bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Dissipative Losses in Modular Reconfigurable Energy Storage Systems Using SystemC TLM and SystemC-AMS
Authors: Zimmermann Thomas , Mora Mathias , Steinhorst Sebastian , Mueller-Gritschneder Daniel , Jossen Andreas 
Published: May 2019

Battery storage systems are becoming more popular in the automotive industry as well as in stationary applications. To fulfill the requirements in terms of power and energy, the literature is increasingly discussing electrically reconfigurable interconnection topologies. However, these topologies use switching elements on the cell and module level that exhibit an electric resistance due to their design and hence generate undesirable dissipative losses. In this article, we propose a new analysis and optimization framework to examine and minimize the losses in such topologies.
For this purpose, we develop a SystemC model to investigate static and dynamic load scenarios, e.g., from the automotive domain. The model uses SystemC TLM for the digital subsystem, SystemC-AMS for the mixed-signal subsystem, and host-compiled simulation for the microcontroller executing the embedded software. Here, we analyze the impact of the dissipative losses on the system efficiency that depend on the modularization level, implying the number of serial and parallel switching elements.
Our analysis clearly shows that in reconfigurable topologies, the modularization level has a significant influence on the losses, which in our automotive example covers several orders of magnitude. For the topologies we have investigated, the highest efficiency can be reached when a parallel-only modularization is aspired and the number of serial switching elements is minimized.
It is also shown that the losses of the state-of-the-art topology with one battery pack protection switch are almost as high as in a smart cell approach in which each energy storage cell has its own switching element. However, due to the high number of switching elements, this results in a reduction of energy density and increases the system costs, showing that this is a multi-criteria optimization problem.
AMPK mediates inhibition of electrolyte transport and NKCC1 activity by reactive oxygen species
Authors: King Stephanie J. , Bunz Michael , Chappell Alfred , Scharl Michael , Docherty Michael , Jung Barbara , Lytle Christian , McCole Declan F. 
Published: May 2019

Reactive oxygen species such as H2O2are believed to play a prominent role in the injury and loss of transport function that affect the intestinal epithelium in inflammatory conditions such as inflammatory bowel diseases. Defects in intestinal epithelial ion transport regulation contribute to dysbiosis and inflammatory phenotypes. We previously showed that H2O2inhibits Ca2+-dependent Cl−secretion across intestinal epithelial cells (IECs) via a phosphatidylinositol 3-kinase (PI3K)- and extracellular signal-regulated kinase (ERK)-dependent mechanism that occurs, at least in part, through inhibition of the basolateral Na+-K+-2Cl−cotransporter NKCC1. NKCC1 governs Cl−entry into crypt IECs and thus plays a critical role in maintaining the driving force for Cl−secretion. Electrolyte transport consumes large amounts of cellular energy, and direct pharmacological activation of the cellular energy sensor AMP-activated protein kinase (AMPK) has been shown to inhibit a number of ion transport proteins. Here, we show that H2O2activates AMPK in human IEC lines and ex vivo human colon. Moreover, we demonstrate that the inhibitory effect of H2O2on Ca2+-dependent Cl−secretion and NKCC1 activity is AMPK-dependent. This inhibitory effect is associated with a physical interaction between AMPK and NKCC1, as well as increased phosphorylation (Thr212,217) of NKCC1, without causing NKCC1 internalization. These data identify a key role for AMPK-NKCC1 interaction as a point of convergence for suppression of colonic epithelial ion transport by inflammatory reactive oxygen species.NEW & NOTEWORTHY H2O2inhibition of intestinal epithelial Ca2+-dependent Cl−secretion involves recruitment of AMP-activated protein kinase (AMPK) downstream of ERK and phosphatidylinositol 3-kinase signaling pathways, physical interaction of AMPK with the Na+-K+-2Cl−cotransporter NKCC1, and AMPK-dependent suppression of NKCC1-mediated electrolyte influx without causing NKCC1 internalization. It is intriguing that, in human intestinal epithelial cell lines and human colon, H2O2activation of AMPK increased phosphorylation of NKCC1 residues required for promoting, not inhibiting, NKCC1 activity. These data identify an elevated complexity of AMPK regulation of NKCC1 in the setting of an inflammatory stimulus.
Distinct muscle-tendon interaction during running at different speeds and in different loading conditions
Authors: Werkhausen Amelie , Cronin Neil J. , Albracht Kirsten , Bojsen-Møller Jens , Seynnes Olivier R. 
Published: May 2019

The interaction between the Achilles tendon and the triceps surae muscles seems to be modulated differently with various task configurations. Here we tested the hypothesis that the increased forces and ankle joint work during running under contrasting conditions (altered speed or load) would be met by different, time-dependent adjustments at the muscle-tendon level. Ultrasonography, electromyography, kinematics, and ground reaction force measurements were used to examine Achilles tendon, gastrocnemius, and soleus muscle mechanics in 16 runners in four different running conditions, consisting of a combination of two different speeds (preferred and +20% of preferred speed) and two loading conditions (unloaded and +20% of body mass). Positive ankle joint work increased similarly (+13%) with speed and load. Gastrocnemius and soleus muscle fascicle length and peak velocity were not altered by either condition, suggesting that contractile conditions are mostly preserved despite the constraints imposed in this experimental design. However, at higher running speed, tendon length changes were unaltered but mean muscle electromyographic activity increased in gastrocnemius (+10%, P < 0.01) and soleus (+14%, P < 0.01). Conversely, when loading was increased, mean muscle activity remained similar to unloaded conditions but the mean velocity of gastrocnemius fascicles was reduced and tendon recoil increased (+29%, P < 0.01). Collectively, these results suggest that the neuromuscular system meets increased mechanical demands by favoring economical force production when enough time is available. NEW & NOTEWORTHY We demonstrate that muscle-tendon mechanics are adjusted differently when running under constraints imposed by speed or load, despite comparable increases in work. The neuromuscular system likely modulates the way force is produced as a function of availability of time and potential energy.
Atomic Layer Deposition of TiO2 Nanocoatings on ZnO Nanowires for Improved Photocatalytic Stability
Authors: Kao Emmeline , Park Hyun Sung , Zang Xining , Lin Liwei 
Published: May 2019

Photocatalytic water splitting represents an emerging technology well positioned to satisfy the growing need for low-energy, low CO2, economically viable hydrogen gas production. As such, stable, high-surface-area electrodes are increasingly being investigated as electrodes for the photochemical conversion of solar energy into hydrogen fuel. We present a titanium dioxide (TiO2)/zinc oxide (ZnO) nanowire array using a hybrid hydrothermal/atomic layer deposition (ALD) for use as a solar-powered photoelectrochemical device. The nanowire array consists of single crystalline, wurtzite ZnO nanowires with a 40 nm ALD TiO2 coating. By using a TiO2 nanocoating on the high surface area-ZnO array, three advancements have been accomplished in this work: (1) high aspect ratio nanowires with TiO2 for water splitting (over 8 μm), (2) improved stability over bare ZnO nanowires during photocatalysis, and (3) excellent onset voltage. As such, this process opens up new class of the micro/nanofabrication process for making efficient photocatalytic gas harvesting systems.
Rethinking T Cells in Pancreas Cancer
Authors: Medina Benjamin D. , Miller George 
Published: May 2019

Abstract
Patients with pancreatic ductal adenocarcinoma do not benefit from checkpoint blockade. However, human tumors harbor evidence of adaptive immunity in clonally expanded T-cell populations. Immune intact modeling of human tumors identifies stromal sequestration as a mechanism of immune escape. Targeting the stroma combined with checkpoint blockade unleashes antitumor immunity.
See related article by Seo et al., p. 3934
Targeting PARP-1 with Alpha-Particles Is Potently Cytotoxic to Human Neuroblastoma in Preclinical Models
Authors: Makvandi Mehran , Lee Hwan , Puentes Laura N. , Reilly Sean W. , Rathi Komal S. , Weng Chi-Chang , Chan Ho Sze , Hou Catherine , Raman Pichai , Martinez Daniel , Xu Kuiying , Carlin Sean D. , Greenberg Roger A. , Pawel Bruce R. , Mach Robert H. , Maris John M. , Pryma Daniel A. 
Published: May 2019

Abstract
Alpha-emitters can be pharmacologically delivered for irradiation of single cancer cells, but cellular lethality could be further enhanced by targeting alpha-emitters directly to the nucleus. PARP-1 is a druggable protein in the nucleus that is overexpressed in neuroblastoma compared with normal tissues and is associated with decreased survival in high-risk patients. To exploit this, we have functionalized a PARP inhibitor (PARPi) with an alpha-emitter astatine-211. This approach offers enhanced cytotoxicity from conventional PARPis by not requiring enzymatic inhibition of PARP-1 to elicit DNA damage; instead, the alpha-particle directly induces multiple double-strand DNA breaks across the particle track. Here, we explored the efficacy of [211At]MM4 in multiple cancers and found neuroblastoma to be highly sensitive in vitro and in vivo. Furthermore, alpha-particles delivered to neuroblastoma show antitumor effects and durable responses in a neuroblastoma xenograft model, especially when administered in a fractionated regimen. This work provides the preclinical proof of concept for an alpha-emitting drug conjugate that directly targets cancer chromatin as a therapeutic approach for neuroblastoma and perhaps other cancers.
Abstract CN01-04: Imaging-guided therapy in different tumor models using positron emission tomography (PET) and optical imaging
Authors: Winkeler Alexandra , Waerzeggers Yannic , Ullrich Roland , Boisgard Raphael , Tavitian Bertrand , Jacobs Andreas H. 
Published: May 2019

Abstract
Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in vivo. With the achievements in detector technology, spatial resolution of PET has been improved (1–2mm) enabling investigations in small experimental animals such as mice. With the development in tracer technology a variety of endogenously expressed and exogenously introduced genes can be analyzed by PET. This opens up the exciting and rapidly evolving field of molecular imaging aiming towards the non-invasive localization of the dynamics of disease specific molecular alterations and biological processes in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This allows non-invasive characterization of animal models of human disease at various disease stages and after therapeutic intervention.
Optical imaging (OI) is a non-invasive molecular imaging technology that uses light to interrogate cellular and molecular function in the living body. Although OI technologies are still limited by light scattering and depth of light penetration they provide a low cost and rapid alternative to the more expensive and time-consuming PET imaging. By introducing multi-modality reporter constructs (PET, fluorescence and/or bioluminescence) drawbacks of each modality can be overcome and advantages will complement one another. Thus, allowing on the one side rapid, cost-effective optical reporter imaging and on the other side tomographic as well as quantitative imaging of reporter gene expression by PET. With PET being a modality well developed for imaging in human subjects as well as small animals it provides a link from bench-to-bedside and may facilitate translation into clinical applications.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):CN01-04.
Abstract PL01-03: Drug resistance and tumor maintenance in genetically engineered mice
Authors: Lowe Scott W. 
Published: May 2019

Abstract
Cancer arises through an evolutionary process whereby normal cells acquire mutations that erode growth controls, leading to the inappropriate expansion of aberrantly proliferating cells. Such mutations can involve activation of oncogenes or inactivation of tumor-suppressor genes, each contributing one or more new capabilities to the developing cancer cell. However, cancer is not an inevitable consequence of oncogenic mutations; instead, cells acquiring such mutations can be eliminated or kept in check by innate tumor-suppressor programs that can be activated in these damaged cells. Our laboratory studies tumor-suppressor networks controlling apoptosis and senescence and how their disruption influences malignant behavior. We previously showed that apoptosis and cellular senescence are potent barriers to oncogene-driven tumorigenesis and that each contributes to the antitumor action of many chemotherapeutic drugs. Thus, not only do mutations that disrupt apoptosis and senescence promote tumor progression but, depending on the particular lesion, they can also reduce the efficacy of cancer therapy. To facilitate our research, we have recently developed new mouse cancer models based on the genetic manipulation of stem and progenitor cells ex vivo followed by transplantation of the altered cells into the appropriate organ of syngeneic recipient mice. This approach allows us to rapidly study the impact of many genes and gene combinations on tumorigenesis in a “mosaic” setting where tumor-initiating cells are embedded in normal tissues. Furthermore, we have developed powerful methods for using RNAi to suppress gene function in vivo in either a stable and reversible manner. Current efforts in the laboratory strive to integrate mosaic mouse models, RNA interference, and cancer genomics to identify new components of tumor suppressor gene networks and characterize their impact on tumorigenesis and treatment response. In addition, we are developing new RNAi interference methods to explore the role of tumor suppressor genes in tumor maintenance, and the cell death mechanisms involved in tumor regression.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):PL01-03.
Abstract PL02-01: Targeting the PI3K pathway in cancer
Authors: Sellers William R. 
Published: May 2019

Abstract
The role of PI3K activation in transformation was first brought to light by virtue of its association with the transforming oncoprotein Middle T antigen of the Polyoma virus. Subsequently, the discovery of the PTEN tumor suppressor gene and its characterization as a lipid phosphatase with preference for PI-3,4-P2 and PI-3,4,5-P3 brought therapeutic targeting of the PI3K pathway back to the fore. Following the discovery of PTEN direct oncogenic activation of PI3K was found to occur through gene amplification and through the acquisition of activating point mutations in PIK3CA (the gene encoding the catalytic subunit p110α) in a diverse set of malignancies. Lastly, activated oncogenic receptor tyrosine kinases including HER2 and EGFR mediated their transforming activity, at least in part, through PI3K-dependent signaling. Thus, we can envision at least 3 prevalent cancer-genetic states that may elicit a dependence on PI3K, namely, loss-of-function of PTEN, gain-of-function of PIK3CA and oncogenic mutation in receptor tyrosine kinases.
The mTOR kinase is a key regulator of cell growth downstream of PI3K. mTOR activity in cancer states is more specifically deregulated in the absence of the normal function of the Tuberous Sclerosis Complex genes (TSC1 and 2). Similarly mutations in LKB1 and PTEN may elicit dependence on mTOR activity. In addition, mTOR activity is a critical regulator of hypoxia signaling. mTOR inhibitors have shown promising clinical activity in states predicated on these pre-clinical discoveries.
These observations/discoveries have motivated and set the stage for the development of therapeutic molecules targeting key pathway components. These include the aformentioned allosteric inhibitors of mTOR already registered as oncology therapeutics, and the more recent entrance of PI3K and AKT inhibitors into the clinic. These events herald the opportunity to answer critical therapy based questions in man. The data emerging from the pre-clinical and clinical development of a series of distinct pathway inhibitors targeting mTOR and PI3K will be discussed with a focus on understanding pathway dependence pre-clinically and the role of relevant biomarker data emerging from the clinic and their potential relationship to efficacious dosing.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):PL02-01.
Abstract A05: Validation of breast cancer risk prediction model using Nurses Health and Nurse Health II Studies
Authors: Gao Chi , Choudhury Parichoy Pal , Maas Paige , Tamimi Rulla , Eliassen Heather , Chatterjee Nilanjan , Garcia-Closas Montserrat , Kraft Peter 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR02) of the Conference Proceedings.
Citation Format: Chi Gao, Parichoy Pal Choudhury, Paige Maas, Rulla Tamimi, Heather Eliassen, Nilanjan Chatterjee, Montserrat Garcia-Closas, Peter Kraft. Validation of breast cancer risk prediction model using Nurses Health and Nurse Health II Studies. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A05.
Abstract A06: Association of environmental risk factors, family history, and polygenic risk scores with chronic lymphocytic leukemia
Authors: Kleinstern Geffen , Robinson Dennis , Call Tim G. , Liebow Mark , Sanjosé Silvia de , Benavente Yolanda , Cerhan James R. , Slager Susan L. 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR03) of the Conference Proceedings.
Citation Format: Geffen Kleinstern, Dennis Robinson, Tim G. Call, Mark Liebow, Silvia de Sanjosé, Yolanda Benavente, James R. Cerhan, Susan L. Slager. Association of environmental risk factors, family history, and polygenic risk scores with chronic lymphocytic leukemia. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A06.
Abstract B04: Development of a comprehensive colorectal cancer risk prediction tool (CRiPT) incorporating known and unknown major genes and polygenes
Authors: Win Aung Ko , Jenkins Mark A. , Dowty James G. , Antoniou Antonis C. , Lee Andrew , Zheng Yingye , Lindor Noralane M. , Newcomb Polly A. , Hopper John L. , MacInnis Robert J. 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR10) of the Conference Proceedings.
Citation Format: Aung Ko Win, Mark A. Jenkins, James G. Dowty, Antonis C. Antoniou, Andrew Lee, Yingye Zheng, Noralane M. Lindor, Polly A. Newcomb, John L. Hopper, Robert J. MacInnis. Development of a comprehensive colorectal cancer risk prediction tool (CRiPT) incorporating known and unknown major genes and polygenes. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B04.
Abstract B06: Utah familial colorectal cancer risk model
Authors: MacInnis Robert J. , Jenkins Mark A. , Hopper John L. , Cannon-Albright Lisa A. 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR11) of the Conference Proceedings.
Citation Format: Robert J. MacInnis, Mark A. Jenkins, John L. Hopper, Lisa A. Cannon-Albright. Utah familial colorectal cancer risk model. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B06.
Abstract B16: Development of breast cancer risk prediction for the UK population using the UK Biobank dataset
Authors: Alajmi Kawthar , Lophatananon Artitaya , Muir Kenneth 
Published: May 2019

Abstract
Breast cancer is the most common female cancer and is the second most common cause of cancer death among females. The UK has the highest age standardised incidence and mortality rates in the world, with two in every 1000 women aged 50 and above developing breast cancer annually. Several risk prediction models have been developed to estimate the likelihood for developing breast cancer based on specific risk factors in currently healthy individuals within a specific period of time. The available models are derived principally from either genetic or non-genetic factors. The majority of these models are however not user-friendly, do not focus on modifiable factors entirely and are not specifically designed for the general public.
Our research group is developing an individualised risk prediction model for breast cancer focusing on the modifiable risk factors using the UK Biobank data. A nested case-control study within the 273,467 female participants is being used to develop the model. We have split the data into training and testing sets and will carry out all statistical tests to ensure our model calibrates well. For model validation, we will further seek external validation cohorts. The model will provide risk scores derived from the presence or absence of specific risk factors and will be compared to the general public score. The model will allow people to modify their risk profile with appropriate prevention measures. The main goal of the model is to be used in cancer education and prevention.
The results from exploratory analyses suggested positive associations between breast cancer risk and age, breast cancer family history, menopause age, age at first child, BMI, height, null-parity, smoking, alcohol intake, and family history of other cancer. An algorithmic model will be developed based on these factors. We will also evaluate public perceptions using focus group technique. We will be presenting the results of the model development from the training set and the results of the internal validation from the testing set.
In conclusion, we are developing an individualised breast cancer risk prediction model for the UK population based on the modifiable risk factors. The model will enable us to educate and to design appropriate interventions tailored to the individual with the aim of assisting them to make appropriate changes to modify their cancer risk profile.
Citation Format: Kawthar Alajmi, Artitaya Lophatananon, Kenneth Muir. Development of breast cancer risk prediction for the UK population using the UK Biobank dataset. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B16.