cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of mitochondrial function by Epac2 contributes to acute inflammatory hyperalgesia

Gαs-coupled receptors signaling through cAMP provide a key mechanism for the sensitization of nociceptive sensory neurons, and the cAMP effector Epac has been implicated in the transition from acute to chronic pain. Epac exerts its effects through Rap1 and protein kinase C (PKC). To identify targets of Epac-PKC signaling in sensory neurons of the mouse dorsal root ganglion (DRG), we profiled PKC substrate proteins phosphorylated in response to the activation of Epac with the proinflammatory prostaglandin E2 (PGE2). A prominent Epac-dependent phospho-protein band induced by PGE2 was identified by mass spectrometry as the mitochondrial enzyme pyruvate dehydrogenase (Pdha1). In dissociated DRG from both males and females, the recruitment of Pdha1 to phospho-protein fractions was rapidly induced by PGE2 and prevented by selective inhibition of Epac2. Epac activation increased mitochondrial respiration, consistent with an increase in Pdha1 function mediated by Epac2. Hindpaw injection of PGE2 induced heat hyperalgesia in males and females, but Pdha1 phosphorylation occurred only in males. Hyperalgesia was attenuated in males but not in females by systemic inhibition of Epac2, and also by a mitochondrial membrane potential uncoupler, dinitrophenol, supporting a role for mitochondrial regulation in acute hyperalgesia. These findings identify a mechanism for the regulation of mitochondrial function by Epac2 that contributes to acute inflammatory hyperalgesia in male mice. Systemic administration of the cyclooxygenase 2 inhibitor celecoxib suppressed both PGE2-induced heat hyperalgesia and Pdha1 phosphorylation in DRG of males but not females, suggesting that prostaglandin synthesis within the DRG mediates the phosphorylation of Pdha1 in response to hindpaw insult.SIGNIFICANCE STATEMENT There has been extensive investigation of mitochondrial dysfunction as a causative factor in neuropathic pain disorders. In contrast, results reported here implicate enhanced mitochondrial function as a contributing factor in the development of acute inflammatory hyperalgesia. We describe a mechanism in which Epac2 activation by prostaglandin receptors leads to phosphorylation of pyruvate dehydrogenase and an increase in mitochondrial respiration in peripheral sensory neurons. Although Epac2 activation leads to Pdha1 (pyruvate dehydrogenase) phosphorylation in dissociated neurons from mice of both sexes, induction of this pathway in vivo by hindpaw insult is restricted to males and appears to require intraganglionic prostaglandin synthesis. These findings support a model in which Gs-coupled receptor modulation of mitochondrial function promotes acute nociceptive signaling and inflammatory hyperalgesia.
Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies.

Background Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. Objective To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. Design Active-comparator, new-user, retrospective cohort studies. Setting Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). Participants Immunocompetent adults with diverticulitis in the outpatient setting. Intervention Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. Measurements 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. Results In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). Limitation Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. Conclusion Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. Primary funding source National Institutes of Health.
Differences in Burden Severity in Adult-Child Family Caregivers and Spousal Caregivers of Persons with Dementia.

Researchers are continuing to focus on the nature and sources of burden of family caregivers of persons living with dementia. Caregiving stress and burden are assessed and addressed by social worke...
AOSLO imaging in poppers maculopathy shows high resolution loss of central macular cones

Abstract Purpose To use new adaptive optics scanning laser ophthalmoscopy (AOSLO) technology to better image macular pathology in poppers maculopathy. Observations A 40-year-old patient was found to have poppers maculopathy. Best corrected visual acuity was decreased to 20/40 OD and 20/50 OS, spectral domain optical coherence tomography found outer retinal disruption of the fovea, and AOSLO imaging showed significant decrease in cone density of the fovea of both eyes. Conclusions and importance Poppers maculopathy is a rare, but visually significant, complication of popper abuse. AOSLO technology demonstrates significant cone damage in poppers maculopathy. The striking loss of cones revealed by AOSLO imaging shows how AOSLO imaging can elucidate macular pathology.
Insulin‐like growth factor‐I and Bcl‐XL inhibit c‐jun N‐terminal kinase activation and rescue Schwann cells from apoptosis

We previously reported that Schwann cells undergo apoptosis after serum withdrawal. Insulin-like growth factor-I, via phosphatidylinositol-3 kinase, inhibits caspase activation and rescues Schwann cells from serum withdrawal-induced apoptosis. In this study, we examined the role of c-jun N-terminal protein kinase (JNK) in Schwann cell apoptosis induced by serum withdrawal. Activation of both JNK1 and JNK2 was detected 1 h after serum withdrawal with the maximal level detected at 2 h. A dominant negative JNK mutant, JNK (APF), blocked JNK activation induced by serum withdrawal and Schwann cell apoptosis, suggesting JNK activation participates in Schwann cell apoptosis. Serum withdrawal-induced JNK activity was caspase dependent and inhibited by a caspase 3 inhibitor, Ac-DEVD-CHO. Because insulin-like growth factor-I and Bcl-XL are both Schwann cell survival factors, we tested their effects on JNK activation during apoptosis. Insulin-like growth factor-I treatment decreased both JNK1 and JNK2 activity induced by serum withdrawal. LY294002, a phosphatidylinositol-3 kinase inhibitor, blocked insulin-like growth factor-I inhibition on JNK activation, suggesting that phosphatidylinositol-3 kinase mediates the effects of insulin-like growth factor-I. Overexpression of Bcl-XL also resulted in less Schwann cell death and inhibition of JNK activation after serum withdrawal. Collectively, these results suggest JNK activation is involved in Schwann cell apoptosis induced by serum withdrawal. Insulinlike growth factor-I and Bcl family proteins rescue Schwann cells, at least in part, by inhibition of JNK activity.
Continuum percolation theory for natural porous media

The ratio of the solute diffusion constant in a porous medium to the product of its value in water and the moisture content of the medium is equal to the difference of the moisture content and a critical value of the moisture content at which the diffusion vanishes. A phenomenological relationship for the critical moisture content was obtained in experiments. Continuum percolation theory predicts the observed relationship, an approximate value for the critical moisture content, and the hydraulic conductivity as a function of saturation. Deviations in the fractal scaling of the pressure-saturation curves both at the wet end and at the dry end set on at moisture contents closely related to the critical value for percolation. Hysteresis in pressure-saturation is also predicted using the percolation result for the fraction of sites accessible to the infinite cluster (for imbibition). The values of the parameters extend across major solid types, and even country of origin of the soil. Thus it is claimed that the best way to represent natural porous media is through truncated random fractals, and the best way to try to understand their behavior is within the context of percolation theory.
Quantitative spectrochemical analysis of silicate rocks, silicate minerals, and allied materials: Preliminary report on a scheme of analysis

Abstract A system of quantitative spectrochemical analysis of silicates (rocks, minerals, soils, meteorites and allied material) using DC arc excitation, is outlined and discussed briefly. The object in devising this analytical scheme is to reach an effective compromise between so-called specific, accurate methods which handle a very limited number of elements in one procedure, and the general methods by means of which many elements are determined semi-quantitatively in one operation. In the simple analytical scheme outlined here, a complete quantitative analysis of a silicate involves a limited number of arcings. Volatilization is considered the most important property in the grouping of elements for each arcing and for choosing an internal standard for each group. Standard deviations invariably fall within the range of 2.5–8%. Included in the analytical scheme are fluorine, all alkali metals and the so-called major constituent elements.
Planning for the Delivery of Special Services in Public Schools: A Multidimensional Needs Assessment Framework.

Abstract Public Law 94–142 requires that public school districts provide special service programs to handicapped and potentially handicapped children with diverse psychological, educational, and physical needs. In order for such programs to be developed and implemented in an appropriate and timely manner, procedures for assessment of pupil needs as well as assessment of school district resources that might address those needs, have been considered as important service delivery prerequisites. Toward that end, a Multidimensional Needs Assessment Framework, which has been developed by the authors and used in numerous public schools, is described in this paper. The Framework, which allows needs assessment to be seen as an integral part of the program planning process, requires that needs assessment and program planning activities occur in relation to three distinct, yet interrelated dimensions: Special Service Recipients, Special Service Resources, and Organizational Unit. Considerations necessary for design and implementation of needs assessment using the Framework are discussed, and suggestions for further development of the approach are noted.
Sherrington, Charles Scott

1857–1952Britishphysiologistwho elucidated the workings of the nervous system. Keywords: physiology; nervous system; synapse; reflex; neuron theory; Michael Foster; Virchow; Koch
Do prolonged peripherally inserted central venous catheter dwell times increase the risk of bloodstream infection

From the Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland (all authors). Received April 6, 2010; accepted May 17, 2010; electronically published October 1, 2010. Infect Control Hosp Epidemiol 2010; 31(11):1184-1187 2010 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2010/3111-0013$15.00. DOI: 10.1086/656589 Peripherally inserted central venous catheters (PICCs) have become increasingly popular as a result of the ease of their placement at the bedside and their long-term viability with relatively minimal mechanical complications. Although PICCs were initially intended for short-term vascular access, these catheters often remain in place for weeks to months. No prospective trials have evaluated whether replacement of central venous catheters (CVCs) beyond 7 days after insertion can reduce rates of central line–associated bloodstream infection (CLABSI). Similarly, no prospective trials have evaluated whether scheduled replacement of PICCs can reduce incidence of CLABSI. In this commentary, we discuss why longer catheter dwell times may increase the risk of CLABSI at an accelerated pace in patients with PICCs and why, in some instances, PICC replacement or an alternative intervention may prevent CLABSI.
Schwinger’s Variational Principle in Einstein-Cartan Gravity

By applying Schwinger's variational principle to the Einstein-Cartan action for the gravitational field, we derive quantum commutation relations between the metric and torsion tensors.
Man in space.

The Challenger disaster focused attention on the hazards as well as the possibilities of man in space. The physiological effects of prolonged weightlessness include important changes in vestibular, bone, muscle, cardiovascular, blood, renal, and pulmonary function. Much has been learned from US and Soviet experiments, but large areas of ignorance remain. Exceptional opportunities for physiological research are provided by Spacelab, a pressurized laboratory planned as a payload of the Space Shuttle.
Paper 38: Water Drainage from a Cascade of Hollow Slotted Low-Pressure Turbine Blades

To prevent or minimize the erosion of the last row rotor blades in large high-speed steam turbines it has been proposed to remove the film of water on the surfaces of the last row stator blades before it reaches the trailing edges and is swept off by the steam drag into the path of the rotor blades.The paper describes experiments with a cascade of hollow stator blades with various dispositions of slots providing communication from the blade surfaces to the hollow cavity. The same cascade was used in turn with three different wet air tunnels, the experiments thus covering a wide range of Mach number and Reynolds number.With suitably disposed slots, and bleeding a very small proportion of the working fluid, about 90 per cent of the deleterious water can be removed, thus preventing it from striking the moving blades.
Studies of electron irradiation and annealing effects on TiO2 surfaces in ultrahigh vacuum using high-resolution electron microscopy

Abstract Electron-beam-induced surface damage and subsequent annealing processes in rutile crystals have been investigated with a 300 keV high-resolution electron microscope which has been modified for ultrahigh vacuum and equipped with a specimen heating holder. Room temperature irradiation produced a reduction sequence identical to that observed previously in conventional microscope vacuum, except for some evidence of enhanced sputtering. Irradiation at higher temperatures (200–400°C) increased the damage rate resulting in approximately the same amount of the surface TiO phase but producing larger areas of the intermediate TiO2-II phase. Sputter pits in both rutile and TiO2-II phases became markedly more facetted as the temperature was increased. Irradiation at temperatures greater than 500°C resulted in the formation of well-facetted holes in the rutile, but no accumulation of crystalline reduced phases was observed. Annealing of the damaged areas in the absence of the electron beam, as shown by the reformation of crystalline rutile, revealed a temperature dependence for the restoration of the stoichiometry of the reduced areas, while complete removal of the sometimes extensive sputter pits was observed at temperatures in excess of 200 ° C.
A stochastic model for the study of oviposition evolution of the pest callosobruchus maculatus on mung beans, Phaseolus aureus

Abstract Mitchell (1975) experimentally investigated the oviposition behavior of bruchid beetles on mung beans. In this paper, we develop a stochastic model to study the oviposition tactics of the bean weevils on beans. This model identifies an avoidance probability that is invariant among weevils, and explains the nuances in egg laying behavior of different weevils by varying the rate parameter λ alone.
II. Multicentre clinical trial of diets for low birthweight infants: interim analysis of short term clinical and biochemical effects of diet

In 3 of 5 collaborating centres, two clinical trials comparisons are being made between infants randomly assigned to a preterm formula (PTF) or banked milk (BBM) fed as sole diets or in conjunction with maternal milk. (n=200 at second interim analysis). BBM fed infants showed: 1. increased incidence of: severe hyponatraemia (Na 1.3, p<0.01); 2. higher peak plasma bilirubin and more prolonged hyperbilirubinaemia (p<0.01), 3. higher plasma prolactin and growth hormone concentration (p<0.01). PTF fed infants showed 1. increased: growth rates (reported elsewhere), gastric pooling (p<0.01) and latent systemic anaphylactic sensitisation to cows milk (basophil histamine release to cowsmilk and anti IgE challenge, p<0.01); 2. faster postnatal fall in plasma IgG and rise in IgM (p<0.05); 3. lower plasma calcium (week 1) and potassium (p<0.02) 4. higher platelet count (p<0.05) and plasma concentration of some amino acids, notably threonine (p<0.0001). We conclude that patterns of short term response to diet are complex and cannot be used to predict an overall clinical benefit of a feeding regime - their clinical significance can be assessed only by follow up studies, the principle concern of these trials.
A parallel machine replacement model

This paper considers a finite horizon parallel machine replacement problem where a fixed number of machines is in operation at all times. The operating cost for a machine goes up as the machine gets older. An older machine may have to be replaced by a new one when its operating cost becomes too high. There is a fixed order cost associated with the purchase of new machines. Machine purchase prices and salvage values may depend on the period in which they were purchased. The objective is to find a replacement plan that minimizes the total discounted cost over the problem horizon. We believe that the costs in our model are more commonly observed in practice than those previously used in the literature. The paper develops properties of optimal solutions and an efficient forward-time algorithm to find an optimal replacement plan. A dominance property is developed that further limits the options to be considered, and a simple forecast horizon result is also presented. Future research possibilities are mentioned. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 275–287, 2002; Published online in Wiley InterScience (http://www.interscience.wiley.com). DOI 10.1002/nav.10012
Alkyl Ether Analogs of Chlorophyll‐a Derivatives: Part 1. Synthesis, Photophysical Properties and Photodynamic Efficacy

The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-alpha analogs are described. For short-chain carbon ethers (1-7 carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n-hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1-bromoethyl)-2-devinylpyropheophorbide-alpha with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-alpha analogs were found to be more active than related chlorin e6 derivatives, in which the isocyclic ring (ring "E") was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-alpha analogs. The photosensitizers prepared from pyropheophorbide-alpha methyl ester and chlorin e6 trimethyl ester have long wavelength absorption at 660 nm (epsilon 45 000 to 50 000). Reduction of the carbonyl group in the pyropheophorbide-alpha to methylene (ring E) resulted in a blue shift to 648 nm (epsilon 38 000).
In-house preparation of technetium 99m-labeled human serum albumin for evaluation of protein-losing gastroenteropathy.

Objective To develop an in-house preparation method for technetium 99m-labeled human serum albumin ( 99m Tc-HSA) to meet the clinical need for gastrointestinal (GI) protein loss evaluation in our institution. Design/Setting Our in-house HSA was prepared by slowly adding 2 mL of 25% HSA to 50 mL nitrogen-purged, sterilized water. We then continued the nitrogen purging process for another 15 minutes before adding 0.5 mL of stannous chloride (SnCl 2 ) in concentrated hydrochloride (40 mg/mL) to the HSA solution. Next, we transferred 1 mL of the mixture to a 5 mL vial containing 0.5 mL of 30 mCi (1,110 MBq) 99m Tc. Using a paper chromatography method during a 6-hour postpreparation time period, we evaluated the effects of filtration (0.2 m membrane filter versus no filtration) and storage temperature (25 C versus 37 C) on the in vitro stability of 99m Tc-HSA. Patients or Other Participants In this study, we employed the in-house 99m Tc-HSA preparation to study GI protein loss in two patients. Interventions Not applicable. Main Outcome Measures We used a radiochemical purity (RCP) value of not less than 90% as the index for determining in vitro stability of the in-house 99m Tc-HSA preparation. The nuclear medicine physician interpreted the image to determine the location and extent of protein loss in the GI tract. Results Our results demonstrate that the overall RCP of 99m Tc-HSA was 95.0% 2.2% (mean SD). We found no statistically significant difference in RCP value between filtered and nonfiltered 99m Tc-HSA preparations across the sampled time points. However, RCP values tended to increase with time for each of the temperature-controlled preparations ( P P P 99m Tc-HSA within the first hour in one patient, and the imaging results indicate that both patients had protein-losing enteropathy. Conclusion It is relatively easy to prepare 99m Tc-HSA inhouse, achieving a high RCP level as well as extended in vitro stability. The clinical data further indicate that our in-house preparation of 99m Tc-HSA may be useful for the study of GI protein loss; however, further clinical evaluation is needed.
Properties of the Driving Behavior Survey among individuals with motor vehicle accident-related posttraumatic stress disorder.

Data suggest anxious drivers may engage in problematic behaviors that place themselves and others at increased risk of negative traffic events. Three domains of problematic behavior – exaggerated safety/caution, performance deficits, and hostile/aggressive behaviors – previously were identified during development of the Driving Behavior Survey (DBS), a novel measure of anxiety-related behavior. Extending this research, the current study examined the psychometric properties of DBS scores among individuals with posttraumatic stress disorder (PTSD) subsequent to motor vehicle trauma (N = 40). Internal consistencies and 12-week test–retest reliabilities for DBS scales ranged from good to excellent. Comparison of scores to normative student data indicated dose–response relationships for safety/caution and performance deficit subscales, with increased frequency of anxious behavior occurring within the PTSD sample. Associations with standard clinical measures provide additional evidence for anxiety-related driving behavior as a unique marker of functional impairment, distinct from both avoidance and disorder-specific symptoms.
Reply to comment by Jason E. Smerdon et al. on “Robustness of proxy‐based climate field reconstruction methods”

[1] Smerdon et al. [2008] correctly conclude that the initial regridding method used by Mann et al. [2007] (hereafter M07) to map ECHO-g output to the resolution of surface observation data resulted in enhanced variability of the Northern Hemisphere (NH) mean series compared to the original model output (Figure 1a of Smerdon et al. [2008]). They also correctly conclude that the gridding method has no effect whatsoever on the conclusions of M07 because those conclusions were primarily based on results using the CSM model, and because the ECHO-g Figure 1. Results of experiments ‘‘y’’ (red line) and ‘‘z’’ (blue line) (a) from M07 and (b) using the regridding method described here. The use of the alternative regridding method does not change the results and conclusion of M07. JOURNAL OF GEOPHYSICAL RESEARCH, VOL. 113, D18107, doi:10.1029/2008JD009964, 2008 Click Here for Full Article
During ontogeny, Ia-bearing accessory cells are found early in the thymus but late in the spleen.

Abstract The ontogeny of Ia-bearing accessory cells was studied in mice. Ia-bearing adherent cells from the thymus, consisting predominantly of macrophages, were found from birth. These adherent cells were able to present antigen, as measured by their ability to induce immune T-cell proliferation. In contrast, Ia-bearing adherent cells from the spleen were not found until the second week of life, and their antigen-presentation function was not present until later. The differential ontogeny of Ia-bearing accessory cells at these sites may be important in both development of immune competence and the restriction of autoimmunity.
Interfacial polymer phase segregation and self-assembly of square colloidal crystals

Polystyrene colloids exhibit unique bimodal dynamics at the air–water interface in the presence of PEG polymers. We attribute this to agglomeration of the polymer into polymer-rich and polymer-sparse domains at the interface. Colloids adsorbed to polymer-depleted regions retain mobility and self-assemble into two-dimensional crystals with square symmetry, which is ascribed to an undulated contact line on the particles and the droplet's negative Gaussian curvature. To our knowledge, this is the first example of thermodynamically favoured two-dimensional square crystals formed by means of interfacial colloid assembly.
The Interpretation of Nonverbal Behavior in a Role-Defined Interaction Sequence: The Police-Citizen Encounter

Videotapes of staged police-citizen interactions were shown to subjects. Nonverbal behaviors of the citizen were programmed to reflect empirically derived reactions to spatial intrusion versus nonintrusion conditions by the police officer. In the first study subjects made attributional ratings of the citizen based on the nonverbal behaviors only with the physical distance between the interactants held constant. Citizens exhibiting spatial intrusion reaction behaviors were judged to be significantly more deceptive, guilty, anxious, and generally more suspicious and unfavorable than citizens not exhibiting such behaviors. In the second study physical distance was explicitly manipulated to create a close versus distant condition. The behavioral cue manipulation from the first study was reproduced in each of these proximity conditions. Many replications of results from the first study were obtained indicating that the preponderant cause of impression formation of the citizen was based upon spatial intrusion behavioral cues, regardless of the perceived physical distance between the interactants. However, significant interaction effects between proximity and behavioral cue conditions were obtained and confirmed an attribution theory prediction regarding degree of confidence in impression-formation ratings made of the citizen.
Realm: an event-based low-level runtime for distributed memory architectures

We present Realm, an event-based runtime system for heterogeneous, distributed memory machines. Realm is fully asynchronous: all runtime actions are non-blocking. Realm supports spawning computations, moving data, and reservations, a novel synchronization primitive. Asynchrony is exposed via a light-weight event system capable of operating without central management. We describe an implementation of Realm that relies on a novel generational event data structure for efficiently handling large numbers of events in a distributed address space. Microbenchmark experiments show our implementation of Realm approaches the underlying hardware performance limits. We measure the performance of three real-world applications on the Keeneland supercomputer. Our results demonstrate that Realm confers considerable latency hiding to clients, attaining significant speedups over traditional bulk-synchronous and independently optimized MPI codes.
In Vivo Lipid Peroxidation in Rat Brain Following Intracortical Fe2+ Injection

Cerebral contusion, cortical laceration, intracerebral hematoma formation, and hemorrhagic cortical infarction cause extravasation of red blood cells, followed by hemolysis, decompartmentalization of iron, formation and deposition of hemosiderin, and an increased incidence of epilepsy. In this experiment, 10 microliter of an aqueous solution containing 100 mmol/L FeCl2, 100 mmol/L CoCl2, or 0.9% (wt/vol) NaCl were injected at a depth of 1.8 mm into rat isocortex. The rate of formation of fluorescent compounds was measured in chloroform-methanol extracts of isocortical homogenates. Significant increases in the quantity of fluorescent products of lipid peroxidation were found 120 min after the injection of 100 mmol/L FeCl2. Cobaltous chloride and saline injection had no effect on the levels of fluorescent products found in the cortical homogenates. Although the intracortical deposition of aqueous solutions containing CoCl2 or FeCl2 in rodent cortex causes acute epileptiform discharges, the epileptogenic effect of CoCl2 is transient, while the injection of iron salts causes persistent seizures. Since CoCl2 injection failed to cause formation of lipid peroxidation products while the isocortical injection of iron caused significant increase in fluorescence within the injected hemisphere, we suggest that the occurrence of iron-induced lipid peroxidation may be of importance in initiation of recurrent seizures in the rat.
Bulk viscosity via nonequilibrium and equilibrium molecular dynamics

Two new nonequilibrium methods for determining the bulk viscosity via molecular dynamics are described. These methods are applied to a soft-sphere dense fluid. Viscosities obtained from the equilibrium Green-Kubo-correlation-function method agree with the nonequilibrium results. The viscosities found are considerably smaller than those predicted by the Enskog theory of dense fluids.
Preparation, interconversion and characterization of nanometer-sized molybdenum carbide catalysts

Nanometer-sized molybdenum carbide particles have been shown to have hydrogenation and other catalytic properties similar to those of the more-expensive noble metals. However, current preparation techniques for molybdenum carbide require the high-temperature reduction of unsupported molybdenum oxide in the presence of CH{sub 4} and H{sub 2}. Although this method is effective, it yields particles of relatively large size, 11 nm. Different, simpler, synthesis procedures starting with ammonium heptamolybdate impregnated on carbon yield carbides of different stoichiometries. Particle sizes are in the 2--10 nm range, which are generally smaller than those previously obtained, and can be altered by changing the method of preparation. The focus of this work is to characterize the new procedures, specifically the bulk transitions of the new starting material to the different molybdenum carbides, using time-resolved X-ray diffraction, temperature-programmed reduction, and temperature-programmed desorption.
Relaxation of exciton confinement in CdSe quantum dots by modification with a conjugated dithiocarbamate ligand.

Coordination of phenyldithiocarbamate (PTC) ligands to solution-phase colloidal CdSe quantum dots (QDs) decreases the optical band gap, Eg, of the QDs by up to 220 meV. These values of ΔEg are the largest shifts achieved by chemical modification of the surfaces of solution-phase CdSe QDs and are—by more than an order of magnitude in energy—the largest bathochromic shifts achieved for QDs in either the solution or solid phases. Measured values of ΔEg upon coordination to PTC correspond to an apparent increase in the excitonic radius of 0.26 ± 0.03 nm; this excitonic delocalization is independent of the size of the QD for radii, R = 1.1−1.9 nm. Density functional theory calculations indicate that the highest occupied molecular orbital of PTC is near resonant with that of the QD, and that the two have correct symmetry to exchange electron density (PTC is a π-donor, and the photoexcited QD is a π-acceptor). We therefore propose that the relaxation of exciton confinement occurs through delocalization of the ph...
Response to Letter Regarding Article, “Inhibition of Interleukin-1β Decreases Aneurysm Formation and Progression in a Novel Model of Thoracic Aortic Aneurysm”

We thank Dr Usui and colleagues for their insightful comments on the upstream mechanism of interleukin-1β (IL-1β) production in aortic aneurysms. As mentioned, we have demonstrated that IL-1β is key in aortic aneurysm formation and progression.1 IL-1β binds to its receptor to incite a host of inflammatory cytokines. Inhibition of IL-1β by genetic deletion or pharmacological inhibition reduces experimental aortic aneurysm size and halts small aneurysm growth. Because IL-1β triggers multiple inflammatory cytokines and pathways, targeting downstream mediators may have limited effect. Therefore, upstream triggers of IL-1β release must be identified for further potential treatment …
Experimental methodology and heat transfer model for identification of ignition kinetics of powdered fuels

Abstract A methodology for investigating and quantifying the thermal processes leading to ignition of rapidly heated metal powders was developed. The simple experiment involves observing ignition of a powder coated on the surface of an electrically heated filament and is well suited for a variety of powdered fuels. In an experimental case study, the ignition temperature of spherical Mg powder was detected optically at different heating rates. To interpret the results, a heat transfer model was developed for a multilayer powder coating on the heated cylindrical filament. The thermal contact resistance between particles was determined from the measured bulk thermal diffusivity of the powder considering the experimental particle size distribution. An Arrhenius type expression was used to describe the exothermic chemical processes leading to ignition with the pre-exponent as an adjustable parameter. For Mg, a pre-exponent value identified by matching the calculations with the experimental data was found to be 10 10 kg/m 2 s. The match between the experimental and predicted temperatures and times of ignition was good for different heating rates, which validated the proposed heat transfer model and indicated that the developed methodology is practically useful.
Building, Using, and Maximizing the Impact of Concept Inventories in the Biological Sciences: Report on a National Science Foundation–sponsored Conference on the Construction of Concept Inventories in the Biological Sciences

The meeting “Conceptual Assessment in the Biological Sciences” was held March 3–4, 2007, in Boulder, Colorado. Sponsored by the National Science Foundation and hosted by University of Colorado, Boulder's Biology Concept Inventory Team, the meeting drew together 21 participants from 13 institutions, all of whom had received National Science Foundation funding for biology education. Topics of interest included Introductory Biology, Genetics, Evolution, Ecology, and the Nature of Science. The goal of the meeting was to organize and leverage current efforts to develop concept inventories for each of these topics. These diagnostic tools are inspired by the success of the Force Concept Inventory, developed by the community of physics educators to identify student misconceptions about Newtonian mechanics. By working together, participants hope to lessen the risk that groups might develop competing rather than complementary inventories.
Iso-coenzyme A

Iso-coenzyme A is an isomer of coenzyme A in which the monophosphate is attached to the 2'-carbon of the ribose ring. Although iso-CoA was first reported in 1959 (Moffatt, J. G., and Khorana, H. G. (1959) J. Am. Chem. Soc. 81, 1265-1265) to be a by-product of the chemical synthesis of CoA, relatively little attention has been focused on iso-CoA or on acyl-iso-CoA compounds in the literature. We now report structural characterizations of iso-CoA, acetyl-iso-CoA, acetoacetyl-iso-CoA, and beta-hydroxybutyryl-iso-CoA using mass spectrometry (MS), tandem MS, and homonuclear and heteronuclear NMR analyses. Although the 2'-phosphate isomer of malonyl-CoA was recently identified in commercial samples, previous characterizations of iso-CoA itself have been based on chromatographic analyses, which ultimately rest on comparisons with the degradation products of CoA and NADPH or have been based on assumptions regarding enzyme specificity. We describe a high performance liquid chromatography methodology for separating the isomers of several CoA-containing compounds. We also report here the first examples of iso-CoA-containing compounds acting as substrates in enzymatic acyl transfer reactions. Finally, we describe a simple synthesis of iso-CoA from CoA, which utilizes beta-cyclodextrin to produce iso-CoA with high regioselectivity, and we demonstrate a plausible mechanism that accounts for the existence of iso-CoA isomers in commercial preparations of CoA-containing compounds. We anticipate that these results will provide methodology and impetus for investigating iso-CoA compounds as potential pseudo-substrates or inhibitors of the >350 known CoA-utilizing enzymes.
Structure of Phosphorus-Containing Peptide Ligands. X-ray and NMR Structural Study of Free Ligand and Rhodium Complex

The structure of a series of phosphorus-containing peptides was studied. The X-ray structure of a phosphorus-containing dodecapeptide is reported. Analysis of the solution structure of similar phosphorus-containing peptides before and after coordination of rhodium is also reported. In both the solid state and in solution, the peptides were found to exist in a mixture of α-helical and 310 helical conformations. Coordination of rhodium to the i, i + 4 orientated phosphine groups appears to alter the conformational preference.
Differing effects of inotropic agents on length change deactivation of isolated rat myocardium.

Background A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced. Methods Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation. Results Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12±4% (mean±SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16±5%, decreased time to peak by 34±3%, and increased the deactivation slope by 106±9% (P Conclusions The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity.
GLIAL CELLS METABOLICALLY COOPERATE: A POTENIAL REQUIREMENT FOR GENE REPLACEMENT THERAPY: 102

GLIAL CELLS METABOLICALLY COOPERATE: A POTENIAL REQUIREMENT FOR GENE REPLACEMENT THERAPY: 102
Properties distinguishing mitochondrial and synaptosomal protein synthesis

Abstract Mouse brain synaptosomal protein synthesis in vitro is inhibited by chloramphenicol, cycloheximide, emetine, and chloroquine,whereas mouse brain mitochondria are sensitive to inhibition only by chloramphenicol. These results, and others cited, confirm that: (1) brain mitochondria do not differ from other mitochondria except for their capacity for a faster rate of in vitro protein synthesis; (2) isolated synaptosomes apparently possess two protein synthetic systems. Furthermore, based upon the effects of combinations of inhibitiors, the two systems are in some manner interdependent.
Scale-space representation of remote sensing images using an object-oriented approach

Today's high resolution remotely sensed images (<1m) pose several challenges which require solutions that go beyond the traditional spectral based methodologies. With the rapid increase in the level of detail present in these images, there is also an increase in the complexity. To deal with this complexity a consistent framework and image representation is needed. An object-based scale-space representation is proposed. Principles of objectbased design are explained and the application of these principles to image regions is introduced. Given an input image, the scale-tree is automatically constructed using low-level information, starting with single pixels (as objects) and ending with the root node indicating the complete image. The scale-tree is a hierarchical structure where each level in the hierarchy differs from the next in the size of the objects/regions present at that level. Hence, the scale-tree reflects the scale-space breakdown of the image. From another point of view the scaletree can also be seen as a collection of multiple segmentations with varying level of detail going from fine to coarse. Synthetic and real high resolution satellite images were used to evaluate our image representation. The goal of the proposed representation is to facilitate applications such as target/anomaly detection, image region classification and change detection.
Batch-operated universal closed arc furnace for making steel directly from briquets obtained using an iron-ore-bearing monocharge

This article examines a direct-reduction method of steelmaking that employs a single-stage cycle and a universal batch-operated arc furnace developed by the authors. First, the reducing operation is carried out in the furnace with the electrodes submerged in the charge. After the charge has melted and slag has been removed through an opening in the upper part of the furnace, the electrodes are raised and the switch on the transformer is changed to the electrical regime in which refining and alloying are carried out. The finished steel is tapped through an opening in the lower part of the furnace at the completion of the process.
Emergence of Carbapenem Resistance Due to the Novel Insertion Sequence ISPa8 in Pseudomonas aeruginosa

Chronic lung infections due to the persistence of Pseudomonas aeruginosa in cystic fibrosis patients are typically associated with the emergence of antibiotic resistance. The purpose of this study was to investigate the mechanisms responsible for the emergence of carbapenem resistance when a clinical isolate of P. aeruginosa collected from a patient with cystic fibrosis was challenged with meropenem. Nine carbapenem-resistant mutants were selected with subinhibitory concentrations of meropenem from a clinical isolate of P. aeruginosa and characterized for carbapenem resistance. Increased carbapenem MICs were associated with the identification of the novel insertion sequence ISPa8 within oprD or its promoter region in all the mutants. The position of ISPa8 was different for each of the mutants evaluated. In addition, Southern blot analyses identified multiple copies of ISPa8 within the genomes of the mutants and their parent isolate. These data demonstrate that transposition of IS elements within the Pseudomonas genome can influence antibiotic susceptibility. Understanding the selective pressures associated with the emergence of antibiotic resistance is critical for the judicious use of antimicrobial chemotherapy and the successful treatment of bacterial infections.
EPISODES OF SPONTANEOUS HYPOXEMIA IN INTUBATED VERSUS EXTUBATED VERY LOW BIRTH WEIGHT (VLBW) INFANTS WITH CHRONIC LUNG DISEASE (CLD).† 1356

Episodes of spontaneous hypoxemia are frequent in V LBW(≤ 1000g) infants with CLD (FIO2 >0.21, age > 28 days, Chest X-ray changes). It has been suggested that prompt extubation in these infants may allow them to actively maintain their lung volume and therefore decrease episodes of hypoxemia (J of Ped 1995; 127:767-773). To test this hypothesis, we monitored spontaneous episodes of hypoxemia in 35 intubated VLBW infants (mean BW=748g, GA=26.3 wks, postnatal age (PNA)=38 days, study weight=1024g, FIO2=0.34, mean airway pressure=5.0 cm H2O) vs episodes of hypoxemia in 38 extubated VLBW infants with CLD (mean BW=781g, GA=26.1 wks, PNA=44 days, study weight=1228g, FIO2=0.27). Oxygen saturation (SaO2) was measured with a Nellcor N-200 oximeter for one hour time intervals with the infant supine, quietly asleep, and on the FIO2 used for patient care. The oxygenation data was quantified with a computer program (Pediatr Pulmonol 1992; 13: 136-142). The average SaO2 in the intubated infants was 92.0% versus 92.2% in the extubated (p>0.05). Values are mean ± SEM. When studied on the FIO2 used for clinical care, both intubated and extubated VLBW infants with CLD demonstrated a similar average SaO2, as well as comparable percentages of time to less than 90%, 85%, and 80% SaO2. However, the intubated infants experienced more episodes of spontaneous hypoxemia, despite continuous ventilation. Our preliminary data demonstrates that the presence of an endotracheal tube does not protect these infants from episodes of spontaneous hypoxemia. We speculate that these episodes of hypoxemia in VLBW infants with CLD may be due to sudden decreases in lung volume and/or increased intrapulmonary shunting. Prompt extubation in stable VLBW infants with CLD may indeed allow them to more adequately maintain their own lung volume and decrease these episodes of spontaneous hypoxemia.Table