bluuebunny/crossref_metadata_2025 huggingface dataset:
Between the Dictates of Conscience and Political Expediency: Hitler’s Conservative Alliance Partner and Antisemitism during the Nazi Seizure of Power
Authors: Beck Hermann
Published: October 2006

This article investigates the plight of German Jews during the Nazi seizure of power in 1933 and, in particular, how DNVP leaders and members reacted to nazi transgressions and violence. The first section reviews the existing literature, which clearly reveals the gap in our present knowledge of the DNVP's role during the Machtergreifung. The second section examines the plethora of violent attacks on Jewish-owned businesses and individual Jews following the elections of 5 March 1933 and the reaction of the German authorities. The third section highlights the DNVP's reaction to the dilemma of national-minded German Jews, a large number of whom fought for Germany in the first world war. The fourth section analyses the few cases of conservative protest and attempted help and the fifth section focuses on the more numerous cases of rejection and disapprobation. The sixth section discloses the often contradictory reactions of the DNVP's Berlin headquarters and local DNVP associations when baptized Jews or half-Jews applied for party membership. The investigation reveals the spectrum of inconsistent, conflicting and at times outright contradictory reactions that the DNVP displayed toward the inherent plight of German Jews in the winter of 1932 and spring of 1933. The evidence shows that the DNVP failed completely to live up to its professed ideals, thereby undermining the very principles to which its members so tenaciously clung and setting the stage for the further erosion of the rights of German Jews.
Germany’s Staatssekretäre, Mass Starvation and the Meeting of 2 May 1941
Authors: Kay Alex J.
Published: October 2006

On 2 May 1941, seven weeks before the launch of Operation Barbarossa, a meeting of senior German officials, including many ministers' deputies, or Staatssekretšre, took place, which would establish the nature of the economic policy of ruthless exploitation pursued by the invaders and occupiers in the Soviet Union. In a chillingly matter-of-fact way, those present declared that 'x million people will doubtlessly starve, if that which is necessary for us is extracted from the land'. This article focuses on the meeting, its minutes and the men who attended, whilst placing it firmly in the context of the planning for German economic policy in the occupied Soviet territories. In addition, the article considers the importance of gatherings of the Staatssekretšre, the equivalent of British Permanent Secretaries, in National Socialist Germany, as a forum for inter-ministerial policy co-ordination, and draws comparisons between the meeting in Berlin on 2 May 1941 and the disproportionately better-known Wannsee Conference of 20 January 1942, the most infamous of all the Staatssekretšre discussions.
The Secretary of State versus the Secretary of Peace: The Dulles-Stassen Controversy and US Disarmament Policy, 1955-58
Authors: Tal David
Published: October 2006

Eisenhower's appointment in March 1955 of Harold Edward Stassen as his special assistant on Disarmament caused tensions within his administration, as secretary of state John Foster Dulles did not like the appointment that was commonly dubbed as 'secretary of peace'. The two competed not only over personal issues - their stand within the administration, but also over policy - with Stassen acting to turn Eisenhower's Open Skies Plan into a practical disarmament policy, while Dulles seeing it mainly as propaganda tool. Conceptually, that meant a struggle between two schools of thought within the administration: one advocating an 'all or nothing approach' toward disarmament and the other calling for making progress through negotiations and compromises. Dulles, who belonged to the first school of thought, won the struggle with Stassen, who was forced to resign, but in the end it was Stassen who had his way, as US disarmament policy was based on Dulles's 'all or nothing approach' was shifted along the practical lines set by Stassen.
Biocompatibility of Poly-DL-lactic acid (PDLLA) for Lung Tissue Engineering
Authors: Lin Y. M. , Boccaccini A. R. , Polak J. M. , Bishop A. E. , Maquet V.
Published: October 2006

This study explores the possibility of growing lung cells on poly-DL-lactic acid (PDLLA) scaffolds, with a view to in future engineer pulmonary tissue for human implantation. As a first step in this process, the ability of PDLLA to maintain the growth of lung epithelium is tested using a robust cell line. Poly-DL-lactic acid has been investigated in two forms, as planar discs and as 3-D foams, and it has been demonstrated that PDLLA is not only nontoxic to pneumocytes but it also actively supports their growth. The initial findings suggest that the material is an appropriate matrix for engineering of distal lung tissue.
Comparison of the Electrical Resistance and Potential Techniques for the Self-sensing of Damage in Carbon Fiber Polymer-Matrix Composites
Authors: Wang Daojun , Wang Shoukai , Chung D. D. L. , Chung Jaycee H.
Published: October 2006

The electric potential method, which involves measuring the potential at a distance from the line of current application, is effective for damage sensing of carbon fiber polymer-matrix composites when the distance is sufficiently small, such as 1.0 mm (8 laminae) in the through-thickness direction. It is ineffective when this distance is 2.1 mm (16 laminae). The electrical resistance method, which involves measuring the potential on the line of current application, has no thickness limitation. However, it suffers from current path distortion upon damage and the consequent reduced sensitivity for damage. A minor phenomenon of the measured resistance decreasing with increasing damage is observed for the regions of the composite not containing the point of impact. The major phenomenon of the resistance increasing with damage overshadows this minor phenomenon for the region containing the point of impact.
A Finite Strain Plastic-damage Model for High Velocity Impact using Combined Viscosity and Gradient Localization Limiters: Part I - Theoretical Formulation
Authors: Abu Al-Rub Rashid K. , Voyiadjis George Z.
Published: October 2006

During dynamic loading processes, large inelastic deformation associated with high strain rates leads, for a broad class of ductile metals, to degradation and failure by strain localization. However, as soon as material failure dominates a deformation process, the material increasingly displays strain softening and the finite element computations are considerably affected by the mesh size and alignment. This gives rise to a non-physical description of the localized regions. This article presents a theoretical framework to solve this problem with the aid of nonlocal gradient-enhanced theory coupled to viscoinelasticity. Constitutive equations for anisotropic thermoviscodamage (rate-dependent damage) mechanism coupled with thermo-hypoelasto-viscoplastic deformation are developed in this work within the framework of thermodynamic laws, nonlinear continuum mechanics, and nonlocal continua. Explicit and implicit microstructural length-scale measures, which preserve the well-posedness of the differential equations, are introduced through the use of the viscosity and gradient localization limiters. The gradient-enhanced theory that incorporates macroscale interstate variables and their high-order gradients is developed here to describe the change in the internal structure and to investigate the size effect of statistical inhomogeneity of the evolution related plasticity and damage. The gradients are introduced in the hardening internal state variables and are considered dependent on their local counterparts. The derived microdamage constitutive model is destined to be applied in the context of high velocity impact and penetration damage mechanics. The theoretical framework presented in this article can be considered as a feasible thermodynamic approach that enables to derive various gradient (visco) plasticity/(visco) damage theories by introducing simplifying assumptions. Besides the clear physical significance of the proposed framework, it also defines a very convenient context for the efficient numerical integration of the resulting constitutive equations. This aspect is explored in Part II of this work and the application of the framework proposed herein to the numerical simulation of high velocity impacts on metal plates.
Fatigue Damage Tolerance of Bainitic and Pearlitic Rail Steels
Authors: Aglan Heshmat A. , Fateh Mahmood
Published: October 2006

The microstructure-properties relationships, fatigue crack growth, and fracture surface morphology of J6 bainitic and premium pearlitic rail steels are studied. Specimens are cut from the middle of each railhead along the longitudinal direction of the rail using electrical discharge machining. Fatigue crack propagation tests are conducted under load control conditions using a servo hydraulic material testing system. A simple form of the fatigue power law is used to rank the fatigue crack growth kinetics of the two materials. The results show that bainitic steel has superior fatigue damage tolerance as represented by the fatigue lifetime, fatigue crack propagation kinetics, and fatigue fracture surface morphological features. Fracture surface analysis of fatigue failed specimens revealed the various mechanisms by which bainitic steel acquired its superior resistance to fatigue crack growth. Bainitic rail steel displayed more ductile fracture features such as tearing, and extensive ridge formation during the stable crack propagation process than pearlitic steel. These features are responsible for the crack deceleration and indicate a considerably high energy consuming process associated with the crack propagation of bainitic steel. Pulled-up pearlitic lamella, limited microcracks, and microvoid coalescence are found on the fracture surface of pearlitic rail steel during the stable crack process. The unstable crack propagation region of bainitic steel exhibits both large and small dimples indicative of high resistance to material separation. On the other hand, cleavage and intergranular separation are associated with the unstable crack region in pearlitic steel.
Identification of Casein Phosphopeptides in β-casein and Commercial Hydrolysed Casein by Mass Spectrometry
Authors: Miquel E. , Gómez J. A. , Alegría A. , Barberá R. , Farré R. , Recio I.
Published: October 2006

Casein phosphopeptides (CPPs) in commercial hydrolysed casein (CE90CPP) and in β-CN (β-CN) after simulated gastrointestinal digestion (gastric stage pepsin, pH =2, 37°C 2h) and intestinal stage (pancreatic-bile extract, pH =5.2, 37°C 2h) were sequenced by on-line reversed-phase high performance liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (RP-HPLC-ESIMS/MS). In β-CN digest five peptides that contained four to five phosphate groups and the cluster sequence SpSpSpEE (residues 17-21) were identified. All CPPs with one exception β-CN(1-24)4P, had the protein fragment β-CN(1-25)4P, which is one of the main CPPs produced in vivo digestion of casein and the results of in vitro studies showed that this fragment enhanced calcium, iron and zinc absorption. In commercial hydrolysed casein CE90CPP 13 peptides were identified, only one of them, αs2-CN (1-13)3P, contained the cluster sequence SpSpSpEE but all the peptides have one or two phosphoserine residues with mineral binding capacity. These CPPs were shorter (527-2061 Da vs 2966-6512 Da) and less phosphorylated (1-3 P vs 4-5 P) than those released after simulated gastrointestinal digestion of β-CN. In both samples, the potential mineral chelating properties of these peptides in relation to their amino acid sequences and the presence of the phosphorylated cluster are discussed.
State Denunciation of Crime
Authors: Bennett Christopher
Published: October 2006

In this paper I am concerned with a problem for communicative theories of punishment. On such theories, punishment is justified at least in part as the authoritative censure or condemnation of crime. But is this compatible with a broadly liberal political outlook? For while liberalism is generally thought to take only a very limited interest in its citizens’ attitudes (seeing moral opinion as a matter of legitimate debate), the idea of state denunciation of crime seems precisely to be focused on the attitudes expressed in action. In this paper I analyse the elements of the communicative theory of punishment, assessing the extent to which they can be considered anti-liberal. I argue that, understood in a certain way, the communicative theory, though in some sense communitarian, is compatible with at least one central and attractive non-perfectionist strand in liberalism.
Effect of Framing Factor on Clear Wall R-value for Wood and Steel Framed Walls
Authors: Syed Azam Mohiuddin , Kośny Jan
Published: October 2006

In the current practice of testing and theoretical analysis of building envelope assemblies, the amount of structural members incorporated into the total wall area is commonly called a framing factor. It used to be expressed as a percent of the total wall area. Traditionally, for wood-framed walls, the framing factor has been considered to be between 10 and 14%. According to the report prepared in 2002 by Enermodal Engineering for California Energy Commission, there is 27% framing in current residential walls in California. A similar study performed by the American Society of Heating Refrigeration and Air-conditioning Engineers in 2003 has concluded an average 25% of framing factor for all US residential buildings.

In order to incorporate this finding into theoretical and experimental procedures of heat transfer analysis, representative geometries for wood and steel-framed walls need to be redefined. In this article, R-values for various percentages of framing according to different methods of calculation are examined. Also, thermal effects of various configurations of installation, structural components in wood and steel-framed walls with studs installed at 16 in. on-center (for 27% of framing) are analyzed numerically using a 3D heat conduction code. In addition, consequences of installation imperfections in cavity insulation are analyzed from a thermal perspective. The performed numerical study demonstrated significant sensitivity of some residential walls for insulation installation imperfections.
Down-regulation of RXRα expression is essential for neutrophil development from granulocyte/monocyte progenitors
Authors: Taschner Sabine , Koesters Christina , Platzer Barbara , Jörgl Almut , Ellmeier Wilfried , Benesch Thomas , Strobl Herbert
Published: October 2006

Neutrophil granulocytes (Gs) represent highly abundant and short-lived leukocytes that are constantly regenerated from a small pool of myeloid committed progenitors. Nuclear receptor (NR) family members are ligand-activated transcription factors that play key roles in cellular proliferation and differentiation processes including myelopoiesis. Retinoid X receptor alpha (RXRα) represents the predominant NR types I and II homo- and heterodimerization partner in myeloid cells. Here we show that human myeloid progenitors express RXRα protein at sustained high levels during macrophage colony-stimulating factor (M-CSF)–induced monopoiesis. In sharp contrast, RXRα is down-regulated during G-CSF–dependent late-stage neutrophil differentiation from myeloid progenitors. Down-regulation of RXRα is critically required for neutrophil development since ectopic RXRα inhibited granulopoiesis by impairing proliferation and differentiation. Moreover, ectopic RXRα was sufficient to redirect G-CSF–dependent granulocyte differentiation to the monocyte lineage and to promote M-CSF–induced monopoiesis. Functional genetic interference with RXRα signaling in hematopoietic progenitor/stem cells using a dominant-negative RXRα promoted the generation of late-stage granulocytes in human cultures in vitro and in reconstituted mice in vivo. Therefore, our data suggest that RXRα down-regulation is a critical requirement for the generation of neutrophil granulocytes.
Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups
Authors: Zhang Chi-Yu , Wei Ji-Fu , He Shao-Heng
Published: October 2006

Background

It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS) coronavirus (CoV) is the cause of the SARS outbreak worldwide. The spike (S) protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown.

Results

By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163) in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24%) of positively selected sites was located in receptor-binding domain (RBD) than in heptad repeat (HR)1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208), and a greater percentage (25%) of these sites occurred in HR1–HR2 region than in RBD in 03-early-mid epidemic group (p = 0.0721). These suggest that functionally different domains of S protein may not experience same positive selection in each epidemic group. In addition, three specific replacements (F360S, T487S and L665S) were only found between 03-human SARS-CoVs and strains from 02–04 interspecies epidemic group, which reveals that selective sweep may also force the evolution of S genes before the jump of SARS-CoVs into human hosts. Since certain residues at these positively selected sites are associated with receptor recognition and/or membrane fusion, they are likely to be the crucial residues for animal-to-human transmission of SARS-CoVs, and subsequent adaptation to human hosts.

Conclusion

The variation of positive selective pressures and positively selected sites are likely to contribute to the adaptive evolution of S protein from animals to humans.
Elevated serum triglycerides is the strongest single indicator for the presence of metabolic syndrome in patients with type 2 diabetes
Authors: Kompoti Maria , Mariolis Anargiros , Alevizos Alevizos , Kyriazis Ioannis , Protopsaltis Ioannis , Dimou Eleni , Lentzas Ioannis , Levisianou Dimitrios , Gova Afroditi , Melidonis Andreas
Published: October 2006

Background

Patients with diabetes already fulfill one diagnostic criterion for MS according to the existing classifications. Our aim was to identify one single clinical parameter, which could effectively predict the presence of MS in patients with type 2 diabetes.

Methods

We studied all patients with type 2 diabetes who attended our Diabetes Outpatient Clinic during a three-month period. Waist circumference, blood pressure and serum lipids were measured. Establishment of MS diagnosis was based a) on National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria and b) on International Diabetes Federation (IDF) criteria. Receiver operating characteristic (ROC) analysis was applied in order to identify the clinical parameter with the highest predictive capability for MS. Among the 500 participating patients (231 males, 269 females), MS was diagnosed in 364 patients (72.8%) according to the NCEP ATP III criteria and in 408 patients (81.6%) according to the IDF criteria.

Results

For the NCEP ATP III classification, serum triglycerides (in the overall population), waist and HDL (in female population) demonstrated the highest predictive capability for MS (AUCs:0.786, 0.805 and 0.801, respectively). For the IDF classification, no single parameter reached an AUC > 0.800 in the overall population. In females, HDL displayed a satisfactory predictive capability for MS with an AUC which was significantly higher than the one in males (0.785 vs. 0.676, respectively, p < 0.05).

Conclusion

Elevated serum triglycerides strongly indicate the presence of MS in patients with type 2 diabetes. In female patients with type 2 diabetes, central obesity was the second stronger predictor of MS besides hypertriglyceridemia.
Migrating leukocytes are the source of Peroxiredoxin V during inflammation in the airways
Authors: Krutilina Raisa I , Kropotov Andrei V , Leutenegger Christian , Serikov Vladimir B
Published: October 2006

Background

We characterized changes in expression of the antioxidant protein Peroxiredoxin V (PRXV) during airway inflammation.

Methods

Studies in anesthetized rats and mice; PRXV expression determined by Western blot analyses and immunohistochemistry; PRXV m-RNA expression determined by Taq-Man RT-PCR.

Results

Bacterial lung inflammation did not change expression of PRXV in murine epithelia but produced massive influx of leukocytes highly expressing PRXV. Endotoxin and f-MLP induced leukocyte migration in rat trachea but did not change mRNA levels and PRXV protein expression in tracheal epithelial cells. In primary airway cell culture (cow), alveolar epithelial cells A549, or co-culture of A549 with murine macrophages RAW264.7, exposure to live bacteria increased expression of PRXV, which required serum. PRXV was secreted in vitro by epithelial and immune cells.

Conclusion

Inflammation increased expression of PRXV in airways by at least 2 mechanisms: cell population shift by massive influx of leukocytes expressing PRXV, and moderate post-transcriptional up-regulation of PRXV in epithelial cells.
Primary Hyperparathyroidism and the Presence of Kidney Stones Are Associated with Different Haplotypes of the Calcium-Sensing Receptor
Authors: Scillitani Alfredo , Guarnieri Vito , Battista Claudia , De Geronimo Simona , Muscarella Lucia Anna , Chiodini Iacopo , Cignarelli Mauro , Minisola Salvatore , Bertoldo Francesco , Francucci Cristiano M. , Malavolta Nazzarena , Piovesan Alessandro , Mascia Maria Lucia , Muscarella Silvana , Hendy Geoffrey N. , D’Agruma Leonardo , Cole David E. C.
Published: October 2006

Introduction: Three single-nucleotide polymorphisms in the calcium-sensing receptor gene (CASR) encoding the missense substitutions A986S, R990G, and Q1011E have been associated with normal variation in extracellular calcium homeostasis, both individually and in haplotype combination. The aim of this study was to examine haplotype associations in primary hyperparathyroidism (PHPT).

Patients and Methods: Patients with sporadic PHPT (n = 237) were recruited from endocrine clinics and healthy controls (n = 433) from a blood donor clinic, and levels of serum calcium, albumin, and PTH were measured. In PHPT patients, urinary calcium/creatinine clearances and bone mineral density at spine and femoral neck were measured and the presence of kidney stones and vertebral fractures identified. The CASR single-nucleotide polymorphisms were haplotyped by allele-specific sequencing.

Results: Four haplotypes (ARQ, SRQ, AGQ, and ARE) of eight were observed, in keeping with significant linkage disequilibrium, but haplotype frequencies did not show significant Hardy-Weinberg disequilibrium. The SRQ haplotype was more common in PHPT (125 of 474 alleles) than in controls (170 of 866 alleles, P = 0.006) and showed a significant (P = 0.006) gene-dosage effect. There was no significant association between haplotype and bone mineral density or fractures, but association with kidney stones was significant (P = 0.0007). In the stone-forming subgroup, the SRQ haplotype was underrepresented and AGQ overrepresented. Patients bearing the AGQ haplotype had an odds ratio of 3.8 (95% confidence interval, 1.30–11.3) for presentation with renal stones compared with the rest.

Conclusion: Our data indicate that the CASR SRQ haplotype is significantly associated with PHPT in our population. Within the PHPT patient population, the AGQ haplotype is significantly associated with kidney stones.
A Common Polymorphism in the Mineralocorticoid Receptor Modulates Stress Responsiveness
Authors: DeRijk Roel H. , Wüst Stefan , Meijer Onno C. , Zennaro Maria-Christina , Federenko Ilona S. , Hellhammer Dirk H. , Giacchetti Gilberta , Vreugdenhil Erno , Zitman Frans G. , de Kloet E. Ronald
Published: October 2006

Context: Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes.

Objective: The objective of the study was to investigate the role of the MR gene variant I180V in the neuroendocrine response to a psychosocial stressor and in electrolyte regulation.

Design: Associations between the MRI180V and outcome variables in a healthy cohort subjected to psychosocial challenge (Trier Social Stress Test) and in a mild hypertensive cohort exposed to acute salt loading (Weinberger’s test) were investigated. In vitro transactivational assays were applied to compare the effects of cortisol and aldosterone on the MRI180V.

Results: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma cortisol (P < 0.01), and heart rate responses (P < 0.05) to the Trier Social Stress Test than noncarriers (MR180I). After 3 d of a normal salt diet and the Weinberger’s test, no association was found with urinary sodium excretion, plasma aldosterone, and plasma renin activity or with changes in blood pressure, aldosterone, and renin responses. In vitro testing of the MR180V allele revealed a mild loss of function using cortisol as a ligand, compared with the MR180I allele. Significantly higher doses of cortisol were needed for half-maximal induction on the TAT-1 (P < 0.002), TAT-3 (P < 0.03), or mouse mammary tumor virus (P < 0.02) promoters, whereas maximal induction was not different. These differences were not observed using aldosterone as a ligand.

Conclusion: The findings reveal that cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the MR180V variant.
Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog
Authors: Ionescu Madalina , Frohman Lawrence A.
Published: October 2006

Context: Pulsatile GH secretion is considered important for many of the hormone’s physiological effects. Short-term GHRH infusions enhance GH pulsatility and increase IGF-I, but the short GHRH half-life limits its therapeutic use. A synthetic GHRH analog (CJC-1295) that binds permanently to endogenous albumin after injection (half-life = 8 d) stimulates GH and IGF-I secretion in several animal species and in normal human subjects and enhances growth in rats.

Objective: Our objective was to assess GH pulsatility after a single injection of CJC-1295 and determine which GH secretion parameters correlated to the increase in IGF-I production.

Methods: GH pulsatility was assessed by 20-min blood sampling during an overnight 12-h period in healthy 20- to 40-yr-old men before and 1 wk after injection of either 60 or 90 μg/kg CJC-1295.

Results: GH secretion was increased after CJC-1295 administration with preserved pulsatility. The frequency and magnitude of GH secretory pulses were unaltered. However, basal (trough) GH levels were markedly increased (7.5-fold; P < 0.0001) and contributed to an overall increase in GH secretion (mean GH levels, 46%; P < 0.01) and IGF-I levels (45%; P < 0.001). No significant differences were observed between the responses to the two drug doses. The IGF-I increases did not correlate with any parameters of GH secretion.

Conclusions: CJC-1295 increased trough and mean GH secretion and IGF-I production with preserved GH pulsatility. The marked enhancement of trough GH levels by continuous GHRH stimulation implicates the importance of this effect on increasing IGF-I. Long-acting GHRH preparations may have clinical utility in patients with intact pituitary GH secretory capability.
Slx9p facilitates efficient ITS1 processing of pre-rRNA in Saccharomyces cerevisiae
Authors: Bax Ralph , Raué Hendrik A. , Vos Jan C.
Published: October 2006

Slx9p (Ygr081cp) is a nonessential yeast protein previously linked genetically with the DNA helicase Sgs1p. Here we report that Slx9p is involved in ribosome biogenesis in the yeast Saccharomyces cerevisiae. Deletion of SLX9 results in a mild growth defect and a reduction in the level of 18S rRNA. Co-immunoprecipitation experiments showed that Slx9p is associated with 35S, 23S, and 20S pre-rRNA, as well as U3 snoRNA and, thus, is a bona fide component of pre-ribosomes. The most striking effects on pre-rRNA processing resulting from deletion of SLX9 is the accumulation of the mutually exclusive 21S and 27SA2 pre-rRNA. Furthermore, deletion of SLX9 is synthetically lethal with mutations in Rrp5p that block cleavage at either site A2 or A3. We conclude that Slx9p has a unique role in the processing events responsible for separating the 66S and 43S pre-ribosomal particles. Interestingly, homologs of Slx9p were found only in other yeast species, indicating that the protein has been considerably less well conserved during evolution than the majority of trans-acting processing factors.
Deficient immunity in head and neck cancer due to excessive monocyte production of prostaglandins
Authors: Berlinger Norman T.
Published: October 2006

Monocytes from patients with head and neck cancer produce excessive PGE2 which seems to be associated with decreased lymphoproliferation in vitro. This may be n pathological exaggeration of a normal homeostatic mechanism. It is speculated that a stimulus for excessive PGE2 production could be immune complexes. Although PGE2 suppresses many important immune processes relevant for neoplasia, it can also have complex and diverse effects on tumor cells. Caution should be exercised with human trials of prostaglandin synthctase inhibitors such as indomethacin.
Individual‐level and group‐level mediators of contact effects in Northern Ireland: The moderating role of social identification
Authors: Tausch Nicole , Tam Tania , Hewstone Miles , Kenworthy Jared , Cairns Ed
Published: October 2006

We tested a model which considered individual‐level (intergroup anxiety) and group‐level (perceived realistic and symbolic threats to the in‐group) threats as simultaneous mediators in the relationship between the quantity and quality of cross‐community contact and intergroup attitudes (Study 1, N =166) and trust (Study 2, N =163) in Northern Ireland. The studies tested the hypothesis that the strength of group‐identification moderates the importance of individual‐ vs. group‐level threats as predictors of attitudes and trust and as mediators of contact effects. Both anxiety and symbolic threat, but not realistic threat, emerged as predictors of the criterion variables and mediated contact effects. Our results provide support for the moderating role of identification and suggest that while symbolic threat predicts attitudes and trust for high, but not low identifiers, anxiety is a somewhat more important predictor for low than for high identifiers. We discuss these results against the background of current intergroup relations in Northern Ireland.
Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation
Authors: Oakley Holly , Cole Sarah L. , Logan Sreemathi , Maus Erika , Shao Pei , Craft Jeffery , Guillozet-Bongaarts Angela , Ohno Masuo , Disterhoft John , Van Eldik Linda , Berry Robert , Vassar Robert
Published: October 2006

Mutations in the genes for amyloid precursor protein (APP) and presenilins (PS1, PS2) increase production of β-amyloid 42 (Aβ42) and cause familial Alzheimer's disease (FAD). Transgenic mice that express FAD mutant APP and PS1 overproduce Aβ42and exhibit amyloid plaque pathology similar to that found in AD, but most transgenic models develop plaques slowly. To accelerate plaque development and investigate the effects of very high cerebral Aβ42levels, we generated APP/PS1 double transgenic mice that coexpress five FAD mutations (5XFAD mice) and additively increase Aβ42production. 5XFAD mice generate Aβ42almost exclusively and rapidly accumulate massive cerebral Aβ42levels. Amyloid deposition (and gliosis) begins at 2 months and reaches a very large burden, especially in subiculum and deep cortical layers. Intraneuronal Aβ42accumulates in 5XFAD brain starting at 1.5 months of age (before plaques form), is aggregated (as determined by thioflavin S staining), and occurs within neuron soma and neurites. Some amyloid deposits originate within morphologically abnormal neuron soma that contain intraneuronal Aβ. Synaptic markers synaptophysin, syntaxin, and postsynaptic density-95 decrease with age in 5XFAD brain, and large pyramidal neurons in cortical layer 5 and subiculum are lost. In addition, levels of the activation subunit of cyclin-dependent kinase 5, p25, are elevated significantly at 9 months in 5XFAD brain, although an upward trend is observed by 3 months of age, before significant neurodegeneration or neuron loss. Finally, 5XFAD mice have impaired memory in the Y-maze. Thus, 5XFAD mice rapidly recapitulate major features of AD amyloid pathology and may be useful models of intraneuronal Aβ42-induced neurodegeneration and amyloid plaque formation.
Age-Independent Synaptogenesis by Phosphoinositide 3 Kinase
Authors: Martín-Peña Alfonso , Acebes Angel , Rodríguez José-Rodrigo , Sorribes Amanda , de Polavieja Gonzalo G. , Fernández-Fúnez Pedro , Ferrús Alberto
Published: October 2006

Synapses are specialized communication points between neurons, and their number is a major determinant of cognitive abilities. These dynamic structures undergo developmental- and activity-dependent changes. During brain aging and certain diseases, synapses are gradually lost, causing mental decline. It is, thus, critical to identify the molecular mechanisms controlling synapse number. We show here that the levels of phosphoinositide 3 kinase (PI3K) regulate synapse number in bothDrosophilalarval motor neurons and adult brain projection neurons. The supernumerary synapses induced by PI3K overexpression are functional and elicit changes in behavior. Remarkably, PI3K activation induces synaptogenesis in aged adult neurons as well. We demonstrate that persistent PI3K activity is necessary for synapse maintenance. We also report that PI3K controls the expression and localization of synaptic markers in human neuroblastoma cells, suggesting that PI3K synaptogenic activity is conserved in humans. Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders.
Effects in Neocortical Neurons of Mutations of the Nav1.2 Na+Channel causing Benign Familial Neonatal-Infantile Seizures
Authors: Scalmani Paolo , Rusconi Raffaella , Armatura Elena , Zara Federico , Avanzini Giuliano , Franceschetti Silvana , Mantegazza Massimo
Published: October 2006

Mutations of voltage-gated Na+channels are the most common cause of familial epilepsy. Benign familial neonatal-infantile seizures (BFNIS) is an epileptic trait of the early infancy, and it is the only well characterized epileptic syndrome caused exclusively by mutations of Nav1.2 Na+channels, but no functional studies of BFNIS mutations have been done. The comparative study of the functional effects and the elucidation of the pathogenic mechanisms of epileptogenic mutations is essential for designing targeted and effective therapies. However, the functional properties of Na+channels and the effects of their mutations are very sensitive to the cell background and thus to the expression system used. We investigated the functional effects of four of the six BFNIS mutations identified (L1330F, L1563V, R223Q, and R1319Q) using as expression system transfected pyramidal and bipolar neocortical neurons in short primary cultures, which have small endogenous Na+current and thus permit the selective study of transfected channels. The mutation L1330F caused a positive shift of the inactivation curve, and the mutation L1563V caused a negative shift of the activation curve, effects that are consistent with neuronal hyperexcitability. The mutations R223Q and R1319Q mainly caused positive shifts of both activation and inactivation curves, effects that cannot be directly associated with a specific modification of excitability. Using physiological stimuli in voltage-clamp experiments, we showed that these mutations increase both subthreshold and action Na+currents, consistently with hyperexcitability. Thus, the pathogenic mechanism of BFNIS mutations is neuronal hyperexcitability caused by increased Na+current.
Individual Differences in Amygdala Activity Predict Response Speed during Working Memory
Authors: Schaefer Alexandre , Braver Todd S. , Reynolds Jeremy R. , Burgess Gregory C. , Yarkoni Tal , Gray Jeremy R.
Published: October 2006

The human amygdala has classically been viewed as a brain structure primarily related to emotions and dissociated from higher cognition. We report here findings suggesting that the human amygdala also has a role in supporting working memory (WM), a canonical higher cognitive function. In a first functional magnetic resonance imaging (fMRI) study (n= 53), individual differences in amygdala activity predicted behavioral performance in a 3-back WM task. Specifically, higher event-related amygdala amplitude predicted faster response time (RT;r= −0.64), with no loss of accuracy. This relationship was not contingent on mood state, task content, or personality variables. In a second fMRI study (n= 21), we replicated the key finding (r= −0.47) and further showed that the correlation between the amygdala and faster RT was specific to a high working memory load condition (3-back) compared with a low working memory load condition (1-back). These results support models of amygdala function that can account for its involvement not only in emotion but also higher cognition.
M-Like K+Currents in Type I Hair Cells and Calyx Afferent Endings of the Developing Rat Utricle
Authors: Hurley Karen M. , Gaboyard Sophie , Zhong Meng , Price Steven D. , Wooltorton Julian R. A. , Lysakowski Anna , Eatock Ruth Anne
Published: October 2006

Type I vestibular hair cells have large K+currents that, like neuronal M currents, activate negative to resting potential and are modulatable. In rodents, these currents are acquired postnatally. In perforated-patch recordings from rat utricular hair cells, immature hair cells [younger than postnatal day 7 (P7)] had a steady-state K+conductance (g−30) with a half-activation voltage (V1/2) of −30 mV. The size and activation range did not change in maturing type II cells, but, by P16, type I cells had added a K conductance that was on average fourfold larger and activated much more negatively. This conductance may comprise two components:g−60(V1/2of −60 mV) andg−80(V1/2of −80 mV).g−80washed out during ruptured patch recordings and was blocked by a protein kinase inhibitor.

M currents can include contributions from KCNQ and ether-a-go-go-related (erg) channels. KCNQ and erg channel blockers both affected the K+currents of type I cells, with KCNQ blockers being more potent at younger than P7 and erg blockers more potent at older than P16. Single-cell reverse transcription-PCR and immunocytochemistry showed expression of KCNQ and erg subunits. We propose that KCNQ channels contribute tog−30andg−60and erg subunits contribute tog−80.

Type I hair cells are contacted by calyceal afferent endings. Recordings from dissociated calyces and afferent endings revealed large K+conductances, including a KCNQ conductance. Calyx endings were strongly labeled by KCNQ4 and erg1 antisera. Thus, both hair cells and calyx endings have large M-like K+conductances with the potential to control the gain of transmission.
Bidirectional Trafficking of Prostaglandin E2Receptors Involved in Long-Term Potentiation in Visual Cortex
Authors: Akaneya Yukio , Tsumoto Tadaharu
Published: October 2006

Although prostaglandin E2(PGE2) has a broad spectrum of biological activities that have been confirmed by previous studies, the roles of PGE2in synaptic plasticity such as long-term potentiation (LTP) in the CNS have yet to be characterized in detail. The present results of electrophysiological and biochemical studies indicated that PGE2is actually produced in acute visual cortex slices in response to theta-bust stimulation (TBS) and is involved postsynaptically in TBS-induced LTP. RNA interference (RNAi) for PGE2receptor subtypes EP2 and EP3, which are known to upregulate and downregulate the level of cAMP, respectively, induced significant decreases and increases of LTP, respectively. Moreover, analysis of the localization of receptor subtypes at the membrane surface or cytosol showed that stimuli such as TBS regulate the trafficking of EP2 and EP3 between the membrane and cytosol of the postsynapses, rising up to and leaving the membrane, respectively, resulting in increased and decreased expression of EP2 and EP3 at the membrane, respectively. Increased activation of EP2 and decreased activation of EP3 by PGE2synergistically induce an increase in cAMP level, which may induce LTP. This causes activation of CREB (cAMP response element-binding protein) in the postsynaptic cells, which may be involved in the maintenance of LTP. These observations indicate that in TBS-induced LTP of the visual cortex, PGE2is released from the postsynaptic cells and then activates PGE2receptors at the postsynaptic membranes, which is regulated by trafficking of the differential PGE2receptor subtypes in an activity-dependent bidirectional manner.
The Innovation Activity in a Stagnating County of Hungary
Authors: Inzelt Annamaria , Szerb László
Published: October 2006

Despite recent theoretical and empirical developments, our knowledge about innovation is still limited. The major aim of this study is twofold: to examine innovation activities carried out in a region (county) of Hungary and to devote attention to the innovation characteristics of small and micro size businesses. The Oslo Manual-based survey technique was successfully adopted for the purposes of this investigation. Highly innovative small businesses employing highly educated workforce, producing mainly for local (domestic) markets were found to exist even in a lagging region of a developing country. However, typical innovation activity consists in a cheap, minor change of the product that does not increase the export propensity of the business. In addition to an insignificant influence of foreign ownership, low level of co-operation, limited use of outside help (government support) and lack of R&D activity are found to be the most important obstacles to further development and diffusion of innovation. The research method, as well as the lessons of this study, could be valuable for other regions and other less advanced countries.
Determination of phase relations in the Co–Cu–Ti system by the diffusion triple technique
Authors: Liu H.S. , Wang Y.M. , Zhang L.G. , Chen Q. , Zheng F. , Jin Z.P.
Published: October 2006

Two isothermal sections of the Co–Cu–Ti ternary system at 973 and 1123 K were experimentally determined using the diffusion triple technique together with scanning electron microscopy and electron probe microanalysis. The solubility of Cu (substituting Co) in CoTi increased from 22.8 at.% at 973 K to 28.1 at.% at 1123 K while that of Co (substituting Cu) in CuTi decreased from 11.1 to 8.8 at.% accordingly. In addition, the solubility limits of the third element in the binary compounds CoTi2, CuTi2, Cu4Ti3, and Cu3Ti2 were remarkable. Besides the solubility change, we found the Cu2Ti phase was stable at 1123 K but disappeared at 973 K. A ternary compound “m” with a composition range covering Co10Cu57Ti33 was detected at both isothermal sections. An invariant reaction Cu4Ti3 + CoTi ↔ CuTi + m at a temperature between 973 and 1023 K was deduced. Further investigations are necessary to confirm the reactions among Cu, Cu4Ti, Cu2Ti, Cu3Ti2, and “m” between 1023 and 1123 K.
Properties of ceramics in the system ZrB2–Ta5Si3
Authors: Talmy I.G. , Zaykoski J.A. , Opeka M.M. , Smith A.H.
Published: October 2006

Ceramics in the system ZrB2–Ta5Si3 were studied as candidates for the development of new ultra high-temperature ceramic materials. The ceramics were prepared by hot pressing at 1900–2200 °C in He. Mutual additions of ZrB2 and Ta5Si3 even in small amounts had significant densifying effects due to chemical interactions and solid solubility between the components, which have not been reported in the literature. Materials containing between 8 and 30 vol% Ta5Si3 exhibited less oxidation than pure ZrB2, which is the result of phase separation in surface borosilicate glass induced by Ta2O5. For higher concentrations, oxidation resistance substantially decreased with increasing Ta5Si3 content. The trend in the oxidation behavior of the materials showed significant dependence on the volume of oxidation products. Ceramics containing up to 10 mol% (30 vol%) Ta5Si3, which showed the highest oxidation resistance, also had the highest strength and hardness in the system, and are of interest for high-temperature structural applications in oxidizing environments.
A critical examination of the relationship between plastic deformation zone size and Young's modulus to hardness ratio in indentation testing
Authors: Chen J. , Bull S.J.
Published: October 2006

Existing indentation models (both analytical models and numerical analysis) show a linear relationship between δr/δm and H/Er, where δr and δm are the residual and maximum indentation depth, and Er and H are the reduced Young's modulus and hardness of the test material. Based on the analysis of Oliver and Pharr, a new relationship between δr/δm and H/Er has been derived in a different way without any additional assumptions, which is nonlinear, and this has been verified by finite element analysis for a range of bulk materials. Furthermore, this new relationship for residual depth is used to derive an analytical relationship for the radius of the plastic deformation zone Rp in terms of the residual depth, Young’s modulus, and hardness, which has also been verified by finite element simulations for elastic perfectly plastic materials with different work hardening behavior. The analytical model and finite element simulation confirms that the conventional relationship used to determine Rp developed by Lawn et al. overestimates the plastic deformation, especially for those materials with high E/H ratio. The model and finite element analysis demonstrate that Rp scales with δr, which is sensible given the self-similarity of the indentations at different scales, and that the ratio of Rp/δr is nearly constant for materials with different E/H, which contradicts the conventional view.