cssi/SciSciGPT-SciSciNet huggingface dataset:
Predicting Drug Toxicity: Early Detection of Likely Failures in Drug Development

It remains a challenge to predict whether or not a new drug candidate will have undesirable side-effects in the clinic. Many biologically active molecules, including drugs and drug-leads, are amphiphiles that partition into lipid bilayers, which may alter bilayer physical properties, thereby modulating membrane protein function. Such bilayer-modifying molecules may be promiscuous modifiers of membrane protein function, raising the possibility that they have off-target effects. Thus, it may be possible to predict whether a compound will have important off-target effects based on quantitative studies on the compound's bilayer-modifying potential. We developed an assay to quantify the bilayer-modifying potential of large numbers of compounds. Using a gramicidin-based fluorescence assay (GBFA), which reports how a compound alters the gramicidin monomer dimer equilibrium, we have shown that many drug and drug-leads alter lipid bilayer properties at the concentrations where these compounds become indiscriminate modifiers of membrane protein function. Such indiscriminate modifiers of membrane protein function are likely to have off target effects; we pursued this question in a study on a library of compounds that had been tested for cytotoxicity in “high-content” screening assays that quantified cellular ATP levels, nuclear morphology, nuclear membrane integrity, and apoptosis in immortalized liver, lung, and neuronal cell lines. We tested 134 compounds (40 non-toxic, 40 moderately toxic and 54 highly toxic) using the GBFA (the library was “blinded” until the results of the GBFA were known) and found that the GBFA predicts cellular toxicity, with the Area Under The Curve of the Receiver-Operating Characteristic being 0.84. These results further support a mechanism by which amphiphiles exert their toxicity, namely by altering lipid bilayer physical properties and that such an in vitro measurement could be used as a warning sign for off-target biological effects in drug discovery efforts.
Effect of smoking status and abciximab use on outcome after percutaneous coronary revascularization: Pooled analysis from EPIC, EPILOG, and EPISTENT.

Abstract Background Tobacco use has been studied in relation to the development of atherosclerotic heart disease and outcome after acute coronary syndromes, though outcome data after percutaneous coronary intervention (PCI) are limited. Tobacco use has been associated with increased fibrinogen levels, thrombin generation, and increased platelet aggregation, and these factors may cause ischemic events after PCI. Methods We assessed whether smokers undergoing PCI have more ischemic events and if glycoprotein IIb/IIIa receptor blockade is particularly beneficial in preventing ischemic events in this cohort. We examined clinical outcomes for smokers and nonsmokers by using pooled analysis from 3 large, placebo-controlled trials of the glycoprotein IIb/IIIa antagonist abciximab during PCI. Results Among 6519 patients, 34% were smokers. The primary end point of death, myocardial infarction, or urgent revascularization within 30 days was reduced by abciximab from 12.3% to 6.4% (relative risk reduction, 48%; P P P P P =.03). Conclusions This pooled analysis demonstrates that after PCI, smokers had worse 30-day outcomes than did nonsmokers. However, both groups had a comparable degree of benefit with platelet inhibition through the use of abciximab. (Am Heart J 2001;141:599-602.)
Inhibition of androgen synthesis in human testicular and prostatic microsomes and in male rats by novel steroidal compounds.

The C17,20-lyase and 5α-reductase are key enzymes in the biosynthesis of androgens. The effects of novel steroidal compounds were evaluated as inhibitors against both human C17,20-lyase and 5α-reductase in vitro. The concentrations of testosterone (T) and dihydrotestosterone (DHT) in the prostate, testis and serum and changes in the tissue weights were also determined in rats treated with the novel inhibitors. L-12 and L-26 showed potent inhibition of human testicular C17,20-lyase with IC50 values of 50 and 25 nm, respectively. L-12, L-38, and I-47 showed moderate inhibition of human testicular C17,20-lyase with IC50 values of 75, 108, and 70 nm, respectively similar to ketoconazole (78 nm). Interestingly, L-6, L-26, and L-38 also showed some inhibitory activity against 5α-reductase with IC50 values of 75, 125, and 377 nm, respectively. Finasteride, an inhibitor of 5α-reductase had an IC50 value of 33 nm. However, ketoconazole did not inhibit 5α-reductase nor did finasteride inhibit C17,20-lyase. Treatmen...
Effect of radiative heat transfer on combustion chamber flows

Abstract The importance of radiative heat transfer in the hydrodynamics of a parabolic combusting flow has been explored. Numerical studies have been performed of turbulent, nonpremixed flames confined within cylindrical and two-dimensional enclosures in order to produce a definitive answer to the question as to when radiation is important in determining the flow properties. A new method, called the effective angle model, has been employed to calculate the radiation source term that converts the inherently elliptic problem into a parabolic one, saving substantial computer time. The analysis shows that neglecting radiation in the hydrodynamic code can cause overprediction of the mean velocity and temperature by more than a factor of 2, and of the wall heat flux by a factor of 5. The optically thin approximation has been found to underpredict velocity and temperature in most cases considered. It is concluded that some radiation model must be included when the radiation/convection parameter, defined as т= σaL p i u i c p (T a 4 −T w 4 ) (T a −T i ) is significantly larger than unity; however, the model need not create an excessive computational penalty.
Predominant modes of winter surface wind variability over the Gulf of Alaska.

Two distinct modes extracted from winter (Dec.–Mar.) monthly mean surface wind variability over the Gulf of Alaska (GOA) and part of the northeast Pacific Ocean have been identified along with their associations with sea surface temperature (SST), coastal downwelling, surface air temperature (SAT) and sea level pressure (SLP). The leading mode of surface wind variability, accounting for 45% of the variance, is characterized by two distinct and alternating modes or their linear combination, and shows strong interannual and interdecadal variations with the transition years in the mid-1970s and the beginning and late of 1990s. One mode (M1) features a coherent cyclonic or anticyclonic surface wind anomaly in the GOA and part of the northeast Pacific Ocean, and reflects wind field variability related to the intensity of large scale atmosphere-ocean interactions associated with the Aleutian Low, the Pacific/North American (PNA) pattern, the Pacific decadal oscillation (PDO), and the South Oscillation (SO). This mode significantly influences SAT over the GOA and the entire northeast Pacific and influences downwelling along the eastern and southeastern GOA. It does not significantly influence SST in the northern GOA. The other (M2) characterizes dominant southerly or northerly anomalies, and significantly influences coastal downwelling in the northern and southeastern GOA. It is also correlated with SAT over the GOA, the Bering Sea shelf, and much of Alaska. The impact of M2 on SST is greater than that of M1 in the GOA and the Bering Sea. M1 and M2, respectively, correspond to the PNA pattern and a dipole pattern, and the later is characterized by the third mode of the empirical orthogonal function (EOF) analysis of winter SLP variability over the domain 20° –70°N and 160°E–100°W, accounting for 13% of the variance. The dipole pattern is a new mode of winter atmospheric variability, with opposite anomalous centres over the southern Bering Sea and the west coast of the USA and part of the northeast Pacific Ocean. Copyright © 2009 Royal Meteorological Society
The Influence of Dietary Protein Deficiency on the Performance of Isolated Muscle Preparations from the Rat Left Ventricle

ABSTRACT The contractile performance of isolated muscle preparations from the left ventricle of rats receiving a 3% casein protein deficient diet for two to three weeks was compared with the performance of muscle preparations from animals receiving a normal diet. The right and left ventricular weights from protein deficient animals were significantly decreased, but left ventricle/body weight and right ventricular/body weight ratios did not differ from control animals. The performance of the isolated muscle preparations revealed no differences in the following parameters measured at the apex of the length tension curve: peak active tension, resting tension, maximum rate of tension development and time to peak tension, RT 1/2 , an index of relaxation, and maximum rate of tension decline indicated relaxation rate was increased in preparations from protein deficient animals. We conclude that, while a protein deficient diet of two to three weeks duration results in proportionate decreases in body and cardiac chamber weight in comparison to control animals, no evidence for impaired contractile activity is seen.
Mapping microscope object polarized emission to the back focal plane pattern

The back focal plane (BFP) intensity pattern from a high-aperture objective separately maps far- and near-field emission from dipoles near a bare glass or metal-film-coated glass/aqueous interface. Total internal reflection (TIR) excitation of a fluorescent sample gave a BFP pattern interpreted in terms of fluorescent dipole orientation and distance from the interface. Theoretical consideration of this system led to identification of emission characteristics that remove a dipole orientation degeneracy in conventional microscope fluorescence polarization measurements. BFP pattern inspection removes the degeneracy. Alternatively, a BFP mask blocking a small fraction of emitted light in a standard imaging microscope prevents uniform collection of the BFP intensity and also eliminates the degeneracy. The BFP pattern from a single photoactivated photoactivatable green fluorescent protein (PAGFP) tagged myosin in a muscle fiber was observed despite the large background light from the highly concentrated myosin tagged with unphotoactivated PAGFP. This was accomplished by imaging the pattern from a nontelecentric plane, where most of the background intensity's pattern was translated laterally from the single-molecule object's pattern. TIR/BFP pattern imaging requires a simple alteration of the fluorescence microscope and is consistent with single-molecule imaging in a fluorophore dense three-dimensional object like a muscle fiber.
Severity of middle cerebral artery occlusion determines retinal deficits in rats.

Middle cerebral artery occlusion (MCAO) using the intraluminal suture technique is a common model used to study cerebral ischemia in rodents. Due to the proximity of the ophthalmic artery to the middle cerebral artery, MCAO blocks both arteries, causing both cerebral ischemia and retinal ischemia. While previous studies have shown retinal dysfunction at 48h post-MCAO, we investigated whether these retinal function deficits persist until 9days and whether they correlate with central neurological deficits. Rats received 90min of transient MCAO followed by electroretinography at 2 and 9days to assess retinal function. Retinal damage was assessed with cresyl violet staining, immunohistochemistry for glial fibrillary acidic protein (GFAP) and glutamine synthetase, and TUNEL staining. Rats showed behavioral deficits as assessed with neuroscore that correlated with cerebral infarct size and retinal function at 2days. Two days after surgery, rats with moderate MCAO (neuroscore <5) exhibited delays in electroretinogram implicit time, while rats with severe MCAO (neuroscore ≥5) exhibited reductions in amplitude. Glutamine synthetase was upregulated in Muller cells 3days after MCAO in both severe and moderate animals; however, retinal ganglion cell death was only observed in MCAO retinas from severe animals. By 9days after MCAO, both glutamine synthetase labeling and electroretinograms had returned to normal levels in moderate animals. Early retinal function deficits correlated with behavioral deficits. However, retinal function decreases were transient, and selective retinal cell loss was observed only with severe ischemia, suggesting that the retina is less susceptible to MCAO than the brain. Temporary retinal deficits caused by MCAO are likely due to ischemia-induced increases in extracellular glutamate that impair signal conduction, but resolve by 9days after MCAO.
Data Acquisition and Process Control System for the Hot Fuel Examination Facility

A data acquisition and process control system has been developed to control the remote examination of reactor fuel elements in a hot cell. The computer system, positioning stages, CAMAC controls, and detection equipment are described. One of the examinations performed, precision gamma scanning, illustrates the use of this system. The development of both hardware and software, the logic for controlling the examination, and the utilization of the CAMAC standard are discussed. Expansion of this system to include several new examinations will determine whether or not further automation of the facilities is feasible.
Intracellular responses of raphe magnus neurons during the jaw-opening reflex evoked by tooth pulp stimulation

Abstract Neurons in the nucleus raphe magnus (RM) may play an important role in the modulation of nociception. To determine how RM neurons are activated during a nociceptive reflex, the intracellular responses or raphe neurons were studied during the jaw-opening reflex (JOR) elicited by tooth pulp shock in lightly anesthetized cats. Tooth pupl stimulation produces reflex EMG activation of the digastric muscle at a latency of 7–11 ms, resulting in jaw opening. Tooth pulp shok that elicits the JOR also produces an EPSP in a subset of raphe neurons. This EPSP consists of an early small depolarization that occurs at a latency of 10–15 ms followed by a larger depolarization stimulation of the 4 paws elicits oligosynaptic EPSPs in the same cells at a latency of 16–20 ms. Electrical train stimulation of the midbrain periaqueductal gray region (PAG) suppresses the JOR. Single shock stimulation at the same PAG sites that suppress the JOR evokes monosynaptic EPSPs in the large majority of raphe neurons. In all cases, the threshold for EPSP is below the threshold for suppression of the JOR. The EPSP amplitude is a direct function of PAG stimulus intensity and there is temporal summation of EPSPs evoked by paired PAG shocks. At condition-test intervals of 40–90 ms, train stimulation of PAG suppresses the tooth pupl-evoked EPSP in raphe neurons. The threshold for EPSP suppression occurs at a PAG stimulation intensity below that required for suppression of the JOR. The present findings provide evidence that RM neurons may play an important role in the modulation of the tooth pulp-evoked JOR, but only after the initial withdrawal reflex has occurred.
Writing user selectable data on the extended header of seismic recordings made on the Texas instruments DFS-V

Abstract A circuit has been developed to allow the writing of up to 192 digits of user-selectable data on a portion of tape called extended header, which is always available for use before each DFS-V seismic record is written. Such data could include navigation information, air gun and streamer depth and shot times.
Interdomain communication between weak structural elements within a disease-related human tRNA.

The structure of the human mitochondrial (hs mt) tRNALeu(UUR) features several domains that are predicted to exhibit limited thermodynamic stability. An elevated frequency of disease-related mutations within these domains suggests a link between structural instability and the functional effects of pathogenic mutations. A series of tRNAs featuring mutations within the D and anticodon stems were prepared and investigated using nuclease probing. Structural mapping studies indicated that these domains were partially denatured for the wild type (WT) hs mt tRNALeu(UUR) and were significantly stabilized by mutations introducing additional or stronger base pairs into the stem regions. In addition, trends in the aminoacylation activities of the D stem mutants suggested that the loose structure is required for function, with mutants displaying the most ordered structures exhibiting the lowest levels of aminoacylation activity. A pronounced interdependence of the structures of the anticodon and D stems was observed,...
Artificial Perception of Actions

This paper has to do with the visual perception of actions that are discretely conceptualized. The intent is to develop a vision system that produces causal or intentional descriptions of actions, thus providing the conceptual underpinnings of natural language descriptions. The computational theory is developed in linking a “point of action definition” analysis to an analysis of how the physical events will elicit appropriate verbal descriptions. Out of this theory of direct computational linkages between physical events, points of action definition, and verbal descriptions, comes a theory of perception that provides some insight into how to go about constructing systems that can watch the world and report on what they are watching.
Preference for Commercially Processed Dill Pickles in Relation to Sodium Chloride, Acid, and Texture

Commercially processed dill pickles from 15 companies were evaluated for levels of NaCl, acetic acid, and texture by objective mcasurements and for preference by a consumer panel. Although differences in preference were significant, the concentrations of NaCl and acid, or the values of texture were not significantly related to these differences. The results indicated that NaCl in processed dill pickles could be reduced from present levels without affecting sensory preference for the product.
A MULTIPLE LEVEL INVESTIGATION OF PERSONNEL RATINGS

A multiple levels of analysis approach was used to assess whether job performance and skill importance ratings were based on individual differences, incumbent/supervisor dyadic agreement, group membership, or functional department. Data were collected as part of a managerial training needs analysis conducted at a large gold and silver mining organization. Participants included 140 incumbent managers and their immediate supervisors, who were embedded in 140 incumbent/supervisor dyads, 39 managerial work groups, and eight departments of the organization. Results from Within and Between Analysis (WABA) suggested that (a) incumbent ratings of both performance and skill importance were characterized by individual differences, (b) supervisory ratings of both performance and skill importance were primarily characterized by between-groups (supervisors) differences, (c) matched incumbent-supervisory performance ratings displayed individual differences, and (d) matched incumbent-supervisory importance ratings displayed dyadic agreement (i.e., between-dyads differences). Practical implications of these results for interpreting these and other types of personnel-related data are discussed.
"That I could look ... on my own crucifixion and bloody crowning": Walt Whitman's Anti-Gallows Writing and the Appeal to Christian Sympathy

Traces “Whitman’s involvement in the anti-capital punishment movement . . . from his impassioned anti-gallows editorials for various periodicals to his transference of these expressions” into Leaves of Grass, “especially in terms of his arguments for sympathy for condemned criminals and his use of the rhetoric of ‘Christian sympathy,’ a rhetoric very common in antebellum anti-gallows arguments.”
Ordering Transition of Block Copolymer Films

It is well-known that a bulk, symmetric, A-b-B diblock copolymer forms a lamellar morphology, with period L, below an order-disorder transition (T(ODT)) temperature, for chiN < 10.5; chi is the Flory-Huggins interaction parameter and N is the degree of polymerization of the copolymer. The ordering temperatures of poly(styrene-b-methyl methacrylate) (PS-b-PMMA) thin film diblock copolymers of thickness h </= 2L, supported by SiO(x)/Si substrates, in vacuum environments, are shown to increase beyond the bulk, and estimates of the temperature shifts indicate that small changes of chiN are associated with unusually large shifts of the transition temperature. Further, we find that in compressed CO(2) environments, these films are ordered at temperatures where the films are disordered in vacuum (or air) environments. This latter observation is of particular significance because small molecule diluents, including compressed CO(2), are known to decrease the ODT of the bulk (enhanced miscibility).
Mitoxantrone and prolonged infusion gemcitabine as salvage therapy in patients with acute myelogenous leukemia

Abstract In a recent phase I study, a combination of gemcitabine at 10 mg/(m 2 min) for 12 h and mitoxantrone 12 mg/m 2 daily for 3 days, achieved a complete remission (CR) in 3 of 12 (25%) patients with refractory leukemia. A pilot assessment of this regimen was conducted to determine its tolerability in patients with refractory acute myeloid leukemia (AML). In a cohort of 18 patients with very refractory disease (6 primary refractory, 12 relapsed, mean initial CR duration 3.5 months), one patient achieved a CR, a second CR with incomplete platelet recovery (CRp). Sepsis and mucositis were significant extramedullary toxicities. The gemcitabine and mitoxantrone regimen was feasible to administer even in heavily pre-treated patients. It was not active in patients who had failed a prior salvage regimen. It may warrant further study in patients with primary resistant AML.
Evaluation of the robustness of the fathead minnow, Pimephales promelas, larval survival and growth test, U.S. EPA method 1000.0

An intralaboratory study was conducted to evaluate the robustness of the Fathead minnow (Pimephales promelas) Larval Survival and Growth Test, Method 1000.0. Toxicity tests were conducted with the reference toxicants hexavalent chromium (Cr{sup 6+}) and copper (Cu), and the data were statistically analyzed using hypothesis testing. Differences in age, size, feeding regimes, and water quality did not cause more than a twofold difference in 13 subchronic values (SCVs) for Cr{sup 6+}. These tests involved side-by-side tests initiated with 1-, 4-, and 7-d larvae or initiated with 1-d larvae and two size groups of 4-d larvae fed differently. The mean SCV was 3,600 {mu}g Cr{sup 6+}/L, and the values ranged from 2,100 to 4,200 {mu}g Cr{sup 6+}/L. Eleven of these tests with a homogeneous variance gave an average minimum significant difference (MSD) of 14.3%. The no-observed-effect concentration (NOEC) for growth was always lower than the effect on survival. In the side-by-side tests with 1-, 4-, and 7-d larvae exposed in hard water the SCV was 35 {mu}g Cu/L for each age group. Except for one test with Cu in soft water, the effects of Cr{sup 6+} and Cu on growth were more sensitive than the effect on survival. These toxicity testsmore » along with some nontoxicant studies indicated that reasonable differences in methods parameters did not cause any changes greater than a factor or two in analytical results despite the noise of biological variability.« less
Statistical model based video segmentation and its application to very low bit rate video coding

We present a statistical model-based video segmentation algorithm for typical videophone and video-conference applications. This algorithm makes use of online information and tries to build statistical models for both background and foreground and update the models on the fly. A hierarchical system structure is designed and segmentation is combined with tracking. Two possible applications are discussed: to generate VOP for MPEG-4 and to introduce subjective rate control for DCT-based algorithms. A rate distortion based rate control algorithm for H.263 is proposed and implemented as an example.
REJOINDER TO HOLCOMBE ON THE INEVITABILITY OF GOVERNMENT

Holcombe (2004) argued that government was inevitable. In Block (2005) I maintained that this institution was not unavoidable. Holcombe (2007) takes issue with that response of mine to his earlier paper, and the present essay is, in turn, a response to his latest missive in this conversation. In section I, I deal with what I can consider an anomaly in Holcombe's argument. Section II is devoted to a consideration of his dismissal of my paper on grounds of fallacy of composition. The burden of section III is to consider Holcombe's supposed refutation of my views on the basis of his comments about the price ceiling; in section IV, I comment on the examples offered by this author, and in section V, I examine his claim that he is not actually supporting government. I conclude in section VI.
Outcomes in non-metastatic colorectal cancer.

The measurement of outcomes in non-metastatic colon and rectal cancer patients is a multi-dimensional endeavor involving prediction tools, standard of care, and best treatment guidelines. Socioeconomic, demographic, and racial impacts on outcome must be carefully considered. Consideration must also be given to measures of cost, quality, and healthcare delivery in response to initiatives meant to optimize patient health while maintaining quality of life. J. Surg. Oncol. 2014 110:518–526. © 2014 Wiley Periodicals, Inc.
Automatic Application of the Data-State Model in Data-Flow Contexts

The data-state and data-flow models of information visualization are known to be expressively equivalent. Each model is most effective for different combinations of analysis processes and data characteristics. Visualization frameworks tend to either (1) work within a single model or (2) permit either model in separate sub-frameworks. In either case, converting between the two models falls entirely to the programmer. The theoretical basis for automatic translation between the two models was established by Chi. However, that process is insufficiently specified to be directly implemented. This paper characterizes the practical advantages of the data-state model. This is used to identify when such a transformation is beneficial. It then expands on Chi's theoretical framework to provide the tools for translating visualization program fragments from the data-flow to the data-state model. A partial implementation of the expanded theory is described for the Stencil visualization environment.
Feedback Petri net control design in the presence of uncontrollable transitions

This paper describes a computationally efficient method for synthesizing feedback controllers for plants modeled by Petri nets which may contain uncontrollable transitions. The controller, a Petri net itself, enforces a set of linear constraints on the plant. The original set of plant behavioral constraints is transformed to yield a controller which enforces the original constraints without influencing any uncontrollable transitions.
High-power intrastep quantum well electroabsorption modulator using single-sided large optical cavity waveguide

A novel electroabsorption modulator (EAM) using intrastep quantum wells (IQWs) and a single-sided large optical cavity waveguide is demonstrated to operate at up to 100 mW of input optical power. When the IQW EAM with uncoated facets is tested in an analog fiber link, the radio-frequency link gain reaches -16.1 dB at 100-mW optical power. We have measured a single-octave spurious-free dynamic range (SFDR) of 121 dB/spl middot/Hz/sup 4/5/ and multioctave SFDR of 110 dB/spl middot/Hz/sup 2/3/ for this EAM.
General method for analyzing three-dimensional effects in free-electron laser amplifiers

Free-electron laser (FEL) configurations in which the parameters of the electron beam vary along the undulator become relevant when considering new aspects of existing FELs or when exploring novel concepts. This paper describes a fully three-dimensional, analytical method suitable for studying such systems. As an example, we consider a seeded FEL driven by a beam with varying transverse sizes. In the context of the Vlasov-Maxwell formalism, a self-consistent equation governing the evolution of the radiation field amplitude is derived. An approximate solution to this equation is then obtained by employing an orthogonal expansion technique. This approach yields accurate estimates for both the amplified power and the radiation beam size. Specific numerical results are presented for two different sets of x-ray FEL parameters.
Noise suppression characteristics of InP-based monolithically integrated guided wave balanced photodiodes

Measurements were made of the noise suppression and signal enhancement properties of dual In/sub 0.53/Ga/sub 0.47/As-InP metal-semiconductor-metal (MSM) photodiodes integrated with a leaky mode In/sub 0.52/Al/sub 0.48/As waveguide directional coupler, and an electro-optic phase shifter. The experiments were done with a 1.3- mu m laser as the local oscillator. A noise suppression of 11 dB and signal enhancement of 1.3 dB were recorded for the MSM photodiodes. >
Interoception: the sense of the physiological condition of the body.

Abstract Converging evidence indicates that primates have a distinct cortical image of homeostatic afferent activity that reflects all aspects of the physiological condition of all tissues of the body. This interoceptive system, associated with autonomic motor control, is distinct from the exteroceptive system (cutaneous mechanoreception and proprioception) that guides somatic motor activity. The primary interoceptive representation in the dorsal posterior insula engenders distinct highly resolved feelings from the body that include pain, temperature, itch, sensual touch, muscular and visceral sensations, vasomotor activity, hunger, thirst, and ‘air hunger’. In humans, a meta-representation of the primary interoceptive activity is engendered in the right anterior insula, which seems to provide the basis for the subjective image of the material self as a feeling (sentient) entity, that is, emotional awareness.
A Gradient of ATP Affinities Generates an Asymmetric Power Stroke Driving the Chaperonin TRIC/CCT Folding Cycle

The eukaryotic chaperonin TRiC/CCT uses ATP cycling to fold many essential proteins that other chaperones cannot fold. This 1 MDa hetero-oligomer consists of two identical stacked rings assembled from eight paralogous subunits, each containing a conserved ATP-binding domain. Here, we report a dramatic asymmetry in the ATP utilization cycle of this ring-shaped chaperonin, despite its apparently symmetric architecture. Only four of the eight different subunits bind ATP at physiological concentrations. ATP binding and hydrolysis by the low-affinity subunits is fully dispensable for TRiC function in vivo. The conserved nucleotide-binding hierarchy among TRiC subunits is evolutionarily modulated through differential nucleoside contacts. Strikingly, high- and low-affinity subunits are spatially segregated within two contiguous hemispheres in the ring, generating an asymmetric power stroke that drives the folding cycle. This unusual mode of ATP utilization likely serves to orchestrate a directional mechanism underlying TRiC/CCT's unique ability to fold complex eukaryotic proteins.
msatcommander: detection of microsatellite repeat arrays and automated, locus-specific primer design

msatcommander is a platform-independent program designed to search for microsatellite arrays, design primers, and tag primers using an automated routine. msatcommander accepts as input DNA sequence data in single-sequence or concatenated, fasta-formatted files. Search data and locus-specific primers are written to comma-separated value files for subsequent use in spreadsheet or database programs. Binary versions of the graphical interface for msatcommander are available for Apple OS X and Windows XP. Users of other operating systems may run the graphical interface version using the available source code, provided their environment supports at least Python 2.4, Biopython 1.43, and wxPython 2.8. msatcommander is available from http://code.google.com/p/msatcommander/.
Twinning and Microcracking Associated with Monoclinic Zirconia in the Eutectic System Zirconia–Mullite

Crystallography and morphology of twins and microcracks in the eutectic system mullite–zirconia are discussed in view of the tetragonal-to-monoclinic transformation and associated toughening mechanisms. Specific twin relationships were observed in monoclinic ZrO2. Highly symmetric and crystallographically well-defined microcracks were observed at the mullite–ZrO2 interface. Microdiffraction revealed closely related crystallography of monnoclinic twins and microcracks. The number of twin variants depend on the monoclinic ZrO2 particle size. A method to calculate twinning shear strain using microcrack morphology is suggested. This parameter is essential in several fracture-mechanics calculations.
A usability evaluation of a home monitoring system

In this paper, we describe results from a laboratory-based study of user interactions with the Home Heartbeat system, which allows customers to monitor sensor data about their residence. Our study focused on usability, privacy, and security.
Impact of Chronic Left Ventricular Preload and Afterload on Doppler Tissue Imaging Velocities: A Study in Congenital Heart Disease

Background Doppler tissue imaging (DTI) velocities have been reported to be relatively independent of changes in ventricular loading conditions in adult studies. The clinical impact of altered left ventricular (LV) preload and afterload on DTI velocities in children with congenital heart disease has not been adequately evaluated. The purpose of this study was to evaluate the impact of chronic LV preload and afterload on DTI velocities in children with isolated ventricular septal defect and aortic valve stenosis compared with age-matched normal and abnormal (dilated cardiomyopathy) control groups. Methods From an apical 4-chamber view, DTI velocities were obtained at the cardiac base at the lateral mitral annulus, lateral tricuspid annulus, and interventricular septum in early diastole, late diastole, and ventricular systole. Results The majority of DTI velocities did not change significantly in patients with increased LV preload. Patients with increased LV afterload had significantly decreased systolic and early diastolic DTI velocities at both the lateral mitral annulus and ventricular septum compared with control subjects. Children with dilated cardiomyopathy had significantly decreased DTI velocities at all myocardial annular locations. Conclusions We conclude that increases in chronic LV preload do not significantly affect the majority of DTI velocities in children with ventricular septal defects. In addition, significantly increased chronic LV afterload in children with aortic valve stenosis is associated with decreased DTI velocities in the absence of other identifiable abnormalities of LV function. Decreased DTI velocity may be secondary to increased afterload or may alternatively be an early marker of subclinical LV longitudinal dysfunction.
Spatial variation of harmful algae and their toxins in flowing-water habitats: a theoretical exploration

Flow in riverine reservoirs and impoundments can be strong enough to wash out phytoplankton populations, including harmful algae. However, fringing coves and shoreline features can comprise a hydraulic storage zone that enhances algal persistence. Mathematical models of this situation were constructed to represent populations of toxic flagellates or cyanobacteria, and complementary models represented dynamics of exchange between a single cove and a main lake. Steady-state analyses predict that spatial variation in algal abundance and toxin concentration along the axis of flow in a riverine reservoir is most likely to arise for critical flows just below those causing washout, which can be identified by the Peclet number. Spatial variation in algal abundance and toxin concentration between a single cove and the main lake is predicted to occur when a cove is hydraulically isolated from the main lake, or as a transient phenomenon during strong flow events. This modeling suggests a potential for managing harmful algal blooms through flow manipulations in some instances, or by localized controls of abundance or toxicity in relatively isolated coves.
Somatic Evolution of Acquired Drug Resistance in Cancer

Acquired drug resistance is a central problem in cancer medicine. The diverse molecular mechanisms of acquired drug resistance all arise through the same process of somatic (within-body) cellular evolution. Even targeted drugs are subject to this failure. Genetic instability causes high genetic diversity among the cells of most cancers, but because somatic evolution results from selection as well as mutation, some classes of therapies are less prone than others to failure through acquired resistance. Cytotoxins, whether targeted or not, are especially prone to acquired drug resistance. Among the most promising classes of therapies expected to be robust against acquired resistance are: those that target systemic cancer symptoms instead of cancer cells, those that target cell motility rather than survival and proliferation, and those that target secreted metabolites of cancer cells rather than the cells themselves.
Fluid Mechanics Teaching and Research: A View from a Dean's Office

Teaching and research in a field such as fluid mechanics must be administered by the dean to form an integral part of a many-membered curricular structure characterized by balance, coherence, and stability. The undergraduate aspects of the subject are inherently collegiate, and the graduate, properly departmental—whatever the basis for professional division. However, the civil engineering topics in fluid mechanics have their counterparts in most of the other professional fields, so that all stand to gain by generalization of approach.
Data in context: Using case studies to generate a common understanding of data in academic libraries

Abstract As new expectations emerge in librarianship, librarians find themselves engaging with researchers throughout the entire research process. This includes during early stages, when research outputs are in their infancy. This shift means that any librarian might be faced with a ‘data question’ and be able to assist without necessarily being a ‘data’ expert. As libraries approach professional development in this field, additional difficulties occur as data cannot be easily understood without context. Instead of attempting to comprehensively cover this broad, nuanced, and sometimes vague topic, the authors took a different approach. In order to place ‘data’ in definable contexts, the authors created local, real-world case studies to introduce this topic to the library. This article describes the professional development event, complete with case studies, their development, discussion questions, and observations. As faculty and staff answered guided questions, they self-identified the value of existing librarian capabilities such as the reference interview, information location, and referral systems. This enabled library faculty and staff from across the library to engage positively and proactively, without any extensive background in this field.
Adverse Event and Complication Management in Gastrointestinal Endoscopy

Gastrointestinal endoscopy is a remarkably safe set of diagnostic and therapeutic techniques, and yet a small number of significant complications and adverse events are expected. Serious complications may have a material effect on the patient's health and well-being. They need to be anticipated and prevented if possible and managed effectively when identified. When complications occur they need to be discussed frankly with patients and their families. Informed consent, prevention, early detection, reporting, and systems improvement are critical aspects of effective complication management. Optimal complication management may improve patient satisfaction and outcome, as well as preserving the reputation and confidence of the endoscopist, and may minimize litigation.
Genetic determinants of acute hypoxic ventilation: patterns of inheritance in mice.

Acutely lowering ambient O2 tension increases ventilation in many mammalian species, including humans and mice. Inheritance patterns among kinships and between mouse strains suggest that a robust g...
Reading in the Crawl Space: A Study of an Urban School's Literacy-Focused Community of Practice.

Background/ContextThe pressure to understand “what works” to advance adolescents’ reading development has increased as the Common Core State Standards’ call for youth to grapple with a range of com...
Solid-State NMR Characterization of Mixed Phosphonic Acid Ligand Binding and Organization on Silica Nanoparticles.

As ligand functionalization of nanomaterials becomes more complex, methods to characterize the organization of multiple ligands on surfaces is required. In an effort to further the understanding of ligand–surface interactions, a combination of multinuclear (1H, 29Si, 31P) and multidimensional solid-state nuclear magnetic resonance (NMR) techniques was utilized to characterize the phosphonic acid functionalization of fumed silica nanoparticles using methylphosphonic acid (MPA) and phenylphosphonic acid (PPA). 1H → 29Si cross-polarization (CP)–magic angle spinning (MAS) solid-state NMR was used to selectively detect silicon atoms near hydrogen atoms (primarily surface species); these results indicate that geminal silanols are preferentially depleted during the functionalization with phosphonic acids. 1H → 31P CP-MAS solid-state NMR measurements on the functionalized silica nanoparticles show three distinct resonances shifted upfield (lower ppm) and broadened compared to the resonances of the crystalline lig...
The study of reacting, high energy flows using pulsed electron-beam fluorescence

The pulsed electron Iwam fluorescence technique for the measurement of gas specie densities along with rotational and vibrational population distributions is being developed for use in high enthalpy, chemically reacting flows. The fluorescence generated by a very high current, short duration pulse of 40keV electrons is spectroscopically analyzed. If measurements are made sufficiently early in the excitation-emission sequence the effects of collisional quenching as well as energy deposition in the gas caused by the beam's electrons are both minimized. We present spectroscopic and operational considerations that are important for the application of this new diagnostic technique to the study of nonequilibrium flow fields about a test model in the Calspan-University of Buffalo Research Center's Large Energy National Shock Tunnel. Flovvfield calculations using different chemistry models were performed to anticipate the nonequilibrium flowfield properties and to determine how reliably differences between the models could be measured.
Opposition to Home Rule 1

Local self-government has so long prevailed in English constitutional practice, and in recent times has been so generously extended to colonies and dominions, that it might seem an anomaly for Home Rule to be ardently desired in Ireland, yet bitterly contested and thus far withheld. Many favorable generally to the idea of autonomy without special reference to the condition of Ireland have believed this to result from a stubborn obstinacy and blind perverseness, perpetuating in tragic fashion a tragedy of olden times. But it might be suspected that such reluctance arose in part from circumstances of a great while ago, which continue or have bequeathed consequences not to be neglected; and an examination of the controversial literature which appeared just before the war reveals many objections which, in so far as they were actual and honestly held, were undoubtedly valid and potent. Certainly a great many people believed that Home Rule was not only unnecessary for the interests of Ireland, and really to the detriment of the Irish people, but that whatever might be the results with respect to that country, without doubt self-government, so far as it tended to separation and the erecting of an independent or hostile government, would be fatal to some of the largest interests of England and the British Empire.
Glycemic crises in patients with hematologic malignancies.

Glycemic crises associated with hematologic malignancies include diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic nonketotic syndrome (HHNS). The treatment of hematologic malignancies often includes administering high doses of steroids. Steroid therapy in patients with known diabetes can lead to uncontrolled hyperglycemia. Patients who have undiagnosed diabetes but present with risk factors may develop diabetes as a result of the steroids. This article reviews the pathophysiology and treatment of DKA and HNNS, two complications of uncontrolled hyperglycemia.
Do Menu Labeling Laws Translate into Results? Impacts on Population Obesity and Diabetes

We separately use the difference-in-differences technique and the synthetic control method on county-level data to test the impact of mandatory menu labeling laws on obesity and diabetes rates. Results show a decline in the growth of obesity rates following passage of the law at the state level in California and for six counties on the East Coast. We identify no significant impact to diabetes rates.
Analysis of Algaecide Exposures: an Evaluation of the I3− Method to Measure Sodium Carbonate Peroxyhydrate Algaecides

Algaecides are commonly used to control noxious algal growths in water resources. In order to make accurate predictions about responses of target and non-target species to algaecide exposures, reliable methods are needed to confirm exposures in the laboratory and the field. The focus of this research was to evaluate the I3 − method for measuring hydrogen peroxide (H2O2) exposures associated with applications of a sodium carbonate peroxyhydrate (SCP)-based algaecide. To meet this overall objective, method detection limits, interferences from field waters (turbidity, color, and algal cell density), and storage stability of samples were measured. The method detection limits were 0.2 (p < 0.0001) and 0.25 mg H2O2/L (p = 0.0002) for laboratory and field waters, respectively. The upper method detection limit was 7.5 mg H2O2/L for both waters. Turbidity (25.3 NTU) and color of field-collected water did not interfere with measurements. Algal cell densities of 104, 105, and 106 cells/mL of two planktonic algal species in laboratory water did not interfere with measurements. Measurements of samples stored in dark refrigeration and on ice remained stable over 4 days, while measurements of samples stored in direct sunlight in ambient temperatures were altered after 1 day. The I3 − method accurately measured H2O2 exposures in the laboratory water, field water, and laboratory water containing planktonic algae used in this experiment within the range of concentrations that would be applied in a field setting. These data demonstrated that this method has utility for confirming exposures after laboratory and field treatments of SCP-based algaecides.
Time-of-Flight Secondary Ion Mass Spectrometry profiling for arsenic in silicon dioxide matrix

This paper showed that 75As was a better analyte species than 28Si75As in silicon dioxide for accurate quantitative profiling by Time-Of-Flight Secondary Ion Mass Spectrometry. Contrary to silicon matrix, the ion yield of 75As showed 1 order higher than 28Si 75As in silicon dioxide matrix. The average RSF for 75As in silicon dioxide was determined to be 5.62E20 and lower variation of 75As RSF was observed.