cssi/SciSciGPT-SciSciNet huggingface dataset:
Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1)

The nuclear erythroid 2-like 2 transcription factor (NRF2), is a major regulator of cellular redox balance. Although NRF2 activation is generally regarded as beneficial to human health, recent studies have identified that sustained NRF2 activation is over-represented in many cancers. This raises the question regarding the role of NRF2 activation in the development and progression of those cancers. This review focuses on the mechanisms and the effects of NRF2 activation in two hereditary cancer predisposition syndromes: hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary tyrosinemia type 1 (HT1). Because the cancer initiating mutations in these hereditary syndromes are well defined, they offer a unique opportunity to explore the roles of NRF2 activation in the early stages of carcinogenesis. Over the years, a variety of approaches have been utilized to study the biology of HLRCC and HT1. In HLRCC, in vitro studies have demonstrated the importance of NRF2 activation in sustaining cancer cell proliferation. In the mouse model of HT1 however, NRF2 activation seems to protect cells from malignant transformation. In both HT1 and HLRCC, NRF2 activation promotes the clearance of electrophilic metabolites, enabling cells to survive cancer-initiating mutations. Biological insights gained from the hereditary syndromes’ studies may shed light on to the roles of NRF2 activation in sporadic tumours. * CUL3, : CULLIN 3; FAA, : fumarylacetoacetate; FAH, : fumarylacetoacetate hydrolase gene; FH, : fumarate hydratase; FN, : Fah/Nrf2 double knockout; HCC, : hepatocellular carcinoma; HLRCC, : hereditary leiomyomatosis and renal cell cancer; HPD, : 4-hydroxyphenylpyruvate dioxygenase; Ht1, : hereditary tyrosinemia type 1; KEAP1, : Kelch-like ECH-associated protein 1; LOH, : loss-of-heterozygosity; NRF2, : nuclear erythroid 2-like 2 transcription factor; NTBC, : 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione; PRCC2, : type 2 papillary renal cell carcinoma; ROS, : radical oxygen species; TCA, : tricarboxylic acid
Are We Putting the Cart Before the Horse? A Microcosm of Intended and Unintended Outcomes of Electronic Medical Record Implementation

Leaders in health care are calling for the implementation of electronic medical records (EMR) systems to help alleviate high costs of care delivery, high error rates, and uneven access to care. However, many of these leaders seem to be overlooking unintended outcomes of EMR implementation. Specifically, they may be overlooking the critical role physician beliefs and relationships play in the use of EMRs and in generating both intended and unintended outcomes. We studied a microcosm of the health care system through a qualitative field study examining EMR use in four clinics operating within a multi-specialty medical organization. We found that beliefs held by physicians about medical practice and the patterns of relationships in clinics influence EMR use behaviors in both expected and unexpected ways. Our contribution is to call attention to unintended outcomes of EMR implementation and to suggest that EMRs can be used as artifacts for learning.
What Can Science Do for the President

In Sputnik's Shadow . The President's Science Advisory Committee and Cold War America. By Zuoyue Wang . Rutgers University Press, New Brunswick, NJ, 2008. 477 pp. $49.95. ISBN 9780813543314. Through his examination of the functioning and effectiveness of the U.S. President's Science Advisory Committee, Wang explores the evolution of scientists' roles in executive policy-making during the 1950s and 1960s.
Differential absorption lidar detection of ozone in the troposphere and lower stratosphere

The distribution of ozone (O3), in the atmosphere has important implications for pollution, chemistry, and climate related processes in the troposphere and for the screening of solar ultraviolet radiation, chemistry, and thermal equilibrium in the stratosphere. The large spatial variability of O3 in the troposphere and in the vicinity of O3 depletion episodes in the stratosphere makes in situ sampling of O3 from balloons and aircraft inadequate for these types of O3 investigations. The Differential Absorption Lidar (DIAL) technique has been used since the early 1970’s for ground-based remote measurements of O3 and aerosols in the lower atmosphere. This has permitted frequent measurements of O3 and aerosols in the lower atmosphere. This has permitted frequent measurements of O3 profiles above or around a specific location, which is an improvement over infrequent balloon measurements and even more infrequent aircraft measurements. To address the regional- and large-scale processes associated with O3 transport and chemistry, an airborne DIAL system was developed in 1980 at the NASA Langley Research Center (LaRC) for the measurement of O3 and aerosol distributions along the aircraft ground track. This DIAL system currently has the capability to measure O3 and multiple-wavelength aerosol profiles to a range of over 8 km above and below the aircraft simultaneously. Over 12 major field experiments have been conducted with the NASA airborne DIAL system since 1980 to study the transport and chemistry related to O3 and aerosols.
Central respiratory control of A5 and A6 pontine noradrenergic neurons

Sympathetic nerve discharge (SND), phrenic nerve discharge (PND), and unit activity of locus ceruleus (LC) and of putative A5 noradrenergic cells were recorded in vagotomized rats anesthetized with urethan. SND was activated by stimulation of carotid chemoreceptors with hypoxia (N2 inhalation, 5-15 s or 12% O2 inhalation, 2-5 min) and displayed a prominent central respiratory modulation during the hypoxic challenge (postinspiratory pattern). LC cells were also activated by peripheral chemoreceptor stimulation. The discharge of most LC units (28 of 31) exhibited central respiratory modulation. 15 LC units had a postinspiratory pattern and 11 had an inspiratory one. Putative A5 cells were also excited by hypoxia and also displayed a clear central respiratory modulation (mostly postinspiratory pattern). These experiments indicate that 1) the firing rate of most pontine noradrenergic cells is increased by peripheral chemoreceptor stimulation, and 2) pontine noradrenergic neurons receive afferent information of a respiratory nature, possibly from their ventrolateral medullary inputs.
Heat Transfer Analysis of the Thermoplastic Filament Winding Process

The quality of thermoplastic composites depends on the thermal history during processing. Therefore it is important to determine the temperature distribution in the composite during the fabrication process. An ABAQUS transient heat transfer finite element model of the thermoplastic filament winding process was developed and used to predict the temperature inside the composite-mandrel assembly. The model relates the material properties, the winding speed, and the hot-gas heater temperature to thermal response of the composite. The results show that the predicted temperature distributions agree well with the temperature data measured during winding and consolidation.
Timing of Tone Presentation Does Alter Training Performance but Not Retention Performance of a Point-to-Point Sequence Task

Objective: To investigate whether the timing of presentation of tones while practicing a serial reaction time task affects retention. Design: Thirty-eight young adults practiced 4 different 12-sequence aiming tasks. There was one control condition without a tone and three experimental conditions in which a tone was presented; i.e., a tone could appear before the next target onset, at the next target onset, or after the next target onset. Sequence learning for each condition was assessed with a retention block in which no tones were presented. Performance changes as compared to the control condition were analyzed to assess if acquisition and/or learning was affected by the presentation of the tones. Results: Tone condition affected mainly reaction time. It was shown that if a tone was presented 150 ms before displaying the next target in the sequence the reaction time of the aiming movement decreased significantly. Furthermore, it was shown that tone onset 150 ms before target presentation and tone onset at target presentation resulted in a benefit during acquisition after block 5 and 6 respectively. However, the benefit disappeared during retention, because none of the tone conditions showed differential performance as compared to the control condition. Conclusions: Timing of tones affects the acquisition of serial reaction time tasks, but it does not alter learning. It is suggested that this pattern of findings supports the notion that tones result in a non-specific activation of the motor system, which affect immediate performance but not learning.
Extending NMR data for permeability estimation in fine-grained sediments

Abstract We combine nuclear magnetic resonance (NMR) transverse relaxation time data and gamma ray data to estimate lithology-dependent permeability in silt- and clay-rich sediments. This approach extends the utility of the Schlumberger-Doll Research (SDR) permeability equation from reservoirs to aquicludes and seals, and thus improves the value and robustness of NMR data. Data from Keathley Canyon, northern Gulf of Mexico show that NMR data can be used to define permeability from 10 −18 to 10 −14 m 2 (0.001–10 millidarcies) as calibrated and tested by direct measurements on core samples. We performed uniaxial, constant rate-of-strain consolidation experiments on sediments from Keathley Canyon to determine core-scale permeability. Permeabilities from these experiments were compared to permeabilities calculated from logging-while-drilling data. A better fit between log-derived permeability and laboratory-measured permeability was obtained using the SDR equation with a variable coefficient A , rather than a constant A as is typically used. We show how A is a function of lithology and can be modeled from gamma ray data. The relationship between A and gamma ray values suggests that variations in A are caused by platy clay minerals and the effect they have on the pore system. Our results provide improved means for permeability estimation for application in basin flow modeling, hydrocarbon migration modeling, and well completion design.
Design of guaranteed safe maneuvers using reachable sets: Autonomous quadrotor aerobatics in theory and practice

For many applications, the control of a complex nonlinear system can be made easier by modeling the system as a collection of simplified hybrid modes, each representing a particular operating regime. An example of this is the decomposition of complex aerobatic flights into sequences of discrete maneuvers, an approach that has proven very successful for both human piloted and autonomously controlled aircraft. However, a critical step when designing such control systems is to ensure the safety and feasibility of transitions between these maneuvers. This work presents a hybrid dynamics framework for the design of guaranteed safe switching regions and is applied to a quadrotor helicopter performing an autonomous backflip. The regions are constructed using reachable sets calculated via a Hamilton-Jacobi differential game formulation, and experimental results are presented from flight tests on the STARMAC quadrotor platform.
Is the Bad Lot Objection Just Misguided

In this paper, I argue that van Fraassen’s “bad lot objection” against Inference to the Best Explanation [IBE] severely misses its mark. First, I show that the objection holds no special relevance to IBE; if the bad lot objection poses a serious problem for IBE, then it poses a serious problem for any inference form whatever. Second, I argue that, thankfully, it does not pose a serious threat to any inference form. Rather, the objection misguidedly blames a form of inference for not achieving what it never set out to achieve in the first place.
Replacing Asn207 by aspartate at the neck of the D channel in the aa3-type cytochrome c oxidase from Rhodobacter sphaeroides results in decoupling the proton pump.

Cytochrome oxidase catalyzes the reduction of O2 to water and conserves the considerable free energy available from this reaction in the form of a proton motive force. For each electron, one proton is electrogenically pumped across the membrane. Of particular interest is the mechanism by which the proton pump operates. Previous studies of the oxidase from Rhodobacter sphaeroides have shown that all the pumped protons enter the enzyme through the D channel, and that a point mutant, N139D, in the D channel completely eliminates proton pumping without reducing the oxidase activity. N139 is one of three asparagines near the entrance of the D channel where there is a narrowing or neck, through which a single file of water molecules pass. In the current work, it is shown that replacement of a second asparagine in this region by an asparate, N207D, also decouples the proton pump without altering the oxidase activity of the enzyme. Previous studies demonstrated that the N139D mutant results in an increase in the apparent pKa of E286, a functionally critical residue which is located 20 A away from N139 at the opposite end of the D channel. In the current work, it is shown that the N207 mutation also increases the apparent pKa of E286. This finding re-enforces the proposal that the elimination of proton pumping is the result of an increase of the apparent proton affinity of E286 which, in turn, prevents the timely proton transfer to a proton accepter group within the exit channel of the proton pump.
The Conversational Geography of Word-of-Mouth Communication and Marketing Practices

This study was a test of the utility of a diary-based methodology for revealing how word-of-mouth (WOM) marketing agents perceive their campaign and non-campaign-related WOM communication episodes. A modified version of the Iowa Communication Record, originally designed for presenting the “geography of everyday conversation,” was the base for the collection of 2,088 self-reports of the agents' WOM episodes. Data were subjected to a principal components factor analysis. The resulting factors—communication quality, value, impact, relational change, and conversational control—served to gauge differences attributable to the institutional nature of the WOM, sex of respondent and conversational partner, relationship type, and day of week.
Longevity of moons around habitable planets

We consider tidal decay lifetimes for moons orbiting habitable extrasolar planets using the constant Q approach for tidal evolution theory. Large moons stabilize planetary obliquity in some cases, and it has been suggested that large moons are necessary for the evolution of complex life. We find that the Moon in the Sun–Earth system must have had an initial orbital period of not slower than 20 h rev−1 for the moon's lifetime to exceed a 5 Gyr lifetime. We assume that 5 Gyr is long enough for life on planets to evolve complex life. We show that moons of habitable planets cannot survive for more than 5 Gyr if the stellar mass is less than 0.55 and 0.42 M ⊙ for Q p=10 and 100, respectively, where Q p is the planetary tidal dissipation quality factor. Kepler-62e and f are of particular interest because they are two actually known rocky planets in the habitable zone. Kepler-62e would need to be made of iron and have Q p=100 for its hypothetical moon to live for longer than 5 Gyr. A hypothetical moon of Kepler-62f, by contrast, may have a lifetime greater than 5 Gyr under several scenarios, and particularly for Q p=100.
Constraining pathways of microbial mediation for carbonate concretions of the Miocene Monterey Formation using carbonate-associated sulfate

Abstract Carbonate concretions can form as a result of organic matter degradation within sediments. However, the ability to determine specific processes and timing relationships to particular concretions has remained elusive. Previously employed proxies (e.g., carbon and oxygen isotopes) cannot uniquely distinguish among diagenetic alkalinity sources generated by microbial oxidation of organic matter using oxygen, nitrate, metal oxides, and sulfate as electron acceptors, in addition to degradation by thermal decarboxylation. Here, we employ concentrations of carbonate-associated sulfate (CAS) and δ34SCAS (along with more traditional approaches) to determine the specific nature of concretion authigenesis within the Miocene Monterey Formation. Integrated geochemical analyses reveal that at least three specific organo-diagenetic reaction pathways can be tied to concretion formation and that these reactions are largely sample-site specific. One calcitic concretion from the Phosphatic Shale Member at Naples Beach yields δ34SCAS values near Miocene seawater sulfate (∼+22‰ VCDT), abundant CAS (ca. 1000 ppm), depleted δ13Ccarb (∼−11‰ VPDB), and very low concentrations of Fe (ca. 700 ppm) and Mn (ca. 15 ppm)—characteristics most consistent with shallow formation in association with organic matter degradation by nitrate, iron-oxides and/or minor sulfate reduction. Cemented concretionary layers of the Phosphatic Shale Member at Shell Beach display elevated δ34SCAS (up to ∼+37‰), CAS concentrations of ∼600 ppm, mildly depleted δ13Ccarb (∼−6‰), moderate amounts of Mn (ca. 250 ppm), and relatively low Fe (ca. 1700 ppm), indicative of formation in sediments dominated by sulfate reduction. Finally, concretions within a siliceous host at Montana de Oro and Naples Beach show minimal CAS concentrations, positive δ13C values, and the highest concentrations of Fe (ca. 11,300 ppm) and Mn (ca. 440 ppm), consistent with formation in sediments experiencing methanogenesis in a highly reducing environment. This study highlights the promise in combining CAS analysis with more traditional techniques to differentiate among diagenetic reactions as preserved in the geologic record and shows potential for unraveling subsurface biospheric processes in ancient samples with a high degree of specificity.
Literacy Challenges and Opportunities for Students with Learning Disabilities in Social Studies and History

The Common Core State Standards for literacy in history and social studies present opportunities and challenges for teachers of and adolescents with learning disabilities (LD). In addition to reading challenges, students must engage in higher order thinking and reasoning. To provide opportunities for students to successfully respond to such challenges, teachers must have an understanding of the expectations in the Standards, and of the learning needs of students with LD. Teachers can assure success for adolescents with LD by selecting proven instructional procedures and engaging in collaboration to provide students with the supports they need. Examples of one evidence-based practice, Content Enhancement, are provided to illustrate instructional protocols for teachers of diverse classes that include adolescents with LD.
Screening designs for model discrimination

We introduce new criteria for model discrimination and use these and existing criteria to evaluate standard orthogonal designs. We show that the capability of orthogonal designs for model discrimination is surprisingly varied. In fact, for specified sample sizes, number of factors, and model spaces, many orthogonal designs are not model discriminating by the definition given in this paper, while others in the same class of orthogonal designs are. We also use these criteria to construct optimal two-level model-discriminating designs for screening experiments. The efficacy of these designs is studied, both in terms of estimation efficiency and discrimination success. Simulation studies indicate that the constructed designs result in substantively higher likelihoods of identifying the correct model.
Polyurethanes from Vegetable Oils

Vegetable oils are excellent but very heterogeneous renewable raw materials for polyols and polyurethanes. This review discusses the specific nature of vegetable oils and the effect of their structures on the structure of polyols and polyurethanes. One section is dedicated to polyols for rigid and flexible foams and methods of their preparation such as direct oxidation of oils, epoxidation followed by ring opening, hydroformylation, ozonolysis, and transesterification. The next section deals with preparation and structure‐property relationships in polyurethanes from different groups of polyols, different isocyanates, and different degrees of crosslinking. The final section covers the environmental aspects of bio‐based polyurethanes, i.e., thermal stability, hydrolytic stability, and some aspects of biodegradability.
Modeling of buildings: evolution and concepts

Abstract This presentation reviews the concepts of building modeling as they evolved historically, through research and previous and current products. It points out some limitations of current systems and concepts and identifies some additional ones that will probably be integrated into an eventual production quality building model.
Induction of interleukin‐1/and interleukin‐8 mRNAs and proteins by TGFβ1 in rat lung alveolar epithelial cells

The transforming growth factor-beta (TGF-beta) has been shown to increase in lung injury and in fibrotic states of the lung. In the current study, we sought to investigate whether TGF beta 1 induced the expression of IL-1 alpha and IL-8 in rat alveolar epithelial cells. We evaluated TGF beta 1, IL-1 alpha, and IL-8 expression by immunofluorescence in silica-injured and saline-treated control rat lungs. Antibodies to IL-1 alpha, IL-8, and TGF beta 1 showed intense staining in silica-injured lungs as compared to saline-instilled lungs. Primary isolated type II cells from silica-injured lungs showed increased expression of IL-1 alpha as compared to saline-instilled lungs. To evaluate the effects of TGF beta 1, we treated an immortalized rat type II cell-derived cell line (LM5) with 100 pg/ml of TGF beta 1 in serum-free medium for 0-24 hours and analyzed the expression of IL-1 alpha and IL-8 mRNAs and proteins using semiquantitative RT-PCR, Northern blot analysis, Western blot analysis, and immunohistochemistry. Densitometric analysis of Northern blots showed modest constitutive expression of IL-1 alpha gene in untreated control LM5 cells. TGF beta 1 treatment resulted in an increase in IL-1 alpha mRNA, that reached maximum levels (4-fold) by 2 hours and remained elevated for 4-16 hours, with a subsequent decline by 24 hours. Similarly, Northern blot and RT-PCR analysis demonstrated that TGF beta 1 treatment resulted in maximum induction of IL-8 mRNA (6- 8.5-fold) within 1-4 hours. The levels remained elevated for up to 24 hours afterwards. Western blot analysis results further confirmed the expression of both IL-1 alpha and IL-8 proteins by LM5 cells. TGF beta 1 treatment resulted in increased expression of both IL-1 alpha and IL-8 proteins. Immunofluorescence studies demonstrated increased staining of IL-1 alpha by TGF beta 1 as compared to untreated cells. These results suggest that TGF beta 1 may regulate IL-1 alpha and IL-8 expression in alveolar epithelial cells and contribute to polymorphonuclear leukocyte recruitment and lung injury in clinical states with increased TGF beta 1.
Formal verification of tail distribution bounds in the HOL theorem prover

Tail distribution bounds play a major role in the estimation of failure probabilities in performance and reliability analysis of systems. They are usually estimated using Markov's and Chebyshev's inequalities, which represent tail distribution bounds for a random variable in terms of its mean or variance. This paper presents the formal verification of Markov's and Chebyshev's inequalities for discrete random variables using a higher-order-logic theorem prover. The paper also provides the formal verification of mean and variance relations for some of the widely used discrete random variables, such as Uniform(m), Bernoulli(p), Geometric(p) and Binomial(m, p) random variables. This infrastructure allows us to precisely reason about the tail distribution properties and thus turns out to be quite useful for the analysis of systems used in safety-critical domains, such as space, medicine or transportation. For illustration purposes, we present the performance analysis of the coupon collector's problem, a well-known commercially used algorithm.
Sources of debris flow material in burned areas

Abstract The vulnerability of recently burned areas to debris flows has been well established. Likewise, it has been shown that many, if not most, post-fire debris flows are initiated by runoff and erosion and grow in size through erosion and scour by the moving debris flow, as opposed to landslide-initiated flows with little growth. To better understand the development and character of these flows, a study has been completed encompassing 46 debris flows in California, Utah, and Colorado, in nine different recently burned areas. For each debris flow, progressive debris production was measured at intervals along the length of the channel, and from these measurements graphs were developed showing cumulative volume of debris as a function of channel length. All 46 debris flows showed significant bulking by scour and erosion, with average yield rates for each channel ranging from 0.3 to 9.9 m 3 of debris produced for every meter of channel length, with an overall average value of 2.5 m 3 /m. Significant increases in yield rate partway down the channel were identified in 87% of the channels, with an average of a three-fold increase in yield rate. Yield rates for short reaches of channels (up to several hundred meters) ranged as high as 22.3 m 3 /m. Debris was contributed from side channels into the main channels for 54% of the flows, with an average of 23% of the total debris coming from those side channels. Rill erosion was identified for 30% of the flows, with rills contributing between 0.1 and 10.5% of the total debris, with an average of 3%. Debris was deposited as levees in 87% of the flows, with most of the deposition occurring in the lower part of the basin. A median value of 10% of the total debris flow was deposited as levees for these cases, with a range from near zero to nearly 100%. These results show that channel erosion and scour are the dominant sources of debris in burned areas, with yield rates increasing significantly partway down the channel. Side channels are much more important sources of debris than rills. Levees are very common, but the size and effect on the amount of debris that reaches a canyon mouth is highly variable.
Comparison of the biochemical, immunologic and allergenic properties of vespid venoms collected in early and late summer

The biochemical, immunologic and allergenic properties of yellow hornet (Vespula arenaria) and bald-faced hornet (Vespula maculata) venoms collected in early and late summer were compared. The phospholipase A content of both hornet venoms decreased in late summer while protease, hyaluronidase and acid phosphatase contents were unchanged. The antigenic and allergenic properties of the two venoms, as measured by their reaction with rabbit antisera and sera from insect-allergic patients, respectively, were unchanged. These results suggest no changes in venom properties during the summer which influence the allergic response to insect stings.
The message of SUPPORT: Change is long overdue

The major findings of the Study to Understand Prognosis and Preferences for Outcomes and Risks of Treatment (SUPPORT), a multimillion dollar, multisite investigation of the process of dying in American hospitals, were extremely disappointing to the medical community. The major conclusion of this intervention study was that increased efforts to improve communication about patients' preferences for end-of-life care to physicians did not have a significant impact on the care that is provided in hospitals. In a commissioned series of papers to examine the conclusions of the study, numerous factors were identified as the possible reasons for the SUPPORT findings. Among the factors was the role of nurses in communicating patients' preferences to physicians. Nurses, however, were not participants in the design and conduct of this study nor were they among those who were respondents to the conclusions of SUPPORT. In this manuscript, an analysis of the report of the SUPPORT study itself and the commentaries commissioned by its funding agency are reported. Numerous issues about the scientific rigor of SUPPORT, the perceived roles of nurses in end-of-life decision making, and the need for interdisciplinary collaboration in health care and health care research are presented in an effort to ensure that nurses' contributions to the quality of patient care are recognized, acknowledged, and valued in the future.
A numerical study of plasticity models and finite element types

Abstract The available experimental results for the cyclic loading of a simply supported circular plate using a rigid circular punch is utilized to compare the numerical results obtained from computations performed using the four most popular work hardening plasticity models, namely, the isotropic, kinematic, mechanical sublayer and the Mroz models. The mechanical sublayer model appears to be the most efficient in this group. Using the mechanical sublayer model the computational efficiencies of the 3, 4 and 8-node finite elements are studied. The 8-node element emerges as the most suitable element type for the present problem.
Small angle X-ray diffraction studies on the topography of cannabinoids in synaptic plasma membranes

Abstract In a previous publication, we have described in detail how we used small angle x-ray diffraction to determine the topography of (−)- Δ 8 -tetrahydrocannabinol ( Δ 8 -THC) in dimyristoylphophatidylcholine (DMPC) bilayers, and to deduce the conformation of the THC side chain by using the iodo-analog (5′-I- Δ 8 -THC) in the model membrane. We have now extended our studies to synaptic plasma membrane systems where the cannabinoids are believed to exert part of their pharmacological effects. Synaptic plasma membranes (SPM) were isolated from fresh bovine brains and Δ 8 -THC was incorporated into the membranes. By comparing the electron density profiles of drug free and drug-containing SPM preparations, we observed an electron density increase due to the presence of Δ 8 -THC in a region centered at 9.2 A from the terminal methyl groups of the membrane bilayer. In an attempt to dissect the effects of different membrane components on the topography of Δ 8 -THC, we carried out parallel experiments using membrane preparations from the synaptosomal membrane total lipid extract (TLX) as well as from bovine brain phosphatidyl choline extract (PCX) containing 30 mole percent cholesterol (Chol). Our results regarding the topography of Δ 8 -THC and 5′-I- Δ 8 -THC in these lipid membranes show that the TLX bilayer simulates the natural membrane environment very closely whereas in the PCX/Chol bilayer Δ 8 -THC resides at a location approximately 4 A closer to the membrane interface, similar to that found in our previous study using DMPC model membrane. These x-ray diffraction results provide insights regarding the location of the binding sites on the cannabinoid receptor and indicate that preparations of the total lipid extract from synaptosomal membranes duplicate very well the properties of the intact membrane preparation.
Abstract A108: Reproductive and hormonal factors in relation to risk of fatal versus non-fatal invasive epithelial ovarian cancer

Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the 7th most fatal worldwide. Reproductive and hormonal exposures are known to influence risk of ovarian cancer. We therefore investigated whether these exposures also influence ovarian cancer survival. We studied survival in relation to hormonal and reproductive history in invasive epithelial ovarian cancer cases and controls from the New England based Case-Control Studies (NECC, 1,642 cases and 2,100 controls). Cases and controls were identified between 1992 and 2008 in New Hampshire and eastern Massachusetts. At the time of enrollment, participants were interviewed in person on a wide range of known and suspected risk factors, including hormone use, childbearing, lifestyle habits and anthropometric characteristics. Polytomous logistic regression was applied to evaluate whether a risk factor was associated differently with fatal (those that died within 3 years of diagnosis) versus non-fatal cases while controlling for other covariates and P-values for heterogeneity (comparing the Odds Ratios (ORs) for fatal ovarian cancer to the ORs for non-fatal ovarian cancer) were calculated based on the maximum likelihood estimates. A total of 360 of the 1642 women with ovarian cancer (22%) died within 3 years. We found that fatal ovarian cancer was associated with increasing age (multivariate OR 1.05 per 1 year increase in age, 95% CI 1.04 − 1.07, P-value These results suggest that the most aggressive subset of invasive epithelial ovarian cancer exhibits important differences in its reproductive and hormonal risk factor profile as compared with non-fatal cases, and that selected protective factors such as oral contraceptive pill use may be especially important for the prevention of the most aggressive subgroup of disease. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A108.
Molecular Sequelae of Topographically Guided Peripheral Nerve Repair

Peripheral nerve injuries cause severe disability with decreased nerve function often followed by neuropathic pain that impacts the quality of life. Even though use of autografts is the current gold standard, nerve conduits fabricated from electrospun nanofibers have shown promise to successfully bridge critical length nerve gaps. However, in depth analysis of the role of topographical cues in the context of spatio-temporal progression of the regenerative sequence has not been elucidated. Here, we explored the influence of topographical cues (aligned, random, and smooth films) on the regenerative sequence and potential to successfully support nerve regeneration in critical size gaps. A number of key findings emerged at the cellular, cytokine and molecular levels from the study. Higher quantities of IL-1α and TNF-α were detected in aligned fiber based scaffolds. Differential gene expression of BDNF, NGFR, ErbB2, and ErbB3 were observed suggesting a role for these genes in influencing Schwann cell migration, myelination, etc. that impact the regeneration in various topographies. Fibrin matrix stabilization and arrest of nerve-innervated muscle atrophy was also evident. Taken together, our data shed light on the cascade of events that favor regeneration in aligned topography and should stimulate research to further refine the strategy of nerve regeneration using topographical cues.
Direct Functional Interactions between Insulin-like Growth Factor-binding Protein-3 and Retinoid X Receptor-α Regulate Transcriptional Signaling and Apoptosis

Insulin-like growth factor-binding protein (IGFBP)-3 regulates apoptosis in an IGF-independent fashion and has been shown to localize to nuclei. We cloned the nuclear receptor retinoid X receptor-α(RXR-α) as an IGFBP-3 protein partner in a yeast two-hybrid screen. Multiple methodologies showed that IGFBP-3 and RXR-α bind each other within the nucleus. IGFBP-3-induced apoptosis was abolished in RXR-α-knockout cells. IGFBP-3 and RXR ligands were additive in inducing apoptosis in prostate cancer cells. IGFBP-3 enhanced RXR response element and inhibited RARE signaling. Thus, RXR-α-IGFBP-3 interaction leads to modulation of the transcriptional activity of RXR-α and is essential for mediating the effects of IGFBP-3 on apoptosis.
Attenuation of vaccinial virus by interfacial adsorption.

SummaryVaccinia can be attenuated by interfacial adsorption so that it will no longer produce the lesions of this virus when injected endermically into rabbits but will produce an immunity to the action of the untreated virus.
South Korea as an ‘Ordinary’ Country: A Comparative Inquiry into the Prospects for ‘Permanent’ Immigration to Korea

South Korea has often been portrayed as a special country. Certainly, its rapid rise from a poor, technologically backward economy in the 1950s to a significant, even dominant, economic player in high-tech consumer and industrial markets by the 1990s has been exceptional. There is no denying, moreover, that the country has unique historical and cultural characteristics. Nonetheless, this paper argues that, in terms of those processes related to economic, social and political transformation, South Korea is an ‘ordinary’ country. One of the most salient of these processes is associated with migration which, in almost every industrialised democracy, moves from temporary foreign-worker migration to permanent settlement. Because of South Korea's rigidly monocultural and exclusionary heritage, however, many observers have assumed that the permanent settlement of large numbers of ‘foreigners’ was out of the question. Yet, a close and comparative analysis of the economic, political and social dynamics of internat...
Characterization of a herpes simplex virus type 2 deoxyuridine triphosphate nucleotidohydrolase and mapping of a gene conferring type specificity for the enzyme.

Abstract The herpes simplex virus type 2 (HSV-2)-induced deoxyuridine triphosphate nucleotidohydrolase (dUTPase) was purified approximately 600 ± 43-fold using a combination of affinity, hydrophobic, absorption, and ion-exchange chromatography techniques. The only substrate for the dUTPase was dUTP with a Km of 3.6 ± 1.1 μM. There was no apparent divalent cation requirement, but the HSV-2-induced dUTPase was inhibited by EDTA (0.1 mM) and this inhibition was reversed by either Co2+ (0.5 mM) or Mgt2+ (0.5 mM). The HSV-2-induced dUTPase was distinguished from the HSV-1-induced and cellular dUTPases based upon differences in sensitivity to substrate inhibition, thermostability, and electrophoretic migration in nondenaturing polyacrylamide gels. Analysis of HSV-1 temperature-sensitive (ts) mutants demonstrated that is A15 and is K13 did not induce significant amounts of dUTPase activity at the permissive or nonpermissive temperatures. Mutants with defects in HSV-induced DNA polymerase or in the major DNA binding protein induced dUTPase at both temperatures. In contrast is mutants defective in the α polypeptide VP175 (ICP4) did not induce normal levels of dUTPase at the nonpermissive temperature. The location of a gene encoding for the type specificity of the HSV induced dUTPase was mapped to the left 20% of the genome in Us in the region 0.060 to 0.100 or from 0.148 to 0.204.
The Co-construction of Credibility in Online Product Reviews

Reviews of products on Web sites like Epinions.com make explicit the ways in which credible identities are co-constructed. Product reviews reveal not only how reviewers construct credibility for themselves but also how readers of reviews, through their comments about reviews, ratify and contribute to reviewer credibility. I present a framework and analyze examples of reviews of digital cameras to examine how reviewers of a technical product convey credibility and how review readers coconstruct reviewers' credibility. The framework and analysis can help identify those reviewers who are likely to influence review Web site users.
Adenosine 3',5'-Monophosphate-Dependent Protein Kinase from Brain

Adenosine 3',5'-monophosphate at a concentration of 5 x 10-7 mole per liter causes a 400 percent increase in the rate of phosphorylation of histone catalyzed by a partially purified enzyme preparation from rabbit brain. The data provide the first direct evidence of a biochemical action of adenosine 3',5'-monophosphate in the brain.
Common Concerns Faced by Lesbian Elders: An Essential Context for Couple's Therapy

ABSTRACT It is important that family therapists working with older lesbian couples, or their surviving members, consider the full and complex contexts of these clients. An exploration of the day-to-day challenges and strengths of these couples requires consideration of the roles of age, gender, and sexuality. Regardless of the modality that is applied, an awareness of common concerns for this population is necessary to yield ethical and effective work in sessions. This article will present information on older lesbians and their relationship characteristics with a focus on clinical application regarding demographics, income and retirement, housing, care giving, end of life issues, and access to health care.
A Whole Genome Pairwise Comparative and Functional Analysis of Geobacter sulfurreducens PCA

Geobacter species are involved in electricity production, bioremediations, and various environmental friendly activities. Whole genome comparative analyses of Geobacter sulfurreducens PCA, Geobacter bemidjiensis Bem, Geobacter sp. FRC-32, Geobacter lovleyi SZ, Geobacter sp. M21, Geobacter metallireducens GS-15, Geobacter uraniireducens Rf4 have been made to find out similarities and dissimilarities among them. For whole genome comparison of Geobacter species, an in-house tool, Geobacter Comparative Genomics Tool (GCGT) has been developed using BLASTALL program, and these whole genome analyses yielded conserved genes and they are used for functional prediction. The conserved genes identified are about 2184 genes, and these genes are classified into 14 groups based on the pathway information. Functions for 74 hypothetical proteins have been predicted based on the conserved genes. The predicted functions include pilus type proteins, flagellar proteins, ABC transporters, and other proteins which are involved in electron transfer. A phylogenetic tree from 16S rRNA of seven Geobacter species showed that G. sulfurreducens PCA is closely related to G. metallireducens GS-15 and G. lovleyi SZ. For evolutionary study, acetate kinase protein is used, which showed closeness to Pelobacter propionicus, Pelobacter carbinolicus, and Deferribacteraceae family bacterial species. These results will be useful to enhance electricity production by using biotechnological approaches.
In silico Kinetic Model of iNOS expression in macrophages

Macrophages are a key component in the host innate response and are major contributors to the proinflammatory response against pathogens. One of the key players in the proinflammatory response is induced nitric oxide synthase (iNOS), an enzyme that provides the nitric oxide needed by phagocytic cells to create reactive nitrogen species, which are highly damaging to intracellular pathogens. To model the macrophage intracellular mechanism of iNOS gene expression, we use a systems biology approach to capture the dynamics of the iNOS gene expression system stimulated by bacterial lipopolysaccharide (LPS) and IFN-y. Our simulation results agree with in vitro assays of iNOS gene expression and provide a platform for further investigating the potential impact of LPS and IFN-y variations on macrophage effector function.
919 NK CELL ACUTE LYMPHOBLASTIC LEUKEMIA (ALL), A SUBSET OF T-ALL

To determine the proportion and subtype of acute lymphoblastic leukemias which have natural killer (NK) phenotype and activity, we examined leukemic blasts from 31 children with ALL (14 with T-ALL, 17 with non-T-ALL) for expression of antigens detected by NK-specific monoclonal antibodies Leu llb, Leu 7, and 1G2 (an antibody we have developed which cross-reacts with Leu 7). None of the patients had leukemic blasts which reacted with Leu llb. However, leukemic blasts from 4 T-ALL patients were Leu 7+/1G2+. Blasts from 2 of these had spontaneous lytic activity against standard NK target cell line K562; blasts from one killed K562 only when incubated with interferon; blasts from the other had no lytic activity against K562 but did manifest antibody-dependent cell-mediated cytotoxicity against antibody-coated cells from NK-resistant cell line SB. When leukemic blasts from 6 Leu 7−1G2− leukemic patients (2 with T-ALL, 3 with non-T-ALL, 1 with AML) were tested, none had NK activity against K562. Blasts from all 4 Leu 7+/1G2+ patients had L2 morphology. In one, the leukemic blasts had azurophilic cytoplasmic granules similar to those found in NK-enriched normal populations of large granular lymphocytes.
Hydroxamic acid oxidation--pharmacological considerations.

Abstract Both primary and secondary hydroxamic acids were found to be quite susceptible to oxidation by 2,6-dichlorophenolindophenol at physiological pH. Among the primary hydroxamates, substituted benzhydroxamic acids were more easily oxidized than aliphatic derivatives, resonance being an important factor determining relative rates. In the case of secondary hydroxamic acids, a wide range of oxidation rates was observed with steric hindrance and inductive effects being of prime concern. In that hydroxamates are of considerable interest, both as possible chemotherapeutic agents and as proximate carcinogens, we sought to correlate their relative rates of oxidation with carcinogenic potential. DNA binding studies showed that the rapidly oxidized o-hydroxybenzhydroxamic acid was not incorporated into DNA while N-hydroxy-2-acetylaminofluorene, which is less susceptible to oxidation, was incorporated rapidly.
Effect of propranolol on ethanol metabolism-evidence for the role of mitochondrial NADH oxidation.

Abstract Ethanol metabolism in the rat as measured in vivo by 14CO2 production or in vitro by the removal of ethanol by liver slices was inhibited approximately 30 per cent by propranolol. There was no inhibitory effect of propranolol on rat liver alcohol dehydrogenase, catalase. NADPH-dependent microsomal ethanol oxidation or formate oxidation to 14CO2. Propranolol inhibited fatty acid oxidation to 14CO2in vivo as well as by liver slices and isolated hepatic mitochondria. NADH oxidation by hepatic mitochondria was also reduced by propranolol. 2,4-Dinitrophenol treatment or chronic ethanol feeding of rats stimulated alcohol metabolism as well as hepatic mitochondrial NADH oxidation. These increases were abolished by propranolol. The effect of propranolol in blocking the increase in ethanol oxidation after chronic alcohol feeding appears to be related to its action on the mitochondrial re-oxidation of NADH to NAD. Propranolol inhibits mitochondrial NADH oxidation, while 2,4-dinitrophenol or chronic ethanol feeding stimulates this process. The present studies support the concept that the rate of hepatic ethanol metabolism is limited, at least in part, by the mitochondrial oxidation of NADH.
Theory of broadband spin decoupling

Abstract The NMR spectrum of a spin S coupled to another spin I which is undergoing an arbitrary time-dependent irradiation is analyzed. The efficacies of various schemes for spin decoupling are compared using the average Hamiltonian method, and the limitations of this method are pointed out. A procedure for exact numerical analysis is outlined. This analysis leads to a very simple criterion, namely: decoupling will be effective over a bandwidth δ o if the net precessional angle φ of a spin is insensitive to offset δ for 0 δ δ 0 . The application of this criterion in quantitative form permits us to exhibit decoupling sequences which are somewhat superior to any previously described.
Scene segmentation from vector-valued images using anisotropic diffusion

Scene segmentation is a pre-processing step for many vision systems. We are concerned with segmentation as a precursor to 3D scene modeling. Segmentation of a scene for this purpose usually involves dividing an image into areas that are relatively uniform in some value (e.g. intensity, range, or curvature). This single segmented image represents the analogous segmented scene. This paper presents a segmentation method that uses features to indicate boundaries or edges between regions. We incorporate features from multiple images types to obtain an more accurate segmentation of objects or object parts in the scene. Multiple features are not only combined directly to improve segmentation results, but they are also used to guide a smoothing operation. This smoothing technique preserves features representing edges while smoothing noise in the images.