bluuebunny/crossref_metadata_2025 huggingface dataset:
Biphasic effects of angiotensin II and receptor antagonism on aggregability and protein kinase C phosphorylation in human platelets
Authors: Kizawa Hideki , Nagane Yuriko , Kondoh Ryushi , Iwa Yoko , Akutsu Hitomi , Tohgi Hideo , Terayama Yasuo , Utsugisawa Kimiaki
Published: October 2005

In order to define the role of angiotensin II (AngII) receptor subtypes, AT1 and AT2, in platelet activation, we examined the effects of AngII and receptor antagonists on both aggregability and phosphorylation status of protein kinase C (PKC) isoforms in human platelets obtained from 56 healthy volunteers. AngII promoted both spontaneous and agonist (collagen and ADP) stimulated platelet aggregation at concentrations of 10 nM or less, but the promotion effects were lost at 100 nM. Antagonism of AT1 receptor inhibited the promotion effects of AngII at 10 nM or less. On the other hand, antagonism of AT2 receptor enhanced platelet aggregability modestly with AngII at 10 nM or less, and markedly with 100 nM AngII. Furthermore, with 10 nM AngII, phospho-PKCα/βII expression in platelets was increased after collagen stimulation and was inhibited by antagonism of AT1 receptor. With 100 nM AngII, expression levels of phospho-PKCα/ βII remained low even after collagen stimulation but were markedly enhanced by antagonism of AT2 receptor. These findings suggest that at 10 nM or below, AngII promotes aggregability and PKC phosphorylation in human platelets through the AT1 receptor, which can be inhibited by AT1 receptor antagonists, but at higher concentrations, the promotion effects were lost through the opposing action of the AT2 receptor. The present study may provide an additional mechanism for AT1 receptor antagonism, which would provide clinical benefit to patients with stroke or cardiovascular disease accompanied by hypertension.
Differences in the clinically effective molar concentrations of four direct thrombin inhibitors explain their variable prothrombin time prolongation
Authors: Greinacher Andreas , Craven Sharon , Dewar Lori , Sheppard Jo-Ann , Ofosu Frederick , Warkentin Theodore
Published: October 2005

Four direct thrombin inhibitors (DTIs), lepirudin, bivalirudin, argatroban, and melagatran, differ in their ability to prolong the prothrombin time (PT). Paradoxically, the DTI in clinical use with the lowest affinity for thrombin (argatroban) causes the greatest PT prolongation. We compared the effects of these DTIs on various clotting assays and on inhibition of human and bovine factor Xa (FXa). On a mole-for-mole basis, lepirudin was most able to prolong the PT, activated partial thromboplastin time (APTT), and thrombin clotting time (TCT), whereas argatroban had the least effect. At concentrations that doubled the APTT (argatroban, 1 μmol/l; melagatran, 0.5 μmol/l; bivalirudin, 0.25 μmol/l; lepirudin, 0.06 μmol/l), the rank order for PT prolongation was: argatroban > melagatran > bivalirudin > lepirudin. Although the Ki’s associated with inhibition of human FXa by melagatran (1.4 μmol/l) and argatroban (3.2 μmol/l) approach their therapeutic concentrations, inhibition of FXa did not appear to be a major contributor to PT prolongation, since argatroban also prolonged the PT of bovine plasma (despite a Ki for bovine FXa of 2,600 μmol/l). Only melagatran inhibited prothrombinase-bound FXa. We conclude that the differing effects of the DTIs on PT prolongation are primarily driven by their respective molar plasma concentrations required for clinical effect. DTIs with a relatively low affinity for thrombin require high plasma concentrations to double the APTT; these higher plasma concentrations, in turn, quench more of the thrombin generated in the PT, thereby more greatly prolonging the PT.
Pravastatin reduces thrombogenicity by mechanisms beyond plasma cholesterol lowering
Authors: Casani Laura , Sanchez-Gomez Sonia , Vilahur Gemma , Badimon Lina
Published: October 2005

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely used in the management and prevention of cardiovascular disease. In addition to its major activity, plasma lipid lowering, statins have shown a wide spectrum of additional effects that may contribute to their benefits in the prevention of cardiovascular disease. Our objective was to study whether treatment with a statin, pravastatin, could reduce thrombosis triggered by damaged vessels without changing plasma cholesterol levels. A cholesterol-clamp animal model was developed by feeding swine for 100 days on an hypercholesterolemic (HL) diet; in the last 50 days, they were randomly assigned to receive either placebo (HLC) or pravastatin (5mg . kg−1. day−1) (HLP) in addition to the hypercholesterolemic diet. A normocholesterolemic control group (NLC) was simultaneously studied. There were no significant differences in total cholesterol, LDL and HDL plasma levels between the two groups; however, mural thrombosis triggered by both an eroded and disrupted vessel wall was significantly inhibited by pravastatin (P<0.05). Axial dependence analysis of platelet deposition revealed that pravastatin treatment reduced the increase in platelet deposition associated to the shear rate increase at the stenosis. Additionally, pravastatin treatment significantly reduced platelet membrane RhoA expression (P <0.05) and vascular wall tissue factor (TF) protein expression (P <0.05). In addition to its lipid lowering effects, pravastatin can reduce blood thrombogenicity by mechanisms independent of plasma cholesterol lowering.
Combinatorial peptides directed to inhibitory antibodies against human blood clotting factor VIII
Authors: Kopecky Eva-Maria , Greinstetter Sabine , Pabinger Ingrid , Buchacher Andrea , Römisch Jürgen , Jungbauer Alois
Published: October 2005

The development of antibodies against blood clotting factorVIII is a major complication affecting 20–30% of hemophilia A patients receiving replacement with FVIII concentrates. This study investigated generating peptides acting as broadly neutralizing agents to block factor VIII antibodies. These peptides were selected from dual positional scanning decapeptide libraries on cellulose membranes. From this library comprising 6.8×1012 peptides we selected 468 peptides for further screening rounds. Finally we identified two decapeptides with the ability to block 8 out of 10 inhibitory antibodies from sera of patients with FVIII inhibitors demonstrated by competition assays. Sequence alignment of the peptides showed similarity with several domains in the FVIII molecule demonstrating the mimotope nature of the selected peptides. Our results show the efficiency of the combinatorial library approach and show the potential of combinatorial peptides to compete out polyclonal inhibitor IgG from a broad range of patients’ sera. Combinatorial peptides could be novel and highly effective drug candidates for alternative treatment in patients with factor VIII inhibitors.
Protein C Sapporo (protein C Glu 25 → Lys): A heterozygous missense mutation in the Gla domain provides new insight into the interaction between protein C and endothelial protein C
receptor
Authors: Nakabayashi Toru , Mizukami Kazuhiro , Naitoh Sumiyoshi , Takeda Mika , Shikamoto Yasuo , Nakagawa Takafumi , Kaneko Hiroki , Tarumi Takashi , Mizoguchi Itaru , Mizuno Hiroshi , Koike Takao , Ieko Masahiro
Published: October 2005

Interaction of the γ-carboxyglutamic acid (Gla) domain of protein C with endothelial protein C receptor (EPCR) is a critical step for efficient activation of protein C, though interactions by mutants in the Gla domain of protein C with EPCR have been rarely evaluated. We identified a 44-year-old Japanese woman with a history of recurrent thromboembolism as an inherited missense mutation, the first such case reported in Japan, which involved a protein C Gla 25 mutation. Total protein C antigen and Gla protein C antigen levels in the proband were normal. Protein C activity measured with an anticoagulant assay was reduced, whereas that measured with an amidolytic assay was normal. She was therefore phenotypically diagnosed as type IIb protein C deficiency. Direct sequencing of the PCR fragments revealed a heterozygous G toA transition at nucleotide position 1462 in exon 3, which predicted an amino acid substitution of Glu 25 by Lys. Her mother and one son were also heterozygous for this mutation. A molecular dynamics simulation of Gla 25→Lys/EPCR complex in water suggested that the affinity between the molecules was decreased compared to the wild type Gla domain/EPCR complex. Since Gla 25 has been shown to play an important role in protein C function, not only in membrane phospholipid binding but also in binding to EPCR, our findings provide new insight into the mechanism by which the Glu 25→Lys mutation induces type IIb protein C deficiency in individuals.
Modulation of the intestinal response to ionizing radiation by anticoagulant and non-anticoagulant heparins
Authors: Wang Junru , Zheng Huaien , Qiu Xiaohua , Kulkarni Ashwini , M. Fink Louis , Hauer-Jensen Martin
Published: October 2005

Endothelial dysfunction is involved in radiation responses in many normal tissues, including intestine. Endothelium-directed interventions ameliorate intestinal radiation injury (radiation enteropathy) in animal models, and anecdotal reports also suggest a beneficial effect of heparin. This study assessed low molecular weight heparin as an intestinal radiation response modifier. Rats underwent localized small bowel irradiation. Groups of rats were treated with saline, nadroparin (3 mg/kg/d), or a nonanticoagulant heparin (SR80258, 3 mg/kg/d), from 3 days before to 2 weeks after irradiation. The intestinal radiation response was assessed 2 weeks and 6 weeks after irradiation using quantitative histology; morphometry, and cellular and molecular endpoints. Compared to vehicle-treated controls, nadroparin sig-nificantly exacerbated structural radiation injury, neutrophil infiltration, and TGFβ and collagen I immunoreactivity levels 2 weeks after irradiation. SR80258 was associated with increased TGFβ levels, but the other parameters did not reach statistical significance. At 6 weeks, structural, cellular, and molecular injury was similar in the three experimental groups. Heparin, in contrast to antiplatelet agents and direct thrombin inhibitors, does not ameliorate, but exacerbates acute intestinal radiation toxicity. These data underscore the importance of heparin as an inhibitor of physiological anti-inflammatory mechanisms during tissue injury, as well as the non-anticoagulant effects of heparin. Moreover, these data may have implications for the use of heparin during radiation therapy.
Multiplex fluorescent analysis of four short tandem repeats for rapid haemophilia A molecular diagnosis
Authors: Sánchez-García Jorge , Gallardo Dominique , Ramírez Lorena , Vidal Francisco
Published: October 2005

Indirect molecular diagnosis of hemophilia A (HA) is carried out by analyzing intragenic polymorphic markers described along the coagulation factorVIII (FVIII) gene. Several studies have demonstrated that the two commonly used intronic short tandem repeats (STR13 and STR22) located in the FVIII gene are highly informative for this task. Two extragenic markers closely linked to FVIII (DXS1073 and DXS1108) have also been described as valuable tools for gene tracking. The objective of the present work was to develop a rapid, single-tube automated method to simultaneously analyze these four STRs. Consistent amplification was achieved by quadruplex fluorescent PCR and the products were analyzed by capillary electrophoresis. Validation of the method included DNA analysis of 88 individuals from a control population, 45 HA patients and 32 individuals from 10 HA-affected families. Statistical study showed that the STR13, STR22 and DXS1108 loci were in significant linkage disequilibrium, whereas DXS1073 was not. Nevertheless, the combination of the four markers offered a high heterozygosity rate (>90%) that improved tracing of FVIII gene inheritance. Optimal results with application to single cells in a HA preimplantation genetic diagnosis (PGD) protocol demonstrated the sensitivity of the technique. In conclusion, the automated fluorescent method described is an extremely rapid, simple and highly informative one that is easy to standardize and allows direct comparison of results among different groups working with genetic counseling, prenatal diagnosis and PGD in HA-affected families.
Complement C3 and C-reactive protein levels in patients with stable coronary artery disease
Authors: Ajjan Ramzi , Futers Timothy , Brown Jane , Cymbalista Charlotte , Boothby May , Carter Angela , Grant Peter
Published: October 2005

The aim of this study was to determine whether complement C3 is an indicator of coronary artery disease (CAD). We measured plasma C3 and CRP levels in 278 patients undergoing coronary angiography for typical symptoms of CAD and 269 healthy age and sex matched controls. C3 levels were significantly higher in patients compared with controls (1.15 g/l and 0.92 g/l respectively; p<0.001). In the patient group, C3 levels correlated with BMI, fasting glucose, HbA1c, fibrinogen, CRP and HDL in both men and women. CRP levels were also higher in patients compared with controls (1.14 mg/l and 0.86 mg/l respectively; p=0.005) and correlated with markers of the metabolic syndrome. In a logistic regression model including C3, smoking, hypertension, cholesterol and diabetes, C3 was independently associated with CAD with an odds ratio of 3.20 for a 1 SD increase in C3 levels. In contrast, CRP was not independently associated with CAD in a similar regression analysis. In conclusion, both C3 and CRP plasma levels are elevated in patients with symptoms of CAD. However, C3 seems to be a better indicator of CAD than CRP in this study, suggesting that C3 could be an additional marker for risk stratification in atherosclerosis.
Large deletions of the PROS1 gene in a large fraction of mutation-negative patients with protein S deficiency
Authors: Hillarp Andreas , Säll Torbjörn , Zöller Bengt , Dahlbäck Björn , Halldén Christer , Johansson Anna
Published: October 2005

Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS1 gene. Conventional mutation detection techniques fail to detect a pathogenic PROS1 mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS1 are found in families where mutations in the PROS1 gene have not been found despite sequencing. For this purpose, a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions encompassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis showed that the three large deletions and the five other disease haplotypes were all different. All of the eight disease haplotypes co-segregated with protein S deficiency, but each of the five non-deletion haplotypes were present also in normal individuals. In conclusion: Large deletions of PROS1 are relatively common in protein S deficiency patients and screening for large deletions in PROS1 mutation-negative individuals are therefore warranted.
Immunoglobulin M-to-Immunoglobulin G Anti-Human Leukocyte Antigen Class II Antibody Switching in Cardiac Transplant Recipients Is Associated With an Increased Risk of Cellular Rejection and Coronary Artery Disease
Authors: Lietz Katherine , John Ranjit , Burke Elizabeth , Schuster Michael , Rogers Tyson B. , Suciu-Foca Nicole , Mancini Donna , Itescu Silviu
Published: October 2005

Background—

Activation of T cells induces immunoglobulin (Ig)M-to-IgG B-cell isotype switching via costimulatory regulatory pathways. Because rejection of transplanted organs is preceded by alloantigen-dependent T-cell activation, we investigated whether B-cell isotype switching could predict acute cellular rejection and the subsequent development of transplantation-related coronary artery disease (TCAD) in cardiac transplant recipients.

Methods and Results—

Among 267 nonsensitized heart transplant recipients, switching from IgM to IgG anti-human leukocyte antigens (HLA) antibodies directed against class II but not against class I antigens was associated with a shorter duration to high-grade rejection, defined as International Society for Heart and Lung Transplantation grade 3A or higher (
P
<0.001), a higher cumulative rejection frequency (
P
=0.002), accelerated development of TCAD (
P
=0.04), and decreased late survival (
P
=0.03). Conversely, the persistence of IgM anti-HLA antibodies against class II but not against class I antigens for >30 days and the lack of IgG isotype switching were associated with protection against both acute rejection (
P
=0.02) and TCAD (
P
=0.05). Alloisotype switching coincided with T-cell activation, as evidenced by increased serum levels of soluble CD40 ligand costimulatory molecules. Finally, a case-control study showed that reduction of cardiac allograft rejection by mycophenolic acid was accompanied by reduced CD40 ligand serum levels and the prevention of IgM-to-IgG anti-HLA class II antibody switching.

Conclusions—

T-cell-dependent B-cell isotype switching and the consequent production of IgG anti-HLA class II antibodies are strongly correlated with acute cellular rejection, a high incidence of recurrent rejections, TCAD, and poor long-term survival. Detecting this isotype switch is a clinically useful surrogate marker for in vivo T-cell activation and may provide a noninvasive approach for monitoring the efficacy of T-cell targeted immunosuppressive therapy in heart transplant recipients.
Abnormal Uterine Doppler Is Related to Vasculopathy in Pregestational Diabetes Mellitus
Authors: Pietryga Marek , Brązert Jacek , Wender-Oėgowska Ewa , Biczysko Romuald , Dubiel Mariusz , Gudmundsson Saemundur
Published: October 2005

Background—

The aim of the study was to evaluate the relation between maternal placental Doppler velocimetry, levels of the maternal glucose, and clinical signs of vasculopathy in pregnancy complicated by pregestational diabetes mellitus.

Methods and Results—

A retrospective study of 155 pregestational diabetic women between the 22nd and 40th weeks of pregnancy, categorized in White classification as B, 49; C, 40; D, 22; R, 20; F, 5; and RIF, 19. Cases in classes R, F, and R/F were defined as having vasculopathy. Doppler velocimetry of umbilical and uterine arteries was evaluated for vascular impedance, both in terms of pulsatility index (PI) for both arteries and a notch in early diastole in the uterine arteries. The last examination before delivery was used for analysis. Increased umbilical artery PI was seen in 19 and a uterine artery abnormality in 45 cases. There was a correlation between levels of HbA
lc
and increased vascular impedance in the uterine and umbilical arteries. Signs of increased uterine artery vascular impedances were significantly related to pregestational vasculopathy. In cases of small-for-gestational-age newborn infants, PI was significantly increased in uterine and umbilical arteries. Furthermore, PI in macrosomic fetuses was significantly lower than in normal infants. Abnormal uterine artery Doppler was also strongly related to adverse outcome.

Conclusions—

Abnormal uterine artery Doppler is related to pregestational vasculopathy and adverse outcome of pregnancy. The results suggest that the uterine arteries are affected in women with clinical signs of pregestational vasculopathy. This may influence placental perfusion and fetal well-being.
Ability of Serum to Decrease Cellular AcylCoA:Cholesterol Acyl Transferase Activity Predicts Cardiovascular Outcomes
Authors: Chirinos Julio A. , Zambrano Juan P. , Chakko Simon , Schob Alan , Goldberg Ronald B. , Perez Guido , Mendez Armando J.
Published: October 2005

Background—

We evaluated whether cholesterol efflux activity of serum is associated with the presence of angiographic coronary artery disease (CAD) and the risk of major adverse cardiovascular events (MACE) and death.

Methods and Results—

We studied 168 men undergoing coronary angiography. Cholesterol efflux activity was measured in vitro by incubation of patient serum with human skin fibroblasts and defined as the ability of serum to decrease the pool of cholesterol available for esterification by the acylCoA:cholesterol acyl transferase (ACAT) reaction. We evaluated whether this activity was associated with the presence of CAD and the risk of MACE and death during a 4.5-year follow-up. Serum-induced changes in ACAT activity did not correlate with HDL levels or the presence of CAD. Patients in the highest tertile of change in ACAT activity had a significantly higher risk for MACE (HR, 2.15; 95% CI, 1.36 to 3.39;
P
=0.001) and death (HR, 2.23; 95% CI, 1.17 to 4.26;
P
=0.01). These correlations were independent of other risk markers including LDL, HDL, and C-reactive protein levels.

Conclusions—

Serum-induced depletion of cellular cholesterol available for esterification by ACAT was a strong, independent predictor of MACE and death. We speculate that the ability of serum to decrease ACAT activity depends on ATP binding cassette transporter A1 (ABCA1)–mediated efflux. Furthermore, serum samples that induce larger changes in ACAT activity contain increased levels of HDL particles that preferentially interact with ABCA1 and that these particles accumulate in the serum of patients because of low activity of ABCA1 in vivo preventing or limiting the extent of apoA-I lipidation.
Prevalence and Risks of Undiagnosed Diabetes Mellitus in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Lauruschkat Achim H. , Arnrich Bert , Albert Alexander A. , Walter Jörg A. , Amann Berthold , Rosendahl Ulrich P. , Alexander Tejas , Ennker Jürgen
Published: October 2005

Background—

Numerous studies have shown that diabetes mellitus (DM) is not identified and, consequently, inadequately treated in a substantial proportion of the patients in the general population. We know very little about the extent and the consequences of undiagnosed diabetes in the risk group of patients with coronary heart diseases. The objective of this study was therefore to determine the prevalence and the risks of undiagnosed DM among patients with coronary artery bypass.

Methods and Results—

The data of 7310 patients who have undergone coronary bypass operations between 1996 and 2003 were analyzed. Depending on their diagnosis on admission and their fasting plasma glucose (FPG) level, these patients were classified as known diabetics, undiagnosed diabetics (FPG ≥126 mg/dL), or as nondiabetics (FPG <126 mg/dL) and were compared in terms of their preoperative, intraoperative, and postoperative characteristics. Among the patients with coronary bypass that we examined, we found a prevalence of diagnosed diabetics of 29.6%. The prevalence of patients with undiagnosed DM (FPG ≥126 mg/dL) was 5.2%. In comparison with the other groups (non-DM versus undiagnosed DM versus known DM), the undiagnosed diabetics more frequently required resuscitation (1.7% versus 4.2% versus 1.5%;
P
<0.01) and reintubation (2.1% versus 5.0% versus 3.5%;
P
<0.01) and often showed a longer period of ventilation >1 day (5.6% versus 10.5% versus 7.4%;
P
<0.01). Perioperative mortality rate was highest in this group (0.9% versus 2.4% versus 1.4%;
P
<0.01).

Conclusions—

This study is the first to publish the prevalence of undiagnosed diabetes mellitus in cardiac surgery. During the perioperative and postoperative courses, these patients displayed a substantially higher morbidity and mortality rate.
Delayed Arteriogenesis in Hypercholesterolemic Mice
Authors: Tirziu Daniela , Moodie Karen L. , Zhuang Zhen W. , Singer Katie , Helisch Armin , Dunn Jeff F. , Li Weiming , Singh Jaipal , Simons Michael
Published: October 2005

Background—

Hypercholesterolemia has been reported to inhibit ischemia-induced angiogenesis. To address its effects on arteriogenesis, we investigated arterial growth in hypercholesterolemic low-density lipoprotein receptor
−/−
/ApoB-48
−/−
(HCE) mice.

Methods and Results—

The extent and the time course of arteriogenesis after femoral artery ligation was evaluated in HCE and strain-matched control mice. Distal limb perfusion was measured by laser Doppler imaging, whereas MRI was used to visualize arterial flow and micro-computed tomography to assess vascular growth. After femoral artery ligation, serial laser Doppler imaging demonstrated significantly delayed restoration of perfusion in untreated HCE compared with control mice (day 3, 0.09 versus 0.19,
P
<0.05). Treatment with Ad-PR39 in control mice led to a significant restoration of arterial blood flow and tissue perfusion at day 3, whereas in HCE mice, hindlimb perfusion began increasing only by day 7. Micro-CT analysis confirmed increased growth of smaller arterioles (16 to 63 μm in diameter) in the Ad-PR39–treated control compared with HCE mice. The delay in arteriogenesis in HCE mice correlated with delayed tissue appearance of F4/80
+
cells. Analysis of gene expression after Ad-PR39 treatment demonstrated that HCE mice had significantly reduced expression of FGF receptor 1, hypoxia-inducible factor-1α, vascular cell adhesion molecule-1, macrophage scavenger receptor-1, and cyclophilin A compared with controls 3 days after arterial ligation that equalized by day 7, mimicking relative changes in arteriogenesis and tissue perfusion.

Conclusions—

Hypercholesterolemia results in delayed native arteriogenesis because of reduced early monocyte/macrophage influx and delayed and impaired arterial growth response to growth factor therapy.
Melissus And His Opponents: The Argument of DK 30 B 8
Authors: Makin Stephen
Published: October 2005

In this paper I offer a new interpretation of Melissus' argument at DK 30 B8.In this passage Melissus uses an Eleatic argument against change to challenge an opponent who appeals to the authority of perception in order to support the view that there are a plurality of items in the world. I identify an orthodox type of approach to this passage, but argue that it cannot give a charitable interpretation of Melissus' strategy. In order to assess Melissus' overall argument we have to identify the opponent at whom it is aimed. The orthodox interpretation of the argument faces a dilemma: Melissus' argument is either a poor argument against a plausible opponent or a good argument against an implausible opponent.My interpretation turns on identifying a new target for Melissus' argument. I explain the position I call Bluff Realism (contrasting it with two other views: the Pig Headed and the Fully Engaged). These are positions concerning the dialectical relation between perception on the one hand, and arguments to counter-perceptual conclusions on the other. I argue that Bluff Realism represents a serious threat from an Eleatic point of view, and is prima facie an attractive position in its own right.I then give a charitable interpretation of Melissus' argument in DK 30 B8, showing how he produces a strong and incisive argument against the Bluff Realist position I have identified. Melissus emerges as an innovative and astute philosopher.
Zahlensymbolik in Kirchenliedern Paul Gerhardts
Authors: Körber Esther-Beate
Published: October 2005

This essay is the first attempt to demonstrate the numerical symbolism of Paul Gerhardt's hymns. In his hymns for morning and evening, the number of each verse has a symbolic meaning also expressed in the contents of the verse. Gerhardt presumably used numerical symbolism to convey the harmony of God's creation.
Jugendbewegung und Nationalsozialismus
Authors: Niemeyer Christian
Published: October 2005

Werner Kindt's sourcebook exemplifies the obvious interest of German-speaking pedagogy in reflexive denial. This reflexive denial had its beginnings in the affected generation, which after 1945 became appalled by the authors it had admired in its youth. This generation simply began to deny that these authors as well as the resulting literary works (in the youth movement) had ever existed as they were.
History Undone. The Appropriation of Thucydides
Authors: Aiken David Wyatt
Published: October 2005

Many of the classic texts of the west have ,,disappeared" beneath the weight of interpretative tradition. In this essay I argue that in the evolution of the western rationalist tradition of 'History', the historical texts of Thucydides have now become effectively absent from the hermeneutical equation. As a result, there is at present a disjunction between the historical Thucydides as he is present in his writings, and the interpretative assumptions about the writings of Thucydides that have grown up in the critical literature.
Retrieval of Model Grid-Scale Heat Capacity Using Geostationary Satellite Products. Part I: First Case-Study Application
Authors: McNider Richard T. , Lapenta William M. , Biazar Arastoo P. , Jedlovec Gary J. , Suggs Ronnie J. , Pleim Jonathan
Published: October 2005

In weather forecast and general circulation models the behavior of the atmospheric boundary layer, especially the nocturnal boundary layer, can be critically dependent on the magnitude of the effective model grid-scale bulk heat capacity. Yet, this model parameter is uncertain both in its value and in its conceptual meaning for a model grid in heterogeneous conditions. Current methods for estimating the grid-scale heat capacity involve the areal/volume weighting of heat capacity (resistance) of various, often ill-defined, components. This can lead to errors in model performance in certain parameter spaces. Here, a technique is proposed and tested for recovering bulk heat capacity using time tendencies in satellite-retrieved surface skin temperature (SST). The technique builds upon sensitivity studies that show that surface temperature is most sensitive to thermal inertia in the early evening hours. The retrievals are made within the context of a surface energy budget in a regional-scale model [the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5)]. The retrieved heat capacities are used in the forecast model, and it is shown that the model predictions of temperature are improved in the nighttime during the forecast periods.
Improved Radar Ice Water Content Retrieval Algorithms Using Coincident Microphysical and Radar Measurements
Authors: Heymsfield Andrew J. , Wang Zhien , Matrosov Sergey
Published: October 2005

Airborne radar reflectivity measurements at frequencies of 9.6 and 94 GHz, with collocated, in situ particle size distribution and ice water content measurements from the Cirrus Regional Study of Tropical Anvils and Cirrus Layers (CRYSTAL) Florida Area Cirrus Experiment (FACE) in Florida in July 2002, offer one of the first opportunities to evaluate and improve algorithms for retrieving ice water content from single-wavelength spaceborne radar measurements. Both ice water content and radar reflectivity depend on the distribution of particle mass with size. It is demonstrated that single, power-law, mass dimensional relationships are unable to adequately account for the dominating contribution of small particles at lower reflectivities and large particles at higher reflectivities. To circumvent the need for multiple, or complex, mass dimensional relationships, analytic expressions that use particle ensemble mean ice particle densities that are derived from the coincident microphysical and radar observations are developed. These expressions, together with more than 5000 CRYSTAL FACE size distributions, are used to develop radar reflectivity–ice water content relationships for the two radar wavelengths that appear to provide improvements over earlier relationships, at least for convectively generated stratiform ice clouds.
Urban Modifications in a Mesoscale Meteorological Model and the Effects on Near-Surface Variables in an Arid Metropolitan Region
Authors: Grossman-Clarke Susanne , Zehnder Joseph A. , Stefanov William L. , Liu Yubao , Zoldak Michael A.
Published: October 2005

A refined land cover classification for the arid Phoenix (Arizona) metropolitan area and some simple modifications to the surface energetics were introduced in the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5). The single urban category in the existing 24-category U.S. Geological Survey land cover classification used in MM5 was divided into three classes to account for heterogeneity of urban land cover. Updated land cover data were derived from 1998 Landsat Thematic Mapper satellite images. The composition of the urban land use classes in terms of typical fractions of vegetation and anthropogenic surfaces was determined from ground-truth information, allowing a variety of moisture availability for evaporation by land cover class. Bulk approaches for characteristics of the urban surface energy budget, such as heat storage, the production of anthropogenic heat, and radiation trapping, were introduced in MM5’s Medium Range Forecast boundary layer scheme and slab land surface model. A 72-h simulation was performed with MM5 on a 2 km × 2 km grid during June 1998. The new land cover classification had a significant impact on the turbulent heat fluxes and the evolution of the boundary layer and improved the capability of MM5 to simulate the daytime part of the diurnal temperature cycle in the urban area. The nighttime near-surface air temperatures were improved significantly by adding radiation trapping, heat storage, and anthropogenic heating to the model.
Statistical distributions of optimal global alignment scores of random protein sequences
Authors: Pang Hongxia , Tang Jiaowei , Chen Su-Shing , Tao Shiheng
Published: October 2005

Background

The inference of homology from statistically significant sequence similarity is a central issue in sequence alignments. So far the statistical distribution function underlying the optimal global alignments has not been completely determined.

Results

In this study, random and real but unrelated sequences prepared in six different ways were selected as reference datasets to obtain their respective statistical distributions of global alignment scores. All alignments were carried out with the Needleman-Wunsch algorithm and optimal scores were fitted to the Gumbel, normal and gamma distributions respectively. The three-parameter gamma distribution performs the best as the theoretical distribution function of global alignment scores, as it agrees perfectly well with the distribution of alignment scores. The normal distribution also agrees well with the score distribution frequencies when the shape parameter of the gamma distribution is sufficiently large, for this is the scenario when the normal distribution can be viewed as an approximation of the gamma distribution.

Conclusion

We have shown that the optimal global alignment scores of random protein sequences fit the three-parameter gamma distribution function. This would be useful for the inference of homology between sequences whose relationship is unknown, through the evaluation of gamma distribution significance between sequences.
Characterization of a likelihood based method and effects of markers informativeness in evaluation of admixture and population group assignment
Authors: Yang Bao-Zhu , Zhao Hongyu , Kranzler Henry R , Gelernter Joel
Published: October 2005

Background

Detection and evaluation of population stratification are crucial issues in the conduct of genetic association studies. Statistical approaches useful for understanding these issues have been proposed; these methods rely on information gained from genotyping sets of markers that reflect population ancestry. Before using these methods, a set of markers informative for differentiating population genetic substructure (PGS) is necessary. We have previously evaluated the performance of a Bayesian clustering method implemented in the software STRUCTURE in detecting PGS with a particular informative marker set. In this study, we implemented a likelihood based method (LBM) in evaluating the informativeness of the same selected marker panel, with respect to assessing potential for stratification in samples of European Americans (EAs) and African Americans (AAs), that are known to be admixed. LBM calculates the probability of a set of genotypes based on observations in a reference population with known specific allele frequencies for each marker, assuming Hardy Weinberg equilibrium (HWE) for each marker and linkage equilibrium among markers.

Results

In EAs, the assignment accuracy by LBM exceeded 99% using the most efficient marker FY, and reached perfect assignment accuracy using the 10 most efficient markers excluding FY. In AAs, the assignment accuracy reached 96.4% using FY, and >95% when using at least the 9 most efficient markers. The comparison of the observed and reference allele frequencies (which were derived from previous publications and public databases) shows that allele frequencies observed in EAs matched the reference group more accurately than allele frequencies observed in AAs. As a result, the LBM performed better in EAs than AAs, as might be expected given the dependence of LBMs on prior knowledge of allele frequencies. Performance was not dependent on sample size.

Conclusion

The performance of the LBM depends on the efficiency and number of markers, and depends greatly on how representative the available reference allele frequencies are for those of the population being assigned. This method is of value when the parental population is known and relevant allele frequencies are available.
A New Route to the Synthesis of Indolo[2,3-a]carbazoles
Authors: Banerji Avijit , Bandyopadhyay Debasish , Basak Bidyut , Biswas Pizush Kanti , Banerji Julie , Chatterjee Asima
Published: October 2005

A straightforward, easy and smooth process of synthesizing indolo[2,3-a]carbazoles, which can frequently serve as a nucleus of several natural products is reported. The process involves only two steps viz. single electron transfer reaction and subsequent reductive cyclization with hydrazine.
Concentration-dependent Size Control of Germanium Nanocrystals
Authors: Hope-Weeks Louisa J
Published: October 2005

A room temperature solution phase preparation of germanium nanocrystals has been examined by means of varying the germanium precursor concentration. By varying the germanium tetrachloride concentration, it is possible to control the size distribution of nanocrystals formed.
Haterumadienone: A New Puupehenone Congener from an Okinawan Marine Sponge, Dysidea sp.
Authors: Ueda Katsuhiro , Ueta Tomoyuki , Siwu Eric Richard Oktavianus , Kita Masaki , Uemura Daisuke
Published: October 2005

Haterumadienone (1), a ring-contracted derivative of puupehenone (2), was isolated from a sponge Dysidea sp., along with the artificial acetone adducts 3 and 4 of a trione hydrate 5 which could be detected in the sponge. The structures of 1 and the acetone adducts 3 and 4 were successfully determined by detailed spectroscopic analysis. These compounds showed the ability to inhibit the division of fertilized sea urchin eggs.
Carbophosphinylation of Arynes with Cyanomethyldiphenylphosphine Oxide
Authors: Yoshida Hiroto , Watanabe Masahiko , Ohshita Joji , Kunai Atsutaka
Published: October 2005

A methylene–phosphorus σ-bond of cyanomethyldiphenylphosphine oxide was found to add across a carbon–carbon triple bond of arynes, leading to the simultaneous introduction of cyanomethyl and diphenylphosphinyl moieties into 1,2-positions of the aromatic skeletons.
Highly Selective Oxidation of Diphenylmethane to Benzophenone over Co/MCM-41
Authors: Chang Fang , Li Wanyi , Xia Fei , Yan Zhiyin , Xiong Jie , Wang Jiaqiang
Published: October 2005

Highly selective formation of benzophenone (99.1%) from diphenylmethane is reported for the first time using H2O2 (30%) as an oxidant and Co/MCM-41 as the catalyst.
Preparation of Fluorous DMF Solvents and Their Use for Some Pd-catalyzed Cross-coupling Reactions
Authors: Matsubara Hiroshi , Maeda Louis , Ryu Ilhyong
Published: October 2005

N,N-Dimethylformamide derivatives 1a (Rf6-DMF) and 1b (Rf8-DMF) with a C6 or C8 fluorous ponytail, respectively, have been synthesized and examined for some physical properties. Rf6-DMF was tested as a solvent for Mizoroki–Heck arylation of butyl acrylate and Sonogashira coupling reaction of iodobenzene with phenylacetylene. Both reactions proceeded as smoothly as in DMF to give the products in high yield. Fluorous DMF derivative 1a can be recovered easily from the reaction mixture by a fluorous/organic biphasic workup and recycled.
Self-assembly of Mixed-valent Ruthenium(II,III) Pivalate and Octacyanotungstate(V) Building Blocks
Authors: Matoga Dariusz , Mikuriya Masahiro , Handa Makoto , Szklarzewicz Janusz
Published: October 2005

One-dimensional coordination polymer of [Ru2(piv)4(μ-CN)W(CN)7]n2n− (Hpiv = pivalic acid) has been synthesized in the presence of PPh4+. The X-ray crystal structure reveals an alternating arrangement of ruthenium(II,III) dimers and [W(CN)8]3− ions in a 1-D chain. The magnetic susceptibility data (4.5–300 K) shows a ferrimagnetic behavior of this complex.
An Unnatural Amino Acid Bearing Bipyridyl Backbone: Selective Formation of mer-Isomers for Iron(II) Tris-chelate Complexes
Authors: Kyakuno Masato , Oishi Shigero , Ishida Hitoshi
Published: October 2005

The fac/mer-ratios of the iron(II) complexes with the derivatives of an unnatural amino acid, 5′-N-acetylamino-2,2′-bipyridine-5-carboxylic acid, were investigated. It was found that the amide derivatives with secondary amines selectively yielded the mer-isomers independently of the ligand structures. On the other hand, for the amides with primary amines, the ratios of the fac- and mer-complexes increased and decreased, respectively, with the increasing sizes of the substituents, suggesting stabilization of the fac-isomers by electrostatic interaction (or hydrogen bondings) between the ligands.
Conversion of Glycerin into Lactic Acid by Alkaline Hydrothermal Reaction
Authors: Kishida Hisanori , Jin Fangming , Zhou Zhouyu , Moriya Takehiko , Enomoto Heiji
Published: October 2005

Hydrothermal decomposition experiments of glycerin with an alkali showed that glycerin could be converted into lactic acid with a high yield of about 90 mol % based on glycerin used. Discussion on the pathway for the conversion of glycerin to lactic acid suggests that glycerin is first decomposed to pyruvaldehyde with elimination of hydrogen by a H− shift to the adjacent hydrogen. Pyruvaldehyde formed is then converted into lactic acid ion by the benzilic acid rearrangement.
A cavernous haemangioma of the thyroid gland
Authors: Kano Motohiro , Kameyama Kaori , Hosoda Yasuhiro , Sugino Kiminori , Ito Koichi
Published: October 2005

Haemangioma of the thyroid gland is extremely rare. We report a case of a cavernous haemangioma of the neck that was located both inside and outside the thyroid gland of a 21-year-old man. Ultrasonography of the neck revealed numerous calcified nodules. Computed tomography (CT) showed a large calcified soft tissue mass in the right lobe of the thyroid. Based on the imaging findings a papillary thyroid carcinoma was suspected, but examination of the surgical specimen revealed a huge cavernous haemangioma containing numerous phleboliths.
Colonic carcinoma metastasis to the thyroid: a case of skip metastasis
Authors: Phillips J S , Lishman S , Jani P
Published: October 2005

Colonic carcinoma metastasis to the thyroid is rare. Here the authors present the case of an 81-year-old lady who presented with metastatic colonic adenocarcinoma in her thyroid gland. This case is unique as it is the first to demonstrate metastasis from the colon to the thyroid with no other site involvement. The use of cytokeratin immunohistochemical staining is reviewed along with the current perspectives on the concept of skip metastasis.
Tonsillectomy: haemorrhaging ideas
Authors: McClelland L , Jones N S
Published: October 2005

Tonsil surgery has been described for over 3000 years. Haemorrhage following tonsillectomy remains the most serious complication of surgery. Over recent years several audits have been gathering data on current trends in tonsil surgery and clinical outcomes throughout England, Scotland and Northern Ireland. The results support a return to traditional dissection with ties to reduce the risk of post-operative haemorrhage. We describe the changes that have occurred to improve efficacy and safety during the evolution of the modern tonsillectomy.
An Assessment of Endocrine Disrupting Activity Changes during Wastewater Treatment through the Use of Bioassays and Chemical Measurements
Authors: Drewes Jörg E. , Hemming Jocelyn , Ladenburger Sarah J. , Schauer James , Sonzogni William
Published: October 2005

The objective of this study was to assess the removal efficiencies of secondary wastewater treatment processes for compounds causing endocrine disrupting activity. The study used bioassays and chemical measurements, such as gas chromatography with mass spectrometry and enzyme immunosorbent assays. A total of seven full‐scale water reclamation facilities using different unit operations and two pilot‐scale membrane bioreactors were examined. Findings of this study imply that estrogenic disrupting activity in primary effluent is mainly caused by two steroidal hormones (17β‐estradiol and estriol) and, to a lesser extent, by synthetic chemicals, such as bisphenol A, 4‐nonylphenol, and 4‐tert‐octylphenol. During secondary treatment, steroidal hormones were removed to a higher degree than nonylphenol and bisphenol A. The total estrogenic activity was removed by an average of 96%. The remaining concentrations of targeted steroids in secondary effluents, except for estriol, still had the potential to elicit a positive response in the human breast cell cancer assay. For the majority of facilities, the remaining activity was likely attributed to residual concentrations of two steroidal hormones (17β‐estradiol and estriol).
Sources and Fate of Nitrosodimethylamine and its Precursors in Municipal Wastewater Treatment Plants
Authors: Sedlak David L. , Deeb Rula A. , Hawley Elisabeth L. , Mitch William A. , Durbin Timothy D. , Mowbray Sam , Carr Steve
Published: October 2005

To assess the occurrence and fate of nitrosodimethylamine (NDMA) and its precursors in wastewater treatment plants, samples from wastewater treatment plants and industrial sources were analyzed for NDMA, total NDMA precursors, and dimethylamine (DMA). The median concentration of NDMA in untreated wastewater was approximately 80 ng/L, with maximum concentrations up to 790 ng/L presumably occuring because of sources unrelated to domestic wastewater. Concentrations of DMA in untreated wastewater ranged from approximately 50 to 120 μg/L and accounted for a majority of the NDMA precursors. The removal of NDMA during secondary biological treatment exhibited considerable variability, with overall removal ranging from 0 to 75%. In contrast, removal of NDMA precursors and DMA generally exceeded 70%. The median concentration of NDMA in secondary effluent before disinfection was 46 ng/L. Although DMA was removed during secondary treatment, other NDMA precursors in wastewater effluent will result in formation of additional NDMA upon disinfection with chloramines.