bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical optimization of digital subtraction mammography with contrast medium using a commercial unit
Authors: Rosado‐Méndez I. , Palma B. A. , Brandan M. E.
Published: December 2008

Contrast‐medium‐enhanced digital mammography (CEDM) is an image subtraction technique which might help unmasking lesions embedded in very dense breasts. Previous works have stated the feasibility of CEDM and the imperative need of radiological optimization. This work presents an extension of a former analytical formalism to predict contrast‐to‐noise ratio (CNR) in subtracted mammograms. The goal is to optimize radiological parameters available in a clinical mammographic unit (x‐ray tube anode/filter combination, voltage, and loading) by maximizing CNR and minimizing total mean glandular dose , simulating the experimental application of an iodine‐based contrast medium and the image subtraction under dual‐energy nontemporal, and single‐ or dual‐energy temporal modalities. Total breast‐entrance air kerma is limited to a fixed (1 R, similar to screening studies). Mathematical expressions obtained from the formalism are evaluated using computed mammographic x‐ray spectra attenuated by an adipose/glandular breast containing an elongated structure filled with an iodinated solution in various concentrations. A systematic study of contrast, its associated variance, and CNR for different spectral combinations is performed, concluding in the proposal of optimum x‐ray spectra. The linearity between contrast in subtracted images and iodine mass thickness is proven, including the determination of iodine visualization limits based on Rose's detection criterion. Finally, total breast‐entrance air kerma is distributed between both images in various proportions in order to maximize the figure of merit . Predicted results indicate the advantage of temporal subtraction (either single‐ or dual‐energy modalities) with optimum parameters corresponding to high‐voltage, strongly hardened spectra. For temporal techniques, CNR was found to depend mostly on the energy of the iodinated image, and thus reduction in could be achieved if the spectral energy of the noniodinated image is decreased and the breast‐entrance air kerma is evenly distributed between both acquisitions. Predicted limits, in terms of iodine concentration, are found to guarantee the visualization of common clinical angiogenic concentrations in the breast.
Response of an implantable MOSFET dosimeter to HDR radiation
Authors: Fagerstrom Jessica M. , Micka John A. , DeWerd Larry A.
Published: December 2008

New in vivo dosimetry methods would be useful for clinical HDR brachytherapy. An implantable MOSFET Dose Verification System® designed by Sicel Technologies, Inc. was examined for use with HDR applications. This investigation demonstrated that varying the dose rate from did not change detector response. The detectors exhibited a higher sensitivity to energies than energies. A nonlinear accumulated dose effect was characterized by three third‐order polynomials fit to data from detectors placed at three different distances from the source. The detectors were found to have minimal rotational angular dependence. A strong longitudinal angular dependence was found when the detector's copper coil and electronics assembly were aligned between the MOSFETs and incident radiation. This orientation showed a 16% decrease in response relative to other orientations tested.
A correction‐based dose calculation algorithm for kilovoltage x rays
Authors: Ding George X. , Pawlowski Jason M. , Coffey Charles W.
Published: December 2008

Frequent and repeated imaging procedures such as those performed in image‐guided radiotherapy (IGRT) programs may add significant dose to radiosensitive organs of radiotherapy patients. It has been shown that kV‐CBCT results in doses to bone that are up to a factor of 3–4 higher than those in surrounding soft tissue. Imaging guidance procedures are necessary due to their potential benefits, but the additional incremental dose per treatment fraction may exceed an individual organ tolerance. Hence it is important to manage and account for this additional dose from imaging for radiotherapy patients. Currently available model‐based dose calculation methods in radiation treatment planning (RTP) systems are not suitable for low‐energy x rays, and new and fast calculation algorithms are needed for a RTP system for kilovoltage dose computations. This study presents a new dose calculation algorithm, referred to as the medium‐dependent‐correction (MDC) algorithm, for accurate patient dose calculation resulting from kilovoltage x rays. The accuracy of the new algorithm is validated against Monte Carlo calculations. The new algorithm overcomes the deficiency of existing density correction based algorithms in dose calculations for inhomogeneous media, especially for CT‐based human volumetric images used in radiotherapy treatment planning.
Locating and targeting moving tumors with radiation beams
Authors: Dieterich Sonja , Cleary Kevin , D’Souza Warren , Murphy Martin , Wong Kenneth H. , Keall Paul
Published: December 2008

The current climate of rapid technological evolution is reflected in newer and better methods to modulate and direct radiation beams for cancer therapy. This Vision paper focuses on part of this evolution, locating and targeting moving tumors. The two processes are somewhat independent and in principle different implementations of the locating and targeting processes can be interchanged. Advanced localization and targeting methods have an impact on treatment planning and also present new challenges for quality assurance (QA), that of verifying real‐time delivery. Some methods to locate and target moving tumors with radiation beams are currently FDA approved for clinical use—and this availability and implementation will increase with time. Extensions of current capabilities will be the integration of higher order dimensionality, such as rotation and deformation in addition to translation, into the estimate of the patient pose and real‐time reoptimization and adaption of delivery to the dynamically changing anatomy of cancer patients.
The Long-Run Benefits of Punishment
Authors: Gächter Simon , Renner Elke , Sefton Martin
Published: December 2008

Experiments have shown that punishment enhances socially beneficial cooperation but that the costs of punishment outweigh the gains from cooperation. This challenges evolutionary models of altruistic cooperation and punishment, which predict that punishment will be beneficial. We compared 10- and 50-period cooperation experiments. With the longer time horizon, punishment is unambiguously beneficial.
Tough, Bio-Inspired Hybrid Materials
Authors: Munch E. , Launey M. E. , Alsem D. H. , Saiz E. , Tomsia A. P. , Ritchie R. O.
Published: December 2008

The notion of mimicking natural structures in the synthesis of new structural materials has generated enormous interest but has yielded few practical advances. Natural composites achieve strength and toughness through complex hierarchical designs that are extremely difficult to replicate synthetically. We emulate nature's toughening mechanisms by combining two ordinary compounds, aluminum oxide and polymethyl methacrylate, into ice-templated structures whose toughness can be more than 300 times (in energy terms) that of their constituents. The final product is a bulk hybrid ceramic-based material whose high yield strength and fracture toughness [∼200 megapascals (MPa) and ∼30 MPa·m
1/2
] represent specific properties comparable to those of aluminum alloys. These model materials can be used to identify the key microstructural features that should guide the synthesis of bio-inspired ceramic-based composites with unique strength and toughness.
Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis
Authors: Steingart Karen R. , Dendukuri Nandini , Henry Megan , Schiller Ian , Nahid Payam , Hopewell Philip C. , Ramsay Andrew , Pai Madhukar , Laal Suman
Published: December 2008

Serological antibody detection tests for tuberculosis may offer the potential to improve diagnosis. Recent meta-analyses have shown that commercially available tests have variable accuracies and a limited clinical role. We reviewed the immunodiagnostic potential of antigens evaluated in research laboratories (in-house) for the serodiagnosis of pulmonary tuberculosis and conducted a meta-analysis to evaluate the performance of comparable antigens. Selection criteria included the participation of at least 25 pulmonary tuberculosis patients and the use of purified antigens. Studies evaluating 38 kDa, MPT51, malate synthase, culture filtrate protein 10, TbF6, antigen 85B, α-crystallin, 2,3-diacyltrehalose, 2,3,6-triacyltrehalose, 2,3,6,6′-tetraacyltrehalose 2′-sulfate, cord factor, and TbF6 plus DPEP (multiple antigen) were included in the meta-analysis. The results demonstrated that (i) in sputum smear-positive patients, sensitivities significantly ≥50% were provided for recombinant malate synthase (73%; 95% confidence interval [CI], 58 to 85) and TbF6 plus DPEP (75%; 95% CI, 50 to 91); (ii) protein antigens achieved high specificities; (iii) among the lipid antigens, cord factor had the best overall performance (sensitivity, 69% [95% CI, 28 to 94]; specificity, 91% [95% CI, 78 to 97]); (iv) compared with the sensitivities achieved with single antigens (median sensitivity, 53%; range, 2% to 100%), multiple antigens yielded higher sensitivities (median sensitivity, 76%; range, 16% to 96%); (v) in human immunodeficiency virus (HIV)-infected patients who are sputum smear positive, antibodies to several single and multiple antigens were detected; and (vi) data on seroreactivity to antigens in sputum smear-negative or pediatric patients were insufficient. Potential candidate antigens for an antibody detection test for pulmonary tuberculosis in HIV-infected and -uninfected patients have been identified, although no antigen achieves sufficient sensitivity to replace sputum smear microscopy. Combinations of select antigens provide higher sensitivities than single antigens. The use of a case-control design with healthy controls for the majority of studies was a limitation of the review. Efforts are needed to improve the methodological quality of tuberculosis diagnostic studies.
Bacterin That Induces Anti-OspA and Anti-OspC Borreliacidal Antibodies Provides a High Level of Protection against Canine Lyme Disease
Authors: LaFleur Rhonda L. , Dant Jennifer C. , Wasmoen Terri L. , Callister Steven M. , Jobe Dean A. , Lovrich Steven D. , Warner Thomas F. , Abdelmagid O. , Schell Ronald F.
Published: December 2008

Groups of 15 laboratory-bred beagles were vaccinated and boosted with either a placebo or adjuvanted bivalent bacterin comprised of a traditionalBorrelia burgdorferistrain and a uniqueospA- andospB-negativeB. burgdorferistrain that expressed high levels of OspC and then challenged withB. burgdorferi-infectedIxodes scapularisticks. The vaccinated dogs produced high titers of anti-OspA and anti-OspC borreliacidal antibodies, including borreliacidal antibodies specific for an epitope within the last seven amino acids at the OspC carboxy terminus (termed OspC7) that was conserved among pathogenicBorreliagenospecies. In addition, spirochetes were eliminated from the infected ticks that fed on the bacterin recipients,B. burgdorferiwas not isolated from the skin or joints, and antibody responses associated specifically with canine infection withB. burgdorferiwere not produced. In contrast,B. burgdorferiwas recovered from engorged ticks that fed on 13 (87%) placebo-vaccinated dogs (P< 0.0001), skin biopsy specimens from 14 (93%) dogs (P< 0.0001), and joint tissue specimens from 8 (53%) dogs (P= 0.0022). In addition, 14 (93%) dogs developed specific antibody responses againstB. burgdorferiproteins, including 11 (73%) with C6 peptide antibodies (P< 0.0001). Moreover, 10 (67%) dogs developed Lyme disease-associated joint abnormalities (P< 0.0001), including 4 (27%) dogs that developed joint stiffness or lameness and 6 (40%) that developed chronic joint inflammation (synovitis). The results therefore confirmed that the bacterin provided a high level of protection against Lyme disease shortly after immunization.
Comparison of
Neisseria gonorrhoeae
Multiantigen Sequence Typing and
porB
Sequence Analysis for Identification of Clusters of
N. gonorrhoeae
Isolates
Authors: Liao Mingmin , Helgeson Sarah , Gu Wei-Ming , Yang Yang , Jolly Ann M. , Dillon Jo-Anne R.
Published: December 2008

porB
DNA sequence analysis and
Neisseria gonorrhoeae
multiantigen sequence typing (NG-MAST) methods were compared for their abilities to discriminate strains and to identify epidemiologically congruent pairs of
N. gonorrhoeae
. Both methods provided high-level discrimination of strains. NG-MAST further differentiated large
porB
-based clusters. However, considerations of cost suggest that
porB
DNA sequence analysis is a useful tool for preliminary molecular analysis of the epidemiology of
N. gonorrhoeae
.
MyD88 Intrinsically Regulates CD4 T-Cell Responses
Authors: Zhou Shenghua , Kurt-Jones Evelyn A. , Cerny Anna M. , Chan Melvin , Bronson Roderick Terry , Finberg Robert W.
Published: December 2008

Myeloid differentiation factor 88 (MyD88) is an essential adaptor protein in the Toll-like receptor-mediated innate signaling pathway, as well as in interleukin-1 receptor (IL-1R) and IL-18R signaling. The importance of MyD88 in the regulation of innate immunity to microbial pathogens has been well demonstrated. However, its role in regulating acquired immunity to viral pathogens and neuropathogenesis is not entirely clear. In the present study, we examine the role of MyD88 in the CD4+T-cell response following lymphocytic choriomeningitis virus (LCMV) infection. We demonstrate that wild-type (WT) mice developed a CD4+T-cell-mediated wasting disease after intracranial infection with LCMV. In contrast, MyD88 knockout (KO) mice did not develop wasting disease in response to the same infection. This effect was not the result of MyD88 regulation of IL-1 or IL-18 responses since IL-1R1 KO and IL-18R KO mice were not protected from weight loss. In the absence of MyD88, naïve CD4+T cells failed to differentiate to LCMV-specific CD4 T cells. We demonstrated that MyD88 KO antigen-presenting cells are capable of activating WT CD4+T cells. Importantly, when MyD88 KO CD4+T cells were reconstituted with an MyD88-expressing lentivirus, the rescued CD4+T cells were able to respond to LCMV infection and support IgG2a antibody production. Overall, these studies reveal a previously unknown role of MyD88-dependent signaling in CD4+T cells in the regulation of the virus-specific CD4+T-cell response and in viral infection-induced immunopathology in the central nervous system.
A Histidine Switch in Hemagglutinin-Neuraminidase Triggers Paramyxovirus-Cell Membrane Fusion
Authors: Krishnan Anuja , Verma Santosh K. , Mani Prashant , Gupta Rahul , Kundu Suman , Sarkar Debi P.
Published: December 2008

Most paramyxovirus fusion proteins require coexpression of and activation by a homotypic attachment protein, hemagglutinin-neuraminidase (HN), to promote membrane fusion. However, the molecular mechanism of the activation remains unknown. We previously showed that the incorporation of a monohistidylated lipid into F-virosome (Sendai viral envelope containing only fusion protein) enhanced its fusion to hepatocytes, suggesting that the histidine residue in the lipid accelerated membrane fusion. Therefore, we explored whether a histidine moiety in HN could similarly direct activation of the fusion protein. In membrane fusion assays, the histidine substitution mutants of HN (H247A of Sendai virus and H245A of human parainfluenza virus 3) had impaired membrane fusion promotion activity without significant changes in other biological activities. Synthetic 30-mer peptides corresponding to regions of the two HN proteins containing these histidine residues rescued the fusion promoting activity of the mutants, whereas peptides with histidine residues substituted by alanine did not. These histidine-containing peptides also activated F-virosome fusion with hepatocytes both in the presence and in the absence of mutant HN in the virosome. We provide evidence that the HN-mimicking peptides promote membrane fusion, revealing a specific histidine “switch” in HN that triggers fusion.
Diverse and Newly Recognized Effects Associated with Short Interfering RNA Binding Site Modifications on the
Tomato Bushy Stunt Virus
P19 Silencing Suppressor
Authors: Hsieh Yi-Cheng , Omarov Rustem T. , Scholthof Herman B.
Published: December 2008

The
Tomato bushy stunt virus
-encoded P19 forms dimers that bind duplex short interfering RNAs (siRNAs) to suppress RNA silencing. P19 is also involved in multiple host-specific activities, including the elicitation of symptoms, and in local and/or systemic spread. To study the correlation between those various roles and the siRNA binding by P19, predicted siRNA-interacting sites were modified. Twenty-two mutants were generated and inoculated onto
Nicotiana benthamiana
plants, to reveal that (i) they were all infectious, (ii) symptom differences did not correlate strictly with mutation-associated variation in P19 accumulation, and (iii) substitutions affecting a central domain of P19 generally exhibited symptoms more severe than for mutations affecting peripheral regions. Three mutants selected to represent separate phenotypic categories all displayed a substantially reduced ability to sequester siRNA. Consequently, these three mutants were compromised for systemic virus spread in P19-dependent hosts but had differential plant species-dependent effects on the symptom severity. One mutant in particular caused relatively exacerbated symptoms, exemplified by extensive morphological leaf deformations in
N. benthamiana
; this was especially remarkable because P19 was undetectable. Another striking feature of this mutant was that only within a few days after infection, viral RNA was cleared by silencing. One more original property was that host RNAs and proteins (notably, the P19-interactive Hin19 protein) were also susceptible to degradation in these infected
N. benthamiana
plants but not in spinach. In conclusion, even though siRNA binding by P19 is a key functional property, compromised siRNA sequestration can result in novel and diverse host-dependent properties.
Motion control shoe affects temporal activity of quadriceps in runners
Authors: Cheung R T H , Ng G Y F
Published: December 2008

Objective:

Delay onset of the vastus medialis obliquus (VMO) has often been reported to happen in people with patellofemoral pain (PFP). Previous studies revealed that a motion control shoe could check rearfoot pronation in overpronators. Literature suggested that movements of the lower leg could affect patellar tracking; thus motion control shoe may help prevent PFP by controlling excessive foot movements. This study aimed to compare the vasti muscle activities in people with excessive foot pronation when running with different footwear.

Methods:

Twenty female subjects with rearfoot pronation >6° were tested by running for 10 km on a treadmill on two separate days. During each test, subjects either wore a motion-control running shoe or a neutral running shoe. EMG activities of their right VMO and vastus lateralis (VL) were recorded. Their EMG onset timing and median frequency (MF) were compared between the two shoe conditions.

Results:

A more significant delay in VMO onset of the running duty cycle was observed in the neutral shoe condition than in the motion control shoe (p<0.001). In the neutral shoe condition, the delay in VMO increased with running mileage (Pearson correlation = 0.948), whereas no such pattern was observed in the motion control shoe. A significant drop in MF of the quadriceps after the 10 km run in both shoe conditions was observed (p ranged from <0.001 to 0.008), and there was a larger drop in VMO MF when running with the neutral shoe.

Conclusions:

The findings suggest that the motion control shoe may facilitate a stable temporal activation of VMO during running.
Would a morphomolecular approach help in defining pseudosarcomatous myofibroblastic proliferations? A study of a heart polypoid lesion: Figure 1
Authors: Nemolato S , Dettori T , Caria P , Frau D V , Faa G , Vanni R
Published: December 2008

Many cardiac neoplasms lack pathognomonic clinical features, and this leads to controversial interpretations. As genomic changes may correlate with these malignancies and possibly aid in diagnosis, fluorescence in situ hybridisation (FISH) was used to study a polypoid lesion found incidentally at autopsy on the septal wall of the left ventricle of a 75-year-old man who had died from a heart attack. Histology and immunohistochemistry disclosed atypical stromal cells with irregular voluminous nuclei positive for vimentin and smooth muscle actin; these cells were reminiscent of those previously reported in a subset of nasal polyps showing aneuploidy. The scarce lymphoplasmocytic infiltrate hindering the diagnosis of inflammatory myofibroblastic tumours (IMT), and the presence of atypical cells, prompted the use of FISH: lack ofALKgene rearrangement and aneuploidy were observed in the irregular nuclei, supporting the diagnosis of a pseudosarcomatous myofibroblastic proliferation (PMP). These results stress that IMT and PMP may represent variants within a spectrum of myofibroblastic proliferations/tumours.
Relationship between job strain and smoking cessation: the Finnish Public Sector Study
Authors: Kouvonen A , Vahtera J , Väänänen A , De Vogli R , Heponiemi T , Elovainio M , Virtanen M , Oksanen T , Cox S J , Pentti J , Kivimäki M
Published: December 2008

Aims:

To examine whether job strain (ie, excessive demands combined with low control) is related to smoking cessation.

Methods:

Prospective cohort study of 4928 Finnish employees who were baseline smokers. In addition to individual scores, coworker-assessed work unit level scores were calculated. A multilevel logistic regression analysis, with work units at the second level, was performed.

Results:

At follow-up, 21% of baseline smokers had quit smoking. After adjustment for sex, age, employer and marital status, elevated odds ratios (ORs) for smoking cessation were found for the lowest vs the highest quartile of work unit level job strain (OR 1.43, 95% CI 1.17 to 1.75) and for the highest vs the lowest quartile of work unit level job control (OR 1.61, 95% CI 1.31 to 1.96). After additional adjustment for health behaviours and trait anxiety, similar results were observed. Further adjustment for socioeconomic position slightly attenuated these associations, but an additional adjustment for individual strain/control had little effect on the results. The association between job strain and smoking cessation was slightly stronger in light than in moderate/heavy smokers. The results for individual job strain and job control were in the same direction as the work unit models, although these relationships became insignificant after adjustment for socioeconomic position. Job demands were not associated with smoking cessation.

Conclusions:

Smoking cessation may be less likely in workplaces with high strain and low control. Policies and programs addressing employee job strain and control might also contribute to the effectiveness of smoking cessation interventions.
WIDE AREA SPECTROMETRIC BIOAEROSOL MONITORING IN CANADA: FROM SINBAHD TO BIOSENSE
Authors: JEAN-ROBERT SIMARD , SYLVIE BUTEAU , PIERRE LAHAIE , PIERRE MATHIEU , GILLES ROY , VINCENT LAROCHELLE , BERNARD DERY , JOHN MCFEE , JIM HO
Published: December 2008

Threats associated with bioaerosol weapons have been around for several decades. However, with the recent political developments that changed the image and dynamics of the international order and security, the visibility and importance of these bioaerosol threats have considerably increased. Over the last few years, Defence Research and Development Canada has investigated the spectrometric LIDAR-based standoff bioaerosol detection technique to address this menace. This technique has the advantages of rapidly monitoring the atmosphere over wide areas without physical intrusions and reporting an approaching threat before it reaches sensitive sites. However, it has the disadvantages of providing a quality of information that degrades as a function of range and bioaerosol concentration. In order to determine the importance of these disadvantages, Canada initiated in 1999 the SINBAHD (Standoff Integrated Bioaerosol Active Hyperspectral Detection) project investigating the standoff detection and characterization of threatening biological clouds by Laser-Induced Fluorescence (LIF) and intensified range-gated spectrometric detection techniques. This article reports an overview of the different lessons learned with this program. Finally, the BioSense project, a Technology Demonstration Program aiming at the next generation of wide area standoff bioaerosol sensing, mapping, tracking and classifying systems, is introduced.
INEXPENSIVE CHEMICAL DEFENSE NETWORK FOR A FIXED SITE
Authors: SEELEY JULIETTE A. , ANGEL MATTHEW , AGGARWAL ROSHAN L. , JEYS THOMAS H. , SANCHEZ-RUBIO ANTONIO , DINATALE WILLIAM , RICHARDSON JONATHAN M.
Published: December 2008

The Inexpensive Chemical Agent Detection System (ICADS) consists of a network of affordable line-of-sight sensors, each designed to detect chemical threats passing between two points with high sensitivity and a low false-alarm rate. Each leg of the ICADS system is composed of two devices, a broadband IR transmitter, and a receiver containing a long-wave-IR spectrometer. The spectrometer continually measures the spectrum of the radiation emitted by the transmitter, which is separated from the receiver by up to several hundred meters, forming a line of protection. A chemical vapor or aerosol plume with sufficient long-wave-IR absorption causes a characteristic change in the spectrum of light collected by the receiver as the plume crosses the protected line, signaling a threat. Background measurements were conducted to determine background-limited performance. Additionally, a sensor composed of a long-wave-IR fixed-grating spectrometer and a hot-filament transmitter was designed and built. Measurements of the signal-to-noise ratio (SNR) and resolution agree with our analytical model and meet sensor requirements.
RARE-EARTH DOPED POTASSIUM LEAD BROMIDE MID-IR LASER SOURCES FOR STANDOFF DETECTION
Authors: MANDAL KRISHNA C. , KANG SUNG H. , CHOI MICHAEL , RAUH R. DAVID
Published: December 2008

The single crystal growth of KPb 2 Br 5 by vertical Bridgman technique using in-house processed zone refined PbBr 2 and KBr with rare-earth terbium doping has been studied. The grown moisture resistant crystals (1.5 cm diameter and 10 cm length) have shown high promise for low phonon energy room temperature solid-state laser applications in the longer side of mid-IR (4-15 µm) due to their high storage lifetimes, wide tunability, and excellent optical quality. The processed crystals are highly transparent ( T = ≥80%) in the 0.4-25 µm spectral region. Repeated melting-freezing cycles during differential scanning calorimetry (DSC) experiments did not reveal any appreciable variation in the melting point or phase transitions, which is indicative of their excellent thermal stability. The emission spectra pumped with a 2 µm source show broadband emissions with peak wavelength of 3 µ m (7 F 4→ 7 F6), 5µ m (7 F 5→ 7 F 6) and 7.9µ m (7 F 4→ 7 F 5). The KPb 2 Br 5: Tb laser crystals will be highly useful for standoff detection of incoming chemical and biological threats using unique infrared absorption signatures.
SYMBOLIC EXPRESSION ANALYSIS FOR COMPILED COMMUNICATION
Authors: JONES ALEX K. , SHAO SHUYI , ZHANG YU , MELHEM RAMI
Published: December 2008

Compiled communication can benefit the parallel application design and performance in several ways such as analyzing the communication pattern to optimize a configurable network for performance improvement or to visualize the communication requirements to study and improve the application design. In this article we present symbolic expression analysis techniques in a MPI parallel compiler. Symbolic expression analysis allows the identification and representation of the communication pattern and also assists in the determination of communication phases in MPI parallel applications at compile-time. We demonstrate that using compiler analysis based on symbolic expression analysis to determine the communication pattern can provide an accurate visualization of the communication requirements. Using information from the compiler to program a circuit switching interconnect in multiprocessor systems has the potential to achieve more efficient communication with lower cost compared to packet/wormhole switching. For example, we demonstrate that our compiler approach provides an average of 2.6 times improvement in message delay over a threshold-based runtime system for our benchmarks with a maximum improvement of 9.7 times.
DECAY OF THE MAXWELL FIELD ON THE SCHWARZSCHILD MANIFOLD
Authors: BLUE PIETER
Published: December 2008

We study solutions of the decoupled Maxwell equations in the exterior region of a Schwarzschild black hole. In stationary regions, where the Schwarzschild radial coordinate takes values in a bounded interval away from the event horizon, we obtain decay for all components of the Maxwell field at a rate which is bounded by the inverse of the standard time coordinate. We use vector field methods and no not require a spherical harmonic decomposition.

In outgoing regions, where the Regge–Wheeler tortoise coordinate grows at least linearly with the time coordinate, we obtain decay rates for each of the null components. These rates are similar to the rates in flat space but weaker. Along the event horizon and in ingoing regions, where the Regge–Wheeler coordinate is negative and the outgoing, Eddington–Finkelstein null-coordinate is positive, all components (normalized with respect to an ingoing null basis) decay at a rate which is bounded by the inverse of the outgoing null coordinate.
Applying practice to theory
Authors: Williams Ryan
Published: December 2008

How can complexity theory and algorithms benefit from practical advances in computing? We give an overview of some prior work using practical computing to attack problems in computational complexity and algorithms, informally describe how linear program solvers may be used to help prove new lower bounds for satisfiability, and suggest a research program for developing new understanding in circuit complexity.
Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation
Authors: Lee Jin Hee , Palaia Thomas , Ragolia Louis
Published: December 2008

Insulin resistance associated with Type 2 diabetes contributes to impaired vasorelaxation. Previously, we showed the phosphorylation of myosin-bound phosphatase substrate MYPT1, a marker of the vascular smooth muscle cell (VSMC) contraction, was negatively regulated by Akt (protein kinase B) phosphorylation in response to insulin stimulation. In this study we examined the role of Akt phosphorylation on impaired insulin-induced vasodilation in the Goto-Kakizaki (GK) rat model of Type 2 diabetes. GK VSMCs had impaired basal and insulin-induced Akt phosphorylation as well as increases in basal MYPT1 phosphorylation, inducible nitric oxide synthase (iNOS) expression, and nitrite/nitrate production compared with Wistar-Kyoto controls. Both iNOS expression and the inhibition of angiotensin (ANG) II-induced MYPT1 phosphorylation were resistant to the effects of insulin in diabetic GK VSMC. We also measured the isometric tension of intact and denuded GK aorta using a myograph and observed significantly impaired insulin-induced vasodilation. Adenovirus-mediated overexpression of constitutively active Akt in GK VSMC led to significantly improved insulin sensitivity in terms of counteracting ANG II-induced contractile signaling via MYPT1, myosin light chain dephosphorylation, and reduced iNOS expression, S-nitrosylation and survivin expression. We demonstrated for the first time the presence of Akt-independent iNOS expression in the GK diabetic model and that the defective insulin-induced vasodilation observed in the diabetic vasculature can be restored by the overexpression of active Akt, which advocates a novel therapeutic strategy for treating diabetes.
The Na+/I− symporter mediates active iodide uptake in the intestine
Authors: Nicola Juan Pablo , Basquin Cécile , Portulano Carla , Reyna-Neyra Andrea , Paroder Monika , Carrasco Nancy
Published: December 2008

Absorption of dietary iodide, presumably in the small intestine, is the first step in iodide (I−) utilization. From the bloodstream, I− is actively taken up via the Na+/I− symporter (NIS) in the thyroid for thyroid hormone biosynthesis and in such other tissues as lactating breast, which supplies I− to the newborn in the milk. The molecular basis for intestinal I− absorption is unknown. We sought to determine whether I− is actively accumulated by enterocytes and, if so, whether this process is mediated by NIS and regulated by I− itself. NIS expression was localized exclusively at the apical surface of rat and mouse enterocytes. In vivo intestine-to-blood transport of pertechnetate, a NIS substrate, was sensitive to the NIS inhibitor perchlorate. Brush border membrane vesicles accumulated I− in a sodium-dependent, perchlorate-sensitive manner with kinetic parameters similar to those of thyroid cells. NIS was expressed in intestinal epithelial cell line 6, and I− uptake in these cells was also kinetically similar to that in thyrocytes. I− downregulated NIS protein expression and its own NIS-mediated transport both in vitro and in vivo. We conclude that NIS is functionally expressed on the apical surface of enterocytes, where it mediates active I− accumulation. Therefore, NIS is a significant and possibly central component of the I− absorption system in the small intestine, a system of key importance for thyroid hormone biosynthesis and thus systemic intermediary metabolism.
In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters
Authors: Hama Kotaro , Provost Elayne , Baranowski Timothy C. , Rubinstein Amy L. , Anderson Jennifer L. , Leach Steven D. , Farber Steven A.
Published: December 2008

Optical clarity of larvae makes the zebrafish ideal for real-time analyses of vertebrate organ function through the use of fluorescent reporters of enzymatic activities. A key function of digestive organs is to couple the generation of enzymes with mechanical processes that enable nutrient availability and absorption. However, it has been extremely difficult, and in many cases not possible, to directly observe digestive processes in a live vertebrate. Here we describe a new method to visualize intestinal protein and lipid processing simultaneously in live zebrafish larvae using a quenched fluorescent protein (EnzChek) and phospholipid (PED6). By employing these reagents, we found that wild-type larvae exhibit significant variation in intestinal phospholipase and protease activities within a group but display a strong correlation between the activities within individuals. Furthermore, we found that pancreas function is essential for larval digestive protease activity but not for larval intestinal phospholipase activity. Although fat-free ( ffr) mutant larvae were previously described to exhibit impaired lipid processes, we found they also had significantly reduced protease activity. Finally, we selected and evaluated compounds that were previously suggested to have altered phospholipase activity and are known or suspected to have inflammatory effects in the intestinal tract including nonsteroidal anti-inflammatory drugs, and identified a compound that significantly increases intestinal phospholipid processing. Thus the multiple fluorescent reporter-based methodology facilitates the rapid analysis of digestive organ function in live zebrafish larvae.
Nutrient-induced gastrointestinal hyperemia and specific dynamic action in rainbow trout (Oncorhynchus mykiss)—importance of proteins and lipids
Authors: Seth Henrik , Sandblom Erik , Axelsson Michael
Published: December 2008

Mechanical gastric distension induces a dorsal aortic pressor response in rainbow trout ( Oncorhynchus mykiss) with no change in gastrointestinal blood flow. To elucidate what role chemical stimuli from the digested food has on the postprandial cardiovascular response, a new method was developed to investigate the contribution of individual nutrient components. Three predigested experimental diets were injected directly into the proximal intestine of rainbow trout and cardiac output (CO), gut blood flow (Qcma), heart rate (HR), and stroke volume (SV) were recorded. Specific dynamic action (SDA) was estimated by measuring oxygen consumption. When a balanced diet (50% protein, 25% fat, 15% carbohydrate) was injected, Qcmaand CO increased within 1 h by 45 and 27%, respectively. The response to a high-protein diet (70% protein, 5% fat, 15% carbohydrate) was quantitatively similar but delayed, with a maximal blood flow response after 2 h. With a high-lipid diet (60% fat, 15% protein, 15% carbohydrate), the peak increase in Qcmaby 22% occurred after 30 min and thereafter declined rapidly. The SDA response (19%) to the balanced diet was temporally matched with the hyperemia. With a high-protein diet, the response is delayed and enlarged (34%) compared with the balanced diet. The high-lipid diet gave no significant SDA response. We conclude that the chemical composition of the food influences the postprandial hyperemia and the SDA, such that the components appear to work in a synergistic fashion. The present results also demonstrate that both redistribution of blood flow and an overall increase in CO contribute to the postprandial increase in gut blood flow in this species.
Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor
Authors: Andrews Matthew T. , Russeth Kevin P. , Drewes Lester R. , Henry Pierre-Gilles
Published: December 2008

Hibernating mammals use reduced metabolism, hypothermia, and stored fat to survive up to 5 or 6 mo without feeding. We found serum levels of the fat-derived ketone, d-β-hydroxybutyrate (BHB), are highest during deep torpor and exist in a reciprocal relationship with glucose throughout the hibernation season in the thirteen-lined ground squirrel ( Spermophilus tridecemlineatus). Ketone transporter monocarboxylic acid transporter 1 (MCT1) is upregulated at the blood-brain barrier, as animals enter hibernation. Uptake and metabolism of 13C-labeled BHB and glucose were measured by high-resolution NMR in both brain and heart at several different body temperatures ranging from 7 to 38°C. We show that BHB and glucose enter the heart and brain under conditions of depressed body temperature and heart rate but that their utilization as a fuel is highly selective. During arousal from torpor, glucose enters the brain over a wide range of body temperatures, but metabolism is minimal, as only low levels of labeled metabolites are detected. This is in contrast to BHB, which not only enters the brain but is also metabolized via the tricarboxylic acid (TCA) cycle. A similar situation is seen in the heart as both glucose and BHB are transported into the organ, but only 13C from BHB enters the TCA cycle. This finding suggests that fuel selection is controlled at the level of individual metabolic pathways and that seasonally induced adaptive mechanisms give rise to the strategic utilization of BHB during hibernation.
Omega-3 fatty acid rich diet prevents diabetic renal disease
Authors: Garman Joseph H. , Mulroney Susan , Manigrasso Michaele , Flynn Elizabeth , Maric Christine
Published: December 2008

Omega-3 polyunsaturated fatty acids (n-3 PUFA) show beneficial effects in cardiovascular disease, IgA, and diabetic nephropathy; however, the mechanisms underlying these benefits are unknown. The study was performed in male Sprague-Dawley rats randomly divided into four treatment groups: nondiabetic (ND), streptozotocin-induced diabetic (D), diabetic and fed a high n-3 PUFA diet (D+canola), and diabetic and fed a high n-6 (omega-6) PUFA diet (D+corn). Study treatments were carried out for 30 wk. D+canola significantly decreased diabetes-associated increases in urine albumin excretion (ND 17.8 ± 6.4; D 97.3 ± 9.4; D+canola 8.3 ± 2.2 mg/day); systolic blood pressure (ND 153 ± 9; D 198 ± 7; D+canola 162 ± 9 mmHg); glomerulosclerosis (ND 0.6 ± 0.2; D 1.8 ± 0.2; D+canola 0.8 ± 0.1 AU); and tubulointerstitial fibrosis in the renal cortex (ND 1.2 ± 0.2; D 2.0 ± 0.2; D+canola 1.1 ± 0.1) and the inner stripe of the outer medulla (ND 1.0 ± 0.2; D 2.1 ± 0.2; D+canola 1.1 ± 0.2 AU). D+corn also exerted renoprotection, but not to the same degree as D+canola (urine albumin excretion, 33.8 ± 6.1 mg/day; systolic blood pressure, D+corn 177 ± 6 mmHg; glomerulosclerosis, D+corn 1.2 ± 0.3 AU; cortical tubulointerstitial fibrosis, D+corn 1.6 ± 0.1 AU; medullary tubulointerstitial fibrosis, D+corn 1.5 ± 0.1 AU). In addition, D+canola attenuated D-associated increase in collagen type I and type IV, IL-6, MCP-1, transforming growth factor-β, and CD68 expression. These observations indicate a beneficial effect of high dietary intake of n-3 PUFA in reducing diabetic renal disease.
cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells
Authors: Montesano Roberto , Ghzili Hafida , Carrozzino Fabio , Rossier Bernard C. , Féraille Eric
Published: December 2008

Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCDcl1cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forskolin or cholera toxin) or of membrane-permeable cAMP analogs (CPT-cAMP) resulted in rapid and progressive dilatation of existing tubules, leading to the formation of cystlike structures. When grown on filters, mCCD-N21 cells exhibited a high transepithelial resistance as well as aldosterone- and/or vasopressin-induced amiloride-sensitive and -insensitive current. The latter was in part inhibited by Na+-K+-2Cl−cotransporter (bumetanide) and chloride channel (NPPB) inhibitors. Real-time PCR analysis confirmed the expression of NKCC1, the ubiquitous Na+-K+-2Cl−cotransporter and cystic fibrosis transmembrane regulator (CFTR) in mCCD-N21 cells. Tubule enlargement and cyst formation were prevented by inhibitors of Na+-K+-2Cl−cotransporters (bumetanide or ethacrynic acid) or CFTR (NPPB or CFTR inhibitor-172). These results further support the notion that cAMP signaling plays a key role in renal cyst formation, at least in part by promoting chloride-driven fluid secretion. This new in vitro model of tubule-to-cyst conversion affords a unique opportunity for investigating the molecular mechanisms that govern the architecture of epithelial tubes, as well as for dissecting the pathophysiological processes underlying cystic kidney diseases.
Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans
Authors: Arai T. J. , Henderson A. C. , Dubowitz D. J. , Levin D. L. , Friedman P. J. , Buxton R. B. , Prisk G. K. , Hopkins S. R.
Published: December 2008

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O2 fraction (FiO2) = 0.21; hypoxia, FiO2 = 0.125; hyperoxia, FiO2 = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm3; normoxia, 0.47(0.18) g water/cm3; hyperoxia, 0.48(0.17) g water/cm3; P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml·min−1·g−1; normoxia, 4.94(1.88) ml·min−1·g−1; hyperoxia, 5.32(1.83) ml·min−1·g−1; P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.
Effect of elevated local temperature on cutaneous vasoconstrictor responsiveness in humans
Authors: Wingo Jonathan E. , Low David A. , Keller David M. , Brothers R. Matthew , Shibasaki Manabu , Crandall Craig G.
Published: December 2008

Cutaneous vascular conductance (CVC) increases in response to local skin heating. Although attenuation of vasoconstrictor responsiveness due to local heating has been demonstrated, the mechanism(s) responsible for this attenuation remains unclear. Nitric oxide has been shown to at least partially contribute to this response, but other mechanisms also may be involved. The purpose of this study was to test the hypothesis that local heating diminishes cutaneous vasoconstrictor responsiveness through a nitric oxide-independent mechanism by altering postsynaptic reactivity to norepinephrine. A follow-up protocol tested the hypothesis that local heating attenuates the presynaptic release of neurotransmitters that cause vasoconstriction, also via non-nitric oxide mechanisms. In protocol I, CVC was assessed in eight subjects during administration of increasing doses of norepinephrine (via intradermal microdialysis) at adjacent sites separately heated to 34°C and 40°C. In protocol II, which was identical to, but separate from, protocol I, CVC was assessed in seven subjects during administration of increasing doses of tyramine, which causes release of neurotransmitters from adrenergic nerves. At each site for both protocols, nitric oxide synthesis was inhibited (via microdialysis administration of NG-nitro-l-arginine methyl ester) and flow was matched (via microdialysis administration of adenosine); therefore, temperature was the only variable that differed between the sites. For both protocols, nonlinear regression analysis revealed no difference ( P > 0.05) in the effective drug concentration causing 50% of the vasoconstrictor response. Minimum CVC [6.3 ± 2.0 and 9.0 ± 4.0% of peak CVC (mean ± SD) for protocol I and 19.3 ± 9.3 and 20.5 ± 11.9% of peak CVC for protocol II at 34°C and 40°C sites, respectively] was not different between sites. Independent of nitric oxide, local skin heating to 40°C does not attenuate adrenergically mediated cutaneous vasoconstriction through pre- or postsynaptic mechanisms.