cssi/SciSciGPT-SciSciNet huggingface dataset:
Bio-effectiveness of Tat-catalase conjugate: a potential tool for the identification of H2O2-dependent cellular signal transduction pathways ☆

Reactive oxygen species such as hydrogen peroxide (H(2)O(2)) have taken center stage as bona fide second messengers in various signaling pathways. Here, we report the synthesis, metabolic fate, and effectiveness in modulating such pathways of a Tat-catalase conjugate. Incubation of L2 cells with Tat-catalase greatly increased cell-associated enzymatic activity, reaching close to a plateau by 30 min. The cell-associated catalase activity and antibody-detectable Tat-derivatives declined over time after changing medium, although still remaining at significantly higher levels than baseline even at 4h. While most cell-associated Tat-catalase was apparently tightly attached to the cell surface, a small fraction entered the cells as the proteasome inhibitor MG-132 slightly prevented the disappearance of the enzyme. Tat-catalase, either membrane-bound or intracellular, but not native catalase, inhibited serum-induced Elk phosphorylation and anisomycin- and/or MG-132-induced ERK phosphorylation, suggesting the involvement of H(2)O(2). Thus, Tat-catalase should be a useful tool to dissect H(2)O(2)-dependent events in signaling pathways.
Hypersonic vehicle thermal protection system model optimization and validation with vibration tests

Abstract Damage detection for thermal protection systems is crucial for hypersonic flight. Since fastener failure is a critical failure mode for many thermal protection systems, an efficient methodology that does not require a significant amount of experimental data collection and analysis for implementation is desired. In a coming paper, we develop a methodology for localizing fastener failure in a thermal protection system utilizing an experimentally validated finite element model. This paper focuses on validating the finite element model in its healthy state versus low-frequency experimental results obtained on the composite structure for future research in damage quantification. The experimental validation is implemented in three steps to individually account for the unknown composite material properties, insulation effects, and the assembly with the connecting brackets and backing structure. The inverse optimization problem implemented in the first level of experimental validation demonstrated excellent agreement between the finite element model and the experimental results. The overall assembly also demonstrated good agreement between the low-frequency dynamics of the experimental results and the finite element model. The validated finite element-model will then be used to simulate damage in the structure to investigate the effectiveness of vibration mode-based damage detection metrics.
The application of network analysis to criminal intelligence: An assessment of the prospects

Abstract This paper explores the opportunities for the application of network analytic techniques to the problems of criminal intelligence analysis, paying particular attention to the identification of vulnerabilities in different types of criminal organization — from terrorist groups to narcotics supply networks. A variety of concepts from the network analysis literature are considered in terms of the promise they hold for helping law enforcement agencies extract useful information from existing collections of link data. For example, six different notions of “centrality” and the three major notions of “equivalence” are examined for their relevance in revealing the mechanics and vulnerabilities of criminal enterprises.
SET-THEORETIC STRUCTURE MODELLING

The set-theoretic notion of a system relation is reviewed and structural modelling based on it is shown to be very similar to methods now in existence which are based upon a probabilistic system relation. A relational calculus is proposed which provides a quantitative assessment of the strength of a relation and of the difference between relations; this calculus is isomorphic to Constraint Analysis and information theory. Structure modelling using the set relation is demonstrated. A law of emergent constraints is given as a warning against an attractive reductionist fallacy.
Online information services for the German government's audiences

Abstract The Internet is used by a great variety of people who play different roles and who have different interests. On the one hand, private users have different physical connections to the Internet; and on the other hand, professionals use the Internet as a source of information for their job. This paper describes how the German government's Internet offer meets these different user requirements. The Web site offers German, English, French, and Spanish information about Germany, its political system, its country and people, its institution, and its economic system for the public in general. Employees of the German government and of the communities can access more detailed data about political events and laws, whereas journalists are dependent on news in the forms of press releases, topical incidents, and political dates. Schools, universities or research institutes need printed information material for educational purposes. There are several mainstream technologies put into service to fulfill the demands of each user group: The Web site as a whole, which is updated around the clock, webcasting for the dissemination of timecritical information, and online ordering for printed material. Increasing user support is the focal motivation point to expand the services step by step. User acceptance shows how successful the whole implementation has been in the user's point of view. The described services have been integrated under consideration of high security requirements by GMD — German National Research Center for Information Technology — together with its cooperation partners. We achieved the results during a two-year project with the Press and Information Office of the German government.
The Natural History of Active Retinopathy of Prematurity

Abstract Two hundred twenty-one premature infants were examined in the premature nursery. Thirty-seven of the 221 (16.2%) had retinopathy of prematurity (ROP). Eight patients (21.5%) went blind and three other infants lost sight in one eye for a total of 19 sightless eyes (25.7%). The remaining 55 eyes (74.3%) retained vision. Birth weight was the most critical prognostic factor. Of eight babies who became blind all were under 1000 grams at birth, while babies who showed little change from active ROP were generally over 1300 grams. Nine of 14 eyes with only peripheral shunts (64%) resolved without dragging of the retina in the posterior pole. Sixteen eyes developed peripheral retinal detachment, and six of the sixteen (37.4%) had associated dilation and tortuosity of vessels in the posterior pole. Only one of these eyes resolved with minimal sequelae, suggesting that peripheral retinal detachment with dilated tortuous vessels was the most significant indicator of serious consequences.
Retrieval cues and meaningfulness in short-term recall

The effect of retrieval cues (RCs) on the short-term recall of CCC items was explored. Three types of RCs were used: facilitative (correct letter), interfering (wrong letter), and neutral (no letter). It was hypothesized that the effect of RCs would be accentuated with high-meaningfulness (M) items and attenuated with low-M items. Forty-two college Ss were individually run through 36 Peterson short-term memory trials. Although the main effects of both RC and M were significant, the RC by M interaction was not significant, contrary to prediction.
Conformal invariance and the conformal-traceless decomposition of the gravitational field

Einstein’s theory of general relativity is written in terms of the variables obtained from a conformaltraceless decomposition of the spatial metric and extrinsic curvature. The determinant of the conformal metric is not restricted, so the action functional and equations of motion are invariant under conformal transformations. With this approach the conformal-traceless variables remain free of density weights. The conformal invariance of the equations of motion can be broken by imposing an evolution equation for the determinant of the conformal metric g. Two conditions are considered, one in which g is constant in time and one in which g is constant along the unit normal to the spacelike hypersurfaces. This approach is used to write the Baumgarte-Shapiro-Shibata-Nakamura system of evolution equations in conformally invariant form. The presentation includes a discussion of the conformal thin sandwich construction of gravitational initial data, and the conformal flatness condition as an approximation to the evolution equations.
S-parameter-based IC interconnect transmission line characterization

A methodology for extracting high-frequency IC interconnect transmission parameters directly from S-parameter measurements has been demonstrated using on-chip test structures. The methodology consists of: (1) building on-chip interconnect structures for microwave test, (2) characterizing and subtracting measurement system parasitics, (3) extracting the transmission line impedance and propagation constant (attenuation constant and phase constant) from the calibrated data, and (4) extracting the Telegrapher's Equation transmission parameters (R, L, C, and G). Additional on-chip calibration permits subtraction of pad parasitic effects. This methodology is demonstrated over a 45-MHz to 20-GHz frequency range using an example 1-cm-long, 4- mu m-wide IC interconnect built in an advanced BiCMOS technology. Variations in interconnect impedance and capacitance indicate two signal propagation modes. Significant substrate-based loss is measured at microwave frequencies. >
Physiology of Pupal Ecdysis in the Tobacco Hornworm, Manduca Sexta: I. Evidence for Control by Eclosion Hormone

The time of pupal ecdysis in Manduca sexta can be accurately predicted by the appearance of external markers late in pupal development. Eclosion hormone injections resulted in premature ecdysis of staged pharate pupae. The latency between injection and initiation of ecdysis movements was inversely correlated with dosage and served as the basis for a sensitive, rapid, and quantitative bioassay for the hormone. Behavioural responsiveness to the hormone arose about 8 h before normal ecdysis at 23 °C. When insects were injected at these early times the larval cuticle was not sufficiently digested to allow its rupture and these animals remained permanently trapped inside the larval cuticle. Measurement of eclosion hormone in the blood of pharate pupae showed the appearance of biological activity in the blood about 30 min before the onset of ecdysis. It is concluded that pupal ecdysis is under endocrine control and that the hormone involved is likely to be the eclosion hormone.
Context as communication: Mcdonald's vs. Burger King

Abstract This study focused on context as communication. The distinctive micro‐environments at McDonald's and Burger King's suburban restaurants were compared and contrasted. The theory‐based conceptualization of high‐load environments generates the prediction that McDonald's customers are more involved and less comfortable than Burger Bang's customers. Results supported this prediction. Communicative and design implications of these results are discussed.
Amygdala responses to averted vs direct gaze fear vary as a function of presentation speed

We examined whether amygdala responses to rapidly presented fear expressions are preferentially tuned to averted vs direct gaze fear and conversely whether responses to more sustained presentations are preferentially tuned to direct vs averted gaze fear. We conducted three functional magnetic resonance imaging (fMRI) studies to test these predictions including: Study 1: a block design employing sustained presentations (1 s) of averted vs direct gaze fear expressions taken from the Pictures of Facial Affect; Study 2: a block design employing rapid presentations (300 ms) of these same stimuli and Study 3: a direct replication of these studies in the context of a single experiment using stimuli selected from the NimStim Emotional Face Stimuli. Together, these studies provide evidence consistent with an early, reflexive amygdala response tuned to clear threat and a later reflective response tuned to ambiguous threat.
Theory of Q switching in actively mode-locked lasers

An analytic theory is proposed that characterizes Q switching in an active mode-locked cavity as the nonlinear interaction of two unstable modes: one symmetric, another antisymmetric. The phase difference between these modes generates a nonlinear beating interaction that gives rise to quasi-periodic behavior in the laser cavity. This quasi-periodic behavior is responsible for the Q-switching phenomenon and is controlled by the interaction and overlap between neighboring pulses. With a linear stability analysis, a simple qualitative description of the Q-switching phenomenon is given that is verified with numerical simulations of the governing active mode-locked equations. This model characterizes the Q switching as a function of the physical parameters of the laser cavity and elucidates the mechanisms for controlling its behavior.
Sucker Punched by the Invisible Hand: the World Financial Markets and the Globalization of the U.S. Mortgage Crisis*

The worldwide financial crisis that began in 2007 was set off by the collapse of the subprime mortgage market in the USA. The crisis simultaneously reverberated to banks around the world, and event ...
BIOGEOGRAPHY OF BACTERIOPLANKTON IN LAKES AND STREAMS OF AN ARCTIC TUNDRA CATCHMENT

Bacterioplankton community composition was compared across 10 lakes and 14 streams within the catchment of Toolik Lake, a tundra lake in Arctic Alaska, during seven surveys conducted over three years using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified rDNA. Bacterioplankton communities in streams draining tundra were very different than those in streams draining lakes. Communities in streams draining lakes were similar to communities in lakes. In a connected series of lakes and streams, the stream communities changed with distance from the upstream lake and with changes in water chemistry, suggesting inoculation and dilution with bacteria from soil waters or hyporheic zones. In the same system, lakes shared similar bacterioplankton communities (78% similar) that shifted gradually down the catchment. In contrast, unconnected lakes contained somewhat different communities (67% similar). We found evidence that dispersal influences bacterioplankton communities via advection and dilution (mass effects) in streams, and via inoculation and subsequent growth in lakes. The spatial pattern of bacterioplankton community composition was strongly influenced by interactions among soil water, stream, and lake environments. Our results reveal large differences in lake-specific and stream-specific bacterial community composition over restricted spatial scales (<10 km) and suggest that geographic distance and connectivity influence the distribution of bacterioplankton communities across a landscape.
An Economic Theory of Referendum Voting: School Construction and Stock Adjustment

Local public project referenda provide the voter a unique opportunity to shape public activity. Prior studies of these votes fail to develop a behavioral model of this choice, usually relying on ad hoc explanations of variables that, for one reason or another, contribute to forecasts of referendum results. Our paper outlines a stock adjustment model of school bond referenda and tests this model using data from a set of school elections in West Virginia. The unique features of our model are treatment of the bond voting decision as an input decision and, hence, as involving derived demand; analysis of the bond referendum as a stock adjustment decision; and concentration on voting as a decision between discrete, mutually exclusive options.
Concurrent channel access and estimation for scalable multiuser MIMO networking

This paper presents MIMO/CON, a PHY/MAC cross-layer design for multiuser MIMO wireless networks that delivers throughput scalable to many users. MIMO/CON supports concurrent channel access from uncoordinated and loosely synchronized users. This new capability allows a multi-antenna MIMO access point (AP) to fully realize its MIMO capacity gain. MIMO/CON draws insight from compressive sensing to carry out concurrent channel estimation. In the MAC layer, MIMO/CON boosts channel utilization by exploiting normal MAC layer retransmissions to recover otherwise undecodable packets in a collision. MIMO/CON has been implemented and validated on a 4×4 MIMO testbed with software-defined radios. In software simulations, MIMO/CON achieves a 210% improvement in MAC throughput over existing staggered access protocols in a 5-antenna AP scenario.
Fatigue of mammalian skeletal muscle in situ during repetitive contractions.

When the gastrocnemius–plantaris muscle group of the dog is stimulated to contract repetitively for 30 min at frequencies high enough to generate levels at or near max, and mechanical performance decline with time. This decline with time is fatigue, and it occurs during twitch and tetanic contractions that are isometric or isotonic. There is oxidation of the mitochondrial electron transport system, and net lactic acid output is transient, ending after 20 min of contractions. Energy and substrate stores and intracellular pH are only moderately changed and do not appear to be well correlated with the development of fatigue. Blood flow through the muscle is well correlated with the development of fatigue and decreases as fatigue develops in a manner that keeps the blood arteriovenous O2 difference nearly constant. Changing the blood flow alters the rate of development of fatigue as an inverse relation, and this response does not appear to be related to changes in the availability of O2 in the mitochondria. N...
An improved RF cavity search for halo axions

The axion is a hypothetical elementary particle and cold dark matter candidate. In this RF cavity experiment, halo axions entering a resonant cavity immersed in a static magnetic field convert into microwave photons, with the resulting photons detected by a low-noise receiver. The ADMX Collaboration presents new limits on the axion-to-photon coupling and local axion dark matter halo mass density from a RF cavity axion search in the axion mass range 1.9-2.3 {micro}eV, broadening the search range to 1.9-3.3 {micro}eV. In addition, we report first results from an improved analysis technique.
Runtime system for autonomic rescheduling of MPI programs

Intensive research has been conducted on dynamic job scheduling, which dynamically allocates jobs to computing systems. However, most of the existing work is limited to redistribute independent tasks or at the algorithm design level. There is no runtime system available to support automatic redistribution of a running process in a heterogeneous network environment. In this study, we present the design and implementation of a system that dynamically reschedules running processes over a network of computing resources via automatic decision-making and process migration. The system is implemented on top of MPI-2 and HPCM (high performance computing mobility) middleware. Experimental and analytical results show that the runtime system works well. It makes dynamic rescheduling of running tasks possible and improves system performance considerably. While the implementation is for MPI programs and using HPCM, the design of the system is general and can be extended to other distributed environments as well.
Hepatitis C Virus (HCV) Induces Formation of Stress Granules Whose Proteins Regulate HCV RNA Replication and Virus Assembly and Egress

Stress granules (SGs) are cytoplasmic structures that are induced in response to environmental stress, including viral infections. Here we report that hepatitis C virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)-dependent manner. Moreover, we show an inverse correlation between the presence of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and USP18, in HCV-infected cells despite high-level expression of the corresponding MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is inhibited in stress granule-containing HCV-infected cells. Finally, in short hairpin RNA (shRNA) knockdown experiments, we found that the stress granule proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for efficient HCV RNA and protein accumulation at early time points in the infection and that G3BP1 and TIA-1 are required for intracellular and extracellular infectious virus production late in the infection, suggesting that they are required for virus assembly. In contrast, TIAR downregulation decreases extracellular infectious virus titers with little effect on intracellular RNA content or infectivity late in the infection, suggesting that it is required for infectious particle release. Collectively, these results illustrate that HCV exploits the stress granule machinery at least two ways: by inducing the formation of SGs by triggering PKR phosphorylation, thereby downregulating the translation of antiviral interferon-stimulated genes, and by co-opting SG proteins for its replication, assembly, and egress.
Noncollaborative telepresentations come of age

A Telepresentation is a presentation in which the presenter and/or some of the audience members are not physically present but are telepresent – in a different location and/or at a different time. Telepresentations promise to reach a wider audience by transmitting and/or recording the presentation for viewing at a different place and/or time and time-scale. The result dramatically reduces travel costs, increases communication, and provides a meeting record. Today, telepresentations are being used for training, product introductions, and general information meetings. We believe telepresentations will soon find regular use for courses and conferences. It is now possible for anyone, anywhere to produce a telepresentation at low cost, on PCs, using today’s internet/intranet and telephony infrastructure. We call for all technical conferences to be telepresent. Telepresentations may just be the next “killer app”.
Performance comparison of MPEG1 and MPEG2 video compression standards

MPEG1 and MPEG2 are generally accepted by the industry as the international video compression standards for a broad range of video transmission and storage applications. Both schemes are fundamentally similar-based on motion compensation and DCT encoding-but their performance differ depending on the characteristics of the video. MPEG2 typically performs better when encoding interlaced video with a large object or camera motion; however, when encoding progressive scanned video it may not achieve better results over MPEG1, and in many instances it is actually inferior. The video quality of MPEG1 and MPEG2 is compared using various types of sequences, and the statistical distribution of the bits among various elements in the bitstreams-such as motion vectors, DCT coefficients, and overheads-are investigated to gain a better understanding of their performance differences.
Proposal of three-dimensional phase contrast holographic microscopy

We propose a three-dimensional phase contrast digital holographic microscopy. The object to be observed is a low-contrast transparent refractive index distribution sample, such as biological tissue. Low contrast phase objects are converted to high contrast images through the microscopy we propose. In order to gain high three-dimensional resolution, the direction of pump plane wave is scanned, and separate holographic images produced at each angle are acquired and decoded into complex amplitude in Fourier space. The three-dimensional image is reconstructed in a computer from all information acquired through the system. The resolution in the direction of the optical axis is increased by utilizing a 4π configuration of objective lenzes.
Aluminum and lead absorption from dietary sources in women ingesting calcium citrate

Animal models suggest that citrate-containing compounds augment absorption of aluminum from food and tap water, causing aluminum accumulation in bone and brain despite normal renal function. Citrate also enhances lead absorption in animals. We questioned whether use of calcium citrate by women as a calcium supplement causes an increase in aluminum or lead absorption from dietary sources. Changes in 24-hour urine aluminum and lead excretion, plasma aluminum level, and whole blood lead level were assessed in 30 healthy women before and during treatment with calcium citrate (800 mg of elemental calcium per day). During calcium citrate therapy, urinary aluminum excretion and plasma aluminum level increased significantly. In contrast, there were no changes in urine or whole blood lead levels. We conclude that treatment with calcium citrate significantly increases absorption of aluminum from dietary sources. Additional studies are needed to determine whether long-term use of calcium citrate leads to aluminum accumulation and toxicity.
High-resistance state of phase coherent nanoscale thin-film Al superconducting nanorings in magnetic fields

An interesting and novel effect has been observed in the form of a high-resistance state below the superconducting transition temperature of Al nanorings. The resistance exceeded 15 times the value of the normal-state resistance even though the ring was superconducting. This counterintuitive effect can be explained in terms of charge imbalance caused by the nonequilibrium accumulation of quasiparticles near tilted normal-superconductor interfaces that occur naturally in highly constricted nanostructures. Simulations using finite-element analysis have been performed which support the experimental results. Similar results have been observed in wires and disks, but the results of this work clarify and extend this previous work.
Bone marrow in HIV infection. A comparison of fluorescent staining and cultures in the detection of mycobacteria.

Fifty-one bone marrow aspirates and biopsies from 47 human immunodeficiency virus–(HIV) infected patients (42 with acquired immune deficiency syndrome [AIDS], 5 with AIDS-related complex [ARC]) were processed by standard methods for smears and paraffin sections. Aspirates were cultured for Mycobacteria. The sections, imprints, and smears were examined by fluorescent microscopy with the use of Truant’s modification of the auramine–rhodamine stain. Mycobacterial cultures had positive results from 35%. Sensitivity of fluorescent staining was 72% and specificity was found to be 94%. If the fluorescent stain had positive results, the positive predictive value for recovering Mycobacteria on culture was 87%. Fluorescent microscopy with the use of Truant’s auramine–rhodamine staining of routinely processed bone marrow aspirates and biopsies is a fairly sensitive, very specific, and rapid technique for determining the presence of Mycobacteria in bone marrow specimens from patients with HIV infection.
Multipoint Transmission Scheduling in an Underwater Distributed Antenna System

This paper considers a distributed antenna system (DAS) with two remote transmitters to communicate with one mobile node, and investigates two transmission schemes: antenna switching and Alamouti coding. The time splitting factor between two transmitters in the antenna switching scheme and the power splitting factor in the Alamouti coding scheme are optimized to minimize the outage probability, as a function of the distances of the mobile node to the transmitters.
Demographic, Insurance, and Health Characteristics of Newly Enrolled HIV-Positive Patients After Implementation of the Affordable Care Act in California.

Objectives. To examine changes in HIV-positive patient enrollment in a large health care delivery system before and after key Affordable Care Act (ACA) provisions went into effect in 2014.Methods. Analyses compared HIV-positive patients newly enrolled in Kaiser Permanente Northern California between January and June 2012 (n = 339) to those newly enrolled between January and June 2014 through the California insurance exchange or via other mechanisms (n = 549).Results. After the ACA, the HIV-positive patient enrollment increased. These new enrollees were more likely to be male (93.6% vs 89.1%; P = .01), to be enrolled in high-deductible benefit plans (≥ $1000; 18.8% vs 5.5%; P = .01), and to have better HIV viral control (HIV RNA levels below limits of quantification 79.5% vs 73.6%; P = .05) compared with pre-ACA new enrollees. Among post-ACA new enrollees, there were more patients in the lowest and highest age groups. Post-ACA exchange enrollees (22%) were more likely to be male and to have high-deductible...
FDA guidelines for endoscope reprocessing

The Food and Drug Administration (FDA) relies on guidance documents, such as voluntary consensus standards and professional practice standards when reviewing the manufacturer's endoscope reprocessing instructions included in the instructions for use manual. The FDA does not perform endoscope reprocessing validation studies. The device manufacturer must certify that the reprocessing instructions included in the user manual have been or will be validated. This article discusses the regulatory review of gastrointestinal endoscopes and endoscope reprocessing instructions required prior to marketing.
Cognitive styles in equivalence range.

With the aim of appraising the generality and construct validity of the concept of equivalence range, defined as the preferred span of objects or qualities that an individual is willing to consider in one category, a number of cognitive tasks were devised to appraise different facets of styles of categorizing behavior. Several sorting tasks were employed, some original and some adapted from previous research, to sample the breadth of an individual's preferred mode of categorization. These included an object sorting test employing real objects, object sorting tests substituting the names of objects for real objects, tasks in which photographs of people and descriptions of people were sorted, and a drawing sorting task. In addition several perceptual “bandwidth” tasks were especially developed to study Ss' characteristic range of equivalence judgments and categorizations. Also included were tests of criticalness response style and associational ease to appraise the relevance of styles of verbal categorizati...
Sources of Variation

Because of the open pattern of plant growth, a primary, and often misleading, source of variation is the phenotypic variability of many genotypes. If the range of phenotypic expression of a genotype is large, or, as stated in the previous chapter, if the primary control of the phenotype is environmental, a single plant, or plants of a single genotype, may vary considerably under different environments. The resulting variation pattern may be similar to a variation pattern that is primarily under genetic control. For example, a plant may have a tall form and a dwarf form; however, possession of the “tall” genotype does not in itself insure that the plant actually will fulfill its genetic potential and produce a tall phenotype. Some environmental factors or a combination of factors—such as moisture, temperature, soil nutrients, light—might be so inadequate as to limit the growth of this potentially tall plant and, therefore, we might get a dwarf plant that will be morphologically similar to a genetically dwarfed plant. The difference would be that the genetic dwarf, when self-pollinated, would probably breed true and produce only dwarf offspring regardless of the environment, whereas seed from the environmental dwarf could, under better growing conditions, produce the appropriate ratio of tall plants.
Abstract 3682: Phosphorylation mediated conformational changes defines nuclear role of phosphatase and tensin homology (PTEN) in tumor suppression

Loss of function of tumor suppressor PTEN (Phosphatase and tensin homolog) causes cancer in various tissues. PTEN C-terminal phosphorylation (pPTEN) inactivates PTEN, leading to multiple malignancies with increased severity. However, little is known about the molecular mechanisms underlying such inactivation. Therefore, the objective of our work is to ascertain the molecular mechanisms by which PTEN phosphorylation drives lung cancer. PTEN C-terminal phosphorylation at a serine-threonine cluster (Ser380, Thr382, Thr383 and Ser385) conformationally inactivates PTEN, abrogating its tumor suppressor function. Replacement of these serine/threonine residues with alanine generated an artificial phosphorylation-deficient mutant of PTEN (PTEN-4A), which is constitutively active. PTEN-4A suppressed cell proliferation and migration to a greater extent as compared to PTEN-WT. PTEN-4A preferentially localized to the nucleus and suppressed the E2F-mediated transcription of cell cycle genes. The nuclear localization sequence and phosphatase activity of PTEN-4A is critical for this transcriptional suppression. Immuno-precipitation assays show that PTEN physically associates with the transcription factor E2F1, a likely mechanism for its suppressive effect on E2F1 related genes. Further, deletion analysis of PTEN-4A protein revealed that the C2 domain is indispensable for suppression of E2F-related genes. Systematic transcriptional assays identify disease-associated C2 domain mutations that lose their ability to suppress E2F-mediated transcription, supporting the concept that these mutations are oncogenic in patients. Taken together, we reveal nuclear functions of PTEN-4A in tumor suppression that can be therapeutically leveraged for developing adjunctive cancer therapies. Small molecule inhibitors that hinder PTEN phosphorylation maybe utilized to activate PTEN nuclear function in tumors. Such adjunctive therapy has a high likelihood to reduce toxic doses of chemotherapeutic agents and targeted inhibitors, including kinase inhibitors that are being used in clinical settings. Citation Format: Prerna Malaney, Jonathan Semidey-Hurtado, Jamaal Hardee, Deepal Patel, Daniel Hennessey, Kate Stanford, Emily Palumbo, Zhi Tian, Diane Allen-Gipson, Vrushank Dave. Phosphorylation mediated conformational changes defines nuclear role of phosphatase and tensin homology (PTEN) in tumor suppression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3682.
“You have the right to protect your health”: Perceptions of Secondhand Smoke and Exposure Mitigation Strategies in Low-Income Patients With Heart Disease, San Francisco, 2011–2012

We examined the understanding of the harms of secondhand smoke (SHS) exposure among low-income, hospitalized adults with cardiovascular disease. Participants were 15 nonsmokers reporting daily SHS exposure and 15 light or nondaily cigarette smokers. We coded responses from audiotaped semistructured interviews for themes. No participant spontaneously identified heart risks related to SHS exposure. Strategies to avoid SHS included verbal requests to not smoke and physically avoiding smoke; both smokers and nonsmokers prioritized politeness over urgency. Most participants thought a blood test quantifying SHS exposure would be clinically useful. Health education, assertiveness communication training, and protective policies (eg, smoke-free multiunit housing) also were supported.
Chipping away at neurologist burnout, one refill request at a time

There has been growing awareness of the issue of neurologist burnout over the past several years.1,2 Based in part on the results of a national survey in which more than 50% of neurologist respondents had at least one symptom of burnout and in which neurologists had the third highest incidence across specialties, American Academy of Neurology (AAN) leadership now views burnout as a neurologic crisis.1 A number of factors have been proposed to contribute to neurologist burnout, including loss of professional autonomy, increasing barriers to practicing quality medicine, and increased administrative duties or busywork.1,2 Redesign of suboptimal health care processes and workflows may be a critical step in reducing burnout and improving physician well-being.1,2 While considerable efforts are being directed toward this problem, including the formation of an AAN task force focused solely on neurologist burnout, there have been few studies examining potential interventions.
A Divided Nation: Military Traditions, Democratic Third Way, and Liberation Theology

[It was in the] “Third World,” that the Church would discover what it really was and what it really had to do. – Enrique Krauze, Mexican historian The rebels spared no effort to impress the American visitors, providing ample meals of steak, fresh orange juice and baked bread, as well as beds, a video television screen and trucks for transportation. A well-known revolutionary priest, Miguel Ventura, offered a mass in the bullet-pocked local church. A rebel chorus sang hymns of liberation theology. The first song began: “Christ, Christ Jesus, identify yourself with us. Have solidarity with us, not with the oppressor class, with us.” – James LeMoyne, New York Times correspondent, reporting from guerrilla-controlled territory, 1985 Once you had to be a colonel to get rich, now even the lower ranks steal. – Joaquin Ventura, retired Salvadoran Army captain, December 1989 Las Catorce The decades leading up to the civil war were a tumultuous time that up-ended El Salvador's relatively predictable and stable political climate. To give a full sense of this harrowing story, this chapter addresses several key actors and movements that emerged on the left, right, and center of Salvadoran politics and society in the 1960s and ’70s. It seems appropriate to begin with the power that stood the test of time in this tiny Central American country – the oligarchy. When foreign journalists during the war years wrote about the Salvadoran oligarchy, they almost invariably used the term “las catorce” for the fourteen families that were said to rule the country. The revolutionary left also described the oligarchs in such terms. According to one guerrilla leader interviewed in Havana in 1980, “Some 14 families own most of the land in El Salvador. These families are also linked to North American capital through the interests they have in the American-controlled industries.” While the term las catorce was widely used, there were in fact around 100 clans that were the effective owners of Salvadoran industries and land. But even that number was suspect as some contended that it was in fact much larger, even if a tiny fraction compared to the country's total population. According to Jorge Sol Castellanos, a 66-year-old businessman and minister of the economy, “It's different from an aristocracy, which we also have. It's an oligarchy because these families own and run almost everything that makes money in El Salvador.
Intravenous Topiramate: Pharmacokinetics in Dogs with Naturally Occurring Epilepsy

Barriers to developing treatments for human status epilepticus (SE) include the inadequacy of experimental animal models. In contrast, naturally-occurring canine epilepsy is similar to the human condition and can serve as a platform to translate research from rodents to humans. The objectives of this study were to characterize the pharmacokinetics (PK) of an intravenous (IV) dose of topiramate (TPM) in dogs with epilepsy, and evaluate its effect on intracranial electroencephalographic (iEEG) features. Five dogs with naturally occurring epilepsy were used for this study. Three were getting at least one antiseizure drug as maintenance therapy including phenobarbital (PB). Four (ID 1-4) were used for the 10 mg/kg IV TPM + PO TPM study, and three (ID 3-5) were used for the 20 mg/kg IV TPM study. IV TPM was infused over 5 minutes at both doses. The animals were observed for vomiting, diarrhea, ataxia, and lethargy. Blood samples were collected at scheduled pre- and post-dose times. Plasma concentrations were measured using a validated HPLC-MS method. Non-compartmental and population compartmental modeling were performed (Phoenix WinNonLin and NLME) using plasma concentrations from all dogs in the study. Intracranial EEG (iEEG) was acquired in one dog. The difference between averaged iEEG energy levels at 15 minutes pre- and post-dose was assessed using a Kruskal-Wallis test. No adverse events were noted. Topiramate concentration-time profiles were best fit by a two-compartment model. PB co-administration was associated with a 5.6 fold greater clearance and a ~4 fold shorter elimination half-life. iEEG data showed that TPM produced a significant energy increase at frequencies >4 Hz across all 16 electrodes within 15 minutes of dosing. Simulations suggested that dogs on an enzyme inducer would require 25 mg/kg, while dogs on non-inducing drugs would need 20 mg/kg to attain the target concentration (20-30 µg/mL) at 30-minutes post-dose. This study shows that IV TPM has a relatively rapid onset of action, loading doses appear safe, and the presence of PB necessitates a higher dose to attain targeted concentrations. Consequently, it is a good candidate for further evaluation for treatment of seizure emergencies in dogs and people.
Quality of Care at Hospitals Identified as Outliers in Publicly Reported Mortality Statistics for Percutaneous Coronary Intervention

Background:Public reporting of percutaneous coronary intervention (PCI) outcomes may create disincentives for physicians to provide care for critically ill patients, particularly at institutions wi...
Retailers’ extent of involvement in sustainability and role in creating sustainable apparel and textiles from South Africa

ABSTRACTThe purpose of this comparative case study research was to identify the sustainability-focused influencing power and involvement of retailers in the buyer-driven apparel and textiles industry in South Africa. Four textile and apparel retailers’ businesses were studied through desktop review of documents and field research. The Sustainable Apparel Coalition’s Higg 2.0 Brand Modules (environment and social/labour) and a beta Retail Environmental Module were used as a theoretical framework. The retailers varied in their pursuit of various environmental and social/labour sustainability practices. The qualitative analysis identified that all three retailers based in South Africa sourced at least some of their apparel and textile products locally, whereas the international retailer used a global sourcing strategy that did not include South Africa. The three local retailers were also all committed to job creation under the Broad-Based Black Economic Empowerment initiative. South Africa-based retailers ar...
Optical phase retrieval using conical refraction imaging in structured media

We present a new optical phase retrieval method using the conical refraction imaging in structured media, which enables a single simultaneous measurement of multiple images and allows a stable recovery of the optical phase.
Synergistic protection against acute flurothyl-induced seizures by adjuvant treatment of the ketogenic diet with the type 2 diabetes drug pioglitazone

SummaryObjective We have previously found that the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) contributes to the mechanism of action of the ketogenic diet (KD), an established treatment for pediatric refractory epilepsy. We have found that the KD increases brain PPARγ and that inhibition or genetic loss of PPARγ prevents the antiseizure effects of the KD on (1) acutely induced seizures in nonepileptic mice and (2) spontaneous recurrent seizures in epileptic mice. Here, we tested the hypothesis that adjuvant treatment of KD-treated mice with a PPARγ agonist, pioglitazone, would result in an additive effect. Methods Acute seizures were induced in three groups of C57Bl/6 mice by inhalation exposure to flurothyl gas. In Group 1, mice were weaned onto either a standard diet or KD comprised of a fat:carbohydrate/protein ratio of either 6:1, 3:1, or 1:1 for 2 weeks. In Group 2, vehicle or pioglitazone (0.1, 1, 10, 80 mg/kg) was administered 4 h prior to flurothyl exposure. In Group 3, vehicle or increasing doses of pioglitazone were administered to KD-treated mice 4 h prior to flurothyl exposure. Latency times to clonic seizures and generalized tonic–clonic (GTC) seizures were recorded, and isobolographic analysis was used to determine combinatorial interactions. Results Neither KD treatment nor pioglitazone alone or in combination affected clonic seizures. However, the latency to GTC seizures was dose-dependently and significantly increased by both KD (~57%, p < 0.05) and pioglitazone (~28%, p < 0.05). Coadministration of an ineffective 1:1 KD and pioglitazone resulted in ~47–55% (p < 0.05) increase in latency to GTC. Isobolographic analysis indicated a synergistic interaction of the KD and pioglitazone. Significance These results suggest coadministration may enable reduction of the KD ratio without loss of seizure protection. Such adjuvant treatment could improve quality of life and limit adverse effects of a classic KD or high-dose pioglitazone.
Introduction to remote sensing image registration

For many applications, accurate and fast image registration of large amounts of multi-source data is the first necessary step before subsequent processing and integration. Image registration is defined by several steps and each step can be approached by various methods which all present diverse advantages and drawbacks depending on the type of data, the type of applications, the a priori information known about the data and the type of accuracy that is required. This paper will first present a general overview of remote sensing image registration and then will go over a few specific methods and their applications.
When disaster hits home: diaspora engagement after disasters

Sudden natural disasters can create a massive need for immediate relief and long-term reconstruction efforts. Such support can come from various individuals and organizations, both within the count...
Acute characterization of tissue and functional deficits in a clinically translatable pig model of ischemic stroke

Abstract The acute stroke phase is a critical time frame used to evaluate stroke severity, therapeutic options, and prognosis while also serving as a major target for the development of diagnostics. To better understand stroke pathophysiology and to enhance the development of treatments, our group developed a translational pig ischemic stroke model. In this study, the evolution of acute ischemic stroke tissue damage, immune response, and functional deficits were further characterized in the pig model. Stroke was induced by middle cerebral artery occlusion in Landrace pigs. At 24 hours post-stroke, magnetic resonance imaging revealed a decrease in ipsilateral diffusivity and an increase in hemispheric swelling and intracranial hemorrhage resulting in notable midline shift. Stroke negatively impacted white matter integrity leading to decreased fractional anisotropy. Similar to acute clinical patients, stroked pigs showed a reduction in circulating lymphocytes and a surge in neutrophils and band cells. Functional responses corresponded with structural changes with reduced exploration in open field testing and impairments in spatiotemporal gait parameters. This novel, acute ischemia characterization provides important insights into tissue and functional level changes in a pig model that can be used to identify treatment targets and future testing of therapeutics and diagnostics.