cssi/SciSciGPT-SciSciNet huggingface dataset:
Adaptive responses of monkey somatosensory cortex to peripheral and central deafferentation

Abstract This study deals with two kinds of activity-dependent phenomena in the somatosensory cortex of adult monkeys, both of which may be related: (1) mutability of representational maps, as defined electrophysiologically; (2) alterations in expression of genes important in the inhibitory and excitatory neurotransmitter systems. Area 3b of the cerebral cortex was mapped physiologically and mRNA levels or numbers of immunocytochemically stained neurons quantified after disrupting afferent input peripherally by section of peripheral nerves, or centrally by making lesions of increasing size in the somatosensory thalamus. Survival times ranged from a few weeks to many months. Mapping studies after peripheral nerve lesions replicated results of previous studies in showing the contraction of representations deprived of sensory input and expansion of adjacent representations. However, these changes in representational maps were in most cases unaccompanied by significant alterations in gene expression for calcium calmodulin-dependent protein kinase isoforms, for glutamic acid decarboxylase, GABA A receptor subunits, GABA B receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) or N-methyl- D -aspartate (NMDA) receptor subunits. Mapping studies after lesions in the ventral posterior lateral nucleus (VPL) of the thalamus revealed no changes in cortical representations of the hand or fingers until >15% of the thalamic representation was destroyed, and only slight changes until approximately 45% of the representation was destroyed, at which point the cortical representation of the finger at the center of a lesion began to shrink. Lesions destroying >60% of VPL resulted in silencing of the hand representation. Although all lesions were associated with a loss of parvalbumin-immunoreactive thalamocortical fiber terminations, and of cytochrome oxidase staining in a focal zone of area 3b, no changes in gene expression could be detected in the affected zone until >40–50% of VPL was destroyed, and even after that changes in mRNA levels or in numbers of GABA-immunoreactive neurons in the affected zone were remarkably small. The results of these studies differ markedly from the robust changes in gene expression detectable in the visual cortex of monkeys deprived of vision in one eye. The results confirm the view that divergence of the afferent somatosensory pathways from periphery to cerebral cortex is sufficiently great that many fibers can be lost before neuronal activity is totally silenced in area 3b. This divergence is capable of maintaining a high degree of cortical function in the face of diminishing inputs from the periphery and is probably an important element in promoting representational plasticity in response to altered patterns of afferent input.
Characterization of 14C-naphthol uptake in excised root segments of clover (Trifolium pratense L.) and fescue (Festuca arundinaceae Screb.)

An isolated root uptake test (IRUT) was used to characterize the bioaccumulation of 14C-naphthol in excised root segments obtained from 6-month-old hydroponically grown plants: two varieties of fescue (Festuca arundinaceae Schreb.) and one variety of clover (Trifolium pratense L.). Naphthol uptake rates were directly related to naphthol concentration in the range 0.01 to 0.2 uM. The incubation time required for equilibrium to be reached between naphthol in root tissue and in solution was between 9 and 12 h. Tests using metabolic inhibitors, KCN, NaN3, and DNP, indicated that naphthol uptake may be the result of both passive and active mechanisms. Q10 values for naphthol uptake ranged from 1.05 to 1.16.
Natural gas consumption and climate : A comprehensive set of predictive state-level models for the United States

Abstract Separate models correlating natural gas (NG) consumption to climate have been developed for the residential and commercial sectors of the 50 U.S. states. The models relate a population-weighted average temperature to state per capita NG consumption on a monthly basis. The majority of the models have Pearson correlation coefficients greater than 0.90 supporting the use of temperature as the sole independent parameter. The sensitivities of the models to a 1°C increase in temperature, are compared for each state and the monthly sensitivity to climate integrated over the entire U.S. is investigated for a range of temperature perturbations. The predicted impact of a 1°C increase in mean monthly temperature on U.S. consumption is an 8.1% decrease in the residential sector and a 5.9% decrease in the commercial sector. In terms of the net consumption normalized over the study period (1984–1993) this corresponds to a 111.8 TWh decrease in the residential sector and a 47.0 TWh decrease in the commercial sector. The largest change for a single month occurs in January when consumption would decrease 19.7 TWh in the residential sector and 7.4 TWh in the commercial sector.
Simon Ball, The Bitter Sea: The Brutal World War II Fight for the Mediterranean

Simon Ball (London: Harper Press, 2010), Pp.380, £9.99, Pb, ISBN 978-0-00-720305-5 The question of the Mediterranean's significance in the strategy of European wars has fascinated leaders and histo...
Irradiation plus 5-fluorouracil: Cellular mechanisms of action and treatment schedules

The use of external irradiation and 5-fluorouracil continues because of the proven benefits of this combination in the treatment of a variety of human malignancies. There are probably several mechanisms of action on the cellular level that account for radiation sensitization. One main feature of both laboratory and applied clinical research in this area is the apparent superiority of prolonged exposure of this S-phase cytotoxic agent when administered with fractionated irradiation. Also reviewed here are schedules using protracted infusional chemoradiation with this agent that are being tested in ongoing clinical trials.
Ecological Design for a Network Scheduling Interface

A motivation in the design of Ecological Interfaces for process control is to augment the strengths of the human operator with the strengths of the automation in the computer system. This is especially important when building interfaces for managing the use of Wide Area Networks (WANs) in enterprise computing. This domain requires network operators to be able to control the allocation of resources and to monitor the occurrence of structural and functional failures. The relationship between the network architecture, infrastructure, traffic characteristics, and pricing scheme is dynamic and highly inter-related. A “Tetris-like”, bin-packing interface is designed based on principles drawn from an ecological user model and a situation theoretic representation of the problem space and the user's task. The effectiveness of this display is based on a number of ecological features whose design is automatically generated through the determination and selection of the interface context.
Stereoselective synthesis of β-hydroxy-α-methylcarboxylic acid thiol esters via vinyloxyboranes

Abstract Both threo - and erythro -β-hydroxy-α-methylcarboxylic acid thil esters are stereoselectively synthesized through an aldol-type condensation of vinyloxyboranes derived formally from s- tert -butyl propanethioate.
A data-mining approach to improving polycythemia vera diagnosis

This paper presents a data-mining approach to the extraction of new decision rules for Polycythemia Vera (PV) diagnosis, based on a reduced and optimized set of lab parameters. Ten laboratory and other clinical findings (eight parameters from the Polycythemia Vera Study Group (PVSG) criteria + sex and hematocrit (HCT)) on 431 PV patients from the original PVSG cohort, and records on 91 patients with other myeloproliferative disorders that can be easily misdiagnosed with PV, were included in this study. Significant differences were not found in the correctness of diagnostic classification of patients using either a trained artificial neural network (98.1%) or a support vector machine (95%) versus using PVSG diagnostic criteria, which are considered as a 'gold-standard' for the diagnosis of PV. Reducing the original parameters of our dataset to only four parameters: HCT, PLAT, SPLEEN and WBC, we still have obtained good classification results. New rules for improved differential diagnosis of PV are specified based on these four parameters. These rules may be used as a complement to the standard PVSG criteria, particularly in the differential diagnosis between PV and other myeloproliferative syndromes.
CHARACTERIZATION OF PROTEINS DURING AGGREGATION USING TURBIDIMETRY

The dissolution process for hydrophobic proteins as well as protein denaturation-renaturation reactions often lead to the formation of aggregates. The characterization of the aggregates in terms of sire and the characterization of the physico-chemical changes undergone by the proteins are key to the elucidation of the kinetics of both, the aggregation processes and the denaturation-renaturation reactions. The aggregation processes and the denaturation-renaturation reactions are amenable to characterization through spectroscopy techniques. This paper reports on a technique for the estimation of the particle size and the absorption coefficients of proteins in solution and in protein aggregates present during denaturation-renaluration reactions. The technique reported is based on the application of Mie theory to turbidity measurements of polydisperse particulate systems. Mie theory is applied to both, the region where the particles are non-absorbing and, to the spectral region where the protein intrinsic chr...
Confidence and decision speed in the revision of opinion

Abstract The present experiment examined decision speed, measured without the subject's knowledge, and sequential confidence revision in a two-choice decision task. Subjects were presented with ten sequences of 20 events from one of two data-generating devices. Before each event was presented, the subjects predicted the event outcome, and after each event they decided which of the two data-generating devices was being used and gave a judgment of confidence in this decision. Following events that disconfirmed their favored hypothesis, subjects demonstrated a marked resistance to decreasing their confidence level (Inertia Effect). Two possible explanations of the Inertia Effect were postulated and their predictions were compared with the data. A commitment hypothesis assumed that subjects were unwilling to reduce their stated confidence following commitment to a decision, while a pattern-effect hypothesis was based upon a subject's hypothetical expectancies, reflected in his predictions. Both hypotheses were partially supported; the Inertia Effect was a function of subjects' predictions and was accompanied by a decrease in decision speed.
Microwave-assisted iridium-catalyzed [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes

Abstract The [Ir(COD)Cl] 2 /dppe system effectively catalyzes the solid-phase [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes under microwave conditions. The reaction results in high purity of isoindoline derivatives with moderate yields.
Selective determination of inorganic mercury in the presence of organomercurial compounds in biological material.

Abstract We have described a method which selectively measures radioactive inorganic mercury in the presence of organomercurial compounds labeled with the 203Hg isotope. This method may be used for the study of the cleavage of the carbon-mercury bond in animals injected with labeled organomercurial compounds. The principle of the method is the selective reduction of inorganic mercury by SnCl2 to elemental vapor. The latter is swept from the sample by an air stream collected on a specific absorbent, Hopcalite, where the radioactivity is determined by γ scintillation counting.
An overview of the CORBA portable object adapter

An Object Adapter is an integral part of the Common Object Request Broker Architecture (CORBA). An Object Adapter assists an Object Request Broker (ORB) in delivering client requests to server object implementations (servants). Services provided by an Object Adapter include: (1) generating and interpreting object references, (2) activating and deactivating servants, (3) demultiplexing requests to map object references onto their corresponding servants, and (4) collaborating with automatically-generated IDL skeletons to invoke operations on servants. This paper provides two contributions to the study of Object Adapters. First, it outlines the CORBA Portable Object Adapter (POA) specification, which is a recent addition to the CORBA standard that greatly simplifies the development of portable and extensible servants and server applications. The design goals, architectural components, and semantics of the POA are explained. Second, the paper describes the design choices made to adapt the POA for the TAO Real-time ORB. Key design issues regarding efficient demultiplexing, upcall and collocation optimizations, ORB and POA concurrency configurations, POA synchronization, and predictability are covered.
Solving the molecular diagnostic testing conundrum for Mendelian disorders in the era of next-generation sequencing: single-gene, gene panel, or exome/genome sequencing

Next-generation sequencing is changing the paradigm of clinical genetic testing. Today there are numerous molecular tests available, including single-gene tests, gene panels, and exome sequencing or genome sequencing. As a result, ordering physicians face the conundrum of selecting the best diagnostic tool for their patients with genetic conditions. Single-gene testing is often most appropriate for conditions with distinctive clinical features and minimal locus heterogeneity. Next-generation sequencing-based gene panel testing, which can be complemented with array comparative genomic hybridization and other ancillary methods, provides a comprehensive and feasible approach for heterogeneous disorders. Exome sequencing and genome sequencing have the advantage of being unbiased regarding what set of genes is analyzed, enabling parallel interrogation of most of the genes in the human genome. However, current limitations of next-generation sequencing technology and our variant interpretation capabilities caution us against offering exome sequencing or genome sequencing as either stand-alone or first-choice diagnostic approaches. A growing interest in personalized medicine calls for the application of genome sequencing in clinical diagnostics, but major challenges must be addressed before its full potential can be realized. Here, we propose a testing algorithm to help clinicians opt for the most appropriate molecular diagnostic tool for each scenario.
Simulation of particle dispersion in a two‐dimensional mixing layer

Calcul numerique des trajectoires de particules dans une couche cisaillee libre simulee par des tourbillons discrets
Sintering of titanium dioxide nanoparticles: a comparison between molecular dynamics and phenomenological modeling

Molecular dynamics simulations were used to determine the melting points of anatase and rutile nanoparticles. The melting points decrease with decrease in particle diameter and are in reasonable agreement with the empirical formula derived by Buffat and Borel. The phenomenological model of Koch and Friedlander is unable to predict the temperature rise during initial stages of sintering with acceptable accuracy. It is argued that the Koch and Friedlander assumption of linear surface reduction rate upon sintering may be inadequate for the time scales under consideration. A theoretical model using direct area measurement from molecular dynamics simulations and a single adjustable parameter is able to predict temperature rise during initial stages of sintering within acceptable error limits.
Influence of Donor Microbiota on the Severity of Experimental Graft-versus-Host-Disease

Abstract The link between microbial flora and the shaping of immune responses is being increasingly appreciated, and recent data have uncovered a role for recipient microbiota in the severity of graft-versus-host disease (GVHD). The impact of donor microbiota on T cell–mediated alloresponses and GVHD is not known, however. Using multiple clinically relevant murine models, we analyzed the effect of donor microbiota on the severity of GVHD induced by T cells from specific pathogen-free and germ-free donors, and found that donor microbiota does not alter the expansion or differentiation of alloreactive T cells or the severity of GVHD.
Adsorption of Methanol on the MgO(100) Surface: An Infrared Study at Room Temperature

Methanol adsorbed on the (100) face of MgO has been studied at room temperature and elevated methanol pressures using transmission Fourier transform infrared spectroscopy. From these investigations, we find evidence of two structures for the adsorbed methanol. At low coverages, the methanol molecules congregate into two-dimensional islands that are strongly associated with the substrate. The properties of this submonolayer-to-monolayer thin film are similar to those of solid methanol. Once the available surface sites are occupied and a complete monolayer has formed, the methanol begins to condense in multilayers, creating a thin film on the surface with properties similar to liquid methanol.
Borders, Voices, Classes: A Response to Mary Ann Duffy's Review of Out of Our Minds: Anti‐Intellectualism and Talent Development in American Schooling

(1999). Borders, Voices, Classes: A Response to Mary Ann Duffy’s Review of Out of Our Minds: Anti-Intellectualism and Talent Development in American Schooling. Curriculum Inquiry: Vol. 29, No. 2, pp. 221-226.
Monthly carbon emissions from natural-gas flaring and cement manufacture in the United States

Annual data on carbon emissions from fossil-fuel combustion and cement manufacture have been used in studies of the carbon cycle for the last few decades. However, annual data do not specify carbon emissions on the seasonal timescales relevant to biospheric uptake and other processes affecting the carbon cycle. Estimates of monthly emissions from fossil-fuel consumption in the United States (US) have shown that an increasing percentage of the annual emissions are occurring during the growing season; however, carbon emitted from flaring natural gas at well sites was not accounted for in those emissions estimates, nor was carbon emitted during cement manufacture. Here we show that emissions from flaring, which amount to around 0.1 % of all fossil-fuel carbon emissions in the US, have no clear and persistent annual pattern that can be detected in the data. In contrast, carbon emissions from cement manufacture, which add about 0.7% to carbon emissions from fossil fuels in the US, have a clear and persistent annual pattern including low values in late winter and early spring. In this paper, we provide a few remarks on carbon emissions from natural-gas flaring before presenting monthly emissions estimates. We then focus on the methodology for calculating carbon emissions from cement manufacture before presenting and discussing the monthly emissions estimates. DOI: 10.1111/j.1600-0889.2006.00195.x
Using the top quark for testing standard-model polarization and CP predictions

Once top quarks are found, because they are heavy they will allow many new tests of the standard model (SM) and new probes of physics at the 100-GeV scale. In this paper we show how to test the standard-model QCD predictions for the transverse polarization of a top quark produced at the Fermilab Tevatron, Superconducting Super Collider, CERN Large Hadron Collider, and the Next Linear Collider. We also examine the most general form of the {ital W}-{ital t}-{ital b} vertex, and show how to detect effects of non-SM operators. Ways of detecting non-SM {ital CP}-violation effects in either the production or the decay of the top quarks and top antiquarks are examined.
Tool Time: Gender and Students' Use of Tools, Control, and Authority.

In this study, we examined how students used science equipment and tools in constructing knowledge during science instruction. Within a geographical metaphor, we focused on how students use tools when constructing new knowledge, how control of tools is actualized from pedagogical perspectives, how language and tool accessibility intersect, how gender intersects with tool use, and how competition for resources impacts access to tools. Sixteen targeted students from five elementary science classes were observed for 3 days of instruction. Results showed gender differences in students' use of exclusive language and commands, as well as in the ways students played and tinkered with tools. Girls tended to carefully follow the teacher's directions during the laboratory and did little playing or tinkering with science tools. Male students tended to use tools in inventive and exploratory ways. Results also showed that whether or not a student had access to his or her own materials became indicative of the type of verbal interactions that took place during the science investigation. Gender-related patterns in how tools are shared, how dyads relate to the materials and each other, and how materials are used to build knowledge are described. © 2000 John Wiley & Sons, Inc. J Res Sci Teach 37: 760–783, 2000
Hillslope-Scale Controls on Remote Sensing of Soil Moisture with Microwave Radiometry

Microwave radiometry is emerging as an important tool for global remote sensing of near-surface soil moisture in the coming decade. In a modeling study, we find that hillslope-scale topography (tens of meters) influences predicted microwave brightness temperatures at significantly coarser scales (kilometers). Through the physics of microwave remote sensing, topography is understood to effect brightness temperature observations in two important ways: (1) modulating the spatial distribution of factors affecting emission like vegetation biomass, moisture, and surface and canopy temperatures, and (2) determining the incidence angle and polarization rotation the observing sensor makes with the local land surface. Local incidence and polarization rotation angles can be explicitly computed knowing local terrain slope and aspect and sky position of the sensor. In an analysis of two synthetic domains, predicted hillslope-scale brightness temperatures within a less rugged landscape that is presented here can vary from approximately 224 to 302 K in the horizontal polarization and from approximately 298 to 320 K in the vertical polarization. Impacts of hillslope-scale heterogeneity in factors effecting emission account for at most approximately 2 K in predicted watershed-scale brightness temperature, while impacts of hillslope-scale topography on observing geometry can account for up to 28 K in predicted watershed-scale brightness temperatures in a topographically rugged area.
Adenosine A1 receptor mediates delayed cardioprotective effect of sildenafil in mouse

Sildenafil induces powerful cardioprotection against ischemia/reperfusion (I/R) injury. Since adenosine is known to be a major trigger of ischemic preconditioning, we hypothesized that A1 adenosine receptor (A1AR) activation plays a role in sildenafil-induced cardioprotective signaling. Adult male C57BL wild-type (WT) mice or their corresponding A1AR knockout (A1AR-KO) mice were treated intraperitoneally (i.p.) with either sildenafil (0.71 mg/kg, equivalent to 50 mg dose for a 70 kg patient) or volume-matched saline. The selective A1AR antagonist 8cyclopentyl-1,3-dipropyxanthine (DPCPX; 0.1 mg/kg, i.p.) was administered 30 min before sildenafil. The hearts were isolated 24 h later and subjected to 30 min of global ischemia and 1 h of reperfusion in Langendorff mode. Post-ischemic myocardial infarct size (mean±SEM; % of risk area) was reduced in C57BL-WT mice treated with sildenafil (5.6±0.9) versus saline control group (27.3±2.1; pb0.05; n=6/each). However, sildenafil failed to protect the A1AR-KO hearts (31.6±1.9 vs. 32.3±1.5 with saline, pN0.05). Additionally, DPCPX treatment abolished the infarct limiting effect of sildenafil (27.3±3.2, pb0.05). DPCPX alone had no effect on infarct size as compared with the control group. No significant changes in post-ischemic recovery of left ventricular pressure and heart rate were observed in the sildenafil-treated group. We further examined the effect of sildenafil in protection against simulated ischemia and reoxygenation injury in adult cardiomyocytes derived from WT and A1AR-KO mice. WT myocytes treated with sildenafil (1 μM) demonstrated significantly lower trypan blue-positive necrotic cells. However, cardiomyocytes derived from A1AR-KO mice or DPCPX-treated WT cells failed to show protection against necrosis with sildenafil. These results suggest that A1AR activation following treatment with sildenafil plays an integral role in the signaling cascade responsible for delayed protection against global I/R injury.
Multiwavelets: Theory and bioinformatic applications

Multiwavelets imply a better spatial and temporal resolution than uniwavelets. Nonetheless, they are practically unknown to statisticians and practitioners, and multiwavelet statistical literature is practically next to none. This article is devoted to the theory and applications of multiwavelets in microarray analysis and functional magnetic resonance imaging.
Time multiplexing and control for optical cellular-hypercube arrays

We discuss the cellular-hypercube optical free-space interconnection architecture and its implementation by two-dimensional smart-pixel optoelectronic cellular arrays. We emphasize the behavior of the cellular hypercube in performing shift-invariant parallel shifts of data, a basic requirement of most single-instruction multiple-data algorithms. We present a time-multiplexing scheme for realizing the cellular hypercube, showing that the communication time is inversely proportional to the number of optical detectors per cell. We also present an improved hybrid interconnection network with improved performance that combines the cellular hypercube and mesh, using optics for the longer-distance connections and electronics for nearest-neighbor connections.
Multicategory Support Vector Machines

Two-category support vector machines (SVM) have been very popular in the machine learning community for classification problems. Solving multicategory problems by a series of binary classifiers is quite common in the SVM paradigm; however, this approach may fail under various circumstances. We propose the multicategory support vector machine (MSVM), which extends the binary SVM to the multicategory case and has good theoretical properties. The proposed method provides a unifying framework when there are either equal or unequal misclassification costs. As a tuning criterion for the MSVM, an approximate leave-one-out cross-validation function, called Generalized Approximate Cross Validation, is derived, analogous to the binary case. The effectiveness of the MSVM is demonstrated through the applications to cancer classification using microarray data and cloud classification with satellite radiance profiles.
Effect of Changes in Technical Parameters in Radiological Safety

This work analyzes the generation of secondary radiation that affects the professionals of health during interventional X ray procedures in first level hospitals. The research objectives were, on the one hand, to quantify the amount of radiation and to compare it with norms in force with respect to magnitudes, and on the other hand to evaluate the elements of protection used. The measurements will help to improve the radiological safety, to assess the eventuality of risks and, in the last term, to the possibility of norms modification for the improvement of the protection, especially that of the personnel who daily make a certain amount of interventional procedures guided by radiation, like angiographic cine applications, using continuous or pulsed fluoroscopy. The motivation of the study is in the suspicion that present interventionism is made with a false sensation of safety, based only in the use of lead apron and protection elements incorporated in the equipment by the manufacturer, nevertheless not always the health personnel are conscious that an excessive proximity with the tube and the patient body becomes a risky source of secondary and scattered radiation. The obtained results allow us to demonstrate the existence of conditions of risk, even possible iatrogenic events, in particular when the procedures imply the use of certain techniques of radiographic exploration, thus reaching the conclusion that the radiographic methodology must be changed in order to rationalize so much?. In order to achieve this we propose modifications to the present norms and legislation referred to the radiological safety in Chile.
Comparison of in-hospital outcomes with low-dose fibrinolytic therapy followed by urgent percutaneous coronary intervention versus percutaneous coronary intervention alone for treatment of ST-elevation myocardial infarction

In patients with acute ST-elevation myocardial infarction (STEMI), a strategy of prehospital reduced dose fibrinolytic administration coupled with urgent percutaneous coronary intervention (PCI), termed FAST-PCI strategy, has been found to be superior to primary PCI (PPCI) alone. A coordinated STEMI system of care that includes FAST-PCI should offer better outcomes than a system in which prehospital diagnosis of STEMI is followed by PPCI alone. The aim of this study was to compare the in-hospital outcomes for patients treated with the FAST-PCI approach with outcomes for patients treated with the PPCI approach in a common system. The in-hospital data for 253 STEMI patients (March 2003–December 2009) treated with a FAST-PCI protocol were compared with 124 patients (January 2010–August 2011) treated with PPCI strategy alone. In-hospital mortality was the primary comparator. Stroke, major bleeding, and reinfarction during index hospitalization were also compared. The in-hospital mortality was significantly lower with FAST-PCI than with PPCI (2.77% vs 10.48%, p = 0.0017). Rates of stroke, reinfarction, and major bleeding were similar in the 2 groups. There was a lower frequency of pre-PCI Thrombolysis In Myocardial Infarction 0 flow (no patency) seen in patients treated with FAST-PCI compared with the PPCI patients (26.7% vs 62.7%, p
Review: Quantitative structure/activity relations based on use-dependent block and repriming kinetics in myocardium

Different class 1 antiarrhythmic drugs have differing capabilities for producing a rate-dependent modulation of cardiac excitability. Structural hypotheses regarding these drug actions, both in terms of their widely differing abilities for blocking myocardial sodium channels during individual action potentials and their associated repriming kinetics, have been proposed. Recent studies on the channel blocking actions of these drugs, assessed using maximum upstroke velocities of intracellularly recorded actions potentials (APs), are reviewed in order to test these hypotheses. The size/solubility hypothesis, which says that smaller antiarrhythmic drugs with good lipid distribution capabilities provide more rapid repriming kinetics, is supported by results on 36 of 40 drugs having molecular weights up to 350. Blocking abilities during individual APs are also examined, with lipid distribution coefficients describing this blocking capability within selected classes of drug structures. However overall “potency” must include consideration of drug repriming kinetics which allows for accumulation of excitability block. Evidence which suggests that the kinetically slower drugs may be more cardiotoxic (arrhythmogenic) is presented. A model for the steep size dependence of drug recovery times is provided by a cylindrical pore having a radius of 4.1 Angstroms. Finally the different drug pools that drive the hypothesized hydrophilic and hydrophobic pathways to the receptor are considered in order to explain why drug lipid distribution characteristics might play a role in recovery kinetics.
A synthetic three-color scaffold for monitoring genetic regulation and noise.

Background: Current methods for analyzing the dynamics of natural regulatory networks, and quantifying synthetic circuit function, are limited by the lack of well-characterized genetic measurement tools. Fluorescent reporters have been used to measure dynamic gene expression, but recent attempts to monitor multiple genes simultaneously in single cells have not focused on independent, isolated measurements. Multiple reporters can be used to observe interactions between natural genes, or to facilitate the ‘debugging’ of biologically engineered genetic networks. Using three distinguishable reporter genes in a single cell can reveal information not obtainable from only one or two reporters. One application of multiple reporters is the use of genetic noise to reveal regulatory connections between genes. Experiments in both natural and synthetic systems would benefit from a well-characterized platform for expressing multiple reporter genes and synthetic network components. Results: We describe such a plasmid-based platform for the design and optimization of synthetic gene networks, and for analysis of endogenous gene networks. This network scaffold consists of three distinguishable fluorescent reporter genes controlled by inducible promoters, with conveniently placed restriction sites to make modifications straightforward. We quantitatively characterize the scaffold in Escherichia coli with single-cell fluorescence imaging and time-lapse microscopy. The three spectrally distinct reporters allow independent monitoring of genetic regulation and analysis of genetic noise. As a novel application of this tool we show that the presence of genetic noise can reveal transcriptional co-regulation due to a hidden factor, and can distinguish constitutive from regulated gene expression. Conclusion: We have constructed a general chassis where three promoters from natural genes or components of synthetic networks can be easily inserted and independently monitored on a single construct using optimized fluorescent protein reporters. We have quantitatively characterized the baseline behavior of the chassis so that it can be used to measure dynamic gene regulation and noise. Overall, the system will be useful both for analyzing natural genetic networks and assembling synthetic ones.
Reconstructive perspectives of cutaneous defects involving the nasal tip: a retrospective review.

Objectives To create an algorithm that derives our preferred reconstruction technique for cutaneous defects involving the nasal tip and to review the management and outcomes of patients with nasal tip cutaneous defects after their initial reconstruction. Methods A retrospective review of patients undergoing repair of cutaneous defects involving the nasal tip between January 2006 and January 2009. After data compilation, a defect-based algorithm deriving our repair technique was created. Results Seventy-two patients were indentified: 57% underwent full-thickness skin graft repair (n = 41), 19% underwent forehead flap repair (n = 14), and 17% underwent bilobe flap repair (n = 12). The remaining 7% underwent repair using nasal cutaneous flaps harvested adjacent to the defect (n = 5). Nasal tip defect involvement of an adjacent nasal aesthetic unit was the most critical factor in selecting a reconstruction technique. Further categorization by the presence of nasal ala involvement, cartilage exposure, and defect surface area allowed reliable prediction of our reconstruction technique. Dermabrasion was routinely performed early in the postoperative course (25% [18 of 72 patients]). Corticosteroid injection was commonly used for those undergoing forehead flap (71% [10 of 14 patients]) and bilobe flap (50% [6 of 12 patients]) repair. Aesthetic revision surgery was infrequently required (15% [11 of 72 patients]). All aesthetic outcomes were good or satisfactory. Conclusion The included algorithm offers a systematic approach for managing cutaneous defects involving the nasal tip and derives our preferred technique with high reliability.
A Tool for Automated Revision of Grammars for NLP Systems

We present an algorithm and a tool for automatically revising grammars for natural language processing (NLP) systems to disallow specifically identified sentences or sets of sentences. We also outline an approach for automatically revising attribute value grammars using counter-examples. Developing grammars for NLP systems that are both general enough to accept most sentences about a domain, but constrained enough to disallow other sentences is very tedious. Our approach of revising grammars automatically using counter-examples greatly simplifies the development and revision of tightly constrained grammars. We have successfully used our tool to constrain over-generalizing grammars of speech understanding systems and obtained higher recognition accuracy.
Cataract surgery complications in 1 year at an academic institution.

Abstract Purpose To delineate all complication rates of cataract surgery and define normative rates, trends, and outliers as part of continuous quality management. Setting John A. Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City, Utah, USA. Methods All cataract surgeries done at the John A. Moran Eye Center from July 1, 1996, to June 30, 1997 (1 complete academic year) were reviewed for intraoperative complications using operative reports. Cases with documented preoperative zonular dehiscence, traumatic capsule breakage, previous vitreous in the anterior chamber, or an accompanying major secondary procedure (e.g., trabeculectomy, corneal transplantation) were eliminated from the study. Over this year, 1729 cataract surgeries were performed by 12 attending physicians, 3 fellows, and 4 residents. Cases of cataract removal with intraocular lens implantation ranged from 18 to 510 per surgeon. Results There were 44 cases (2.54%) of posterior capsule rupture, with 29 (1.68%) requiring vitrectomy. Most capsule breakages occurred during phacoemulsification. The Student t test showed no statistically significant difference in the incidence of capsule breakage among surgeons (incidence from 0% to 6.25%). All cases were started as phacoemulsification, with 6 conversions (0.35%) to planned extracapsular cataract extraction. Conclusions In evaluating continuous quality management, no outliers were found within our center. Phacoemulsification was the part of cataract surgery most likely to cause posterior capsule rupture.
Algorithm-Enabled Low-Dose Micro-CT Imaging

Micro-computed tomography (micro-CT) is an important tool in biomedical research and preclinical applications that can provide visual inspection of and quantitative information about imaged small animals and biological samples such as vasculature specimens. Currently, micro-CT imaging uses projection data acquired at a large number (300-1000) of views, which can limit system throughput and potentially degrade image quality due to radiation-induced deformation or damage to the small animal or specimen. In this work, we have investigated low-dose micro-CT and its application to specimen imaging from substantially reduced projection data by using a recently developed algorithm, referred to as the adaptive-steepest-descent-projection-onto-convex-sets (ASD-POCS) algorithm, which reconstructs an image through minimizing the image total-variation and enforcing data constraints. To validate and evaluate the performance of the ASD-POCS algorithm, we carried out quantitative evaluation studies in a number of tasks of practical interest in imaging of specimens of real animal organs. The results show that the ASD-POCS algorithm can yield images with quality comparable to that obtained with existing algorithms, while using one-sixth to one quarter of the 361-view data currently used in typical micro-CT specimen imaging.
Fine Particle Emissions from Heavy Fuel Oil Combustion in a Firetube Package Boiler

Abstract Combustion is a significant source of fine particulate matter (PM) emissions, and heavy oil combustion is suspected of producing particulate emissions with potentially significant toxicity. This paper is concerned with the characterization of particulate emissions from a practical boiler burning heavy fuel oils, The purpose of the study was to identify possible mechanisms that might relate both the combustion process and the fuel burned to the size segregated characterization of the fine particles formed, and consequently to their propensity to cause pulmonary injury. The data presented, therefore, help suggest specific fundamental issues which define directions for future research in this area. In this initial study, samples of PM were taken from the stack of a commercial 732kW (2.5 x 10° Btu/hr) rated firetube boiler burning four different heavy fuel oils, including two grades and three sulfur contents. Submicron and superrnicron particle size distributions (PSDs) were measured using an in-stac...
Laminar Shear Stress Mechanisms by Which Endothelial Cells Transduce an Atheroprotective Force

Mechanical forces are important modulators of cellular function in many tissues and are particularly important in the cardiovascular system. The endothelium, by virtue of its unique location in the vessel wall, responds rapidly and sensitively to the mechanical conditions created by blood flow and the cardiac cycle. In this study, we examine data which suggest that steady laminar shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. We explore the ability of shear stress to modulate atherogenesis via its effects on endothelial-mediated alterations in coagulation, leukocyte and monocyte migration, smooth muscle growth, lipoprotein uptake and metabolism, and endothelial cell survival. We also propose a model of signal transduction for the endothelial cell response to shear stress including possible mechanotransducers (integrins, caveolae, ion channels, and G proteins), intermediate signaling molecules (c-Src, ras, Raf, protein kinase C) and the mitogen activated protein kinases (ERK1/2, JNK, p38, BMK-1), and effector molecules (nitric oxide). The endothelial cell response to shear stress may also provide a mechanism by which risk factors such as hypertension, diabetes, hypercholesterolemia, and sedentary lifestyle act to promote atherosclerosis.
The nonreceptor protein-tyrosine kinase CSK complexes directly with the GTPase-activating protein-associated p62 protein in cells expressing v-Src or activated c-Src.

CSK is a predominantly cytosolic protein-tyrosine kinase (PTK) that negatively regulates Src family PTKs by phosphorylation of a conserved tyrosine near their C termini. Little is known about how CSK itself is regulated. On the basis of immunofluorescence studies, a model has been proposed that when c-Src is activated, it is redistributed to podosomes, in which substrates become phosphorylated, creating binding sites for CSK. CSK is recruited to these sites of c-Src activation via its SH2 and SH3 domains and is then in a position to downregulate c-Src activity (B. W. Howell and J. A. Cooper, Mol. Cell. Biol. 14:5402-5411, 1994). To identify phosphotyrosine (P.Tyr)-containing proteins that may mediate translocation of CSK due to c-Src activation, we have examined the whole spectrum of P.Tyr-containing proteins that associate with CSK in v-Src NIH 3T3 cells by anti-P.Tyr immunoblotting. Nine P.Tyr-containing proteins coimmunoprecipitated with CSK from v-Src NIH 3T3 cells. One of these, an approximately 62-kDa protein, also associated with CSK in NIH 3T3 cells treated with vanadate prior to lysis and in NIH 3T3 cells expressing an activated c-Src mutant. This 62-kDa protein was shown to be identical to the GTPase-activating protein (GAP)-associated p62 (GAP-A.p62) protein. The interaction between CSK and GAP-A.p62 could be reconstituted in vitro with glutathione S-transferase fusion proteins containing full-length CSK or the CSK SH2 domain. Furthermore, our data show that CSK interacts directly with GAP.A-p62 and that the complex between the two proteins is localized in subcellular membrane or cytoskeletal fractions. Our results suggest that GAP-A.p62 may function as a docking protein and may mediate translocation of proteins, including GAP and CSK, to membrane or cytoskeletal regions upon c-Src activation.
Taking Psych 101: A View from the Back of the Room

Hoping to refresh my memory on how students might study for (1 first-year college course, I took introductory psychology. I found that certain study skills, such as identifying main ideas and using the SQ3R system, were of little benefit. Information from (1 single source, either the textbook or the lectures, was often insufficient for adequate comprehension. With only the vaguest understanding of important concepts, it was possible to perform well on multiple-choice tests. Based on my experience in this course, I offer some suggestions for helping students to learn introductory psychology.
Taste Receptors in the Gastrointestinal Tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing

Changes in the luminal contents of the gastrointestinal tract modulate gastrointestinal functions, including absorption of nutrients, food intake, and protection against harmful substances. The current notion is that mucosal enteroendocrine cells act as primary chemoreceptors by releasing signaling molecules in response to changes in the luminal environment, which in turn activate nerve terminals. The recent discovery that taste receptors and G protein subunits α-gustducin and α-transducin, involved in gustatory signal transduction, are expressed in the gastrointestinal mucosa supports the concept of a chemosensory machinery in the gastrointestinal tract. An understanding of luminal sensing processes responsible for the generation of the appropriate functional response to specific nutrients and nonnutrients is of clinical importance since aberrant or unsteady responses to changes in luminal contents might result in disease states ranging from intoxication to feeding disorders and inflammation. The purpose of this theme article is to discuss the functional implications of bitter taste signaling molecules in the gastrointestinal tract deduced by their localization in selected populations of epithelial cells and their relationship with neural pathways responsible for the generation of specific responses to luminal contents.
Hardware Containers for Software Components: A Trusted Platform for COTS-Based Systems

Much of modern software development consists of assembling together existing software components and writing the glue code that integrates them into a unified application. The term COTS-Based System (CBS) is often used to describe such applications, for which the components assembled are understood to be Commercial-Off-The-Shelf (COTS) components written by a multitude of independent third parties. The manner of assembly in CBS includes full-source components that are integrated at compile-time, pure-binary libraries incorporated at load-time, and plugins that are loaded into the application at execution time by the user.Because components have access to system resources, applications may crash due to faulty components or may be compromised by malicious components. In this paper, we ask the question: can hardware support the development and deployment of CBS by providing applications with a trusted platform for managing components and their interactions?We present an architecture that places each CBS component in a hardware-enforced container. The hardware then detects improper usage of system resources (unauthorized memory accesses or denial-of-service) and enables applications to undertake a hardware-supervised recovery procedure. Furthermore, the hardware also maintains a violation record to enable developers to recreate the violation for the purpose of debugging and further development. Taken together, the purpose of the architecture we propose is to enable executing untrusted CBS code on trusted hardware.