bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumor activity of an epithelial cell adhesion molecule–targeted nanovesicular drug delivery system
Authors: Hussain Sajid , Plückthun Andreas , Allen Theresa M. , Zangemeister-Wittke Uwe 
Published: November 2007

Abstract
Site-specific delivery of anticancer agents to tumors represents a promising therapeutic strategy because it increases efficacy and reduces toxicity to normal tissues compared with untargeted drugs. Sterically stabilized immunoliposomes (SIL), guided by antibodies that specifically bind to well internalizing antigens on the tumor cell surface, are effective nanoscale delivery systems capable of accumulating large quantities of anticancer agents at the tumor site. The epithelial cell adhesion molecule (EpCAM) holds major promise as a target for antibody-based cancer therapy due to its abundant expression in many solid tumors and its limited distribution in normal tissues. We generated EpCAM-directed immunoliposomes by covalently coupling the humanized single-chain Fv antibody fragment 4D5MOCB to the surface of sterically stabilized liposomes loaded with the anticancer agent doxorubicin. In vitro, the doxorubicin-loaded immunoliposomes (SIL-Dox) showed efficient cell binding and internalization and were significantly more cytotoxic against EpCAM-positive tumor cells than nontargeted liposomes (SL-Dox). In athymic mice bearing established human tumor xenografts, pharmacokinetic and biodistribution analysis of SIL-Dox revealed long circulation times in the blood with a half-life of 11 h and effective time-dependent tumor localization, resulting in up to 15% injected dose per gram tissue. These favorable pharmacokinetic properties translated into potent antitumor activity, which resulted in significant growth inhibition (compared with control mice), and was more pronounced than that of doxorubicin alone and nontargeted SL-Dox at low, nontoxic doses. Our data show the promise of EpCAM-directed nanovesicular drug delivery for targeted therapy of solid tumors. [Mol Cancer Ther 2007;6(11):3019–27]
Cysteine-Rich 61 (CCN1) Enhances Chemotactic Migration, Transendothelial Cell Migration, and Intravasation by Concomitantly Up-Regulating Chemokine Receptor 1 and 2
Authors: Lin Been-Ren , Chang Cheng-Chi , Chen Li-Ro , Wu Ming-Hsun , Wang Ming-Yang , Kuo I-Hsin , Chu Chia-Yu , Chang King-Jen , Lee Po-Huang , Chen Wei-Jao , Kuo Min-Liang , Lin Ming-Tsan 
Published: November 2007

AbstractCysteine-rich 61 (Cyr61; CCN1) plays an important role in tumor development and progression in many kinds of human malignancies. Here, we further show the enforced expression of the Cyr61 gene or treatment with recombinant Cyr61 protein enhanced expression of chemokine receptors CXCR1 and CXCR2 in gastric cancer AGS cells. Attenuation of Cyr61 levels in MKN-45 cells by transfecting with antisense Cyr61 significantly reduced the level of CXCR1 and CXCR2. It is suggested that Cyr61 tightly regulates the downstream genes CXCR1 and CXCR2 in gastric cancer cells. Supportively, reverse transcription–PCR and immunohistochemical analysis of human gastric adenocarcinoma showed that there was a high correlation between the expression level of Cyr61 and CXCR1/CXCR2. The up-regulated functionality of CXCR1 andCXCR2 in Cyr61-overexpressing AGS cells could facilitate their chemotactic migration toward interleukin-8, a physiologic ligand of CXCR1 and CXCR2. In addition, the Cyr61-mediated up-regulation of CXCR1/CXCR2 also contributed to transendothelial migration, as well as intravasation in a chick embryo model. Pharmacologic and genetic approaches revealed that phosphoinositide 3-kinase (PI3K)/Akt, but not extracellular signal-regulated kinase 1/2 or p38, signaling pathway is requisite for the up-regulation of CXCR1/CXCR2 mRNA and protein induced by Cyr61. Function-neutralizing antibody to integrin αvβ3, but not α2β1, effectively abolished Cyr61-elicited Src activation and the subsequent PI3K/Akt pathway. Antagonists toward integrin αvβ3, Src kinase, and PI3K/Akt not only suppressed CXCR1/CXCR2 elevation but also blocked chemotactic migration induced by Cyr61. In conclusion, we suggest that Cyr61 promotes interleukin-8–dependent chemotaxis, transendothelial migration, and intravasation by induction of CXCR1/CXCR2 through integrin αvβ3/Src/PI3K/Akt–dependent pathway. (Mol Cancer Res 2007;5(11):1111–23)
Cyclin-Dependent Kinase Inhibitors Sensitize Tumor Cells to Nutlin-Induced Apoptosis: a Potent Drug Combination
Authors: Cheok Chit Fang , Dey Anwesha , Lane David P. 
Published: November 2007

AbstractCurrent chemotherapy focuses on the use of genotoxic drugs that may induce general DNA damage in cancer cells but also high levels of toxicity in normal tissues. Nongenotoxic activation of p53 by targeting specific molecular pathways therefore provides an attractive therapeutic strategy in cancers with wild-type p53. Here, we explored the antitumor potential of cyclin-dependent kinase (CDK) inhibitors in combination with a small molecule inhibitor of p53-murine double minute 2 (MDM2) interaction. We show that low doses of CDK inhibitors roscovitine and DRB synergize with the MDM2 antagonist nutlin-3a in the induction of p53 activity and promote p53-dependent apoptosis in a dose- and time-dependent manner. Statistical measurement of the combination effects shows that the drug combination is additive on the reduction of cell viability and synergistic on inducing apoptosis, a critical end point of cytotoxic drugs. The degree of apoptosis observed 24 to 48 h after drug treatment correlated with the accumulation of p53 protein and concomitant induction of proapoptotic proteins Puma and PIG3. The antiproliferative and cytotoxic effects of this drug combination are validated in a range of tumor-derived cells including melanoma, colon carcinoma, breast adenocarcinoma, and hepatocarcinoma cells. Furthermore, this drug combination does not induce phosphorylation of Ser15 on p53 and does not induce genotoxic stress in the cell. Given that many cytotoxic drugs rely on their ability to induce apoptosis via DNA damage–mediated activation of p53, the data presented here may provide a new therapeutic approach for the use of CDK inhibitors and MDM2 antagonists in combinatorial drug therapy. (Mol Cancer Res 2007;5(11):1133–45)
A Note on Problem Difficulty Measures in Black-Box Optimization: Classification, Realizations and Predictability
Authors: He Jun , Reeves Colin , Witt Carsten , Yao Xin 
Published: November 2007

Various methods have been defined to measure the hardness of a fitness function for evolutionary algorithms and other black-box heuristics. Examples include fitness landscape analysis, epistasis, fitness-distance correlations etc., all of which are relatively easy to describe. However, they do not always correctly specify the hardness of the function. Some measures are easy to implement, others are more intuitive and hard to formalize. This paper rigorously defines difficulty measures in black-box optimization and proposes a classification. Different types of realizations of such measures are studied, namely exact and approximate ones. For both types of realizations, it is proven that predictive versions that run in polynomial time in general do not exist unless certain complexity-theoretical assumptions are wrong.
Association of Eating Attitudes Between Teenage Girls and Their Parents
Authors: Yanez Aina A. , Peix Maria A. , Atserias Neus , Arnau Anna , Brug Johannes , Yanez Aina A. , Peix Maria A. , Atserias Neus , Arnau Anna , Brug Johannes 
Published: November 2007

Background: Mothers of eating disordered adolescents were more likely to have an eating disorder. However, some contradictory findings were reported because some studies failed to find this association. Aims: The main objective of the study was to determine the association of eating attitudes in adolescent girls with eating attitudes in their parents. Methods: A sample of 969 girls from Osona County (Barcelona, Spain) and their parents participated in the study. Girls completed the Eating Attitudes Test (EAT-26) and their weight and height were measured. Parents completed questionnaire with self-reported weight and height, demographic characteristics and EAT-26. Results: 10.1% of girls showed high EAT-26 scores (> 20 points), indicating abnormal eating attitudes. Female adolescents were almost three times more likely to have abnormal eating attitudes if their mothers scored high on EAT-26 (OR = 2.8; 95% CI 1.5—5.2). Other significant predictors of high EAT-26 scores were age and obesity. Conclusions: An abnormal eating attitude of the mother was identified as a potential risk factor in the development of eating disorders in female adolescents.
Ethnic Disparities in Mental Health and Educational Attainment: Comparing Migrant and Native Children
Authors: Van Oort Floor V.A. , Van der Ende Jan , Crijnen Alfons A.M. , Verhulst Frank C. , Mackenbach Johan P. , Joung Inez M.A. 
Published: November 2007

Study background and aims: Ethnic disparities in mental health in adolescence may play a role in the development of ethnic disparities in educational attainment. The aim of this study was to assess the contribution of ethnic disparities in mental health problems in adolescence to ethnic disparities in educational attainment in adulthood. Methods: We followed two community samples of respectively 486 Dutch native and 168 Turkish migrant adolescents (11—15 years old) into adulthood (21—25 years old). Mental health was measured in adolescence, and educational attainment was assessed in adulthood. The contribution of mental health disparities to educational disparities was estimated by the degree of attenuation of the odds ratio (OR) for low education after adjustment for mental health problems. Results: Adult Turkish men more often had attained lower education than Dutch men (OR 1.81 (1.01—3.25)). Additional adjustment for mental health problems during adolescence did not change the OR. In Turkish women, however, the OR was 1.94 (1.04—3.62), and adjustment for mental health problems lowered it by 96% to 1.04 (0.51—2.14). The contribution was mostly due to ethnic disparities in internalizing problems. Conclusion: In women, but not in men, ethnic disparities in mental health, especially internalizing problems, were a strong predictor for the development of ethnic disparities in educational attainment. Prevention or treatment of internalizing problems among Turkish girls will probably contribute to the prevention of educational disparities.
Changes in Social Network Diversity and Perceived Social Support After Psychiatric Hospitalization: Results From a Longitudinal Study
Authors: Müller Brigitte , Nordt Carlos , Lauber Christoph , Rössler Wulf 
Published: November 2007

Background: There is a large empirical basis for the importance of social networks and support for people with a mental illness. However, only a few studies have eXamined the predictors, changes and correlations of these constructs within a longitudinal framework. Aim: To analyze changes in social network diversity as measured by the number of social roles and perceived social support over the course of three years after a psychiatric hospitalization while controlling for sociodemographic and clinical variables. A further aim was to inquire whether some social roles are perceived as being more supportive than others. Method: Random coefficient models were applied to the data of a longitudinal study on the life circumstances of people with affective disorders or schizophrenia ( N = 183). Results: The majority of participants had relatives, friends and co-workers, while a markedly smaller proportion had a spouse/partner or children. Social network diversity increased during the time period observed while the perception of social support did not change. Being male, without a job (competitive or sheltered), or having a low income predicted less diverse networks. Partners and friends were perceived as most supportive. Persons without a close friendship perceived less overall support, but only at baseline (hospitalization), while persons with a job on the competitive labor market felt better supported. Conclusions: Social disintegration in the course of mental illness that is found in some studies has no equivalent in our study in what concerns network diversity and perceived support. According to our results, characteristics of vocational and economic integration are of much greater relevance, as they enhance or hinder access to social participation.
Mental Illness Stigma in the Israeli Context: Deliberations and Suggestions
Authors: Tal Amir , Roe David , Corrigan Patrick W. 
Published: November 2007

Background: In this paper we deliberate mental illness stigma in the Israeli conteXt and suggest ways to reduce it, emphasizing the community's role in the rehabilitation of persons with mental illness.Material: A literature review of Israeli and international literature of mental illness stigma.Discussion: Community mental health, in addition to its traditional focus on developing community-based services, should focus also on community-based interventions such as the delivery of anti-stigma interventions.Conclusions: Providing individualized rehabilitation services in the community while addressing stigma-induced social barriers may create a better recovery ground for Israelis with mental illness.
Reducing resistance against polio drops
Authors: Athar Ansari M. , Khan Z. , Khan I.M. 
Published: November 2007

Aims: The present study was carried out to impart correct health education regarding polio eradication programme and to assess the impact of social mobilization of a Muslim community carried out by medical interns. Methods: One round of a polio immunization campaign was selected randomly. Five highly resistant areas were included in the study. During house to house A-Team activity, teams of health workers visited the houses and resistant families were identified. These families refused to give polio drops to their children. On the second day of A-Team activity, medical interns visited those identified resistant families. They imparted correct health education and tried to convince them to give polio drops. However, after prolonged persuasion, some of the families were not ready to give polio drops. These more resistant families were again visited by more motivated and enthusiastic teams during B-Team activity, started two to three days after the completion of A-Team activity. Data were collected, tabulated and analysed. Results: Total number of resistant families identified during house to house A-Team activity was 1025 in five high risk areas of Aligarh, India. Out of 1025 resistant houses, 510 (49.76%) houses were converted to P houses where polio drops were given to the children. Five hundred and fifteen (50.24%) houses remained resistant even after social mobilization by A-Team members. These most resistant houses were again visited by B-team members. Out of these 515 houses, polio drops were administered in 303 (58.83%). The overall number of converted houses was 813 (79.32%) after A and B-team activities. 20.68% of families remained resistant and their children could not be given polio drops. Conclusions: In all high risk areas, maximum numbers of resistant houses were converted to P houses. These families were persuaded and convinced by the teams of interns, social workers and influential persons that polio drops did not have any side effects. They were more receptive to the advice given by medical interns compared to other staff members of the Government District Hospital because of quality of health services provided to the community. There is a need to impart correct health education regarding importance of polio drops and routine immunization more vigorously through information, education and communication (IEC) activities.
Social support for stress prevention in hospital settings
Authors: Park Kyoung-Ok 
Published: November 2007

Aims: The purpose of this study was to identify the effects of social support, interacting with work stressors, on psychological stress prevention in a public hospital, based on Karasek's demand-control-support (DCS) model. Methods: A self-administered survey was conducted with 240 employees of a public hospital in the south-east of the United States. The survey asked for demographic information, details on job demands and job control as work stressors, social support, and depressive symptoms as the representative psychological stress symptoms. Results: Social support was detected as a primary interpersonal positive factor buffering depressive symptoms. Social support was also related to job control and depressive symptoms in the simple correlation. Only the main effect model with general characteristics was significantly accepted in hierarchical regression analysis (p=.04). High social support was associated with low depressive symptom scores, which means that social support had a positive association with health care employees' mental well being. However, any two-way or three-way interaction model was not accepted. The main effect part of the demand-control-support model was supported; however, interactions between demands, control, and support failed to be supported.
Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase
Authors: Aiba Yuichi , Kameyama Megumi , Yamazaki Tetsuo , Tedder Thomas F. , Kurosaki Tomohiro 
Published: November 2007

Abstract
Despite the importance of phosphoinositide 3-kinase (PI3K) in B-cell development, its activation mechanism still remains elusive. In this study, we show that deletion of both BCAP and CD19 leads to an almost complete block of BCR-mediated Akt activation and to severe defects in generation of immature and mature B cells. The YXXM motifs in BCAP and CD19 are crucial for regulating B-cell development in that mutation of these motifs abrogated their ability to induce BCR-mediated Akt activation as well as to promote B-cell development. Furthermore, the developmental defect in CD19−/−BCAP−/− B cells was partly relieved by introducing a constitutively active form of PI3K or PDK1. Together, our data suggest that BCAP and CD19 have complementary roles in BCR-mediated PI3K activation, thereby, at least in part, contributing to B-cell development.
Passive mechanical properties of human gastrocnemius muscle–tendon units, muscle fascicles and tendonsin vivo
Authors: Hoang P. D. , Herbert R. D. , Todd G. , Gorman R. B. , Gandevia S. C. 
Published: November 2007

SUMMARYThis study provides the first in vivo measures of the passive length–tension properties of relaxed human muscle fascicles and their tendons. A new method was used to derive passive length–tension properties of human gastrocnemius muscle–tendon units from measures of ankle stiffness obtained at a range of knee angles. Passive length–tension curves of the muscle–tendon unit were then combined with ultrasonographic measures of muscle fascicle length and pennation to determine passive length–tension curves of the muscle fascicles and tendons. Mean slack lengths of the fascicles, tendons and whole muscle–tendon units were 3.3±0.5 cm, 39.5±1.6 cm and 42.3±1.5 cm, respectively (means ± s.d., N=6). On average, the muscle–tendon units were slack (i.e. their passive tension was zero) over the shortest 2.3±1.2 cm of their range. With combined changes of knee and ankle angles, the maximal increase in length of the gastrocnemius muscle–tendon unit above slack length was 6.7±1.9 cm, of which 52.4±11.7% was due to elongation of the tendon. Muscle fascicles and tendons underwent strains of 86.4±26.8% and 9.2±4.1%, respectively, across the physiological range of lengths. We conclude that the relaxed human gastrocnemius muscle–tendon unit falls slack over about one-quarter of its in vivo length and that muscle fascicle strains are much greater than tendon strains. Nonetheless, because the tendons are much longer than the muscle fascicles, tendons contribute more than half of the total compliance of the muscle–tendon unit.
Phosducin interacts with the G-protein βγ-dimer of ciliate protozoanBlepharisma japonicumupon illumination
Authors: Sobierajska Katarzyna , Fabczak Hanna , Fabczak Stanislaw 
Published: November 2007

SUMMARYImmunological techniques and high-resolution FRET analysis were employed to investigate the in vivo colocalization and interaction of phosducin(Pdc) with the βγ-subunits of G-protein (Gβγ) in the ciliate Blepharisma japonicum. Immunological techniques revealed that illumination of cells resulted in a decrease in phosphorylation levels of Pdc and its colocalization with Gβγ. The observed light-induced Pdc dephosphorylation was also accompanied by significant enhancement of Gβγ binding by this molecule. Possible formation of the Pdc–Gβγ complex in cells exposed to light was corroborated by FRET between these proteins. Treatment of cells with okadaic acid, an inhibitor of phosphatase activity, entirely prevented Pdc dephosphorylation by light, colocalization of this phosphoprotein with Gβγ and generation of the Pdc–Gβγ complex. Cell fractionation and immunoblotting revealed that in cells exposed to light, the formation of Pdc–Gβγ complex and its translocation into the cytoplasm occur simultaneously with a change in the gel migration of Gβ. Moreover, a 33 kDa immunoanalog of 14-3-3 protein was identified and we showed that this protein is bound by phosphorylated Pdc in a cell adapted to darkness. The results of this study provide additional detailed characterization of the functional properties of the ciliate Pdc. The likely functional role of Pdc in Blepharisma is discussed.
The flow generated by an active olfactory system of the red swamp crayfish
Authors: Denissenko P. , Lukaschuk S. , Breithaupt T. 
Published: November 2007

SUMMARYCrayfish are nocturnal animals that mainly rely on their chemoreceptors to locate food. On a crayfish scale, chemical stimuli received from a distant source are dispersed by an ambient flow rather than molecular diffusion. When the flow is weak or absent, food searching can be facilitated by currents generated by the animal itself. Crayfish employ their anterior fan organs to produce a variety of flow patterns. Here we study the flow generated by Procambarus clarkii in response to odour stimulation. We found that while searching for food the crayfish generates one or two outward jets. These jets induce an inflow that draws odour to the crayfish's anterior chemoreceptors. We quantified velocity fields in the inflow region using Particle Image Velocimetry. The results show that the inflow velocity decreases proportionally to the inverse distance from the animal so that it takes about 100 s for an odour plume to reach the animal's chemoreceptors from a distance of 10 cm. We compare the inflow generated by live crayfish with that produced by a mechanical model. The model consists of two nozzles and an inlet and provides two jets and a sink so that the overall mass flux is zero. Use of the model enabled us to analyze the inflow at various jet parameters. We show that variation of directions and relative intensities of the jets allows the direction of odour attraction to be changed. These results provide a rationale for biomimetic robot design. We discuss sensitivity and efficiency of such a robot.