cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery of XB05, a potent antiproliferative agent and novel non-nucleoside inhibitor of DNA methyltransferase 1

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 3298 While investigating the biological properties of fluorine-containing organic molecules, we recently identified a novel small molecule, named XB05, which has tumor-selective antiproliferative activity. The molecule was submitted to the Developmental Therapeutics Program (DTP) at the National Cancer Institute (NCI) for testing in the 60 human tumor cell line screen. The results confirmed that XB05 has potent activity against a diverse range of cancer cell lines and also revealed an unusual activity profile, with a more than 1000-fold difference in GI50 values between the most and least sensitive lines. For example, colon, brain, renal, prostate and breast tumor cells were particularly sensitive to XB05, whereas other tumor types were substantially less responsive. The GI50 values for the sensitive cell lines were in the 10 - 100 nM range. We analyzed the DTP data using the on-line COMPARE program, which allows comparison of the activity profile with the 43,000 compounds in the public database and which has been validated as grouping together agents with similar mechanisms of action, irrespective of their structure. When we used XB05 as a COMPARE seed, we found a strong correlation (Pearson coefficient 0.82) with a compound known as halomon. Halomon is a marine-derived natural product, which has promising anticancer activity. However, its development has been severely limited because attempts to re-isolate it from its natural source or to develop an efficient synthesis have not enabled production of sufficient compound for testing. Halomon was recently reported to be an inhibitor of human DNA methyltransferase 1 (DNMT1), the enzyme responsible for maintaining DNA methylation after each cell division. DNMT1 is considered an attractive target for epigenetic therapy of cancer because methylation-induced silencing of tumor suppressor genes occurs frequently in cancer cells. XB05 has now been tested in various cell-free and cell-based assays of DNA methylation. We find that it is a potent inhibitor of recombinant DNMT1 activity in vitro, with an IC50 of 10 nM. Moreover, XB05 could reactivate expression of several silenced tumor suppressor genes in cancer cells at concentrations of 100 nM or less. In conclusion, XB05 is a novel agent with potent antiproliferative activity against cell lines derived from common cancers and a new type of DNMT1 inhibitor. XB05 is a mechanistic mimic of a natural product named halomon, but, in contrast to halomon, XB05 can be easily and inexpensively synthesized in large quantities. XB05 may also have substantial advantages over other existing DNMT inhibitors such as 5-azacytidine and decitabine. XB05 is more active than these agents in cell-free or cell-based DNMT assays and will likely be less toxic because it cannot be incorporated into DNA. Also, whereas 5-azacytidine and decitabine are rapidly degraded in aqueous solutions, XB05 appears to be completely stable.
Toxicity and Transcendence: two faces of the human

A truly enlightened anthropocentrism that understood the human in its essential interdependency with other creatures but nonetheless concluded that the human species was toxic to the planet could identify with the life-stream (of which we are a part) and, on the basis of values it cherished, in the absence of necessary radical transformation, will its own demise. The distinctive value of the human cannot rest on virtues of which we are in principle capable but which we repeatedly fail to realize. Is there a logical or metaphysical link, as Schelling and Derrida in different ways suggest, between our seemingly suicidal and toxic behavior as a species and what we might broadly call our capacity for “transcendence”? Or should we lay the blame more concretely on the form that global capitalism has taken (Speth)? Even if we do in fact have the resources to overcome our species narcissism, an even more disturbing question awaits us. Human evolution could generate a predictable (post)human being with whom we wou...
High Temperature States of Disordered Systems

We return now to the more realistic models where \(\mathop J\nolimits_e^\Lambda = {J_e}\), with no dependence on Λ. The couplings J e , for \(e \in {E^d}\), are i.i.d. random variables on (Ω,ℱ,ν) with common distribution μ. Since we will not be considering ground states here, we do not require μ to be continuous. Indeed, except where otherwise noted, we make no particular restriction on μ. Ferromagnetic (where μ is supported on [0, ∞)) and spin glass (where μ is symmetric) models are of course important special cases. The topic of this chapter is a percolation-based approach to obtaining bounds for β c , the critical value of β (or equivalently bounds for the critical temperature), defined here as the supremum of β’s for which there is a unique infinite volume Gibbs distribution (regardless of b.c. ’s) for all inverse temperatures ≤ β.
Improving civil gang injunctions: how implementation can affect gang dynamics, crime, and violence

Civil gang injunctions (CGIs) are an increasingly popular street gang control technique. Although admired by criminal justice officials, we know relatively little about how differing implementation approaches might affect their efficacy. In this study, we interviewed youth in contrasting neighborhoods—some under a CGI and others not—to observe the ways gang injunctions may strengthen or weaken the gang as a group. We conclude that improved knowledge of social psychological processes will help policy makers more effectively craft gang injunctions to achieve sustained neighborhood change. Street gangs play a major role in the socialization of youth, the social and organizational context of neighborhoods, and the level of crime and fear of crime in many communities. In 2008, close to 774,000 gang members belonging to 27,900 gangs were reported
A simulation-based assessment of the value of enhancing the credibility of policy analysis

Credibility has been proposed recently as a standard for assessing the value of policy analysis. While various strategies for enhancing the credibility of policy analysis are available, little evidence exists concerning to what extent and under what circumstances implementing such strategies does, in fact, increase the value of policy analysis in terms of improving organizational decisionmaking. In this paper computer simulation—a methodological approach that has not been widely used to date in the field of knowledge application—is used to begin, to fill this gap. Specifically, the “garbage-can” model of decisionmaking developed by Cohen, March and Olsen (1972) has been modified to reflect a possible contribution of policy analysis to decisionmaking. Using this model, the extent to which enhancing credibility results in improved organizational decisionmaking under various circumstances is examined.
SYNTHESIS OF BI- AND TRIDENTATE IMIDAZOLE LIGANDS

A number of imidazole derivatives were prepared in the course of studying the limits of carbon-metal bond formation in complexes of imidazole with first-row transition metals. Seven of the compounds were new. The 4- and 5-methyl and 4,5-dimethyl derivatives of l-(2-pyridyl)-imidazole were prepared by reaction of the appropriate imidazole with 2-bromopyridine. Alkylation of imidazole, 4,5-dimethylimidazole, and benzimidazole with 2-chloromethylpyridine gave a series of 1-(2-pyridylmethyl)imidazoles. 1-(2,3-Diaminopropyl)imidazole was prepared in six steps via a Gabriel sequence.
Construction of bivariate S-distributions with copulas

S-distributions are univariate statistical distributions with four parameters. They have a simple mathematical structure yet provide excellent approximations for many traditional distributions and also contain a multitude of distributional shapes without a traditional analog. S-distributions furthermore have a number of beneficial features, for instance, in terms of data classification and scaling properties. They provide an appealing compromise between generality in data representation and logistic simplicity and have been applied in a variety of fields from applied biostatistics to survival analysis and risk assessment. Given their advantages in the single- variable case, it is desirable to extend S-distributions to several variates. This article proposes such an extension. It focuses on bivariate distributions whose marginals are S-distributions, but it is clear how more than two variates are to be addressed. The construction of bivariate S- distributions utilizes copulas, which have been developed quite rapidly in recent years. It is demonstrated here how one may generate such copulas and employ them to construct and analyze bivariate-and, by extension, multivariate-S-distributions. Particular emphasis is placed on Archimedean copulas, because they are easy to implement, yet quite flexible in fitting a variety of distributional shapes. It is illustrated that the bivariate S-distributions thus constructed have considerable flexibility. They cover a variety of marginals and a wide range of dependences between the variates and facilitate the formulation of relationships between measures of dependence and model parameters. Several examples of marginals and copulas illustrate the flexibility of bivariate S-distributions.
The effect of change of surface microstructure of carbon oral implants on gingival structures

Abstract Failure of oral implants is usually due to the breakdown of the soft tissue barrier or “seal” around the implant, followed by the invasion of microorganisms and subsequent infection. This study investigates the effect of different implant surfaces on gingival structures.
Reducing Customer Wait Time at a Fast Food Restaurant on Campus

In a typical fast food restaurant, the customer expects to receive service quickly. A restaurant manager will want to keep the customer's wait time to a minimum. If a customer's wait time is higher than their expectation, their satisfaction level will decrease. Most believe that improving a customer's wait time will increase operating cost. Therefore, this results in a tradeoff between customer's wait time and cost of operation. A study is conducted at a restaurant on the Wichita State University campus to improve its service time. A simulation model is used to analyze the system. A survey is conducted to determine the customer's expected wait time. The result of the study is to recommend adding one more server during peak hours to improve customer wait time. An economic cost analysis is also provided to discuss the cost impact of adding one more server.
NETMET: A program for generating and interpreting metaphors

Metaphors have computable semantics. A program called NETMET both generates metaphors and produces partial literal interpretations of metaphors. NETMET is based on Kittay's semantic field theory of metaphor and Black's interaction theory of metaphor. Input to NETMET consists of a list of literal propositions. NETMET creates metaphors by finding topic and source semantic fields, producing an analogical map from source to topic, then generating utterances in which terms in the source are identified with or predicated of terms in the topic. Given a metaphor, NETMET utilizes if-then rules to generate the implication complex of that metaphor. The literal leaves of the implication complex comprise a partial literal interpretation.
Comparative performance study of heavy-ion injector systems for high-energy synchrotrons

Abstract The increased particle current demands on both ion source and injection facility by a heavy-ion synchrotron collider are analyzed. Also, the existing injector arrangement and performance for most of the world's fixed-target heavy-ion synchrotrons are compared. At the present time, the Drookhaven relativistic heavy-ion collider (RHIC) requirements for the heaviest ions can be met by an injector with a front end consisting of a negative ion source and electrostatic tandem Van de Graaff accelerator. For the heaviest ions, considerable research and development is necessary on both ECR and EBIS high-charge state ion sources before required particle currents can be met.
Enthalpic relaxation in frozen aqueous trehalose solutions

Abstract Our object was to investigate the effect of annealing on the glass transition temperatures and enthalpic recovery of frozen aqueous solutions of trehalose. Trehalose solutions were subjected to differential scanning calorimetry wherein they were first cooled from room temperature to −60 °C, and heated to the annealing temperature, which ranged between −34 and −48 °C. Following isothermal annealing for the desired time period, the glass transition temperatures and the enthalpic recovery were determined in the final heating scan. Frozen unannealed trehalose solutions were characterized by two glass transition events. At a heating rate of 2 °C/min, the observed Tg 1 ′ and Tg 2 ′ were ∼−45 and −31 °C, respectively. Annealing resulted in an increase in the lower transition temperature, Tg 1 ′, while the higher transition temperature, Tg 2 ′, was unaffected. Enthalpic recovery due to annealing was associated only with Tg 2 ′. Annealing at −36 °C resulted in the highest value of Tg 1 ′ and the maximum enthalpic recovery. Irrespective of the heating rates, the magnitude of enthalpic recovery and Tg 1 ′ showed a similar trend (first an increase, followed by a decrease) as a function of annealing temperature. This suggests that annealing led to crystallization of ice and subsequently the system became maximally freeze-concentrated. Annealing, at temperatures higher than −36 °C, led to a reduction in enthalpic recovery associated with Tg 2 ′ and a lowering of Tg 1 ′. These observations are consistent with the hypothesis that the higher transition temperature coincides with the onset of ice melting. We have attempted to bridge two conflicting schools of thought regarding the origin of multiple glass transitions in frozen aqueous sugar solutions. The two glass transitions are attributed to the formation of two “populations” in the freeze-concentrated phase during “non-equilibrium” or rapid cooling—one, that is maximally freeze-concentrated and the other that contains a higher amount of water. The higher transition temperature also overlaps with the onset of ice melting.
Recent studies on aspergillosis in turkey poults

A review of the studies on aspergillosis in turkey poults at the National Animal Disease Center include limited field studies, pathogenicity studies, and vaccine development. Natural ventilation in turkey rearing houses was effective in reducing airborne propagules of four major fungal genera, but the effectiveness of ventilation appeared to be limited by the width of the building. Aspergillus fumigatus was more effective than A. flavus in producing mortalities in aerosol exposed poults. Toxigenicity of A. flavus did not enhance its pathogenicity, and no apparent aflatoxin production occurred during pathogenesis in infected turkey poults. Spores of A. fumigatus were disseminated quite rapidly in poults exposed to aerosols, and alveolar macrophages from respiratory lavages taken immediately after exposure contained spores of A. fumigatus. Vaccines produced from germlings of A. fumigatus and administered to turkey poults were the most efficacious of five vaccines tested against challenge exposure to aerosols of A. fumigatus spores.
The minimum internal and external sequence requirements for transposition of the eukaryotic transformation vector piggyBac

The piggyBac element from Trichoplusia ni is recognized as a useful vector for transgenesis of a wide variety of species. This transposable element is 2472 bp in length, and has a complex repeat configuration consisting of an internal repeat (IR), spacer, and terminal repeat (TR) at both ends, and a single ORF encoding the transposase. Excision assays performed in microinjected T. ni embryos using plasmids deleted for progressively larger portions of the piggyBac internal sequence reveal that the 5′ and 3′ IR, spacer, and TR configuration is sufficient for precise excision of piggyBac when transposase is provided in trans. Interplasmid transposition assays using plasmids carrying varying lengths of intervening sequence between the piggyBac termini in T. ni demonstrate that a minimum of 55 bp of intervening sequence is required for optimal transposition, while lengths less than 40 bp result in a dramatic decrease in transposition frequency. These results suggest that the piggyBac transposase may bind both termini simultaneously before cleavage can occur, and/or that the formation of a transposition complex requires DNA bending between the two termini. Based on these results we constructed a 702-bp cartridge with minimal piggyBac 5′ and 3′ terminal regions separated by an intervening sequence of optimal length. Interplasmid transposition assays demonstrate that the minimal terminal configuration is sufficient to mediate transposition, and also verify that simply inserting this cartridge into an existing plasmid converts that plasmid into a non-autonomous piggyBac transposon. We also constructed a minimal piggyBac vector, pXL-Bac, that contains an internal multiple cloning site sequence between the minimal terminal regions. These vectors should greatly facilitate the utilization of the piggyBac transposon in a wide range of hosts.
Management of hypercalcemia of malignancy

Abstract Hypercalcemia is an oncologic emergency that is associated with a median life expectancy of approximately 30 days. Despite this, antihypercalcemic therapy is often indicated to reduce morbidity and improve quality of life. Although at least four mechanisms are operative in producing hypercalcemia of malignancy, the treatment is consistent regardless of the underlying mechanism. Initial management consists of vigorous rehydration, followed by administration of agents that enhance renal calcium excretion or inhibit bone resorption. The purpose of this review is to discuss the current management of hypercalcemia of malignancy.
Formulation of Reduced-Taskload Optimization Models for Conflict Resolution

This paper explores methods to include aspects of controller taskload into conflict-resolution programs through a parametric approach. We are motivated by the desire to create conflict-resolution decision-support tools that operate within a human-in-the-loop control architecture by actively accounting for, and moderating, controller taskload. Specifically, we introduce two conflict-resolution programs with the objective of managing controller conflict-resolution taskload, i.e., the number of maneuvers used to separate air traffic. Managing conflict-resolution taskload is accomplished by penalizing aircraft maneuvers through their L1 norm in the cost function or constraining the number of maneuvers directly. Analysis of the programs reveals that both approaches are successful at managing controller conflict-resolution taskload and minimizing fuel burn. Directly constraining conflict-resolution taskload is more successful at minimizing the variation in the number of aircraft maneuvers issued and returning the aircraft to their desired exit point. Penalizing maneuvers through L1 norm costs is more successful at reducing controller conflict-resolution taskload at lower traffic volumes. Ultimately, results demonstrate that the inclusion of such parametric models can successfully regulate controller conflict-resolution taskload.
Cryptosporidium in acquired immunodeficiency syndrome.

Une observation de cette protozoose chez un malade de 31 ans, homosexuel, atteint de SIDA. Diagnostic par etude de biopsies en microscopie electronique
Special Issue on Robot Learning from Demonstration

Algorithms for robot Learning from Demonstration (LfD) seek to enable human users to expand the capabilities of robots through interactive teaching instead of explicit programming. This special issue includes a collection of articles that span some of the issues and challenges that arise when LfD is done in the context of a social interaction with a human partner. The importance of designing algorithms and interactions with non-expert end-users in the loop is highlighted in the article by Suay et al. In one of the first comparative user studies of its kind, non-experts used and evaluated three different learning by demonstration algorithms/interactions in the same domain. Their results point out the non-trivial challenges that arise in getting learning input from a non-expert human teacher. One common problem domain tackled with Learning from Demonstration is that of learning low-level motion control policies to achieve some particular task or skill. Several of the articles in this special issue are working in this domain, touching on various important questions that come to bare when this type of LfD is done in a social context with a human teacher. In their article, Grollman et al. address an important topic for social LfD, learning from failed demonstrations. When demonstrations are to come from naive non-expert humans,
SU-E-J-142: A Comparison of TomoTherapy and Respiratory-Gated IG-IMRT for the Treatment of Pancreatic Cancer

Purpose: Respiratory gating and high‐quality image guidance allow for use of smaller PTV margin, while non‐gated RT, such as TomoTherapy, must account for respiratory motion by increasing PTV margin. It is not clear whether this increased margin can be compensated by the fact that Tomotherapy usually offers improved normal tissues sparing. The purpose of this study is to compare the dosimetric differences between these two RT methods for pancreas irradiation. Methods: 4DCT datasets of 6 patients with pancreas irradiated previously were analyzed. The PTV for Tomotherapy was the ITV of all respiration phases plus 10 mm margin, while the PTV for the gated IG‐IMRT was the ITV for the 2 gating phases plus a 5 mm margin. This smaller margin is because a high quality CT, such as in‐room CT, is used for daily repositioning. Plans were generated for two PTVs with a prescription dose of 50.4Gy using the Tomotherapy and Prowess treatment planning systems. Results: The gated IG‐IMRT reduced the duodenum V45Gy by 15.8% (p<0.05) and the mean dose by 7.4 Gy (p<0.05) compared to the Tomotherapy. However, since the TomoTherapy generally has a more homogeneous dose distribution and since the duodenum often overlaps the PTV, the duodenum V52Gy for the gated IG‐IMRT plans was 0.9 ± 0.7 cc (p<0.05) while the TomoTherapy plans all had maximum doses below 52Gy. The mean dose to the liver was found to be 3.2 Gy less for the gated IG‐IMRT plan (p<0.05). The right kidney V45Gy for the gated IG‐IMRT plan was found to irradiate 9.2% less kidney volume (p<0.05) compared to the TomoTherapy plan. Conclusions: For pancreas irradiation with significant respiration motion, the combined effect of respiration gating and daily high‐quality CT guidance for IMRT leads to reduced doses to duodenum, liver, and right kidney as compared to Tomotherapy.
Application of experimental data to a new model of tissue oxygen transport.

A recently published equation for oxygen uptake in cells (Hills, 1970) is corrected and applied to data gathered under appropriate experimental conditions. The result is found to support the hypothesis of facilitated intracellular oxygen transport.
Chromium cross-links glutathione and cysteine to DNA

The formation of chromium-DNA adducts, and chromium-mediated peptide-DNA or amino acid-DNA cross-links was measured after treatment of calf thymus DNA and defined DNA polynucleotides in vitro with potassium dichromate in the presence of glutathione or cysteine. The level of chromium bound to DNA after reaction with chromium(VI) in the presence of glutathione increased with increasing glutathione concentration to a level of approximately 1.4 x 10(-2) chromium per nucleotide. Glutathione and chromium were associated with the DNA in a 1:1 ratio. Reaction of chromium(VI) with DNA in the presence of cysteine led to a maximal level of chromium binding that was 10-fold lower than that measured with glutathione, with 2-4 cysteine bound per chromium. The thiol-chromium-DNA complexes were stable to dialysis at room temperature against diethylenetriaminepentaacetic acid, orthophenanthroline and ethylenediaminetetraacetic acid. However, when the chromium-DNA complexes were dialyzed against ethylenediaminetetraacetic acid at 37 degrees C to chelate bound chromium, equivalent amounts of chromium and thiol were lost from the DNA, suggesting that thiol was associated with the DNA-bound chromium. These results suggest that chromium mediates cross-linking of cysteine and glutathione to DNA, to form glutathione-chromium-DNA and (cysteine)2-4-chromium-DNA complexes. In order to probe the DNA base and sequence specificity of glutathione-chromium-DNA adduct formation, chromium and glutathione binding to polynucleotides of defined composition was determined. Preferential binding of chromium to guanine-containing polynucleotides was observed. These results suggest that the interaction of chromium with thiol-containing amino acids and peptides may be important in chromium genotoxicity, and indicate that the thiol-activated chromium may target guanine bases in DNA.
Demographic Patterns and Treatment Outcomes of Patients With Recurrent Corneal Erosions Related to Trauma and Epithelial and Bowman Layer Disorders

Purpose To evaluate demographics and outcomes of patients with recurrent corneal erosions related to trauma and epithelial and Bowman layer disorders. Design Retrospective case series. Methods setting: Wills Eye Institute, Philadelphia, Pennsylvania. study population: Two hundred seventy-two eyes (230 patients) presenting between 2008 and 2011 with recurrent corneal erosions related to trauma and epithelial and Bowman layer disorders. procedure: Conservative management, diamond burr polishing, excimer laser phototherapeutic keratectomy (PTK), and epithelial debridement alone. main outcome measure: Recurrence of erosions, more than 6 weeks after commencing treatment. Results Mean age was 46.5 ± 14.6 (2-85) years. Female subjects accounted for 53% of patients and 18.3% had bilateral involvement. Etiology included epithelial basement membrane dystrophy in 52.9% (144/272) and trauma in 25.7% (70/272). One hundred sixty-six eyes with more than a single visit were initially managed conservatively, 68 of 166 (40.9%) had diamond burr polishing, 7 of 166 (4.2%) had PTK, and 4 of 166 (2.4%) had epithelial debridement alone. Many eyes had >6 weeks follow-up: 120 of 166 (72.3%) after conservative management, 54 of 68 (79.4%) after diamond burr polishing, 7 of 7 (100%) after PTK, and 4 of 4 (100%) after epithelial debridement. Percentage of eyes with recurrence was 56.7% (68/120) after conservative management, 14.8% (8/54) after diamond burr polishing, and 28.6% (2/7) after PTK. Rate of recurrence (eye-years) was 0.74, 0.19, and 0.23 with conservative management, diamond burr polishing, and PTK, respectively. Mild haze was seen in 22.2% of eyes (12 eyes) after diamond burr polishing and 28.6% (2 eyes) after PTK. Conclusion Recurrent corneal erosions are most commonly associated with epithelial basement membrane dystrophy. Patients are generally initially managed conservatively, with recurrence in more than half of eyes. Diamond burr polishing is the most common surgical intervention and is effective in a majority of eyes.
Bargaining and command by heads of U.S. government departments

Abstract The 13 department of heads of the president's cabinet are among the most important and powerful people in the United States government. Laws, presidemtial authority, and administrative theory say that they should command. In fact, they spend much of their time bargaining. They dicker with the president, the White House staff, their own assistant secretaries, their civil service subordinates, and thier clientele. These powerful men and women bargain for the same reasons that they command: to acquire information, to mobilize resources, to implement their programs, and to advance their own positions. Besides standard published sources, the author draws on his personal experience as a presidential appointee in the Carter Administration. On certain points, he compares the American system to the British government.
Continuous in vitro evolution of a ribozyme that catalyzes three successive nucleotidyl addition reactions.

Variants of the class I ligase ribozyme, which catalyzes joining of the 3' end of a template bound oligonucleotide to its own 5' end, have been made to evolve in a continuous manner by a simple serial transfer procedure that can be carried out indefinitely. This process was expanded to allow the evolution of ribozymes that catalyze three successive nucleotidyl addition reactions, two template-directed mononucleotide additions followed by RNA ligation. During the development of this behavior, a population of ribozymes was maintained against an overall dilution of more than 10(exp 406). The resulting ribozymes were capable of catalyzing the three-step reaction pathway, with nucleotide addition occurring in either a 5' yieldig 3' or a 3' yielding 5' direction. This purely chemical system provides a functional model of a multi-step reaction pathway that is undergoing Darwinian evolution.
Inhibition of microglial CD40 expression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10

Microglia are intrinsic mediators of the central nervous system (CNS) immune response induced by a variety of insults. Activated microglia express costimulatory molecules CD40 and B7 that are important equally for T-cell activation and further activation of microglia. In this study, we sought to investigate the regulation of costimulatory molecule expression on primary microglia and microglial cell line, BV-2, by pituitary adenylyl cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), potent anti-inflammatory neuropeptides. The neuropeptides inhibited CD40 and B7-2 mRNA expression in activated microglia. PACAP decreased surface expression of CD40 and B7-2 on activated microglia. The inclusion of an anti-IL-10 antibody completely abrogated PACAP inhibition of lipopolysaccharide (LPS)-induced CD40 expression, suggesting that PACAP inhibition is at least in part mediated by IL-10. Indeed, PACAP enhanced LPS-induced IL-10 mRNA and protein levels in microglia. These data indicate that PACAP, through an increase in IL-10 protein, can down-regulate important costimulatory molecule expression on microglia, thereby possibly affecting CNS immunity.
Surgeries on one component of the Whitehead link are virtually fibered

Abstract In this paper we will show that every Dehn filling on one component of the boundary of the exterior of the Whitehead link is virtually fibered. As a corollary we produce what seem to be the first examples of knot exteriors in S3 which are virtually fibered but not fibered.
Controlling Symbolic Dynamics in an Exact Folded-Band Chaotic Oscillator

Abstract Control of symbolic dynamics in exactly solvable chaotic oscillator is investigated and numerically demonstrated. The oscillator is a hybrid dynamical system containing a linear ordinary differential equation and a nonlinear switching condition. Bounded oscillations exhibit a folded-band topology and are provably chaotic, and successive waveform maxima yield a one-dimensional piecewise-linear return map. An exact solution is written as a linear convolution of a basis pulse and a discrete binary sequence, from which an exact symbolic dynamics is defined. A dynamic limiter is effectively used to control symbolic dynamics using an analytic inverse coding function.
Rotational magnetic processes in a dirty superconductor

Magnetization-vector ({rvec M}) measurements were made on a thin disk of impure Nb rotated relative to a fixed field {rvec H} at 4.2 K. For all H, {rvec M} is found to be separable into a non-rotating diamagnetic component {rvec M}{sub d} plus a penetrating-flux component {rvec M}{sub p} that turns rigidly with the sample for small rotation angles. For H below H{sub c1} on a hysteresis loop, {rvec M}{sub p} diminishes in size but continues to rotate rigidly up to 360{degree}. For H between H{sub c1} and H{sub c2}, {rvec M}{sub p} rotates up to and then remains at some critical angle, indicating a constant frictional torque between {rvec M}{sub p} and the sample, which presumably arises from vortex-flux jumps between pinning centers. Moreover, {rvec M}{sub d} closely equals {minus}{rvec H}/4{pi} for H above as well as below H{sub c1}. 6 refs., 3 figs.
SU-E-J-226: Propagation of Pancreas Target Contours On Respiratory Correlated CT Images Using Deformable Image Registration

Purpose: Respiratory Correlated CT (RCCT) scans to assess intra-fraction motion among pancreatic cancer patients undergoing radiotherapy allow for dose sparing of normal tissues, in particular for the duodenum. Contour propagation of the gross tumor volume (GTV) from one reference respiratory phase to 9 other phases is time consuming. Deformable image registration (DIR) has been successfully used for high contrast disease sites but lower contrast for pancreatic tumors may compromise accuracy. This study evaluates the accuracy of Fast Free Form (FFF) registration-based contour propagation of the GTV on RCCT scans of pancreas cancer patients. Methods: Twenty-four pancreatic cancer patients were retrospectively studied; 20 had tumors in the pancreatic head/neck, 4 in the body/tail. Patients were simulated with RCCT and images were sorted into 10 respiratory phases. A radiation oncologist manually delineated the GTV for 5 phases (0%, 30%, 50%, 70% and 90%). The FFF algorithm was used to map deformations between the EE (50%) phase and each of the other 4 phases. The resultant deformation fields served to propagate GTV contours from EE to the other phases. The Dice Similarity Coefficient (DSC), which measures agreement between the DIR-propagated and manually-delineated GTVs, was used to quantitatively examine DIR accuracy. Results: Average DSCmore » over all scans and patients is 0.82 and standard deviation is 0.09 (DSC range 0.97–0.57). For GTV volumes above and below the median volume of 20.2 cc, a Wilcoxon rank-sum test shows significantly different DSC (p=0.0000002). For the GTVs above the median volume, average +/− SD is 0.85 +/− 0.07; and for the GTVs below, the average +/− SD is 0.75 +/−0.08. Conclusion: For pancreatic tumors, the FFF DIR algorithm accurately propagated the GTV between the images in different phases of RCCT, with improved performance for larger tumors.« less
Molecular characterization of the histone gene family of Caenorhabditis elegans.

Abstract The core histone genes (H2A, H2B, H3 and H4) of Caenorhabditis elegans are arranged in approximately 11 dispersed clusters and are not tandemly arrayed in the genome. Three well-characterized genomic clones, which contain histone genes, have one copy of each core histone gene per cluster. One of the clones (λCeh-1) carries one histone cluster surrounded by several thousand base-pairs of non-histone DNA, and another clone (λCeh-3) contains a histone cluster duplication surrounded by non-histone DNA. A third clone (λCeh-2) carries a cluster of core histone genes flanked on one side (12,000 base-pairs away) by a single H2B gene and on the other by non-histone DNA. A fourth cluster (clone BE9) has one copy each of H3 and H4 and two copies each of H2A and H2B. This cluster is also flanked by non-histone DNA. Analysis of cosmid clones which overlap three of the clusters shows that no other histone clusters are closer than 8000 to 60,000 base-pairs, although unidentified non-histone transcription units are present on the flanking regions. Gene order within the histone clusters varies, and histone mRNAs are transcribed from both DNA strands. No H1 sequences are found on these core histone clones. Restriction fragment length polymorphisms between two related nematode strains (Bristol and Bergerac) were used as phenotypic markers in genetic crosses to map one histone cluster to linkage group V and another to linkage group IV. Hybridization of gene-specific probes from sea urchin to C. elegans RNA identifies C. elegans core histone messenger RNAs of sizes similar to sea urchin early stage histone mRNAs (H2A. H2B, H3 and H4). The organization of histone genes in C. elegans resembles the clustering found in most vertebrate organisms and does not resemble the tandem patterns of the early stage histone gene family of sea urchins or the major histone locus of Drosophila .
Novel cationic copper coordination frameworks constructed from copper phosphate 8-rings and 4,4′-bisimidazolylbiphenyl as a bridging ligand

Abstract Two cationic hybrid networks, the first one-dimensional and the second three-dimensional, comprising unique cationic copper–phosphate 8-rings that are linked by the rigid difunctional ligand 4,4′-bisimidazolylbiphenyl are reported. These complexes have been characterized fully by single-crystal X-ray diffraction and magnetic studies.
Procedure and instructions in kindergartners’ matching-to-sample

An observing response procedure and instructions designed to induce a problem-solving set were examined in a study of 48 kindergartners presented with, matching-to-sample problems. The antecedent variables were found to facilitate performance. Analysis of individual records suggested that solution was on an all-or-none basis, that the observing response requirement influenced the probability of early solution, and that the problem-solving instructions influenced later performance.
Predicted Lightcurves of Phobos and Deimos

Using Mariner 9 results on the shapes, rotation periods, and photometric functions of Phobos and Deimos, approximate orbital light curves are calculated for the two Martian satellites. The prediction is that both Phobos and Deimos should show orbital brightness fluctuations detectable from earth. For Phobos, the detectable amplitude is predicted to be about 0.1 mag; for Deimos, 0.2 mag.
Myocardial catechol-O-methyl transferase activity after chronic cardiac denervation.

IN a recent study of the denervated dog heart1, we noted a marked increase in cardiac sensitivity to norepinephrine, a finding anticipated from previous investigations of denervated organs2. Catechol-O-methyl transferase activity was measured in these denervated hearts to determine whether this pharmacological supersensitivity might be accompanied by a decreased ability of the myocardium to O-methylate norepinephrine. The results showed that cardiac denervation produces a decrease in the catechol-O-methyl transferase activity of the myocardium; whether this decrease is related to the phenomenon of supersensitivity, however, is open to considerable doubt.
The influence of gatekeeping and utilization review on patient satisfaction.

OBJECTIVE: To examine the influence of utilization review and denial of specialty referrals on patient satisfaction with overall medical care, willingness to recommend one’s physician group to a friend, and desire to disenroll from the health plan.
Collaborative Computing On-demand: Harnessing Mobile Devices in Executing On-the-Fly Jobs

Systems employing mobile devices (e.g., sensors, smart phones, robots) are emerging with growing capabilities in performing a wide variety of tasks. Due to their abundance and wide deployments, they are posed to play a dominant role in providing a rich mobile computing platform for various jobs, especially for new ones that are created on-the-fly. Realizing this platform is challenging since it is hard to predict the exact equipment present in an environment, what types of information need to be communicated to the devices to execute their tasks, and how to reprogram these devices. This work proposes a new on-demand collaborative computing framework that maps a new job as a set of tasks onto the mobile devices for execution. The mapping is done in a manner that takes into account the capabilities of the devices, the dependency between the tasks, the adjacency of the devices, and the requirements of the requested new job. Our proposed framework is implemented as a test-bed in our Mobile Cyber-Physical Systems lab with MICAz sensors and iRobot Create robots.
Accessory cell signals regulate Th-cell responses: from basic immunology to a model of helminthic disease

Schistosome helminths inflict serious tissue damage by eliciting T helper (Th)-cell-mediated granulomatous inflammation around parasite eggs. The egg granulomas are large in acute disease and smaller in chronic disease. To explain this downregulation in chronic disease, Miguel Stadecker and Pedro Flores Villanueva describe a mechanism whereby CD4+ Th1-type lymphocytes, which are associated with the initial vigorous granuloma formation, are rendered anergic to subsequent antigenic stimulation. This results in the reduction of granuloma size and in the dominance of Th2-type lymphocyte responses.
Developmental potential of day 13 porcine embryonic disk under in vitro culture conditions.

Embryonic disks were microsurgically isolated from adjacent trophoblast tissue, and cultured for varying periods in vitro. During the first 24 h of culture, vesicles (1 to 4/disk) composed of mesoderm and endoderm formed from the ventral surface. In the subsequent culture period, the vesicles continued to increase in size and by 96 h in vitro, most originally multivesiculated explants possessed a single vesicle formed by delamination and coalescence of smaller vesicles. Scanning electron microscopy revealed the formation of grooves and ridges in abnormal attempts at differentiation by the embryonic ectoderm. Endoderm comprising the outer tissue layer of the vesicle underwent a gradual alteration in surface morphology during in vitro culture. Initially flat, with a paucity of microvilli, these cells became dome-shaped with an abundance of microvilli. In addition, they became highly secretory as revealed by the presence of numerous secretory droplets at their surface. After culture for periods of up to 10 d, several explants displayed areas containing pulsating tissue, with contractions occurring at a rate of 20 to 30/minute, indicative of mesoderm differentiation. Culture of porcine isolated embryonic disk in vitro should enhance investigations into the regulation of germ, layer formation and differentiation and assist in determining the tissue source of conceptus secretory products.
Diagnosis and treatment of childhood mitochondrial diseases.

Mitochondrial cytopathies are caused by genetic alterations of nuclear- or mitochondrial-encoded genes involved in the synthesis of subunits of the electron transport chain. Mutations of mitochondrial DNA are associated with a wide range of clinical presentations [1-4]. The ubiquitous nature of mitochondria and the role of the mitochondria in cellular metabolism result in the potential for any tissue in the body to be affected [5–7,8,9]. Although some children with mitochondrial disease present with life-threatening lactic acidosis in the newborn period, the majority of children come to clinical attention for nonspecific problems, including failure to thrive, developmental delay, seizures, hypotonia, and loss of developmental milestones. The diagnosis of these disorders is made through careful clinical evaluation, coupled with biochemical, morphologic, and molecular biologic techniques. Genetic counseling is difficult due to unique aspects of mitochondrial genetics. Despite advances in our understanding of mitochondrial biochemistry and genetics, treatment options remain limited.
Pyrimidine nucleoside metabolism in mammalian cells: an in vitro comparison of two rodent species.

Abstract The incorporation of thymidine into DNA has been studied in splenic and cultured cells of the golden hamster ( Mesocricetus auratus ) and the goldenmantled ground squirrel ( Citellas lateralis ). Considerably less uptake was observed in cells of the latter species. The reduced incorporation of thymidine found in cells of the ground squirrel is not due to a defective intracellular permeability, an inability to synthesize thymidine kinase or to trapping in an abnormally large nucleotide pool. It appears to derive from an unusually active catabolic pathway for thymidine and other pyrimidine nucleosides including deoxyuridine, uridine, deoxycytidine and cytidine. At critical concentrations the breakdown of nucleosides is sufficient to deplete the medium of these substances. Little, if any, difference is observed in the degradation of thymidine by liver slices from the same animals.
Measurement of the dispersive and refractive indices of germanium using diode lasers.

Germanium Fabry-Perot etalons are commonly used in diode laser spectroscopy to establish relative frequency calibration scales for molecular absorption spectra. Typically the channel spectrum of the etalon is recorded simultaneously with the molecular spectrum as the laser injection current is tuned linearly, and the etalon free spectral range (fringe spacing) is used to measure the frequency separations among lines in the molecular spectrum. For this purpose, the etalon free spectral range must be known for the measurement wavelength, and this in turn relies on knowledge of the etalon length and the dispersive index at this wavelength. It is pointed out that the most satisfactory approach is to measure directly the free spectral range or dispersive index of the etalon at the wavelength of interest. A description is presented of measurements of this type, performed near 7.9 and 10.1 micrometers for a 7.7-cm long germanium etalon.
Thioredoxin converts the Syrian hamster (29-231) recombinant prion protein to an insoluble form

Abstract The prion protein (PrP) is an essential, and probably the only, component of the infectious agent responsible for the transmissible spongiform encephalopathies. In its cellular (PrP C ) form, it is a soluble, α-helix–rich protein of yet unknown function attached to the outer membrane of neurons through a glycosylphosphatidyl inositol anchor. In its pathogenic, “scrapie” form (PrP Sc ), it appears as an aggregate showing no detectable covalent modifications but displaying a profoundly altered conformation enriched in β-sheet structure. Reduction of the single disulfide bridge in the prion protein with millimolar concentrations of dithiothreitol results in transformation of the α-helix–rich to the β-sheet–rich conformation, with concomitant decrease in solubility. We report here that thioredoxin coupled with thioredoxin reductase and NADPH efficiently reduces recombinant Syrian hamster (29-231) prion protein under physiologically relevant conditions. The reduced prion protein immediately becomes insoluble and precipitates, although it does not gain significant resistance to proteinase K. The thioredoxin/thioredoxin reductase system is ∼7000 times more efficient than dithiothreitol.
UBIQUITOUS CHROMOSPHERIC STRUCTURES OBSERVED IN THE QUIET SUN AT MILLIMETER AND CENTIMETER WAVELENGTHS

Unique long-term visibility variations are detected when the quiet Sun is observed with interferometers operating at 8 mm and 11 cm wavelength with angular resolutions of ∽0.5′. Quasiperiodic fluctuations in fringe amplitude are observed with periods between 20 and 30 min, and with amplitude nulls which are correlated with 180° phase changes. These variations are interpreted in terms of a changing projected baseline while viewing a few sources with angular sizes of ∽0.5′ which are distributed within the main interferometer beam with typical angular separations of 7′. The observed variations cannot be due to expanding or contracting sources of the type envisaged by Bocchia and Poumeyrol (1976) when explaining similar variations observed at 8 mm wavelength. A comparison of the flux observed at 8 mm and 11 cm indicates that the individual sources are optically thick thermal radiators with a flux which decreases with increasing wavelength, but with a temperature which increases with increasing wavelength where higher, hotter levels of the chromosphere are observed. For a source whose angular size is 0.5′, the observed flux values correspond to respective temperatures of 5000 K and 19 000 K at 8 mm and 11cm - suggesting that elements of the chromospheric network are being observed. A thermal origin for the individual sources is consistent with the lack of any detectable circular or linear polarization (< 10%) in the interferometer signal.