bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome sequencing reveals potential targets for therapy in patients with refractory KRASmutated metastatic colorectal cancer
Authors: Shanmugam Vijayalakshmi , Ramanathan Ramesh K , Lavender Nicole A , Sinari Shripad , Chadha Manpreet , Liang Winnie S , Kurdoglu Ahmet , Izatt Tyler , Christoforides Alexis , Benson Hollie , Phillips Lori , Baker Angela , Murray Christopher , Hostetter Galen , Von Hoff Daniel D , Craig David W , Carpten John D 
Published: June 2014

Abstract

Background
The outcome of patients with metastatic colorectal carcinoma (mCRC) following first line therapy is poor, with median survival of less than one year. The purpose of this study was to identify candidate therapeutically targetable somatic events in mCRC patient samples by whole genome sequencing (WGS), so as to obtain targeted treatment strategies for individual patients.

Methods
Four patients were recruited, all of whom had received > 2 prior therapy regimens. Percutaneous needle biopsies of metastases were performed with whole blood collection for the extraction of constitutional DNA. One tumor was not included in this study as the quality of tumor tissue was not sufficient for further analysis. WGS was performed using Illumina paired end chemistry on HiSeq2000 sequencing systems, which yielded coverage of greater than 30X for all samples. NGS data were processed and analyzed to detect somatic genomic alterations including point mutations, indels, copy number alterations, translocations and rearrangements.

Results
All 3 tumor samples had KRAS mutations, while 2 tumors contained mutations in the APC gene and the PIK3CA gene. Although we did not identify a TCF7L2-VTI1A translocation, we did detect a TCF7L2 mutation in one tumor. Among the other interesting mutated genes was INPPL1, an important gene involved in PI3 kinase signaling. Functional studies demonstrated that inhibition of INPPL1 reduced growth of CRC cells, suggesting that INPPL1 may promote growth in CRC.

Conclusions
Our study further supports potential molecularly defined therapeutic contexts that might provide insights into treatment strategies for refractory mCRC. New insights into the role of INPPL1 in colon tumor cell growth have also been identified. Continued development of appropriate targeted agents towards specific events may be warranted to help improve outcomes in CRC.
In Silicotarget fishing: addressing a “Big Data” problem by ligand-based similarity rankings with data fusion
Authors: Liu Xian , Xu Yuan , Li Shanshan , Wang Yulan , Peng Jianlong , Luo Cheng , Luo Xiaomin , Zheng Mingyue , Chen Kaixian , Jiang Hualiang 
Published: June 2014

Abstract

Background
Ligand-based in silico target fishing can be used to identify the potential interacting target of bioactive ligands, which is useful for understanding the polypharmacology and safety profile of existing drugs. The underlying principle of the approach is that known bioactive ligands can be used as reference to predict the targets for a new compound.

Results
We tested a pipeline enabling large-scale target fishing and drug repositioning, based on simple fingerprint similarity rankings with data fusion. A large library containing 533 drug relevant targets with 179,807 active ligands was compiled, where each target was defined by its ligand set. For a given query molecule, its target profile is generated by similarity searching against the ligand sets assigned to each target, for which individual searches utilizing multiple reference structures are then fused into a single ranking list representing the potential target interaction profile of the query compound. The proposed approach was validated by 10-fold cross validation and two external tests using data from DrugBank and Therapeutic Target Database (TTD). The use of the approach was further demonstrated with some examples concerning the drug repositioning and drug side-effects prediction. The promising results suggest that the proposed method is useful for not only finding promiscuous drugs for their new usages, but also predicting some important toxic liabilities.

Conclusions
With the rapid increasing volume and diversity of data concerning drug related targets and their ligands, the simple ligand-based target fishing approach would play an important role in assisting future drug design and discovery.
The risk of acute coronary syndrome in rheumatoid arthritis in relation to tumour necrosis factor inhibitors and the risk in the general population: a national cohort study
Authors: Ljung Lotta , Askling Johan , Rantapää-Dahlqvist Solbritt , Jacobsson Lennart ,   for the ARTIS Study Group
Published: June 2014

Abstract
Introduction
The elevated risk of ischaemic heart disease in patients with rheumatoid arthritis (RA) has been linked to inflammation and disease severity. Treatment with tumour necrosis factor inhibitors (TNFis) is often effective in reducing disease activity and could possibly modify cardiovascular risk. Our objective in the study was to evaluate the risk of acute coronary syndrome (ACS) in patients with RA treated with TNFis compared with the risk among biologic-naïve RA patients and the general population.

Methods
By linkage of the Swedish National Patient Register and the Swedish Biologics Register, we identified a cohort of patients who were started on their first biologic, a TNFi, between 2001 and 2010 (N = 7,704), and a cohort comprising matched biologic-naïve RA patient referents at a 3:1 ratio. Furthermore, a matched comparator cohort (5:1 ratio) was extracted from the Swedish population register. The incidence rates of a first ACS event were calculated and compared between cohorts using Cox proportional hazards regression in three different risk windows: ‘ever-exposed’, ‘actively on TNFi’ and ‘short-term exposure’ (active treatment maximized to 2 years). The models were adjusted for disease duration, joint surgery, comorbidity and socioeconomic factors, and, in a sensitivity analysis including a subpopulation started on therapy beginning 1 January 2006 or later, for dispensed drugs.

Results
Based on 221 events in 7,704 patients (comprising 32,621 person-years) treated with TNFi biologics, the hazard ratio ((HR); ever-exposed) for ACS among the TNFi-exposed RA patients compared with biologic-naïve RA patients was 0.8 (95% confidence interval (CI) = 0.7 to 0.95). In comparison with the general population referents, statistical analysis using fully adjusted models resulted in a HR of 2.0 (95% CI = 1.8 to 2.3) for biologic-naïve RA patients and a HR of 1.6 (95% CI = 1.4 to 1.9) for the TNFi-exposed group. Similar risk estimates were obtained using the other two risk windows. A sensitivity analysis in which we compared the TNFi-exposed patients included from 1 January 2006 onward with biologic-naïve patients resulted in a HR (ever-exposed) of 0.7 (95% CI = 0.5 to 1.0).

Conclusions
RA patients treated with TNFi had a lower risk of ACS compared with biologic-naïve RA patients. Compared with the general population, the risk among patients with RA was elevated, although the difference was less pronounced among the TNFi-exposed patients. This finding could be attributable to the TNFi as such, or it could correspond to a lower degree of inflammation in the TNFi-treated group.
Credibly reaching a reliability target using a model initially constructed by expert elicitation
Authors: Pado Lawrence E 
Published: June 2014

AbstractThe Defense Advanced Research Projects Agency Defense Science Office (DARPA/DSO) is sponsoring Open Manufacturing (OM), an initiative to develop new technologies, new computational tools, and rapid qualification to accelerate the manufacturing innovation timeline. Certification Methodology to Transition Innovation (CMTI), an OM program, has developed a methodology to quantify the effect of manufacturing variability on product performance to address the risk to cost and performance associated with failure to take manufacturing capability and material and fabrication/assembly variation into account early in the design process. An important aspect of this program is the use of Bayesian networks (BN) to evaluate risk. The BN is used as a graphical representation of the contributing factors that lead to manufacturing defects. The reliability of the final product is then analyzed using the contributing factors. There are many types of programs where there is little relevant data to support the probabilities needed to populate the BN model. This is very likely the case for new programs or at the end of long programs when obsolescence challenges servicing a product when original vendors are no longer in business. In these cases, probabilities must be obtained from expert opinion using a technique called expert elicitation. Even under objective ‘Good Faith’ opinions, the expert himself has a lot of uncertainty in that opinion. This paper details an approach to obtaining credible model output based on the idea of having a hypothetical expert whose unconscious bias influences the model output and discovering and using countermeasures to find and prevent these biases. Countermeasures include replacing point probabilities with beta distributions to incorporate uncertainty, 95% confidence levels, and using a multitude of different types of sensitivity analyses to draw attention to potential trouble spots. Finally, this paper uses a new technique named ‘confidence level shifting’ to optimally reduce epistemic uncertainty in the model. Taken together, the set of tools described in this paper will allow an engineer to cost effectively determine which areas of the manufacturing process are most responsible for performance variance and to determine the most effective approach to reducing that variance in order to reach a target reliability.
Synthesis and Characterization of Polystyrene Composites with Oxidized and Ethylbenzene Functionalized Multiwall Carbon Nanotubes
Authors: Faraguna Fabio , Jukic Ante , Vidovic Elvira 
Published: June 2014

Polystyrene nanocomposite materials prepared with differently functionalized multiwall carbon nanotubes (CNT) as nanofillers were investigated. Two types of functionalized multiwall carbon nanotubes were used: oxidized (CNT-COOH) and their ester analogue with ethylbenzene groups (CNT-COOEtBz) introduced by further functionalization of the fore. The functionalized nanotubes were examined by thermogravimetric analysis and contact angle method that both revealed differences between them. Also, their dispersion was investigated in polar methanol and non-polar toluene with the assistance of UV-Vis spectrophotometer. Good dispersion of CNT-COOH in methanol and CNT-COOEtBz in toluene is in accordance with polarity introduced on the surfaces of carbon nanotubes. Mixtures of styrene monomer and 1 wt. % of CNT-COOH or CNT-COOEtBz in toluene were reacted in a radical in-situ polymerization reaction in order to prepare corresponding nanocomposites. Prior to the reaction nanotubes were dispersed by sonication of the reaction mixture. The synthesized composites were characterized by the SEC, TGA, DSC, DMA, SEM and contact angle method. The DSC measurements show a significant Tg shift towards lower temperature since Tg of studied PS is around 60 °C and Tg of PS composites with CNT-COOH at 35 °C and CNT-COOEtBz at 33 °C. The storage modulus increase in the PS/CNT-COOEtBz composite can be assigned to a larger similarity of matrix and filler structure. This is corroborated with the SEM micrographs where much lesser extent of agglomeration can be seen.
Influence of Filler Materials on Pinned Joints of Woven Glass Fiber Reinforced Epoxy Composites
Authors: Harsha H.M. , Murugesh M.C. , Bharath K.N. 
Published: June 2014

Fiber reinforced composite materials have been gaining wide application in aircraft submarine and spacecraft constructions, to strengthen bridges and other civil engineering structures. Joints are formed using mechanical fasteners and load sharing in these joints depends on the number, size, and material of the bolts and the stiffness of the joining members. Therefore, suitable revealing methods for the failure strength would help in selecting the appropriate joint size in a given application.
The objective of the present work is to determine the bearing or failure load of filler added woven glass fiber/epoxy composites through single and double serial pinned joints with different parameters by experimental methods. The effect of the distance from free edge to the diameter of first hole (E/D) ratio, the width of plate to diameter of hole (W/D) ratio and the effect of filler materials on Titanium dioxide (TiO2) and Zinc Sulphide (ZnS) on bearing load are experimentally investigated using laminated woven glass fiber composite plate with single and double serial pinned joints.
Beirut in Berlin? Interreligiöse Bildung in der Spannung zwischen Globalem und Lokalem
Authors: Simojoki Henrik 
Published: June 2014

Abstract
Religious pedagogy largely agrees that within religious education, interreligious instruction has to be aligned to the living environment of present-day children and youths. Yet in current concepts, this environmental context is normally interpreted in terms of the social proximity of the students, thus neglecting that the concept of religious contextuality has to be broadened as it develops in the interaction of global and local realities.
Based on a case-study from the multi-religious context of Berlin, the present contribution discusses the initial conditions of interreligious education which are being changed by globalization. In a first step, the ambivalent presence of remoteness within the religious environment of modern youths is analyzed from an external sociological perspective. This is done in dialogue with selected sociological theories of reference which help to understand the »new contextuality « of the interreligious sphere as regards its basic dynamics of motivation. Subsequently, the essay focuses on inside aspects of this development: It addresses the question of how the spatial melting of the world influences the perception of the self and the other. Finally an approach is presented that substantiates the increasing globalization of religious environments from a youth-sociological perspective and makes it accessible to empirical analysis.
Kindertaufe und Elternwille zwischen Sakrament und Selbstbestimmung Erkenntnisse aus einer Taufelternbefragung
Authors: Schulz Claudia 
Published: June 2014

Abstract
This contribution starts with a standardized poll among protestant parents of non-baptized children in the southern German city of Stuttgart. Its results convey the opinions of parents on the appropriate time and meaning of baptism. The deliberate decision of their child is a decisive factor for parents. Important obstacles are lacking opportunities, the feeling of alienation from the church, the difficulty to find godparents, as well as denominationally heterogeneous constellations within the family. Finally the essay makes suggestions for follow-up with these findings in a theoretical and practical-theological perspective.
Integrality of Stickelberger elements and the equivariant Tamagawa number conjecture
Authors: Nickel Andreas 
Published: June 2014

Abstract
Let

L
/
K

${L/K}$

be a finite Galois CM-extension of number fields with Galois group G.
In an earlier paper, the author has defined a module

SKu
⁢

(

L
/
K

)

${\mathrm{SKu}(L/K)}$

over the center
of the group ring

ℤ
⁢
G

${\mathbb{Z}G}$

which coincides with the Sinnott–Kurihara ideal if G is abelian and,
in particular, contains many Stickelberger elements.
It was shown that a certain conjecture on the integrality of

SKu
⁢

(

L
/
K

)

${\mathrm{SKu}(L/K)}$

implies
the minus part of the equivariant Tamagawa number conjecture at an odd prime p
for an infinite class of (non-abelian) Galois CM-extensions of number fields which are at most tamely ramified
above p, provided that Iwasawa’s μ-invariant vanishes. Here, we prove a relevant part of this
integrality conjecture which enables us to deduce the minus-p-part of the equivariant Tamagawa number conjecture
from the vanishing of μ for the same class of extensions. As an application we prove the non-abelian
Brumer and Brumer–Stark conjecture outside the 2-primary part for every monomial Galois extension of

ℚ

${\mathbb{Q}}$

provided that certain μ-invariants vanish.
Testing Game-Based Performance in Team-Handball
Authors: Wagner Herbert , Orwat Matthias , Hinz Matthias , Pfusterschmied Jürgen , Bacharach David W. , von Duvillard Serge P. , Müller Erich 
Published: June 2014

Abstract
Wagner, H, Orwat, M, Hinz, M, Pfusterschmied, J, Bacharach, DW, von Duvillard, SP, and Müller, E. Testing game-based performance in team-handball. J Strength Cond Res 30(10): 2794–2801, 2016—Team-handball is a fast paced game of defensive and offensive action that includes specific movements of jumping, passing, throwing, checking, and screening. To date and to the best of our knowledge, a game-based performance test (GBPT) for team-handball does not exist. Therefore, the aim of this study was to develop and validate such a test. Seventeen experienced team-handball players performed 2 GBPTs separated by 7 days between each test, an incremental treadmill running test, and a team-handball test game (TG) (2 × 20 minutes). Peak oxygen uptake (V̇o
2peak), blood lactate concentration (BLC), heart rate (HR), sprinting time, time of offensive and defensive actions as well as running intensities, ball velocity, and jump height were measured in the game-based test. Reliability of the tests was calculated using an intraclass correlation coefficient (ICC). Additionally, we measured V̇o
2peak in the incremental treadmill running test and BLC, HR, and running intensities in the team-handball TG to determine the validity of the GBPT. For the test-retest reliability, we found an ICC >0.70 for the peak BLC and HR, mean offense and defense time, as well as ball velocity that yielded an ICC >0.90 for the V̇o
2peak in the GBPT. Percent walking and standing constituted 73% of total time. Moderate (18%) and high (9%) intensity running in the GBPT was similar to the team-handball TG. Our results indicated that the GBPT is a valid and reliable test to analyze team-handball performance (physiological and biomechanical variables) under conditions similar to competition.
Influence of the substrate on the anomalous Nernst effect of magnetite thin films
Authors: Ramos R. , Anadón A. , Lucas I. , Farrell L. , Aguirre M.H. , Sofin R.G.S. , Shvets I.V. , Algarabel P.A. , Morellón L. , Ibarra M.R. 
Published: June 2014

ABSTRACTWe present a comparative study of the anomalous Nernst effect (ANE), measured at room temperature for magnetite thin films deposited on different substrates in order to study the effects induced by the substrate, compressive or tensile strain and structural defects as anti-phase boundaries (APB), on the observed ANE. From our preliminary results we have observed an increase of the measured ANE in the case of compressive strain compared with the tensile one. Moreover our results also suggest that the density of APBs also play an important role in the ANE values.
Charge Transport through Methylated DNA Strand
Authors: Qi Jianqing , Anantram M. P. 
Published: June 2014

ABSTRACTCharge transport through an eight-base pair methylated DNA strand and its native counterpart have been investigated. We focus on three factors, contact coupling, decoherence and temperature, which can contribute to DNA charge transport. Our results show that with the same choice of contact coupling, in the phase-coherent limit the transmission of the methylated strand is smaller in the bandgap at energies close to the highest occupied molecular orbital (HOMO), while inside the HOMO band, the transmission is oscillatory and the methylated DNA may have a larger transmission in certain energy windows. The trend in transmission also holds in the presence of the decoherence though there is a crossover in the transmission of the native and methylated strands away from the HOMO level. We also find that the transport depends on the strength of contact coupling and the measurement temperature.
Resistive Switching Behavior and Electrical Properties of TiO2:Ho2O3 and HoTiOx Based MIM Capacitors
Authors: García H. , Castán H. , Dueñas S. , Pérez E. , Bailón L. A. , Kukli K. , Ritala M. , Leskelä M. 
Published: June 2014

ABSTRACTHo2O3-TiO2 based metal-insulator-metal capacitors were grown by ALD, using Ho(thd)3, Ti(OCH(CH3)2)4 and ozone as precursors. The thicknesses of the films were in the range of 7.7 to 25 nm. Some of the films were post-deposited annealed in order to study the treatment effects. The capacitors were electrically characterized. Leakage current decreases as the amount of holmium increased in the films. Resistive switching behavior was obtained in the samples where the leakage current was low. This effect was also observed in Ho2O3 films, where no titanium was present in the films.
Cardiac troponin I concentrations in horses with colic
Authors: Díaz Olga M. Seco , Durando Mary M. , Birks Eric K. , Reef Virginia B. 
Published: June 2014

Abstract
Objective—To determine prevalence of myocardial injury in horses with colic on the basis of high concentrations of cardiac troponin I (cTnI), frequency of cardiac arrhythmias within the first 24 to 48 hours after hospital admission or surgery because of colic, and associations between high cTnI concentrations and cardiac arrhythmias, clinical course, and outcome (survival to discharge from hospital vs nonsurvival [death or euthanasia]).
Design—Prospective observational study.
Animals—111 horses with colic.
Procedures—Blood was drawn at admission and 12 and 24 hours after admission if horses were treated medically or 12 and 24 hours after surgery if treated surgically. A 24-hour ambulatory ECG was recorded beginning the morning after admission in medically treated cases or after surgery and evaluated for arrhythmias. Clinical and clinicopathologic data and outcome were obtained. Associations between cTnI concentrations and other variables were determined.
Results—An abnormal cTnI concentration (≥ 0.10 ng/mL) at admission was significantly associated with the occurrence of ventricular arrhythmias, outcome, and surgical treatment.
Conclusions and Clinical Relevance—The data suggested that horses with colic and high cTnI concentrations at admission were more likely to have ventricular arrhythmias and have a less favorable prognosis for recovery. High cTnI concentrations in horses with colic were suggestive of myocardial damage.