cssi/SciSciGPT-SciSciNet huggingface dataset:
Pulsed Doppler echocardiographic assessment of patterns of venous flow after the modified Fontan operation: potential clinical implications

To assess the effect of a modified Fontan operation on systemic venous blood flow and the hepatic circulation, we compared 11 patients having an atriopulmonary connection and 35 with total cavopulmonary anastomosis. The Doppler echocardiographic study of the caval venous, hepatic venous and portal venous flow was performed so as to calculate the pulsatility ratio and the variation of flow with respiration. All patients had undergone cardiac catheterization. In addition, we included specific laboratory investigations to assess function of various organs.Significantly lower maximum velocities of flow at inspiration (0.31±0.12 rn/sec vs 0.45±0.14 m/sec) and expiration (0.23±0.09 rn/sec vs 0.32±0.11 m/sec), less pulsatility (0.43 vs 0.16) and a lower ratio of systolic to diastolic velocity (1.22 vs 1.85) were found in the patients having a cavopulmonary as compared to an atriopulmonary anastomosis. Peak velocities of hepatic venous flow during inspiration and expiration were significantly lower in those with a cavopulmonary anastornosis (p=O.OOl and p<O.OOl, respectively). In these patients, forward flow was extremely dependent on respiration, with decrease or cessation of antegrade flow during expiration in 22 patients. The velocity of portal venous flow was also significantly lower in these patients, although the pulsatility ratio did not differ significantly between the groups (0.5 ± 0.21 and 0.57 ± 0.23, respectively). The ratio of inspiratory and expiratory velocities showed no significant difference between the groups, nor was there any correlation between the pulsatility ratio of the venous vessels or the ratio of peak flow velocities during expiration and the mean systemic venous/right atrial pressure on postoperative cardiac catheterization. Hypoproteinemia was found in 8 patients after total cavopulmonary anastomosis; 9 of 10 patients with protein C deficiency belonged to this group.The dependence of hepatic venous flow on respiration in the presence of a chronically elevated systemic venous pressure in patients after the total cavopulmonary anastornosis may influence hepatic function in the postoperative period.
Astemizole and an analogue promote fungicidal activity of fluconazole against Cryptococcus neoformans var. grubii and Cryptococcus gattii.

Cryptococcus neoformans is the leading cause of fungal meningitis, a life-threatening infection that occurs predominately in immuocompromised patients. Current drug therapies are limited to amphotericin B, fl ucytosine and the azoles since the echinocandins have no demonstrated activity against yeast like pathogens. Fluconazole, a drug belonging to the azole class and often the only available antifungal in the developing world, is fungistatic and therefore not effective in clearing cryptococcal infections in immunosuppressed individuals. Here we report that astemizole and a closely related analog (A2) promoted in vitro fungicidal activity of fl uconazole against Cryptococcus neoformans var. grubii and Cryptococcus gattii . Astemizole, a second-generation antihistamine drug used as an H 1 antagonist, has also been found to have antimalarial activity. Disk diffusion assays and MIC and MFC analysis confi rmed that the inhibitory concentrations of these drug combinations were fungicidal. When tested in vivo , astemizole or A2 in combination with fl uconazole signifi cantly improved the survival of Galleria mellonella (wax moth caterpillar) that had been previously challenged with C. neoformans but not when caterpillars were challenged with a fl uconazole-resistant strain. The fi ndings reported here suggest that fungicidal combinations between azoles and other existing drugs may represent an alternative strategy for improving treatments for fungal infections.
Ultra high conductivity of isotropic conductive adhesives

Electrical properties of the isotropic conductive adhesives filled with micron sized silver flakes and nanosized silver particles were investigated. By using appropriate surfactants, the resistivity of the silver flakes and silver nanoparticles incorporated conductive adhesives was dramatically reduced to as low as 5 /spl times/ 10-6 /spl Omega/.cm. Morphology studies showed that the decreased resistivity resulted from the sintering of silver nanoparticles. The contact resistance of the conductive adhesives under 85/spl deg/C/85%RH was significantly stable with respect to aging time due to the further sintering of silver nanoparticles.
Calibration challenges for low frequency radio astronomy

A major challenge for all high resolution low frequency radio astronomy is measuring and removing the effects of the ionosphere. The isoplanatic patch size for frequencies below a few hundred MHz is generally much smaller than the field of view. In addition, aperture arrays have beams on the sky which vary dramatically with observing geometry. These beams require careful calibration to be stable and known in order to allow imaging. Various approaches to these problems will be discussed.
Effects of CO2 and Photosynthetic Photon Flux on Yield, Gas Exchange and Growth Rate of Lactuca Sativa L. ‘Waldmann’s Green'

Enrichment of CO2 to 46 mmol m-3 (1000 mm3 dm-3) at a moderate photosynthetic photon flux (PPF) of 450 micromoles m-2 s-1 stimulated fresh and dry weight gain of lettuce leaves 39% to 75% relative to plants at 16 mmol m-3 CO2 (350 mm3 dm-3). Relative growth rate (RGR) was stimulated only during the first several days of exponential growth. Elevating CO2 above 46 mmol m-3 at moderate PPF had no further benefit. However, high PPF of 880-900 micromoles m-2 s-1 gave further, substantial increases in growth, RGR, net assimilation rate (NAR) and photosynthetic rate (Pn), but a decrease in leaf area ratio (LAR), at 46 or 69 mmol m-3 (1000 or 1500 mm3 dm-3) CO2, the differences being greater at the higher CO2 level. Enrichment of CO2 to a supraoptimal level of 92 mmol m-3 (2000 mm3 dm-3) at high PPF increased leaf area and LAR, decreased specific leaf weight, NAR and Pn and had no effect on leaf, stem and root dry weight or RGR relative to plants grown at 69 mmol m-3 CO2 after 8 d of treatment. The results of the study indicate that leaf lettuce growth is most responsive to a combination of high PPF and CO2 enrichment to 69 mmol m-3 for several days at the onset of exponential growth, after which optimizing resources might be conserved.
Optimal Nesting of Species for Exact Cover of Resources: Two Against One

Experiments for resource-defined fitness sharing (RFS) show a remarkable ability to find tilings in shape nesting problems (Horn, 2002, 2005). These tilings are essentially exact covers for a set of resources, and represent a maximally sized set of cooperating (non-competing) species. This paper initiates a formal analysis of this empirical phenomenon by examining a minimal case: two species a and b "cooperate" to exactly cover the resources, while a third species c "competes" with a and b by overlapping both in terms of covered resources. The analysis reveals that in cases in which a and b maximally compete with c for resources, species c will become extinct, while the optimal set of species, a and b, will survive. This result is clearly proven using algebra on the niching equilibrium equations for RFS, a purely static analysis
The study of gas-solid equilibrium at high pressures by gas-chromatography: Part I. Ethane, propane, and n-butane at essentially infinite dilutions in the methane-silica gel system

The measurement of vapor-solid distribution coefficients or K values of a solute distributed between a gas phase and an adsorbed phase at essentially infinite dilutions has been investigated. Gas-solid chromatography is the technique employed in which the solute of interest is eluted through a tube packed with a solid adsorbent by a flowing gas phase which may or may not be appreciably adsorbed. The data taken for the eluted solute samples were then related to the K value and isobaric heat of adsorption for the solutes in the vapor-solid system. A previous mathematical solution describing the chromatographic process is extended to include the case of an appreciably adsorbed pure component elution gas. This theory allows the calculation of solute K values and heats of adsorption for a solute at essentially infinite dilution in the vapor-solid system. It is necessary to have adsorption data for the elution gas covering the range of interest. For this reason the necessary elution gas adsorption isotherms were determined gravimetrically for the temperature and pressure range of the study. For comparison purposes a single ethylene adsorption isotherm at 25°C. was obtained along with retention volume data for methane, ethane, and propane at essentially infinite dilution in the ethylene-silica gel system at 25°C. Agreement of the data of this study and the literature was thought to be sufficiently good to warrant further use of the technique. Methane adsorption isotherms on silica gel were gravimetrically measured at −40°, −20°, 0°, 20°, and 40°C. from 100 to 2,000 lb./sq.in.abs. Retention volume data over the same pressure and temperature ranges were taken for ethane, propane, and n-butane at essentially infinite dilution in the methane-silica gel system.
Remote monitoring and expert diagnostic support for the pulp and paper industry

As pricing and margin pressures in the pulp & paper industry continue to increase, overall equipment effectiveness (OEE) has become more than just a catch phrase; it is an essential element in the viability of any player in the industry. Every level of the organization can have an impact on OEE - positive, and negative. This paper discusses how remote monitoring and expert diagnostic support fill the need to improve OEE by supporting operations, maintenance, engineering and management. These programs assure assets are in operation longer, machines perform at or above design production speed for a given product and ultimately delivering more saleable product. This is accomplished by reducing or eliminating instances of unscheduled down time, reducing the duration of such down time, increasing the effectiveness, availability and value of support resources, increasing quality by optimizing system performance and by delivering return on investment (ROI) to management. Real-world pulp & paper industry case examples are used to demonstrate how remote monitoring and expert diagnostic support programs actually affect ROI for existing users. These case examples range from predictive failures of simple devices to deep dive (in-depth), system design, performance and product issue analyses and resolutions.
Implementing virtual secure circuit using a custom-instruction approach

Although cryptographic algorithms are designed to resist at least thousands of years of cryptoanalysis, implementing them with either software or hardware usually leaks additional information which may enable the attackers to break the cryptographic systems within days. A Side Channel Attack (SCA) is such a kind of attack that breaks a security system at a low cost within a short time. SCA uses side-channel leakage, such as the cryptographic implementations' execution time, power dissipation and magnetic radiation. This paper presents a countermeasure to protect software-based cryptography from SCA by emulating the behavior of the secure hardware circuits. The emulation is done by introducing two simple complementary instructions to the processor and applying a secure programming style. We call the resulting secure software program a Virtual Secure Circuit (VSC). VSC inherits the idea of a secure logic circuit, a hardware SCA countermeasure. It not only maintains the secure circuits' generality without limitation to a specific algorithm, but also increases its flexibility. Experiments on a prototype implementation demonstrated that the new countermeasure considerably increases the difficulty of the attacks by 20 times, which is in the same order as the improvement achieved by the dedicated secure hardware circuits. Therefore, we conclude that VSC is an efficient way to protect cryptographic software.
Suppression of linearly responsive residual water

The residual water, coming from a region away from the center of the RF coil and therefore experiencing a much smaller flip-angle than the designed one, may not be well suppressed in certain water-suppression experiments. To suppress the residual water efficiently, a composite 90°x90°y90°-x90°-y pulse is used in the WET sequence, which de-excites molecules experiencing small flip-angles. The composite pulse, however, has two null excitation points near on-resonance, causing a severe loss of spectrum intensity and baseline distortion toward the null points. A phase inversion at each null point is found in the excitation profile of the composite pulse. This phenomenon is explored in detail. Because the residual water experiences a very small flip-angle, it can be treated as a linear spin system, i.e., its peak intensity is proportional to the flip-angle. Based on this principle, the residual water can be reduced dramatically by replacing the 90° pulse in the WET sequence with a 270° pulse for one out of every four scans. Unlike the composite pulse, this scheme does not introduce noticeable loss of spectrum intensity and baseline distortion.
Electron beam observation opportunity

Ionospheric researchers will have the opportunity to conduct coordinated radio, radar, and optical observations in conjunction with other space-based electron beam experiments as part of the upcoming Cooperative High-Altitude Rocket Gun Experiments (CHARGE) 3 rocket flight in November 1988 at White Sands Missile Range (WSMR, White Sands, N.Mex.). The flight will be particularly interesting because of the high power planned for the electron gun (3.5 kV at 5 A), which is based, in part, on technology developments planned for the successful Excede series of rockets. CHARGE 3 is the third in a series of U.S. flights made in collaboration with investigators from Utah State University (Logan), Stanford University (Stanford, Calif.), the Institute for Space and Astronautical Sciences (Sendai, Japan), and the University of Michigan (Ann Arbor). The general objectives for CHARGE 3 are fourfold: to study vehicle charging and diagnosecontributory effects at higher beam currents and energy, to study ELF/VLF wave generation and propagation from dc and modulated electron beams, to diagnose beam propagation remotely by studying E region ionization and optical excitation, and to investigate voltage and current distribution in an electrically tethered space vehicle system at higher beam currents.
Educational software and the Sisyphus effect

The author discusses the acceptance and widespread use of educational software for physics teaching. He considers software authoring, the Internet and the JiTT paradigm.
Guest Editorial Special Section on Human-Centered Automation

The papers in this special section are devoted to the topic of human-centered automation. The central theme of these papers are the tools and methods for the design and analysis of human-centered automation systems including: the design and validation of computational models of systems that integrate models of the human with models of autonomous and semi-autonomous systems; the design of systems that ease the transfer of information between humans and autonomous systems; the analysis and prediction of potential conflicts between the human and the automation in semi-autonomous systems; the design of autonomy to accommodate varying levels of human experience, training, and acuity; the analysis of information asymmetry in collaborative, semi-autonomous systems; the design of autonomy for off-nominal conditions, such as multiple sensor failures, human error, or other cascading events; and the design of autonomy to support systems with multiple humans; the design of autonomous systems which are “self-aware,” so that humans are prompted to intervene when necessary.
THE EARLY PHASE OF BLOOD COAGULATION

Factor XII (Hageman factor) is a plasma protein that participates in the early phase of the intrinsic and extrinsic pathways of blood coagulation. Bovine factor XII is a single-chain molecule which is converted to factor XII a by minor proteolysis. Factor XII a is composed of a heavy and a light chain held together by a disulfide bond(s), The active site in this protein is in the light chain of the molecule. In the intrinsic pathway, factor XII a converts factor XI to factor XI a in the presence of high molecular weight kininogen. In the extrinsic pathway, factor XII a converts factor VII to factor VII a .
Global Medical Imaging, LLC

Appropriate for courses on entrepreneurship, managing small businesses, and strategy. This is the story of how a growth company's processes, business model, management team, and founders evolve in response to growth. The case shows the difficulty of growing while undergoing process and people changes and raises the issue of whether the people or the process should follow or precede growth. It illustrates the necessity for people and processes to reininvent themselves in order to handle new management challenges.
New state of nuclear matter: Nearly perfect fluid of quarks and gluons in heavy-ion collisions at RHIC energies: From charged particle density to jet quenching

This article reviews several important results from RHIC experiments and discusses their implications. They were obtained in a unique environment for studying QCD matter at temperatures and densities that exceed the limits wherein hadrons can exist as individual entities and raises to prominence the quark-gluon degrees of freedom. These findings are supported by major experimental observations via measuring of the bulk properties of particle production, particle ratios and chemical freeze-out conditions, and elliptic flow; followed by hard probe measurements: high- $ p_{T}$ hadron suppression, dijet fragment azimuthal correlations, and heavy-flavor probes. These measurements are presented for particles of different species as a function of system sizes, collision centrality, and energy carried out in RHIC experiments. The results reveal that a dense, strongly interacting medium is created in central $Au+Au$ collisions at $ \sqrt{s_{NN}} = 200$ GeV at RHIC. This revelation of a new state of nuclear matter has also been observed in measurements at the LHC. Further, the IP-Glasma model coupled with viscous hydrodynamic models, which assumes the formation of a QGP, reproduces well the experimental flow results from $Au+Au$ at $ \sqrt{s_{NN}} = 200$ GeV. This implies that the fluctuations in the initial geometry state are important and the created medium behaves as a nearly perfect liquid of nuclear matter because it has an extraordinarily low ratio of shear viscosity to entropy density, $ \eta/s\approx 0.12$ . However, these discoveries are far from being fully understood. Furthermore, recent experimental results from RHIC and LHC in small $ p+A$ , $ d+ Au$ and 3He+Au collision systems provide brand new insight into the role of initial and final state effects. These have proven to be interesting and more surprising than originally anticipated; and could conceivably shed new light in our understanding of collective behavior in heavy-ion physics. Accordingly, the focus of the experiments at both facilities RHIC and the LHC is on detailed exploration of the properties of this new state of nuclear matter, the QGP.
A framework and typology of adjustment responses to extra-cultural disorientation experienced during intercultural assignments

Abstract The psychological mobility required in global work assignments creates an exigency for psychological adjustment. The new framework presented in this paper conceptualizes adjustment as a person's efforts to adapt to episodes of disorientation encountered when working in intercultural contexts. Specifically, individuals experience “extra-cultural” disorientation when they lack interpretive frames during episodes of cross-cultural interaction, and this disorientation triggers the psychological adjustment process. Adjustment responses will vary along a continuum between applying one's own familiar cultural patterns and learning from new situational cues during interactions with others. Individual adaptation theory offers a generalizable model for understanding adjustment, and four key elements of individual adaptation (managing stress, learning and sense-making, organizing behavioral routines, and negotiating personal versus organizational demands) mirror recurring themes in the cross-cultural management literature. A typology of adjustment responses is offered to illustrate a person's psychological state after responding to one or more extra-culturally disorienting episodes. Adjustment responses may be integrated into behavioral routines, mindsets, and identities, and different types of responses may facilitate different roles or work assignments.
La continuità e le funzioni di Baire

Un teorema fondamentale dell’analisi classica asserisce che per una topologia compatta metrica su un insieme (non banale)E, esistono funzioni ed insiemi di tutti gli ordini di Baire ordinalmente numerabili. La conferenza presente rivela la maniera radicale con la quale si cambia l’ordine di Baire quando si sostituisce ad una topologia data inizialmente una topologia coerente — cioe, una topologia che porta alle stesse funzioni di Baire.
Who Perceives Supermarket Prices Most Validly

information which she must sort and process in order to make a purchase decision. An individual shopper differs in her shopping behavior patterns, attitudes toward shopping, and demographic characteristics from others. All of these factors influence the perceptual process, but which are most closely associated with forming valid perceptions? The identification of the most valid perceivers would be valuable to two action-oriented groups: (1) those concerned with consumer protection and (2) supermarket executives. The first want to provide information, guidance, and legal action where appropriate. Such advocates must know what information and what be-
A Case of Pseudothrombocytopenia in a Patient Undergoing Emergency Laparotomy

症例は48歳,女性.骨盤内膿瘍,卵巣腫瘍あるいは子宮体癌が疑われ緊急開腹術となった.術前検査成績では炎症反応の上昇以外はほぼ正常で血小板数は28.7万/μlであった.執刀時実施の血算で血小板数8,000/μlと著しく低値を示したが,術野の出血傾向はなくこの値と一致しなかった.癒着剥離など手術の進行とともに出血量が増加,血小板製剤の確保を依頼した.極端な血小板減少について血液内科専門医に問い合わせたところ,この患者は採血管に含まれる抗凝固剤EDTA (ethylene diamine tetra acetic acid)により血小板が凝集し,見かけ上血小板数が減少する偽性血小板減少症を合併していることが明らかになった.
The Ratio of Emergency Department Visits for ILI to Seroprevalence of 2009 Pandemic Influenza A (H1N1) Virus Infection, Florida, 2009.

BACKGROUND A seroprevalence survey carried out in four counties in the Tampa Bay area of Florida provided an estimate of cumulative incidence of infection due to the 2009 influenza A (H1N1) as of the end of that year's pandemic in the four counties from which seroprevalence data were obtained Methods. Excess emergency department (ED) visits for influenza-like illness (ILI) during the pandemic period (compared to four non-pandemic years) were estimated using the ESSENCE-FL syndromic surveillance system for the four-county area. RESULTS There were an estimated 44 infections for every ILI ED visit. Age-specific ratios rose from 19.7 to 1 for children aged 64 years. CONCLUSIONS These ratios provide a way to estimate cumulative incidence. These estimated ratios can be used in real time for planning and forecasting, when carrying out timely seroprevalence surveys is not practical. Syndromic surveillance data allow age and geographic breakdowns, including for children.
Stress and Satisfaction in the Diagnostic Process

Diagnosis can be a complex, time-consuming, and stressful process. Parents and individuals with autism spectrum disorder are consumers, and their reaction is critical. This chapter discusses the research on these topics, factors to consider when providing a diagnosis, and issues requiring further study.
Exports and Job Training

This paper examines whether export participation matters for job training. The paper draws on longitudinal worker-firm data for Brazilian manufacturing, linked with detailed records on training activity from the main provider. The analysis uses industry-specific exchange rate movements to generate exogenous variation in export status at the firm-level. The findings indicate that export participation tends to increase the share of workers who receive technical upgrading. The results also reveal that technical upgrading has positive returns to trainees within exporting firms. These findings support the hypothesis that exporting requires skill upgrading, and suggest that this is partially achieved by training firms' existing workforce.
Abstract IA25: Regulatory control of lincRNA function through formation of complex RNA structural motifs

While the regulatory role of lincRNAs is becoming increasingly appreciated, the functional role of RNA structures within these molecules is not well understood. We have embarked on a study to understand the folding of lincRNA molecules, and to identify functional structural modules within large RNA transcripts. Using approaches to promote the native folding of large RNA molecules, we have been purifying lincRNAs, mapping their structures with chemical probes, and then using this information to construct structural maps of lincRNA architecture. This work is complemented by phylogenetic and genetic approaches for exploring the functional relevance of RNA structures identified in our study. In this way, we have mapped the structure of lincRNAs such as HOTAIR and lincRNA p21, identifying novel structural motifs, enabling evolutionary comparisons and facilitating targeted mutational studies of lincRNA function. Citation Format: Isabel Chillon, Srinivas Somarowthu, Fei Liu, Anna Marie Pyle. Regulatory control of lincRNA function through formation of complex RNA structural motifs. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr IA25.
Management of the infected penile implant--concepts on salvage techniques.

SSI Grand Master Lecture 5 ‘Management of the infected penile implant—concepts on salvage techniques’
Expert services on the Web: The commercial competition for libraries

Competition entre d'une part des bibliothecaires de service de reference offrant leur service comme experts pour la recherche d'information sur le web et d'autre part des experts fournissant des services payants ou gratuits sur le web
Role of the Interosseous Membrane in Preventing Distal Radioulnar Gapping.

Background Damage to the interosseous membrane (IOM) can alter load transmission between the radius and ulna and decrease their axial stability. Less is known about the effect of IOM sectioning on the transverse stability between the radius and ulna. Purpose The purpose of this study was to quantify the radioulnar gapping at the distal radioulnar joint (DRUJ) during forearm rotation when the IOM was experimentally sectioned while maintaining the integrity of the distal radioulnar ligaments. Methods In 12 fresh-frozen cadaver forearms tested in a combined wrist–forearm simulator, the increase in gap between the radius and ulna, at the level of the DRUJ, was determined during cyclic forearm rotation following IOM sectioning. Results IOM sectioning caused a significant increase in dorsal gapping at the DRUJ by 2.1 mm in supination and 0.6 mm in pronation. It also caused an increase in palmar gapping by 1.3 mm in supination and 0.5 mm in pronation. Conclusion This experiment has shown that the IOM has an important role in stabilizing the DRUJ, especially in supination, and that IOM sectioning caused greater loads on the palmar and dorsal radioulnar ligaments. Since DRUJ instability is primarily treated by fixing the laxity at the dorsal radioulnar ligament (DRUL) and palmar radioulnar ligament (PRUL), untreated IOM damage could permit additional injury and instability to the radioulnar ligaments or their reconstruction. Clinical Relevance Reconstruction of a torn IOM should be considered in the presence of persistent DRUJ instability following DRUJ reconstruction.
Electronic and Vibrational Dephasing in Solution by Dynamic Symmetry Breaking

A new type of Raman dephasing due to interconversion between two symmetrically related structures is described. The line is broadened by fluctuations not in the vibrational frequency but in the sign of the Raman polarizability.
Disruptive Innovations in Manufacturing – An Alternative for Re-shoring Strategy

This paper examines the U.S. manufacturing re-shoring trend, argues its inherent limitations and discusses that there is no evidence implying significant impacts of such renaissance on domestic employment since the organizational structure of manufacturing production has changed over the past years. This research proposes a different definition of disruptive innovation and introduces examples of disruptive innovation in textile and apparel manufacturing industry, based on mega trends by 2025. Finally, it recommends a studious focus on facilitation of disruptive innovation in manufacturing, rather than encouraging re-shoring policies, by more and consistent investment in research and development.
One electron oxidation of 3-methylcholanthrene: A chemical model for its mechanism of carcinogenesis

Abstract One electron transfer oxidation has long been proposed as a route to the ultimate electrophilic and carcinogenic metabolites of both methylated and non-methylated polycyclic aromatic hydrocarbons (PAH). The carcinogenic hydrocarbon 3-methylcholanthrene (3-MC) has a methyl-analogous function at its meso-anthracenic center in the form of a dimethylene bridge, and treatment of this compound with the one electron transfer oxidizing reagent ferric ferricyanide, FeIII(FeIII(CN)6), in mixed aqueous-organic media generated multiple oxygenated species, many of which duplicate those found in mammalian metabolism including known carcinogens 1-hydroxy-3MC and 1-keto-3MC. These results are in agreement with a Unified Theory for PAH Carcinogenicity which predicts in vivo generation of a proximate benzylic alcohol metabolite from the 3-MC procarcinogen and conjugation with a moiety such as sulfate intended for rapid urinary excretion. The sulfate instead acts as a leaving group and generates an electrophilic carbocation capable of reacting with sensitive nucleophiles such as DNA in cellular nuclei. The products of one electron transfer oxidation align well with predictions of the Unified Theory since in many cases these products provide substrates or precursors for conjugation reactions.
Myeloid cells as a target for oligonucleotide therapeutics: turning obstacles into opportunities

Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers. To overcome challenges in the development of pharmacological STAT3 inhibitors, we recently developed oligonucleotide-based strategies for cell-selective, in vivo STAT3 targeting. Conjugation of a STAT3siRNA or decoy STAT3 inhibitors to synthetic Toll-like Receptor 9 (TLR9) agonists, CpG oligonucleotides, allowed for selective delivery into TLR9-positive cells. Cellular target for CpG-STAT3 inhibitors include non-malignant, tumor-associated myeloid cells, such as polymorphonuclear MDSCs, as well as cancer cells in acute myeloid leukemia, B cell lymphoma and in certain solid tumors. The chemically modified CpG-STAT3 inhibitors resist serum nucleases and thus can be administered intravenously. Their potency relies on the intracellular gain-of-function effect: release of the central immune checkpoint regulator (STAT3) to unleash proinflammatory signaling (CpG/TLR9) in the same antigen-presenting cell. At the cellular level, CpG-STAT3 inhibitors exert two-pronged effect by rescuing T cells from the immune checkpoint control while decreasing survival of cancer cells. In this article, we review the preclinical data on CpG-STAT3 inhibitors and discuss perspectives of using TLR9-targeted delivery of oligonucleotide therapeutics for the generation of novel, more effective and safer cancer immunotherapies.
Extension of the lattice-boltzmann method for direct simulation of suspended particles near contact

Computational methods based on the solution of the lattice-Boltzmann equation have been demonstrated to be effective for modeling a variety of fluid flow systems including direct simulation of particles suspended in fluid. Applications to suspended particles, however, have been limited to cases where the gap width between solid particles is much larger than the size of the lattice unit. The present extension of the method removes this limitation and improves the accuracy of the results even when two solid surfaces are near contact. With this extension, the forces on two moving solid particles, suspended in a fluid and almost in contact with each other, are calculated. Results are compared with classical lubrication theory. The accuracy and robustness of this computational method are demonstrated with several test problems.
Determinants of Inflation - The Phillips Curve Model

This chapter develops and tests a relatively sophisticated version of the Phillips curve. Determinants of inflation were found to be unemployment, the money supply, the negative ratio of the trade deficit to GDP, and the ratio of savings to GDP, the positive effect of foreign borrowing on inflation, and the oil price shocks of the 1970s.
Design of a virtual computer lab environment for hands-on information security exercises

There is an increasing demand from both students and industry for more computer science students to have experience in information security. One area that is difficult for smaller colleges to implement is hands-on security exercises for students. This paper describes a method and our design considerations for constructing a virtual computer lab environment to be used for such courses. This system uses a single server to host virtual machines that can be configured into small networks and made available for student assignments. These machines for each student group can communicate amongst themselves but are isolated from each other and from the rest of the campus network. Students can be given administrative access to the machines without compromising the security of the campus network. While our initial focus is on an information security course, this type of system would also be useful for laboratory exercises in operating systems, networking, and system administration classes. This software is under active development and is being made freely available for use in other courses and at other institutions.
Understanding changes in the b-wave of the ERG caused by heterogeneous receptor damage

PURPOSE To understand better the relationship between heterogeneous receptor damage and the changes in the b-wave of the rod ERG. METHODS A computational model of the b-wave is used to simulate b-waves from retinas with two regions (a healthier and a more affected region) differing in area and sensitivity. The peak-to-peak amplitudes of the simulated b-waves are fitted with a Naka-Rushton equation, and the parameters log K and Vmax are estimated. Insights gained from these simulations are tested against rod ERGs and rod visual fields from patients with autosomal dominant retinitis pigmentosa (n = 11) and cone-rod dystrophy (n = 17). RESULTS In the simulated retinas, Vmax decreases when the more affected region of receptors is less sensitive than the healthier region by more than 0.5 log unit. However, the relative change in Vmax does not match the relative area of the more affected region unless this region is depressed by 2.0 log units or more. As the more affected region loses sensitivity, log K at first increases but then decreases and approaches the log K of the healthier region for losses greater than 2.0 log units or so relative to the healthier region. For the patients' data, the simulations predict the general relationships observed between the summary statistics of the visual fields (e.g., area of field and mean of log sensitivity changes in the field) and the changes in log K and Vmax. CONCLUSION A decrease in Vmax indicates that regions of the patient's retina have lost 0.5 log unit or more of sensitivity. An increase in log K indicates that either the healthiest part of the patient's retina is abnormal by at most delta log K, a large part of the retina has lost considerable sensitivity (i.e., 0.5 to 2.0 log units) but is still contributing to the response, or both.
Protein-Metal-Ion Interactions Studied by Mass Spectrometry-Based Footprinting with Isotope-Encoded Benzhydrazide.

Metal ions, usually bound by various amino-acid side chains in proteins, play multiple roles in protein folding, conformational change, cellular communication, and catalysis. Ca(II) and Mg(II), abundant among biologically relevant cations, execute their cellular functions associated with the conformational change of bound proteins. They bind with proteins where carboxylic acid residues are dominant ligands. To develop mass spectrometry for mapping protein-binding sites, we implemented a new carboxyl group footprinter, benzhydrazide, and refined it with isotope encoding. The method uses carbodiimide chemistry to footprint carboxylic residues, whereby 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide activates a carboxyl group followed by nucleophilic attack by benzhydrazide forming a stable labeled product. We tested the effectiveness of isotope-encoded benzhydrazide by studying Ca2+ and Mg2+ binding of calmodulin, an EF-hand protein. The footprinting results indicate that the four active sites for metal-ion...
Specification and negotiation in incomplete contracts

We investigate contractors' bargaining power and holdup on buyers in procurement auctions of incomplete contracts held by California Department of Transportation. Using a model where contractors bid competitively in response to a buyer's choice of initial contract design, we infer the contractors' costs and bargaining power from the bids and transfers negotiated after the auction. We find that the contract winners have substantial bargaining power in post‐auction negotiation. The average holdup on the buyer is about 20% of project costs. Counterfactual cost‐plus contracts would reduce the buyer's surplus in 72% of the projects, with an average reduction over $382,000.
Regional Organizations and Conflict Management in Africa: A Contextual Assessment of the Inter-Governmental Authority on Development (IGAD) in Somalia

The role of regional organizations in managing protracted conflicts within and among Member States cannot be overemphasized. This has been the case of the Inter-Governmental Authority on Development (IGAD) in the Horn of Africa, a region characterised by protracted conflict, instability and state failure as in the case of Somalia. Established in 1986 as Intergovernmental Authority on Drought and Development (IGADD), the organization was re-established in 1996 as IGAD with its mandate expanded to include regional peace and security. Adopting diplomacy of conflict management as an approach towards conflicts in the Horn of Africa, IGAD has visibly been involved in the continued search for peace in the embattled state of Somalia. Political stability and sustainable peace in Somalia however remains elusive as new actors and interest in the conflict emerge. While acknowledging IGAD’s critical role towards political stability in Somalia and the larger Horn of Africa, I argue that IGAD lacks institutional capacity to sustainably resolve complex and protracted conflicts as in the case of Somalia, which calls for multiple approaches to conflict management than those provided for in the IGAD’s founding Agreement.
Fludarabine Is Superior to Cladribine When Added to Busulfan and Low Dose TBI as Reduced Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation (HCT): A Prospective Randomized Trial.

Purine analogues have been combined with alkylator/irradiation as immunosuppressive and anti-tumor conditioning prior to allogeneic hematopoietic stem cell transplantation (HCT) though differing purine analogues have not been compared. We prospectively tested Fludarabine (F) 40 mg/m2/d x 5d vs. Cladribine (C) 10 mg/m2/d x 5d plus Busulfan (Bu) (2mg/kg q12h x 2d) and total body irradiation (T) 200cGy followed by cyclosporine and mycophenylate mofetil in 19 recipients of matched sibling peripheral blood stem cell and 13 unrelated donor (URD) marrow HCT. Patients in each randomly assigned cohort [FBuT vs. CbuT] were similar in age (median 52 years in both groups), diagnosis (leukemia/MDS 38 vs. 31%; lymphoid malignancy 57 vs 69%), extensive pre-HCT therapy (56 vs. 63%), high risk disease status (81 vs. 93%) and Karnofsky (median 90 in each)[all p= NS] though fewer FBuT were URD recipients 25% vs. CBuT 56%, p=0.07. Engraftment was prompt in both groups (median 11 vs. 12 days), but the cumulative incidence of neutrophil engraftment was 75% (95% C.I. 54–96%) using CBuT vs. 100% with FBuT (p 50,000/μL by day +180, p=0.19. The cumulative incidence of GVHD after FBuT vs. CbuT was similar (acute grade II/IV 56 vs. 69%, p=0.26) and (chronic 50 vs. 31%, p=0.27). Transplant related mortality at day +180 was also similar [FBuT 25% (4–46) vs. CbuT 38% (14–61), p=0.47]. Survival was equivalent: at 1 year 50% in each group; at 3 years FBuT 25% vs. CBuT 38%, p=0.55. Multivariate analyses adjusted for age, donor type, diagnosis and stage as well as conditioning regimen showed lower relative risk (RR) of engraftment with CBuT (RR 0.6 (95% C.I. 0.2–1.3) p=0.16) and with URD RR 0.4 (0.2–1.0) p=0.04). RR of Platelet recovery was equivalent with FBuT (RR 0.7 (0.3–1.7) p=0.45) but inferior with URD (RR .16 (.05–.5) p<0.01). RR of GHVD II/IV similar with FBuT RR 1.1, p=0.95, but more frequent with URD RR 2.0, p=.2 and high risk status patients (RR 4.5, 1.5–13.5, =<0.01). Prevalence of remission (CR or PR) at 18 months was high and was similar in both groups (FBuT 100% vs CBuT 86%, p=NS). These data suggest that older patients with advanced hematologic malignancies can achieve satisfactory post-transplant outcomes using either of these combination/reduced intensity conditioning regimens. Fludarabine may be superior to cladribine as a component of pre-HCT conditioning with Bu/TBI due to reduced risks of graft failure. Further modifications of the regimen may confirm universal engraftment with even lower peri-transplant morbidity.
An Interesting and Productive Research and Clinical Career.

To begin, I wish to thank the Academy of Toxicological Sciences for bestowing this honor on me. I have had a rewarding career in basic research and clinical medicine, beginning with research in hig...
Contemporary Enterovirus D68 strains show enhanced replication and translation at 37°C

ABSTRACT Enterovirus D68 (EV-D68) emerged in 2014 as an important pathogen linked to severe lower respiratory disease and acute flaccid myelitis outbreaks. Historically associated with mild common-cold-like symptoms, clusters of severe disease attributed to EV-D68 appeared during a series of outbreaks in 2014, 2016, and 2018. Previous studies of historic EV-D68 strains demonstrated attenuated replication at temperatures of the lower respiratory tract (37°C), when compared to the upper respiratory tract (32°C). By testing a panel of historic and contemporary EV-D68 strains at 32°C and 37°C, we demonstrate that contemporary strains of EV-D68 undergo little to no attenuation at increased temperatures. Contemporary strains produced higher levels of viral proteins at 32°C and 37°C than historic strains, although both strains infected similar numbers of cells and had comparable amounts of replication complexes. IRES activity assays with dual-luciferase reporter plasmids demonstrated enhanced translation in recent EV-D68 strains mapped to regions of variability in the 5’ UTR found only in contemporary strains. Using an infectious clone system, we demonstrate that the translation advantage dictated by the 5’ UTR does not solely mediate temperature sensitivity. The strain-dependent effects of temperature on the EV-D68 life cycle gives insight into the susceptibility of the lower respiratory system to contemporary strains. IMPORTANCE Enterovirus-D68 (EV-D68) emerged in 2014 as a causative agent of biannual severe pediatric respiratory disease and acute flaccid myelitis (AFM). We show that recent EV-D68 viruses have gained the ability to replicate at 37°C. Enhanced virus protein translation seemed to correlate with enhanced virus replication at 37°C but other genetic factors are also contributing to this phenotype. An enhanced ability to replicate at core body temperature may have allowed EV-D68 to penetrate both lower in the respiratory tract and into the central nervous system, explaining the recent surge in severe disease associated with virus infection.
Biochips:valuable vehicles for translational medicine

Biochips have become important analytical tools in biomedical research and clinical diagnostics because they have the advantage to integrate many different analytical steps, such as sample preparation, chemical reactions, analytical separation, all on the same device. There are various types of biochips including microfluidic chips, microarray chips and bioelectronic chips. This article describes the progress of biochip technology, clinical applications and limitations, and technical outlook. Key words: Microchip analytical procedures; Laboratory techniques and procedures
Broca's area

> Bienvenue , one and all, to my neighborhood—my area, as it were > > Or perchance best understood > > As my district, zone, locality, or quarter > > Though I do apologize, there is no porter > > Mais oui ! A porter, garcon, a carrier— > > Someone to assist with your paraphernalia > > But fear not, for I am your host, Monsieur Broca! and if I may say, > > Enchante , pleased to make your acquaintance, here in my oasis > > I shall embody, as always, a manner most gregarious and gracious, > > But please forgive my unrestrained proclivity—that is, my speech, my parlance— > > For I am eternally and reflexively loquacious
Analysis of archival specimens confirms White-nose syndrome in little brown bats (Myotis lucifugus) from New York, USA, in spring 2007

White-nose syndrome (WNS), an emerging fungal disease of North American bats, was first diagnosed in January 2008, although mortality and photodocumentation suggest the disease might have been present earlier. Using archived samples, we describe a definitive case of WNS in little brown bats (Myotis lucifugus) from New York, US, in spring 2007.
Transport Modeling of Kinetically Limited Microscale Extraction Systems: Droplet and Supported Liquid Membrane Separations

Microfluidic droplet extraction devices can be used to efficiently measure solute phase transfer kinetics in liquid–liquid extraction systems. In this work, a droplet extraction apparatus was const...