bluuebunny/crossref_metadata_2025 huggingface dataset:
The complete Apennines orogenic cycle preserved in a transient single outcrop near San Fele, Lucania, southern Italy
Authors: Tavarnelli Enrico , Prosser Giacomo
Published: October 2008

Orogenic cycles may be viewed as comprising two extensional stages that are separated by a stage of contraction. This sequence has characterized the evolution of most mountain belts resulting from continental collision, and the structural signature of individual stages is recognized on a wide variety of scales, i.e. from microscopic to regional. Whereas the history of mountain belts is generally inferred from observations carried out at different sites, the entire sequence of deformation is very rarely recorded in single exposures. The double switch in tectonic regime that led to the development of the Lucanian Apennines in southern Italy, from pre-orogenic drifting through synorogenic thrusting to post-orogenic extension, is preserved in a superb metre-scale outcrop at Serra Manarella, in the vicinity of San Fele. A Late Jurassic, synsedimentary normal fault is sealed by strata affected by a Mid-Pliocene thrust-related fold. This composite structure, in turn, is truncated by a Mid-Pleistocene normal fault. Observation of these relationships represents a unique opportunity to unequivocally establish the relative chronology of deformations in the Lucanian Apennines, and may provide useful constraints for regional cross-section restoration.
Cardiomyopathic and Channelopathic Causes of Sudden Unexplained Death in Infants and Children
Authors: Tester David J. , Ackerman Michael J.
Published: October 2008

In the past decade there has been an increasing awareness of distinct, potentially lethal heritable cardiomyopathic and channelopathic syndromes as they pertain to sudden cardiac death in infants and children. This review highlights current clinical and molecular findings of two highly relevant structural cardiac abnormalities evident at autopsy, namely hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, as well as the cardiac channelopathies of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome, which may account for one third of autopsy-negative sudden unexplained deaths (SUDs) during childhood and adolescence. We also explore the role of postmortem genetic analysis (molecular autopsy) in cases of SUD, provide a critical analysis of the current spectrum and prevalence of channelopathies as the pathogenic basis for sudden infant death syndrome (SIDS), and provide a brief synopsis on genetic testing for such potentially lethal cardiac disorders.
Nanofabrication of Plasmonic Structures
Authors: Henzie Joel , Lee Jeunghoon , Lee Min Hyung , Hasan Warefta , Odom Teri W.
Published: October 2008

This review focuses on nanofabrication tools, based on soft lithography, which can generate a wide range of noble-metal structures with exceptional optical properties. These techniques offer a scalable and practical approach for producing arrays of complementary plasmonic structures (nanoholes and nanoparticles) and, in addition, expand the possible architectures of plasmonic materials because the metal building blocks can be organized over multiple length scales. We describe the preparation and characterization of five different systems: subwavelength nanohole arrays, finite arrays of nanoholes, microscale arrays of nanoholes, multiscale arrays of nanoparticles, and pyramidal particles. We also discuss how the surface plasmon resonances of these structures can be tuned across visible and near-infrared wavelengths by varying different parameters. Applications and future prospects of these nanostructured metals are addressed.
Neuroendocrine Control of the Gut During Stress: Corticotropin-Releasing Factor Signaling Pathways in the Spotlight
Authors: Stengel Andreas , Taché Yvette
Published: October 2008

Stress affects the gastrointestinal tract as part of the visceral response. Various stressors induce similar profiles of gut motor function alterations, including inhibition of gastric emptying, stimulation of colonic propulsive motility, and hypersensitivity to colorectal distension. In recent years, substantial progress has been made in our understanding of the underlying mechanisms of stress's impact on gut function. Activation of corticotropin-releasing factor (CRF) signaling pathways mediates both the inhibition of upper gastrointestinal (GI) and the stimulation of lower GI motor function through interaction with different CRF receptor subtypes. Here, we review how various stressors affect the gut, with special emphasis on the central and peripheral CRF signaling systems.
The total cavopulmonary connection resistance: a significant impact on single ventricle hemodynamics at rest and exercise
Authors: Sundareswaran Kartik S. , Pekkan Kerem , Dasi Lakshmi P. , Whitehead Kevin , Sharma Shiva , Kanter Kirk R. , Fogel Mark A. , Yoganathan Ajit P.
Published: October 2008

Little is known about the impact of the total cavopulmonary connection (TCPC) on resting and exercise hemodynamics in a single ventricle (SV) circulation. The aim of this study was to elucidate this mechanism using a lumped parameter model of the SV circulation. Pulmonary vascular resistance (1.96 ± 0.80 WU) and systemic vascular resistances (18.4 ± 7.2 WU) were obtained from catheterization data on 40 patients with a TCPC. TCPC resistances (0.39 ± 0.26 WU) were established using computational fluid dynamic simulations conducted on anatomically accurate three-dimensional models reconstructed from MRI ( n = 16). These parameters were used in a lumped parameter model of the SV circulation to investigate the impact of TCPC resistance on SV hemodynamics under resting and exercise conditions. A biventricular model was used for comparison. For a biventricular circulation, the cardiac output (CO) dependence on TCPC resistance was negligible (sensitivity = −0.064 l·min−1·WU−1) but not for the SV circulation (sensitivity = −0.88 l·min−1·WU−1). The capacity to increase CO with heart rate was also severely reduced for the SV. At a simulated heart rate of 150 beats/min, the SV patient with the highest resistance (1.08 WU) had a significantly lower increase in CO (20.5%) compared with the SV patient with the lowest resistance (50%) and normal circulation (119%). This was due to the increased afterload (+35%) and decreased preload (−12%) associated with the SV circulation. In conclusion, TCPC resistance has a significant impact on resting hemodynamics and the exercise capacity of patients with a SV physiology.
Keratinizing Squamous Metaplasia of the Bladder: A Review
Authors: Ahmad Imran , Barnetson Robert J. , Krishna Nalagatla Sarath
Published: October 2008

Aims: Keratinizing squamous metaplasia is infrequently found in bladder biopsies and its clinical significance remains unclear, with studies linking it to the development of invasive squamous cell carcinoma. Once diagnosed, there is a dilemma how to treat and follow-up this group. Methods: We reviewed the literature on the topic with particular emphasis on natural history, management and subsequent follow-up. Results: Keratinizing squamous metaplasia of the bladder is rare. Pathognomonic findings on biopsy are required to confirm the diagnosis. Both synchronous diagnosis of urothelial tumour and subsequent tumour development on follow-up has been identified. Risk of malignant transformation increases in the presence of dysplasia as well as with extensive keratinization. Lesions should be treated with local transurethral resection. Considering the lack of evidence cystectomy cannot be justified for those with extensive lesions. Conclusion: Currently there is not enough data to identify keratinizing squamous metaplasia of the bladder as a pre-malignant condition; this term being reserved for those with obvious histological dysplasia. However at present all patients should undergo regular follow-up.
Heritability of Lung Function in Severe Alpha-1 Antitrypsin Deficiency
Authors: DeMeo D.L. , Campbell E.J. , Brantly M.L. , Barker A.F. , Eden E. , McElvaney N.G. , Rennard S.I. , Stocks J.M. , Stoller J.K. , Strange C. , Turino G. , Sandhaus R.A. , Silverman E.K.
Published: October 2008

Severe alpha-1 antitrypsin (AAT) deficiency is a proven genetic risk factor for COPD, but there is marked variation in the development of COPD among AAT deficient subjects. To investigate familial aggregation of lung function in subjects with AAT deficiency, we estimated heritability for forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) in 378 AAT deficient subjects from 167 families in the AAT Genetic Modifiers Study; all subjects were verified homozygous for the Z AAT deficiency allele. Heritability was evaluated for models that included and excluded an ascertainment correction, as well as for models that excluded, included and were stratified by a cigarette smoking covariate. In models without an ascertainment correction, and in all models without a covariate for smoking, no evidence for familial aggregation of lung function was observed. In models conditioned on the index proband with covariates for smoking, post-bronchodilator FEV1/FVC demonstrated significant heritability (0.26 ± 0.14, p = 0.03). When we limited the analysis to subjects with a smoking history, post-bronchodilator FEV1demonstrated significant heritability (0.47 ± 0.21, p = 0.02). Severity rate phenotypes were also assessed as potential phenotypes for genetic modifier studies. Significant heritability was found with all age-of-onset threshold models that included smoking and ascertainment adjustments. Using the t-distribution, the heritability estimates ranged from 0.43 to 0.64, depending on the age-of-onset of FEV1 decline used for the severity rate calculation. Correction for ascertainment and consideration of gene-by-smoking interactions will be crucial for the identification of genes that may modify susceptibility for COPD in families with AAT deficiency.
Epidemiology of Gliomas in Israel: A Nationwide Study
Authors: Sadetzki Siegal , Zach Leor , Chetrit Angela , Nass Dvora , Hoffmann Chen , Ram Zvi , Zaaroor Menashe , Umansky Felix , Rappaport Zvi Harry , Cohen Avi , Wald Uriel , Rothman Sigmund , Hadani Moshe
Published: October 2008

Background: Glial brain tumors span a wide range of neoplasms with distinct clinical and histopathological features. This report presents the descriptive epidemiology of glial tumors by histological subtype and tumor behavior. Methods: The study population included all incident cases of glial tumors diagnosed in Israel during March 2001 to July 2003. Age-standardized incidence rates (ASR) were calculated using the world population as a standard. Results: A total of 548 tumors were diagnosed, of which 520 had histological confirmation. The ASR of all adult (>20 years) glial tumors was 5.82/100,000 (7.11 for males; 4.75 for females, p < 0.001). The majority of tumors (78%) were classified as high grade; astrocytic tumors were the most frequent (85%), with glioblastoma multiforme accounting for 70% of them. A significant positive association was shown between age at diagnosis and grade. The highest ASR was seen for Europe- and-American-born, followed by Israeli, Asian and African-born individuals (6.78, 5.86, 4.94 and 3.84/100,000, respectively). Conclusions: In general, these results describing data of incident cases of pathologically validated glial tumors are consistent with previous reports. To enhance our understanding of these diseases, epidemiological studies should rely on well-defined histological tumor types, incorporating comprehensive information which will allow comparability between different groups of patients.
Sustained Persistence of Transplanted Proangiogenic Cells Contributes to Neovascularization and Cardiac Function After Ischemia
Authors: Ziebart Thomas , Yoon Chang-Hwan , Trepels Thomas , Wietelmann Astrid , Braun Thomas , Kiessling Fabian , Stein Stefan , Grez Manuel , Ihling Christian , Muhly-Reinholz Marion , Carmona Guillaume , Urbich Carmen , Zeiher Andreas M. , Dimmeler Stefanie
Published: October 2008

Circulating blood–derived vasculogenic cells improve neovascularization of ischemic tissue by a broad repertoire of potential therapeutic actions. Whereas initial studies documented that the cells incorporate and differentiate to cardiovascular cells, other studies suggested that short-time paracrine mechanisms mediate the beneficial effects. The question remains to what extent a physical incorporation is contributing to the beneficial effects of cell therapy. By using the inducible suicide gene thymidine kinase to deplete transplanted cells, we determined the contribution of physical incorporation in 3 animal models. After acute myocardial infarction, depletion of cells 14 days after infusion resulted in a reduction of capillary density and a substantial deterioration of heart function. Likewise, neovascularization of Matrigel plugs and ischemic limbs was significantly suppressed when infused cells were depleted 7 days after infusion. Induction of cell death in the previously transplanted cells reduced perfusion and led to vascular leakage as evidenced by Evans blue extravasation. These results indicate that physical incorporation and persistence of cells contribute to cell-mediated improvement of neovascularization and cardiac function. Long-term paracrine activities and/or cell intrinsic mechanisms may have contributed to the maintenance of functional improvement.
Mesencephalic Astrocyte-Derived Neurotrophic Factor Is an Ischemia-Inducible Secreted Endoplasmic Reticulum Stress Response Protein in the Heart
Authors: Tadimalla Archana , Belmont Peter J. , Thuerauf Donna J. , Glassy Matthew S. , Martindale Joshua J. , Gude Natalie , Sussman Mark A. , Glembotski Christopher C.
Published: October 2008

The endoplasmic reticulum (ER) stress response (ERSR) is activated when folding of nascent proteins in the ER lumen is impeded. Myocardial ischemia was recently shown to activate the ERSR; however, the role of this complex signaling system in the heart is not well understood. ER stress activates the transcription factor ATF6, which induces expression of proteins targeted to the ER, where they restore protein folding, thus fostering cytoprotection. We previously developed a transgenic mouse line that expresses a conditionally activated form of ATF6 in the heart. In this mouse line, ATF6 activation decreased ischemic damage in an ex vivo model of myocardial ischemia/reperfusion and induced numerous genes, including mesencephalic astrocyte-derived neurotrophic factor (MANF). In the present study, MANF expression was shown to be induced in cardiac myocytes and in other cell types in the hearts of mice subjected to in vivo myocardial infarction. Additionally, simulated ischemia induced MANF in an ATF6-dependent manner in neonatal rat ventricular myocyte cultures. In contrast to many other ER-resident ERSR proteins, MANF lacks a canonical ER-retention sequence, consistent with our finding that MANF was readily secreted from cultured cardiac myocytes. Knockdown of endogenous MANF with micro-RNA increased cell death upon simulated ischemia/reperfusion, whereas addition of recombinant MANF to media protected cultured cardiac myocytes from simulated ischemia/reperfusion-mediated death. Thus, a possible function of the ERSR in the heart is the ischemia-mediated induction of secreted proteins, such as MANF, that can function in an autocrine/paracrine manner to modulate myocardial damage from ER stresses, including ischemia.
Multivariable Analysis of Outcome Predictors and Adjustment of Main Outcome Results to Baseline Data Profile in Randomized Controlled Trials
Authors: Wahlgren Nils , Ahmed Niaz , Eriksson Niclas , Aichner Franz , Bluhmki Erich , Dávalos Antoni , Erilä Terttu , Ford Gary A. , Grond Martin , Hacke Werner , Hennerici Michael G. , Kaste Markku , Köhrmann Martin , Larrue Vincent , Lees Kennedy R. , Machnig Thomas , Roine Risto O. , Toni Danilo , Vanhooren Geert
Published: October 2008

Background and Purpose—

The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.

Methods—

The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until
P
≤0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (
P
<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.

Results—

The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.

Conclusions—

The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.
Metabolic Impact of Shivering During Therapeutic Temperature Modulation
Authors: Badjatia Neeraj , Strongilis Evangelia , Gordon Errol , Prescutti Mary , Fernandez Luis , Fernandez Andres , Buitrago Manuel , Schmidt J. Michael , Ostapkovich Noeleen D. , Mayer Stephan A.
Published: October 2008

Background and Purpose—

Therapeutic temperature modulation is widely used in neurocritical care but commonly causes shivering, which can hamper the cooling process and result in increases in systemic metabolism. We sought to validate a grading scale to assist in the monitoring and control of shivering.

Methods—

A simple 4-point Bedside Shivering Assessment Scale was validated against continuous assessments of resting energy expenditure, oxygen consumption, and carbon dioxide production as measured by indirect calorimetry. Therapeutic temperature modulation for fever control or the induction of hypothermia was achieved with the use of a surface or endovascular device. Expected energy expenditure was calculated using the Harris–Benedict equation. A hypermetabolic index was calculated from the ratio of resting of energy expenditure to energy expenditure.

Results—

Fifty consecutive cerebrovascular patients underwent indirect calorimetry between January 2006 and June 2007. Fifty-six percent were women, and mean age 63±16 years. The majority underwent fever control (n=40 [80%]) with a surface cooling device (n=44 [87%]) and had signs of shivering (Bedside Shivering Assessment Scale >0, 64% [n=34 of 50]). Low serum magnesium was independently associated with the presence of shivering (Bedside Shivering Assessment Scale >0; OR, 6.8; 95% CI, 1.7 to 28.0;
P
=0.01). The Bedside Shivering Assessment Scale was independently associated with the hypermetabolic index (
W
=16.3,
P
<0.001), oxygen consumption (
W
=26.3,
P
<0.001), resting energy expenditure (
W
=27.2,
P
<0.001), and carbon dioxide production (
W
=18.2,
P
<0.001) with a high level of interobserver reliability (κ
w
=0.84, 95% CI, 0.81 to 0.86).

Conclusion—

The Bedside Shivering Assessment Scale is a simple and reliable tool for evaluating the metabolic stress of shivering.
The Potential for Differential Findings Among Invariance Testing Strategies for Multisample Measured Variable Path Models
Authors: Mann Heather M. , Rutstein Daisy W. , Hancock Gregory R.
Published: October 2008

Multisample measured variable path analysis is used to test whether causal/structural relations among measured variables differ across populations. Several invariance testing approaches are available for assessing cross-group equality of such relations, but the associated test statistics may vary considerably across methods. This study is a population analysis, examining five different strategies for invariance testing using an illustrative measured variable path model. The results demonstrate how inferences about parameters across populations can depend greatly upon the invariance testing approach used, thereby potentially leading to improper inference regarding the true invariance status of relevant parameters.
Bone Biopsy of the Parasymphyseal Pubic Bone Region in Athletes with Chronic Groin Injury Demonstrates New Woven Bone Formation Consistent with a Diagnosis of Pubic Bone Stress Injury
Authors: Verrall Geoffrey M. , Henry Lachlan , Fazzalari Nicola L. , Slavotinek John P. , Oakeshott Roger D.
Published: October 2008

Background

There is little scientific evidence available regarding the pathologic basis for chronic groin injury in athletes, a known difficult clinical problem.

Hypothesis

Histological analysis of the superior pubic ramus in athletes with diagnosed chronic groin injury may reveal the nature of the pathologic process.

Study Design

Case series; Level of evidence, 4.

Methods

Ten athletes with a diagnosis of chronic groin injury by clinical criteria (at least 6 weeks of pain) and magnetic resonance imaging criteria (unequivocal increase in T2 signal intensity) underwent bone biopsy of the superior pubic ramus. The biopsy site was located in the parasymphyseal region in the area of increased magnetic resonance image signal intensity. Histologic analysis of the specimens was then undertaken.

Results

Evidence of new woven bone was seen in all biopsy specimens. Signs of old bony injury were seen in 8 of the 10 specimens. There was no evidence of inflammation or osteonecrosis.

Conclusion

Histologic analysis of bone biopsy specimens taken from the parasymphyseal pubic bone region with magnetic resonance imaging T2-weighted increased signal intensity of athletes diagnosed by clinical and magnetic resonance imaging criteria as having chronic groin injury demonstrates new woven bone formation. This is consistent with the athlete having a bone stress injury that may contribute significantly to athletic groin pain.
Maintenance of the BMP4-dependent stress erythropoiesis pathway in the murine spleen requires hedgehog signaling
Authors: Perry John M. , Harandi Omid F. , Porayette Prashanth , Hegde Shailaja , Kannan Arun K. , Paulson Robert F.
Published: October 2008

The production of mature cells necessitates that lineage-committed progenitor cells be constantly generated from multipotential progenitors. In addition, the ability to respond rapidly to physiologic stresses requires that the signals that regulate the maintenance of progenitor populations be coordinated with the signals that promote differentiation of progenitors. Here we examine the signals that are necessary for the maintenance of the BMP4-dependent stress erythropoiesis pathway. Our previous work demonstrated that BMP4, stem cell factor, and hypoxia act in concert to promote the expansion of a specialized population of stress erythroid progenitors in the spleen during the recovery from acute anemia. Our analysis shows that acute anemia leads to an almost complete mobilization of BMP4-responsive stress erythroid burst-forming units; therefore, new stress progenitors must be recruited to the spleen to replenish this system. We show that bone marrow cells can home to the spleen and, in response to a signal in the spleen microenvironment, Hedgehog, they develop into BMP4-responsive stress progenitors. Hedgehog induces the expression of BMP4, and together these 2 signals are required for the development of BMP4-responsive stress progenitors. These data demonstrate that the interplay between these 2 signals is crucial for maintenance of this stress response pathway.
Balance between Id and E proteins regulates myeloid-versus-lymphoid lineage decisions
Authors: Cochrane Shawn W. , Zhao Ying , Welner Robert S. , Sun Xiao-Hong
Published: October 2008

Hematopoiesis consists of a series of lineage decisions controlled by specific gene expression that is regulated by transcription factors and intracellular signaling events in response to environmental cues. Here, we demonstrate that the balance between E-protein transcription factors and their inhibitors, Id proteins, is important for the myeloid-versus-lymphoid fate choice. Using Id1-GFP knockin mice, we show that transcription of the Id1 gene begins to be up-regulated at the granulocyte-macrophage progenitor stage and continues throughout myelopoiesis. Id1 expression is also stimulated by cytokines favoring myeloid differentiation. Forced expression of Id1 in multipotent progenitors promotes myeloid development and suppresses B-cell formation. Conversely, enhancing E-protein activity by expressing a variant of E47 resistant to Id-mediated inhibition prevents the myeloid cell fate while driving B-cell differentiation from lymphoid-primed multipotent progenitors. Together, these results suggest a crucial function for E proteins in the myeloid-versus-lymphoid lineage decision.
Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain
Authors: Mullins Eric S. , Kombrinck Keith W. , Talmage Kathryn E. , Shaw Maureen A. , Witte David P. , Ullman Joni M. , Degen Sandra J. , Sun William , Flick Matthew J. , Degen Jay L.
Published: October 2008

Mice carrying a conditional prothrombin knockout allele (fIIlox) were established to develop an experimental setting for exploring the importance of thrombin in the maintenance of vascular integrity, the inflammatory response, and disease processes in adult animals. In the absence of Cre-mediated recombination, homozygous fIIlox/lox mice or compound heterozygous mice carrying one fIIlox allele and one constitutive-null allele were viable. Young adults exhibited neither spontaneous bleeding events nor diminished reproductive success. However, the induction of Cre recombinase in fIIlox mice using the poly I:C-inducible Mx1-Cre system resulted in the rapid and near-complete recombination of the fIIlox allele within the liver, the loss of circulating prothrombin, and profound derangements in coagulation function. Consistent with the notion that thrombin regulates coagulation and inflammatory pathways, an additional early consequence of reducing prothrombin was impaired antimicrobial function in mice challenged with Staphylococcus aureus peritonitis. However, life expectancy in unchallenged adults genetically depleted of prothrombin was very short (∼5-7 days). The loss of viability was associated with the development of severe hemorrhagic events within multiple tissues, particularly in the heart and brain. Unlike the constitutive loss of either clotting or platelet function alone, the conditional loss of prothrombin is uniformly not compatible with maintenance of hemostasis or long-term survival.
Functional assessment of perforin C2 domain mutations illustrates the critical role for calcium-dependent lipid binding in perforin cytotoxic function
Authors: Urrea Moreno Ramon , Gil Juana , Rodriguez-Sainz Carmen , Cela Elena , LaFay Victor , Oloizia Brian , Herr Andrew B. , Sumegi Janos , Jordan Michael B. , Risma Kimberly A.
Published: October 2008

Perforin-mediated lymphocyte cytotoxicity is critical for pathogen elimination and immune homeostasis. Perforin disruption of target cell membranes is hypothesized to require binding of a calcium-dependent, lipid-inserting, C2 domain. In a family affected by hemophagocytic lymphohistiocytosis, a severe inflammatory disorder caused by perforin deficiency, we identified 2 amino acid substitutions in the perforin C2 domain: T435M, a previously identified mutant with disputed pathogenicity, and Y438C, a novel substitution. Using biophysical modeling, we predicted that the T435M substitution, but not Y438C, would interfere with calcium binding and thus cytotoxic function. The capacity for cytotoxic function was tested after expression of the variant perforins in rat basophilic leukemia cells and murine cytotoxic T lymphocytes. As predicted, cells transduced with perforin-T435M lacked cytotoxicity, but those expressing perforin-Y438C displayed intact cytotoxic function. Using novel antibody-capture and liposome-binding assays, we found that both mutant perforins were secreted; however, only nonmutated and Y438C-substituted perforins were capable of calcium-dependent lipid binding. In addition, we found that perforin-Y438C was capable of mediating cytotoxicity without apparent proteolytic maturation. This study clearly demonstrates the pathogenicity of the T435M mutation and illustrates, for the first time, the critical role of the human perforin C2 domain for calcium-dependent, cytotoxic function.
Positron Emission Tomography (PET) radiotracers in oncology – utility of 18F-Fluoro-deoxy-glucose (FDG)-PET in the management of patients with non-small-cell lung cancer (NSCLC)
Authors: Miele Evelina , Spinelli Gian Paolo , Tomao Federica , Zullo Angelo , De Marinis Filippo , Pasciuti Giulia , Rossi Luigi , Zoratto Federica , Tomao Silverio
Published: October 2008

PET (Positron Emission Tomography) is a nuclear medicine imaging method, frequently used in oncology during the last years. It is a non-invasive technique that provides quantitative in vivo assessment of physiological and biological phenomena. PET has found its application in common practice for the management of various cancers.

Lung cancer is the most common cause of death for cancer in western countries.

This review focuses on radiotracers used for PET scan with particular attention to Non Small Cell Lung Cancer diagnosis, staging, response to treatment and follow-up
Simultaneous color contrast in the foraging swallowtail butterfly, Papilio xuthus
Authors: Kinoshita Michiyo , Takahashi Yuki , Arikawa Kentaro
Published: October 2008

This study demonstrates that the color vision of foraging Japanese yellow swallowtail butterflies, Papilio xuthus, involves simultaneous color contrast. We trained newly emerged Papilio to select a disk of pale green among a set of differently colored disks presented on a black background. When the same set of disks was presented on blue background, the pale green-trained butterflies selected blue-green. The difference in spectra between pale green and blue green was similar to the spectrum of yellow for human vision, suggesting that blue induces yellow. Similarly, the pale green-trained Papilio selected a more bluish spring green on yellow background. We also trained Papilio with orange disks and tested on a green and violet background. The results showed that green induced violet and vice versa. Taken together, we concluded that simultaneous color contrast of Papilio is similar to the effect of complementary colors in human color vision.
Control of swimming in the hydrozoan jellyfishAequorea victoria: subumbrellar organization and local inhibition
Authors: Satterlie Richard A.
Published: October 2008

The subumbrella of the hydrozoan jellyfish Aequorea victoria(previously classified as Aequorea aequorea) is divided by numerous radial canals and attached gonads, so the subumbrellar musculature is partitioned into subumbrellar segments. The ectoderm of each segment includes two types of muscle: smooth muscle with a radial orientation, used for local(feeding and righting) and widespread (protective) radial responses, and striated muscle with a circular orientation which produces swim contractions. Two subumbrellar nerve nets were found, one of which stained with a commercial antibody produced against the bioactive peptide FMRFamide. Circular muscle cells produce a single, long-duration action potential with each swim,triggered by a single junctional potential. In addition, the circular cells are electrically coupled so full contractions require both electrotonic depolarization from adjacent cells and synaptic input from a subumbrellar nerve net. The radial cells, which form a layer superficial to the circular cells, are also activated by a subumbrellar nerve net, and produce short-duration action potentials. The radial muscle cells are electrically coupled to one another. No coupling exists between the two muscle layers. Spread of excitation between adjacent segments is decremental, and nerve net-activated junctional potentials disappear during local inhibition of swimming (such as with a radial response). Variable swim contractions are controlled by a combination of synaptic input from the motor network of the inner nerve ring, synaptic input from a subumbrellar nerve net, and electrotonic depolarization from adjacent, active muscle cells.
Molecular and biological characterization of the Amblyomma americanum organic anion transporter polypeptide
Authors: Mulenga Albert , Khumthong Rabuesak , Chalaire K. C. , Strey Otto , Teel Pete
Published: October 2008

The organic anion transporting polypeptides (Oatps in rodents and other organism; OATPs in human) are Na+-independent transporters that shuttle a wide range of endogenous and xenobotic amphipathic compounds across plasma membranes. We previously discovered an Amblyomma americanumtick (Aam) Oatp cDNA among genes that were upregulated or induced in ticks that were stimulated to start feeding. In this study, we have characterized a 2860 bp full-length cDNA that encode a 724 amino acid putative protein. Bioinformatics and hydropathy analyses revealed that, in addition to the kazal-type serine proteinase inhibitor motif, AamOatp possess typical features that characterize the Oatp/OATP protein family, including 12 transmembrane (TM) domains, the consensus amino acid motif D-X-RW-(I,V)-GAWW-X-G-(F,L)-L and 11 consensus cysteine residues in the large extracellular domain between TM9 and TM10. AamOatp is constitutively and ubiquitously expressed, as determined by RT-PCR amplification of the transcript, in all organs of ticks that fed for 1–7 days. Analysis of the normalized transcript abundance revealed that from days 1 to 5 of feeding, AamOatp mRNA expression in the midgut (MG) was 60–80-fold higher than levels found in the salivary gland (SG), ovary (OV) and carcass(CA). By contrast, by day 7 of feeding, the AamOatp mRNA was 60–80-fold more strongly expressed in the OV than in the SG, MG and CA. These data strongly indicate that changing physiological needs during the tick feeding process influences transcriptional regulation of AamOatp. Our data also show that RNAi-mediated suppression of the AamOatp caused ticks to obtain smaller blood meals, which consequently resulted in ticks laying fewer eggs. The results are discussed in the context of AamOatp as a potential pharmacological or anti-tick vaccine target.
Effectiveness of peer education in HIV/STD prevention at different types of senior high schools in Shanghai, People's Republic of China
Authors: Shen L X , Hong H , Cai Y , Jin X M , Shi R
Published: October 2008

The epidemic of HIV/AIDS greatly threatens Chinese youth. Our study was intended to examine the effectiveness of the peer education method in HIV/AIDS prevention in different types of senior high schools in Shanghai. A peer education intervention was conducted in 10 different types of senior high schools, including three key senior schools, four ordinary senior schools and three vocational schools in Shanghai for three months. A cohort of 1910 students was surveyed ( n = 976 intervention group, n = 934 control group) through anonymous questionnaires, both pre- and postintervention. There were significant differences in the results among these different types of senior schools. Peer education is an efficient method of increasing the knowledge of AIDS/sexually transmitted diseases in senior school students. However, the contents and the schedule should be different between different types of schools, and students in vocational schools require more health education.
HIV-associated nephropathy in Caucasians: case report and review of literature
Authors: Yalavarthy R , Smith M L , Edelstein C L
Published: October 2008

HIV-associated nephropathy (HIVAN) is almost exclusively seen in African-Americans (AA) and is rare in Caucasians. The mechanisms responsible for the predilection of HIVAN in AA are not well understood. In transgenic mouse studies, genetic background plays a vital role in the development of the HIVAN phenotype. Larger studies in humans have been initiated to study genetic polymorphisms responsible for HIVAN. As our case illustrates, HIVAN should be considered in Caucasian patients with HIV infection complicated by nephrotic syndrome and renal failure.
Compliance with hand hygiene in a genitourinary medicine department
Authors: Samraj S , Westbury J , Pallett A , Rowen D
Published: October 2008

The ability to control hospital-acquired infections is highly dependent upon control of cross-contamination from health-care workers to patients, and from one anatomical area of the patient to another anatomical area. Hand hygiene has been demonstrated to be an essential prerequisite in preventing cross-contamination. Wearing gloves does not afford complete protection against cross-contamination. Hand hygiene includes handwashing between patients, the use of alcohol-based skin cleansers and changing or removing gloves between examining different anatomical sites. There are no previously published audits regarding compliance to hand hygiene in genitourinary (GU) medicine clinics. A validated observation tool was employed in this audit. Doctors and nurses were observed in clinical practice. The adherence to hand hygiene protocols was overall poor. Doctors were more likely to adhere to protocols than nurses (83.3% vs. 66%). However, techniques of glove removal were universally satisfactory. Strategies for improvement in hand hygiene are suggested. These include performance feedback and use of posters.
Direct and Simple Shear Testing of Two Canadian Sensitive Clays
Authors: Silvestri V , Karam G , Tonthat A , St-Amour Y
Published: October 2008

Several series of consolidated undrained direct translatory shear (DTS) and direct simple shear (DSS) tests have been performed on two sensitive clays of eastern Canada. Before shearing, the specimens were consolidated to pressures varying between 20 and 350 kPa. The investigation was performed with the aim of determining both the anisotropic nature and the effect of the consolidation pressure level on the response of the tested clays. To study the anisotropic nature of the sensitive clays, the specimens were cut at various inclination angles with respect to the in-situ horizontal plane, consolidated to predetermined normal stress levels, thus altering the fabric, and then sheared under undrained conditions. The range of the normal stress levels used was such as to be able to investigate the response of the soil from very high overconsolidation ratios to normally consolidated or destructured states. The results show that for consolidation pressures less than the preconsolidation pressures of the inclined specimens, the undrained shear strengths are anisotropic. In this case, the specimens that are sheared along the horizontal in-situ direction show the lowest strength, while those that are sheared along the vertical in-situ direction have the highest strength. However, for the specimens that are consolidated under pressures in excess of the preconsolidation pressures, the undrained shear strengths are found to be independent of shearing direction.
A Nonlinear One-Dimensional Wave Analysis of a Triaxial Soil Specimen
Authors: Carroll WF
Published: October 2008

A fast triaxial shear device (FTRXD) loads cylindrical soil specimens, displacing the top of the specimen downward and axially at a controlled and very rapid rate. Load and displacement at the specimen top and load at the bottom are measured; specimens are subjected to constant confining pressures. Nonlinear, one-dimensional wave analysis of the specimen was undertaken, using finite-difference methods, to assess the effects of longitudinal inertia in the specimen and to gain insights into its behavior as stress and strain approach failure levels during rapid transient loading. For conditions where radial inertia and radial shear stress do not affect normal axial stress and strain significantly, axial load measured at the top and bottom of the specimen plotted against nominal axial strain permit deducing the specimen's correct principal stress difference-axial strain curve.
A Nondestructive, Specimen-Specific Method for Measurement of Membrane Penetration in the Triaxial Test
Authors: Kramer SL , Sivaneswaran N
Published: October 2008

An experimental procedure for nondestructive, specimen-specific measurement of membrane penetration volume change is presented. The procedure involves measurement of the annular volume between two membranes as an outer ported membrane is “consolidated” over the deformed surface of an inner membrane. With minor adjustments for the effects of membrane thickness and pore-pressure change, the double membrane procedure yields the membrane penetration volume change behavior of the inner membrane. The procedure is conducted in such a manner that the effective stresses in the specimen remain unchanged, allowing the specimen to be tested after its membrane penetration characteristics have measured. Agreement with measured membrane penetration behavior has been very good.
The Use of Hall Effect Semiconductors in Geotechnical Instrumentation
Authors: Clayton CRI , Khatrush SA , Bica AVD , Siddique A
Published: October 2008

For the past five years or so Hall effect semiconductors have been increasingly used in the geotechnical engineering laboratories at the University of Surrey. They have been incorporated as sensing elements in local radial and axial strain measuring devices, for the small-strain instrumentation of triaxial specimens, and in small diameter boundary normal and shear stress cells. Triaxial internal load cells are currently being built incorporating Hall effect semiconductors.

This paper describes the Hall effect principle and the methods of configuring magnet/sensor systems to achieve suitable measuring systems. Some geotechnical instruments built at the University of Surrey are detailed, and their characteristics discussed. The calibrations of the instruments described in the paper show a performance generally at least as good as might be expected from some commercially available instruments. Hall effect semiconductors are shown to be of use in a range of situations where displacement can form the basis of measurement. The displacements measured can vary from as little as 5 µm to as much as 10 mm, and the best repeatability so far obtained has been of the order of 1/100 of a micrometre.
Calibration of Thermal Conductivity Sensors for Measuring Soil Suction
Authors: Fredlund DG , Wong DKH
Published: October 2008

The accuracy of suction measurements using thermal conductivity sensors is dependent upon their calibration. Therefore, a calibration study was undertaken by using a modified, commercially available, pressure plate extractor. The experimental setup along with the calibration procedure are described. Typical calibration results are presented. In general, results showed reasonable agreement between the calibration curve determined in this study compared to those provided by the manufacturer for matric suction ranging from 0 to 175 kPa. However, large deviations in the calibration curves were observed at suctions above 175 kPa. The sensors were found to be quite sensitive to the changes in matric suction in the range of 0 to 175 kPa. For matric suction above 175 kPa, the sensitivity of the sensor is reduced.
Enhancement of the Uplift Capacity of Buried Pipelines by the Use of Geogrids
Authors: Selvadurai APS
Published: October 2008

The paper presents the results of preliminary tests that were conducted to investigate the possible use of geogrids for increasing the uplift resistance of buried pipelines. The results of the preliminary experimental investigations suggest that the uplift capacity of a pipeline section can be increased quite significantly by the incorporation of geogrids at the crown region of the pipeline in an advantageous and practicable configuration.
A Large-Capacity Batch Filling Water Balloon Apparatus for Deep In-situ Density Tests
Authors: Cooper MR , Fleming PR
Published: October 2008

A large-capacity water balloon aparatus has been developed specifically for measuring the in-situ density of compacted high-way trench backfill. In operation water is expelled from a calibrated 6-L reservoir to displace a rubber membrane. A dual-valve system enables larger volumes to be measured by repeated filling of the reservoir. The apparatus is simple, robust, and inexpensive, and has been used to measure hole volumes up to 30 L, with depths up to 0.8 m. It is much smaller and more easily handled that previous medium capacity apparatuses. Proving trials have shown that the apparatus can reliably determine hole volumes to an accuracy of +0/−0.6%, which is a significant improvement over the performance of the standard small volume equipment.
A Technique for Reducing Membrane Penetration and Bedding Errors
Authors: Lo S-CR , Chu J , Lee IK
Published: October 2008

An expedient technique of reducing, significantly, membrane penetration errors and bedding errors at the platens is presented. This technique consists of coating the specimen/membrane and specimen/platen interfaces with a film of liquid rubber of appropriate thickness and properties. This film of liquid rubber is then squeezed into the interstices by a small seatting load/pressure before completion of curing. The effectiveness of this technique is demonstrated by a series of testing.
The Influence of the Shape of a Pile Shoe on a Model Pile Penetrating Layered Soil
Authors: Rowlands GO
Published: October 2008

This is an account of a small-scale model study to examine the influence of the shape of pile shoes on the behavior of piles. A model pile 32 mm diameter was driven at a constant rate of penetration into sand overlying a layered clay in a container and with four different shapes of pile shoes. The test results indicate that the load penetration curves assume constant values in the sand and the clay, respectively, but the values at the interactive stage of the sand and the clay lie between the two extreme values obtained in the two strata. The final shape of the plug of sand driven ahead of the pile is independent of the shape of the pile shoe in every case.