bluuebunny/crossref_metadata_2025_split huggingface dataset:
Casino Cities
Authors: Hannigan John 
Published: May 2007

AbstractThe recent upsurge in licensed, themed gambling emporiums in Macao, South Africa, and Britain signals the emergence of the casino city as a global model of urban development and consumer culture. Casino cities thrive at the intersection of three complementary commercial spheres: the luxury goods and services industry, the corporate gaming (gambling) sector, and the international tourist trade. Critics have expressed concern that the casino city is encased in a straightjacket of blandness and predictability. Furthermore, it tends to steamroll indigenous culture and heritage, or alternately, co‐opt it in order to create the illusion of the exotic. Finally, the casino city is a dual city where enclaves of conspicuous consumption and spectatorship are juxtaposed to areas of poverty and despair.
Modeling Pre‐ and Post‐Dam Removal Sediment Dynamics: The Kalamazoo River, Michigan1
Authors: Wells Robert R. , Langendoen Eddy J. , Simon Andrew 
Published: May 2007

Abstract: The state of Michigan is interested in removing two low‐head dams in an 8.8 km reach of the Kalamazoo River between Plainwell and Otsego, Michigan, while minimizing impacts locally and to downstream reaches. The study was designed to evaluate the erosion, transport, and deposition of sediments over a 37.3‐year period using the channel evolution model CONCEPTS for three simulation scenarios: Dams In (DI), Dams Out (DO), and Design (D). The total mass of sediment emanating from the channel boundary, for the DI case, shows net deposition of 4,100 T/y for the study reach, with net transport (suspended and bed load) of 10,500 T/y passing the downstream boundary. For the DO case, net erosion is 19,200 T/y with net transport of 30,100 T/y (187% increase) passing the downstream boundary. For the D case, net deposition is 2,570 T/y (37% decrease) with transport of 14,200 T/y (35% increase) passing the downstream boundary. The most significant findings were: (1) removal of the low‐head dams will cause significant erosion of sediments stored behind the dams and increased sediment loads passing the downstream boundary and (2) sediment loads for the proposed channel design are similar to existing conditions and offer reduced fine‐sediment loadings.
Effect of static stretching of muscles surrounding the knee on knee joint position sense
Authors: Ghaffarinejad Farahnaz , Taghizadeh Shohreh , Mohammadi Farshid 
Published: May 2007

Background:Muscle stretching is widely used in sport training and in rehabilitation. Considering the important contribution of joint position sense (JPS) to knee joint stability and function, it is legitimate to question if stretching might alter the knee JPS.Objective:To evaluate if a stretch regimen consisting of three 30 s stretches alters the knee JPS.Design and setting:A blinded, randomised design with a washout time of 24 h was used.Subjects:39 healthy students (21 women, 18 men) volunteered to participate in this study.Methods and main outcome measures:JPS was estimated by the ability to reproduce the two target positions (20° and 45° of flexion) in the dominant knee. The absolute angular error (AAE) was defined as the absolute difference between the target angle and the subject perceived angle of knee flexion. AAE values were measured before and immediately after the static stretch. Measurements were repeated three times. The static stretch comprised a 30 s stretch followed by a 30 s pause, three times for each muscle.Results:The AAE decreased significantly after the stretching protocols for quadriceps (3.5 (1.3) vs 0.7 (2.4); p<0.001), hamstring (3.6 (2.2) vs 1.6 (3.1); p = 0.016) and adductors (3.7 (2.8) vs 1.7 (2.4); p = 0.016) in 45° of flexion, but no differences were found for values of the gastrocnemius and popliteus muscles in this angle and for the values of all muscles in 20° of flexion (p>0.05).Conclusion:The accuracy of the knee JPS in 45° of flexion is improved subsequent to a static stretch regimen of quadriceps, hamstring and adductors in healthy subjects.
Salbutamol exhibits androgenic activity in vitro
Authors: von Bueren André O , Ma Risheng , Schlumpf Margret , Lichtensteiger Walter 
Published: May 2007

Background:Salbutamol has been shown to mediate anabolic effects after intravenous administration. However, the mechanism responsible for the anabolic actions of salbutamol remains unknown.Aim:To investigate the potential mechanism by which salbutamol mediates anabolic effects in vitro.Methods:The potential androgenic activity of salbutamol was investigated in vitro by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1.Results:The assay was validated with three known androgens; methyltrienolone (R1881), 5α-dihydrotestosterone (DHT) and danazol. IC50values of R1881, DHT and danazol, 4.41×10−11, 4.44×10−11and 1.08×10−8M, respectively, were in the ranges known from earlier studies. Our results demonstrate that salbutamol exhibits androgenic activity, with an IC50value of 8.93×10−6M. Anti-estrogenic or cytotoxic effects, which might have interfered with the assay, were excluded by additional experiments on wild-type MCF7 and MCF7-AR1 cells, respectively.Conclusion:These data indicate that salbutamol exerts anabolic effects through androgen receptor agonistic activity in vitro.
The influence of velocity of stretch–shortening contractions on muscle performance during chronic exposure: age effects
Authors: Cutlip Robert G. , Baker Brent A. , Geronilla Ken B. , Kashon Michael L. , Wu John Z. 
Published: May 2007

Aging increases injury susceptibility and impairs the ability to adapt to repetitive exposures of mechanical loading. The objective of this research was to investigate if movement velocity affects muscle response to a chronic administration of stretch–shortening cycles (SSCs) differently in young vs. old rats. Dorsiflexor muscles of old (30 months, n = 5) and young rats (12 weeks, n = 6) were exposed 3 times/week for 4.5 weeks to a protocol of 80 maximal SSCs per exposure in vivo. Skeletal muscle response was characterized by high- (500°/s) and low- (60°/s) velocity dynamic performance, which was evaluated using peak eccentric force, isometric pre-stretch force, eccentric force enhancement above the isometric pre-stretch force, negative work, and positive work. The performance of the young and old groups was not statistically different at the start of the exposure. By the end of the exposure, however, a statistical difference was noted—performance increased significantly in the young animals and decreased significantly in the old animals. The SSC velocity had a profound effect on muscle response. The young animals’ high- and low-velocity performances increased during the chronic exposure period, whereas the old animals’ performances declined. High-velocity performance increased more than low-velocity performance in young animals. In contrast, old animals suffered the most loss in high-velocity performance over the chronic exposure period. A chronic exposure of SSCs results in a significant performance increase in young animals, and a significant performance decrease in old animals. These differences are more profound during high-velocity movements. These findings suggest that age may impair the ability of skeletal muscle to adapt to repetitive mechanical loading, particularly during high-velocity movements.
Neither gender nor menstrual cycle phase influences exercise-induced lymphocyte apoptosis in untrained subjects
Authors: Navalta James W. , Sedlock Darlene A. , Park Kyung-Shin , McFarlin Brian K. 
Published: May 2007

Lymphocyte apoptosis increases following maximal exercise. Estrogen hormones (E2) have been shown to protect lymphocytes from apoptosis in vitro, but it is unknown whether they can attenuate the apoptotic response to maximal exercise. The purpose of this study was to examine the effect of menstrual cycle variation on exercise-induced lymphocyte apoptosis in humans following exercise. Untrained healthy young men and regularly menstruating women not using hormonal contraceptives volunteered for the study. Women performed a maximal effort treadmill test for VO2 max once in the follicular phase (FOL) and once in the mid-luteal phase (ML) of their cycles. Men completed two VO2 max tests with periods of time between tests matched to those of the female subjects. Blood was collected before (PRE) and immediately after exercise (POST), and analyzed for apoptotic lymphocytes and estradiol. E2 concentrations in women were significantly greater during ML versus during FOL, both PRE and POST (p < 0.0001). The percent of exercise-induced lymphocyte apoptosis was similar between women (23.2% ± 1.0%) and men (21.5% ± 0.4%). In women, the apoptotic response to maximal exercise was similar regardless of menstrual cycle phase (FOL = 23.7% ± 0.9%, ML = 22.7% ± 1.1%). Although elevated female sex hormones in vitro may exert anti-apoptotic effects, these data suggest that in vivo concentrations confer no protection to lymphocytes during exhaustive exercise.
Thermoregulation as a function of thermal quality in a northern population of painted turtles, Chrysemys picta
Authors: Edwards A.L. , Blouin-Demers G. 
Published: May 2007

Body temperature affects nearly all processes of ectotherms. Reptiles do not generate sufficient body heat to regulate their body temperature internally and therefore use behavioural thermoregulation. We determined whether thermoregulatory effort varied among seasons in an environment where large temporal differences in environmental temperatures (Te) exist. We took 31 297 internal body temperature (Tb) measurements from 18 painted turtles ( Chrysemys picta (Schneider, 1783)) throughout their active season. We estimated Te with physical models and water temperatures. We measured the range of preferred body temperatures (Tset) in a thermal gradient. Tset was 21.3–25.0 °C. We used Tb, Te, and Tset to calculate standard thermoregulation indices (Ex and de – db). An Ex of 40.7% and a de – db of 2.4 °C indicated that painted turtles are moderate thermoregulators, despite inhabiting a high-cost environment. Effort to regulate Tb increased as the thermal quality of the habitat decreased. Thermoregulatory effort was higher when Tset could not be achieved. Painted turtles put more effort in thermoregulation in the early season than in the rest of the season. This within-species pattern follows the pattern seen among species. This study is the first to measure Tb internally and to apply standard thermoregulation indices to free-ranging turtles.
Expression of p16Ink4a Compensates for p18Ink4c Loss in Cyclin-Dependent Kinase 4/6–Dependent Tumors and Tissues
Authors: Ramsey Matthew R. , Krishnamurthy Janakiraman , Pei Xin-Hai , Torrice Chad , Lin Weili , Carrasco Daniel R. , Ligon Keith L. , Xiong Yue , Sharpless Norman E. 
Published: May 2007

Abstract
Cell cycle progression from G1 to S phase depends on phosphorylation of pRb by complexes containing a cyclin (D type or E type) and cyclin-dependent kinase (e.g., cdk2, cdk4, or cdk6). Ink4 proteins function to oppose the action of cdk4/6-cyclin D complexes by inhibiting cdk4/6. We employed genetic and pharmacologic approaches to study the interplay among Ink4 proteins and cdk4/6 activity in vivo. Mouse embryo fibroblasts (MEF) lacking p16Ink4a and p18Ink4c showed similar growth kinetics as wild-type MEFs despite increased cdk4 activity. In vivo, germline deficiency of p16Ink4a and p18Ink4c resulted in increased proliferation in the intermediate pituitary and pancreatic islets of adult mice, and survival of p16Ink4a−/−;p18Ink4c−/− mice was significantly reduced due to aggressive pituitary tumors. Compensation among the Ink4 proteins was observed both in vivo in p18Ink4c−/− mice and in MEFs from p16Ink4a−/−, p18Ink4c−/−, or p16Ink4a−/−;p18Ink4c−/− mice. Treatment with PD 0332991, a specific cdk4/6 kinase inhibitor, abrogated proliferation in those compartments where Ink4 deficiency was associated with enhanced proliferation (i.e., islets, pituitary, and B lymphocytes) but had no effect on proliferation in other tissues such as the small bowel. These data suggest that p16Ink4a and p18Ink4c coordinately regulate the in vivo catalytic activity of cdk4/6 in specific compartments of adult mice. [Cancer Res 2007;67(10):4732–41]
Molecular Basis of the Synergistic Antiangiogenic Activity of Bevacizumab and Mithramycin A
Authors: Jia Zhiliang , Zhang Jun , Wei Daoyan , Wang Liwei , Yuan Ping , Le Xiangdong , Li Qiang , Yao James , Xie Keping 
Published: May 2007

Abstract
The impact of antiangiogenic therapy on the Sp1/vascular endothelial growth factor (VEGF) pathway and that of alteration of Sp1 signaling on the efficacy of antiangiogenic therapy is unclear, yet understanding their interactions has significant clinical implications. Treatment with bevacizumab, a neutralizing antibody against VEGF, suppressed human pancreatic cancer growth in nude mice. Gene expression analyses revealed that this treatment substantially up-regulated the expression of Sp1 and its downstream target genes, including VEGF and epidermal growth factor receptor, in tumor tissues, whereas it did not have this effect on pancreatic cancer cells in culture. Treatment with mithramycin A, an Sp1 inhibitor, suppressed the expression of Sp1 and its downstream target genes in both cell culture and tumors growing in nude mice. Combined treatment with bevacizumab and mithramycin A produced synergistic tumor suppression, which was consistent with suppression of the expression of Sp1 and its downstream target genes. Thus, treatment with bevacizumab may block VEGF function but activate the pathway of its expression via positive feedback. Given the fact that Sp1 is an important regulator of the expression of multiple angiogenic factors, bevacizumab-initiated up-regulation of Sp1 and subsequent overexpression of its downstream target genes may profoundly affect the potential angiogenic phenotype and effectiveness of antiangiogenic strategies for human pancreatic cancer. Therefore, this study is the first to show the significance and clinical implications of alteration of Sp1 signaling in antiangiogenic therapy for pancreatic cancer and other cancers. [Cancer Res 2007;67(10):4878–85]
Differential Effects of Targeted Disruption of Thiopurine Methyltransferase on Mercaptopurine and Thioguanine Pharmacodynamics
Authors: Hartford Christine , Vasquez Erick , Schwab Matthias , Edick Mathew J. , Rehg Jerold E. , Grosveld Gerard , Pui Ching-Hon , Evans William E. , Relling Mary V. 
Published: May 2007

Abstract
The recessive deficiency in thiopurine methyltransferase (TPMT), caused by germ-line polymorphisms in TPMT, can cause severe toxicity after mercaptopurine. However, the significance of heterozygosity and the effect of the polymorphism on thioguanine or in the absence of thiopurines is not known. To address these issues, we created a murine knockout of Tpmt. Pharmacokinetic and pharmacodynamic studies of mercaptopurine and thioguanine were done in Tpmt−/−, Tpmt+/−, and Tpmt+/+ mice and variables were compared among genotypes. Methylated thiopurine and thioguanine nucleotide metabolites differed among genotypes after treatment with mercaptopurine (P &lt; 0.0001 and P = 0.044, respectively) and thioguanine (P = 0.011 and P = 0.002, respectively). Differences in toxicity among genotypes were more pronounced following treatment with 10 daily doses of mercaptopurine at 100 mg/kg/d (0%, 68%, and 100% 50-day survival; P = 0.0003) than with thioguanine at 5 mg/kg/d (0%, 33%, and 50% 15-day survival; P = 0.07) in the Tpmt−/−, Tpmt+/−, and Tpmt+/+ genotypes, respectively. Myelosuppression and weight loss exhibited a haploinsufficient phenotype after mercaptopurine, whereas haploinsufficiency was less prominent with thioguanine. In the absence of drug challenge, there was no apparent phenotype. The murine model recapitulates many clinical features of the human polymorphism; indicates that mercaptopurine is more affected by the TPMT polymorphism than thioguanine; and provides a preclinical system for establishing safer regimens of genetically influenced antileukemic drug therapy. [Cancer Res 2007;67(10):4965–72]
The Combined Effects of Xeroderma Pigmentosum C Deficiency and Mutagens on Mutation Rates in the Mouse Germ Line
Authors: Miccoli Laurent , Burr Karen L-A. , Hickenbotham Peter , Friedberg Errol C. , Angulo Jaime F. , Dubrova Yuri E. 
Published: May 2007

Abstract
Spontaneous and induced mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germ line of xeroderma pigmentosum group C (Xpc) knockout mice defective in global genome nucleotide excision repair. Spontaneous and radiation-induced mutation rates in homozygous Xpc−/− males were significantly higher than those in isogenic wild-type (Xpc+/+) and heterozygous (Xpc+/−) mice. In contrast, exposure to the monofunctional alkylating agent ethylnitrosourea resulted in similar increases in ESTR mutation rates across all genotypes. ESTR mutation spectra in the germ line of Xpc−/−, Xpc+/− and Xpc+/+ did not differ. Considering these data and the results of other publications, we propose that the Xpc-deficient mice possess a mutator phenotype in their germ line and somatic tissues that may significantly enhance carcinogenesis across multiple tissues. [Cancer Res 2007;67(10):4695–9]
Chemotherapy-Induced Thrombocytopenia Derives from the Selective Death of Megakaryocyte Progenitors and Can Be Rescued by Stem Cell Factor
Authors: Zeuner Ann , Signore Michele , Martinetti Daniela , Bartucci Monica , Peschle Cesare , De Maria Ruggero 
Published: May 2007

AbstractThrombocytopenia is a common side effect of chemotherapy, responsible for increased risk of bleeding and delay of treatment schedules in cancer patients. It is currently unknown how chemotherapeutic agents affect platelet production and whether the platelet precursors megakaryocytes represent a direct target of cytotoxic drugs. We investigated the effects of chemotherapeutic agents on primary megakaryocytes by using a culture system that recapitulates in vitro human megakaryopoiesis and found that cytotoxic drugs predominantly destroyed megakaryocytic progenitors at early stages of differentiation. Immature megakaryocytes could be protected from chemotherapeutic agents by the cytokine stem cell factor (SCF), which binds the c-kit receptor expressed on hematopoietic stem and progenitor cells. In chemotherapy-treated megakaryocytes, SCF activated Akt, neutralized the mitochondrial apoptotic machinery, and inhibited caspase activity. Interfering with Akt activation abrogated the antiapoptotic effects of SCF, whereas exogenous expression of constitutively active Akt inhibited drug-induced apoptosis of primary megakaryocytes, indicating the Akt pathway as primarily responsible for SCF-mediated protection of megakaryocyte progenitors. These results indicate apoptosis of megakaryocyte progenitors as a major cause of chemotherapy-induced thrombocytopenia and suggest that SCF may be used to prevent platelet loss in cancer patients with c-kit–negative tumors. [Cancer Res 2007;67(10):4767–4773]
Transcriptional Control of the Human High Mobility Group A1 Gene: Basal and Oncogenic Ras-Regulated Expression
Authors: Cleynen Isabelle , Huysmans Christel , Sasazuki Takehiko , Shirasawa Senji , Van de Ven Wim , Peeters Kristel 
Published: May 2007

Abstract
Several studies have already shown that the high mobility group A1 (HMGA1) gene is up-regulated in most common types of cancer and immortalized tissue culture cell lines. HMGA1 expression is also much higher during embryonic development than in adult life. The elevated expression of HMGA1 in cancer thus likely occurs through oncofetal transcriptional mechanisms, which to date have not been well characterized. In the present study, we have cloned and functionally analyzed the TATA-less 5′-flanking regulatory region of human HMGA1. We identified two proximal regulatory regions that are important for basal transcription and in which specificity protein 1 (SP1) and activator protein 1 (AP1) transcription factors seem to be the regulating elements. In addition, we showed that the HMGA1 promoter is strongly inducible by oncogenic Ras, via a distal regulatory region. An AP1 site and three SP1-like sites are responsible for this inducible activity. An even more convincing finding for a role of oncogenic Ras in the regulation of HMGA1 in cancers is the discovery that HMGA1 up-regulation in the HCT116 colon cancer cell line is abolished when the mutated Ras allele is removed from these cells. Our data constitute the first extensive study of the regulation of basal and Ras-induced human HMGA1 gene expression and suggest that the elevated expression of HMGA1 in cancer cells requires, among others, a complex cooperation between SP1 family members and AP1 factors by the activation of Ras GTPase signaling. [Cancer Res 2007;67(10):4620–9]
Armed Antibodies Targeting the Mucin Repeats of the Ovarian Cancer Antigen, MUC16, Are Highly Efficacious in Animal Tumor Models
Authors: Chen Youjun , Clark Suzanna , Wong Terence , Chen Yongmei , Chen Yvonne , Dennis Mark S. , Luis Elizabeth , Zhong Fiona , Bheddah Sheila , Koeppen Hartmut , Gogineni Alvin , Ross Sarajane , Polakis Paul , Mallet William 
Published: May 2007

Abstract
MUC16 is a well-validated cell surface marker for serous adenocarcinomas of the ovary and other gynecologic malignancies that is distinguished by highly repetitive sequences (“mucin repeats”) in the extracellular domain (ECD). We produced and compared two monoclonal antibodies: one (11D10) recognizing a unique, nonrepeating epitope in the ECD and another (3A5) that recognizes the repeats and binds multiple sites on each MUC16 protein. 3A5 conjugated to cytotoxic drugs exhibited superior toxicity against tumor cells in vitro and in tumor xenograft models compared with antibody-drug conjugates of 11D10. Importantly, drug conjugates of 3A5 were well tolerated in primates at levels in excess of therapeutic doses. Additionally, the presence of circulating CA125 in a rat model did not exacerbate the toxicity of 3A5 drug conjugates. We conclude that targeting the repeat MUC16 domains, thereby increasing cell-associated levels of drug-conjugated antibody, provides superior efficacy in vitro and in vivo without compromising safety. [Cancer Res 2007;67(10):4924–32]