bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infrequent Delivery of a Long-Acting PTH-Fc Fusion Protein Has Potent Anabolic Effects on Cortical and Cancellous Bone
Authors: Kostenuik Paul J , Ferrari Serge , Pierroz Dominique , Bouxsein Mary , Morony Sean , Warmington Kelly S , Adamu Steven , Geng Zhaopo , Grisanti Mario , Shalhoub Victoria , Martin Steve , Biddlecome Gloria , Shimamoto Grant , Boone Tom , Shen Victor , Lacey David 
Published: June 2007

Abstract
Skeletal anabolism with PTH is achieved through daily injections that result in brief exposure to the peptide. We hypothesized that similar anabolic effects could be achieved with less frequent but more sustained exposures to PTH. A PTH-Fc fusion protein with a longer half-life than PTH(1–34) increased cortical and cancellous BMD and bone strength with once- or twice-weekly injections.
Introduction: The anabolic effects of PTH are currently achieved with, and thought to require, daily injections that result in brief exposure to the peptide. We hypothesized that less frequent but more sustained exposures to PTH could also be anabolic for bone, provided that serum levels of PTH were not constant.
Materials and Methods: PTH(1–34) was fused to the Fc fragment of human IgG1 to increase the half-life of PTH. Skeletal anabolism was examined in mice and rats treated once or twice per week with this PTH-Fc fusion protein.
Results: PTH-Fc and PTH(1–34) had similar effects on PTH/PTHrP receptor activation, internalization, and signaling in vitro. However, PTH-Fc had a 33-fold longer mean residence time in the circulation of rats compared with that of PTH(1–34). Subcutaneous injection of PTH-Fc once or twice per week resulted in significant increases in bone volume, density, and strength in osteopenic ovariectomized mice and rats. These anabolic effects occurred in association with hypercalcemia and were significantly greater than those achievable with high concentrations of daily PTH(1–34). PTH-Fc also significantly improved cortical bone volume and density under conditions where daily PTH(1–34) did not. Antiresorptive co-therapy with estrogen further enhanced the ability of PTH-Fc to increase bone mass and strength in ovariectomized rats.
Conclusions: These results challenge the notion that brief daily exposure to PTH is essential for its anabolic effects on cortical and cancellous bone. PTH-derived molecules with a sustained circulating half-life may represent a powerful and previously undefined anabolic regimen for cortical and cancellous bone.
Evaluation of 41Calcium as a New Approach to Assess Changes in Bone Metabolism: Effect of a Bisphosphonate Intervention in Postmenopausal Women With Low Bone Mass
Authors: Denk Eberhard , Hillegonds Darren , Hurrell Richard F , Vogel John , Fattinger Karin , Häuselmann Hans J , Kraenzlin Marius , Walczyk Thomas 
Published: June 2007

Abstract
A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4–8 wk in each individual.
Introduction: Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate.
Materials and Methods: Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood.
Results: Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by −36% for bone alkaline phosphatase (BALP; p = 0.002) and −59% for procollagen type I propeptides (PINP;p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by −21% (p = 0.019) and −23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by −60% (p = 0.001) and −57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by −47 ± 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45–58%).
Conclusions: Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.
The Poncelet grid
Authors: Schwartz Richard Evan 
Published: June 2007

Abstract
Given a convex polygon P in the projective plane we can form a finite “grid” of points by taking the pairwise intersections of the lines extending the edges of P. When P is a Poncelet polygon we show that this grid is contained in a finite union of ellipses and hyperbolas and derive other related geometric information about the grid.
On hyperbolic Coxeter n-polytopes with n + 2 facets
Authors: Felikson A , Tumarkin P , Zehrt T 
Published: June 2007

Abstract
A convex polytope admits a Coxeter decomposition if it is tiled by finitely many Coxeter polytopes such that any two tiles having a common facet are symmetric with respect to this facet. In this paper, we classify all Coxeter decompositions of compact hyperbolic Coxeter n-polytopes with n + 2 facets. Furthermore, going out from Schläfli‘s reduction formula for simplices we construct in a purely combinatorial way a volume formula for arbitrary polytopes and compute the volumes of all compact Coxeter polytopes in ℍ4 which are products of simplices.
Surjectivity of Gaussian maps for curves on Enriques surfaces
Authors: Knutsen Andreas Leopold , Lopez Angelo Felice 
Published: June 2007

Abstract
Making suitable generalizations of known results we prove some general facts about Gaussian maps. These facts are then used, in the second part of the article, to give a set of conditions that insure the surjectivity of Gaussian maps for curves on Enriques surfaces. To do this we also solve a problem of independent interest: a tetragonal curve of genus g ≥ 7 lying on an Enriques surface and general in its linear system, cannot be, in its canonical embedding, a quadric section of a surface of degree g − 1 in ℙ
g−1.
Mikrobiologische Diagnostik der Lyme-Borreliose / Microbiological diagnostics of Lyme borreliosis
Authors: Fingerle Volker , Wilske Bettina 
Published: June 2007

Zusammenfassung
Die Multisystemerkrankung Lyme-Borreliose wird in Europa durch mindestens vier verschiedene Borrelia burgdorferi sensu lato Spezies verursacht. Die genetische und antigenetische Heterogenität der Erreger muss deshalb bei der Entwicklung diagnostischer Methoden berücksichtigt werden. Die serologische Diagnostik soll als Stufendiagnostik durchgeführt werden. Als Suchtest wird ein sensitiver, IgG und IgM differenzierender ELISA empfohlen, der nur bei Reaktivität durch den Immunoblot bestätigt werden soll. Nur bei positivem Immunoblot kann von einem positiven Antikörpernachweis ausgegangen werden. Die Sensitivität liegt bei 20 bis 50% im Stadium I, 70% bis 90% im Stadium II und nahe 100% im Stadium III. Der Einsatz rekombinanter Antigene, wie z.B. primär in vivo exprimierter Proteine wie VlsE oder Homologe immundominanter Antigene verschiedener Stämme (z.B. DbpA), führt zu einer deutlichen Verbesserung der serologischen Diagnostik. Der auf spezielle Indikationen beschränkte Erregernachweis (Kultur und PCR) kann aus Hautbiopsien, Liquor und Gelenkpunktaten oder – biopsien durchgeführt werden. Die Sensitivität liegt bei 50% bis 70% für Hautbiopsien oder Gelenkpunktate (letztere nur PCR) und bei 10% bis 30% für Liquorproben. Nicht empfohlen werden Antigentests aus Körperflüssigkeiten, PCR aus Urin oder Blut/Serum, Lymphozyten-Transformationstest, Nachweis CD3 negativer/CD57 positiver Lymphozyten und Untersuchung von vom Menschen entfernten Zecken auf Borrelien, um daraus eine Indikation zur Antibiotikaprophylaxe herzuleiten.
Anwendung der SELDI-TOF-Massenspektrometrie zur Identifizierung neuer Biomarker: Möglichkeiten und Grenzen / Application of SELDI-TOF-mass spectrometry for biomarker identification: potentials and limitations
Authors: Kiehntopf Michael , Siegmund Robert , Deufel Thomas 
Published: June 2007

Zusammenfassung
Die SELDI-TOF-Massenspektrometrie (MS) ist eine der wichtigsten aktuell verfügbaren Technologien zur Hochdurchsatzanalyse von komplexen Proteinmischungen. In zahlreichen Untersuchungen der letzten Jahre konnte gezeigt werden, dass sich durch die Methode des vergleichenden Proteinprofilings mittels SELDI-TOF-MS neue Wege in der diagnostischen Proteinanalytik und insbesondere in der Identifizierung neuer Biomarker beschreiten lassen. Gleichzeitig haben diese Untersuchungen aber auch die Grenzen der Methode verdeutlicht und die besondere Bedeutung der Standardisierung und Qualitätskontrolle sowohl der präanalytischen und analytischen Einflussfaktoren, als auch der nachfolgenden bioinformatischen Auswertung belegt. So hat sich gezeigt, dass das Studiendesign, die Auswahl entsprechender Kontrollgruppen und die Verwendung besonderer, aus der Analyse von Microarraydaten bekannter, statistischer Methoden eine wesentliche Bedeutung für die Reduktion der Rate falsch-signifikanter Peaks haben. Obwohl eine essentielle Forderung zur Validierung der in Pilotstudien identifizierten potentiellen diagnostischen Peakmuster darin besteht, diese in entsprechend großen prospektiven und multizentrischen Studien zu validieren, mangelt es in einer Vielzahl von Studien gerade daran. Bevor diese Untersuchungen nicht in ausreichendem Maße durchgeführt und an einer größeren Anzahl von Fragestellungen gezeigt werden konnte, dass sich die unter standardisierten Bedingungen erhobenen Proteinprofile auch noch Monate/Jahre später unabhängig vom Untersucher und dem verwendeten Gerät reproduzierbar zur Unterscheidung distinkter Patientenpopulationen verwenden lassen, ist die Translation dieser Technologie in die klinische Routinediagnostik potentiell möglich, aber nicht konkret absehbar.
Freie Fettsäuren als kardiovaskulärer Risikofaktor / Free fatty acids as a cardiovascular risk factor
Authors: Pilz Stefan , März Winfried 
Published: June 2007

Zusammenfassung
Freie Fettsäuren (FFS) sind physiologisch wichtige Energiesubstrate, deren Freisetzung durch Lipolyse im Fettgewebe an die Energiebedürfnisse des Körpers angepasst ist. Die vor allem bei adipösen Patienten erhöhten Konzentrationen an FFS stehen in Zusammenhang mit Typ 2-Diabetes, Leberzellverfettung und kardiovaskulären Erkrankungen. Vor allem bei Herzinsuffizienz und dem akuten Koronarsyndrom sind die FFS durch die lipolytische Wirkung von Katecholaminen und natriuretischen Peptiden erhöht. FFS können zur myokardialen Dysfunktion beitragen, haben ein proarrhythmogenes Potenzial und führen bei erhöhter Aufnahme und Oxidation im Herzmuskel zu einem im Vergleich zur Energiegewinnung durch Glukose erhöhten Sauerstoffbedarf. In diesem Zusammenhang gibt es bereits Therapieansätze einer so genannten „metabolischen Therapie” für koronare Herzkrankheit und Herzinsuffizienz, die darauf abzielen, den Stoffwechsel bzw. die Oxidation von Fettsäuren im Myokard zu reduzieren. Die Anwendbarkeit von FFS als diagnostischer Routineparameter ist hingegen durch ihre große Schwankungsbreite mit starker Abhängigkeit von der Nahrungsaufnahme, bzw. von hormonellen Einflüssen, limitiert. Weiterhin ist offen, ob Nüchternwerte, postprandiale Messungen oder dynamische, z.B. durch Stressfaktoren evozierte Veränderungen der FFS, bessere Parameter für ein erhöhtes kardiovaskuläres Risiko darstellen. Im vorliegenden Übersichtsartikel wird das derzeitige Wissen über den Stoffwechsel und die Bedeutung von FFS als kardiovaskulärer Risikofaktor zusammengefasst und das Potenzial von FFS in Diagnostik und Therapie kardiovaskulärer Erkrankungen diskutiert.
Untersuchungen zur diagnostischen Wertigkeit des Lymphozytentransformationstestes bei Patienten mit Borreliose / Evaluation of the diagnostic significance of the lymphocyte proliferation test in patients with Lyme borreliosis
Authors: von Baehr Volker , Liebenthal Christa , Gaida Brita , Schmidt Frank-Peter , von Baehr Rüdiger , Volk Hans-Dieter 
Published: June 2007

Zusammenfassung
Borrelienspezifische Antikörper sind erst mehrere Wochen nach Infektion nachweisbar und allein kein Beweis für eine aktive Borreliose. Die Sensitivität von Kultur und PCR ist für den Nachweis bzw. Ausschluss einer Borreliose zu gering. Es bedarf einer Methode, die ausschließlich eine aktive Borrelieninfektion möglichst früh anzeigt. Es wurde dazu ein Lymphozytentransformationstest (LTT) mit drei Borrelienlysatantigenen (Borrelia B. sensu stricto, B. afzelii und B. garinii) sowie rekombinantem OspC entwickelt und mit Untersuchungen von seronegativen (n=100) und seropositiven Gesunden (n=36) sowie seropositiven Patienten mit klinischer Borreliose (n=44) validiert. Die Sensitivität des Borrelien-LTT für eine klinische Borreliose vor antibiotischer Behandlung wurde mit 91%, die Spezifität mit 94% ermittelt. Bei 820 Patienten mit klinischem Verdacht auf Borreliose wurde eine Übereinstimmung positiver und negativer serologischer und LTT-Ergebnisse von 77,3% gefunden. Serologisch positiv und im LTT negativ waren 165 Patienten (20,1%), überwiegend mit Borreliose nach antibiotischer Therapie. Serologisch negativ und im LTT positiv waren 21 Patienten (2,6%), davon sieben mit Erythema migrans. Nach antibiotischer Behandlung wird der Borrelien-LTT bei Patienten mit Frühmanifestationen der Borreliose (n=90) negativ bis grenzwertig, bei Spätmanifestationen (n=70) rückläufig mit verbleibender Restaktivität. Verlaufsuntersuchungen über ein Jahr von sechs Patienten mit Frühmanifestationen zeigten nur eine Reaktivierung. Bei acht von zehn Patienten mit Spätmanifestationen wurden häufig Reaktivierungen bzw. persistierend positive LTT-Reaktionen beobachtet. Als Indikation für den Borrelien-LTT wird deshalb besonders die Verlaufskontrolle bei disseminierten Borrelieninfektionen vorgeschlagen.
Crystal chemistry of RE(CO3)OH
Authors: Tahara Takeshi , Nakai Izumi , Miyawaki Ritsuro , Matsubara Satoshi 
Published: June 2007

Rare earth carbonate hydroxides, RE(CO3)OH, were hydrothermally synthesized from formic acid and the hydroxide gels of Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Y. An orthorhombic phase with a kozoite-type structure was obtained for RE = Nd and Sm. Another orthorhombic modification of the kozoite-type structure was obtained for RE = Eu, Gd, Tb, Dy, Ho, Er, Tm, and Y. The latter phase has a lower symmetry (space group: P212121) in comparison to the true kozoite-type structure (Pnma). A new tetragonal phase (space group: P42/nmc) was found for RE = Tm and Yb.
The crystal structures of RE(CO3)OH were refined for Pnma (RE = Nd and Sm), P212121 (RE = Eu, Gd, Tb, Dy, Ho, Er, Tm and Y), and P42/nmc phases (RE = Tm and Yb) using single-crystal X-ray diffraction intensity data. The distinct features of the differences among the three structures are the coordination numbers of the RE3+ ions: 10, 9, and 8 for the Pnma, P212121, and P42/nmc phases, respectively. A systematic comparison of the two orthorhombic structures revealed a dynamic variation in the coordination environment of the RE3+ ions accompanied by variations in their ionic radii. Although the interatomic RE—O distances tend to decrease with the lanthanide contraction, exceptions were observed for two of the RE—O distances. The mutual close proximity of CO3
2– anions caused by the lanthanide contraction led to repulsion between the CO3
2– anions, which decreased the symmetry of the configuration of CO3
2– anions around the central RE3+ ion, and some oxygen atoms of CO3
2– moved away from the first coordination shell of the RE3+ ions due to the elongation of the RE-O distances.
The crystal structures of the tetragonal RE(CO3)OH are distinct from those of the orthorhombic phases. They consist of ladders of RE3+ ions 8-coordinated by the CO3
2– and OH– anions arranged in the form of a double cross. The powder XRD patterns of the tetragonal RE(CO3)OH are identical to that of a synthetic material previously reported as Tm6(OH)4(CO3)7.
High-temperature neutron powder diffraction study of scandia/nitrogen co-doped zirconia
Authors: Lerch Martin , Boysen Hans , Rödel T. Christoph , Kaiser-Bischoff Ines , Hoelzel Markus , Senyshyn Anatoliy 
Published: June 2007

The structural evolution of a scandia/nitrogen co-doped zirconia sample, Sc0.148Zr0.852O1.72N0.14, was investigated by neutron powder diffraction up to 1700 °C. At ambient temperature it has an anion-deficient fluorite related β′-type structure with ordered anion vacancies (space group R-3, a = 9.5611 Å, c = 17.5020 Å). With increasing temperature a gradual transformation into a cubic fluorite-type phase (Fm3m) with randomly distributed vacancies takes place which is accompanied by an enrichment of Sc in the rhombohedral phase and completed at ∼1050°C. At higher temperatures probability densities and single particle potentials of the anions were determined. The incorporation of nitrogen into the scandia-zirconia material significantly increased the activation energy for anion migration to values above 1 eV. The anions migrate predominantly along the <100>-directions to neighbouring sites.
High temperature structural behaviour of Li2VOSiO4
Authors: Zema Michele , Tarantino Serena C. , Ghigna Paolo , Montagna Gabriele 
Published: June 2007

Structural investigations at high temperature were carried out on compound Li2VOSiO4, which crystallises with a natisite-type structure. Unit-cell parameters were measured and diffracted intensities collected at regular intervals in the temperature range 25–500 °C using single crystal X-ray diffraction techniques. Thermal expansion coefficients showed positive expansion of lattice constants, greater along the c direction, and of cell volume. Reversibility of thermal expansion in the investigated temperature range was checked by measuring unit-cell parameters after the crystal was cooled down from 500 °C to room temperature. Structure refinements revealed that the [VOSi4]n
2− layers are almost rigid and that the most relevant modifications occur at the intercalated ion layer.
Cardiovascular Effects of Sibutramine in the Treatment of Obese Adolescents: Results of a Randomized, Double-Blind, Placebo-Controlled Study
Authors: Daniels Stephen R. , Long Barbara , Crow Scott , Styne Dennis , Sothern Melinda , Vargas-Rodriguez Ileana , Harris Lisa , Walch Julia , Jasinsky Olga , Cwik Kristine , Hewkin Ann , Blakesley Vicky ,   for the Sibutramine Adolescent Study Group
Published: June 2007

BACKGROUND. Adolescent obesity is a major public health problem. Treatment options in addition to behavioral therapy could include pharmacotherapy with sibutramine.
OBJECTIVES. Concerns regarding increases in blood pressure and heart rate after sibutramine treatment in some adult patients precipitated the present analysis, which evaluated the cardiovascular safety of sibutramine plus a behavioral therapy program in obese adolescents.
PATIENTS AND METHODS. With this 12-month, randomized, double-blind, placebo-controlled trial in 33 US clinics we studied 498 adolescents aged 12 to 16 years with multiethnic backgrounds and BMIs of 28.1 to 46.3 kg/m2.
RESULTS. The subjects were randomly assigned to behavioral therapy plus 10 mg of sibutramine or behavioral therapy plus placebo daily. At the end point, there was a mean treatment group difference in BMI of 2.6 kg/m2 in favor of sibutramine. Small mean decreases in blood pressure and pulse rate were seen in both sibutramine and placebo groups at the end point (systolic blood pressure: −2.1 vs −2.1 mmHg; diastolic blood pressure: −0.1 vs −1.1 mmHg; pulse rate: −0.2 vs −1.8 bpm). In both treatment groups, these reductions in vital signs were greater at the end point when BMI reduction was ≥5% compared with &lt;5%.
CONCLUSIONS. Sibutramine may have some direct cardiovascular effects on obese adolescents. These cardiovascular effects may be balanced by a reduction in BMI, which, in adolescents, seems to be greater than that observed in adults.
Extirpation of Red Shiner in Direct Tributaries of Lake Texoma (Oklahoma‐Texas): A Cautionary Case History from a Fragmented River‐Reservoir System
Authors: Matthews William J. , Marsh‐Matthews Edie 
Published: June 2007

AbstractThe effects of reservoirs on composition of fish assemblages are well documented in and downstream of reservoirs but are less well known upstream, especially in small tributaries. Here we report that a historically very abundant native minnow species (red shiner Cyprinella lutrensis) has been extirpated from several direct tributaries of Lake Texoma, a large impoundment of the Red and Washita rivers, Oklahoma‐Texas. Using historical and recent data, we document the recent loss of or sharp declines in the red shiner from six of seven creeks that are direct tributaries of Lake Texoma. The red shiner is widespread, tolerant of harsh conditions, and highly invasive, so its demise is particularly noteworthy. The species remains common in direct tributaries of free‐flowing reaches of the rivers that we sampled recently. Centrarchids that are potential predators of or competitors with the red shiner are now more abundant in Texoma‐direct creeks than in tributaries to the rivers. Loss of the red shiner occurred within the past 20 years in Texoma‐direct creeks, although the reservoir is more than 60 years old. We suspect that recent severe droughts initiated loss of the species and that recolonization has been inhibited by the reservoir, which fragments the former river‐creek system. The lower reaches of the Texoma‐direct creeks appear to have undergone habitat modification during recent high‐water episodes, resulting in the formation of deep pools that contain large numbers of centrarchids or other piscivores and are poor habitat for the red shiner. Reservoir effects on the red shiner in these tributary streams did not appear until decades after impoundment, after particular combinations of extreme drought and flood events. The decline of the red shiner in the Lake Texoma system suggests that biologists should be alert for similar changes in native fish populations in direct tributaries to other reservoirs.