bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Integrated Genomic-Based Approach to Individualized Treatment of Patients With Advanced-Stage Ovarian Cancer
Authors: Dressman Holly K. , Berchuck Andrew , Chan Gina , Zhai Jun , Bild Andrea , Sayer Robyn , Cragun Janiel , Clarke Jennifer , Whitaker Regina S. , Li LiHua , Gray Jonathan , Marks Jeffrey , Ginsburg Geoffrey S. , Potti Anil , West Mike , Nevins Joseph R. , Lancaster Johnathan M. 
Published: February 2007

PurposeThe purpose of this study was to develop an integrated genomic-based approach to personalized treatment of patients with advanced-stage ovarian cancer. We have used gene expression profiles to identify patients likely to be resistant to primary platinum-based chemotherapy and also to identify alternate targeted therapeutic options for patients with de novo platinum-resistant disease.Patients and MethodsA gene expression model that predicts response to platinum-based therapy was developed using a training set of 83 advanced-stage serous ovarian cancers and tested on a 36-sample external validation set. In parallel, expression signatures that define the status of oncogenic signaling pathways were evaluated in 119 primary ovarian cancers and 12 ovarian cancer cell lines. In an effort to increase chemotherapy sensitivity, pathways shown to be activated in platinum-resistant cancers were subject to targeted therapy in ovarian cancer cell lines.ResultsGene expression profiles identified patients with ovarian cancer likely to be resistant to primary platinum-based chemotherapy with greater than 80% accuracy. In patients with platinum-resistant disease, we identified expression signatures consistent with activation of Src and Rb/E2F pathways, components of which were successfully targeted to increase response in ovarian cancer cell lines.ConclusionWe have defined a strategy for treatment of patients with advanced-stage ovarian cancer that uses therapeutic stratification based on predictions of response to chemotherapy, coupled with prediction of oncogenic pathway deregulation, as a method to direct the use of targeted agents.
Vascular Targeted Therapy With Anti–Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Advanced Solid Tumors
Authors: Milowsky Matthew I. , Nanus David M. , Kostakoglu Lale , Sheehan Christine E. , Vallabhajosula Shankar , Goldsmith Stanley J. , Ross Jeffrey S. , Bander Neil H. 
Published: February 2007

PurposeBased on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response.Patients and MethodsPatients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues.ResultsTwenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment.ConclusionAcceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.
Real-time PCR Assay for Ultrasensitive Quantification of DNA-Binding Proteins
Authors: Hou Peng , Chen Zaozao , Ji Meiju , He Nongyue , Lu Zuhong 
Published: February 2007

Abstract
Background: The specific binding of proteins to DNA is a key step for many cellular activities, such as transcription regulation, DNA replication, recombination, repair, and restriction. The detection of DNA-binding proteins, as well as the identification of specific binding sites, is therefore important to understand gene expression mechanisms and cellular function. We describe an ultrasensitive method for quantification of DNA-binding proteins.
Methods: We combined the common exonuclease III (ExoIII) footprinting assay and real-time PCR for quantification of DNA-binding proteins, for an assay that does not require antibodies against the target proteins. Double-strand DNA probes were designed to monitor the activities of DNA-binding protein. The protein-binding site is at the 5′ end of the forward primer. When a target protein is present, it will specifically bind to the protein-binding site and produce a physical hindrance to ExoIII, which protects the reverse DNA strand from digestion by ExoIII. The remaining single-strand DNA template can be quantitatively detected by real-time PCR. Conversely, in the absence of the target protein, the naked primer regions will be degraded by ExoIII, which then cannot be amplified by real-time PCR.
Results: We detected the binding of 10 different transcription factors in crude cell extracts. The assay quantitatively detected binding at femtomolar concentrations of protein.
Conclusions: This technique is customizable and easy to establish. It has potential applications in research, medical diagnosis, and drug discovery.
Heritability and clinical features of multigenerational families with obsessive‐compulsive disorder and hoarding
Authors: Mathews Carol A. , Nievergelt Caroline M. , Azzam Amin , Garrido Helena , Chavira Denise A. , Wessel Jennifer , Bagnarello Monica , Reus Victor I. , Schork Nicholas J. 
Published: February 2007

AbstractTo date, only one complete genome screen for obsessive‐compulsive disorder (OCD) has been published. That study identified a region of suggestive linkage (maximum lod score of 2.25) with a relatively small sample size (N = 56; 27 with OCD). Additional complete genome screens are needed to confirm this finding and identify other regions of linkage. We present the clinical characteristics and power to detect linkage of 11 multigenerational families with OCD and hoarding (N = 92; 44 with OCD), as well as heritability estimates for several quantitative traits. Families with at least two individuals with OCD were identified through probands with childhood‐onset OCD. Expected lod scores were calculated for simulated genetic marker data under an additive and two dominant models assuming a dense SNP marker map. All affected individuals had an early age of onset (18 or younger). Hoarding was present in 46% of subjects. Obsessive‐compulsive symptoms and hoarding were highly heritable. The maximum mean expected lod score was 3.31 for OCD and 1.39 for hoarding. We found reasonable power to detect regions of interest (lod = 2) for OCD in these families, but will need to expand our family collection to have adequate power to detect regions of interest for hoarding. © 2007 Wiley‐Liss, Inc.
Growth and developmental outcomes of three high‐risk infant rhesus macaques (Macaca mulatta)
Authors: Dettmer Amanda M. , Houser Lisa A. , Ruppenthal Gerald C. , Capuano Saverio , Hewitson Laura 
Published: February 2007

AbstractInfants classified as “high risk” are born with a greater chance of developing medical complications at birth, and may have cognitive and other developmental complications later in life. Very few reports exist regarding the survival and outcome of such infants in primate colonies. Here we present early growth and developmental data on three high‐risk infant rhesus macaques (one female and two males) that were born either with intrauterine growth restriction (IUGR; born below the 1st birth weight percentile for gestational age) or extremely prematurely (at gestational days 128 and 140; mean full‐term gestation=164 days). We compared the outcome of these infants with that of healthy controls born at term and found no gross developmental delays in these infants with respect to growth, neonatal reflex and motor skill development, early cognitive development, or social behavior. Neurological and cognitive assessments were compared in terms of both postnatal and gestational age. The survival of these infants was dependent on a 24‐hr staffed nursery and a fluid protocol that catered to each high‐risk infant's individual needs. When such measures are implemented, infants such as these have a good chance of survival and can serve as excellent models for high‐risk human babies and their subsequent development. Am. J. Primatol. 69:503–518, 2007. © 2007 Wiley‐Liss, Inc.
Fruit availability, chimpanzee diet, and grouping patterns on Rubondo Island, Tanzania
Authors: Moscovice L.R. , Issa M.H. , Petrzelkova K.J. , Keuler N.S. , Snowdon C.T. , Huffman M.A. 
Published: February 2007

AbstractWe examined seasonal patterns of fruit availability, dietary quality, and group size in the descendants of an introduced chimpanzee population on Rubondo Island, Tanzania. The site has supported a free‐ranging population without provisioning for 40 years. Our goals were to determine whether Rubondo chimpanzees experience periods of fruit shortage, and whether they respond to changes in fruit availability similarly to chimpanzees at endemic sites. We indexed the fruit availability of tree and liana species on transects stratified across three chimpanzee ranging areas. We used fecal analyses to evaluate seasonal changes in diet, and used data on party size and nesting group size to examine seasonal patterns of grouping. Tree fruit availability was positively correlated with rainfall, with a period of relative tree fruit scarcity corresponding with the long dry season. Liana fruit availability was not related to rainfall, and lianas exhibited less variable fruiting patterns across seasons. Fruits made up the majority of the chimpanzee diet, with lianas accounting for 35% of dietary fruit species. Fruits of the liana Saba comorensis were available during all months of phenological monitoring, but they were consumed more when tree fruit was scarce, suggesting that Saba comorensis fruits may be a fallback food for Rubondo chimpanzees. There were no increases in consumption of lower‐quality plant parts between seasons, and there were no changes in group size between seasons. These results contrast with evidence from several endemic chimpanzee study sites, and indicate that Rubondo chimpanzees may have access to abundant and high‐quality foods year round. Am. J. Primatol. 69:487–502, 2007. © 2007 Wiley‐Liss, Inc.
Sich durchdringende polare und unpolare Untergitter in intermetallischen Phasen: die Struktur von NaCd2
Authors: Fredrickson Daniel C. , Lee Stephen , Hoffmann Roald 
Published: February 2007

AbstractIn den 1960er Jahren bestimmte Samson die Strukturen einiger der komplexesten intermetallischen Phasen, darunter NaCd2, Mg2Al3und Cu3Cd4, die jeweils über 1000 Atome pro Elementarzelle aufweisen. Basierend auf den bemerkenswerten Arbeiten von Samson und Andersson verwenden wir quantenmechanische Rechnungen zur Beschreibung dieser Strukturen. Der formale Aufbau der Struktur auf der Grundlage der elektronischen Verhältnisse beginnt mit der relativ einfachen Mg17Al12‐Struktur und setzt sich bis zu Samsons NaCd2‐Struktur fort, wobei die Aufteilung in elektronenreiche und elektronenarme Gitterplätze (bezüglich der durchschnittlichen Elektronenzahl) bei beiden Strukturen das Vorliegen von Fragmenten des MgCu2‐Typs aufdeckt. Die äußeren und inneren Bereiche eines solchen Fragments weisen unterschiedliche Bindungsverhältnisse auf: Der innere Bereich ist eher polar, während die Grenzflächen relativ unpolar sind. Dieser Sachverhalt kann mit der Geometrie der Grenzflächenplätze begründet werden, die zugleich an elektronenreichen wie auch elektronenarmen Gittern beteiligt sind. Die polaren und unpolaren Gitterplätze in NaCd2sind durch eine Minimalfläche, die D‐Fläche, voneinander getrennt. Die Argumente, die für eine solche Struktur sprechen, beruhen auf elektronischen Überlegungen. Ein entscheidendes Merkmal besteht darin, dass sich polare und unpolare Bindungstypen gegenseitig durchdringen. Diese Methode lässt sich auch auf andere Strukturen anwenden.
A Large Scale Synthesis of a Natural Antibiotic, 2,4‐Diacetylophloroglucinol (DAPG)
Authors: Zakrzewski Jerzy , Karpińska Monika , Maliński Zbigniew 
Published: February 2007

AbstractA natural antibiotic, 2,4‐diacetylophloroglucinol (DAPG), has been prepared by the acetylation of phloroglucinol (PhL) with acetic anhydride in the presence of boron trifluoride etherate complex. The crude DAPG is efficiently purified using chromatographic filtration with boiling eluent.
Synthesis of Molecular Wires of Linear and Branched Bis(terpyridine)‐Complex Oligomers and Electrochemical Observation of Through‐Bond Redox Conduction
Authors: Nishimori Yoshihiko , Kanaizuka Katsuhiko , Murata Masaki , Nishihara Hiroshi 
Published: February 2007

AbstractFilms of linear and branched oligomer wires of Fe(tpy)2 (tpy=2,2′:6′,2′′‐terpyridine) were constructed on a gold‐electrode surface by the interfacial stepwise coordination method, in which a surface‐anchoring ligand, (tpyC6H4NNC6H4S)2 (1), two bridging ligands, 1,4‐(tpy)2C6H4 (3) and 1,3,5‐(CCtpy)3C6H3 (4), and metal ions were used. The quantitative complexation of the ligands and FeII ions was monitored by electrochemical measurements in up to eight complexation cycles for linear oligomers of 3 and in up to four cycles for branched oligomers of 4. STM observation of branched oligomers at low surface coverage showed an even distribution of nanodots of uniform size and shape, which suggests the quantitative formation of dendritic structures. The electron‐transport mechanism and kinetics for the redox reaction of the films of linear and branched oligomer wires were analyzed by potential‐step chronoamperometry (PSCA). The unique current‐versus‐time behavior observed under all conditions indicates that electron conduction occurs not by diffusional motion but by successive electron hopping between neighboring redox sites within a molecular wire. Redox conduction in a single molecular wire in a redox‐polymer film has not been reported previously. The analysis provided the rate constant for electron transfer between the electrode and the nearest redox‐complex moiety, k1 (s−1), as well as that for intrawire electron transfer between neighboring redox‐complex moieties, k2 (cm2 mol−1 s−1). The strong effect of the electrolyte concentration on both k1 and k2 indicates that the counterion motion limits the electron‐hopping rate at lower electrolyte concentrations. Analysis of the dependence of k1 and k2 on the potential gave intrinsic kinetic parameters without overpotential effects: k10=110 s−1, k20=2.6×1012 cm2 mol−1 s−1 for [n Fe3], and k10=100 s−1, k20=4.1×1011 cm2 mol−1 s−1 for [n Fe4] (n=number of complexation cycles).
Trading performance, disposition effect, overconfidence, representativeness bias, and experience of emerging market investors
Authors: Chen Gongmeng , Kim Kenneth A. , Nofsinger John R. , Rui Oliver M. 
Published: February 2007

AbstractUsing brokerage account data from China, we study investment decision making in an emerging market. We find that Chinese investors make poor trading decisions: the stocks they purchase underperform those they sell. We also find that Chinese investors suffer from three behavioral biases: (i) they tend to sell stocks that have appreciated in price, but not those that have depreciated in price, consistent with a disposition effect, acknowledging gains but not losses; (ii) they seem overconfident; and (iii) they appear to believe that past returns are indicative of future returns (a representativeness bias). In comparisons to prior findings, Chinese investors seem more overconfident than U.S. investors (i.e., the Chinese hold fewer stocks, yet trade very often) and their disposition effect appears stronger. Finally, we categorize Chinese investors based on proxy measures of experience and find that “experienced” investors are not always less prone to behavioral biases than are “inexperienced” ones. Copyright © 2007 John Wiley & Sons, Ltd.
Maternal plasma pyridoxal‐5′‐phosphate concentrations and risk of isolated oral clefts in the Philippines
Authors: Tamura Tsunenobu , Munger Ronald G. , Nepomuceno Buena , Corcoran Christopher , Cembrano Joselito , Solon Florentino 
Published: February 2007

AbstractBACKGROUND:We report that inadequate vitamin B‐6 status of Filipino mothers, assessed by erythrocyte aspartate aminotransferase activity coefficient (EAST‐AC), is associated with an increased risk for isolated cleft lip with or without cleft palate (CL/P) in their children. Its association with the status assessed by plasma pyridoxal‐5′‐phosphate (PLP) concentrations is unknown.METHODS:In a case‐control study in the Philippines including 46 cases (mothers of a child with CL/P) and 392 controls (mothers of an unaffected child), we evaluated the association between the risk for CL/P and maternal vitamin B‐6 status assessed by PLP and EAST‐AC.RESULTS:The ORs of CL/P were estimated by classifying mothers by PLP (>30, 20–30, and <20 nmol/L). Using the highest PLP group as the reference, ORs (95% CIs) were 1.03 (0.45–2.37) and 2.66 (1.30–5.50) for the middle and lowest groups, respectively (p trend = .01). In multivariate models controlling for various covariates including folate, the risk for CL/P was approximately 12 times higher in mothers with inadequate vitamin B‐6 status, assessed by both PLP and EAST‐AC values, compared to those with adequate status by both values.CONCLUSIONS:Inadequate vitamin B‐6 status assessed by maternal PLP and EAST‐AC values independently and both combined was associated with an increased risk for CL/P. The association was highest when both values were considered, suggesting that the measurement of both PLP and EAST‐AC provides better assessment of vitamin B‐6 status than either measurement alone. Birth Defects Research (Part A) 2007. © 2007 Wiley‐Liss, Inc.
Assessment of developmental toxicity of vorinostat, a histone deacetylase inhibitor, in Sprague‐Dawley rats and Dutch Belted rabbits
Authors: Wise L. David , Turner Katie J. , Kerr Janet S. 
Published: February 2007

AbstractBACKGROUND: The developmental toxicity potential of vorinostat (suberoylanilide hydroxamic acid [SAHA], ZOLINZA™), a potent inhibitor of histone deacetylase (HDAC), was assessed in Sprague‐Dawley rats and Dutch Belted rabbits. HDAC inhibitors have been shown to mediate the regulation of gene expression, induce cell growth, cell differentiation, and apoptosis of tumor cells. Range‐finding studies established oral dose levels of 5, 15, or 50 mg/kg/day and 20, 50, or 150 mg/kg/day in rats and rabbits, respectively. METHODS: Animals were dosed on Gestation Days 6–20 or 7–20, respectively, with litter/fetal parameters evaluated on GD 21 and 28, respectively. Separate studies evaluated toxicokinetic parameters at the mid‐ and high‐dose levels. RESULTS: There was no maternal toxicity observed at the highest dose levels; however, hematology and serum biochemistry changes were characterized in the range‐finding studies. Vorinostat did not induce morphological malformations in either rat or rabbit fetuses. In rats, drug‐related developmental toxicity was observed only in the high‐dose group and consisted of markedly decreased fetal weight and increases in fetuses with a limited number of skeletal variations. In rabbits, drug‐related developmental toxicity was also observed only in the high‐dose group and consisted of slightly decreased fetal weight and increases in fetuses with a short 13th rib and incomplete ossification of metacarpals. Maternal exposures to vorinostat based on AUC and Cmax values were comparable at the high‐dose levels of both species. Rabbits tolerated higher dosages probably due to more extensive metabolism. Maternal concentrations of vorinostat were ∼1,000–fold above the known in vitro HDAC inhibitory concentration. CONCLUSIONS: Review of previous work with valproic acid, another HDAC inhibitor, suggest that the developmental toxicity profiles of these 2 compounds are not the result of HDAC inhibition but involve other mechanisms. Birth Defects Res (Part B) 80:57–68, 2007. © 2007 Wiley‐Liss, Inc.
Die Fossilgeschichte des Menschen: Wie aus den ersten Primaten Homo wurde (Teil 1)
Authors: Welsch Ulrich 
Published: February 2007

AbstractDer Entwicklungsweg des Menschen begann vor circa sechs Millionen Jahren, als sich die Entwicklungslinien von Mensch und Schimpansen trennten. In den vergangenen Jahrzehnten wurden mehr relevante Fossilfunde gemacht als in den gut 100 Jahren zuvor, so dass die Grundzüge der Evolution des Menschen mittlerweile recht gut bekannt sind. Die zunehmende Zahl an Forschern auch außerhalb Europas und der lässt erwarten, dass die Zahl der Funde in Zukunft noch wesentlich anwachsen wird, so dass Wissenslücken geschlossen werden, aber auch neue Interpretationen diskutiert werden müssen. Dieser zweiteilige Artikel bietet einen Überblick über gesicherte Erkenntnisse, spannende Funde – und offene Fragen.
Vegetation – der unterschätzte Klimafaktor: Treib‐ und Eishausklima in der Erdgeschichte
Authors: Mosbrugger Volker , Micheels Arne 
Published: February 2007

AbstractLandpflanzen nehmen auf drei Wegen Einfluss auf die klimatischen Verhältnisse: über Veränderungen der Strahlungsbilanz, der Stoffkreisläufe und des Impulsaustausches. Beispiele aus der Erdgeschichte zeigen, wie groß dieser Einfluss der Vegetation auf das Klimageschehen sein kann. Im Karbon führte offensichtlich die Besiedlung des Festlandes durch Pflanzen zur Entwicklung eines Eishausklimas mit ausgedehnter Vereisung. Umgekehrt erlaubte zu Zeiten von Treibhausklimaten mit hohen CO2‐Konzentrationen die Ausbreitung der Wälder bis in hohe Breiten erst die Entwicklung eines global relativ ausgeglichenen Klimas mit warmen und eisfreien Polarregionen. Für alle Modelle, die das Klima der kommenden Jahrzehnte berechnen sollen, ist diese Wechselwirkung von entscheidender Bedeutung.
Zur Psychologie des Essens und Trinkens: Essen ist mehr als Ernährung
Authors: Pudel Volker 
Published: February 2007

AbstractAus der täglichen Aufgabe, Nahrung zu suchen, ist in der Überflussgesellschaft die Aufgabe geworden, sich für oder gegen Lebensmittel zu entscheiden. Die Verfügbarkeit von Lebensmitteln, der Mangel an körperlicher Aktivität und die auf Notzeiten ausgerichteten evolutionsbiologischen Programme überfordern das Individuum und lassen Ernährungsprobleme entstehen. 50 Jahre Ernährungsaufklärung mit überwiegend kognitiver Information (Verhaltensprävention) haben nicht zu einer Entschärfung der Ernährungsprobleme beigetragen. Mehr Chance wird der Verhältnisprävention eingeräumt, die Lebensbedingungen schaffen sollte, unter denen ein günstiges Ess‐ und ein aktiveres Bewegungsverhalten leichter fallen. Dazu könnte eine Optimierung der Speisenangebote in den öffentlichen Küchen ein wichtiger Schritt sein, wenn gesetzliche Rahmenbedingungen für die Realisierung sorgen.
Feinstaub bewirkt entzündliche Reaktion in der Lunge
Authors: Stöger Tobias , Schulz Holger 
Published: February 2007

AbstractBereits kurzzeitige Belastung mit Feinstaub führt zu entzündlichen Veränderungen in der Lunge, wie eine Studie des Nationalen Genomforschungsnetzes (NGFN) zeigt. In der Lunge von Mäusen, die über 24 Stunden Feinstaubpartikel eingeatmet hatten, sind verstärkt Gene und Proteine aktiv, die entweder an der Akutphase‐Antwort des Immunsystems oder an der Entstehung von Entzündungen beteiligt sind.