Analysis of the construction of the hightemperature gas infrared radiator with the use of virtual prototyping

Method of virtual prototyping with the following mathematical modeling was used to simulate the heat-mass exchange and combustion during the operation of high-temperature gas infrared radiators, and to find optimal technical solutions for its design. The most authoritative and approved software product Ansys Multiphysics was used. The results of the mathematical modeling of heat and mass transfer in a turbulent reaction medium with combustion reproduce the experimental data produced by a measurement in real operating conditions of the gas-fired infrared heat emitter. The temperature distribution along the height of the ceramic nozzle was established. Obtained results enable estimation of the ignition and combustion zones

Data format standards in analytical chemistry

Research data is an essential part of research and almost every publication in chemistry. The data itself can be valuable for reuse if sustainably deposited, annotated and archived. Thus, it is important to publish data following the FAIR principles, to make it findable, accessible, interoperable and reusable not only for humans but also in machine-readable form. This also improves transparency and reproducibility of research findings and fosters analytical work with scientific data to generate new insights, being only accessible with manifold and diverse datasets. Research data requires complete and informative metadata and use of open data formats to obtain interoperable data. Generic data formats like AnIML and JCAMP-DX have been used for many applications. Special formats for some analytical methods are already accepted, like mzML for mass spectrometry or nmrML and NMReDATA forNMRspectroscopy data. Other methods still lack common standards for data. Only a joint effort of chemists, instrument and software vendors, publishers and infrastructure maintainers can make sure that the analytical data will be of value in the future. In this review, we describe existing data formats in analytical chemistry and introduce guidelines for the development and use of standardized and open data formats

Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment

<p>Abstract</p> <p>Background</p> <p>The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer.</p> <p>Methods</p> <p>Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible.</p> <p>Results</p> <p>Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells.</p> <p>Conclusions</p> <p>Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further.</p

Circulating Micro-RNAs as Potential Blood-Based Markers for Early Stage Breast Cancer Detection

INTRODUCTION: MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. METHODS: We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718). RESULTS: Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. CONCLUSIONS: MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use

The Illogicality of Stock-Brokers: Psychological Experiments on the Effects of Prior Knowledge and Belief Biases on Logical Reasoning in Stock Trading

BACKGROUND: Explanations for the current worldwide financial crisis are primarily provided by economists and politicians. However, in the present work we focus on the psychological-cognitive factors that most likely affect the thinking of people on the economic stage and thus might also have had an effect on the progression of the crises. One of these factors might be the effect of prior beliefs on reasoning and decision-making. So far, this question has been explored only to a limited extent. METHODS: We report two experiments on logical reasoning competences of nineteen stock-brokers with long-lasting vocational experiences at the stock market. The premises of reasoning problems concerned stock trading and the experiments varied whether or not their conclusions--a proposition which is reached after considering the premises--agreed with the brokers' prior beliefs. Half of the problems had a conclusion that was highly plausible for stock-brokers while the other half had a highly implausible conclusion. RESULTS: The data show a strong belief bias. Stock-brokers were strongly biased by their prior knowledge. Lowest performance was found for inferences in which the problems caused a conflict between logical validity and the experts' belief. In these cases, the stock-brokers tended to make logically invalid inferences rather than give up their existing beliefs. CONCLUSIONS: Our findings support the thesis that cognitive factors have an effect on the decision-making on the financial market. In the present study, stock-brokers were guided more by past experience and existing beliefs than by logical thinking and rational decision-making. They had difficulties to disengage themselves from vastly anchored thinking patterns. However, we believe, that it is wrong to accuse the brokers for their "malfunctions", because such hard-wired cognitive principles are difficult to suppress even if the person is aware of them

TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes

Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype ‘lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study

Background: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. Methods: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor–positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. Results: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. Conclusions: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. Trial registration Clinical Trials Number: CFEM345DDE1

Clinical and Preclinical Experience with Gefitinib and Sunitinib

Gefitinib and sunitinib are new targeted agents in cancer therapy. As a single-target agent gefitinib was one of the first tyrosine kinase inhibitors in solid cancers. It is an inhibitor of the intracellular domain of the epidermal growth factor receptor (EGFR). Most experience with this drug was made in the treatment of non-small cell lung cancer. Its efficacy in most other solid cancers is limited. Several studies could show an association between the response of non-small cell lung cancers to gefitinib and a mutation of the EGFR gene. This mutation changes the target and alters the sensitivity for the drug. In breast cancer limited data of phase II studies showed response rates lower than 2%. Sunitinib as a multitarget agent inhibits several targets like vascular epidermal growth factor receptors (VEGFR) and other receptor tyrosine kinases. The efficacy of sunitinib against tumors is attributable to a direct antitumor activity and to an inhibition of neoangiogenesis. Most data exist for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Sunitinib could clearly improve the systemic treatment of these diseases. In the treatment of metastatic breast cancer response rates for the single agent therapy of 11% could be reported, which made this agent interesting for further phase III studies. These phase III studies are currently ongoing.Gefitininb und Sunitinib sind neue Medikamente zur Krebstherapie. Sie inhibieren gezielt die intrazelluläre Tyrosinkinase- Domäne von Wachstumsfaktorrezeptoren. Gefitinib hat ein Ziel und inhibiert den Epidermal Growth Factor Receptor (EGFR). Die meisten Erfahrungen wurden beim nicht-kleinzelligen Lungenkarzinom gemacht. Die Wirksamkeit bei anderen soliden Tumoren ist begrenzt. Die Wirksamkeit bei Lungenkarzinomen konnte mit einer Mutation im EGFR-Gen assoziiert werden. Eine solche Mutation erhöht die Sensitivität der Lungenkarzinome für Gefitinib. Bei Patientinnen mit metastasiertem Mammakarzinom sind die Erfahrungen begrenzt. Die Ansprechraten bei vorbehandelten Patientinnen liegt unter 2%. Sunitinib hat mehrere Ziele und inhibiert neben dem Vascular Epidermal Growth Factor Receptor (VEGFR) noch andere Wachstumsfaktorrezeptroren. Es wirkt nicht nur direkt zytostatisch sondern auch durch eine Inhibition der Neoangiogenese. Die meisten Daten gibt es zur Behandlung des Nierenzellkarzinoms und des gastrointestinalen Stromatumors. Hier konnte die systemische Behandlung durch Sunitinib entscheidend verbessert werden. Beim Mammakarzinom liegen die Ansprechraten für das metastasierte Mammakarzinom bei 11%. Phase-III-Studien für das metastasierte Mammakarzinom sind gerade begonnen worden