bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Outcomes in Metastatic Clear Cell Renal Cell Carcinoma by Sequencing Therapy
Authors: Schmidinger Manuela
Published: May 2014

Targeted agents have substantially improved outcomes in metastatic clear cell renal cell carcinoma. However, due to multiple mechanisms of evasive resistance, almost all patients progress at some point and may require subsequent therapies. Various agents have been explored after failure of first-line treatment in randomized clinical trials. However, so far few questions about the optimal sequence have been answered. Both everolimus and axitinib have been considered standard of care after failure of first-line VEGF-TKI; sorafenib has been proposed as an additional option. In clinical practice, several factors may influence the choice of subsequent treatment: these include considerations on appropriate drug exposure in first-line, gained insights on prognostic and predictive factors as well as mechanisms of resistance. Once the decision in second-line has been made and treatment has been initiated, treating physicians may already be challenged by the question of what to offer in third- and later lines. Treatment beyond second-line treatment isn't supported by strong evidence, and at this stage of disease, retrospective reports on rechallenge may help to guide decisions. In addition, local treatment approaches including metastasectomy and stereotactic radiosurgery may help to optimize outcomes in all treatment lines.
Current Approaches to the Management of Bladder Cancer in Older Patients
Authors: Stensland Kristian D. , Galsky Matthew D.
Published: May 2014

Bladder cancer is largely a disease of older adults, with nearly half of diagnoses occurring in those older than age 75. This has led to a disconnect between the efficacy and effectiveness of various treatment strategies. For example, surgical removal of the bladder is a potentially curative approach to muscle-invasive disease, although the large single-center and multicenter series that have established the efficacy of this approach include only a small proportion of older patients. Similarly, clinical trials that have established optimal chemotherapeutic regimens for use in the perioperative and metastatic settings comprise largely younger patients. Extrapolating the available evidence to the population of older patients with bladder cancer requires careful assessment of an individual patient's functional status and comorbidities to estimate the likelihood of treatment-related harms. This should be coupled with an understanding of an individual patient's goals of therapy, independence, estimated longevity, and social support to facilitate a shared medical decision regarding treatment. The use of validated approaches to geriatric assessment may refine risk stratification in older adults, although practical challenges have prevented uniform adoption in routine clinical practice.
Patient-Derived Xenograft Models in Gynecologic Malignancies
Authors: Scott Clare L. , Mackay Helen J. , Haluska Paul
Published: May 2014

In the era of targeted therapies, patients with gynecologic malignancies have not yet been major beneficiaries of this new class of agents. This may reflect the fact that the main tumor types—ovarian, uterine, and cervical—are a highly heterogeneous group of cancers with variable response to standard chemotherapies and the lack of models in which to study the diversity of these cancers. Cancer-derived cell lines fail to adequately recapitulate molecular hallmarks of specific cancer subsets and complex microenvironments, which may be critical for sensitivity to targeted therapies. Patient-derived xenografts (PDX) generated from fresh human tumor without prior in vitro culture, combined with whole genome expression, gene copy number, and sequencing analyses, could dramatically aid the development of novel therapies for gynecologic malignancies. Gynecologic tumors can be engrafted in immunodeficient mice with a high rate of success and within a reasonable time frame. The resulting PDX accurately recapitulates the patient's tumor with respect to histologic, molecular, and in vivo treatment response characteristics. Orthotopic PDX develop complications relevant to the clinic, such as ascites and bowel obstruction, providing opportunities to understand the biology of these clinical problems. Thus, PDX have great promise for improved understanding of gynecologic malignancies, serve as better models for designing novel therapies and clinical trials, and could underpin individualized, directed therapy for patients from whom such models have been established.
Value Considerations in the Treatment of Head and Neck Cancer: Radiation, Chemotherapy, and Supportive Care
Authors: Baxi Shrujal S. , Sher David J. , Pfister David G.
Published: May 2014

The management of head and neck cancer has advanced in many areas, including but not limited to diagnostic imaging and response assessment, radiation delivery, surgical approaches, combined-modality therapy, as well as new drug discovery. These advances have become widely used, however, the associated improvements in outcomes of interest compared with other options may at times be modest in magnitude or supported by limited data. In addition, the price tag of these advancements is often high. There is a growing mandate to look at existing data to identify insights into how to improve the value of care and to better understand the comparative effectiveness of one intervention versus another with regard to tumor control, quality of life, and other important outcomes; such insights become particularly important when considerable disparities exist in related costs. We review selected issues in radiotherapy, chemotherapy and supportive care applicable to the management of head and neck cancer and relevant to ascertaining the value of care.
Global Response to the Burden of Cancer: The WHO Approach
Authors: Ullrich Andreas , Miller Anthony
Published: May 2014

As the burden of many cancer types of major public health relevance worldwide are in part determined by behavioral risks, much of the success of cancer control depends on the up take of prevention strategies at the population level. Over the last decade, the World Health Organization (WHO) has developed global prevention strategies of major relevance for cancer prevention and the prevention of other non-communicable diseases (NCDs), such as the 2003 WHO Framework Convention on Tobacco Control and others. The implementation of these core strategies gained momentum in 2011, when heads of states at the United Nation's (UN) High Level Meeting (HLM) on NCDs declared that NCDs are a global health threat that menaces social and economic development globally and requires urgent action. They asked for a paradigm change of the global health agenda by including NCD prevention and control into the group of priorities set by the Millennium Development Goals. WHO's translation of this call for action by the UN into practice has been consolidated into one clearly defined the WHO Global NCD Action Plan 2013–2020, including the pre-existing prevention strategies. Although cancer risk reduction will profit from the WHO Global NCD Action Plan, comprehensive cancer prevention and control will require other supplementary strategies not included in the plan because they are not shared with other NCDs. Causality of the over 200 cancer types is complex. A myriad of non-behavioral factors such as environmental and infectious risks, require specific attention when planning comprehensive cancer prevention. In reducing the cancer burden globally much will depend on how prevention strategies are implemented and how progress in cancer treatment can be translated into the reality of health systems in less affluent countries.
Should Triple-Negative Breast Cancer (TNBC) Subtype Affect Local-Regional Therapy Decision Making?
Authors: Moran Meena S.
Published: May 2014

The more aggressive biologic characteristics and the current lack of targeted therapy for triple-negative breast cancer (TNBC) make local-regional management decisions challenging for physicians. TNBC is associated with patients of younger age, black race and BRCA1 mutation carriers. Distinctions between BRCA1-associated and sporadic TNBC include increased lifetime risk of ipsilateral and contralateral breast cancer after breast cancer therapy (BCT) for BRCA carriers, which is not shared by sporadic TNBC. However, the presence of a BRCA mutation should not preclude a breast-conservation approach in patients who are otherwise appropriate candidates for BCT. Data suggest that local-regional relapse (LRR) at baseline after BCT appears to be comparable for TNBC and the HER2-positive subgroups, but is about 50% greater than luminal tumors. LRR appears to be similarly increased after mastectomy; thus, TNBC should not be a contra-indication for BCT. Recent hypothesis-generating data suggest less LRR after BCT (where radiation is routinely delivered) than with mastectomy for early-stage TNBC. To date, no specific local-regional guideline recommendations for TNBC exist. Level I outcome data for TNBC using accelerated partial breast irradiation (APBI) and hypofractionated whole-breast irradiation (hWBRT) are lacking. TNBC should be treated with APBI only on clinical trials. Although hWBRT may be considered in TNBC, its association with younger age, advanced disease and use of systemic chemotherapy often precludes its use for this subtype. Until definitive treatment strategies are validated in large datasets and confirmed in randomized trials, TNBC subtype, in and of itself, should not direct local-regional management treatment decisions.
Novel Therapies in AML: Reason for Hope or Just Hype?
Authors: Larkin Karilyn , Blum William
Published: May 2014

We have entered the genomic sequencing era in the treatment of acute myeloid leukemia (AML); our patients increasingly and justifiably demand personalized treatment based on aberrations of their own leukemia. Except in rare cases we are not yet able to provide truly personalized therapy, so the question of “hope or hype?” posed by the American Society for Clinical Oncology (ASCO) for this educational topic is quite timely. The answer based solely on advances in genomic sequencing is “both”. There is an element of expectation among the public that we are “almost there” in solving the genetic cancer puzzle, an expectation indeed based on hype. However, there is no question that ultimate success lies in understanding the genetic underpinnings of disease. When decades of research in molecular biology and immunology are combined with transformative advances in cancer genetics, the answer is undeniably that our patients finally have reason for hope. Here, we review selected novel therapies for AML in areas such as immunotherapeutics, epigenetics, kinase inhibition/pathway inhibition, and the marrow microenvironment.
Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations
Authors: Gerber David E. , Gandhi Leena , Costa Daniel B.
Published: May 2014

Lung cancer accounts for a quarter of all cancer deaths. Non-small cell lung cancer (NSCLC) is currently segregated by the presence of actionable driver oncogenes. This review will provide an overview of molecular subsets of lung cancer, including descriptions of the defining oncogenes ( EGFR, ALK, KRAS, ROS1, RET, BRAF, ERBB2, NTRK1, FGFR, among others) and how these predict for response to small molecule tyrosine kinase inhibitors (TKIs) that are either clinically available or in clinical trial development for advanced NSCLC. Particular focus will be placed on subsets with EGFR mutated and ALK rearranged NSCLC. Somatic TKI-sensitizing EGFR mutations (such as exon 19 deletions and L858R substitutions) are the most robust predictive biomarker for symptom improvement, radiographic response, and increment in progression-free survival (PFS) when EGFR TKIs (gefitinib, erlotinib, and afatinib) are used for patients with advanced NSCLC. However, the palliative benefits that EGFR TKIs afford are limited by multiple biologic mechanisms of tumor adaptation/resistance (such as the EGFR-T790M mutation and oncogene bypass tracks), and future efforts toward delaying, preventing, and treating resistance are underway. Similar to EGFR mutations, ALK rearrangements exemplify an oncogene-driven NSCLC that can be effectively palliated with a precision TKI therapy (the multitargeted ALK/MET/ROS1 TKI crizotinib). When resistance to first-line crizotinib therapy occurs, multiple second generation ALK TKIs have demonstrated impressive rates of disease control in clinical trials, and these may modify long-term outcomes for patients with ALK-positive NSCLC. The development of TKIs for other oncogene-driven NSCLCs may expand the portfolio of precision therapies for this recalcitrant cancer.
Systemic Treatment of Advanced Thymic Malignancies
Authors: Kelly Ronan J.
Published: May 2014

The rarity of thymic malignancies prevents us from performing large randomized clinical trials. As a result, systemic treatment decisions are often guided by a small amount of prospective trial data, retrospective series, and individual case reports. In recent years, we have begun to unravel the molecular biology of thymic tumors. It is becoming more apparent as a result of gene expression profiling and genomic clustering studies that the subclassifications of type A, AB, B1, B2, B3, and thymic carcinoma have different molecular features that may be clinically relevant. Genomic profiling distinguishes type B3 thymoma and thymic carcinoma as distinct entities from type A and type B2 thymoma. Furthermore, type B2 thymomas can be separated from other subgroups in that it has a more distinct lymphocytic component than the other groups where epithelial cells predominate. Next generation RNA sequencing has recently identified a large microRNA cluster on chromosome 19q13.42 in types A and AB thymomas, which is absent in type B thymomas and thymic carcinomas. This cluster has been shown to result in activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway, which suggests a possible role for PI3K inhibitors in these subtypes. The presence of KIT mutations in thymic carcinomas is also well described. Herein we discuss the chemotherapeutic and targeted treatment options for advanced thymic malignancies and highlight important advances in our understanding of the molecular biology of these rare tumors.
Chemotherapy for Lung Cancers: Here to Stay
Authors: Kris Mark G. , Hellmann Matthew D. , Chaft Jamie E.
Published: May 2014

Four decades of clinical research document the effectiveness of chemotherapy in patients with lung cancers. Chemotherapeutic agents can improve lung cancer symptoms, lengthen life in most patients with lung cancers, and enhance curability in individuals with locoregional disease when combined with surgery or irradiation. Chemotherapy's effectiveness is enhanced in patients with EGFR-mutant and ALK-positive lung cancers and can “rescue” individuals whose oncogene-driven cancers have become resistant to targeted agents. As immunotherapies become part of the therapeutic armamentarium for lung cancers, chemotherapeutic drugs have the potential to modulate the immune system to enhance the effectiveness of immune check point inhibitors. Even in this era of personalized medicine and targeted therapies, chemotherapeutic agents remain essential components in cancer care.
Accelerated Aging among Cancer Survivors: From Pediatrics to Geriatrics
Authors: Henderson Tara O. , Ness Kirsten K. , Cohen Harvey Jay
Published: May 2014

There are almost 14-million cancer survivors in the United States and the population is growing. Almost two-thirds of these survivors are age 65 or older. Given this, it is imperative to understand the impact of cancer and its therapies on the aging process. Childhood cancer survivors, diagnosed with cancer at age 21 or younger, particularly females, have rates of frailty similar to rates in older adults. This phenomenon appears to start early, suggesting an aging phenotype. Frailty among childhood cancer survivors increases risk for chronic disease and mortality. Adults diagnosed with cancer are faced with the effects of cancer and its therapies compounded by the issues of multiple morbidities that occur with the typical aging process. Intervention studies to date have focused on smoking cessation, diet, and exercise, as well as improving rates of late effects surveillance in childhood cancer survivors. No intervention studies have specifically addressed the issue of frailty or multiple morbidities in cancer survivors. Concerted efforts must continue to create and disseminate survivorship care plans to all cancer survivors.
Pediatric Melanoma: The Whole (Genome) Story
Authors: Pappo Alberto S.
Published: May 2014

Pediatric melanoma is rare and given the diagnostic challenges it presents in this age group, it is difficult to interpret the literature describing its natural history and outcome. Recent genomic analysis demonstrates that conventional melanoma in children and adolescents shares many of the genomic features that have been described in adult melanoma, including BRAF mutations. Thus, this patient group should be given the opportunity to enroll in National Cancer Institute and pharmaceutically sponsored trials that incorporate novel targeted agents.
Targeting BRAF in Pediatric Brain Tumors
Authors: Kieran Mark W.
Published: May 2014

The role of BRAF in adult malignancy has been well documented over the last decade and recent data have extended these findings to a number of pediatric cancers. In this and the accompanying articles, we will review the importance of the BRAF pathway in signal transduction resulting in cell proliferation, migration, differentiation, and angiogenesis with a focus on three major pediatric diseases: brain tumors, Langerhans cell histiocytosis (LCH), and melanoma. Mutated BRAF proteins are being identified in an increasing number of pediatric cancers and the development of drugs that can target these mutant proteins offers enormous therapeutic opportunity for these diseases. Because of variations in the types of mutations of BRAF observed in different tumors, particularly those of the central nervous system, an understanding of the feedback loops that regulate monomeric and dimeric BRAF signaling will be critical in selecting the optimal targeted inhibitors. The two most commonly observed alterations in BRAF in patients with brain tumor are the BRAF V600E point mutation and the KIAA1549 truncated fusion and targeting of these will need to differ to account for these feedback loops. Many other factors will influence the activity of novel agents in BRAF activated tumors, including their ability to penetrate the blood-brain barrier (for brain tumors and some patients with LCH) as well as the development of drug resistance and toxicity profiles. Well-controlled trials that take these variables into consideration are already underway and highlight the need for molecular classification of pediatric central nervous system tumors.
Biological and Therapeutic Implications of the BRAF Pathway in Histiocytic Disorders
Authors: Arceci Robert J.
Published: May 2014

Langerhans cell histiocytosis (LCH) has historically evolved in its classification from a primary immune dysregulatory disorder to what current evidence supports as a dendritic cell neoplasm with an immune-inflammatory component. A key part of the classification of LCH as a neoplasm has been the identification of BRAF V600E mutations in 35% to 60% of cases. Tumor protein p53 (TP53) and RAS mutations have also been identified, albeit in less than 2% of reported cases. Of note, over 50% of patients with another dendritic cell disease, Erdheim-Chester Disease, have also been shown to have BRAF V600E mutations. Although the BRAF mutations have not been shown to be associated with extent of disease, they may still provide a target for a molecularly guided approach to therapy. In cases of LCH in which no BRAF mutations were identified, there was evidence for activation of the RAS-RAF-MEK-extracellular signal-regulated kinases (ERK) pathway, suggesting that similar to other tumors, this pathway may be therapeutically exploitable. Anecdotal responses have been reported in a few patients with LCH and Erdheim-Chester Disease to vemurafenib, a BRAF V600E inhibitor. Although these results pave the way for careful, prospective clinical testing, selection of the optimal groups in which to test such inhibitors, alone or in combination, will be critical based on the toxicity profile thus far observed in adults with melanoma and other BRAF mutated tumors.
Tumor Boards: Optimizing the Structure and Improving Efficiency of Multidisciplinary Management of Patients with Cancer Worldwide
Authors: El Saghir Nagi S. , Keating Nancy L. , Carlson Robert W. , Khoury Katia E. , Fallowfield Lesley
Published: May 2014

Multidisciplinary management tumor boards are now conducted worldwide for the management of patients with cancer. Studies evaluating their influence on decision making and patient outcome are limited; however, single-center studies have reported significant changes in diagnosis and treatment plans. A survey from Arabic countries showed widespread use and reliance on tumor boards for decision making. A recent multi-institutional survey of veteran affairs (VA) hospitals in the United States found limited association between the presence of tumor boards and care and outcomes. The Cancer Care Outcomes Research and Surveillance Consortium looked at the association between tumor board features and measures of quality of care. Results of overall survival among the patients of these physicians participating in tumor boards is ongoing, but preliminary results are outlined along with a recent ASCO survey of international members on the presence, utilization, and influence of tumor boards in this article. Tumor boards allow for implementation of clinical practice guidelines and may help capture cases for clinical trials. Efforts to improve preparations, structure, and conduct of tumor boards, research methods to monitor their performance, teamwork, and outcomes are outlined also in this article. The concept of mini-tumor boards and more efficient methods for MDM in countries with limited resources are also discussed. In suboptimal settings, such as small community hospitals, rural areas, and areas with limited resources, boundaries in diagnosis and management can be overcome, or at least improved, with tumor boards, especially with the use of video-conferencing facilities. Studies from the United Kingdom showed that special training of multidisciplinary teams (MDT) led to better team dynamics and communication, improved patient satisfaction, and improved clinical outcome. The weight of the benefits versus the time and effort spent to improve efficiency, patient care, and better time management in the United States and in the international oncology community is also reviewed in this article.
Novel Treatment Targets in Sarcoma: More Than Just the GIST
Authors: Shoushtari Alexander N. , Van Tine Brian A. , Schwartz Gary K.
Published: May 2014

Sarcomas are rare tumors comprising a heterogeneous group of more than 50 histologic subtypes, the majority of which do not respond well to cytotoxic chemotherapy. This has fueled research into the distinct molecular mechanisms of tumorigenesis and disease progression for various sarcoma subtypes. Gastrointestinal stromal tumors and liposarcomas are presented as paradigms of molecular classification that have led to the rational development of novel therapeutic strategies for those tumors. Recent advances in understanding of growth signaling pathways, metabolic reprogramming, and immune therapy have identified new treatment targets for many sarcomas. These investigations will form the foundation for further improvements in our ability to care for patients with these tumors and may offer clinical insights into a wide range of other tumors.
Mass Spectrometry-Based Proteomics: From Cancer Biology to Protein Biomarkers, Drug Targets, and Clinical Applications
Authors: Jimenez Connie R. , Verheul Henk M. W.
Published: May 2014

Proteomics is optimally suited to bridge the gap between genomic information on the one hand and biologic functions and disease phenotypes at the other, since it studies the expression and/or post-translational modification (especially phosphorylation) of proteins—the major cellular players bringing about cellular functions—at a global level in biologic specimens. Mass spectrometry technology and (bio)informatic tools have matured to the extent that they can provide high-throughput, comprehensive, and quantitative protein inventories of cells, tissues, and biofluids in clinical samples at low level. In this article, we focus on next-generation proteomics employing nanoliquid chromatography coupled to high-resolution tandem mass spectrometry for in-depth (phospho)protein profiling of tumor tissues and (proximal) biofluids, with a focus on studies employing clinical material. In addition, we highlight emerging proteogenomic approaches for the identification of tumor-specific protein variants, and targeted multiplex mass spectrometry strategies for large-scale biomarker validation. Below we provide a discussion of recent progress, some research highlights, and challenges that remain for clinical translation of proteomic discoveries.
Prevention of Prostate Cancer: Outcomes of Clinical Trials and Future Opportunities
Authors: Thompson Ian , Kristal Alan , Platz Elizabeth A.
Published: May 2014

Prostate cancer is an excellent target for prevention, to reduce both mortality and the burden of overdetection of potential inconsequential disease whose diagnosis increases cost, morbidity, and anxiety. The Prostate Cancer Prevention Trial has demonstrated that finasteride significantly reduces the risk of prostate cancer but only low-grade disease; overall survival is unaffected. In the Selenium and Vitamin E Cancer Prevention Trial (SELECT) clinical trial, selenium had no effect on prostate cancer risk, but alpha tocopherol significantly increased the risk by 17%. The most promising future approaches to prostate cancer prevention will likely focus on nutrition, especially weight control, and through modulation of inflammation.
Memory and Recollection in Plotinus
Authors: Nikulin Dmitri
Published: May 2014

Beginning with an outline of memory and recollection in Plato and Aristotle, this paper argues that establishing the role of memory and recollection in their mutual relation in Plotinus requires a careful reconstruction. Whereas memory for Plotinus is not a storage of images or imprints that come either from the sensible or the intelligible but rather is a power capable of producing memories, recollection takes the form of a discursive rational rethinking and reproduction of the soul’s experience of the noetic objects. Recollection, then, is a triple motion of the descent, stay, and return of the soul to the intelligible.
Ruling out Lucky Proofs
Authors: Shigenaga Tetsuya
Published: May 2014

According to Leibniz’s theory for contingent truths about created individuals, this kind of truth cannot be proved in a finite number of steps, because the analyses of the concepts corresponding to these individuals required for the proofs proceed to infinity. Some commentators pointed out that such truths
Replicated spectrographs in astronomy
Authors: Hill Gary J.
Published: May 2014

As telescope apertures increase, the challenge of scaling spectrographic astronomical instruments becomes acute. The next generation of extremely large telescopes (ELTs) strain the availability of glass blanks for optics and engineering to provide sufficient mechanical stability. While breaking the relationship between telescope diameter and instrument pupil size by adaptive optics is a clear path for small fields of view, survey instruments exploiting multiplex advantages will be pressed to find cost-effective solutions. In this review we argue that exploiting the full potential of ELTs will require the barrier of the cost and engineering difficulty of monolithic instruments to be broken by the use of large-scale replication of spectrographs. The first steps in this direction have already been taken with the soon to be commissioned MUSE and VIRUS instruments for the Very Large Telescope and the Hobby-Eberly Telescope, respectively. MUSE employs 24 spectrograph channels, while VIRUS has 150 channels. We compare the information gathering power of these replicated instruments with the present state of the art in more traditional spectrographs, and with instruments under development for ELTs. Design principles for replication are explored along with lessons learned, and we look forward to future technologies that could make massively-replicated instruments even more compelling.
Identifikation mit achsenschrägen, lokal polynomialen Modellnetzen
Authors: Hartmann Benjamin , Nelles Oliver
Published: May 2014

Der Beitrag stellt eine neue Trainingsmethode für lokale Modellnetze vor, die ein Höchstmaß an Flexibilität ermöglicht. Ausgehend von LOLIMOT werden Möglichkeiten zur Verbesserung aufgezeigt, die das volle Potential heutiger Rechner ausschöpfen können. Neben der achsenschrägen Schnittoptimierung, die von Hinging Hyperplane-Ansätzen bekannt ist, führt die Anwendung einer Strukturabwägung auf viel versprechende Ergebnisse. Dazu wird als Alternative zur Teilung die Möglichkeit der Komplexitätserhöhung eines lokalen Modells durch den Einsatz von Strukturselektionsverfahren gegenübergestellt.
Modelica-Bibliothek für diffraktive Optik zur Modellierung von optomechatronischen Systemen
Authors: Kaden Thomas , Janschek Klaus
Published: May 2014

Zur Modellierung und Simulation von heterogenen Systemen hat
sich die physikalisch objektorientierte Modellbeschreibungssprache
Modelica etabliert. Der Entwurf von optomechatronischen Systemen,
wie z. B. der aktiven oder adaptiven Optik, erfordert die
Beschreibung des gekoppelten optisch-mechatronischen Verhaltens
inklusive Regelung (cloosed-loop). Im folgenden Artikel wird
vorgestellt, wie eine diffraktive Optikfunktionalität in das
Modelica-Konzept als neue Bibliothek integriert werden kann.
Modellierung eines Smart High-Side Power ICs
Authors: Blank Mathias , Glück Tobias , Kugi Andreas , Kreuter Hans-Peter
Published: May 2014

Dieser Beitrag behandelt die mathematische Modellierung eines Smart High-Side Power ICs. Smart Power ICs sind Leistungsschalter mit integrierten Regelungs- und Schutzfunktionen. Ausgehend von der vollständigen Schaltung des ICs wird eine für die Systemanalyse und den Reglerentwurf geeignete Ersatzschaltung abgeleitet und mathematisch modelliert. Damit ist es möglich, das Großsignalverhalten des Smart Power ICs mit Hilfe eines Differentialgleichungssystems fünfter Ordnung zu beschreiben. Anhand von Simulationsergebnissen wird das mathematische Modell mit der vollständigen Schaltung verglichen.
LTI Modell arbiträrer wechselrichtergeführter Inselnetze
Authors: Jostock Markus , Sachau Jürgen , Tuttas Christian
Published: May 2014

Der Beitrag beschreibt die Entwicklung eines regelungstechnischen
Modells wechselrichtergeführter Inselnetze. Der hier vorgestellte
strukturierte Ansatz bildet auf Basis der Zustandsraumdarstellung
eines Wechselrichters ein multi-Wechselrichtermodell und verknüpft
dieses mit der Strukturinformation der Knoteninzidenzmatrix zu einem
geschlossenen Inselnetzmodell. Das Verfahren ermöglicht die Erstellung
von Modellen mit beliebig strukturierten Netzen und großer Anzahl
unterschiedlicher Wechselrichtermodelle im NS-Netz. Abschließend wird
eine Stabilitätsanalyse eines Beispielnetzes präsentiert.
Die Theorie multikultureller Bürgerrechte eröffnet auch eine spannende Perspektive auf die Frage der Tierrechte
Authors: Donaldson Sue , Kymlicka Will , Sezgin Hilal
Published: May 2014

In this interview, Sue Donaldson and Will Kymlicka reply to some questions and objections to their book Zoopolis (Oxford 2011). A distinctive feature of their approach is the idea that domesticated animals should be seen as cocitizens of our political community. Donaldson and Kymlicka discuss how this view of animal citizenship relates to issues regarding the right to vote, the right to political representation, and rights to residence and membership. The authors also explore how their political account of animal rights theory relates to theories of multiculturalism as well as conflicts between individual and group rights. Addressing these issues, they argue, requires attending to the agency of animals themselves, and not just treating them as passive moral patients.
The nature of explanation in synergetic linguistics
Authors: Zámečník Lukáš
Published: May 2014

This investigation focuses on the nature of explanation in synergetic linguistics. After recounting the basic principles of Haken s synergetics, a physicalist stance constitutes the basis of a critique of using the stringent synergetic principle of synergetic linguistics. Jaegwon Kim has convincingly demonstrated that the strict synergetic principle impairs quantitative linguistics with downward causation. The central part of this paper demonstrates that the synergetic principle is not an appropriate principle on which to construct a valid functional explanation of quantitative linguistics. The final section analyses the concept of law in quantitative linguistics. We examine a series of laws as models and economization principles and we outline a conception of laws as various categories of conservation principles.
Crystal structure of 2-aminobenzothiazolinium nitrate and theoretical study of the amino-imino tautomerism of 2-aminobenzothiazole
Authors: Yan Xingchen , Wu Xiaojing , Xu Jiakun , Fan Yuhua , Bi Caifeng , Zhang Xia , Zhang Zhongyu
Published: May 2014

2-Aminobenzothiazolinium nitrate (1) was characterized by elemental analysis, melting point, IR, 1H NMR, and X-ray crystallography. The driving force for the 2-aminobenzothiazole tautomerism in methanol solution was studied using theoretical calculations. It is suggested that the 2-aminobenzothiazolinium cation is an intermediate product between the amino form (2) and imino form (3) of 2-aminobenzothiazole. The tautomerization reaction can proceed in two steps through protonation and deprotonation between the two forms 2 and 3.
Bacterial and abiotic decay in waterlogged archaeological Picea abies (L.) Karst studied by confocal Raman imaging and ATR-FTIR spectroscopy
Authors: Pedersen Nanna Bjerregaard , Gierlinger Notburga , Thygesen Lisbeth Garbrecht
Published: May 2014

Waterlogged archaeological Norway spruce [Picea abies (L.) Karst] poles were studied by means of confocal Raman imaging (CRI) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) analysis to determine lignin and polysaccharide composition and distribution in the cell wall. The waterlogged archaeological wood (WAW) was submerged under anoxic conditions for approximately 400 years and solely decayed by erosion bacteria (EB). CRI showed that decayed tracheids contain a residual material (RM) with heterogeneous lignin distribution; within the same tracheid RM often contained regions with intensities lower than sound S2 layers up to intensity values as high as the compound middle lamella (CML). CRI revealed strong depletion of carbohydrates in RM which indicated that EB are able to utilise the carbohydrate fraction of the cell wall effectively. Raman bands assigned to lignin did not show any difference between RM and sound S2. This is a hint that EB do not modify the lignin structure. Sound WAW free from EB decay showed evidence of loss of acetyl groups in glucomannan, loss of un-conjugated ester linkages in the lignin-carbohydrate complexes between xylan and lignin, and minor oxidation of the lignin polymer compared to recent reference material. This is evidence for abiotic decay in the course of waterlogging.
Protective actions of melatonin and growth hormone on the aged cardiovascular system
Authors: Paredes Sergio D. , Forman Katherine A. , García Cruz , Vara Elena , Escames Germaine , Tresguerres Jesús A.F.
Published: May 2014

Epidemiological studies indicate that certain aspects of lifestyle and genetics act as risk factors for a variety of cardiovascular disorders, including coronary disease, hypertension, heart failure and stroke. Aging, however, appears to be the major contributor for morbidity and mortality of the impaired cardiovascular system. Growth hormone (GH) and melatonin seem to prevent cardiac aging, as they contribute to the recovery of several physiological parameters affected by age. These hormones exhibit antioxidant properties and decrease oxidative stress and apoptosis. This paper summarizes a set of studies related to the potential role that therapy with GH and melatonin may play in the protection of the altered cardiac function due to aging, with a focus on experiments performed in our laboratory using the senescence-accelerated mouse as an aging model. In general, we observed significantly increased inflammation, oxidative stress and apoptosis markers in hearts from senescence-accelerated prone 10-month-old animals compared to 2-month-old controls, while anti-inflammatory and antiapoptotic markers as well as endothelial nitric oxide synthase were decreased. Senescence-accelerated resistant animals showed no significant changes with age. GH or melatonin treatment prevented the age-dependent cardiac alterations observed in the senescence-accelerated prone group. Combined administration of GH plus melatonin reduced the age-related changes in senescence-accelerated prone hearts in an additive fashion that was different to that displayed when administered alone. GH and melatonin may be potential agents for counteracting oxidative stress, apoptosis and inflammation in the aging heart.
Role of the adipocyte-derived hormone leptin in reproductive control
Authors: Garcia-Galiano David , Allen Susan J. , Elias Carol F.
Published: May 2014

Achievement of sexual maturation and maintenance of fertility in adulthood are functions that are sensitive to the metabolic status of the organism, particularly the magnitude of fat reserves. In this sense, the adipocyte-derived hormone, leptin, plays a major role in linking metabolic cues and the control of multiple neuroendocrine axes. The hypothalamus is a key site mediating leptin actions, including those involved in the modulation of the hypothalamus-pituitary-gonads (HPG) axis at different stages of development and in different environmental conditions. In the present review, we provide an update of the role of leptin in reproduction and discuss its interactions with neurons, neurotransmitters and downstream targets of the reproductive axis, with a special emphasis on the actions of leptin in the central nervous system. We hope this review will contribute to the understanding of the mechanisms whereby metabolic signals, especially leptin, influence the reproductive neuroendocrine axis modulating its activity in different nutritional states. Special attention will be given to recent advances in the identification of key hypothalamic sites and signaling pathways relevant to leptin’s action in reproductive control.
Prediction of High Temperature Flow Stress of Alloy 2618-Ti during Hot Deformation
Authors: Liu Ya , Li Jing , Song Yuanfeng , Li Tao , Su Xuping , Wang Jianhua
Published: May 2014

In order to find material parameters of established Zener-Hollomon constitutive equations and predict high-temperature flow stress of alloy 2618-Ti, the hot compressive deformation behaviors of the alloy were investigated at temperatures ranging from 300 to 500 °C at intervals of 50 °C and at constant strain rates of 0.001, 0.01, 0.1 and 1 s
Separation of ZnO from the Stainless Steelmaking Dust and Graphite Mixture by Microwave Irradiation
Authors: Zhou Yun , Wu Liushun , Wang Jue , Wang Haichuan , Dong Yuanchi
Published: May 2014

In this study, microwave was used to treat stainless steelmaking dust containing zinc oxide. The effects of heating time, carbon content and zinc oxide content on the removal efficiency of zinc oxide and the reduction efficiency of iron oxide were investigated. Experimental results show that, for the sample with 16% (mass percent, the same below) graphite heated for 10 minutes by 10 kW power microwave, the removal efficiency of zinc oxide is between 80% and 90% and the metallization ratio of iron oxide is between 40% and 60%; Initial zinc oxide content has a slight effect on the removal efficiency of zinc oxide. The results indicate microwave treatment is one of the feasible ways to process metallurgical solid waste containing the metal with low boiling point.
Thermodynamic Modeling of CaO-CaF2 and CaO-SiO2 Systems
Authors: Shu Qifeng , Chou Kuo-chih
Published: May 2014

CaO-CaF
Intergenerational Relations and the Family Home
Authors: Kreiczer-Levy Shelly
Published: May 2014

This article examines the issue of intergenerational cohabitation in the family home. Its primary purpose is to demonstrate that current analysis of internal conflicts in the home is lacking, both in terms of identifying the parties’ interests and characterizing the tensions involved. It focuses on a specific three-way conflict between two parents and their adult child and identifies each of their points of view: one parent who wants the adult child to move out, one parent who wants to continue to share her home with the adult child, and the adult child who wants to remain in the home.

The article builds on rich multidisciplinary literature on the meaning of the home. This focus sheds new light on the conflict in two significant manners. First, the disagreement between the parents is characterized as a struggle between two conflicting visions of the home. Each of these visions reflects a different perception of the home, the family, and intergenerational commitments. Second, the focus on the home allows lawyers to acknowledge the position of the adult child, whose interest is completely not sufficiently taken into account in the conventional analysis.
Experimental study of cadmium bioaccumulation in three Mediterranean marine bivalve species: correlation with selected biomarkers
Authors: Chalkiadaki Olga , Dassenakis Manos , Paraskevopoulou Vasiliki , Lydakis-Simantiris Nikos
Published: May 2014

An ecotoxicological study is presented, in which three marine bivalve species (Mytilus galloprovincialis, Callista chione, and Venus verrucosa) living in different habitats were studied for Cd bioaccumulation, under laboratory conditions. The bivalves, originating from a relatively polluted marine area of Greece (Saronicos Gulf), were exposed to 0.5 mg Cd L–1 seawater (4.4 μmol Cd L–1 seawater) for 5, 10, 15, and 20 days. Control animals were kept in metal-free seawater as well. Three or four different parts of the organisms (gills, mantle, body, digestive system) were examined for the bioaccumulation of Cd, as well as the levels of three biomarkers (metallothioneins, acetylcholinesterase, lipid peroxidation). A depuration experiment was also carried out. During the experiment, the initial levels of Cd in the control animal tissues either decreased or remained constant and low. The organisms exhibited different behavior regarding Cd bioconcentration and biomarker responses as well as tissue distribution of Cd. After the depuration period, significant amounts of Cd remained in the organisms’ tissues, much higher than the respective levels in control animals.
A difference scheme for equations of ocean dynamics on unstructured grids
Authors: Drutsa Alexey V.
Published: May 2014

A difference scheme on unstructured grids is constructed for the system of equations of large scale ocean dynamics. The properties of the grid problem and grid operators are studied, in particular, a series of a priori estimates and the theorem on existence and uniqueness of the solution are proved.
Quasi-two-layer finite-volume scheme for modelling shallow water flows over an arbitrary bed in the presence of external force. II. Algorithm applications and numerical results
Authors: Karelsky Kirill V. , Petrosyan Arakel S. , Slavin Alexander G.
Published: May 2014

A finite-volume numerical method for studying shallow water flows over an arbitrary bed profile in the presence of external force has been proposed in [33]. This method uses the quasi-two-layer model of hydrodynamic flows over a stepwise boundary with advanced consideration of the flow features near the step. A distinctive feature of the suggested model is a separation of the studied flow into two layers in calculating the flow quantities near each step, and improving by this means the approximation of depth-averaged solutions of the initial three-dimensional Euler equations. We are solving the shallow-water equations for one layer, introducing the fictitious lower layer only as an auxiliary structure in setting up the appropriate Riemann problems for the upper layer. Besides, the quasi-two-layer approach leads to the appearance of additional terms in the one-layer finite-difference representation of balance equations. Numerical simulations are performed based on the proposed in [33] algorithm of various physical phenomena, such as breakdown of the rectangular fluid column over an inclined plane, large-scale motion of fluid in the gravity field in the presence of Coriolis force over amounted obstacle on the underlying surface. Computations are made for the two-dimensional dam-break problem on a slope precisely conform to laboratory experiments. The interaction of the Tsunami wave with the shore line including an obstacle has been simulated to demonstrate the efficiency of the developed algorithm in domains, including partly flooded and dry regions.
Stochastic orderings with respect to a capacity and an application to a financial optimization problem
Authors: Grigorova Miryana
Published: May 2014

By analogy with the classical case of a probability measure, we
extend the notion of increasing convex (concave) stochastic
dominance relation to the case of a normalized monotone (but not
necessarily additive) set function also called a capacity. We give
different characterizations of this relation establishing a link
to the notions of distribution function and quantile function with
respect to the given capacity. The Choquet integral is
extensively used as a tool. In the second part of the paper, we
give an application to a financial optimization problem whose
constraints are expressed by means of the increasing convex
stochastic dominance relation with respect to a capacity. The
problem is solved by using, among other tools, a result
established in our previous work, namely a new version of the
classical upper (resp. lower) Hardy–Littlewood's inequality
generalized to the case of a continuous from below concave
(resp. convex) capacity. The value function of the optimization
problem is interpreted in terms of risk measures (or premium
principles).
Multisensorisches Messsystem zur dreidimensionalen Inspektion technischer Oberflächen
Authors: Keck Alexander , Böhm Michael , Knierim Karl Lukas , Sawodny Oliver , Gronle Marc , Lyda Wolfram , Osten Wolfgang
Published: May 2014

Um die Fertigungsqualität mechanischer Bauteile aus Kleinserienproduktionen sicherzustellen werden flexible Inspektionssysteme benötigt. Zur Erfüllung dieser Anforderungen wird in diesem Beitrag eine multiskalige Inspektionsstrategie und deren Implementierung an einem Demonstrator vorgestellt. Dieser besteht aus mehreren optischen Sensoren sowie einem Aktoriksystem, das mithilfe einer angepassten Messablaufsteuerung und Regelung zur Inspektion von Unvollkommenheiten an kleinen Bauteilen wie Zahnrädern eingesetzt werden kann.
Einsatz eines adaptiven Optiksystems in der
Strömungsmesstechnik
Authors: Leithold Christoph , Büttner Lars , Czarske Jürgen
Published: May 2014

Die adaptive Optik stellt ein heterogenes,
dynamisches, optomechatronisches System
dar. Aufgrund der rasanten Fortentwicklung erobert sie
sich neben der Astronomie und der Ophthalmologie zunehmend neue
Anwendungsfelder. In diesem Beitrag wird ein
interferometrisches Geschwindigkeitsmessverfahren
präsentiert, das ein adaptives Optiksystem für
die Korrektur von Störungen durch eine fluktuierende Phasengrenzschicht
nutzt. Es wird der Fortschritt für die Messtechnik
dargestellt.