bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersion Compensation in 40 Gb/s Non-Return-to-Zero Optical Transmission System Using Coupled-Cavity Photonic Crystals
Authors: Fukamachi Toshihiko , Hosomi Kazuhiko , Sugawara Toshiki , Kikuchi Nobuhiko , Katsuyama Toshio , Arakawa Yasuhiko
Published: October 2005

We experimentally demonstrated the dispersion compensation in a 40 Gb/s non-return-to-zero optical transmission, using photonic crystal coupled-cavity waveguides (PhC CCWs). In this experiment, the PhC CCWs consisted of one-dimensional SiO2/Ta2O5 thin film structures. The deteriorated optical signal after traveling a single-mode fiber (SMF) was compensated for by transmitting three times into a ten-stack PhC CCW. As a result, a well-defined eye pattern was obtained at a distance of 4.5 km for an SMF, although it closed without the CCWs. This indicated that the CCWs compensated for a dispersion of more than 60 ps/nm. This is the first experimental result showing that the PhC can be used to construct a compact dispersion compensator in a 40 Gb/s optical transmission.
Role of Nitrogen Incorporation into Hf-Based High-k Gate Dielectrics for Termination of Local Current Leakage Paths
Authors: Watanabe Heiji , Kamiyama Satoshi , Umezawa Naoto , Shiraishi Kenji , Yoshida Shiniti , Watanabe Yasumasa , Arikado Tsunetoshi , Chikyow Toyohiro , Yamada Keisaku , Yasutake Kiyoshi
Published: October 2005

We studied effects of nitrogen incorporation into Hf-based high-k gate dielectrics on local insulating properties by conductive atomic force microscopy. Nitrogen-incorporated HfSiO/HfO2/SiO2 gate stacks exhibited excellent dielectric reliability, whereas we observed the creation of local leakage sites for untreated gate stacks, i.e., without nitridation. Both types of high-k dielectric layers were crystallized, and there was no relationship between the current leakage sites and surface morphology. These findings indicate that grain boundaries of the high-k films do not act as the leakage sites. Instead, we propose nitrogen incorporation as an important method for terminating the current leakage paths and discuss detailed mechanisms based on first-principles calculations.
Metamorphosed palaeosols associated with Cretaceous fossil forests, Alexander Island, Antarctica
Authors: Howe J. , Francis J.E.
Published: October 2005

Fossil soils are present within mid-Cretaceous fluvial sediments of the Fossil Bluff Group, Alexander Island, Antarctica. The palaeosols contain
in situ
fossil trees and rooted plants. These palaeosols are typically composed of two dominant horizons: an upper organic-rich horizon with identifiable plant remains, and a lower horizon with well-developed blocky ped structures, clay cutans and mottling. These features are typical of modern soils in seasonally dry climates. Although evidence of flooding is apparent from interbedded fluvial sandstones and mudstones, the palaeosols indicate that this high-latitude mid-Cretaceous environment was predominantly seasonally dry. The presence of the zeolites laumontite, prehnite and pumpellyite indicates a later metamorphic overprint on the palaeosols, resulting from burial diagenesis of this region at depths of about 3.8–5.2 km and temperatures of 150–170 °C.
Early Silurian magmatism and the Scandian evolution of the Kalak Nappe Complex, Finnmark, Arctic Norway
Authors: Kirkland C.L. , Daly J.S. , Whitehouse M.J.
Published: October 2005

Three orogenic events, Porsanger (pre-800 Ma), Finnmarkian (490–540 Ma) and Scandian (400–425 Ma) have been proposed to explain the evolution of the Kalak Nappe Complex, a major component of the Caledonian orogen in Norway. The Kalak Nappe Complex has been considered as Baltoscandian passive margin metasediments telescoped eastwards onto the Baltic Shield. Two granitoid bodies with a weighted mean U–Pb zircon age of 438 ± 2 Ma cut the Hellefjord Schist, regarded as the highest stratigraphic unit in the Kalak Nappe Complex. A volcaniclastic unit within the Hellefjord Schist yields an identical U–Pb zircon age of 438 ± 4 Ma. Magmatism and sedimentation are synchronous within analytical error. The Hellefjord Schist cannot have been affected by Finnmarkian or Porsanger orogenesis and cannot be part of a continuous stratigraphic package. A Laurentian affinity for these sediments is suggested and radical revision of the tectonostratigraphy is required. The Hellefjord Schist is reassigned to the Magerøy Nappe of the Upper–Uppermost Allochthon. As the entire stratigraphy is infolded with the Hellefjord Schist a major deformation phase of Scandian age affected the Kalak Nappe Complex. The Hellefjord Schist represents a Laurentian flysch sequence that was juxtaposed with Baltica during the Scandian Orogeny.
Evolution of damage zone geometry and intensity in porous sandstone: insight gained from strain energy density
Authors: Okubo Chris. H. , Schultz Richard A.
Published: October 2005

In porous geological materials such as sandstone or limestone, fault-related damage zones form arrays of deformation bands, which are planar discontinuities characterized by localized shear and porosity change. We show that the geometry and intensity of fault-related deformation band damage zones is systematic and predictable using standard strain energy density-based criteria. These criteria are used to successfully predict the tendencies for the nucleation and for the propagation of deformation bands as observed in a classic outcrop of fault-related damage zones within the brittly deformed Jurassic Wingate Sandstone exposed in the Laramide-aged Uncompahgre fold, in western Colorado, USA. The separate distributions of volumetric and distortional strain energy density are calculated for the interpreted geometry and stress state of the causative Laramide-aged thrust fault displacements from boundary element calculations of the attendant slip-induced local stresses. Volumetric strain energy density predicts the tendency for deformation band nucleation, the growth stage at which the deformation bands are defined by pore space dilatancy or collapse. Deformation band propagation, where shear occurs along the band, is predicted by distortional strain energy density. Further deformation bands at the Uncompahgre are predicted and observed to be characterized by shear-enhanced dilation.
Effects of cold cardioplegia on pH, Na, and Ca in newborn rabbit hearts
Authors: Anderson Steven E. , Liu Hong , Beyschau Andrea , Cala Peter M.
Published: October 2005

Many studies suggest myocardial ischemia-reperfusion (I/R) injury results largely from cytosolic proton (Hi)-stimulated increases in cytosolic Na (Nai), which cause Na/Ca exchange-mediated increases in cytosolic Ca concentration ([Ca]i). Because cold, crystalloid cardioplegia (CCC) limits [H]i, we tested the hypothesis that in newborn hearts, CCC diminishes Hi, Nai, and Cai accumulation during I/R to limit injury. NMR measured intracellular pH (pHi), Nai, [Ca]i, and ATP in isolated Langendorff-perfused newborn rabbit hearts. The control ischemia protocol was 30 min for baseline perfusion, 40 min for global ischemia, and 40 min for reperfusion, all at 37°C. CCC protocols were the same, except that ice-cold CCC was infused for 5 min before ischemia and heart temperature was lowered to 12°C during ischemia. Normal potassium CCC solution (NKCCC) was identical to the control perfusate, except for temperature; the high potassium (HKCCC) was identical to NKCCC, except that an additional 11 mmol/l KCl was substituted isosmotically for NaCl. NKCCC and HKCCC were not significantly different for any measurement. The following were different ( P < 0.05). End-ischemia pHi was higher in the CCC than in the control group. Similarly, CCC limited increases in Nai during I/R. End-ischemia Nai values (in meq/kg dry wt) were 115 ± 16 in the control group, 49 ± 13 in the NKCCC group, and 37 ± 12 in the HKCCC group. CCC also improved [Ca]i recovery during reperfusion. After 40 min of reperfusion, [Ca]i values (in nmol/l) were 302 ± 50 in the control group, 145 ± 13 in the NKCCC group, and 182 ± 19 in the HKCCC group. CCC limited ATP depletion during ischemia and improved recovery of ATP and left ventricular developed pressure and decreased creatine kinase release during reperfusion. Surprisingly, CCC did not significantly limit [Ca]i during ischemia. The latter is explained as the result of Ca release from intracellular buffers on cooling.
Specific serine proteases selectively damage KCNH2 (hERG1) potassium channels and IKr
Authors: Rajamani Sridharan , Anderson Corey L. , Valdivia Carmen R. , Eckhardt Lee L. , Foell Jason D. , Robertson Gail A. , Kamp Timothy J. , Makielski Jonathan C. , Anson Blake D. , January Craig T.
Published: October 2005

KCNH2 ( hERG1) encodes the α-subunit proteins for the rapidly activating delayed rectifier K+ current ( IKr), a major K+ current for cardiac myocyte repolarization. In isolated myocytes IKr frequently is small in amplitude or absent, yet KCNH2 channels and IKr are targets for drug block or mutations to cause long QT syndrome. We hypothesized that KCNH2 channels and IKr are uniquely sensitive to enzymatic damage. To test this hypothesis, we studied heterologously expressed K+, Na+, and L-type Ca2+ channels, and in ventricular myoctyes IKr, slowly activating delayed rectifier K+ current ( IKs), and inward rectifier K+ current ( IK1), by using electrophysiological and biochemical methods. 1) Specific exogenous serine proteases (protease XIV, XXIV, or proteinase K) selectively degraded KCNH2 current ( IKCNH2) and its mature channel protein without damaging cell integrity and with minimal effects on the other channel currents; 2) immature KCNH2 channel protein remained intact; 3) smaller molecular mass KCNH2 degradation products appeared; 4) protease XXIV selectively abolished IKr; and 5) reculturing HEK-293 cells after protease exposure resulted in the gradual recovery of IKCNH2 and its mature channel protein over several hours. Thus the channel protein for IKCNH2 and IKr is uniquely sensitive to proteolysis. Analysis of the degradation products suggests selective proteolysis within the S5-pore extracellular linker, which is structurally unique among Kv channels. These data provide 1) a new mechanism to account for low IKr density in some isolated myocytes, 2) evidence that most complexly glycosylated KCNH2 channel protein is in the plasma membrane, and 3) new insight into the rate of biogenesis of KCNH2 channel protein within cells.
Changes in Endothelial Function Precede the Clinical Disease in Women in Whom Preeclampsia Develops
Authors: Khan Faisel , Belch Jill J.F. , MacLeod Maureen , Mires Gary
Published: October 2005

Endothelial dysfunction is important in the pathophysiology of preeclampsia. No study has examined endothelial function sequentially at different gestations before development of the clinical syndrome and after delivery (to compare maternal from placental influences). We sought to determine whether endothelial function changes before the clinical development of preeclampsia. We measured skin microvascular function using iontophoresis of acetylcholine and sodium nitroprusside, and laser Doppler imaging at 22, 26, 34 weeks’ gestation and 6 weeks postpartum in women identified as being at increased risk of preeclampsia, based on uterine artery Doppler waveforms at 18 to 20 weeks, and controls with normal Doppler waveforms. Fifty-four women remained normotensive and preeclampsia developed in 15. In normotensive and preeclamptic women, acetylcholine responses were augmented during pregnancy compared with postpartum responses (
P
<0.001). Sodium nitroprusside responses were augmented during pregnancy compared with those postpartum (
P
<0.005) in preeclamptic women only. Microvascular responses were augmented in women in whom preeclampsia developed, compared with those in normotensive women, at 26 and 34 weeks for acetylcholine (
P
<0.05 and
P
<0.001, respectively) and at 22 and 26 weeks for sodium nitroprusside (
P
<0.05 and
P
<0.02, respectively). Postpartum acetylcholine and sodium nitroprusside responses were not significantly different between preeclamptic and normal women. Microvascular responses are enhanced during pregnancy in women in whom preeclampsia develops to a level above that seen in normotensive women. These changes precede the onset of clinical disease and might be related to a compensatory increased sensitivity of the microcirculation to nitric oxide.
Changes in Aortic Stiffness and Augmentation Index After Acute Converting Enzyme or Vasopeptidase Inhibition
Authors: Mitchell Gary F. , Lacourcière Yves , Arnold J. Malcolm O. , Dunlap Mark E. , Conlin Paul R. , Izzo Joseph L.
Published: October 2005

Augmentation index (AI), a measure of enhanced wave reflection, has been proposed as a bedside measure of aortic stiffness. However, because AI is potentially sensitive to various factors other than vessel wall stiffness, the utility of AI as a stiffness indicator may be limited. To assess relations between AI and vascular properties, we used arterial tonometry and aortic Doppler flow to evaluate trough (24 hours) and peak (4 hours) pulsatile hemodynamics and pulse wave velocity in 159 individuals with systolic hypertension at the completion of a 12-week period of monotherapy with the vasopeptidase inhibitor omapatrilat (80 mg; n=75) or the converting enzyme inhibitor enalapril (40 mg; n=84). Characteristic impedance (Z
c
) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Systolic ejection period (SEP), timing of wave reflection, and AI were assessed from the carotid waveform. Comparable acute reductions in mean pressure were associated with greater reductions in peripheral resistance with enalapril, whereas neither drug had an acute effect on Z
c
. Both drugs reduced AI, but neither drug altered the timing of wave reflection. Both drugs increased heart rate and shortened SEP. Multiple regression analysis demonstrated that the acute reduction in AI was most affected by reductions in SEP and peripheral resistance. Change in AI was inversely related to change in Z
c
and pulse wave velocity did not enter the model. Our findings indicate that AI is a complex surrogate marker that is inversely related to changes in proximal aortic stiffness in systolic hypertension.
Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice
Authors: Dikalova Anna , Clempus Roza , Lassègue Bernard , Cheng Guangjie , McCoy James , Dikalov Sergey , Martin Alejandra San , Lyle Alicia , Weber David S. , Weiss Daiana , Taylor W. Robert , Schmidt Harald H.H.W. , Owens Gary K. , Lambeth J. David , Griendling Kathy K.
Published: October 2005

Background—

Reactive oxygen species (ROS) have been implicated in the development of cardiovascular pathologies. NAD(P)H oxidases (Noxes) are major sources of reactive oxygen species in the vessel wall, but the importance of individual Nox homologues in specific layers of the vascular wall is unclear. Nox1 upregulation has been implicated in cardiovascular pathologies such as hypertension and restenosis.

Methods and Results—

To investigate the pathological role of Nox1 upregulation in vascular smooth muscle, transgenic mice overexpressing Nox1 in smooth muscle cells (Tg
SMCnox1
) were created, and the impact of Nox1 upregulation on the medial hypertrophic response during angiotensin II (Ang II)–induced hypertension was studied. These mice have increased expression of Nox1 protein in the vasculature, which is accompanied by increased superoxide production. Infusion of Ang II (0.7 mg/kg per day) into these mice for 2 weeks led to a potentiation of superoxide production compared with similarly treated negative littermate controls. Systolic blood pressure and aortic hypertrophy were also markedly greater in Tg
SMCnox1
mice than in their littermate controls. To confirm that this potentiation of vascular hypertrophy and hypertension was due to increased ROS formation, additional groups of mice were coinfused with the antioxidant Tempol. Tempol decreased the level of Ang II-induced aortic superoxide production and partially reversed the hypertrophic and hypertensive responses in these animals.

Conclusions—

These data indicate that smooth muscle-specific Nox1 overexpression augments the oxidative, pressor, and hypertrophic responses to Ang II, supporting the concept that medial Nox1 participates in the development of cardiovascular pathologies.
Matrix Metalloproteinase-13/Collagenase-3 Deletion Promotes Collagen Accumulation and Organization in Mouse Atherosclerotic Plaques
Authors: Deguchi Jun-O , Aikawa Elena , Libby Peter , Vachon Jeffrey R. , Inada Masaki , Krane Stephen M. , Whittaker Peter , Aikawa Masanori
Published: October 2005

Background—

Interstitial collagen plays a crucial structural role in arteries. Matrix metalloproteinases (MMPs), including MMP-13/collagenase-3, likely contribute to collagen catabolism in atherosclerotic plaques.

Methods and Results—

To test the hypothesis that a specific MMP-collagenase influences the development and structure of atherosclerotic plaques, this study used atherosclerosis-susceptible apolipoprotein E–deficient mice that lack MMP-13/collagenase-3 (

Mmp-13
−/−
/apoE
−/−

) or express wild-type MMP-13/collagenase-3 (

Mmp-13
+/+
/apoE
−/−

). Both groups consumed an atherogenic diet for 5 (n=8) or 10 weeks (n=9). Histological analyses of the aortic root of both groups revealed similar plaque size and accumulation of smooth muscle cells (a collagen-producing cell type) and macrophages (a major source of plaque collagenases) after 5 and 10 weeks of atherogenic diet. By 10 weeks, the plaques of

Mmp-13
−/−
/apoE
−/−

mice contained significantly more interstitial collagen than those of

Mmp-13
+/+
/apoE
−/−

mice (
P
<0.01). Furthermore, quantitative optical analyses revealed thinner and less aligned periluminal collagen fibers within the plaques of

Mmp-13
+/+
/apoE
−/−

mice versus those from

Mmp-13
−/−
/apoE
−/−

mice.

Conclusions—

These data support the hypothesis that MMP-13/collagenase-3 plays a vital role in the regulation and organization of collagen in atherosclerotic plaques.
Sustained Whole-Body Functional Rescue in Congestive Heart Failure and Muscular Dystrophy Hamsters by Systemic Gene Transfer
Authors: Zhu Tong , Zhou Liqiao , Mori Satsuki , Wang Zhong , McTiernan Charles F. , Qiao Chunping , Chen Chunlian , Wang Dao Wen , Li Juan , Xiao Xiao
Published: October 2005

Background—

The success of muscular dystrophy gene therapy requires widespread and stable gene delivery with minimal invasiveness. Here, we investigated the therapeutic effect of systemic delivery of adeno-associated virus (AAV) vectors carrying human δ-sarcoglycan (δ-SG) gene in TO-2 hamsters, a congestive heart failure and muscular dystrophy model with a δ-SG gene mutation.

Methods and Results—

A single injection of double-stranded AAV serotype 8 vector carrying human δ-SG gene without the need of any physical or pharmaceutical interventions achieved nearly complete gene transfer and tissue-specific expression in the heart and skeletal muscles of the diseased hamsters. Broad and sustained (>12 months) restoration of the missing δ-SG gene in the TO-2 hamsters corrected muscle cell membrane leakiness throughout the body and normalized serum creatine kinase levels (a 50- to 100-fold drop). Histological examination revealed minimal or the absence of central nucleation, fibrosis, and calcification in the skeletal muscle and heart. Whole-body functional analysis such as treadmill running showed dramatic improvement, similar to the wild-type F1B hamsters. Furthermore, cardiac functional studies with echocardiography revealed significantly increased percent fractional shortening and decreased left ventricular end-diastolic and end-systolic dimensions in the treated TO-2 hamsters. The survival time of the animals was also dramatically extended.

Conclusions—

Systemic gene transfer of δ-SG by the AAV serotype 8 vector could effectively ameliorate cardiac and skeletal muscle pathology, profoundly improve cardiac and whole-body functions, and significantly prolong the lifespan of the treated TO-2 hamsters.
Bioinformatic Analysis of Circadian Gene Oscillation in Mouse Aorta
Authors: Rudic R. Daniel , McNamara Peter , Reilly Dermot , Grosser Tilo , Curtis Anne-Marie , Price Thomas S. , Panda Satchidananda , Hogenesch John B. , FitzGerald Garret A.
Published: October 2005

Background—

Circadian rhythmicity of many aspects of cardiovascular function—blood pressure, coagulation and contractile function—is well established, as is diurnal variation in important clinical events, such as myocardial infarction and stroke. Here, we undertake studies to globally assess circadian gene expression in murine aorta.

Methods and Results—

Aortae from mice were harvested at 4-hour intervals for 2 circadian cycles (48 hours). Gene expression was assessed by expression profiling and subjected to a gene ontology bioinformatics analysis. Three hundred thirty transcripts exhibited a circadian pattern of oscillation in mouse aorta, including those intrinsic to the function of the molecular clock. In addition, many genes relevant to protein folding, protein degradation, glucose and lipid metabolism, adipocyte maturation, vascular integrity, and the response to injury are also included in this subset of roughly 7000 genes screened for circadian oscillation.

Conclusions—

Detection of functional cassettes of vascular genes that exhibit circadian regulation in the mouse will facilitate elucidation of the mechanisms by which the molecular clock may interact with environmental variables to modulate cardiovascular function and the response to therapeutic interventions.
"Creeping Spatiality": The Location of Nous in Plotinus' Universe
Authors:   Wilberding
Published: October 2005

There is a well-known tension in Plotinus' thought regarding the location of the intelligible region. He appears to make three mutually incompatible claims about it: (1) it is everywhere; (2) it is nowhere; and (3) it borders on the heavens, where the third claim is associated with Plotinus' affection for cosmic religion. Traditionally, although scholars have found a reasonable way to make sense of the compatibility of the first two claims, they have sought to relieve the tension generated by (3) by both downplaying the importance of cosmic religion to Plotinus and reinterpreting his spatial language metaphorically. In this paper I argue that both of these maneuvers are unsatisfactory. Rather, it is possible to reconcile Plotinus' metaphysics with the world-view of cosmic religion (CR world-view), i.e., to retain the spatial sense of Plotinus' language without making his metaphysics incoherent.In the first part of this paper, I show that cosmic religion is not just an awkward appendage to Plotinus' metaphysics. After explaining what cosmic religion involves, I argue that the CR world-view is in fact central to his natural philosophy. Then, I turn to the problem of the compatibility between cosmic religion and Plotinus' thought. By carefully considering how Aristotle's Prime Mover is present to his universe, I show how we can make claims (2) and (3) compatible for Plotinus. Then, I argue that Plotinus' own account of the omnipresence of soul and its powers' actualizations in particular locations provides a parallel to the problem of the compatibility between (1) and (3), and further that these two accounts can be combined to resolve completely the tension between the CR world-view and Plotinus' metaphysics. In the final section, I discuss the implications this has for our understanding of the soul's ascent and descent.
Vestigial Scenes in John: Settings without Dramatization
Authors: Hedrick Charles
Published: October 2005

John 2:12 comprises little more than a scene setting and plays no evident role in John's overall narrative. Thus it is surprising to find it in a text whose "author" knows that space is limited (John 21:25) and so narrates things serving a soteriological purpose (John 20:30-31). This paper compares John 2:12 to other similar brief independent "scenes" in the gospel, and identifies their literary character as "vestigial scenes": these are scene settings, which for some reason are not dramatized. The paper concludes by exploring reasonable options for explaining their presence in the text.
Assumptions of the Dialectical Method: The Centrality of Labor for the Human Species, Its History, and Individuals
Authors: Paolucci Paul
Published: October 2005

Critical Sociology has previously published examinations of the ontological assumptions Marx incorporated into his epistemological approach. These principles must be understood if intelligibility is to be made of his overall outlook. However, one such previous work failed to recognize the centrality of labor in Marx's ontological-epistemological assumptions. This omission should be rectified. The dimensions of this assumption involve the importance of labor for the species, the importance of labor for human history, and the importance of labor for individuals. A secondary focus attempts to demonstrate the implication of each of these for the conditions of life under capitalism.
Autonomous and interdependent development of two language systems in Japanese/English simultaneous bilinguals: Evidence from question formation
Authors: Mishina-Mori Satomi
Published: October 2005

The recent finding that two languages develop autonomously in young simultaneous bilinguals has been challenged by several researchers. The current study attempts to show that both independence and interdependence are involved in early bilingual development. Longitudinal analysis of the acquisition of question formation was conducted in two Japanese/English bilingual children. The results indicate that the development of the two grammars is basically autonomous, but cross-language effects are also present, although not in both children. It is suggested that cross-linguistic cue competition best captures the transfer process, and that linguistic environment for each child may be the source of individual differences in the use of cross-linguistic structures. Implications of the current results for language acquisition theories are discussed.
The novel protein KBP regulates mitochondria localization by interaction with a kinesin-like protein
Authors: Wozniak Marcin J , Melzer Martina , Dorner Cornelia , Haring Hans-Ulrich , Lammers Reiner
Published: October 2005

Background

Members of the Kinesin-3 family of kinesin-like proteins mediate transport of axonal vesicles (KIF1A, KIF1Bβ), distribution of mitochondria (KIF1Bα) and anterograde Golgi to ER vesicle transport (KIF1C). Until now, little is known about the regulation of kinesin-like proteins. Several proteins interact with members of this protein family. Here we report on a novel,

K

IF1

b

inding

p

rotein (KBP) that was identified in yeast two-hybrid screens.

Results

KBP was identified by using the yeast-two-hybrid system with an amino-terminal fragment of KIF1C as a bait that is strongly homologous to KIF1B. Here we investigated the interaction of KBP and KIF1B. The full length proteins coimmunoprecipitated after overexpression and in untransfected 293 cells. Immunofluorescence experiments revealed that KBP was mainly localized to mitochondria, as has been described for KIF1Bα. Overexpression of a deletion mutant or reduction of the KBP protein level using an anti-sense construct led to an aggregation of mitochondria. Such an effect is probably due to the lower activity of KIF1Bα in the absence of KBP, as was revealed in motility assays.

Conclusion

KBP is a new binding partner for KIF1Bα that is a regulator of its transport function and thus represents a new type of kinesin interacting protein.
Systematic mutation analysis of KIAA0767 and KIAA1646 in chromosome 22q-linked periodic catatonia
Authors: Stöber Gerald , Kohlmann Bernd , Siekiera Markus , Rubie Claudia , Gawlik Micha , Möller-Ehrlich Kerstin , Meitinger Thomas , Bettecken Thomas
Published: October 2005

Background

Periodic catatonia is a familial subtype of schizophrenia characterized by hyperkinetic and akinetic episodes, followed by a catatonic residual syndrome. The phenotype has been evaluated in two independent genome-wide linkage scans with evidence for a major locus on chromosome 15q15, and a second independent locus on chromosome 22qtel.

Methods

In the positional and brain-expressed candidate genes KIAA0767 and KIAA1646, we searched for variants in the complete exons and adjacent splice-junctions as well as in parts of the 5'- and 3'-untranslated regions by means of a systematic mutation screening in individuals from chromosome 22q-linked pedigrees.

Results

The mutation scan revealed 24 single nucleotide polymorphisms, among them two rare codon variants (KIAA0767: S159I; KIAA1646: V338G). However, both were neither found segregating with the disease in the respective pedigree nor found at a significant frequency in a case-control association sample.

Conclusion

Starting from linkage signals at chromosome22qtelin periodic catatonia, we screened two positional brain-expressed candidate genes for genetic variation. Our study excludes genetic variations in the coding and putative promoter regions of KIAA0767 and KIAA1646 as causative factors for periodic catatonia.
A sonography assisted technique for the removal of a femoral interlocking nail – a technical note
Authors: Tsai Kai-Jow , Shen Po-Wen , Hutton William C
Published: October 2005

Background

Open methods for removal of femoral interlocking nails involve an incision (up to 10 cm) over the trochanter to find the tip of the nail. The distal locking screws are some times difficult to palpate and an incision (up to about 5 cm) is often needed for exposure. Intra-operative fluoroscopy is often used as an adjunct technique to minimize the surgical wound. However, patients and surgeons are exposed to a radiation hazard. Sonography can provide a real-time and efficient alternative to fluoroscopy.

Methods

Sonography of soft tissue has been established to identify a foreign body. A metallic implant has a hyperechoic image; therefore, we can identify the correct position of the screws preoperatively and intraoperatively.

Results

We have developed a technique using sonography and minimal incisions for the removal of a femoral interlocking nail. The proximal wound is 2.5 cm in length and the wound is 0.5 cm in length for each distal locking screw.

Conclusion

The sonography can be used to minimize the length of incision and prevent radiation exposure in the removal of intramedullary femoral nails.
One Size Doesn’t Fit All: Ethics of international nurse recruitment from the conceptual framework of Stakeholder Interests
Authors: Xu Yu , Zhang Jianhui
Published: October 2005

This theoretical study examines the ethics of international nurse recruitment from the conceptual framework of stakeholder interests. It argues that there are stakeholders at individual, institutional, national and international levels, with overlapping but, more often, different or even conflicting interests. Depending on the interests of given stakeholders, different conclusions regarding the ethics of international nurse recruitment may be reached. There is no right or wrong with these varying ethical positions because they reflect different beliefs and philosophies that are not amenable to value judgment. To illustrate and support this line of argument, this article analyzes the underpinnings of two ethical standards published by the International Council of Nurses and the UK Department of Health. In addition, a case study on China augments the argument by demonstrating limitations of the one-size-fits-all approach to the issue. The most important question in understanding and evaluating the ethical standards of international nurse recruitment is to know whose interests they are designed to represent and protect.
Practising Virtue: A challenge to the view that a virtue centred approach to ethics lacks practical content
Authors: Begley Ann Marie
Published: October 2005

A virtue centred approach to ethics has been criticized for being vague owing to the nature of its central concept, the paradigm person. From the perspective of the practitioner the most damaging charge is that virtue ethics fails to be action guiding and, in addition to this, it does not offer any means of act appraisal. These criticisms leave virtue ethics in a weak position vis-à-vis traditional approaches to ethics. The criticism is, however, challenged by Hursthouse in her analysis of the accounts of right action offered by deontology, utilitarianism and virtue ethics. It is possible to defend the action guiding nature of virtue ethics: there are virtue rules and exemplars to guide action. Insights from Aristotle’s practical approach to ethics are considered alongside Hursthouse’s analysis and it is suggested that virtue ethics is also capable of facilitating action appraisal. It is at the same time acknowledged that approaches to virtue ethics vary widely and that the challenges offered here would be rejected by those who embrace a radical replacement virtue approach.
Utilization of Diagnostic Studies in the Pretreatment Evaluation of Invasive Cervical Cancer in the United States: Results of Intergroup Protocol ACRIN 6651/GOG 183
Authors: Amendola Marco A. , Hricak Hedvig , Mitchell Donald G. , Snyder Bradley , Chi Dennis S. , Long Harry J. , Fiorica James V. , Gatsonis Constantine
Published: October 2005

Purpose

To review the current utilization of diagnostic tests prescribed by the International Federation of Gynecology and Obstetrics (FIGO) clinical staging guidelines in the pretreatment work-up of invasive cervical cancer, and to compare the data with those of previous patterns of care studies.

Patients and Methods

This interdisciplinary American College of Radiology Imaging Network/Gynecologic Oncology Group prospective clinical trial was conducted between March 1, 2000, and November 11, 2002. Twenty-five participating institutions, all from the United States, enrolled a total of 208 patients. Only patients scheduled for surgery with biopsy-confirmed cervical cancer of clinical FIGO stage IB or higher were eligible. The patterns of care data analysis was based on 197 patients who met all inclusion criteria. The conventional FIGO-recommended tests used for pre-enrollment FIGO clinical stage classification were at the discretion of the treating physician; overall frequency of use was tabulated for each test.

Results

Use of cystoscopy (8.1%) and sigmoidoscopy or proctoscopy (8.6%) was significantly lower than in 1988 to 1989 (P < .0001 in each instance). Intravenous urography was used in only 1% of patients as compared with 42% in 1988 to 1989 and 91% in 1983. No patient included in the data analysis had barium enema or lymphangiography. Only 26.9% of patients had examination under anesthesia for FIGO clinical staging.

Conclusion

There is a large discrepancy between the diagnostic tests recommended by FIGO and the actual tests used for cervical cancer staging, suggesting a need to reassess the relevance of the FIGO guidelines to current clinical practice in the United States.
Immunohistochemical Expression of DNA Repair Proteins in Familial Breast Cancer DifferentiateBRCA2-Associated Tumors
Authors: Honrado Emiliano , Osorio Ana , Palacios José , Milne Roger L. , Sánchez Lydia , Díez Orland , Cazorla Alicia , Syrjakoski Kirsi , Huntsman David , Heikkilä Päivi , Lerma Enrique , Kallioniemi Anne , Rivas Carmen , Foulkes William D. , Nevanlinna Heli , Benítez Javier
Published: October 2005

Purpose

Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups.

Materials and Methods

We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen.

Results

We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%.

Conclusion

Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.
Ionizing Radiation and Tobacco Use Increases the Risk of a Subsequent Lung Carcinoma in Women With Breast Cancer: Case-Only Design
Authors: Prochazka Michaela , Hall Per , Gagliardi Giovanna , Granath Fredrik , Nilsson Bo N. , Shields Peter G. , Tennis Meredith , Czene Kamila
Published: October 2005

Purpose

To analyze the risk of lung cancer in women treated with radiotherapy for breast cancer. We accessed the lung dose in relation to different radiotherapy techniques, provided the excess relative risk (ERR) estimate for radiation-associated lung cancer, and evaluated the influence of tobacco use.

Patients and Methods

The Swedish Cancer Registry was used to identify 182 women diagnosed with breast and subsequent lung cancers in Stockholm County during 1958 to 2000. Radiotherapy was administered to 116 patients. Radiation dose was estimated from the original treatment charts, and information on smoking history was searched for in case records and among relatives. The risk of lung cancer was assessed in a case-only approach, where each woman contributed a pair of lungs.

Results

The average mean lung dose to the ipsilateral lung was 17.2 Gy (range, 7.1 to 32.0 Gy). A significantly increased relative risk (RR) of a subsequent ipsilateral lung cancer was observed at ≥ 10 years of follow-up (RR = 2.04; 95% CI, 1.24 to 3.36). Squamous cell carcinoma (RR = 4.00; 95% CI, 1.50 to 10.66) was the histopathologic subgroup most closely related to ionizing radiation. The effect of radiotherapy was restricted to smokers only (RR = 3.08; 95% CI, 1.61 to 5.91). The ERR/Gy for women with latency ≥ 10 years after exposure was 0.11 (95% CI, 0.02 to 0.44).

Conclusion

Radiotherapy for breast cancer significantly increases the risk of lung carcinoma more than 10 years after exposure in women who smoked at time of breast cancer.
Dermatofibrosarcoma Protuberans Treated at a Single Institution: A Surgical Disease With a High Cure Rate
Authors: Fiore Marco , Miceli Rosalba , Mussi Chiara , Lo Vullo Salvatore , Mariani Luigi , Lozza Laura , Collini Paola , Olmi Patrizia , Casali Paolo G. , Gronchi Alessandro
Published: October 2005

Purpose

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade, cutaneous sarcoma with autocrine overproduction of the platelet-derived growth factor (PDGF) β-chain from gene rearrangement as a key pathogenetic factor, now susceptible of molecular-targeted therapy. The aim of this retrospective analysis was to explore the outcome of patients with primary or recurrent DFSP.

Patients and Methods

Two hundred eighteen patients surgically treated at the Istituto Nazionale per lo studio e la cura dei Tumori (Milan, Italy) over 20 years were reviewed. Local relapse, distant metastasis, and survival were studied.

Results

One hundred thirty-six patients (62.4%) presented with a primary DFSP, while 82 patients (37.6%) had a recurrent disease. In the primary group, margins were microscopically positive in 11.8%, while in the recurrent group they were positive in 14.6% (P =.613). In the primary group, patients undergoing re-excision after inadequate previous surgery had residual disease in 62% of cases. Reconstructive surgery was needed in 30%, significantly more frequently in patients with a recurrence or a head and neck tumor. The crude cumulative incidence of local relapses was 4% at 10 years, and 2% at 10 years for distant metastases. No significant difference was found between primary and recurrent patients, as well as between positive and negative margins.

Conclusion

This being one of the largest mono-institutional series of DFSP, we confirm that long-term outcome is excellent, in terms of both local and distant control, after a wide excision with negative margins. Reconstructive surgery is often needed. Novel medical therapies will be of use in a limited subgroup of patients.
Prognostic Factors in HIV-Related Diffuse Large-Cell Lymphoma: Before Versus After Highly Active Antiretroviral Therapy
Authors: Lim Soon-Thye , Karim Roksana , Tulpule Anil , Nathwani Bharat N. , Levine Alexandra M.
Published: October 2005

Purpose

To compare the prognostic factors for survival and the validity of the International Prognostic Index (IPI) in patients with HIV-related diffuse large-cell lymphoma (HIV-DLCL) treated with curative intent in the pre–highly active antiretroviral therapy (HAART) era versus the HAART era.

Patients and Methods

We retrospectively reviewed 192 patients with HIV-DLCL diagnosed from 1982 to 2003. Pre-HAART era included 120 patients who did not receive HAART, whereas the HAART era included 72 patients diagnosed after January 1997 who received HAART.

Results

There were no statistically significant differences in terms of either lymphoma or HIV-related characteristics in the two time periods. The complete response rate improved from 32% in the pre-HAART to 57% in the HAART era (P = .0006), and median survival time improved from 8.3 to 43.2 months (P = .0005). In groups with low-, low-intermediate–, and high-intermediate–risk IPI disease, 3-year overall survival rates were 20%, 22%, and 5% in the pre-HAART era and 64%, 64%, and 50% in the HAART era, respectively. On multivariate analysis, factors independently associated with decreased survival in both periods were increasing IPI scores and failure to attain complete remission, whereas CD4 less than 100 cells/μL predicted shorter survival in only the pre-HAART era.

Conclusion

Prognostic factors and overall survival of patients with HIV-DLCC have changed. Clinical outcomes in patients with HIV-DLCL are now approaching the outcomes of patients with de novo lymphoma.
Cardiotoxicity of Cancer Therapy
Authors: Floyd Justin D. , Nguyen Duc T. , Lobins Raymond L. , Bashir Qaiser , Doll Donald C. , Perry Michael C.
Published: October 2005

Because cancer is a leading cause of mortality in the United States, the number of therapeutic modalities available for the treatment of neoplastic processes has increased. This has resulted in a large number of patients being exposed to a wide variety of cancer therapy. Historically, it has been well recognized that antineoplastic agents may have adverse effects on multiple organs and normal tissues. The most commonly associated toxicities occur in tissues composed of rapidly dividing cells and may spontaneously reverse with minimal long-term toxicity. However, the myocardium consists of cells that have limited regenerative capability, which may render the heart susceptible to permanent or transient adverse effects from chemotherapeutic agents. Such toxicity encompasses a heterogeneous group of disorders, ranging from relatively benign arrhythmias to potentially lethal conditions such as myocardial ischemia/infarction and cardiomyopathy. In some instances, the pathogenesis of these toxic effects has been elucidated, whereas in others the precise etiology remains unknown. We review herein the various syndromes of cardiac toxicity that are reported to be associated with antineoplastic agents and discuss their putative mechanisms and treatment.
Hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss and tinnitus: a systematic review of randomized controlled trials
Authors: Bennett M , Kertesz T , Yeung P
Published: October 2005

Background: Idiopathic sudden sensorineural hearing loss (ISSHL) and tinnitus are common. Hyperbaric oxygen therapy (HBOT) may improve hearing loss and/or reduce the intensity of tinnitus.

Methods: We performed a systematic search of the literature for randomized controlled trials, and made pooled analyses of pre-determined clinical outcomes where possible.

Results: Six trials contributed to this review (304 subjects). Pooled analysis suggested a significantly increased chance of a 25 per cent improvement in hearing threshold on pure tone average with HBOT (relative risk (RR) 1.39, 95 per cent confidence interval (CI) 1.05–1.84, p = 0.02; number-needed-to-treat 5, 95 per cent CI 3–20), but not a 50 per cent increase (RR 1.53, 95 per cent CI 0.85–2.78, p = 0.16). The significance of any improvement in tinnitus following HBOT could not be assessed due to poor reporting.

Conclusions: HBOT improved hearing, but the clinical significance of the level of improvement is not clear. Routine application of HBOT to patients with ISSHL is not justified by this review. More research is needed.
Dementia and Alzheimer's Disease in Community-Dwelling Elders Taking Vitamin C and/or Vitamin E
Authors: Fillenbaum Gerda G , Kuchibhatla Maragatha N , Hanlon Joseph T , Artz Margaret B , Pieper Carl F , Schmader Kenneth E , Dysken Maurice W , Gray Shelly L
Published: October 2005

BACKGROUND

Since increased oxidative stress may impair cognition and be a risk factor for dementia, there has been interest in determining whether use of antioxidants could protect against such events.

OBJECTIVE

To determine whether supplement use of vitamins C and/or E in a community-based sample of older African American and white individuals delayed incident dementia or Alzheimer's disease (AD).

METHODS

We selected a subgroup from the Duke Established Populations for Epidemiologic Studies of the Elderly, a longitudinal study of community-representative persons aged 65–105 years living in 5 adjacent counties in North Carolina, and followed them for dementia (1986–1987 through June 2000). Information gathered during in-home interviews included sociodemographic characteristics, health status, health service use, and vitamin use. Diagnosis of dementia and AD was based on evaluations using the clinical and neuropsychological batteries of the Consortium to Establish a Registry for Alzheimer's Disease, with final determination by consensus agreement of specialists using Diagnostic and Statistical Manual of Mental Disorders, third revision, and National Institute for Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders criteria.

RESULTS

Of 616 persons initially dementia-free (mean age 73 y; 62% female; 62% African American), 141 developed dementia, of whom 93 developed AD. Increased age and mobility problems were risk factors for dementia (only age for AD), while an increased number of outpatient visits reduced the likelihood of developing dementia. Neither use of any vitamins C and/or E (used by 8% of subjects at baseline) nor high-dose use reduced the time to dementia or AD.

CONCLUSIONS

In this community in the southeastern US where vitamin supplement use is low, use of vitamins C and/or E did not delay the incidence of dementia or AD.