bluuebunny/crossref_metadata_2025 huggingface dataset:
Parameter identification for on‐line model updating in hybrid simulations using a gradient‐based method
Authors: Chuang Ming‐Chieh , Hsieh Shang‐Hsien , Tsai Keh‐Chyuan , Li Chao‐Hsien , Wang Kung‐Juin , Wu An‐Chien
Published: August 2017

To improve the efficiency of model fitting, parameter identification techniques have been actively investigated. Recently, the applications of parameter identification migrated from off‐line model fitting to on‐line model updating. The objective of this study is to develop a gradient‐based method for model updating to advance hybrid simulation also called hybrid test. A novel modification of the proposed method, which can reduce the number of design variables to improve the identification efficiency, is illustrated in detail. To investigate the model updating, simulated hybrid tests were conducted with a 5‐story steel frame equipped with buckling‐restrained braces (BRBs) utilized in the shaking table tests conducted in E‐Defense in Japan in 2009. The calibrated analytical model that was verified with the test results can serve as the reference model. In the simulated hybrid tests, the physical BRB substructure is numerically simulated by utilizing a truss element with the 2‐surface model identical to the part of the reference model. Such numerical verification allows simulation of measurement errors for investigation on the performance of the proposed method. Moreover, the feasibility of sharing the identified parameter values, which were obtained from the physical substructure responses, with the relevant numerical models is also verified with the artificial component responses derived from the physical experiments.
Seismic retrofit of low‐rise steel buildings in Canada using rocking steel braced frames
Authors: Mottier Paul , Tremblay Robert , Rogers Colin
Published: August 2017

This article examines the use of rocking steel braced frames for the retrofit of existing seismically deficient steel building structures. Rocking is also used to achieve superior seismic performance to reduce repair costs and disruption time after earthquakes. The study focuses on low‐rise buildings for which re‐centring is solely provided by gravity loads rather than added post‐tensioning elements. Friction energy dissipative (ED) devices are used to control drifts. The system is applied to 2‐storey and 3‐storey structures located in 2 seismically active regions of Canada. Firm ground and soft soil conditions are considered. The seismic performance of the retrofit scheme is evaluated using nonlinear dynamic analysis and ASCE 41‐13. For all structures, rocking permits to achieve immediate occupancy performance under 2% in 50 years seismic hazard if the braces and their connections at the building's top storeys are strengthened to resist amplified forces due to higher mode response. Base shears are also increased due to higher modes. Impact at column bases upon rocking induces magnified column forces and vertical response in the gravity system. Friction ED is found more effective for drift control than systems with ring springs or bars yielding in tension. Drifts are sufficiently small to achieve position retention performance for most nonstructural components. Horizontal accelerations are generally lower than predicted from ASCE 41 for regular nonrocking structures. Vertical accelerations in the gravity framing directly connected to the rocking frame are however higher than those predicted for ordinary structures. Vertical ground motions have limited effect on frame response.
An indirect shooting method based on the POD/DEIM technique for distributed optimal control of the wave equation
Authors: Sabeh Z. , Shamsi Mostafa , Navon Ionel Michael
Published: August 2017

This paper presents a fast numerical method, based on the indirect shooting method and Proper Orthogonal Decomposition (POD) technique, for solving distributed optimal control of the wave equation. To solve this problem, we consider the first‐order optimality conditions and then by using finite element spatial discretization and shooting strategy, the solution of the optimality conditions is reduced to the solution of a series of initial value problems (IVPs). Generally, these IVPs are high‐order and thus their solution is time‐consuming. To overcome this drawback, we present a POD indirect shooting method, which uses the POD technique to approximate IVPs with smaller ones and faster run times. Moreover, in the presence of the nonlinear term, to reduce the order of the nonlinear calculations, a discrete empirical interpolation method (DEIM) is applied and a POD/DEIM indirect shooting method is developed. We investigate the performance and accuracy of the proposed methods by means of 4 numerical experiments. We show that the presented POD and POD/DEIM indirect shooting methods dramatically reduce the CPU time compared to the full indirect shooting method, whereas there is no significant difference between the accuracy of the reduced and full indirect shooting methods.
Analytical and numerical studies of the boundary slip in the immersed boundary‐thermal lattice Boltzmann method
Authors: Seta Takashi , Hayashi Kosuke , Tomiyama Akio
Published: August 2017

We analytically and numerically investigate the boundary slip, including the velocity slip and the temperature jump, in immersed boundary‐thermal lattice Boltzmann methods (IB‐TLBMs) with the two‐relaxation‐time collision operator. We derive the theoretical equation for the relaxation parameters considering the effect of the advection velocity on the temperature jump of the IB‐TLBMs. The analytical and numerical solutions demonstrate that the proposed iterative correction methods without the computational cost of the sparse matrix solver reduce the boundary slip and boundary‐value deviation as effectively as the implicit correction method for any relaxation time. Because the commonly used multi‐direct forcing method does not consider the contributions of the body force to the momentum flux, it cannot completely eliminate the boundary slip because of the numerical instability for a long relaxation time. Both types of proposed iterative correction methods are more numerically stable than the implicit correction method. In simulations of flow past a circular cylinder and of natural convection, the present iterative correction methods yield adequate results without the errors of the velocity slip, the temperature jump, and the boundary‐value deviation for any relaxation time parameters and for any number of Lagrangian points per length. The combination of the present methods and the two‐relaxation‐time collision operator is suitable for simulating fluid flow with thermal convection in the multiblock method in which the relaxation time increases in inverse proportion to the grid size.
Evaluation of peanut skin and grape seed extracts to inhibit growth of foodborne pathogens
Authors: Levy Jason , Boyer Renee R. , Neilson Andrew P. , O'Keefe Sean F. , Chu Hyun Sik S. , Williams Robert C. , Dorenkott Melanie R. , Goodrich Katheryn M.
Published: August 2017

Peanut skin extract (PSE) and grape seed extract (GSE) are derived from waste products in the wine and peanut industries, respectively. Both have high concentrations of polyphenols, known to possess antioxidant and antimicrobial properties. PSE primarily contains “A‐type” procyanidins, while GSE primarily contains “B‐type” procyanidins. These differ structurally, but are both isomers of epicatechin dimers. The objective of this study was to evaluate the antimicrobial effects of PSE containing A‐type procyanidins and GSE containing B‐type procyanidins against select foodborne pathogens (Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella Typhimurium). The minimum inhibitory concentration (MIC) of the two extracts on L. monocytogenes, E. coli O157:H7, and S. Typhimurium was determined using the pour plate method. GSE had a significantly lower MIC (p ≤ .05) than PSE for L. monocytogenes (GSE = 60.6 ppm, PSE > 68.2 ppm) and S. Typhimurium (GSE = 45.7 ppm, PSE = 60.6 ppm), but no difference in inhibition of E. coli O157:H7. Since GSE contributed to greater inhibition, GSE extract was fractionated into monomer‐rich (consisting primarily of catechins, epicatechins, and epicatechin gallates) and oligomer‐rich (consisting of dimers, trimers, tetramers, up to decamers) components. Growth curves of all three pathogens in the presence of full extract, monomer and oligomer fractions were compared separately. None of the extracts inhibited S. Typhimurium growth. Generally, the extract containing greater oligomer components inhibited growth of L. monocytogenes and E. coli O157:H7 when compared to the control. Results indicate that an extract with type B procyanidins higher in oligomers may have greater antimicrobial properties.
Partial characterization of starches from major banana (matooke) cultivars grown in Uganda
Authors: Ssonko Umar L. , Muranga Florence I.
Published: August 2017

The SEM of starch from five EAHB cultivars showed a mixture of irregular granule shapes with smooth surfaces. The starches' average diameter size ranged between 16.31 and 21.98 μm. The moisture, protein, and ash content of the starches were: 11.12%–11.84%, 0.1% and 0.23%–0.47% respectively. The amylose content of these starches was between 11% and 13%. The starches peak viscosity ranged between 488.42 and 558.66 RVU. The EAHB starches exhibited relatively low pasting temperatures (<75°C), a high peak viscosity (488.42–558.71 RVU), high level of viscosity breakdown (235.00–311.92 RVU) and low set‐back values (61.21–104.33 RVU). In general, the EAHB starches' WHCs and SPs increased substantially at 80°C with maximum SP (12.43–14.27 g water/g starch) and solubility (12.52%–14.19%) values obtained at 90°C. The starch clarity ranged from 1.7% to 2.3% and followed the same pattern. The starches exhibited poor freeze‐thaw stability as they had high syneresis (68% to 72%) after 10 freeze‐thaw cycles.
Horizontal and vertical variability of observed soil temperatures
Authors: Illston Bradley G. , Fiebrich Christopher A.
Published: August 2017

Two datasets of soil temperature observations collected at Norman, Oklahoma, USA, were analysed to study horizontal and vertical variability in their observations. The first dataset comprised 15‐min resolution soil temperature observations from 20 September 2011 to 18 November 2013 in seven plots across a 10‐m transect. In each plot, sensors were located at depths of 5, 10, and 30 cm. All seven plots observed fairly consistent maximum soil temperature observations during the spring, fall, and winter months. Starting in late May, the observed spread in soil temperatures across the 10‐m transect increased significantly until August when the observed spread in temperatures decreased. The range of observed minimum soil temperature was more consistent year‐round at the shallower depths, but showed similar patterns to the maximum soil temperature ranges at deeper depths. The second dataset comprised 15‐min resolution soil temperature observations from 20 November 2013 to 1 December 2015 in a single plot at the same location as the first dataset. Soil temperature sensors were placed every 2 cm from the surface down to 40 cm deep to study the vertical variability in soil temperature measurements (focusing on a winter and a summer case). Both winter and summer conditions showed that the temperature differences between depths behaved logarithmically with the shallower depths having larger differences than deeper depths.
The genesis of the Xujiagou copper deposit, Mian‐Lue‐Ning area of Shaanxi Province,NWChina: Constraints from mineral chemistry and in situPbisotope composition
Authors: Luan Yan , Wang Ruiting , Qian Zhuangzhi , Li Yongqin , Chen Lixiang , Zhang Tianyun , Ding Kun
Published: August 2017

The Mian‐Lue‐Ning area, bounded by the Hanjiang fault zone in the south and the Mian‐Lue suture in the north, is one of the most important polymetallic mineralization concentration regions in the Qinling orogenic belt. The Xujiagou copper deposit is representative in this area with chalcopyrite and pyrrhotite as the main ore minerals, subordinate sphalerite, and pyrite. However, the source of the ore‐forming materials and the genesis of the Xujiagou copper deposit are still in a controversy due to the lack of detailed study on the mineral composition. In this study, the electron probe micro‐analyzer (EPMA) analysis shows that the pyrrhotite in the Xujiagou copper deposit is mostly monoclinic pyrrhotite of low‐temperature phase, indicating that the metallogenic temperature should be below 304 °C. The percent of FeS molecules in sphalerite is 8.16–12.1%, indicating that the metallogenic temperature is 230–258 °C, which is mesothermal mineralization. The in situ Pb isotope composition of chalcopyrite (206Pb/204Pb = 19.087–20.861;207Pb/204Pb = 15.533–16.062;208Pb/204Pb = 38.121–39.391) and pyrrhotite (206Pb/204Pb = 20.241–20.664;207Pb/204Pb = 15.7–15.996;208Pb/204Pb = 38.659–39.372) in the Xujiagou copper deposit was analysed by fLA‐MC‐ICPMS, and it indicates that the ore‐forming materials were mainly sourced from the upper crust. Moreover, the contents and ratios of Co and Ni in pyrrhotite (Ni: 500–1600 ppm, Co < 630 ppm, Co/Ni = 0.03–1.71) suggest that the ore‐forming material of the Xujiagou copper deposit could be extracted from the spilite of the Guojiagou Formation, and the ore minerals inherited the geochemical characteristics of the spilite. Combined with previous studies of the Tongchang copper deposit in the Mian‐Lue‐Ning area, it is proposed that the Xujiagou and Tongchang copper deposits have similar ore‐forming materials source and evolution processes, and their formations may be related to the breakup event of the Rodinia supercontinent. However, the relatively lower207Pb/204Pb and206Pb/204Pb ratios of the Tongchang chalcopyrite and pyrite than those of the Xujiagou chalcopyrite and pyrrhotite indicate that the Tongchang copper deposit suffered more intense influence of the lower crust materials due to the emplacement of the Tongchang diorite.
Provenance of Middle to Late Triassic sedimentary rocks in the Zoige Depression in theNEpart of the Songpan–Ganzi Flysch Basin: Petrography, heavy minerals, and zircon U–Pb geochronology
Authors: Tang Yan , Zhang Yunpeng , Tong Lili
Published: August 2017

The Zoige Depression is an important depocenter zone within the northeast of the Songpan–Ganzi Flysch Basin, which is bounded by the South China, North China, and Qiangtang blocks, and also forms the northeastern margin of Tibetan Plateau. This paper discusses the provenance of Middle to Late Triassic sedimentary rocks in the Zoige Depression using petrography, heavy mineral assemblages, and zircon U–Pb geochronology. The results demonstrate that the detritus is derived from multiple source regions. Four distinct parent rocks can be distinguished based on the heavy mineral assemblages and lithic fragments: Provenance 1 predominantly comprises intermediate–acidic volcanic rocks; Provenance 2 includes high‐grade metamorphic rocks; Provenance 3 contains a mixture of various detrital components; and Provenance 4 primarily consists of mafic volcanic rocks. The different U–Pb ages of the zircons from the Middle to Late Triassic ranging from 260 to 280, 429–480, 792–974, and 1,800–2,500 Ma represent distinct source regions, which are comparable to the 4 provenances mentioned above: Provenance 1 (260–280 Ma), Eastern Kunlun Orogen; Provenance 2 (429–480 and/or 1,800–2,500 Ma), Qinling orogeny (mainly in North Qinling); Provenance 3 (1,800–2,500 Ma), the North China Block; and Provenance 4 (792–974 Ma), the Yangtze Block. Overall, the detritus in the Middle Triassic (Ladinian, T2zg) primarily originates from the Eastern Kunlun Orogen and North Qinling. During the Late Triassic (Early Carnian, T3z), the southern margin of the North China Block was likely transported westward to the basin by a river network between the North China and South China blocks flowing through the Qinling region, because of the predominance of the detrital zircon age ranging from 1,800 to 2,500 Ma and the occurrence of quartz sandstone with visible enlargement texture. Since the Late Triassic (Middle Carnian, T3zh), great changes have occurred in the source terrains, such as the absence of sources of the Eastern Kunlun Orogen and North China Block and the predominance of Yangtze Block. This drastic change can be explained by the Triassic collision between the South China and North China blocks, and the clockwise rotation of the South China Block progressively closed the basin and uplifted the Qinling orogeny.
Physical aggression among patients with dementia, neuropathologically confirmed post‐mortem
Authors: Liljegren Madeleine , Landqvist Waldö Maria , Englund Elisabet
Published: August 2017

Objective

To investigate the prevalence of physical aggression among patients with dementia of different types and to analyze potential differences in clinical traits, in terms of singular or repetitive behavior and occurrence in early or late stage of the disease. We also aimed at examining against whom the physical aggression was exerted.

Methods

We included 281 cases with a neuropathological dementia diagnosis from the brain bank at the Department of Pathology, Lund University, for this retrospective medical records review. The study covers cases with a post‐mortem examination performed between 1967 and 2013.

Results

Of the 281 patients studied, 97 (35%) patients had a history of exerting physical aggression during the course of their disease. The patients with frontotemporal dementia exerted physical aggression earlier in the course of their disease than Alzheimer's disease patients. The most frequent victims of the patients' physical aggression were health staff and other patients. The aggression also affected family members as well as (to the demented patient) unknown people. The frequency of the physical aggression differed among the different diagnostic groups; frontotemporal dementia patients exhibiting a higher physical aggression frequency score than did Alzheimer's disease patients.

Conclusions

The patterns of manifested physical aggression thus differ between the frontotemporal dementia and Alzheimer's disease patient groups in this study. Knowledge about such differences may be of value in decision making in patient care.
Performance characteristics of vibration‐controlled transient elastography for evaluation of nonalcoholic fatty liver disease
Authors: Vuppalanchi Raj , Siddiqui Mohammad S. , Van Natta Mark L. , Hallinan Erin , Brandman Danielle , Kowdley Kris , Neuschwander‐Tetri Brent A. , Loomba Rohit , Dasarathy Srinivas , Abdelmalek Manal , Doo Edward , Tonascia James A. , Kleiner David E. , Sanyal Arun J. , Chalasani Naga ,   for the NASH Clinical Research Network
Published: August 2017

Vibration‐controlled transient elastography estimates liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), which are noninvasive assessments of hepatic fibrosis and steatosis, respectively. However, prior vibration‐controlled transient elastography studies reported high failure rates in patients with nonalcoholic fatty liver disease. We examined the performance characteristics of the FibroScan 502 Touch with two probes, medium (M+) and extra large (XL+), in patients with nonalcoholic fatty liver disease in a multicenter setting. A total of 1,696 exams were attempted in 992 patients (body mass index, 33.6 ± 6.5 kg/m2) with histologically confirmed nonalcoholic fatty liver disease. Simultaneous assessment of LSM and CAP was performed using the FibroScan 502 Touch with an automatic probe selection tool. Testing was conducted twice in patients by either a single operator (87%) or two operators (13%). Failure was defined as the inability to obtain a valid examination. An examination was considered unreliable if LSM interquartile range/median was >30%. Significant disagreement between two readings was defined as >95% limits of agreement between two readings. A total of 1,641 examinations yielded valid results with a failure rate of 3.2% (55/1,696). The proportion of unreliable scans for LSM was 3.9%. The proportion of unreliable scans with operator experience in the top quartile (≥59 procedures) was significantly lower than that in the lower three quarters combined (1.6% versus 4.7%, P = 0.02 by Fisher's exact test). The significant disagreement between first and second readings for LSM and CAP when obtained back to back was 18% and 11%, respectively. Conclusion: Vibration‐controlled transient elastography for estimation of LSM and CAP can be successfully deployed in a multicenter setting with low failure (3.2%) and high reliability (>95%) rates and high reproducibility. (Hepatology 2018;67:134‐144).
Significance of definitions of relapse after discontinuation of oral antivirals in HBeAg‐negative chronic hepatitis B
Authors: Papatheodoridis George V. , Manolakopoulos Spilios , Su Tung‐Hung , Siakavellas Spyros , Liu Chun‐Jen , Kourikou Anastasia , Yang Hung‐Chih , Kao Jia‐Horng
Published: August 2017

Relapses are observed in most hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B patients who discontinue treatment with nucleos(t)ide analogues (NAs); however, the rates of relapse vary widely among studies, and whether all patients with relapse need retreatment is unclear. The aim of this study was to assess the impact of different definitions on the rates of posttreatment relapse and therefore on the probability of retreatment in patients who have discontinued effective long‐term NA therapy. In total, 130 HBeAg‐negative chronic hepatitis B patients without cirrhosis and before NA treatment were included. All had on‐therapy virological remission for ≥24 months and close follow‐up for ≥12 months after stopping NA treatment or until retreatment, which started on stringent predefined criteria. Relapses rates based on several predetermined definitions of virological and perhaps biochemical criteria were assessed. The median duration of therapy was 60 months and the median duration of on‐therapy virological remission was 43 months. During a median off‐NAs follow‐up of 15 months, no patient experienced liver decompensation or died. Cumulative relapse rates were 2%‐49%, 4%‐73%, 11%‐82%, and 16%‐90% at 3, 6, 12, and 24 months, respectively, whereas cumulative retreatment rates were 15%, 22%, and 40% at 6, 12, and 24 months, respectively, after discontinuation of NA therapy. No patient characteristic was independently associated with the probability of relapse based on at least two definitions or of retreatment. Conclusion: In HBeAg‐negative chronic hepatitis B patients who discontinue NA therapy, the definition of relapse has a great impact on off‐NAs relapse rates and potentially on the probability of retreatment. Regardless of definition, off‐NAs relapses cannot be easily predicted by patient characteristics. A substantial proportion of such patients may not require retreatment if stringent criteria are adopted. (Hepatology 2017).
Cystathionine β‐synthase is required for body iron homeostasis
Authors: Zhou Yu‐Fu , Wu Xiao‐Mei , Zhou Gan , Mu Ming‐dao , Zhang Fa‐Li , Li Fe‐Mi , Qian Christopher , Du Fang , Yung Wing‐Ho , Qian Zhong‐Ming , Ke Ya
Published: August 2017

Cystathionine β‐synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide. In view of the exceptionally high expression of CBS in the liver and the common interleukin‐6 pathway used in the regulatory systems of hydrogen sulfide and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knockout (CBS−/−) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen, and heart, along with severe damage to the liver, displaying a hemochromatosis‐like phenotype. A high level of hepatic and serum hepcidin was also found. A major cause of the systemic iron overload is the reduced iron usage due to suppressed erythropoiesis, which is consistent with an increase in interleukin‐6 and reduced expression of erythropoietin. Importantly, in the liver, absence of CBS caused both a reduction in the transcriptional factor nuclear factor erythroid 2–related factor‐2 and an up‐regulation of hepcidin that led to a decrease in the iron export protein ferroportin 1. The resulting suppression of iron export exacerbates iron retention, causing damage to hepatocytes. Finally, administration of CBS‐overexpressing adenovirus into CBS mutant mice could partially reverse the iron‐related phenotype. Conclusion: Our findings point to a critical role of CBS in iron homeostasis of the body, and the liver in particular; it is likely that a hemochromatosis‐like phenotype in patients can be induced by aberration not only in the expression of key molecules in the hepcidin pathway but also of those related to CBS. (Hepatology 2018;67:21‐35)
Comparative study of mechanical and chemical methods for surface cleaning of a marine shell‐and‐tube heat exchanger
Authors: P.S Kishore , Kumar Rajnish , N Vamsi Venkata
Published: August 2017

In this article, experimental analysis is done on shell‐and‐tube heat exchanger of a marine vessel for removal of fouling using optimum surface‐cleaning techniques. The main objective is to compare the performance of the heat exchanger before and after maintenance. Two identical deteriorated systems of heat exchangers are taken and real‐time analysis is conducted. The log data are taken before and after undergoing maintenance for the two systems. Two different cleaning techniques are used, namely, chemical cleaning and mechanical cleaning. Detailed calculations are made for the shell‐and‐tube heat exchanger. From the obtained data, comparisons are made for different parameters on the tube side such as friction factor, heat transfer coefficient and pressure drop, as well as total heat transfer rate on the shell side. From the analysis and comparison, it was found that greater heat transfer takes place for the tubes cleaned using the chemical cleaning method than for tubes cleaned by the mechanical cleaning method. Pressure drop is found to be less for chemical cleaning method than mechanical cleaning method. This indicates that the fouling effect is reduced for tubes cleaned by the chemical cleaning method, and furthermore these tubes remain corrosion‐resistant for longer periods of time.
Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses’ health study and health professionals follow‐up study
Authors: Momen‐Heravi Fatemeh , Masugi Yohei , Qian Zhi Rong , Nishihara Reiko , Liu Li , Smith‐Warner Stephanie A. , Keum NaNa , Zhang Lanjing , Tchrakian Nairi , Nowak Jonathan A. , Yang Wanshui , Ma Yanan , Bowden Michaela , da Silva Annacarolina , Wang Molin , Fuchs Charles S. , Meyerhardt Jeffrey A. , Ng Kimmie , Wu Kana , Giovannucci Edward , Ogino Shuji , Zhang Xuehong
Published: August 2017

Although experimental evidence suggests calcium‐sensing receptor (CASR) as a tumor‐suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow‐up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer‐specific and all‐cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE‐1 methylation level, expressions of PTGS2, VDR and CTNNB1 and mutations of KRAS, BRAF and PIK3CA. There were 240 colorectal cancer‐specific deaths and 427 all‐cause deaths. The median follow‐up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared with patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer‐specific mortality were 0.80 [95% confidence interval (CI): 0.55–1.16] in patients with moderate CASR expression and 0.50 (95% CI: 0.32–0.79) in patients with intense CASR expression (p‐trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64–1.13) and 0.81 (0.58–1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer‐specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression.
Prevalent somatic BRCA1 mutations shape clinically relevant genomic patterns of nasopharyngeal carcinoma in Southeast Europe
Authors: Fountzilas George , Psyrri Amanda , Giannoulatou Eleni , Tikas Ioannis , Manousou Kyriaki , Rontogianni Dimitra , Ciuleanu Elisabeta , Ciuleanu Tudor , Resiga Liliana , Zaramboukas Thomas , Papadopoulou Kyriaki , Bobos Mattheos , Chrisafi Sofia , Tsolaki Eleftheria , Markou Konstantinos , Giotakis Evangelos , Koutras Angelos , Psoma Elsa , Kalogera‐Fountzila Anna , Skondra Maria , Bamia Christina , Pectasides Dimitrios , Kotoula Vassiliki
Published: August 2017

Genomic patterns of nasopharyngeal carcinomas (NPCs) have as yet been studied in Southeast Asian (SEA) patients. Here, we investigated genomic patterns of locally advanced NPC Southeast European (SEE) patients treated with chemoradiotherapy. We examined 126 tumors (89% EBV positive) from Greek and Romanian NPC patients with massively parallel sequencing. Paired tumor‐cell‐rich (TC) and infiltrating‐lymphocyte‐rich (TILs) samples were available in 19 and paired tumor‐germline samples in 68 cases. Top mutated genes were BRCA1 (54% of all tumors); BRCA2 (29%); TP53 (22%); KRAS (18%). Based on the presence and number of mutations and mutated genes, NPC were classified as stable (no mutations, n = 27); unstable (>7 genes with multiple mutations, all BRCA1 positive, n = 21); and of intermediate stability (1–7 singly mutated genes, n = 78). BRCA1 p.Q563* was present in 59 tumors (48%), more frequently from Romanian patients (p < 0.001). No pathogenic germline mutations were identified. NPC exhibited APOBEC3A/B and nucleotide‐excision‐repair‐related mutational signatures. As compared to TC, TILs demonstrated few shared and a higher number of low frequency private mutations (p < 0.001). In multivariate analysis models for progression‐free survival, EBV positivity was a favorable prognosticator in stable tumors; BRCA1 mutations were unfavorable only in tumors of intermediate stability. In conclusion, other than described for SEA NPC, somatic BRCA1 mutations were common in SEE NPC; these were shared between TC and TILs, and appeared to affect patient outcome according to tumor genomic stability status. Along with the identified mutational signatures, these novel data may be helpful for designing new treatments for locally advanced NPC.
Promoter hypermethylation in plasma‐derived cell‐free DNA as a prognostic marker for pancreatic adenocarcinoma staging
Authors: Henriksen Stine Dam , Madsen Poul Henning , Larsen Anders Christian , Johansen Martin Berg , Pedersen Inge Søkilde , Krarup Henrik , Thorlacius‐Ussing Ole
Published: August 2017

Correct staging of pancreatic cancer is paramount, as treatment is stage specific. However, minimally invasive tools to facilitate staging are lacking. DNA promoter hypermethylation is a hallmark of cancer. The aim of this study is to evaluate promoter hypermethylation in cell‐free DNA as a prognostic marker for stage classification of pancreatic adenocarcinoma. Consecutive patients with pancreatic adenocarcinoma were prospectively included. Plasma samples were obtained before diagnostic work‐up and treatment. Patients were staged according to the TNM classification. Methylation‐specific PCR of 28 genes was performed. Prognostic prediction models for staging of pancreatic adenocarcinoma were developed by multivariable logistic regression analysis using stepwise backwards elimination. Ninety‐five patients with pancreatic adenocarcinoma were included. The mean number of hypermethylated genes was identical for stage I, II and III disease (7.09 (95% CI; 5.51–8.66), 7.00 (95% CI; 5.93–8.07) and 6.77 (95% CI; 5.08–8.46)), respectively, and highly significantly different from stage IV disease (10.24 (95% CI; 8.88–11.60)). The prediction model (SEPT9v2, SST, ALX4, CDKN2B, HIC1, MLH1, NEUROG1, and BNC1) enabled the differentiation of stage IV from stage I‐III disease (AUC of 0.87 (cut point 0.55; sensitivity 74%, specificity 87%)). Model (MLH1, SEPT9v2, BNC1, ALX4, CDKN2B, NEUROG1, WNT5A, and TFPI2) enabled the differentiation of stage I‐II from stage III‐IV disease (AUC of 0.82 (cut point 0.66; sensitivity 73%, specificity 80%)). Cell‐free DNA promoter hypermethylation has the potential to be blood‐based prognostic markers for pancreatic adenocarcinoma, as panels of hypermethylated genes enables the differentiation according to cancer stage. However, further validation is required.
Newcastle disease virus mediates pancreatic tumor rejection via NK cell activation and prevents cancer relapse by prompting adaptive immunity
Authors: Schwaiger Theresa , Knittler Michael R , Grund Christian , Roemer‐Oberdoerfer Angela , Kapp Joachim‐Friedrich , Lerch Markus M , Mettenleiter Thomas C , Mayerle Julia , Blohm Ulrike
Published: August 2017

Pancreatic cancer is the 8th most common cause of cancer‐related deaths worldwide and the tumor with the poorest prognosis of all solid malignancies. In 1957, it was discovered that Newcastle disease virus (NDV) has oncolytic properties on tumor cells. To study the oncolytic properties of NDV in pancreatic cancer a single dose was administered intravenously in a syngeneic orthotopic tumor model using two different murine pancreatic adenocarcinoma cell lines (DT6606PDA, Panc02). Tumor growth was monitored and immune response was analyzed. A single treatment with NDV inhibited DT6606PDA tumor growth in mice and prevented recurrence for a period of three months. Tumor infiltration and systemic activation of NK cells, cytotoxic and helper T‐cells was enhanced. NDV‐induced melting of Panc02 tumors until d7 pi, but they recurred displaying unrestricted tumor growth, low immunogenicity and inhibition of tumor‐specific immune response. Arrest of DT6606PDA tumor growth and rejection was mediated by activation of NK cells and a specific antitumor immune response via T‐cells. Panc02 tumors rapidly decreased until d7 pi, but henceforth tumors characterized by the ability to perform immune‐regulatory functions reappeared. Our results demonstrated that NDV‐activated immune cells are able to reject tumors provided that an adaptive antitumor immune response can be initiated. However, activated NK cells that are abundant in Panc02 tumors lead to outgrowth of nonimmunogenic tumor cells with inhibitory properties. Our study emphasizes the importance of an adaptive immune response, which is initiated by NDV to mediate long‐term tumor surveillance in addition to direct oncolysis.
Using the SoSE Principles Framework
Authors: Pratt Jaci M , Cook Stephen C
Published: August 2017

This paper is concerned with the principles for successful System of Systems Engineering practice and their use. The paper opens with a description of the need for System‐of‐Systems Engineering (SoSE) within the Australian Defense context and the research underway to support its introduction. An overview of previous work by the authors follows describing the three‐layer framework used to hold the SoSE principles (Pratt & Cook, 2017) to provide context. This framework comprises an articulation of the worldview which makes SoSE meaningful, the concepts that drive SoSE methodology design and use (descriptive heuristics), and implementation principles (prescriptive heuristics). The paper discusses the need for substantiation of these principles and the framework, the methods by which this being conducted and some the initial work assessing coverage and applicability. Finally, the paper provides suggestions for how this framework and associated principles can be employed for its stated purpose (utility), with specific regards for different stakeholders and their varied roles and responsibilities.
Cause and Impact Analysis of Cost and Schedule Overruns in Subsea Oil and Gas Projects – A Supplier's Perspective
Authors: Bergli Simen , Falk Kristin
Published: August 2017

This paper identifies drivers for cost and schedule overruns in subsea production system projects from a supplier's point of view. Subsea Production Systems connects subsea wells to offshore vessels, and enable efficient and safe hydrocarbon production.

Using root cause analysis, cause and effect diagram, and Pareto charts in a specific company we identified three main drivers of cost and schedule overruns: qualification of products, changing vendors frequently, and project management.

Detailed analyzes of a reference project found that the supplier identified about half of the technology gaps during the tender phase. Technology qualification programs of key components were not included in the bid, although the project had to pay for related cost overruns. In summary, the project could have eliminated more than two thirds of the cost escalation related to qualification costs by capturing all technology gaps in the early tendering phase, and as a result significantly increased the profitability.
Exploring the Cyber‐Physical Design Space
Authors: Fitzgerald John , Gamble Carl , Payne Richard , Lam Benjamin
Published: August 2017

A major challenge in the model‐based engineering of Cyber‐Physical Systems (CPSs) is that of providing methods and tools that support decision‐making in design. In the CPS design space, system models may be composed of diverse notations and tools, and the range of alternatives to be evaluated is immense. In spite of this, the benefits of trade‐off analysis at an early design stage are significant, making the automation of Design Space Exploration (DSE) an appealing prospect. In bringing DSE to industry scale, there is a clear need for both guidance to engineers in designing DSE, and a theory of cost‐effective DSE algorithms. To address this, we propose and demonstrate a SysML profile that encourages the explicit description of DSE over multi‐disciplinary co‐models, and demonstrate the ability to tune a genetic DSE algorithm across a range of design spaces.
Modeling Legal Requirements
Authors: Webel Christian , Steglich Rainer
Published: August 2017

Ever increasing complexity is one of the key challenges for software‐intensive systems. All phases of the system engineering lifecycle are affected; thus, appropriate methods, techniques, and tools must be provided to manage this increasing complexity. Another challenge arises from the fact that requirements are traditionally documented in natural language. This is especially true for legal artifacts such as laws or standards, since organizations are required to consider these kinds of legal requirements when bringing products to the market. Applying model‐based engineering approaches is one possibility to address these problems, but methodical uncertainties caused by a lack of method support have so far prevented their widespread use in early project phases. This paper addresses these uncertainties by introducing a systematic approach for modeling legal artifacts such as laws or standards. The method is assessed in the context of emission legislation in the automotive domain.
A Model‐Based Method for Design Option Evaluation of Off‐the‐Shelf Naval Platforms
Authors: Morris Brett A. , Cook Stephen C.
Published: August 2017

Off‐the‐Shelf (OTS) strategies have become prevalent in the acquisition of naval platforms because the strategy is perceived as a means of reducing the acquisition cost and schedule risk. This paper covers a method to conduct an evaluation of shortlisted OTS naval platform design options that utilises Model‐Based Systems Engineering (MBSE). MBSE is used as a means of developing and managing the traceability of evaluation criteria, managing the evaluation itself and facilitating reuse of the design patterns present both in naval platforms and acquisition processes. The paper concludes with a description of a pilot test of the method for an Offshore Patrol Vessel, which found it to be useful to manage the evaluation criteria traceability, maintain design data and identify weak spots in OTS design options.
A Hybrid Approach for Supply Chain Analysis: An Application of Network and Cluster Analysis
Authors: Qiao Li , Ryan Michael
Published: August 2017

This study presents a quantitative method for investigating the network characteristics of supply chain management with the help of methodologies derived from the network analysis, which offers many techniques and indicators through measuring the links among nodes to demonstrate the structural patterns of connected systems. More precisely, this investigation derives the structural configuration of each function component within the supply chain by measuring the indicators of network analysis, including degree centrality, closeness centrality, betweenness centrality and PageRank centrality. This study empirically tests an example of supply chain taken from 22 functional organizations based on supply chain operations reference (SCOR) model. The results suggest the proposed method provides an appropriate understanding of each function organization in the supply chain model based on the structural characteristics relating to its network position on informational, material and functional flows. A number of recommendations are made regarding the role of importance be to understand based on the results of the network analysis.
A SE VSE Company Use Case
Authors: Marvin Joseph W. , Bailey Garth V. , Cadigan John J.
Published: August 2017

Prime Solutions Group, Incorporated (PSG) is a systems engineering company and Very Small Entity that has benefited from association with INCOSE and specifically the Very Small Entity Working Group. This paper presents the company's use of the INCOSE Very Small Entity Working Group Deployment Packages for research projects, engineering services and software development. Further tailoring of the Very Small Entity Working Group Deployment Packages derived from ISO/IEC Technical Report 29110 into a System of Research & Development Innovation is discussed. Finally, the current INCOSE Technical Operations policy review and update activity is presented as an example of applying Very Small Entity systems engineering process on INCOSE. The objective of the paper is to describe the application of an INCOSE technical product in the small business world.
Future Proofing Process
Authors: Rehman Obaide Ur , Ryan Michael J. , Efatmaneshnik Mahmoud
Published: August 2017

Future‐proofing (FP) is one of the ways to obtain a system design which deters obsolescence and extends the system's service life. In this paper, the concept of future‐proofing is discussed and a systematic FP process is proposed. The paper discusses in details the difference between system life‐cycle value (LCV) and future‐proofing. In addition, this paper also presents the FP process which helps designer to address systematically the design issues associated with the system which is required to have a significantly long life. To assist in understanding the process, new system categories are proposed taking into account the desired system requirement for FP. Finally, several mechanism to achieve FP is discussed based on the selected system category.
Conceptual Data Modeling for the Functional Decomposition of Mission Capabilities
Authors: Battigaglia Andrew , Brimhall Erika , Ogle Terry
Published: August 2017

To have a complete understanding of implementation‐agnostic functional decompositions of mission capabilities, the data elements consumed and produced by functions must be captured and explained. This paper details a method employing a conceptual data modeling approach to formally document data elements and the interactions between those elements with a structured data architecture. This approach uses the concepts of entities, relationships, and the observable characteristics of those entities and relationships to clearly define the context of the data interchanges and represents the interchanges through different views of the conceptual data model. An example of developing a conceptual data model including views using the Future Airborne Capability Environment (FACETM) data architecture is demonstrated. Finally, the data model and functional decomposition are linked together to give a complete context for the mission capability. The process of developing and linking to the data model improves the functional decomposition and enables communication of decomposition context.
I Don't Need Requirements – I Know What I'm Doing! Usability as a Critical Human Factor in Requirements Management
Authors: Hoehne Oliver
Published: August 2017

The INCOSE Systems Engineering Handbook Version 4.0 lists the word “process” 1,597 times, yet the word “people” only 65 times. This paper argues that human aspect (people) considerations are similarly underrepresented in requirements management (RM), and that RM focuses mainly on processes and products (tools). This is also reflected in the ISO/IEC/IEEE 29148:2011 abstract that refers to “provisions for the processes and products related to the engineering of requirements …”. The paper makes the case that due to the lack of human aspect considerations many requirements specifications do not meet the definition of usability, where requirement specification users can achieve their objectives with effectiveness, efficiency, and satisfaction.

The consumer behavior theory suggests that if (requirements specifications) consumption is made too difficult, then consumers will want to move on to things they actually find satisfying (e.g. design, implementation, testing). By providing requirements specifications that are not readily usable to consumers, an additional processing burden is placed on them, and consumers might succumb to the temptation to cut the requirements analysis phase short. Combined with overconfidence, this may result in requirements consumers to move on, stating: “I have done this before. I don't need requirements. I know what I'm doing!”. This paper will identify the underlying root cause, and propose a method to introduce usability into the requirements management process, making the process more practical and convenient for the requirements consumer, and as a result, achieve better project performance.
Designing Inter‐factory architecture for Higher adaptability of Manufacturing supply chain based on Systems engineering
Authors: Jun‐Yeong Kim , Dae‐Geun Hong , Suk‐Hwan Suh
Published: August 2017

A manufacturing supply chain is a set of multi‐vendors directly connected by one or more upstream and downstream processes producing goods from source materials for customers. From this point of view, management is an activity to optimize its value‐added processes, materials, final goods, and related information among suppliers, manufacturers and customers. Most previous researches regarding optimizing manufacturing supply chain had been concentrated on analyzing statistically and configuring to fix supply chains like vertical or horizontal integrations as there was little possibility of flexible and adaptable production systems.

This research is an extension of a concept of Modular factory. This research proposes Inter‐factory architecture for setting higher flexibility and adaptability on manufacturing supply chains accordance to customer's specific needs. The researched architecture is physically designed as a prototype of inter‐factory order management system. In order to make order acknowledgement from customer's specific needs, this system attributes with primary functions, (1) searching candidates of multi‐vendor, (2) check their factory facility and utility specifications, (3) verifying their enable manufacturing schedules.