cssi/SciSciGPT-SciSciNet huggingface dataset:
Plasma cysteine/cystine redox couple disruption in animal models of temporal lobe epilepsy.

Currently the field of epilepsy lacks peripheral blood-based biomarkers that could predict the onset or progression of chronic seizures following an epileptogenic injury. Thiol/disulfide ratios have been shown to provide a sensitive means of assessing the systemic redox potential in tissue and plasma. In this study, we utilized a rapid, simple and reliable method for simultaneous determination of several thiol-containing amino acids in plasma using HPLC with electrochemical detection in kainic acid (KA) and pilocarpine rat models of epilepsy. In contrast to GSH and GSSG levels, the levels of cysteine (Cys) were decreased by 42% and 62% and cystine (Cyss) were increased by 46% and 23% in the plasma of KA- and pilocarpine-injected rats, respectively after 48 h. In chronically epileptic rats, plasma cysteine was decreased by 40.4% and 37.7%, and plasma GSSG increased by 33.8% and 35.0% following KA and pilocarpine, respectively. Treatment of rats with a catalytic antioxidant, 60 min after KA or pilocarpine significant attenuated the decrease of plasma Cys/Cyss ratios at the 48 h time point in both models. These observations suggest that the decreased cysteine and ratio of Cys/Cyss in plasma could potentially serve as redox biomarkers in temporal lobe epilepsy.
Developmental changes in adrenergic regulation of fetal arginine vasopressin secretion

Fetal adaptation to the extrauterine environment is associated with profound alterations in pulmonary, renal, and cardiovascular functions. Coincident with these changes are a variety of endocrine responses including concomitant increases in plasma catecholamine and arginine vasopressin (AVP) levels. In view of the demonstrated interaction between the sympathoadrenal system and the neurohypophysis in adult mammals, we questioned whether increases in plasma catecholamine levels in the fetus affect fetal plasma AVP levels and whether catecholamine-AVP interactions change developmentally. Chronically catheterized fetal lambs at either 131 +/- 1 (preterm) or 142 +/- 1 days (term) received graded infusions of either epinephrine (E) or norepinephrine (NE) at rates of 0.04, 0.2, 0.75, 1.5, and 3.0 micrograms.min-1.kg-1 during successive 40-min infusion periods. Plasma AVP concentrations in term animals significantly increased (1.4 +/- 0.1 to 5.1 +/- 1.6 pg AVP/ml) in response to E infusion of 0.75 microgram.min-1.kg-1 or greater. The log-linear dose response curves for each animal were used to determine the minimum plasma E concentration required to stimulate AVP secretion or "threshold." The mean plasma E threshold for AVP secretion was significantly lower in term animals (1.4 +/- 0.4 ng/ml) than in preterm animals (6.6 +/- 0.9 ng/ml). Plasma E levels were positively correlated with plasma AVP levels (r = 0.90) above the threshold value in both groups. Changes in plasma AVP levels were observed in preterm or term animals in response to NE only at the highest infusion rate studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Entrevista - George P. Lakoff

George Lakoff is one of the most widely recognized and celebrated scholars in the field of Cognitive Linguistics in the world today. And with good reason, because Lakoff not only helped pioneer this field from its earliest beginnings, but also he has guided and shaped its development down to the present day.
Solar wind sputtering rates of small bodies and ion mass spectrometry detection of secondary ions

Solar wind interactions with the surfaces of asteroids and small moons eject atoms and molecules from the uppermost several nm of regolith grains through a process called sputtering. A small fraction of the sputtered species, called secondary ions, leave the surface in an ionized state, and these are diagnostic of the surface composition. Detection of secondary ions using ion mass spectrometry (IMS) provides a useful method of analysis due to low backgrounds and high instrument sensitivities. However, the sputtered secondary ion yield and the atomic composition of the surface are not 1-to-1 correlated. Thus, relative yield fractions based on experimental measurements are needed to convert measured spectra to surface composition. Here, available experimental results are combined with computationally derived solar wind sputtering yields to estimate secondary ion fluxes from asteroid-sized bodies in the Solar System. The Monte Carlo simulation code SDTrimSP is used to estimate the total sputtering yield due to solar wind ion bombardment for a diverse suite of meteorite and lunar soil compositions. Experimentally measured relative secondary ion yields are then used to determine the abundance of refractory species (Mg+,Al+,Ca+,Fe+) relative to Si+, and it is shown that relative abundances can be used to distinguish whether a body is primitive or has undergone significant geologic reprocessing. Estimates of the sputtered secondary ion fluxes are used to determine the IMS sensitivity required to adequately resolve major element ratios for nominal orbital geometries.
Use of Color Charts in Supervision

A new method helps students recognize an interactional process, identify clients' defense mechanisms, and evaluate their own activities in interviews
A Review of Research Connecting Digital Storytelling, Photovoice, and Civic Engagement:

The purpose of this review is to expand understanding of the ways culturally, ethnically, and racially diverse youth have begun to reimagine urban and rural spaces using digital storytelling and ph...
Multi-Channel Velocity Multiplexing on a PDMS Based Optofluidic Chip

Multi-channel velocimetry for multiplexed particle detection is demonstrated on-chip using a PDMS based optofluidic platform. One liquid-core multimode interference waveguide is used to excite two detection liquid-core channels. Three wavelengths are used with two speeds to demonstrate multiplexing of fluorescent microbeads.
It’s a Numbers Game: Change in the Frequency, Type, and Presentation Form of Statistics Used in NFL Broadcasts

Although scholars have examined numerous facets of broadcast sports, limited research has explored the use of statistics in these broadcasts. Reference to statistical summaries of athlete or team performance have long been a component of sport broadcasts, and for some viewers the rise of fantasy sport has led to even greater interest in quantitative measures of athlete or team performance. To examine the presence and nature of statistical references in sport broadcasts, this study examines National Football League telecasts over time to identify changes in the frequency, type, and presentation form of statistics. Findings revealed an emphasis on individual player statistics over team statistics, as well as an increase in on-screen graphics over time. The study also revealed a simultaneous decrease in statistical references relayed orally by broadcasters. These findings illustrate the importance of statistics as a storytelling tool, as well as reflecting technological innovations in sports broadcasting. In...
The State of Practice

As discussed throughout the earlier chapters in this book, many US government agencies have already begun applying principles of resilience analysis to a variety of infrastructures and systems. Often, such use of resilience has focused on systems-wide shocks to the basic functionality of a particular service’s infrastructure. This is due largely to the system’s high degree of complex interconnectivity with other such systems, such as the inherent dependencies between road infrastructure, energy grids, and the behaviors of people using such roads at given periods of time. A disruption or shock to one of these systems can trigger effects upon others that rely upon it. As it becomes more necessary to prepare for events that have the potential to disrupt or destroy critical functionalities to particular practices or areas of action, it is quite likely that these, and other areas with highly complex and integrated infrastructure will increasingly embrace resilience thinking in the coming years.
Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues.

We report the structural analysis of highly drug-resistant human immunodeficiency virus protease (PR) variant PRS17, rationally selected by machine learning, in complex with substrate analogues. Crystal structures were solved of inhibitor-free inactive PRS17-D25N, wild-type PR/CA-p2 complex, and PRS17 in complex with substrate analogues, CA-p2 and p2-NC. Peptide analogues p2-NC and CA-p2 exhibit inhibition constants of 514 and 22 nM, respectively, for PRS17 or approximately 3-fold better than for PR. CA-p2 is a better inhibitor of PRS17 than are clinical inhibitors (Ki = 50–8390 nM) except for amprenavir (Ki = 11 nM). G48V resistance mutation induces curled flap tips in PRS17-D25N structure. The inner P2–P2′ residues of substrate analogues in PRS17 complexes maintain similar conformations to those of wild-type complex, while significant conformational changes are observed in the peripheral residues P3, P4′ of CA-p2 and P3, P4, and P3′ of p2-NC. The loss of β-branched side chain by V82S mutation initiates ...
DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism.

Comparison of ligand poses generated by protein–ligand docking programs has often been carried out with the assumption of direct atomic correspondence between ligand structures. However, this correspondence is not necessarily chemically relevant for symmetric molecules and can lead to an artificial inflation of ligand pose distance metrics, particularly those that depend on receptor superposition (rather than ligand superposition), such as docking root mean square deviation (RMSD). Several of the commonly-used RMSD calculation algorithms that correct for molecular symmetry do not take into account the bonding structure of molecules and can therefore result in non-physical atomic mapping. Here, we present DockRMSD, a docking pose distance calculator that converts the symmetry correction to a graph isomorphism searching problem, in which the optimal atomic mapping and RMSD calculation are performed by an exhaustive and fast matching search of all isomorphisms of the ligand structure graph. We show through evaluation of docking poses generated by AutoDock Vina on the CSAR Hi-Q set that DockRMSD is capable of deterministically identifying the minimum symmetry-corrected RMSD and is able to do so without significant loss of computational efficiency compared to other methods. The open-source DockRMSD program can be conveniently integrated with various docking pipelines to assist with accurate atomic mapping and RMSD calculations, which can therefore help improve docking performance, especially for ligand molecules with complicated structural symmetry.
Liberal arts student impressions of opportunities in gene editing

The completion of the human genome project led to advances both in technology and information availability. The potential of gene editing is tremendous. In the foreseeable future, scientists and doctors will be capable of repairing defective genes within humans (as is being done in other species) as a means to treat or potentially eliminate specific diseases. There are ethical dilemmas with the use of this technology, including who decides whether someone can or should be treated, and what diseases or traits should be altered. We surveyed undergraduate students from a variety of disciplines about some bioethical issues. With the data collected, we show that, in general, students are in favor of using gene editing technology to help cure disease in adults and children, but less willing to support the use in treating cells prior to fertilization. There is less support for altering non-disease characteristics (e.g. hair color, intelligence, or athletic ability), but male students tend to be more supportive of the use of this technology in this area than female students.
More Than a Click: Exploring College Students' Decision-Making Processes in Online News Sharing

Fake news can be disseminated on social media platforms due to users' inability to distinguish it from true news as well as the nature of heuristic-driven online sharing. We use in-depth semi-structured interviews with 20 college student social media users to help build a picture of their sharing processes that can help platform designers and operators better combat fake news dissemination. Participants reflected on specific recently shared news pieces, including how the stories attracted attention, why they shared them, and their behavior after sharing. Interview results revealed different cognitive processes people engaged: before, during and after sharing. Before sharing, participants assessed the news content and evaluated the social value of sharing the particular news piece. During sharing, the audience of the post was selected. After sharing, users examined the feedback from others and revisited previous sharing decisions. The study highlights that decisions about news sharing involve a myriad of different considerations throughout different cognitive stages. Based on these findings, we discuss design implications for combating the sharing of fake news.
Abstract A76: Efficacy of immunotherapy agents in patients with metastatic breast cancer treated in phase I clinical trials

Background: Immuno-oncology (IO) agents have demonstrated exceptional clinical benefit in patients with many tumor types, including melanoma and lung cancer. The PD-L1 inhibitor, atezolizumab, was recently FDA approved in combination with nab-paclitaxel for patients with PD-L1 positive triple-negative breast cancer (TNBC); however, single-agent PD-1/PD-L1 inhibitors demonstrate modest efficacy in breast cancer. The purpose of this study was to investigate the efficacy of IO agents in patients with metastatic breast cancer treated in phase I clinical trials. Methods: We performed a retrospective analysis using a database of patients with metastatic breast cancer who received treatment with IO agents in phase I/Ib clinical trials at the University of Colorado Anschutz Medical Campus from January 1, 2012 to July 1, 2018. Abstracted data included patient demographics, baseline characteristics, and clinical outcomes. Results: 208 patients with metastatic breast cancer were treated in phase I/Ib clinical trials; 43 were treated with an IO agent. The average age was 53 years old and 55.8% had hormone receptor-positive/HER2-negative breast cancer, 39.5% TNBC, and 4.6% HER2-positive disease. On average, patients received two prior lines of chemotherapy (range 0-7) in the metastatic setting. 31/43 patients (72.1%) received single agent or combination IO, and 12/43 (27.9%) received IO + chemotherapy. Median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 12.1 months in all patients. 9/43 (21%) of patients remained on study > 6 months and had a median PFS of 8.6 months. Patients remaining on study > 6 months were more likely to be treated with IO + chemotherapy compared to patients with a PFS 6 months compared to Conclusions: A subset of patients with metastatic breast cancer treated in phase I clinical trials at our center with an IO agent had derived prolonged clinical benefit. The benefit was not limited to patients with TNBC and was associated with receipt of chemotherapy in combination with IO. Predictors of response to immunotherapy in breast cancer beyond PD-L1 expression remain uncharacterized, and further research is needed to identify these factors. Citation Format: Jodi A. Kagihara, Jennifer A. Weiss, Andrew Nicklawsky, Dexiang Gao, Virginia F. Borges, Peter Kabos, Antonio Jimeno, Jennifer R. Diamond. Efficacy of immunotherapy agents in patients with metastatic breast cancer treated in phase I clinical trials [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A76.
An inhibitor of endothelial ETS transcription factors promotes physiologic and therapeutic vessel regression

During the progression of ocular diseases such as retinopathy of prematurity and diabetic retinopathy, overgrowth of retinal blood vessels results in the formation of pathological neovascular tufts that impair vision. Current therapeutic options for treating these diseases include antiangiogenic strategies that can lead to the undesirable inhibition of normal vascular development. Therefore, strategies that eliminate pathological neovascular tufts while sparing normal blood vessels are needed. In this study we exploited the hyaloid vascular network in murine eyes, which naturally undergoes regression after birth, to gain mechanistic insights that could be therapeutically adapted for driving neovessel regression in ocular diseases. We found that endothelial cells of regressing hyaloid vessels underwent down-regulation of two structurally related E-26 transformation-specific (ETS) transcription factors, ETS-related gene (ERG) and Friend leukemia integration 1 (FLI1), prior to apoptosis. Moreover, the small molecule YK-4-279, which inhibits the transcriptional and biological activity of ETS factors, enhanced hyaloid regression in vivo and drove Human Umbilical Vein Endothelial Cells (HUVEC) tube regression and apoptosis in vitro. Importantly, exposure of HUVECs to sheer stress inhibited YK-4-279–induced apoptosis, indicating that low-flow vessels may be uniquely susceptible to YK-4-279–mediated regression. We tested this hypothesis by administering YK-4-279 to mice in an oxygen-induced retinopathy model that generates disorganized and poorly perfused neovascular tufts that mimic human ocular diseases. YK-4-279 treatment significantly reduced neovascular tufts while sparing healthy retinal vessels, thereby demonstrating the therapeutic potential of this inhibitor.
Spectral guided sparse inverse covariance estimation of metabolic networks in Parkinson's disease

Abstract In neurodegenerative disorders, a clearer understanding of the underlying aberrant networks facilitates the search for effective therapeutic targets and potential cures. [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging data of brain metabolism reflects the distribution of glucose consumption known to be directly related to neural activity. In FDG PET resting-state metabolic data, characteristic disease-related patterns have been identified in group analysis of various neurodegenerative conditions using principal component analysis of multivariate spatial covariance. Notably, among several parkinsonian syndromes, the identified Parkinson's disease-related pattern (PDRP) has been repeatedly validated as an imaging biomarker of PD in independent groups worldwide. Although the primary nodal associations of this network are known, its connectivity is not fully understood. Here, we describe a novel approach to elucidate functional principal component (PC) network connections by performing graph theoretical sparse network derivation directly within the disease relevant PC partition layer of the whole brain data rather than by searching for associations retrospectively in whole brain sparse representations. Using sparse inverse covariance estimation of each overlapping PC partition layer separately, a single coherent network is detected for each layer in contrast to more spatially modular segmentation in whole brain data analysis. Using this approach, the major nodal hubs of the PD disease network are identified and their characteristic functional pathways are clearly distinguished within the basal ganglia, midbrain and parietal areas. Network associations are further clarified using Laplacian spectral analysis of the adjacency matrices. In addition, the innate discriminative capacity of the eigenvector centrality of the graph derived networks in differentiating PD versus healthy external data provides evidence of their validity.
Inspection of notch depths in thin structures using transmission coefficients of laser-generated Lamb waves.

Abstract The non-contact feature of the Laser/EMAT ultrasonic (LEU) technique is attractive for its NDT applications. However, it is challenging to apply it in thin structures because of the difficulties in the signal interpretations. In this work, the LEU technique is used to inspect the notch depths in thin steel plates. A Continuous Wavelet Transform (CWT)-based algorithm is developed to calculate the transmission coefficients of laser-generated Lamb waves. The effect of varying notch depths on Lamb waves’ transmission coefficients is investigated both numerically and experimentally. The transmission coefficients of laser-generated Lamb waves calculated using CWT have been used successfully to predict the notch depths in thin structures.
The Erosion of Coastal Sediment and Regeneration of Rhizophora mangle Following Anthropogenic Disturbance on Turneffe Atoll, Belize

i Acknowledgements iii List of Tables vi List of Figures vii Chapter 1: Introduction 1 Chapter 2: Erosion of Coastal Sediment Resulting From Anthropogenic Mangrove Clearing 4 Introduction 4 Methods 5 Study Site 5 Erosion Pins 9 Data Analysis 10 Results 11 Discussion 13 Chapter 3: Nutrients Enhance Rhizophora Mangle Seedling Regeneration, Turneffe Atoll, Belize 17 Introduction 17 Methods 20 Study Site 20 Anthropogenic Disturbance Events During Study 25 Field Observations and Sampling 25 Intact vs Cleared: Mortality and Growth Parameters ......... 25 Seedling Growth Experiment 26 v Statistical Analysis 28 Intact vs Cleared: Mortality 28 Intact vs Cleared: Growth Parameters 28 Site vs Local 28 Sediment Types 29 Treatments: Seedling Growth Experiment 29 Control vs Nutrient-Control 29 Treatments vs Sediment 30 Nutrient/Wave and Nutrient vs Intact Mangrove 30 Results 31 Intact vs Cleared: Mortality 31 Intact vs Cleared: Growth Parameters 32 Site vs Local 32 Sediment Types 34 Treatments: Seedling Growth Experiment 36 Control vs Nutrient-Control 36 Treatment vs Sediment 37 Treatment vs Site 41 Nutrient/Wave and Nutrient vs Intact Mangrove 45 Discussion 46 Chapter 4: Conclusions 54 Literature Cited 56
Treatment by bone-grafting of aseptic necrosis of the femoral head and non-union of the femoral neck (Phemister technique).

An evaluation has been made of the effect of drilling and bone-grafting for non-union of the fractured femoral neck or aseptic necrosis of the femoral head, or both, in fifty-three patients. The results show that the procedure is effective in restoring continuity to the ununited femoral-neck fracture, and viability to the necrotic femoral head in a sufficient number of instances to warrant its consideration in the management of these complications.
A Framework for Databasing 3D Synthetic Environment Data

Since 1994 the Digital Mapping, Charting and Geodesy Analysis Program at the Naval Research Laboratory has been developing an object-oriented spatial and temporal database, the Geographic Information Database (GIDB™). Recently, we have expanded our research in the spatial database area to include three-dimensional synthetic environment (3D SE) data. This work has focused on investigating an extension to the National Imagery and Mapping Agency's (NIMA's) current Vector Product Format (VPF) known as VPF+. This paper overviews the GIDB and describes the data structures of VPF+ and a prototyped 3D synthetic environment using VPF+. The latter was designed as a 3D Geographic Information System (3D-GIS) that would assist the U.S. Marine Corps with mission preparation and also provide onsite awareness in urban areas.
Narrative Development in Improvisational Theatre

We have investigated the experience of improvisers as they perform to better understand how narrative is constructed by group performance in improvisational theatre. Our study was conducted with improvisers who would perform improv "games" with each iteration video recorded. Each individual participant was shown the video in a retrospective protocol collection, before reviewing it again in a group interview. This process is meant to elicit information about how the cognition involved develops narrative during an improvisation performance. This paper presents our initial findings related to narrative development in improvisational theatre with an ambition to use these and future analyses in creating improvisational intelligent agents. These findings have demonstrated that the construction of narrative is crafted through the making and accepting of scene-advancing offers, which expert improvisers are more readily capable of performing.
Market Share Liability and Its Alternatives

An injured party can sometimes identify the class of product that injured her, but not the particular firm that was the source of harm. One possible approach to liability is a rule based on the market shares of the firms. Some commentators have argued that this approach violates the identification requirement and rarely yields efficient incentives for the reduction of harm; their favored alternative apparently is to impose no liability on defendants. While we agree that market share liability will only rarely yield the perfectly efficient solution, a standard of perfect efficiency is unrealistic, since most situations where market share liability is proposed are ones of imperfect information and thus where a perfectly efficient remedy is unobtainable. We compare the efficiency of the market share liability approach to two alternatives: no liability (i.e., victim liability), and multiple joint and several with no contribution that is, placing 100% of the industry's liability on each defendant. We argue that efficiency often dictates increasing liability from the market-share standard, rather than reducing it to zero.
A Comparison of Independent Depression and Substance‐Induced Depression in Cannabis‐, Cocaine‐, and Opioid‐Dependent Treatment Seekers

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs—independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused—cannabis, cocaine, and opioids—are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n = 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p < .005). Cannabis dependence was highly associated with independent depression (p < .001), while cocaine dependence was highly associated with substance-induced depression (p < .05). Independent depression was associated with higher Hamilton depression scale scores (16 vs. 10, p < .005), and was more highly associated with the comorbid diagnosis of posttraumatic stress disorder (p < .05). Cannabis dependence (p < .001) and female gender (p < .05) were highly significant predictors of major depression specifically. Gender, cannabis dependence, psychiatric severity, and psychiatric comorbidity have variable, statistically significant associations with independent and substance-induced depression, and may be helpful in guiding the diagnostic process. (Am J Addict 2011;00:1–6)
Effect of activated charcoal on ethanol blood levels in dogs

The effect of activated charcoal on ethanol blood levels following oral administration of ethanol was studied. Six healthy laboratory dogs were administered 2 ml/kg of 95% ethanol diluted to a 20% solution. Blood ethanol concentrations were measured at 0.5, 1.2, and 3 hours after dosing. After a one-week washout period, the same animals received an identical dose of ethanol preceded by 50 g of activated charcoal in a water slurry. Blood ethanol concentrations were again determined. Absorption of ethanol was significantly (p less than 0.005) inhibited by activated charcoal during the first hour after administration. Blood ethanol levels remained significantly lower (p less than 0.025) throughout the study in the activated charcoal group. Especially during the initial, critical hours of therapy, activated charcoal can significantly reduce the desired blood ethanol concentration required when ethanol is used as an emergency antidote for methanol or ethylene glycol poisonings. The use of activated charcoal is discouraged in poisoning emergencies where such oral-antidote therapy is necessary.
Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound.

Retinoic acid receptor alpha (RARα) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer. Herein we report a modified synthesis of a known RARα antagonist, 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid. The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step. Structure–activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RARα for both compounds. Molecular modeling within the RARα binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist.
Design, Modeling and Validation of a T-Tail Unmanned Aerial Vehicle

This paper addresses the design and modeling process of a T-tail unmanned aerial vehicle (UAV). A methodology is presented of how to make tradeoffs among the payload requirements, energy efficiency and aerodynamic stability. A linear decoupled model of longitudinal and lateral dynamics is abstracted from a physical airframe. Instead of subjectively estimating the order, error and time delay for system identification (system ID), equations of motion derived from aerodynamics are employed to provide more precise estimation of the model structure. System ID is carried out with regard to the flight data collected by the autopilot data logger. The resulted model is refined based on the simulation and comparison.
Taking total control of voting systems: firmware manipulations on an optical scan voting terminal

The firmware of an electronic voting machine is typically treated as a "trusted" component of the system. Consequently, it is misconstrued to be vulnerable only to an insider attack by someone with an in-depth knowledge of the system and access to the source code. This case study focuses on the Diebold/Premier AccuVote Optical Scan voting terminal (AV-OS) that is widely used in the USA elections. We present three low level manipulations of the above voting terminal's firmware resulting in divergence from its prescribed operation: (i) the first bestows the terminal with a powerful memory card dumping functionality, (ii) the second enables the terminal to leak the ballot details through its serial port thus violating voter privacy during the election, (iii) the final third firmware manipulation is a proof of concept attack that swaps the votes of two candidates thus permanently destroying the election outcome in an undetectable fashion. This demonstrates the extent to which the firmware of the AV-OS can be modified with no insider knowledge or access to the source code.Our results underscore the importance of verifying the integrity of the firmware of electronic voting terminals accompanied by sound auditing procedures to maintain the candor of the electoral process. We also note that this work is performed solely with the purpose of security analysis of AV-OS, and the first and the second firmware manipulations we describe serve a dual purpose in assisting the technological audits of actual voting procedures conducted using AV-OS systems.
Persistence of 10-year old Exxon Valdez oil on Gulf of Alaska beaches: The importance of boulder-armoring

Oil stranded as a result of the 1989 Exxon Valdez spill has persisted for >10 years at study sites on Gulf of Alaska shores distant from the spill's origin. These sites were contaminated by "oil mousse", which persists in these settings due to armoring of underlying sediments and their included oil beneath boulders. The boulder-armored beaches that we resampled in 1999 showed continued contamination by subsurface oil, despite their exposure to moderate to high wave energies. Significant declines in surface oil cover occurred at all study sites. In contrast, mousse has persisted under boulders in amounts similar to what was present in 1994 and probably in 1989. Especially striking is the general lack of weathering of this subsurface oil over the last decade. Oil at five of the six armored-beach sites 10 years after the spill is compositionally similar to 11-day old Exxon Valdez oil. Analysis of movements in the boulder-armor that covers the study beaches reveals that only minor shifts have occurred since 1994, suggesting that over the last five, and probably over the last 10 years, boulder-armors have remained largely unmoved at the study sites. These findings emphasize the importance of particular geomorphic parameters in determining stranded oil persistence. Surface armoring, combined with stranding of oil mousse, results in the unexpectedly lengthy persistence of only lightly to moderately weathered oil within otherwise high-energy wave environments.
SSR markers closely linked to the Pi-z locus are useful for selection of blast resistance in a broad array of rice germplasm

Pi-z is a disease resistance gene that has been effectively used to combat a broad-spectrum of races of the rice blast fungus Magnaporthe grisea. Although DNA markers have been reported for selection of the Pi2(t) and Pi-z resistance genes at the Pi-z locus, markers that are more tightly linked to the Pi-z locus would benefit rapid and effective cultivar development. Analysis of the publicly available genome sequence of Nipponbare near the Pi-z locus revealed numerous SSRs that could be converted into markers. Three SSRs on rice PAC AP005659 were found to be very tightly linked to the Pi-z locus, with one marker, AP5659-3, co-segregating with the Pi-z resistance reaction. The Pi-z factor conferring resistance to two races of blast was mapped to a 57 kb region on the physical map of Nipponbare in a location where the Pi2(t) gene was physically mapped. Two SSR marker haplotypes were unique for cultivars carrying the Pi-z gene, which indicates these markers are useful for selection of resistance genes at the Pi-z locus in rice germplasm.
Computer-mediated instruction: a comparison of online and face-to-face collaboration

This study investigated the effects of collaboration mode and group composition during a computer-mediated collaborative (CMC) program. Six intact sections of a computer literacy course were assigned to either a face-to-face or a virtual, online collaboration treatment condition. Groups consisted of homogeneous lower-ability, homogeneous higher-ability, or heterogeneous-ability pairs. The study examined the effects of collaboration mode and group composition on individual posttest performance, group project performance, collaborative interaction behavior, and attitudes towards the instruction. Results indicated that virtual dyads exhibited significantly more questioning behaviors and significantly better project performance than those who collaborated face-to-face. By comparison, students in the face-to-face condition performed significantly better on the individual posttest than those in the virtual online condition. Findings suggest that both virtual and face-to-face collaboration can be effective in achieving learning goals. However, consideration should be given to the collaborative structure of the lesson and the type of task in the design of CMC environments.
Particle size effects on Lagrangian turbulence

Perturbation methods are used to show that the equations of motion for a small rigid sphere in a steady laminar flow take the form of a dynamical system in which phase volume is not conserved. In the absence of stagnation points, particle inertia and virtual mass effects destroy Lagrangian turbulence and the particles are captured by periodic or quasiperiodic orbits that are associated with the vortices of the flow. When gravitational effects are included, it is found that point particles can sediment chaotically, but that particle inertia and virtual mass effects tend to eliminate the chaotic behavior. An interesting consequence of the latter phenomenon is that finite particles which are denser than the fluid can be permanently suspended in three‐dimensional cellular flows. Numerical results are presented for the Arnold–Beltrami–Childress [C. R. Acad. Sci. Paris 261, 17 (1965)] flows.
Probe-induced distortions in the sampling of one-dimensional flames

A procedure is developed for estimating the influence of a probe on the temperature and residence time distribution of gases sampled from a one-dimensional flame. Estimates are made for stoichiometric methane-oxygen-argon flames at4 and 105 Pa, with particular attention devoted to the influence of the included angle and orifice diameter of the probe. Significant temperature distortions are predicted in the mean temperature of the sampled gas, with the largest distortions corresponding to large cone angles and small orifice diameters. Calculated residence time distributions are found to broaden as the orifice diameter is increased, whereas the mean residence time is essentially unchanged. The residence time distribution is compared with characteristic times for chemical reaction in an effort to characterize composition distributions resulting from homogeneous processes.
Family developmental task assessment: A prerequisite to family treatment

This paper presents a developmental framework for assessing family function. It integrates family systems theory and ego psychological knowledge of growth. The framework organizes family information along four developmental lines, and a socio-biological stressor scale. Although this paper is only a beginning conceptualization and outline, it is hoped that with further study it can lead to family diagnosis and more definitive family treatment.
Sperner's theorem on maximal-sized antichains and its generalization

This paper generalizes previous work by Sperner [8], Erdos [2], Kleitman [5], Katona [3], DeBruijn et al. [1], and Schonheim [7]. Such generalization not only leads to simple proofs of known results but also sharpens some of these results.
A hybrid approach to nonlinear system stability and performance

The problems of stability and performance for nonlinear feedback systems are examined. A hybrid approach that combines input-output and state-space theories is proposed. Within this framework the notions of dynamic gain and dynamic incremental gain of a nonlinear operator are reexamined and their inability to accurately reflect the dynamic behavior of a physical system is demonstrated. The concepts of dynamic gain and dynamic incremental gain over sets are introduced and their connection to a physical system's dynamic behavior is established. Theorems are developed that allow the systematic computation of these gains through nonsmooth optimal control theory. Illustrative examples are provided throughout the paper.
Shear Stress Overshoots in Flow Inception of Semiflexible Thermotropic Liquid Crystalline Polymers: Experimental Test of a Parameter-Free Model Prediction

We explore the origins of shear stress overshoots upon flow inception of main-chain thermotropic liquid crystalline polymers from a random polydomain initial condition. A simple polydomain simulation strategy, based on Ericksen's transversely isotropic fluid model, is capable of predicting a shear stress overshoot arising from the reorientation dynamics of domains toward a steady state flow aligned state. When model parameters are estimated using elementary molecular theories for semiflexible main-chain thermotropes, both the relative magnitude of the shear stress overshoot and the steady state ratio of first normal stress difference to shear stress are determined solely by the “tumbling” parameter, λ. This implies a universal correlation between these two variables. We test this prediction against an extensive data set on semiflexible polyesters and find good qualitative agreement between model and experiment.
Varied responses in gene expression of culturable heterotrophic bacteria isolated from the environment

Gene expression in heterotrophic bacteria isolated from environmental samples was studied using a combination of non-selective and selective plating techniques and gene probe methodology. The gene probes and their respective phenotypes were nahAB, for naphthalene degradation, merA, for narrowlspectrum mercury resistance, and merB, for broad-spectrum mercury resistance. Gene-probe-positive organisms could be placed into one of three categories: (1) organisms that could express their genetic information immediately upon isolation from the environment; (2) organisms that expressed their genotype only after cultivation before selection for the genotype; and (3) organisms that did not express their genotype at all in our hands. For all three probes it was found that most organisms fell into category 2. This phenomenon was also observed with bacteria isolated from lake water that probed positive with the nitrogenase (nifHDK) gene probe. The data suggest that the numbers of isolates identified by gene probes merely reflect the genetic potential of a community whereas various expression data suggest that differences in the actual activity of those genotypes exist in the natural environment.
An assessment of the accuracy of self-assessment for career decision making

Abstract During the past few years, there has been a marked increase in the number of publications which focus on advice for individuals engaged in the process of career decision making. Most of these publications rely on self-assessment as the major input to the decision making process. This study compared the accuracy of self-assessment to expert assessment based on an assessment center procedure for a sample of potential college graduates. Significant discrepancies were found between the student's and assessor's ratings on 10 of the 13 dimensions assessed. Implications of these results are discussed and suggestions for further study are made.
GLIOMA STEM CELL HOMING TO THE HUMAN SUBVENTRICULAR ZONE

BACKGROUND: (blind field) METHODS: Using intraoperatively-derived human tissue, we employ a combination of cell culture, FACS-sorting, and immunohistochemistry techniques to characterize human glioma and GSC homing to the SVZ, as well as identify new, targetable cytokine pathways relevant to this niche. RESULTS: Our analysis identifies glioma cells homing to human SVZ and co-opting the gap layer for tangential migration. Interestingly, we find that human SVZ-invasive glioma cells are 50-fold more likely to function as glioma stem cells. Organotypic slice culture and co-culture assays also identify chemotactic effects, associated integrins, and related extracellular matrix proteins of 3 SVZ-enriched ligands (EGF, PDGF-BB, and SDF1) known to drive pro-migratory glioma pathways. CONCLUSIONS: Despite its quiescence, the adult human SVZ retains the signaling machinery to support cell migration and these mechanisms may be co-opted by glioma stem cells during subependymal spread in humans. SECONDARY CATEGORY: n/a.
Leptomycin B stabilizes and activates p53 in primary prostatic epithelial cells and induces apoptosis in the LNCaP cell line.

Background Previous studies showed that primary cultures of normal and malignant human prostatic epithelial cells are defective in their ability to upregulate the tumor suppressor protein p53 in response to DNA damage. This dysfunctional regulation of p53 may be relevant to both the high incidence of prostate cancer and its resistance to chemotherapy. Leptomycin B (LMB) has recently been found to increase the protein level and transcriptional activity of p53 by interfering with nucleocytoplasmic export and subsequent degradation by the proteasome. We investigated the ability of LMB to activate p53 in prostatic epithelial cells. Methods Primary cultures and the cell lines LNCaP and DU 145 were treated with LMB. p53 protein was evaluated in Western blots and by immunocytochemistry. Induction of downstream targets of p53 was evaluated in Western and Northern blots. Growth inhibition, cell cycle arrest, and apoptosis in response to LMB were measured in clonal growth assays, by flow cytometry, and by Hoescht/propidium iodide staining, respectively. Results Treatment of prostatic epithelial cells with LMB led to post-translational stabilization of p53, activation of downstream target genes, and induction of cell cycle arrest in primary cultures and apoptosis in LNCaP (with wild-type p53) but not DU 145 (with mutant p53) cells. Conclusions p53 in primary cultures of normal and malignant prostate cells, although dysfunctional in that it is not responsive to DNA damage, is activated by LMB. The ability of LMB to stabilize p53 and induce expression of p53-responsive growth inhibitory genes may be a useful lead in the development of chemopreventive or therapeutic small molecules that can modulate p53 function in prostatic epithelial cells. Prostate 54: 258–267, 2003. © 2003 Wiley-Liss, Inc.
The radially swollen 4 separase mutation of arabidopsis thaliana blocks chromosome disjunction and disrupts the radial microtubule system in meiocytes

The caspase-family protease, separase, is required at the onset of anaphase to cleave the cohesin complex that joins replicated sister chromatids. However, in various eukaryotes, separase has acquired additional and distinct functions. A single amino-acid substitution in separase is responsible for phenotypes of the Arabidopsis thaliana mutant, radially swollen 4 (rsw4). This is a conditional mutant, resembling the wild type at the permissive temperature (∼20°C) and expressing mutant phenotypes at the restrictive temperature (∼30°C). Root cells in rsw4 at the restrictive temperature undergo non-disjunction and other indications of the loss of separase function. To determine to what extent separase activity remains at 30°C, we examined the effect of the mutation on meiosis, where the effects of loss of separase activity through RNA interference are known; and in addition, we examined female gametophyte development. Here, we report that, at the restrictive temperature, replicated chromosomes in rsw4 meiocytes typically fail to disjoin and the cohesin complex remains at centromeres after metaphase. Meiotic spindles appear normal in rsw4 male meiocytes; however the mutation disrupts the radial microtubule system, which is replaced by asymmetric arrays. Surprisingly, female gametophyte development was relatively insensitive to loss of separase activity, through either rsw4 or RNAi. These effects confirm that phenotypes in rsw4 result from loss of separase activity and establish a role for separase in regulating cell polarization following male meiosis.