited on sandy or on loamy sediments. Therefore, it is important to study not only the extent of surface spatial Analysis and interpretation of spatial variability of soils is a keyvariability, but also the distribution of subsurface and stone in site-specific farming. Soil survey maps may have up to 0.41ha inclusions of dissimilar soils within a mapping unit. The objectives deep soil horizons. of this study were to determine the degree of spatial variability of soil Among the various soil physical properties, Ks and physical properties and variance structure, and to model the sampling related measures are reported to have the highest statisinterval of alluvial floodplain soils. Soil profiles (n 209) from 18 tical variability (Biggar and Nielsen, 1976). Bouma parallel transects were sampled with a mean separation distance of (1973) stressed the need for more studies on field vari79.4 m. Each profile was classified into surface, subsurface, and deep ability of Ks and soil water retention curves. Stockton horizons. Structural analysis of soil bulk density (b), sand, clay, satu- and Warrick (1971) indicated that variability in K s is rated hydraulic conductivity (Ks), volumetric water content (v )a t both a function of soil depth and position in the landseven pressure potentials (a )( 1, 10, 33, 67, 100, 500, and scape, as well as experimental errors in measuring Ks. 1500 kPa) were modeled for the three horizons. Variance of soil Cameron (1978) sampled clay loam soils at six depths physical properties varied from as low as 0.01% (b) to as high as
Novel approaches to refractory immune thrombocytopenic purpura

Chronic immune thrombocytopenic purpura (ITP) is an organ-specific autoimmune bleeding disorder in which autoantibodies are directed against the individual's own platelets, resulting in increased Fc-mediated platelet destruction by macrophages in the reticuloendothelial system. Although ITP is primarily mediated by IgG autoantibodies, the production of these autoantibodies is regulated by the influence of T lymphocytes and antigen-presenting cells (APC). There is evidence that enhanced T-helper cell/APC interactions in patients with ITP may play an integral role in IgG antiplatelet autoantibody production. New therapies may improve platelet production, decrease platelet antibody production, and decrease monocyte function and/or B-cell and T-cell activities. Understanding these cellular immune responses in ITP may lead to the development of more specific immunoregulatory therapies for the management of this disease.
The HypB protein from Bradyrhizobium japonicum can store nickel and is required for the nickel‐dependent transcriptional regulation of hydrogenase

The HypB protein from Bradyrhizobium japonicum is a metal-binding GTPase required for hydrogenase expression. In-frame mutagenesis of hypB resulted in strains that were partially or completely deficient in hydrogenase expression, depending on the degree of disruption of the gene. Complete deletion of the gene yielded a strain (JH delta Eg) which lacked hydrogenase activity under all conditions tested, including the situation as bacteroids from soybean nodules. Mutant strain JH delta 23H lacking only the N-terminal histidine-rich region (38 amino acids deleted, 23 of which are His residues) expressed partial hydrogenase activity. The activity of strain JH delta 23H was low in comparison to the wild type in 10-50 nM nickel levels, but could be cured to nearly wild-type levels by including 50 microM nickel during the derepression incubation. Studies on strains harbouring the hup promoter-lacZ fusion plasmid showed that the complete deletion of hypB nearly abolished hup promoter activity, whereas the histidine deletion mutant had 60% of the wild-type promoter activity in 50 microM NiCl2. Further evidence that HypB is required for hup promoter-binding activity was obtained from gel-shift assays. HypB could not be detected by immunoblotting when the cells were cultured heterotrophically, but when there was a switch to microaerobic conditions (1% partial pressure O2, 10% partial pressure H2) HypB was detected, and its expression preceded hydrogenase synthesis by 3-6 h. 63Ni accumulation by whole cells showed that both of the mutant strains accumulate less nickel than the wild-type strain at all time points tested during the derepression incubation. Wild-type cultures that received nickel during the HypB expression-specific period and were then washed and derepressed for hydrogenase without nickel had activities comparable to those cells that were derepressed for hydrogenase with nickel for the entire time period. In contrast to the wild type, strain JH delta 23H cultures supplied with nickel only during the HypB expression period achieved hydrogenase activities that were 30% of those cultures supplied with nickel for the entire hydrogenase derepression period. These results indicate that the loss of the metal-binding area of HypB causes a decrease in the ability of the cells to sequester and store nickel for later use in one or more hydrogenase expression steps.
Opposite Responding as a Measure of Creativity.

A proposal for using rapid opposite responding to the Kent-Rosanoff Word Association list as a measure of creativity is presented. Although a complex matter, this measure has the advantage of using...
Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma.

Purpose: A phase I followed by a phase II trial utilizing rIL-2, IFNα, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma. Methods: Treatment consisted of: rIL-2 at 5.0 × 106 IU/m2 SQ on days 1–5 for 4 weeks, rHuIFNα-2a at 5.0 × 106 U/m2 SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1–5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m2, III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU. Results: Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m2. In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12–49%) response rate. Conclusions: The addition of 5-FU to rIL-2 and rHuIFNα-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced.
Order reduction of nonlinear systems with time periodic coefficients using invariant manifolds

Abstract The basic problem of order reduction of nonlinear systems with time periodic coefficients is considered. First, the equations of motion are transformed using the Lyapunov–Floquet transformation such that the linear parts of new set of equations are time invariant. At this stage, the linear order reduction technique can be applied in a straightforward manner. A nonlinear order reduction methodology is also suggested through a generalization of the invariant manifold technique via ‘ Time Periodic Center Manifold Theory ’. A ‘ reducibility condition ’ is derived to provide conditions under which a nonlinear order reduction is possible. Unlike perturbation or averaging type approaches, the parametric excitation term is not assumed to be small. An example consisting of two parametrically excited coupled pendulums is given to show potential applications to real problems. Order reduction possibilities and results for various cases including ‘parametric’, ‘internal’, ‘true internal’ and ‘combination’ resonances are discussed.