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In a field study with 295 factory employees, three hypotheses were tested: (1) Procedural injustice at work is correlated negatively with job satisfaction and psychosomatic well-being. (2) The perception of procedural injustice depends on the person's chronic justice sensitivity. (3) Justice sensitivity moderates the correlation of procedural injustice with satisfaction and well-being, the correlation becoming larger with increasing justice sensitivity. Procedural injustice was defined as the discrepancy between desired (ought) and perceived (is) procedures. Justice sensitivity and procedural fairness according to Leventhal's criteria (consistency, nonpartiality, accuracy, correctability, representativeness) and one additional criterion (open information) were measured via questionnaire. Job satisfaction, number of sick days during the last six months and number of days a person felt sick at work during the last six months served as indicators of psychosomatic well-being. The first and second hypotheses were supported by the data. Partial support was also obtained for the third hypothesis: Justice sensitivity moderated the correlation of procedural unfairness with (a) the number of days the person felt sick at work and (b) the sum of this variable with the number of sick days. Copyright © 1999 John Wiley & Sons, Ltd.

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector inducing invasion and metastasis of tumor cells that express the Met tyrosine kinase receptor. One of the effectors of HGF/SF is the urokinase-type plasminogen activator, a serine protease that facilitates tumor progression and metastasis by controlling the synthesis of the extracellular matrix degrading plasmin. Stimulation of NIH 3T3 cells that were stably transfected with the human Met receptor (NIH 3T3-Methum) with HGF/SF induced a trans-activation of the urokinase promoter and urokinase secretion. Induction of the urokinase promoter by HGF/SF via the Met receptor was blocked by co-expression of a dominant-negative Grb2 and Sos1 expression construct. Further, the expression of the catalytically inactive mutants of Ha-Ras, RhoA, c-Raf, and Erk2 or addition of the Mek1-specific inhibitor PD 098059 abrogated the stimulation of the urokinase promoter by HGF/SF. A sequence residing between -2109 and -1870 base pairs (bp) was critical for stimulation of the urokinase gene by HGF/SF. Mobility shift assays with oligonucleotides spanning an AP-1 site at -1880 bp or a combined PEA3/AP-1 site at -1967 bp showed binding of nuclear factors from NIH 3T3-Methum cells. Expression of an expression plasmid that inhibits DNA binding of AP-1 proteins (A-Fos) abrogated inducible and basal activation of the urokinase promoter. Nuclear extract from unstimulated NIH 3T3-Methum cells contained more JunD and showed a stronger JunD supershift with the AP-1 oligonucleotides, compared with HGF/SF-stimulated cells. Consistent with the levels of JunD expression being functionally important for basal expression of the urokinase promoter, we found that overexpression of wild type JunD inhibited the induction of the urokinase promoter by HGF/SF. These data suggest that the induction of urokinase by HGF/SF is regulated by a Grb2/Sos1/Ha-Ras/c-Raf/RhoA/Mek1/Erk2/c-++ +Jun-dependent mitogen-activated protein kinase pathway.

Ever since Sigmund Freud proposed that many core psychological processes cannot be self-observed because they occur outside of the conscious mind, psychologists have searched for methods that can be used to make diagnostic inferences about a person’s dispositions without having to ask the person directly. On the one hand, the development of such indirect methods was driven by the assumption that persons may have only limited access to the underlying (automatic) processes that may be responsible for their thoughts, feelings, and actions (Nisbett & Wilson, 1977). On the other hand, the search for indirect measures was also motivated by the need to overcome a major weakness of direct (i.e., self-report) measures: their sensitivity to the distorting effects of the need for approval and other self-presentational concerns. Despite many proposals of indirect measures, none received unanimous approval from the scientific community and none obtained the trust that researchers put in self-report measures despite their well-known shortcomings. The limited success of indirect measures can be accounted for by two major reasons: First, little agreement was achieved regarding the kinds of behavior that would be suitable indicators of unconscious processes and the inferences that could be drawn from them. For example, there is little consensus on what a specific comment on a TAT picture tells us about the personality profile of a person. Second, the reliability and validity of indirect measures tends to be disappointingly low when compared to direct measures. With the fruitful exchange between cognitive and social psychology and the advance of computer-based assessment during the last 20 years, a new wave of mostly reaction-timebased indirect measures has been proposed (also referred to as implicit measures). Ten years ago, a general and flexible indirect assessment procedure appeared on the stage that seems to have considerable potential for overcoming the problems of previous indirect measures: the Implicit Association Test (IAT) as proposed by Greenwald, McGhee, and Schwartz (1998; see Schnabel, Asendorpf & Greenwald, 2008, for an up-to-date review). The IAT employs patterns in reaction time that people need for the classification of stimuli (words, pictures, symbols) according to their category membership. Classification is performed via simple motor responses such as pressing a key on a computer keyboard. The IAT is based on the assumption that classification can be performed faster if the classification of stimuli from associated concepts requires the same motor response. In the case of attitude measurement, the IAT presumes that attitudes are stored in memory as associations between an attitude category (nuclear energy) and an evaluative category (bad, evil). Accordingly, personality-IATs assume that traits are stored in memory as associations between the self and attribute concepts (talkative, intelligent, etc). The IAT is a very flexible procedure because it allows for the combination of a large number of concepts whose associations define the constructs to be measured. The publication of the IAT had tremendous impact first on social cognition and attitude research from where it originated, and then soon after on several other research areas such as personality assessment, self-esteem research, special areas of clinical psychology, and consumer behavior. It instigated a renewed interest in indirect measures and promoted the development of other reaction-time-based indirect measures. It also directed attention toward the interplay of automatic versus controlled processes and helped to refine dual-process and dual-system conceptions of the mind. Finally, it prompted a new discussion of the consistency issue that had been a focus of debate in the attitude and personality literature three decades earlier. As is the case with most new diagnostic paradigms, the IAT and other new indirect measures were not incorporated uncritically into the body of psychological assessment methods. Rather, many researchers submitted them to rigorous theoretical, methodological, and empirical analyses. These analyses identified a number of problems and open questions. Many of these ongoing issues will be addressed in the cut

In earlier studies it was shown that two domain-specific variates of belief in a just world, namely belief in immanent justice and belief in ultimate justice concerning severe illness, differ systematically and significantly. Only immanent justice leads to accusation and derogation of innocent victims while ultimate justice is concordant with positive evaluations of victims and helping behavior. With regard to the research project “Justice as a Problem within Reunified Germany” (GiP, from the German “Gerechtigkeit als innerdeutsches Problem”), two new scales were developed for purposes of measuring general belief in immanent and ultimate justice. Using a sample of 929 West Germans and 1,275 East Germans, some of the correlation patterns found in earlier studies could be replicated. For example, immanent justice did correlate with draconian judgments (the proneness to strict and severe judgments), while ultimate justice was associated with mildness. Only ultimate justice correlated with existential guilt about the underprivileged. Beside this confirmation of earlier findings, new correlation patterns were revealed. For example, only immanent justice correlated with the equity principle, whereas ultimate justice corresponded to the need and equality principles.

Elevated levels of the urokinase-type plasminogen activator (uPA) in tumor cells are conductive to tumor cell spread and metastasis. In a previous study we observed that suppression of RelA dramatically reduced endogenous uPA synthesis in the human ovarian cancer cell line OV-MZ-6. Because the uPA promoter contains three potential Rel-like protein binding motifs (RRBE, 5'-NF-kappaB, and 3'-NF-kappaB) we conducted the first thorough systematic uPA promoter analysis to examine the direct impact of Rel proteins on uPA gene transcription. Disruption of RRBE resulted in a approximately 40% decrease in uPA promoter activity, mutation of the 5'-NF-kappaB motif led to an additional 20% decrease. The 3'-NF-kappaB motif was not active. Overexpression of RelA significantly enhanced uPA promoter activity, whereas IkappaB-alpha overexpression reduced uPA promoter activity by 40%. These data were supported by the finding that endogenous uPA was also increased sixfold by overexpression of RelA and decreased by 30% upon overexpression of IkappaB-alpha. Transfection of OV-MZ-6 cells with antisense deoxynucleotides directed to RelA expression reduced uPA promoter activity by at least 40%. Our data clearly suggest that by binding to uPA promoter elements, Rel transcripton factors contribute directly to elevated uPA gene expression in human ovarian cancer cells, thereby promoting the multiple functions of uPA during tumor growth and metastasis.

PURPOSE To compare the prognostic impact of tumor angiogenesis factors (vascular endothelial growth factor [VEGF], angiogenin, and basic fibroblast growth factor [bFGF]), tumor proteolysis factors (urokinase-type plasminogen activator [uPA] and plasminogen activator inhibitor-1 [PAI-1]), and conventional tumor markers (stage, grade, and steroid receptors) in early breast cancer. PATIENTS AND METHODS In the primary clinical study, tumor angiogenesis and other factors were detected in frozen biopsies from 305 primary breast tumors. VEGF expression was assessed by chemiluminescence immunosorbent assay (ICMA); angiogenin, bFGF, uPA, and PAI-1 by enzyme-linked immunosorbent assay (ELISA); and steroid receptors (estrogen receptor [ER] and progesterone receptor [PgR]) by enzyme immunoassay (EIA). In the validating clinical study, another set of 190 node-negative primary breast tumor samples were collected at a separate institution. RESULTS Univariate analysis of the primary study showed that VEGF levels were positively correlated with recurrence (P < .001). Angiogenin levels were positively correlated with disease relapse (P < .005) for the overall collective group, but not within the node-negative subset. No significant correlations were found between tumor bFGF levels and patient survival. In multivariate regression analysis, the only independent predictors of relapse-free survival (RFS) were VEGF, uPA, and lymph node status. In the validation set, the distribution of VEGF and uPA values were similar to those in the primary study; low expression of both VEGF and uPA identified patients with a < or = 20% likelihood of recurrence within 7 years. CONCLUSION Separate primary and validating clinical studies concur that tumor VEGF level is the most important prognostic parameter among several markers of tumor angiogenesis and proteolysis.

The study challenges the commonly assumed symmetry between justice judgments that refer to the distribution of positive and negative outcomes. Based on equity and multiprinciple approaches, and particularly on the theory of framing choices, we propose a conceptual framework for analyzing the dynamics of relations between positive and negative justice judgments. According to this framework, negative judgments are more generalized (simple) and more emphatic than are positive judgments. Data analysis was based on responses of 240 German adults to 39 justice judgment items that were subjected to a Similarity Space Analysis (SSA). The analysis corroborated the hypothesis when the type of resource to be distributed was held constant. Thus, the findings may reflect the primacy and high emotional intensity of negative experiences. They also suggest that, without specification of the distributed resource, this facet of justice judgments (sign of outcome distribution) is devoid of content.

In a questionnaire study, 929 West Germans and 1275 East Germans were asked to appraise East–West differences in life quality on the labor market 7 years after the German unification. Judgments included perceived East–West differences, the justice of East-West differences, and temporal comparisons (changes since the unification and expectations in East and West Germany). Changes and expectations for East and West Germany were combined to obtain social-temporal comparisons. Negative emotions (envy, anxiety, moral outrage, guilt, hopelessness) and positive emotions (gratefulness, pride) regarding the situation of the labor market were also assessed. Mental health indicators included measures of depression, self-esteem, and psychosomatic well-being. Parameters of a path model were estimated by regressing (i) mental health on emotions and judgments and (ii) emotions on judgments. Mental health of East Germans is associated negatively with envy, anxiety, and hopelessness. Moral outrage has a positive suppressor effect. Mental health of West Germans is linked negatively with envy, anxiety, and existential guilt whereas pride, the perception of unfair privileges, and optimistic expectations have positive path effects. Appraising East–West differences as unjust plays a core role in predicting emotions in both samples. Social comparisons and social-temporal comparisons are superior to egocentric temporal comparisons for predicting social emotions (envy, moral outrage, guilt) while egocentric temporal comparisons are generally more important for predicting “nonsocial” emotions (anxiety, hopelessness). Theoretical and practical implications of the findings are discussed.

Gynecological cancers, including malignant tumors of the ovaries, the endometrium and the cervix, account for approximately 10% of tumor-associated deaths in women of the Western world. For screening, diagnosis, prognosis, and therapy response prediction, the group of enzymes known as serine (Ser-)proteases show great promise as biomarkers. In the present review, following a summary of the clinical facts regarding malignant tumors of the ovaries, the endometrium and the cervix, and characterization of the most important Ser-proteases, we thoroughly review the current state of knowledge relating to the use of proteases as biomarkers of the most frequent gynecological cancers. Within the Ser-protease group, the kallikrein-related peptidase (KLK) family, which encompasses a subgroup of 15 members, holds particular promise, with some acting via a tumor-promoting mechanism and others behaving as protective factors. Further, the urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor-1) seem to play an unfavorable role in gynecological tumors, while down-regulation of high-temperature requirement proteins A 1, 2 and 3 (HtrA1,2,3) is associated with malignant disease and cancer progression. Expression/activity levels of other Ser-proteases, including the type II transmembrane Ser-proteases (TTSPs) matriptase, hepsin (TMPRSS1), and the hepsin-related protease (TMPRSS3), as well as the glycosyl-phosphatidylinositol (GPI)-anchored Ser-proteases prostasin and testisin, may be of clinical relevance in gynecological cancers. In conclusion, proteases are a rich source of biomarkers of gynecological cancer, though the enzymes' exact roles and functions merit further investigation.

Previous research has shown that different configurations of the implicit self-concept of intelligence (iSCI) and the explicit self-concept of intelligence (eSCI) are consistently related to individuals’ performance on different intelligence tests (Dislich, Imhoff, Banse, Altstötter-Gleich, Zinkernagel, & Schmitt, 2012). The results indicated that any discrepant configuration between the iSCI and the eSCI impairs performance. In the present study, how correspondence between the iSCI and the eSCI is related to intelligence test performance as well as personality traits of modesty (low eSCI, high iSCI), narcissism (high eSCI, low iSCI), and achievement motivation was investigated. Furthermore, a moderated mediation analysis showed that the relation between the iSCI-eSCI configurations and intelligence test performance was mediated by achievement motivation for modest individuals.

People differ systematically in their vulnerability to injustice. We present two-item scales for the efficient measurement of justice sensitivity from 4 perspectives (victim, observer, beneficiary, perpetrator). In Study 1 using a quota-based sample of German adults, a latent state-trait analysis revealed the factorial validity and high reliabilities of the scales. In Study 2 employing a large random sample, we tested for measurement invariance of the items within the context of our short 2-item scales compared to the original 10-item scales. Multigroup confirmatory factor analyses confirmed that the validity of the indicators and the internal structure of the assessed constructs did not change across item contexts. In both studies, correlations with personality dimensions and life satisfaction provide evidence for the validity of our scales. With the presented instrument, future research can extend scientific knowledge regarding the role of individual differences in reactions to injustice for the explanation of well-being and physical health.

Although Objective Personality Tests (OPTs) have a long history in psychology and the field of psychological assessment, their validity, and reliability have not yet been sufficiently studied. In this study, we examined the convergent and discriminant validity of objective (personality) tests, Implicit Association Tests (IATs), and self-report measures for the assessment of conscientiousness and intelligence. Moreover, the convergent and discriminant validity of these measures was assessed on the trait (stable) and occasion specific (momentary) level by using the multimethod latent state-trait (MM-LST) model proposed by Courvoisier, Nussbeck, Eid, and Cole (2008) which allows for the decomposition of different sources of variance. Data from 367 students assessed on three different measurement occasions was incorporated. Results indicate generally low convergence of OPTs with data gained by other approaches. Additional analyses revealed that the OPTs used assess stable rather than momentary components of the constructs. Reliabilities of different tests ranged from .54 to .95. Furthermore, a substantial amount of trait method specificity revealed that different methods assess trait components that are not shared between OPTs and other measures. Data on the criterion validity of the objective conscientiousness test revealed that it is related to the punctuality of test takers in the laboratory.

At Time 1, 171 students were administered questionnaires for measuring sensitivity to befallen injustice (SBI), trait anger, anger in, anger out, anger control, self-assertiveness, and attitudes toward principles of distributive justice (equality of chances, equity). Two months later (Time 2), 75 of these subjects were treated unfairly in a laboratory situation dealing with competition and achievement behavior. Two justice principles were violated: the equality of chances principle and the equity principle. Four weeks later (Time 3), 32 subjects evaluated the unfair treatment in retrospect. All three occasions were presented as independent studies with the subjects perceiving no connection between them. In line with our hypotheses, we found that immediate and delayed reactions to the unjust treatments depended to a considerable degree on SBI. For example, the combined score of the SBI questionnaire predicted, with a beta weight of .71, a combined rating of three experts who used various sources of objective information (e.g., tape-recorded interactions between subject and experimenter) to estimate the degree to which the subject displayed emotional, verbal, and behavioral resentment against the unfair treatment. At the same time, measures for other constructs (e.g., assertiveness, trait anger, anger expression), which can also be linked theoretically to the criteria, explained either none or a much smaller proportion of variance in reactions to unjust treatment.

The levels of plasminogen activator urokinase (uPA) and of its inhibitor (PAI-1) were measured by use of ELISA in the cytosol of tissue homogenates obtained from endometrial carcinomas and the marginal, tumor-free endometrium of postmenopausal patients ( n = 64). Significantly higher median levels of uPA and PAI-1 were found in malignant endometrium (uPA 1.89 ng/mg, PAI-1 3.04 ng/mg) compared to tumor-free endometrium (uPA 0.84 ng/mg, PAI-1 1.01 ng/mg). Concerning uPA, no significant differences were found in dependence on histomorphological prognostic factors (staging, grading), but the median level of PAI-1 was significantly higher in G2/G3 carcinomas compared to G1 tumors (5.08 ng/mg vs 2.19 ng/mg). Because of the good prognosis of operated patients with endometrial carcinomas, the prognostic value of uPA and PAI-1 can only be decided by a larger number of patients and a long observation time.

The characterization of invisible hydrocarbon micro-seepage intensities in surface sediments is used to evaluate subsurface hydrocarbon potential. A cost-effective multidisciplinary surface prospecting method, termed "BIG", is employed as a supplementary instrument to conventional exploration tools to assess the remaining prospectivity of a licence tract in the Dutch North Sea. Microbial investigations, molecular and isotopic gas characterization as well as UV fluorescence measurements are utilized for direct hydrocarbon detection in surface sediments. The definition and distribution of anomalous intensities is used as an index for the hydrocarbon potential in the deeper sub-surface. In combination with seismic information the BIG method can help to reduce exploration risk. It proves to be an effective instrument to determine the lateral extent of liquid hydrocarbon migration and to localize areas of prospective potential. This case history covers a successful application of the BIG method to investigate undetected hydrocarbon potential in an established producing province.

Extravasation and intravasation of solid malignant tumors is controlled by attachment of tumor cells to components of the basement membrane and the extracellular matrix, by local proteolysis and tumor cell migration. Strong clinical and experimental evidence has accumulated that the tumor-associated serine protease plasmin, its activator uPA (urokinase-type plasminogen activator), the receptor uPA-R (CD87), and the inhibitors PAI-1 and PAI-2 are linked to cancer invasion and metastasis. In cancer, increase of uPA, uPA-R, and/or PAI-1 is associated with tumor progression and with shortened disease-free and/or overall survival in patients afflicted with malignant solid tumors. uPA and/or its inhibitor PAI-1 appear to be one of the strongest prognostic markers so far described. Strong prognostic value to predict disease recurrence and overall survival has been documented for patients with cancer of the breast, ovary, cervix, endometrium, stomach, colon, lung, bladder, kidney, brain, and soft-tissue. Due to the strong correlation between elevated uPA and/or PAI-1 values in primary cancer tissues and the tumor invasion/ metastasis capacity of cancer cells, proteolytic factors have been selected as targets for therapy. Various very different approaches to interfere with the expression or reactivity of uPA or CD87 at the gene or protein level were successfully tested including antisense oligonucleotides, antibodies, enzyme inhibitors, and recombinant or synthetic uPA and uPA-R analogues.

Evidence has accumulated that urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1) and receptor (uPAR) are involved in tumor invasion and metastasis. We analyzed the DNA sequences encoding these factors to see if they are altered in the ovarian cancer cell lines OV-MZ-6, OV-MZ-19, and OVCAR-3. In the uPA-encoding cDNA derived from OV-MZ-6 cells (but not in the uPA-cDNA from OVCAR-3 and OV-MZ-19), a so-far unknown mutation was identified in codon 121, resulting in a proline to leucine exchange. This exchange creates an AluI restriction site making restriction fragment length polymorphism (RFLP) analyses possible. Previously published PAI-1 sequences pointed to a variation of amino acid 15 of the PAI-1 signal sequence representing either threonine or alanine, which was confirmed in the present study. The uPAR cDNAs of all three cell lines encoded the published wild-type sequence. In order to elucidate the possible role of the Pro121Leu exchange in uPA and the Ala/Thr variants in the signal sequence of PAI-1 in the development and/or progression of human ovarian cancer, we studied the presence of these mutants or variants in a series of 22 ovarian cancer tissues. In addition to the wild-type sequence, the Pro121Leu exchange in the uPA sequence was detected in 10 out of 22 tumor tissues; 11 tumors carried exclusively the Pro121 allele; in one case exclusively the Leu121 allele was detected. In 18/22 tumors, triplet 15 in the signal sequence of PAI-1 encoded alanine, four DNAs contained both the Ala and the Thr allele. Furthermore, we analyzed another known common single-base-pair insertion/deletion polymorphism (ins/del allele) found in the promoter region of the PAI-1 gene and thought to be of functional importance in regulating PAI-1 gene expression. The PAI-1 ins-allele was found in 3/22, the del-allele in 6/22 and both alleles in 13/22 ovarian cancer tissues. In genomic DNA isolated from peripheral blood of 23 healthy donors, we observed similar allele frequencies of the three polymorphisms as found in the 22 ovarian carcinomas. Taken together, these results suggest that the polymorphisms observed in the uPA and PAI-1 genes may not be linked to ovarian cancer.

Manfred Schmitt1; Thomas Renne2,3; Andreas Scorilas4 1Clinical Research Unit, Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany; 2Department of Molecular Medicine and Surgery, Karolinska Institutet and University Hospital, Stockholm, Sweden; 3Division of Clinical Chemistry, University Hospital Eppendorf, Hamburg, Germany; 4Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece

Expression of the kallikrein-related peptidase 7 (KLK7) is dysregulated in ovarian cancer. We assessed KLK7 expression by ELISA and quantitative immunohistochemistry and analyzed its association with clinicopathological parameters and patients’ outcome. KLK7 antigen concentrations were determined in tumor tissue extracts of 98 ovarian cancer patients by ELISA. For analysis of KLK7 immunoexpression in ovarian cancer tissue microarrays, a manual quantitative scoring system as well as a software tool for quantitative high-throughput automated image analysis was used. In immunohistochemical analyses, expression levels of KLK7 were not associated with patients’ outcome. However, in multivariate analyses, KLK7 antigen levels in tumor tissue extracts were significantly associated with both overall and progression-free survival: ovarian cancer patients with high KLK7 levels had a significantly, 2-fold lower risk of death [hazard ratio (HR)=0.51, 95% confidence interval (CI)=0.29–0.90, p=0.019] or relapse [HR=0.47, 95% CI=0.25–0.91, p=0.024), as compared with patients who displayed low KLK7 levels. Our results indicate that – in contrast to earlier findings – high KLK7 antigen levels in tumor tissue extracts may be associated with a better prognosis of ovarian cancer patients.

The carbon isotope fractionation between CO2 and CH4 was studied during open system (related to gas flow) culture experiments with CO2-reducing methanogenic Archaea. To study the temperature dependence of isotope fractionation during biological methanogenesis, three representatives of the order Methanococcales were cultivated in the temperature range 35-85°C. In the stationary growth phase, the carbon isotope fractionation factor between CO2 and CH4 was found to range between 1.048 and 1.079, depending on the growth temperature and on the type of fermentor. In contrast to published data derived from culture experiments, our results fall in the range of naturally occurring carbon isotope fractionations of coexisting CO2---CH4 pairs in marine sediments. Moreover, the fractionation closely approached the thermodynamic equilibrium between both gases, although thermal isotope exchange processes are unlikely to occur below 200°C. Our findings suggest that flow-through culture experiments are useful when studying biological methanogenesis and associated (carbon-) isotope fractionation as a means of deciphering complex methanogenic processes in sediments.

Background Neutrophil-platelet adhesion may occur as a consequence of platelet activation. The role of this heterotypic adhesion in ischemic disorders is poorly understood thus far. Methods and Results Systemic venous blood samples were taken from 25 patients with stable angina pectoris and 25 patients with unstable angina pectoris. Neutrophil activation and neutrophil-platelet adhesion were evaluated by two-color flow cytometry. Patients with unstable angina showed a significant increase in neutrophil-platelet adhesion compared with patients with stable angina (mean±SEM, 132.1±20.5 versus 29.8±4.7 anti-glycoprotein IIb/IIIa mean fluorescence intensity, P =.0001). Systemic neutrophil activation was found in patients with unstable angina compared with those with stable angina assessed by cell surface CD11b expression and shedding of L-selectin (115.6±10.3 versus 74.0±6.3 anti-CD11b mean fluorescence intensity, P =.002; 49.8±6.0 versus 72.1±4.0 anti–L-selectin mean fluorescence intensity, P =.006). Markers of neutrophil activation were related to the extent of neutrophil-platelet adhesion (CD11b: r =.5, P =.0005; L-selectin: r =.42, P =.012). In vitro studies revealed that binding of purified platelet membranes to control neutrophils caused a dose-dependent increase in CD11b surface expression, a decrease in surface L-selectin, and the release of superoxide anions. Conclusions Thus, this study demonstrates that increased neutrophil-platelet adhesion may contribute to neutrophil activation in unstable angina.

The study investigates the construct validity of a self-report questionnaire for dispositional sensitivity to befallen injustice (SBI; Schmitt, Neumann, and Montada, 1995). The items of this questionnaire are combinations of four indicators of SBI (frequency of perceived injustice, intensity of anger, intrusiveness/perseverance of thoughts about the event, punitivity) with 18 types of unfair situations (e.g., performing better than others without getting any appreciation or reward). At Occasion 1, SBI, trait anger, anger in, anger out, anger control, self-assertiveness, and attitudes toward equality were measured. At Occasion 2, the subjects (57 advanced psychology students) took part in a lottery for distributing scarce teaching resources among students. The lottery led to objective advantages for some students and to objective disadvantages for others. Four reactions to the event were measured at Occasion 3: judgment of the lottery as injust, anger about the lottery, experiencing the lottery as demotivating, and approval of activities against the lottery. These reactions were regressed on the variables measured at Occasion 1. SBI was the only significant predictor of the justice judgment and the approval of activities. Anger about the lottery depended only on objective disadvantage/advantage. Experiencing the lottery as demotivating depended negatively on anger control and positively on the intrusiveness/perseverance of thoughts about the event, a subscale of the SBI inventory.

Hydrothermal fluids emerge from the seafloor of Paleohori Bay on Milos. The gases in these fluids contain mostly CO2 but CH4 concentrations up to 2% are present. The stable carbon isotopic composition of the CO2 (near 0%) indicates an inorganic carbon source (dissociation of underlying marine carbonates). The carbon and hydrogen isotopes of most CH4 samples are enriched in the heavy species ([delta]13C = -9.4 to -17.8[per mille sign]; [delta]D = -102 to -189[per mille sign]) which is believed to be characteristic for an abiogenic production of CH4 by CO2-reduction (Fischer-Tropsch reactions). Depletions in the deuterium content of three CH4 samples (to -377%) are probably caused by unknown subsurface rock alteration processes. Secondary hydrogen isotope exchange processes between methane, hydrogen and water are most likely responsible for calculated unrealistic methane formation temperatures. We show that excess helium, slightly enriched in 3He, is present in the hydrothermal fluids emerging the seafloor of Paleohori Bay. When the isotopic ratio of the excess component is calculated a 3He/4Heexcess of 3.6 · 10-6 is obtained: This indicates that the excess component consists of about one third of mantle helium and two thirds of radiogenic helium. We infer that the mantle-derived component has been strongly diluted by radiogenic helium during the ascent of the fluids to the surface.

The amino-terminal fragment of human uPA (ATF; amino acids 1-135), which contains the binding site for the uPA receptor (uPAR, CD87) was expressed in the yeast Saccharomyces cerevisiae. Recombinant yeast ATF, modified and extended by an amino-terminal in-frame insertion of a His6 tract, was purified from total protein extracts by nickel chelate affinity chromatography and shown to be functionally active since it efficiently competes with uPA for binding to cell-surface-associated uPAR. The ATF expression plasmid served as a template for the construction of a series of site-directed mutants in order to define those amino acids that are important for binding to uPAR. All mutant ATF proteins but one (deletion of Ser26) were expressed in a stable form (about 20-30 ng/mg total protein) and the binding capacity of each mutant was tested by a uPA-ligand binding assay employing recombinant uPAR immobilized to a microtiter plate. Each of the 11 amino acids of loop B of the binding region of uPA (amino acids 20-30) were individually substituted with alanine. Lys23, Tyr24, Phe25, IIe28, and Trp30 were important determinants for uPAR binding. A systematic alanine scan was also performed with chemically synthesized linear peptides spanning amino acids 14-32 of ATF. Comparable results to those with the yeast ATF mutants were obtained. In a different set of experiments, those amino acids of the uPAR-binding region of uPA that are only conserved between man and baboon but not in other species were altered: whereas substitution of Thr18 by alanine or Asn32 by serine had hardly any effect, replacement of Asn22 by tyrosine and Trp30 by arginine (both positions are strictly conserved in other mammals) led to ATF variants incapable of interacting with human uPAR. Deletion of either Val20, Ser21, Lys23, His29 or Val20 plus Ser21, respectively, also generated non-reactive ATF mutants. Finally, Lys23 in ATF was substituted with certain amino acids: whereas the replacement of Lys23 by alanine, histidine or glutamine generated ATF variants with moderate uPAR-binding activity, the introduction of a negatively charged amino acid (exchange of Lys23 by glutamic acid) completely abolished uPAR-binding activity. The results presented for the ATF mutants and uPA-derived peptides may provide clues necessary to establish the nature of the physical interaction of uPA with its receptor and may help to develop uPA-derived peptide analogues as potential therapeutic agents to block tumor cell-associated uPA/uPAR interaction.

Invasion factors uPA/PAI-1 are guideline-recommended (ASCO, AGO) biomarkers for decision support regarding adjuvant chemotherapy (CTX) in women with primary breast cancer. They define a high-risk group with strong benefit from adjuvant CTX and a low-risk group with uncertain benefit and excellent survival without CTX. In a target population (age > 35/N0/G2/HR+/HER2−), administration of adjuvant CTX is not mandatory in Germany and other countries. Based on existing data, this economic model was developed to determine for the first time health economic impact of uPA/PAI-1 testing. Incremental cost-effectiveness ratio (ICER) resulting from uPA/PAI-1 testing was estimated for the target population by Markov modeling and sensitivity analysis. Survival data, CTX–uPA/PAI-1 interactions, and uPA/PAI-1 hazard ratios were derived from the Chemo N0 trial and other evidence. Incremental costs were computed from a payer’s perspective appropriate to the German setting. Incremental effectiveness in life years (ly) was estimated taking into account age-adjusted life expectancy, disease-free survival (with/without CTX), and 2 years post-relapse survival. Sensitivity analysis was performed by varying residual adjuvant CTX benefit in the low-risk group, denoted HR_CTX(LR), in range 0.8–0.99. All patients receive adjuvant endocrine therapy. Test is restricted to patients willing to forgo CTX if both markers are below specific cut-off values and to undergo CTX otherwise. For a typical 55-year-old patient, comparing to an “all-CTX” strategy without the test, ICER (all-CTX vs. test) > €50,000 if HR_CTX(LR) > 0.85, with savings of €18,500 per low-risk patient attributable to the test. The cost-effectiveness of forgoing CTX is very high as HR_CTX(LR) approaches one. Conversely, comparing to a “no-CTX” strategy (e.g., patients who initially refuse CTX) without the test, the test is very cost-effective at all ages in the target group if high-risk patients are willing to undergo CTX: ICER (test vs. no-CTX)

Breast cancer is the most common malignancy in women of the Western world. One prominent feature of breast cancer is the co- and overexpression of HER2 and protein tyrosine kinase 6 (PTK6). According to the current clinical cancer therapy guidelines, HER2-overexpressing tumors are routinely treated with trastuzumab, a humanized monoclonal antibody targeting HER2. Approximately, 30% of HER2-overexpressing breast tumors at least initially respond to the anti-HER2 therapy, but a subgroup of these tumors develops resistance shortly after the administration of trastuzumab. A PTK6-targeted therapy does not yet exist. Here, we show for the first time that the simultaneous knockdown in vitro, compared with the single knockdown of HER2 and PTK6, in particular in the trastuzumab-resistant JIMT-1 cells, leads to a significantly decreased phosphorylation of crucial signaling proteins: mitogen-activated protein kinase 1/3 (MAPK 1/3, ERK 1/2) and p38 MAPK, and (phosphatase and tensin homologue deleted on chromosome ten) PTEN that are involved in tumorigenesis. In addition, dual knockdown strongly reduced the migration and invasion of the JIMT-1 cells. Moreover, the downregulation of HER2 and PTK6 led to an induction of p27, and the dual knockdown significantly diminished cell proliferation in JIMT-1 and T47D cells. In vivo experiments showed significantly reduced levels of tumor growth following HER2 or PTK6 knockdown. Our results indicate a novel strategy also for the treatment of trastuzumab resistance in tumors. Thus, the inhibition of these two signaling proteins may lead to a more effective control of breast cancer. Mol Cancer Res; 11(4); 381–92. ©2013 AACR.

Marshall and Brown (2006) proposed a Traits as Situational Sensitivities (TASS) Model, which implies a systematic person  situation interaction. We review this model and show that it suffers from several limitations. We extend and modify the model in order to obtain a symmetric pattern of levels and effects for both person and situation factors. Our suggestions result in a general Nonlinear Interaction of Person and Situation (NIPS) Model. The NIPS model bears striking similarities to the Rasch model. Based on the symmetric nature of the NIPS model, we generalize the concept of weak and strong situations to individuals and propose the concepts of weak and strong persons. Finally, we discuss psychological mechanisms that might explain the NIPS pattern and offer ideas for future research.

As theoretical considerations and empirical research suggest, human behaviour is guided by a fundamental justice motive. In the present chapter, we discuss two theoretical constructs that have been proposed to capture inter-individual differences in the strength of the justice motive: belief in a just world and justice sensitivity.

Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Results At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944. Conclusions Integrated molecular characterization of AC and SCC helped identify clinically relevant markers and potential drivers, which are recurrent and stable changes at DNA level that have functional implications at RNA level and have strong association with histological subtypes.

Extravasation and intravasation of tumor cells in solid malignant tumors is controlled by 3 steps: 1) attachment to and interaction of tumor cells with components of the basement membrane and the extracellular matrix, 2) local proteolysis, and 3) tumor cell migration. Evidence has accumulated that different types of tumor-associated proteases, their inhibitors and receptors are involved in tumor invasion and metastasis. Four different classes of proteases are known to be correlated with the malignant phenotype: 1) Matrix metalloproteases; including collagenases, gelatinases and stromelysins. 2) Cysteine proteases; including cathepsins B and L. 3) Aspartyl protease cathepsin D. 4) Serine proteases; including plasmin and tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). A strong independent prognostic value (relapse-free and/or overall survival) has especially been demonstrated for uPA and its inhibitor PAI-1 in patients with cancer of the breast, ovary, stomach, esophagus, colon, lung, and kidney thus predicting the course of the cancer disease. The strong correlation between elevated uPA and/or PAI-1 values in primary cancer tissues and the malignant phenotype of cancer cells has prompted to explore new tumor biology-oriented concepts in order to suppress uPA or uPA receptor (CD87) expression or to abrogate interaction of uPA with CD87. Various very different approaches to interfere with the expression or reactivity of uPA or CD87 at the gene or protein level were successfully tested including antisense oligonucleotides, antibodies, inhibitors and recombinant or synthetic uPA and CD87 analogues.

The essential role of urokinase-type plasminogen activator (uPA) in tumor invasion and metastasis stresses the necessity of a fine-tuned cellular control over its expression. It has been shown that changes in uPA directly correlate with changes in cell invasiveness. We examined the role of Rel-related proteins in uPA synthesis by human ovarian cancer cells by inhibiting their expression using the antisense (AS) oligodeoxynucleotide (ODN) technology. Exposure of OV-MZ-6 cells to 10 microM phosphorothioate (PS)-derivatized AS-ODN directed to Rel A led to a maximal 50% decrease of uPA antigen in cell lysates and a 70% reduction in cell cultures supernatants accompanied by a significant transient decline in uPA mRNA levels. Antisense-PS-ODN directed to NF-kappa B1 (p50) or c-rel had no effect on uPA protein expression. AS-PS-ODN directed to Rel A also affected the proteolytic capacity of OV-MZ-6 cells reflected by an approximately 70% decrease in the fibrinolytic capacity of the cells within 24 h compared to untreated controls. AS-PS-ODN directed to I kappa B alpha expression increased uPA in cell culture supernatants up to 50%. uPA receptor (uPAR) production and synthesis of plasminogen activator inhibitor type-1 (PAI-1) were not altered by either AS-PS-ODN applied. Western blot and gel retardation analyses revealed constitutive expression of Rel-related proteins in nuclear protein extracts of OV-MZ-6 cells. Thus these proteins seem to be implicated in uPA regulation and may thereby contribute to tumor spread and metastasis.

Urokinase-type plasminogen activator (uPA) converts plasminogen to plasmin which degrades various extracellular matrix components. uPA is focused to the cell surface via binding to a specific receptor (uPAR, also termed CD87). uPAR-bound uPA mediates pericellular proteolysis in a variety of biological processes, e.g. cell migration, tissue remodeling and tumor invasion. We have developed a competitive microtiter plate-based chromogenic assay which allows the analysis of uPA/uPAR interaction. The plates are coated with recombinant uPAR expressed in Chinese hamster ovary (CHO) cells. Proteolytically active uPA (HMW-uPA) is added to the microtiter plate-attached uPAR. The amount of receptor-bound uPA is then determined indirectly via addition of plasminogen, which is activated to plasmin, followed by cleavage of a plasmin-specific chromogenic substrate. Substances interfering with binding of HMW-uPA to uPAR diminish the generation of plasmin, as indicated by a reduction of cleaved chromogenic substrate. This assay was used to analyze the inhibitory capacity of a variety of proteins and peptides, respectively, on the uPA/uPAR interaction: i) uPAR and uPAR-variants expressed in CHO cells, yeast or E. coli, ii) the aminoterminal fragment (ATF) of human uPA or yeast recombinant pro-uPA, iii) synthetic peptides derived from the sequence of the uPAR-binding region of uPA, and iv) antibodies directed against uPAR. This assay may be helpful in identifying uPA and uPAR analogues or antagonists which efficiently block uPA/uPAR interaction.

The receptor for urokinase-type plasminogen activator (uPAR) may contribute to the invasive and metastatic capacity of tumor cells by focusing the serine protease urokinase-type plasminogen activator (uPA) to the cell surface. uPA activates plasminogen to plasmin which in turn degrades extracellular matrix proteins or activates other proteases. Mature uPAR is a heavily glycosylated protein of about 284 amino acids attached to the plasma membrane via a glycosyl-phosphatidylinositol (GPI) anchor. A set of different polyclonal uPAR antibodies has been generated in order to investigate the role of uPAR in tumor spreading in more detail. For this purpose, uPAR (lacking the GPI anchor) was expressed in E. coli and Chinese hamster ovary (CHO) cells. Recombinant uPAR from E. coli (corresponding to amino acids 1-284 of human uPAR) was expressed with an N-terminal histidine-tag insertion and purified by nickel chelate affinity chromatography. Soluble uPAR, synthesized by CHO cells (corresponding to amino acids 1-277 of human uPAR), was isolated by ligand (uPA) affinity chromatography. Expression in E. coli led to a nonglycosylated form of uPAR, whereas uPAR produced by CHO cells seemed to be glycosylated to a similar extent as the naturally occurring human form of uPAR (as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Prior to immunization the N-termini of the recombinant uPAR variants were determined by amino acid sequence analysis. Polyclonal antibodies were generated in chickens and purified from egg yolk. The reaction patterns of these antibodies were analyzed by Western blot analyses and flow cytofluorometry.

Theme Issue: Update on the role of the fibrinolysis/ plasminogen activation system in a cellular context

Chemotherapeutic drugs kill cancer cells, but it is unclear why this happens in responding patients but not in non-responders. Proteomic profiles of patients with oesophageal adenocarcinoma may be helpful in predicting response and selecting more effective treatment strategies. In this study, pretherapeutic oesophageal adenocarcinoma biopsies were analysed for proteomic changes associated with response to chemotherapy by MALDI imaging mass spectrometry. Resulting candidate proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated for functional relevance in vitro. Clinical impact was validated in pretherapeutic biopsies from an independent patient cohort. Studies on the incidence of these defects in other solid tumours were included. We discovered that clinical response to cisplatin correlated with pre-existing defects in the mitochondrial respiratory chain complexes of cancer cells, caused by loss of specific cytochrome c oxidase (COX) subunits. Knockdown of a COX protein altered chemosensitivity in vitro, increasing the propensity of cancer cells to undergo cell death following cisplatin treatment. In an independent validation, patients with reduced COX protein expression prior to treatment exhibited favourable clinical outcomes to chemotherapy, whereas tumours with unchanged COX expression were chemoresistant. In conclusion, previously undiscovered pre-existing defects in mitochondrial respiratory complexes cause cancer cells to become chemosensitive: mitochondrial defects lower the cells' threshold for undergoing cell death in response to cisplatin. By contrast, cancer cells with intact mitochondrial respiratory complexes are chemoresistant and have a high threshold for cisplatin-induced cell death. This connection between mitochondrial respiration and chemosensitivity is relevant to anticancer therapeutics that target the mitochondrial electron transport chain.

Etliche empirische Befunde der kulturvergleichenden Psychologie belegen, dass Menschen verschiedenen kulturellen Hintergrunds sich bezuglich einer Reihe von Merkmalen unterscheiden, wahrend andere Merkmale universell geteilt werden (fur einen Uberblick siehe z. B. Berry, 2004; Kagitcibasi & Berry, 1989; Shiraev & Levy, 2004). Unterschiede finden sich auch in der Art, wie das Verhalten von Mitmenschen interpretiert wird (Blimes & Boggs, 1979; Hansen, 2003; Poortinga, Kop & Van de Vijver, 1990; Shiraev & Levy, 2004).

Is there a good end to the suffering of the maltreated child? Will the murderer get caught, and does he deserve capital punishment? Who has to pay for the loss of capital in the aftermath of a financial crisis? Who should have a voice in political decisions on nuclear energy supplements? These and many other questions point to an essential topic in human life: social justice. Results from content analyses have indicated that social justice is a frequenttopic in mass media communication (Britto & Dabney, 2010; Pollak & Kubrin, 2007; Surette, 2007). The primary aim of this chapter is to discuss how justice issues are reflected in the media and how the communication of justice issues in the mass media is related to the social behavior of media consumers. We will focus on three different (but interrelated) functions or effects of justice-related media content: First, media communication about justice issues can promote the mobilization of people in order to oppose existing injustice. Second, justice can be understood as a key to entertainment in media communication. Third, dealing with justice issues in media formats can provide important learning encounters for the development of justice-related norms, beliefs, and attitudes. Before we discuss these different functional roles of justice in the media in more detail, we outline some fundamentals of how justice is understood in social justice research.

The isolation of circulating tumor cells (CTCs) from the blood of patients afflicted with solid malignant tumors becomes increasingly important as it may serve as a 'liquid biopsy' with the potential of monitoring the course of the cancer disease and its response to cancer therapy, with subsequent molecular characterization. For this purpose, we functionalized a structured medical Seldinger guidewire (FSMW), normally used to obtain safe access to blood vessels and other organ cavities, with a chimeric monoclonal antibody directed to the cell surface expressed epithelial cell surface adhesion molecule (EpCAM). This medical device was optimized in vitro and its biocompatibility was tested according to the regulations for medical devices and found to be safe with no noteworthy side effects. Suitability, specificity and sensitivity of the FSMW to catch and enrich CTCs in vivo from circulating peripheral blood were tested in 24 breast cancer or non-small cell lung cancer (NSCLC) patients and in 29 healthy volunteers. For this, the FSMW was inserted through a standard venous cannula into the cubital veins of healthy volunteers or cancer patients for the duration of 30 min. After removal, CTCs were identified by immuno cytochemical staining of EpCAM and/or cyto- keratins and staining of their nuclei and counted. The FSMW successfully enriched EpCAM-positive CTCs from 22 of the 24 patients, with a median of 5.5 (0-50) CTCs in breast cancer (n=12) and 16 (2-515) CTCs in NSCLC (n=12). CTCs could be isolated across all tumor stages, including early stage cancer, in which distant metastases were not yet diagnosed, while no CTCs could be detected in healthy volunteers. In this observa- tory study, no adverse effects were noted. Evidently, the FSMW has the potential to become an important device to enrich CTCs in vivo for monitoring the course of the cancer disease and the efficacy of anticancer treatment.

Several members of the human kallikrein-related peptidase family, including KLK6, are up-regulated in ovarian cancer. High KLK6 mRNA or protein expression, measured by quantitative polymerase chain reaction and enzyme-linked immunoassay, respectively, was previously found to be associated with a shortened overall and progression-free survival (OS and PFS, respectively). In the present study, we aimed at analyzing KLK6 protein expression in ovarian cancer tissue by immunohistochemistry. Using a newly developed monospecific polyclonal antibody, KLK6 immunoexpression was initially evaluated in normal tissues. We observed strong staining in the brain and moderate staining in the kidney, liver, and ovary, whereas the pancreas and the skeletal muscle were unreactive, which is in line with previously published results. Next, both tumor cell- and stromal cell-associated KLK6 immunoexpression were analyzed in tumor tissue specimens of 118 ovarian cancer patients. In multivariate Cox regression analysis, only stromal cell-associated expression, besides the established clinical parameters FIGO stage and residual tumor mass, was found to be statistically significant for OS and PFS [high vs. low KLK6 expression; hazard ratio (HR), 1.92; p=0.017; HR, 1.80; p=0.042, respectively]. These results indicate that KLK6 expressed by stromal cells may considerably contribute to the aggressiveness of ovarian cancer.

Chapter 17 by Anna Baumert and Manfred Schmitt features a triangulation of distributive justice theory, resource theory, and culture theory that sheds new light on cross-cultural differences in preferences for allocation principles. The authors propose that a culture’s standing on power distance, uncertainty avoidance, and masculinity/femininity will determine the importance of status, information, material goods, money, services, and love in allocation decisions. They also propose that the distribution of a culturally important resource increases the preference for equitable allocations. Baumert and Schmitt found that available data from cross-cultural studies are inconclusive as they do not systematically combine justice principles and resources. Future tests of their proposed hypotheses might yield a reinterpretation of previously held views of culturally specific justice preferences.