bluuebunny/crossref_metadata_2025 huggingface dataset:
Resources for academic advising
Authors: Gordon Virginia N.
Published: October 2006

This chapter introduces the many resources available to faculty advisers who are interested in improving the advising services on their campus, are interested in learning more about the field of academic advising, or wish to perform research in this area.
Disciplinary differences in knowledge validation
Authors: Donald Janet G.
Published: October 2006

Validation processes and truth criteria employed in a discipline define the discipline, govern knowledge production and dissemination in the discipline, and suggest ways of improving instruction.
What is taught in an undergraduate lecture? Differences between a matched pair of pure and applied disciplines
Authors: Hativa Nira
Published: October 2006

Two lessons from comparable undergraduate courses in physics and engineering are analyzed to identify content, issues emphasized, and concepts used. Differences reflecting the pure nature of one field (physics) versus the applied nature of the other (engineering) are identified in the two lessons.
Subject‐matter differences in secondary schools: Connections to higher education
Authors: Stodolsky Susan S. , Grossman Pamela L.
Published: October 2006

A study of the role of subject matter in shaping high school teachers' beliefs, curricular concerns, and instructional practices complements studies of the disciplines in higher education and suggests implications for research and practice.
Identifying exemplary teachers: Evidence from colleagues, administrators, and alumni
Authors: Centra John A.
Published: October 2006

Are traditional sources of information about exemplary teaching effective for identifying such teachers?—a review of the research and a proposal.
Consistency within diversity: Guidelines for programs to honor exemplary teaching
Authors: Svinicki Marilla D. , Menges Robert J.
Published: October 2006

A synthesis of suggestions and cautions about establishing recognition programs takes the form of ten guidelines that apply regardless of program format and context.
Ethical principles for college and university teaching
Authors: Murray Harry , Gillese Eileen , Lennon Madeline , Mercer Paul , Robinson Marilyn
Published: October 2006

Designing, carrying out, and analyzing instruction requires taking into account certain ethical guidelines, ideals, and expectations.
Intervening with Colleagues
Authors: Keith‐Spiegel Patricia , Wittig Arno F. , Perkins David V. , Balogh Deborah Ware , Whitley Bernard E.
Published: October 2006

Confronting a colleague who is suspected of unethical conduct is never easy or pleasant. Observing appropriate procedures may help facilitate a successful outcome.
Toward more ethical teaching
Authors: Fisch Lin C.
Published: October 2006

Herein are practical suggestions on how colleges and universities can develop and carry out a variety of initiatives, particularly seminars and workshops, that can be directed toward enhancing engagement with ethical issues and promoting ethical behavior.
The active learning continuum: Choosing activities to engage students in the classroom
Authors: Bonwell Charles C. , Sutherland Tracey E.
Published: October 2006

We believe that all instructors should find ways to include meaningful active learning approaches in their classes. This chapter provides a framework for choosing active learning strategies that take into account course objectives, teaching styles, and students' level of experience.
Encouraging self‐assessment: Writing as active learning
Authors: Hobson Eric H.
Published: October 2006

Writing is a useful tool for helping students achieve the distance they need to begin to critically evaluate their own work.
FROBENIUS SPLITTING OF EQUIVARIANT CLOSURES OF REGULAR CONJUGACY CLASSES
Authors: THOMSEN JESPER FUNCH
Published: October 2006

Let $G$ denote a connected semisimple and simply connected algebraic group over an algebraically closed field $k$ of positive characteristic and let $g$ denote a regular element of $G$. Let $X$ denote any equivariant embedding of $G$. We prove that the closure of the conjugacy class of $g$ within $X$ is normal and Cohen–Macaulay. Moreover, when $X$ is smooth we prove that this closure is a local complete intersection. As a consequence, the closure of the unipotent variety within $X$ shares the same geometric properties.
Disseminated and sustained HIV infection in CD34+cord blood cell-transplanted Rag2−/−γc−/−mice
Authors: Baenziger Stefan , Tussiwand Roxane , Schlaepfer Erika , Mazzucchelli Luca , Heikenwalder Mathias , Kurrer Michael O. , Behnke Silvia , Frey Joachim , Oxenius Annette , Joller Helen , Aguzzi Adriano , Manz Markus G. , Speck Roberto F.
Published: October 2006

Because of species selectivity, HIV research is largely restricted toin vitroor clinical studies, both limited in their ability to rapidly assess new strategies to fight the virus. To prospectively study some aspects of HIVin vivo, immunodeficient mice, transplanted with either human peripheral blood leukocytes or human fetal tissues, have been developed. Although these are susceptible to HIV infection, xenoreactivity, and short infection spans, resource and ethical constraints, as well as biased HIV coreceptor tropic strain infection, pose substantial problems in their use. Rag2−/−γc−/−mice, transplanted as newborns with human CD34+cells, were recently shown to develop human B, T, and dendritic cells, constituting lymphoid organsin situ. Here we tested these mice as a model system for HIV-1 infection. HIV RNA levels peaked to up to 2 × 106copies per milliliter of plasma early after infection, and viremia was observed for up to 190 days, the longest time followed. A marked relative CD4+T cell depletion in peripheral blood occurred in CXCR4-tropic strain-infected mice, whereas this was less pronounced in CCR5-tropic strain-infected animals. Thymus infection was almost exclusively observed in CXCR4-tropic strain-infected mice, whereas spleen and lymph node HIV infection occurred irrespective of coreceptor selectivity, consistent with respective coreceptor expression on human CD4+T cells. Thus, this straightforward to generate and cost-effectivein vivomodel closely resembles HIV infection in man and therefore should be valuable to study virus-induced pathology and to rapidly evaluate new approaches aiming to prevent or treat HIV infection.
THOR: targeted high-throughput ortholog reconstructor
Authors: Bainbridge Matthew N. , Warren René L. , He An , Bilenky Mikhail , Robertson A. Gordon , Jones Steven J.M.
Published: October 2006

Summary: Low-coverage genomes (LCGs) are becoming an increasingly important source of data for phylogenetic studies. However, assembly of these genomes is time consuming, difficult and lags behind sequence generation. THOR is a fast, stringent application for targeted reconstruction of sequence orthologs in unassembled LCGs. Using a 4× coverage set of mouse whole-genome sequence reads, THOR could partially or completely reconstruct 416/1000 human promoter ortholog regions in ∼7.3 min/promoter. THOR's reconstruction rate improves markedly with both higher-coverage, and less divergent target species.

Availability: THOR is implemented in java and is currently available as source code and as a web service (www.bcgsc.ca/services/thor) for reconstructing human sequences.

Contact: matthewb@bcgsc.ca
ssSNPer: identifying statistically similar SNPs to aid interpretation of genetic association studies
Authors: Nyholt Dale R.
Published: October 2006

Summary: ssSNPer is a novel user-friendly web interface that provides easy determination of the number and location of untested HapMap SNPs, in the region surrounding a tested HapMap SNP, which are statistically similar and would thus produce comparable and perhaps more significant association results. Identification of ssSNPs can have crucial implications for the interpretation of the initial association results and the design of follow-up studies.

Availability:  

Contact:  daleN@qimr.edu.au
Human heterochromatin proteins form large domains containing KRAB-ZNF genes
Authors: Vogel Maartje J. , Guelen Lars , de Wit Elzo , Hupkes Daniel Peric , Lodén Martin , Talhout Wendy , Feenstra Marike , Abbas Ben , Classen Anne-Kathrin , van Steensel Bas
Published: October 2006

Heterochromatin is important for gene regulation and chromosome structure, but the genes that are occupied by heterochromatin proteins in the mammalian genome are largely unknown. We have adapted the DamID method to systematically identify target genes of the heterochromatin proteins HP1 and SUV39H1 in human and mouse cells. Unexpectedly, we found that CBX1 (formerly HP1β) and SUV39H1 bind to genes encoding KRAB domain containing zinc finger (KRAB-ZNF) transcriptional repressors. These genes constitute one of the largest gene families and are organized in clusters in the human genome. Preference of CBX1 for this gene family was observed in both human and mouse cells. High-resolution mapping on human chromosome 19 revealed that CBX1 coats large domains 0.1–4 Mb in size, which coincide with the position of KRAB-ZNF gene clusters. These domains show an intricate CBX1 binding pattern: While CBX1 is globally elevated throughout the domains, it is absent from the promoters and binds more strongly to the 3′ ends of KRAB-ZNF genes. KRAB-ZNF domains contain large numbers of LINE elements, which may contribute to CBX1 recruitment. These results uncover a surprising link between heterochromatin and a large family of regulatory genes in mammals. We suggest a role for heterochromatin in the evolution of the KRAB-ZNF gene family.
Right Ventricular Outflow Tract Pacing: Practical and Beneficial. A 9‐Year Experience of 460 Consecutive Implants
Authors: VLAY STEPHEN C.
Published: October 2006

Background: Pacing from the right ventricular apex (RVA) in patients with ventricular dysfunction has been identified as a possible contributor to deterioration of ventricular function. Therefore, alternative pacing sites such as the right ventricular outflow tract (RVOT) are receiving intensified scrutiny. An unresolved question is whether technical, procedural, and stability issues are comparable for the RVA and the RVOT.

Methods: This report details 460 consecutive ventricular pacing lead implants with the primary intended site in the RVOT. Patients were evaluated for success, complication rates, and followed‐up for stability of pacing parameters. The total patient implant population included 300 male and 170 female patients with a mean age of 70.6 years. Ten patients were excluded from the analysis, since there was a primary indication and intention to implant in the RVA, leaving a total of 460 patients for analysis. The indications for pacing were symptomatic bradycardia due to any cause and/or Mobitz II or complete heart block. There was no clinical evidence of heart failure in 420 patients. In 40 patients with heart failure, the indication for pacing was cardiac resynchronization therapy using the RVOT as an alternate site when pacing from a branch vein of the coronary sinus was not possible. Outcome information was obtained from the implanter's clinic.

Results: The overall success rate in the RVOT was 84% over the total 9‐year period with a 92% success rate in the last 4½ years, using the RVOT technique described. At 20 months in a subgroup comparison of RVOT and RVA implants, there was no significant difference in pacing threshold, R‐wave sensing, or pacing lead impedance. Dislodgment occurred in only 1 of 460 patients. Reasons for failure to implant in the RVOT include inability to find a stable position with adequate pacing and sensing thresholds (related to anatomy, scarred myocardium, pulmonary hypertension, tricuspid regurgitation), hemodynamic instability limiting time for implant, and a learning curve. Long‐term stability and lead performance were excellent, and certain acute and chronic complications of RV pacing did not occur.
Does RV Lead Positioning Provide Additional Benefit to Cardiac Resynchronization Therapy in Patients with Advanced Heart Failure?
Authors: SHIMANO MASAYUKI , INDEN YASUYA , YOSHIDA YUKIHIKO , TSUJI YUKIOMI , TSUBOI NAOYA , OKADA TARO , YAMADA TAKUMI , MURAKAMI YOSHIMASA , TAKADA YASUNOBU , HIRAYAMA HARUO , MUROHARA TOYOAKI
Published: October 2006

Background and Objectives: The left ventricular (LV) stimulation site is currently recommended to position the lead at the lateral wall. However, little is known as to whether right ventricular (RV) lead positioning is also important for cardiac resynchronization therapy. This study compared the acute hemodynamic response to biventricular pacing (BiV) at two different RV stimulation sites: RV high septum (RVHS) and RV apex (RVA).

Methods and Results: Using micro‐manometer‐tipped catheter, LV pressure was measured during BiV pacing at RV (RVA or RVHS) and LV free wall in 33 patients. Changes in LV dP/dtmax and dP/dtmin from baseline were compared between RVA and RVHS. BiV pacing increased dP/dtmax by 30.3 ± 1.2% in RVHS and by 33.3 ± 1.7% in RVA (P = n.s.), and decreased dP/dtmin by 11.4 ± 0.7% in RVHS and by 13.0 ± 1.0% in RVA (P = n.s.). To explore the optimal combination of RV and LV stimulation sites, we assessed separately the role of RV positioning with LV pacing at anterolateral (AL), lateral (LAT), or posterolateral (PL) segment. When the LV was paced at AL or LAT, the increase in dP/dtmax with RVHS pacing was smaller than that with RVA pacing (AL: 12.2 ± 2.2% vs 19.3 ± 2.1%, P < 0.05; LAT: 22.0 ± 2.7% vs 28.5 ± 2.2%, P < 0.05). There was no difference in dP/dtmin between RVHS‐ and RVA pacing in individual LV segments.

Conclusions: RVHS stimulation has no overall advantage as an alternative stimulation site for RVA during BiV pacing. RVHS was equivalent with RVA in combination with the PL LV site, while RVA was superior to RVHS in combination with AL or LAT LV site.
Spatial Distribution of Repolarization and Depolarization Abnormalities Evaluated by Body Surface Potential Mapping in Patients with Brugada Syndrome
Authors: YOKOKAWA MIKI , TAKAKI HIROSHI , NODA TAKASHI , SATOMI KAZUHIRO , SUYAMA KAZUHIRO , KURITA TAKASHI , KAMAKURA SHIRO , SHIMIZU WATARU
Published: October 2006

Background: Mutations in sodium channel gene, SCN5A, have been identified in Brugada syndrome, but it is still unclear as to how sodium channel dysfunction relates to arrhythmogenesis. We examined spatial distribution of both repolarization and depolarization abnormalities in patients with Brugada syndrome by using 87‐leads body surface potential mapping (BSPM).

Methods: BSPM was recorded under baseline condition and after pharmacological interventions in 28 patients with Brugada syndrome (27 males, 49 ± 14 years). The ST‐segment amplitude 20 ms after the end of QRS (ST20), QRS duration, and corrected recovery time (RTc) were measured in all 87‐leads, and averaged among 6‐leads (D–F, 5–6) reflecting right ventricular outflow tract (RVOT) potentials and the other 81‐leads.

Results: The ST20 was elevated at baseline, normalized by isoproterenol, and augmented by pilsicainide in only the RVOT. The RTc was longer at baseline and increased by pilsicainide in only the RVOT. On the other hand, the QRS duration was slightly widened at baseline, further increased by pilsicainide, but not changed by isoproterenol in both leads.

Conclusions: The ST‐segment elevation and the RTc prolongation were localized and modulated by agents only in the RVOT region, while the slight QRS widening at baseline and further increase by pilsicainide were observed homogeneously. Our data suggest that depolarization abnormalities are distributed homogeneously, whereas repolarization abnormalities are localized in the RVOT.
Self‐guided brisk walking training with or without poles: a randomized‐controlled trial in middle‐aged women
Authors: Kukkonen‐Harjula K. , Hiilloskorpi H. , Mänttäri A. , Pasanen M. , Parkkari J. , Suni J. , Fogelholm M. , Laukkanen R.
Published: October 2006

Walking with poles (Nordic walking, NW) has become popular. We compared training responses of brisk walking (W) or NW on cardiorespiratory and neuromuscular fitness. We randomized 121 non‐obese sedentary women (aged 50–60) to an NW or W group (NWG, WG), to train 40 min four times weekly for 13 weeks. Intensity was based on subjective perception of exertion. Cardiorespiratory performance was assessed in four levels corresponding to 50%, 65%, 80% and 100% of peak VO2. Fifty‐four NWG and 53 WG subjects completed the study. The mean intensity was about 50% of heart rate (HR) reserve. The baseline peak VO2 was 25.8 (SD 3.9) mL/min/kg. Both groups improved peak VO2 similarly (NWG 2.5 mL/min/kg, 95% confidence interval (CI) 1.9–3.3; WG 2.6, CI 1.9–3.3). In the submaximal stages while walking with or without poles, HR and lactate decreased after training in both groups, but the changes were not statistically significantly different between the groups. Of the neuromuscular tests after training, the only significant difference between the groups was in the leg strength in the one‐leg squat, favoring WG. In conclusion, both training modes improved similarly health‐enhancing physical fitness, and they were feasible and safe.
ANTIBACTERIAL ACTIVITY OF EXTRACTS FROM FAMILY ZINGIBERACEAE AGAINST FOODBORNE PATHOGENS
Authors: VORAVUTHIKUNCHAI S.P. , LIMSUWAN S. , SUPAPOL O. , SUBHADHIRASAKUL S.
Published: October 2006

Chloroformic extracts of selected Thai medicinal plants commonly employed to treat infections were investigated for their antibacterial activity against important foodborne pathogenic bacteria. These included Bacillus cereus, Staphylococcus aureus, methicillin‐resistant S. aureus (MRSA), Escherichia coli O157:H7, Salmonella Typhi and Shigella sp. Among 33 extracts tested, only chloroformic extracts of five plant species exhibited antibacterial properties. Alpinia galanga, Boesenbergia rotunda, Zingiber zerumbet and Piper betel were active against S. aureus. Barleria lupulina was active against B. cereus. Only the extract from P. betel leaves possessed activity against gram‐negative bacteria. As extracts from the three plant species belonging to family Zingiberaceae displayed strong activity against S. aureus, they were further tested against 17 clinical isolates. Minimum inhibitory concentration (MIC) values of B. rotunda, A. galanga and Z. zerumbet extracts against most clinical S. aureus isolates were 0.01, 0.19 and 0.79 mg/mL and the minimum bactericidal concentration (MBC) values were 0.19, 1.57 and >12.5 mg/mL, respectively. Significant growth inhibition of MRSA was observed in the cultures incubated in the presence of the B. rotunda extract, A. galanga and Z. zerumbet. B. rotunda exhibited the greatest activity among the three plant species against S. aureus at MIC, 2MIC and MBC within 2 h.
DUAL‐PHASIC INACTIVATION OF ESCHERICHIA COLI O157:H7 WITH PEROXYACETIC ACID, ACIDIC ELECTROLYZED WATER AND CHLORINE ON CANTALOUPES AND FRESH‐CUT APPLES
Authors: WANG HUA , FENG HAO , LUO YAGUANG
Published: October 2006

The effects of peroxyacetic acid (POAA), acidic electrolyzed water (AEW) and chlorine on inactivation of Escherichia coli O157:H7 on fresh‐cut apples and cantaloupe rinds were investigated. Apple cylinders were dip‐inoculated with E. coli O157:H7 and treated with sterilized water (control), chlorine, AEW or POAA for up to 8 min. Cantaloupe cylinders were spot‐inoculated with E. coli O157:H7 to the rind and treated with sterilized water, AEW or POAA for up to 15 min. All sanitizer treatments showed a significantly (P < 0.05) higher inactivation than the control. The residual counts of E. coli O157:H7 on both fruits exhibited a dual‐phasic reduction behavior, with a fast inactivation (D values: 0.8–5.0 min) in the first minute (phase I) of treatments followed by a much slower inactivation (D values: 14.6–59.8 min) in the remaining time (phase II). The dual‐phasic inactivation seems to be related to fruit surface topography that determines the bacterial distribution.
TRPV1 is a novel target for omega‐3 polyunsaturated fatty acids
Authors: Matta José A. , Miyares Rosa L. , Ahern Gerard P.
Published: October 2006

Omega‐3 (n‐3) fatty acids are essential for proper neuronal function, and they possess prominent analgesic properties, yet their underlying signalling mechanisms are unclear. Here we show thatn‐3 fatty acids interact directly with TRPV1, an ion channel expressed in nociceptive neurones and brain. These fatty acids activate TRPV1 in a phosphorylation‐dependent manner, enhance responses to extracellular protons, and displace binding of the ultrapotent TRPV1 ligand [3H]resiniferatoxin. In contrast to their agonistic properties,n‐3 fatty acids competitively inhibit the responses of vanilloid agonists. These actions occur in mammalian cells in the physiological concentration range of 1–10 μm. Significantly, docosahexaenoic acid exhibits the greatest efficacy as an agonist, whereas eicosapentaenoic acid and linolenic acid are markedly more effective inhibitors. Similarly, eicosapentaenoic acid but not docosahexaenoic acid profoundly reduces capsaicin‐evoked pain‐related behaviour in mice. These effects are independent of alterations in membrane elasticity because the micelle‐forming detergent Triton X‐100 only minimally affects TRPV1 properties. Thus,n‐3 fatty acids differentially regulate TRPV1 and this form of signalling may contribute to their biological effects. Further, these results suggest that dietary supplementation with selectiven‐3 fatty acids would be most beneficial for the treatment of pain.
GAUGE SYMMETRY BREAKING IN ORBIFOLD MODEL BUILDING
Authors: TRAPLETTI MICHELE
Published: October 2006

We review the gauge symmetry breaking mechanism due to orbifold projections in orbifold model building. We explicitly show the existence of a scale of breaking if such a symmetry breaking is due to freely-acting orbifold operators only, i.e. in case the breaking is realized nonlocally in the internal space. We show that such a scale is related to the compactification moduli only, and that there are no extra continuous parameters, at least in semirealistic models with [Formula: see text] SUSY in four dimensions. In this sense, the mechanism is peculiarly different from the standard Higgs (or Hosotani) symmetry breaking mechanism. We show that the mechanism also differs from that present in standard orbifold models where, even in the presence of discrete Wilson lines, a scale of breaking is generically missing, since the breaking is localized in specific points in the internal space.

We review a set of background geometries where the described nonlocal breaking is realized, both in the case of two and six extra dimensions. In the latter case, relevant in string model building, we consider both heterotic and open string compactifications.
EFFECTS OF CORRELATED NOISES IN A SATURATION LASER MODEL
Authors: ZHU P. , CHEN S. B. , MEI D. C.
Published: October 2006

The effects of correlations between additive and multiplicative noises in a saturation laser model are investigated. The approximative Fokker–Planck equation and analytic expressions of the steady-state probability distribution function (SPD) of the laser system are derived. Based on the SPD, the normalized mean, the normalized variance, and the normalized skewness of the steady-state laser intensity are calculated numerically. Our results indicate that: (i) For the laser being operated above threshold, the correlation strength λ reduces the intensity fluctuation; (ii) For the laser being operated near threshold and below threshold, the correlation strength λ enhances the intensity fluctuation.
Inchinkoto, a herbal medicine, and its ingredients dually exert Mrp2/MRP2-mediated choleresis and Nrf2-mediated antioxidative action in rat livers
Authors: Okada Kosuke , Shoda Junichi , Kano Masahito , Suzuki Sachiko , Ohtake Nobuhiro , Yamamoto Masahiro , Takahashi Hiroshi , Utsunomiya Hirotoshi , Oda Koji , Sato Kimi , Watanabe Ayaka , Ishii Tetsuro , Itoh Ken , Yamamoto Masayuki , Yokoi Tsuyoshi , Yoshizato Katsutoshi , Sugiyama Yuichi , Suzuki Hiroshi
Published: October 2006

Inchinkoto (ICKT), a herbal medicine, has been recognized in Japan and China as a “magic bullet” for jaundice. To explore potent therapeutic agents for cholestasis, the effects of ICKT or its ingredients on multidrug resistance-associated protein 2 (Mrp2/ MRP2)-mediated choleretic activity, as well as on antioxidative action, were investigated using rats and chimeric mice with livers that were almost completely repopulated with human hepatocytes. Biliary excretion of Mrp2 substrates and the protein mass, subcellular localization, and mRNA level of Mrp2 were assessed in rats after 1-wk oral administration of ICKT or genipin, a major ingredient of ICKT. Administration of ICKT or genipin to rats for 7 days increased bile flow and biliary excretion of bilirubin conjugates. Mrp2 protein and mRNA levels and Mrp2 membrane densities in the bile canaliculi and renal proximal tubules were significantly increased in ICKT- or genipin-treated rat livers and kidneys. ICKT and genipin, thereby, accelerated the disposal of intravenously infused bilirubin. The treatment also increased hepatic levels of heme oxygenase-1 and GSH by a nuclear factor-E2-related factor (Nrf2)-dependent mechanism. Similar effects of ICKT on MRP2 expression levels were observed in humanized livers of chimeric mice. In conclusion, these findings provide the rationale for therapeutic options of ICKT and its ingredients that should potentiate bilirubin disposal in vivo by enhancing Mrp2/MRP2-mediated secretory capacities in both livers and kidneys as well as Nrf2-mediated antioxidative actions in the treatment of cholestatic liver diseases associated with jaundice.
Sex-related effects on venous compliance and capillary filtration in the lower limb
Authors: Lindenberger M. , Länne T.
Published: October 2006

Recent studies in humans have suggested sex differences in venous compliance of the lower limb, with lower compliance in women. Capillary fluid filtration could, however, be a confounder in the evaluation of venous compliance. The venous capacitance and capillary filtration response in the calves of 12 women (23.2 ± 0.5 years) and 16 men (22.9 ± 0.5 years) were studied during 8 min lower body negative pressure (LBNP) of 11, 22, and 44 mmHg. Calf venous compliance is dependent on pressure and was determined using the first derivative of a quadratic regression equation that described the capacitance-pressure relationship [compliance = β1+ (2·β2· transmural pressure)]. We found a lower venous compliance in women at low transmural pressures, and the venous capacitance in men was increased ( P < 0.05). However, the difference in compliance between sexes was reduced and not seen at higher transmural pressures. Net capillary fluid filtration and capillary filtration coefficient (CFC) were greater in women than in men during LBNP ( P < 0.05). Furthermore, calf volume increase (capacitance response + total capillary filtration) during LBNP was equivalent in both sexes. When total capillary filtration was not subtracted from the calf capacitance response in the calculation of venous compliance, the sex differences disappeared, emphasizing that venous compliance measurement should be corrected for the contribution of CFC.
Oxyntomodulin increases intrinsic heart rate in mice independent of the glucagon-like peptide-1 receptor
Authors: Sowden Gillian L. , Drucker Daniel J. , Weinshenker David , Swoap Steven J.
Published: October 2006

Oxyntomodulin (OXM), a postprandially released intestinal hormone, inhibits food intake via the glucagon-like peptide-1 receptor (GLP-1R). Although OXM may have clinical value in treating obesity, the cardiovascular effects of OXM are not well understood. Using telemetry to measure heart rate (HR), body temperature (Tb), and activity in conscious and freely moving mice, we tested 1) whether OXM affects HR and 2) whether this effect is mediated by the GLP-1R. We found that peripherally administered OXM significantly increased HR in wild-type mice, raising HR by >200 beats/min to a maximum of 728 ± 11 beats/min. To determine the extent to which the sympathetic nervous system mediates the tachycardia of OXM, we delivered this hormone to mice deficient in dopamine-β-hydroxylase [ Dbh(−/−) mice], littermate controls [ Dbh(+/−) mice], and autonomically blocked C57Bl mice. OXM increased HR equally in all groups (192 ± 13, 197 ± 21, and 216 ± 11 beats/min, respectively), indicating that OXM elevated intrinsic HR. Intrinsic HR was also vigorously elevated by OXM in Glp-1R(−/−) mice (200 ± 28 beats/min). In addition, peripherally administered OXM inhibited food intake and activity levels in wild-type mice and lowered Tb in autonomically blocked mice. None of these effects were observed in Glp-1R(−/−) mice. These data suggest multiple modes of action of OXM: 1) it directly elevates murine intrinsic HR through a GLP-1R-independent mechanism, perhaps via the glucagon receptor or an unidentified OXM receptor, and 2) it lowers food intake, activity, and Tb in a GLP-1R-dependent fashion.
Visualizing lung function with positron emission tomography
Authors: Harris R. Scott , Schuster Daniel P.
Published: October 2006

Positron emission tomography (PET) provides three-dimensional images of the distributions of radionuclides that have been inhaled or injected into the lungs. By using radionuclides with short half-lives, the radiation exposure of the subject can be kept small. By following the evolution of the distributions of radionuclides in gases or compounds that participate in lung function, information about such diverse lung functions as regional ventilation, perfusion, shunt, gas fraction, capillary permeability, inflammation, and gene expression can be inferred. Thus PET has the potential to provide information about the links between cellular function and whole lung function in vivo. In this paper, recent advancements in PET methodology and techniques and information about lung function that have been obtained with these techniques are reviewed.
Apolipoprotein CIII-Induced THP-1 Cell Adhesion to Endothelial Cells Involves Pertussis Toxin-Sensitive G Protein- and Protein Kinase Cα-Mediated Nuclear Factor-κB Activation
Authors: Kawakami Akio , Aikawa Masanori , Nitta Noriko , Yoshida Masayuki , Libby Peter , Sacks Frank M.
Published: October 2006

Objective—

Plasma apolipoprotein CIII (apoCIII) independently predicts risk for coronary heart disease (CHD). We recently reported that apoCIII directly enhances adhesion of human monocytes to endothelial cells (ECs), and identified the activation of PKCα as a necessary upstream event of enhanced monocyte adhesion. This study tested the hypothesis that apoCIII activates PKCα in human monocytic THP-1 cells, leading to NF-κB activation.

Methods and Results—

Among inhibitors specific to PKC activators, phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor D609 limited apoCIII-induced PKCα activation and THP-1 cell adhesion. ApoCIII increased PC-PLC activity in THP-1 cells, resulting in PKCα activation. Pertussis toxin (PTX) inhibited apoCIII-induced PC-PLC activation and subsequent PKCα activation, implicating PTX-sensitive G protein pathway. ApoCIII further activated nuclear factor-κB (NF-κB) through PKCα in THP-1 cells and augmented β1-integrin expression. The NF-κB inhibitor peptide SN50 partially inhibited apoCIII-induced β1-integrin expression and THP-1 cell adhesion. ApoCIII-rich VLDL had similar effects to apoCIII alone.

Conclusions—

PTX-sensitive G protein pathway participates critically in PKCα stimulation in THP-1 cells exposed to apoCIII, activating NF-κB, and increasing β1-integrin. This action causes monocytic cells to adhere to endothelial cells. Furthermore, because leukocyte NF-κB activation contributes to inflammatory aspects of atherogenesis, apoCIII may stimulate diverse inflammatory responses through monocyte activation.
Suppression of Rage as a Basis of Simvastatin-Dependent Plaque Stabilization in Type 2 Diabetes
Authors: Cuccurullo Chiara , Iezzi Annalisa , Fazia Maria Luigia , De Cesare Domenico , Di Francesco Andrea , Muraro Raffaella , Bei Roberto , Ucchino Sante , Spigonardo Francesco , Chiarelli Francesco , Schmidt Ann Marie , Cuccurullo Franco , Mezzetti Andrea , Cipollone Francesco
Published: October 2006

Objective—

Receptor for advanced glycation end products (AGEs) (RAGE) plays a central role in the process of plaque rupture in diabetic patients. Recently, it has been reported that RAGE may be downregulated by improving glycemic control. In contrast, despite being well known that RAGE may be induced in human vessels in a glucose-independent fashion, also by myeloperoxidase (MPO)-dependent AGE generation, no data exist regarding the possibility of a pharmacological modulation of glucose-independent RAGE generation. Thus, the aim of this study was to characterize the effect of simvastatin on the expression of RAGE and RAGE-dependent plaque-destabilizing genes in human atherosclerotic plaques.

Methods and Results—

Seventy type 2 diabetic patients with asymptomatic carotid artery stenosis (>70%) were randomized to American Heart Association (AHA) step 1 diet plus simvastatin (40 mg/d) or AHA step 1 diet alone for 4 months before endarterectomy. Plaque expression of MPO, AGEs, RAGE, NF-κB, COX-2, mPGES-1, matrix metalloproteinase (MMP)-2 and MMP-9, lipid and oxidized LDL (oxLDL) content, procollagen 1, and interstitial collagen was analyzed by immunohistochemistry and Western blot; zymography was used to detect MMP activity. Plaques from the simvastatin group had less (
P
<0.0001) immunoreactivity for MPO, AGEs, RAGE, p65, COX-2, mPGES-1, MMP-2, and MMP-9, lipids and oxLDL; reduced (
P
<0.0001) gelatinolytic activity; increased (
P
<0.0001) procollagen 1 and collagen content; and fewer (
P
<0.0001) macrophages, T-lymphocytes, and HLA-DR+ cells. Of interest, RAGE inhibition by simvastatin, observed not only in plaque sections but also in plaque-derived macrophages, was reverted by addition of AGEs in vitro.

Conclusions—

This study supports the hypothesis that simvastatin inhibits plaque RAGE expression by decreasing MPO-dependent AGE generation. This effect in turn might contribute to plaque stabilization by inhibiting the biosynthesis of PGE
2
-dependent MMPs, responsible for plaque rupture.
Plasma Adiponectin Levels in Relation to Carotid Intima Media Thickness and Markers of Insulin Resistance
Authors: Nilsson Peter M. , Engström Gunnar , Hedblad Bo , Frystyk Jan , Persson Margaretha M. , Berglund Göran , Flyvbjerg Allan
Published: October 2006

Background—

Circulating adiponectin is a marker for insulin sensitivity, derived from fat cells. It is largely unknown if adiponectin is also an independent marker for early atherosclerosis.

Methods and Results—

Plasma adiponectin levels were measured in 373 men and 514 women of middle-age by a time-resolved immunofluorometric assay. The subjects were sampled stratified for degree of insulin sensitivity (HOMA-IR). An ultrasound measurement of the right common carotid artery intima media thickness (IMT) was made. When the distribution of adiponectin was stratified into sex-specific quartiles (Q1 to Q4), men in Q4 differed from Q1 in higher mean age and high-density lipoprotein (HDL) cholesterol, but lower blood pressure, HbA
1c
, HOMA-index, and body mass index. Women showed similar associations. Mean IMT for men was significantly lower (
P
=0.03) in adiponectin Q4 as compared with Q1 when adjusted for age, waist, smoking, HDL cholesterol, and diastolic blood pressure. When adding HbA
1c
and HOMA to the model, the association was no longer significant (
P
=0.15). In women no difference in IMT was noticed across adiponectin quartiles.

Conclusion—

Plasma adiponectin is a marker of glucose metabolism and obesity and shows an inverse age-adjusted association with carotid ultrasound IMT in men, but not in women. This association is attenuated after adjustments for other risk factors.
Calmodulin Kinase II Inhibition Shortens Action Potential Duration by Upregulation of K+Currents
Authors: Li Jingdong , Marionneau Céline , Zhang Rong , Shah Vaibhavi , Hell Johannes W. , Nerbonne Jeanne M. , Anderson Mark E.
Published: October 2006

The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by elevated intracellular Ca2+(Ca2+i), and mice with chronic myocardial CaMKII inhibition (Inh) resulting from transgenic expression of a CaMKII inhibitory peptide (AC3-I) unexpectedly showed action potential duration (APD) shortening. Inh mice exhibit increased L-type Ca2+current (ICa), because of upregulation of protein kinase A (PKA) activity, and decreased CaMKII-dependent phosphorylation of phospholamban (PLN). We hypothesized that CaMKII is a molecular signal linking Ca2+ito repolarization. Whole cell voltage-clamp recordings revealed that the fast transient outward current (Ito,f) and the inward rectifier current (IK1) were selectively upregulated in Inh, compared with wild-type (WT) and transgenic control, mice. Breeding Inh mice with mice lacking PLN returnedIto,fandIK1to control levels and equalized the APD and QT intervals in Inh mice to control and WT levels. Dialysis of AC3-I into WT cells did not result in increasedIto,forIK1, suggesting that enhanced cardiac repolarization in Inh mice is an adaptive response to chronic CaMKII inhibition rather than an acute effect of reduced CaMKII activity. Increasing PKA activity, by cell dialysis with cAMP, or inhibition of PKA did not affectIK1in WT cells. Dialysis of WT cells with cAMP also reducedIto,f, suggesting that PKA upregulation does not increase repolarizing K+currents in Inh mice. These findings provide novel in vivo and cellular evidence that CaMKII links Ca2+ito cardiac repolarization and suggest that PLN may be a critical CaMKII target for feedback regulation of APD in ventricular myocytes.
Small-Scale Horizontal Rain-Rate Variability Observed by Satellite
Authors: Varma Atul K. , Liu Guosheng
Published: October 2006

The horizontal distribution of rain rates within an area comparable to the pixel size of satellite microwave radiometers and the grid size of numerical weather prediction models has been studied over the global Tropics using three years of the Tropical Rainfall Measuring Mission satellite precipitation radar (PR) data. The global distribution of rain-rate standard deviation derived from the PR data suggests that the horizontal variability of rain rates is largely influenced by two factors: surface type (land or ocean) and latitudinal location (tropical or extratropical). Except for light stratiform rain, the land–ocean contrast seems to be the dominant feature for the differences in conditional probability density functions (PDFs) of rain rate. That is, oceanic rain-rate distribution is narrower when the rain rate is low, but becomes broader when the rain rate is high. For light stratiform rain, there is no clear difference among the rain-rate PDFs for rain events over land and ocean. The latitudinal variation of rain-rate PDFs seems to be greater for heavy rain than for light rain. In particular, there is no measurable difference in overland convective rain-rate PDFs between the Tropics and extratropics. Based on three years of observational data, two attributes, fractional rain cover and conditional rain-rate PDFs, are parameterized as a function of 0.25° × 0.25° areal rain rate. These parameterizations are particularly useful in satellite microwave rainfall retrieval and assimilation of satellite microwave radiance data in numerical weather prediction models.
The Evolution of Lee-Wave–Rotor Activity in the Lee of Pike’s Peak under the Influence of a Cold Frontal Passage: Implications for Aircraft Safety
Authors: Darby Lisa S. , Poulos Gregory S.
Published: October 2006

A lee-wave–rotor system interacting with an approaching cold front in the lee of Pike’s Peak near Colorado Springs, Colorado, on 1 April 1997 is studied observationally and numerically. Dynamical effects associated with the approaching cold front caused the amplification of the evolving lee wave and rotor, creating increasingly more hazardous flight conditions for nearby airports. The rapidly evolving winds measured by a Doppler lidar and 915-MHz wind profilers, and simulated by the Regional Atmospheric Modeling System (RAMS), produced light-to-moderate turbulence for a research aircraft making missed approaches at the Colorado Springs Airport during the wave amplification phase. As the cold front approached the foothills, the lee-wave–rotor system ended abruptly, reducing hazardous flight conditions.

The Doppler lidar’s detailed measurements of the lee-wave–rotor system allowed for an evaluation of RAMS ability to capture these complex wind features. Qualitative and quantitative comparisons between the lidar range–height measurements and model x–z cross sections are presented. In a broad sense, the numerical simulations were successful in the prediction of the prefrontal amplification and the postfrontal decay of the waves as measured by the lidar. RAMS also predicted observed wind reversals above the lee waves, which were indicators of breaking wave instability. At times RAMS performed poorly by over- or underpredicting the wind speeds in the lee wave, as well as the horizontal extent of the lee wave or rotor.
Fourier-Ray Modeling of Short-Wavelength Trapped Lee Waves Observed in Infrared Satellite Imagery near Jan Mayen
Authors: Eckermann Stephen D. , Broutman Dave , Ma Jun , Lindeman John
Published: October 2006

A time-dependent generalization of a Fourier-ray method is presented and tested for fast numerical computation of high-resolution nonhydrostatic mountain-wave fields. The method is used to model mountain waves from Jan Mayen on 25 January 2000, a period when wavelike cloud banding was observed long distances downstream of the island by the Advanced Very High Resolution Radiometer Version 3 (AVHRR-3). Surface weather patterns show intensifying surface geostrophic winds over the island at 1200 UTC caused by rapid eastward passage of a compact low pressure system. The 1200 UTC wind profiles over the island increase with height to a jet maximum of ∼60–70 m s−1, yielding Scorer parameters that indicate vertical trapping of any short wavelength mountain waves. Separate Fourier-ray solutions were computed using high-resolution Jan Mayen orography and 1200 UTC vertical profiles of winds and temperatures over the island from a radiosonde sounding and an analysis system. The radiosonde-based simulations produce a purely diverging trapped wave solution that reproduces the salient features in the AVHRR-3 imagery. Differences in simulated wave patterns governed by the radiosonde and analysis profiles are explained in terms of resonant modes and are corroborated by spatial ray-group trajectories computed for wavenumbers along the resonant mode curves. Output from a nonlinear Lipps–Hemler orographic flow model also compares well with the Fourier-ray solution horizontally. Differences in vertical cross sections are ascribed to the Fourier-ray model’s current omission of tunneling of trapped wave energy through evanescent layers.
Impacts of Ice Microphysics on Rainfall and Thermodynamic Processes in the Tropical Deep Convective Regime: A 2D Cloud-Resolving Modeling Study
Authors: Gao Shouting , Ran Lingkun , Li Xiaofan
Published: October 2006

The effects of ice microphysics on rainfall and thermodynamic processes in the tropical deep convective regime are examined based on hourly zonal-mean data from a pair of two-dimensional cloud-resolving simulations: one simulation with ice clouds and the other without ice clouds. The model is integrated for 21 days with the imposed large-scale vertical velocity, zonal wind, and horizontal advections obtained from the Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Response Experiment. The experiment without ice clouds produces a larger amount of cloud water and a smaller surface rain rate than the experiment with ice clouds because of the exclusion of vapor deposition processes in the experiment without ice clouds. The experiment without ice clouds produces cold and moist states simply because it generates a smaller cloud heating rate and consumes a smaller amount of vapor than does the experiment with ice clouds.
Ensemble-Based Simultaneous State and Parameter Estimation in a Two-Dimensional Sea-Breeze Model
Authors: Aksoy Altuğ , Zhang Fuqing , Nielsen-Gammon John W.
Published: October 2006

The performance of the ensemble Kalman filter (EnKF) in forced, dissipative flow under imperfect-model conditions is investigated through simultaneous state and parameter estimation where the source of model error is the uncertainty in the model parameters. A two-dimensional, nonlinear, hydrostatic, nonrotating, and incompressible sea-breeze model is used for this purpose with buoyancy and vorticity as the prognostic variables and a square root filter with covariance localization is employed. To control filter divergence caused by the narrowing of parameter variance, a “conditional covariance inflation” method is devised. Up to six model parameters are subjected to estimation attempts in various experiments. While the estimation of single imperfect parameters results in error of model variables that is indistinguishable from the respective perfect-parameter cases, increasing the number of estimated parameters to six inevitably leads to a decline in the level of improvement achieved by parameter estimation. However, the overall EnKF performance in terms of the error statistics is still superior to the situation where there is parameter error but no parameter estimation is performed. In fact, compared with that situation, the simultaneous estimation of six parameters reduces the average error in buoyancy and vorticity by 40% and 46%, respectively.

Several aspects of the filter configuration (e.g., observation location, ensemble size, radius of influence, and parameter variance limit) are found to considerably influence the identifiability of the parameters. The parameter-dependent response to such factors implies strong nonlinearity between the parameters and the state of the model and suggests that a straightforward spatial covariance localization does not necessarily produce optimality.
A Statistical Procedure to Forecast Warm Season Lightning over Portions of the Florida Peninsula
Authors: Shafer Phillip E. , Fuelberg Henry E.
Published: October 2006

Sixteen years of cloud-to-ground lightning data from the National Lightning Detection Network and morning radiosonde-derived parameters are used to develop a statistical scheme to provide improved forecast guidance for warm season afternoon and evening lightning for 11 areas of the Florida peninsula serviced by Florida Power and Light Corporation (FPL). Logistic regression techniques are used to develop equations predicting whether at least one flash will occur during the noon–midnight period in each area, as well as the amount of lightning that can be expected during this same period, conditional on at least one flash occurring. For the amount of lightning, the best results are achieved by creating four quartile categories of flash count based on climatology, and then using three logistic equations and a decision tree approach to determine the most likely quartile. A combination of forward stepwise screening and cross validation are used to select the best combination of predictors that are most likely to generalize to independent data. Results show the guidance equations to be superior to persistence on both the dependent dataset and during cross validation. The greatest skill scores are achieved for predicting whether at least one flash will occur, as well as predicting the number of flashes to within one quartile of that observed. These results demonstrate that the equations possess forecast skill and will provide useful guidance for the probability and amount of lightning in each of the 11 FPL service areas.