Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicenter randomized trial comparing sequential with concomitant administration of doxorubicin and docetaxel as first-line treatment of metastatic breast cancer: a Spanish Breast Cancer Research Group (GEICAM-9903) phase III study.

PURPOSE This randomized, multicenter, phase III trial evaluated whether sequential doxorubicin and docetaxel (A-->T) reduced hematological toxicity, especially febrile neutropenia, compared with concomitant (AT) administration as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS One hundred forty-four patients were randomly assigned to receive three cycles of doxorubicin 75 mg/m(2) every 21 days followed by three cycles of docetaxel 100 mg/m(2), every 21 days (A-->T) or six cycles of the combination doxorubicin 50 mg/m(2) and docetaxel 75 mg/m(2) (AT) every 21 days. Patients previously treated with anthracyclines received two cycles of doxorubicin followed by four cycles of docetaxel (A-->T), or three cycles of AT followed by three cycles of docetaxel 100 mg/m(2) every 21 days. RESULTS Febrile neutropenia was less common in the A-->T arm (29.3% of patients, 6.9% of cycles) compared with the AT arm (47.8% of patients, 14.8% of cycles; P =.02 and P =.0004, respectively). Asthenia, diarrhea, and fever occurred more frequently in the AT arm. The overall responses rates were 61% in the A-->T arm (95% CI, 50% to 72%) and 51% in the AT arm (95% CI, 39% to 63%). The median duration of response was 8.7 months (A-->T) and 7.6 months (AT); the median time to progression was 10.5 months (A-->T) and 9.2 months (AT); the median overall survival was 22.3 months (A-->T) and 21.8 months (AT); and no significant differences were found. CONCLUSION A-->T significantly reduced febrile neutropenia compared with AT in MBC patients and maintains comparable antitumoral efficacy. A-->T represents a valid option for the treatment of MBC.
Determinants of Organisational Transformation: An IT-Business Alignment Perspective

Previous research in organisational sociology has focused on how organisational forms are evolved, transformed and sustained. This paper continues in this line of enquiry and tests the role of IT in organisational transformation. The transformation of an organisation can be gauged by observing key organisational attributes that are likely to feature in transformed (new) organisations. Following a review of previous literature, three major factors, that is, business strategy, IT strategy, IT strategic alignment were hypothesised to influence the dimensions of new organisational forms (NOFs). To test this model, data were collected from a survey of 312 Australian businesses. Structural equation modelling was employed to test the research hypotheses. Results from this study uncovered that the level of strategic alignment was significantly associated with the attributes of NOFs. This implies that organisations that have progressed well in the IT-business alignment maturity ladder are likely to change their structure and control mechanisms. This study concludes by highlighting some of the theoretical and practical implications of the findings.
Action Design Research: Design of e-WIL for the Manufacturing Industry

This paper reports on a design process of e-learning courses for competence development of experienced employees in the manufacturing industry. Through a crossorganizational collaborative action design research project the aim was to design e-learning courses at university level to support work-integrated learning. Two designand learning cycles were evaluated over two years. The first cycle identified challenges that were applied to a pilot course in Industrial automation. From evaluation of this course we derived design principles applied to two further courses in Machining and Negotiation skills. The results from our empirical data suggest general principles as competence mapping work, collaborative manufacturing e-WIL cases and interactive learning technologies for design of e-WIL courses as boundary crossing activities to reach transformative learning integrated in the manufacturing industry.
Why People Pay for Digital Items? Presentation Desire of Online Identity

Recently digital items (e.g., avatars) have been widely used by people in virtual communities (VC) and online games. Some Internet companies generate revenue from sales of digital items to their customers. Sales of digital items provide revenue for Internet companies and VC providers who are suffering from lack of a profitable business model. However there is a lack of understanding about people’s digital item purchase and usage. This study examines why people pay for digital items from the self-presentation perspective, by focusing on online identity, based on social identity theory. The findings show that the presentation desire of online identity leads to intention of purchasing digital items. The results show the significance of online group norm and online group involvement in enhancing the presentation desire from the online social identity perspective. This study also identifies the significance of interaction effects between personal innovativeness and online group involvement in enhancing the presentation desire from the online personal perspective. These findings help to advance theory and offer practical insights in the context of Internet business and VC.
Association of Energy Intake and Energy Balance with Postmenopausal Breast Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Energy restriction remains one of the most effective ways known to prevent breast cancer in animal models. However, energy intake has not been consistently associated with risk of breast cancer in humans. In a prospective study, we assessed whether energy intake, body size, and physical activity each independently influence breast cancer risk in postmenopausal women and estimated the joint effect of combinations of these individual factors. As part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 38,660 women, ages 55 to 74 years and recruited from 10 centers in the United States during 1993 to 2001, were randomized to the screening arm of the trial. At baseline, the women completed a self-administered questionnaire, including a food frequency questionnaire. During follow-up from 1993 to 2003, 764 incident breast cancer cases were ascertained. Women in the highest quartile of energy intake (≥2,084 kcal/d) compared with those in the lowest quartile (<1,316 kcal/d) had a significantly increased risk for breast cancer [multivariate relative risk (RR), 1.25; 95% confidence interval (95% CI), 1.02-1.53; Ptrend continuous = 0.03]. Current body mass index (BMI) was also positively and significantly associated with risk (multivariate RR comparing >30 kg/m2 with <22.5 kg/m2, 1.35; 95% CI, 1.06-1.70; Ptrend = 0.01). Women with ≥4 hours/wk of vigorous recreational physical activity had a significantly reduced risk of breast cancer compared with those who reported no recreational physical activity (multivariate RR, 0.78; 95% CI, 0.60-0.99; Ptrend = 0.15). None of these associations with individual energy balance measures was substantially confounded by the other two measures. When we estimated the joint effect of all three variables, women with the most unfavorable energy balance (the highest energy intake, highest BMI, and least physical activity) had twice the risk (RR, 2.10; 95% CI, 1.27-3.45) of women with the most favorable energy balance (the lowest energy intake, lowest BMI, and most physical activity). Although our estimates of absolute energy intake, based on a food frequency questionnaire, are imperfect, these results suggest that energy intake, in addition to BMI and physical activity may be independently associated with breast cancer risk. In addition, these three aspects of energy balance may act jointly in determining breast cancer risk. (Cancer Epidemiol Prev 2006;15(2):334–41)
Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism

Murine cytomegalovirus (MCMV) gene products dispensable for growth in cell culture are likely to have important functions within the infected host, influencing tissue tropism, dissemination, or immunological responses against the virus. To identify such genes, our strategy was to delete large regions of the MCMV genome likely to contain genes nonessential for virus replication in NIH 3T3 cells. Mutant virus RV7 contained a deletion of 7.7 kb spanning portions of MCMV HindIII-J and -I. This virus grew comparably to wild-type (WT) virus in NIH 3T3 fibroblasts, primary embryo fibroblasts, and bone marrow macrophages. However, RV7 failed to replicate in target organs of immunocompetent BALB/c mice and severe combined immunodeficient mice, which are exquisitely sensitive to MCMV infection. This defect in vivo growth may be related to the observation that RV7 grew poorly in the peritoneal macrophage cell line IC-21, which is highly permissive for growth of WT MCMV. Two other mutant viruses with an insertion or smaller deletion in the region common to the RV7 deletion grew comparably to WT virus in the macrophage cell line and replicated in salivary gland tissue. The poor growth of RV7 in IC-21 cells was due to a block in immediate-early gene expression, as levels of RNA from immediate-early gene IE1 were reduced eightfold compared with levels for WT virus in macrophages infected with RV7. Consequently, levels of RNA from early and late genes were also reduced. The lower expression of IE1 in RV7-infected IC-21 macrophages was not due to defective entry of virus into the cells, as equal amounts of viral DNA were present in cells 3 h after infection with RV7 or WT MCMV. These studies demonstrate that deletion of sequences in HindIII-J and -I confer altered cell and tissue tropism.
The analysis of geographically weighted regression pertaining to gastric cancer and Taiwanese ethnic communities

The aim of this study was to examine the local versions of spatial regression associated with gastric cancer and the 4 major Taiwanese ethnic communities. In this study, we utilize the improvement of geographically weighted regression, in which the significance of parameter estimates was determined by the Benjamini-Hochberg procedure for controlling the false discovery rate, to interpret a correlation between the response and the explanatory variables. Local versions of spatial regression in correlation with gastric cancer and 4 major Taiwanese ethnic communities are mapped, including the sign and magnitude of parameter estimates, the significance determination referred to as the false discovery rate, and local R. The improvement of the GWR model is more powerful in interpreting the outcomes of the GWR version. Based on the improved GWR method, the conclusions indicate that gastric cancer is prevalent in the clusters of the central southern region in which the Hakka community resides and in the area of the major aboriginal townships in which the aboriginal group lives.
Mutations in the COPII Vesicle Component Gene SEC24B are Associated with Human Neural Tube Defects

Neural tube defects (NTDs) are severe birth malformations that affect one in 1,000 live births. Recently, mutations in the planar cell polarity (PCP) pathway genes had been implicated in the pathogenesis of NTDs in both the mouse model and in human cohorts. Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER‐to‐Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis. In this study, we found four rare missense heterozygous SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, and p.Ala1251Gly) in NTDs cases that were absent in all controls. Among them, p.Phe227Ser and p.Phe682Leu affected its protein stability and physical interaction with VANGL2. Three variants (p.Phe227Ser, p.Arg1248Gln, and p.Ala1251Gly) were demonstrated to affect VANGL2 subcellular localization in cultured cells. Further functional analysis in the zebrafish including overexpression and dosage‐dependent rescue study suggested that these four mutations all displayed loss‐of‐function effects compared with wild‐type SEC24B. Our study demonstrated that functional mutations in SEC24B might contribute to the etiology of a subset of human NTDs and further expanded our knowledge of the role of PCP pathway‐related genes in the pathogenesis of human NTDs.
A platelet biomarker for assessing phosphoinositide 3-kinase inhibition during cancer chemotherapy

Thrombin cleavages of selective proteinase-activated receptors (PAR) as well as PAR-activating peptide ligands can initiate the phosphoinositide 3-kinase (PI3K) signaling cascade in platelets. Downstream to this event, fibrinogen receptors on platelets undergo conformational changes that enhance fibrinogen binding. In our study, we used this phenomenon as a surrogate biomarker for assessing effects on PI3K activity. Our method, using flow cytometric measurement of fluorescent ligand and antibody binding, uncovered a 16- to 45-fold signal window after PAR-induced platelet activation. Pretreatment (in vitro) with the PI3K inhibitors wortmannin and LY294002 resulted in concentration-dependent inhibition at predicted potencies. In addition, platelets taken from mice treated with wortmannin were blocked from PAR-induced ex vivo activation concomitantly with a decrease in phosphorylation of AKT from excised tumor xenografts. This surrogate biomarker assay was successfully tested (in vitro) on blood specimens received from volunteer cancer patients. Our results indicate that measurement of platelet activation could serve as an effective drug activity biomarker during clinical evaluation of putative PI3K inhibitors. [Mol Cancer Ther 2007;6(9):2600–7]
XUV diagnostics tailored to resolve short-pulse-laserdriven ultrafast plasma dynamics

Mit der Entwicklung Freier-Elektronen-Laser (FEL), die im Rontgen und extrem ultravioletten Bereich (XUV) arbeiten, erlebte die Erforschung von Materie unter extremen Bedingungen einen Schub. Es ist nun moglich, Plasmen mit Flussigkeitsdichte beziehungsweise bis uber Festkorperdichte hinaus zu erzeugen und zu untersuchen. Photonen im XUV kommt dabei eine besondere Bedeutung zu, da sie in der Lage sind, dichte Plasmen zu durchdringen und so zur Erforschung des Plasmainneren beitragen konnen. Somit werden wichtige Erkenntnisse uber Energietransport und -austausch zwischen Elektronen und Ionen in Plasmen gewonnen. Auserdem lassen sich Voraussagen von Simulationen experimentell uberprufen. XUV Strahlung kann auch in Emission angeregter Plasmen beobachtet werden, beispielsweise nach Laseranregung eines Festkorpers. Die ortsaufgeloste Analyse der Spektrallinien gewahrt Aufschluss uber Dichte, Temperatur und raumliche Ausdehnung des freien Elektronen Plasmas. Auch aufgrund seiner Koharenzeigenschaften ist FEL Strahlung gut geeignet fur Streu- und Beugungsexperimente. Die hohe Koharenz erlaubt zudem den Einsatz interferometrischer Methoden, welche Aufschluss uber dielektrische Eigenschaften, wie beispielsweise den Brechungsindex geben konnen. Ziel dieser Arbeit ist die Entwicklung und Anwendung innovativer Instrumentierung an FELs zur Erforschung dichter Materie unter extremen Bedingungen und ihre Wechselwirkung mit intensiven Laserfeldern. Die Instrumentierung wird dabei speziell auf Quellgrose und zu erwartende Signal- und Repetitionsraten abgestimmt. In dieser Arbeit wird beschrieben, wie der experimentelle Aufbau und die Vorgehensweise fur neuartige Grundlagenexperimente an Grosforschungsanlagen an die Gegebenheiten vor Ort angepasst werden kann. Bei eventuellem Einsatz mehrerer Gerate werden diese miteinander abgeglichen. Die optisch relevanten Einzelteile solcher masgeschneiderten Aufbauten werden dafur zunachst umfassend charakterisiert und kalibriert.
Extracting Emotions and Communication Styles from Vocal Signals

Many psychological and social studies highlighted the two distinct channels we use to exchange information among us—an explicit, linguistic channel, and an implicit, paralinguistic channel. The latter contains information about the emotional state of the speaker, providing clues about the implicit meaning of the message. In particular, the paralinguistic channel can improve applications requiring human-machine interactions (for example, Automatic Speech Recognition systems or Conversational Agents), as well as support the analysis of human-human interactions (think, for example, of clinic or forensic applications). In this work we present PrEmA, a tool able to recognize and classify both emotions and communication style of the speaker, relying on prosodic features. In particular, communication-style recognition is, to our knowledge, new, and could be used to infer interesting clues about the state of the interaction. We selected two sets of prosodic features, and trained two classifiers, based on the Linear Discriminant Analysis. The experiments we conducted, with Italian speakers, provided encouraging results (Ac=71% for classification of emotions, Ac=86% for classification of communication styles), showing that the models were able to discriminate among emotions and communication styles, associating phrases with the correct labels.
Clinical and microbiological effects of systemic antimicrobials combined to an anti-infective mechanical debridement for the management of aggressive periodontitis: a 12-month randomized controlled trial.

AIM To compare the 1-year clinical and microbiological outcomes of an enhanced anti-infective therapy with versus without systemic antimicrobials in patients with generalized aggressive periodontitis (GAP). METHODS In this 12-month randomized, double-blinded, placebo-controlled trial, 35 individuals assigned to a control (n = 17) or test group (n = 18) received full-mouth supra and subgingival ultrasonic debridement followed by scaling and root planing with chlorhexidine rinsing, brushing, and irrigation. Subjects received either amoxicillin (AMX, 500 mg) + metronidazole (MET, 250 mg) or placebos, TID for 10 days. Subgingival samples were obtained and analysed for their composition by checkerboard. Data were subjected to non-parametric tests. RESULTS Both therapeutic protocols resulted in similar significant clinical improvement for most parameters at 1 year (p < 0.01). The AMX + MET group exhibited shallower residual pockets than the placebo (p = 0.05). Most periodontal pathogens decreased, whereas beneficial bacteria increased in counts in both groups over time (p < 0.0012). High levels of some periodontal and other microbial pathogens were associated with disease persistence regardless treatment. CONCLUSIONS The enhanced anti-infective mechanical therapy is comparable with its combination with systemic AMX+MET for most clinical parameters and for maintaining low levels of periodontal pathogens for up to 1 year after treatment of GAP.
Broadcast communication on fading channels using hierarchical coded modulation

Since Cover's (1972) pioneering work on broadcast channels, it has been known that a substantial gain in transmission rate can be achieved by hierarchical modulation with respect to time-sharing. Here, this work is extended in two directions. First, Rayleigh and Rice fading channels are included. Second, limitations imposed by the use of standard signal constellations, such as M-QAM, are discussed. These extensions lead to a refined understanding of the broadcast channel structure as well as practical design rules for hierarchical coded modulation.
Executable Modeling of Deployment Decisions for Resource-Aware Distributed Applications

The increasing popularity of virtualized services and cloud computing, offering elastic and scalable computing resources challenges software engineering methods by asking a number of new questions: How can we integrate deployment-specific information in the overall design of software applications? How can we express and compare deployment decisions in the design phase, so that performance diagnosis can happen early in the software development cycle? How do we design scalable applications? This thesis proposes a methodology for the modeling and analysis of object-oriented distributed applications that are able to adapt to changes in client traffic, so that they can keep desired levels of performance. As a starting point for developing our methodology, we take Core ABS, an abstract, behavioral specification language that targets the executable modeling of concurrent, distributed and object-oriented systems. We extend Core ABS with deployment-specific information such as deployment architectures, flexible application-specific schedulers, deadlines at the application level, resource management primitives, and user-defined resource costs. The extensions are developed following conventions of formal methods, combining rigorous definitions and formal semantics with a user-friendly Java-like syntax and tool support. By exploiting these language extensions, our methodology makes it possible to compare at the modeling level how a software behaves under different deployment choices. Such comparisons allow a better understanding of the trade-offs from different deployment choices, consequently better design decisions for distributed applications can be made early in the software development life cycle. By integrating resource management and deployment decisions in the design phase, our methodology has the potential to improve the software engineering process for virtualized and scalable software applications running in the cloud, both with respect to quality and with respect to development and deployment cost.
Characterization of human ovarian carcinoma‐associated antigens defined by novel monoclonal antibodies with tumor‐restricted specificity

Three new monoclonal antibodies (MAbs) (MOv16, MOv18 and MOv19) were raised against human ovarian carcinoma. To obtain more specific reagents than those produced so far, we adopted the following experimental approach which consisted of: (1) the selection of a poorly differentiated ovarian carcinoma which was unreactive with all the MAb previously selected in our laboratory; and (2) the application of a particular immunization protocol. The reactivity of the selected MAbs was studied by solid‐phase RIA on live and fixed cells from tumor cell lines and by immunofluorescence on frozen sections from surgical specimens. The MAb MOv16 reacted with 60% of ovarian carcinomas as well as with a high percentage of other carcinomas and with some normal tissues. In contrast, MOv18 and MOv19 appeared to have restricted specificities for ovarian carcinomas and cystadenomas. Reactivity on other carcinomas was only observed in a few cases and no reactivity was found on non‐epithelial tumors or normal tissues. Immunoprecipitation experiments indicated that MOv16 recognizes a 48‐50‐kDA protein, whereas MOv18 and MOv19 both identify a 38‐40 kDA glycoprotein band. Cross‐competition experiments, together with a double‐determinant immunoradiometric assay which uses MOv18 as catcher and MOv19 as tracer, suggested that they recognize different epitopes carried by the same molecule. The affinity constants of MOv18 and MOv19 were estimated to be in the range of 108 ‐ 109 M‐1. Taken together, the properties of these antibodies, their restricted ovarian tumor specificities and relative high affinity constants, suggest that they could represent promising tools for in vivo applications.