bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronoamperometric Biosensor for Protease Activity Assay and Inhibitor Screening
Authors: El Harrad Loubna , Amine Aziz
Published: July 2017

Herein, we report an electrochemical biosensor for the measurement of proteins and protease activity using carbon nanopowder paste electrode modified with tyrosinase. The measurement of proteins is based on the amperometric measurement of the enzymatic product, tyrosine, at low applied potential (i.e +0.05 V vs. Ag/AgCl), in a linear range from 1 μg/mL to 10 μg/mL for casein and albumin bovine serum. This biosensor is also used to assess the enzymatic activity of the enzymes namely trypsin and proteinase K, observing a detection limit of 0.02 mU/mL (S/N=3). The ability of this assay to monitor the trypsin activity is exploited to investigate its inhibition by leupeptin. The trypsin kinetic interactions reveal uncompetitive binding of leupeptin with 50 % inhibition equal to 3.75 μM, a dynamic range of 0.25–10 μM, and a detection limit of 0.25 μM. The assay developed can be considered as general activity assay of any protease with the advantages of good storage stability (few weeks), low detection limit and ability to analyse turbid and colored samples.
Finite element analysis of damage and failure of reinforced concrete members under earthquake loading
Authors: Moharrami Mohammadreza , Koutromanos Ioannis
Published: July 2017

This paper presents a three‐dimensional analysis framework, based on the explicit finite element method, for the simulation of reinforced concrete components under cyclic static and dynamic loading. A recently developed triaxial constitutive model for concrete is combined with a material model for reinforcing steel which can account for rupture due to low‐cycle fatigue. The reinforcing bars are represented with geometrically nonlinear beam elements to account for buckling of the reinforcement. The strain penetration effect is also accounted for in the models. The modeling scheme is used in a commercial finite element program and validated with the results of experimental static and dynamic tests on reinforced concrete columns and walls. The analyses are supplemented with a parametric study to investigate the impact of several modeling assumptions on the obtained results.
The role of eddies in solute transport and recovery in rock fractures: Implication for groundwater remediation
Authors: Lee Seung Hyun , Yeo In Wook , Lee Kang‐Kun , Lee Won Sang
Published: July 2017

A better understanding of solute transport and retention mechanism in rock fractures has been challenging due to difficulty in their direct observations in microscale rough‐walled fractures. Six representative troughs in a rough‐walled fracture were selected for microscale observations of eddy formation with increasing flow velocity and its effect on spatiotemporal changes of solute concentration. This experimental study was enabled by a microscale visualization technique of micro particle image velocimetry. With increasing flow velocity (Re ≤ 2.86), no eddies were generated, and solutes along the main streamlines transported rapidly, whereas those near the wall moved slowly. A larger amount of solutes remained trapped at all troughs at Re = 2.86 than Re < 1. For Re = 8.57, weak eddies started to be developed at the troughs on the lee side, which little contributed to overall solute flushing in the fracture. Accordingly, a large of amount of water was needed for solute flushing. The flow condition of 1 < Re < 10, before a full development of eddies, was least favourable in terms of time and amount of remediation fluid required to reach a target concentration. After large eddies were fully developed at troughs on the lee side for Re = 17.13, solutes were substantially reduced by eddies with less amount of water. Fully developed eddies were found to enhance solute transport and recovery, as opposed to a general consensus that eddies trap and delay solutes. Direct inflow into troughs on the stoss side also made a great contribution to solute flushing out of the troughs. This study indicates that fully developed eddies or strong inflows at troughs are highly possible to form for Re > 10 and this flow range could be favourable for efficient remediation.
Degree of conversion and cross‐link density within a resin‐matrix composite
Authors: Al‐Zain Afnan O. , Eckert George J. , Lukic Henry , Megremis Spiro J. , Platt Jeffrey A.
Published: July 2017

The aims of this study were to profile light radiated from two light‐curing units (LCUs) and evaluate profile relationship to polymerization patterns within a resin‐matrix composite (RMC). Beam profiles of one multiple emission peak light‐emitting‐diode and one quartz‐tungsten‐halogen curing‐unit were measured using a beam profiler/spectrometer system. A camera‐based profiler and an integrating sphere/spectrometer assembly were used to evaluate each LCU beam. Polymerization patterns within a nano‐hybrid RMC were investigated using a mapping approach by assessing the degree of conversion utilizing micro‐Raman spectroscopy and indirectly estimating cross‐link‐density by repeated microhardness testing before and after exposure to ethanol (%KH reduction, n = 3). The irradiance received on the top and bottom specimen surfaces from both LCUs was measured using a MARC‐RC system. The investigated beam profile area from both LCUs was non‐uniform and yielded localized discrepancies in DC (55.7–74.9%) and %KH reduction (26.7–54.1%). The LCU irradiance received at the bottom of the specimens was ∼10% of the top value. This study demonstrated that LCU beam profiles were non‐uniform in the area explored. Localized differences in DC and %KH reduction existed throughout the RMC specimens but did not follow a specific pattern. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1496–1504, 2018.
The colonic groove of the plains viscacha (Lagostomus maximus): Histochemical evidence of an abrupt change in the glycosylation pattern of goblet cells
Authors: Tano de la Hoz María Florencia , Flamini Mirta Alicia , Zanuzzi Carolina Natalia , Díaz Alcira Ofelia
Published: July 2017

The ascending colon of most rodent species shows a longitudinal colonic groove that works as a retrograde transport pathway for a mixture of bacteria and mucus toward the cecum. We describe the morphology and glycosylation pattern of the colonic groove of Lagostomus maximus to analyze the role of mucins in this anatomical feature. We also studied the distribution pattern of the interstitial cells of Cajal (ICC) to evaluate their regulatory influence on gut motility. The groove originated near the cecocolic junction and extended along the mesenteric side of the ascending colon, limited at both ends by nonpapillated ridges. These ridges divided the lumen of the ascending colon into two compartments: a narrow channel and a large channel, called the groove lumen and the main lumen, respectively. The histochemical analysis showed differences in the glycosylation pattern of the goblet cells inside and outside the groove. Unlike the mucosa lining the main lumen of the colon, the groove was rich in goblet cells that secrete sulfomucins. The PA/Bh/KOH/PAS technique evidenced an abrupt change in the histochemical profile of goblet cells, which presented a negative reaction in the groove and a strongly positive one in the rest of the colonic mucosa. The anti‐c‐kit immunohistochemical analysis showed different ICC subpopulations in the ascending colon of L. maximus. Of all types identified, the ICC‐SM were the only cells located solely within the colonic groove.
A dual flip angle 3D bSSFP magnetization transfer‐like method to differentiate between recent and old myocardial infarction
Authors: Germain Philippe , El Ghannudi Soraya , Labani Aissam , Jeung Mi Y. , Gangi Afshin , Ohlmann Patrick , Roy Catherine
Published: July 2017

Background

Magnetic resonance imaging (MRI) tissue signal is modulated by magnetization transfer (MT) phenomena, intrinsically induced by balanced steady‐state free precession (bSSFP) imaging.

Purpose

To investigate the possible value of such a MT‐like bSSFP approach in two clinical settings involving focal myocardial lesions highligthed by late gadolinium enhancement (LGE+): edema induced by recent myocardial infarction (MI) and fibrotic scar related to chronic infarction.

Materials and Methods

Population: 48 LGE + patients were studied: 26 with recent MI, 22 with chronic MI. 20 LGE‐normal subjects were considered the control group. Field strength/sequence: Navigator‐based short axis 3D‐bSSFP sequences with 20° and 90° excitation flip angles were acquired (1.5T). Assessment: Pixel‐wise normalized MT Ratio (nMTR) parametric images were calculated according to: nMTR = 100*(S20‐S90*k)/S20, with S20 and S90 signal intensity in 20° and 90° flip angle images and k = Blood20/Blood90 as a normalization ratio. Statistical tests: analysis of variance (ANOVA), receiver operating characteristic (ROC) analysis.

Results

Overall normal myocardial nMTR was 50.2 ± 3.6%. In recent MI, nMTR values were significantly reduced in LGE + regions (–22.3 ± 9.9%, P < 0.0001). In cases of chronic infarct, nMTR was significantly increased in LGE + regions (14.2 ± 11.4%, P < 0.0001). Comparison between observed results and theoretical values obtained with the Freeman‐Hill formula showed that most variations observed in MI are related to MT effects instead of relaxation effects.

Conclusion

In contrast to LGE imaging, which may show a similar hyperenhancement in recent and old infarctions, nMTR imaging demonstrates an opposite pattern: decreased values for recent infarction and increased values for old infarction, thus allowing to discriminate between these two clinical conditions without gadolinium injection.

Level of Evidence: 3

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018;47:798–808.
High‐resolution precipitation downscaling in mountainous areas over China: development and application of a statistical mapping approach
Authors: Zhu Xiaochen , Qiu Xinfa , Zeng Yan , Ren Wei , Tao Bo , Pan Hong , Gao Ting , Gao Jiaqi
Published: July 2017

High‐resolution precipitation distributions in mountainous areas are important for hydrological and ecological assessments, especially in regions with few weather stations. In this study, we proposed an improved model for precipitation downscaling by adding two new parameters, i.e. the maximum precipitation increment direction and the prevailing precipitation direction, which represent the impacts of elevation and the sources of precipitation, respectively. The model parameterization is based on observations made at meteorological stations, terrain factors (e.g. elevation, aspect, and slope), and the new parameters. To evaluate the model, we used six sub‐models, each of which considers different influencing factors, to estimate the precipitation distribution and compare their estimation errors. Based on the mean absolute error (MAE) and the root‐mean‐square error (RMSE) at the validation stations, we found that the sixth sub‐model, which includes all the influencing factors, clearly ranks above the others in terms of precipitation downscaling. The monthly MAE and the RMSE of our downscaled precipitation range from 2.2 to 16.1 mm and from 3.4 to 22.7 mm, respectively, indicating more accurate estimation than the raw tropical precipitation measuring mission (TRMM) products (monthly MAE: 3.6–22.0 mm; monthly RMSE: 5.1–28.6%). Our results also show that the sixth sub‐model performs better than the Auto‐Searched Orographic and Atmospheric Effects Detrended Kriging model (ASOADeK model or Guan's model) due to the inclusion of the elevation and the sources of precipitation. Based on the sixth sub‐model and the TRMM 3B43 products, we developed the monthly precipitation products in China from 2000 to 2007 at a spatial resolution of 1 km. Our improved approach to precipitation downscaling could be used for regions where the precipitation distribution is greatly affected by the terrain and few observations are available for estimating the precipitation distribution.
Attribution of temperature changes in Western China
Authors: Wang Yujie , Sun Ying , Hu Ting , Qin Dahe , Song Lianchun
Published: July 2017

Western China (WC) is located in the arid and semi‐arid belt of the mid‐latitudes. Understanding the causes of the large temperature increases experienced in this region is of great importance because both the fragile ecological environment and the human societies in WC are highly vulnerable to changes in climate. We conducted a detection and attribution analysis on the annual mean temperature using an optimal fingerprinting method by comparing observations based on homogenized station data with simulations conducted using the models that participated in the Coupled Model Intercomparison Project Phase 5 (CMIP5). The results show that the increase in the mean temperature can be attributed to human activities. The effect of anthropogenic (ANT) forcing can be detected in single‐signal detection analyses when the response to the ANT forcing is compared directly with the observations. This effect can also be separated from the influence of the natural external forcing in two‐signal analyses. The warming attributable to the ANT forcing explains most of the observed regional warming. The models appear to have underestimated the observed warming, suggesting that the projected future temperature increases based on raw output from the model simulations may have also been underestimated.
Performances of BATS and CLM land‐surface schemes in RegCM4 in simulating precipitation over CORDEX Southeast Asia domain
Authors: Chung Jing Xiang , Juneng Liew , Tangang Fredolin , Jamaluddin Ahmad F.
Published: July 2017

This study evaluates the sensitivity of precipitation in Southeast Asia (SEA) to the choice of land‐surface schemes available in RegCM4, that is BATS1e (BATS) and CLM4.5 (CLM), over the CORDEX SEA domain. Two similar simulations using different land‐surface schemes were conducted for the period 1989 to 2007, with a horizontal resolution of 25 × 25 km. Four different types of observational data were used to evaluate the performance of these simulations. It was found that both of these simulations reproduced the SEA precipitation climatology spatial patterns reasonably well. However, the BATS simulation systematically produced higher frequency and more intense precipitation over land. The CLM simulation, although overestimating the precipitation frequency, produced a lower amount of on‐land precipitation. The precipitation annual cycle and interannual variability were both insensitive to the choice of land‐surface scheme. The errors in the precipitation simulation were found to originate from the simulated convective precipitation (CPr). Large‐scale precipitation was found to be less sensitive to the choice of land‐surface scheme. The influence of the land‐surface scheme on SEA precipitation simulation took place through the interaction between soil moisture content and CPr. The soil moisture content was consistently higher in the BATS simulation, as was the CPr simulated. During December to February (DJF), the difference in the precipitation amount simulated by BATS and CLM simulations was lower over the SEA mainland, even though the soil moisture content in both simulations was very different. This difference was due to the inactivity of the convective activities over the SEA mainland during DJF. This study concludes that the simulation of SEA precipitation amount was sensitive to the choice of land‐surface scheme, and recommend the use of CLM4.5 land‐surface scheme for simulation of SEA precipitation.
Atmospheric Photopolymerization of Acrylamide Enabled by Aqueous Glycerol Mixtures: Characterization and Application for Surface‐Based Microfluidics
Authors: Gleichmann Tobias , Rostas Arpad , Wörner Jakob , Schleicher Erik , Gutzweiler Ludwig , Hamouda Boris , Zengerle Roland , Koltay Peter , Riegger Lutz
Published: July 2017

Polyacrylamide usually is the material of choice for electrophoretic separation in slab gels, capillaries, and microfluidic devices. So far its polymerization requires anaerobic environments because oxygen impurities inhibit or even terminate the polymerization reaction of acrylamide. Here, it is demonstrated that gel precursor solutions with glycerol contents above 20 vol% enable direct atmospheric photopolymerization of acrylamide with no need for sealing or degassing the solution in advance. The positive effect of glycerol on the polymerization reaction is proven by simulation‐validated electron paramagnetic resonance measurements. Nuclear magnetic resonance reveals that glycerol does not interfere with the reaction indicating that the observed enhancement in polymerization is owed to the low oxygen solubility of aqueous glycerol mixtures. Glycerol concentrations of >60 vol% in the gel precursor solution enable complete polymerization of volumes down to 5 nL within less than 5 s. This enables using liquid handling robots to fabricate channel‐free open microfluidic structures of solid polyacrylamide hydrogel in a low‐cost automated manner in a standard lab environment.
Assessing neurodevelopmental effects of arsenolipids in pre‐differentiated human neurons
Authors: Witt Barbara , Ebert Franziska , Meyer Sören , Francesconi Kevin A. , Schwerdtle Tanja
Published: July 2017

Scope

In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids.

Methods and results

Neurodevelopmental effects of three arsenic‐containing hydrocarbons (AsHC), two arsenic‐containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMAV) were characterized in pre‐differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMAV were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity.

Conclusion

These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment.
A novel approach for the numerical investigation of optimal control problems containing multiple delays
Authors: Marzban Hamid Reza , Pirmoradian Hoda
Published: July 2017

This paper deals with the numerical solution of optimal control problems with multiple delays in both state and control variables. A direct approach based on a hybrid of block‐pulse functions and Lagrange interpolating polynomials is used to convert the original problem into a mathematical programming one. The resulting optimization problem is then solved numerically by the Lagrange multipliers method. The operational matrix of delay for the presented framework is derived. This matrix plays an imperative role to transfer information between 2 consecutive switching points. Furthermore, 2 upper bounds on the error with respect to the L2‐norm and infinity norm are established. Several optimal control problems containing multiple delays are carried out to illustrate the various aspects of the proposed approach. The simulation results are compared with either analytical or numerical solutions available in the literature.
Light‐Emitting Agents for Noninvasive Assessment of Kidney Function
Authors: Huang Jiaguo , Gretz Norbert
Published: July 2017

The noninvasive assessment of kidney function and diagnosis of kidney disease have long been challenges. Traditional methods are not routinely available, because the existing protocols are cumbersome, time consuming, and invasive. In the past few years, significant progress in the area of diagnosing kidney function and disease on the basis of light‐emitting agents has been made. Herein, we briefly review light‐emitting agents, including organic fluorescent agents and inorganic renal clearable luminescent nanoparticles for the noninvasive and real‐time monitoring of kidney function and disease. Moreover, some significant requirements and strategies regarding the design of ideal glomerular filtration rate agents and renal clearable nanoparticles are discussed. Finally, we discuss future challenges in expediting clinical translation of these developed light‐emitting agents, along with considerations of the efforts that need to be made to develop new agents and diagnosing kidney disease.
Quinoline‐Derived Two‐Photon‐Sensitive Octupolar Probes
Authors: Dunkel Petra , Petit Morgane , Dhimane Hamid , Blanchard‐Desce Mireille , Ogden David , Dalko Peter I.
Published: July 2017

A systematic study on quinoline‐derived light sensitive probes, having third‐order rotational symmetry is presented. The electronically linked octupolar structures show considerably improved linear and nonlinear photophysical properties under one‐ and two‐photon irradiation conditions compared to the corresponding monomers. Photolysis of the three acetate derivatives shows strong structure dependency: whereas irradiation of the 6‐ and 7‐aminoquinoline derivatives resulted in fast intramolecular cyclization and only trace amounts of fragmentation products, the 8‐aminoquinoline derivative afforded clean and selective photolysis, with a sequential release of their acetate groups (δu[730]=0.67 GM).
Aortic microcalcification is associated with elastin fragmentation in Marfan syndrome
Authors: Wanga Shaynah , Hibender Stijntje , Ridwan Yanto , van Roomen Cindy , Vos Mariska , van der Made Ingeborg , van Vliet Nicole , Franken Romy , van Riel Luigi AMJG , Groenink Maarten , Zwinderman Aeilko H , Mulder Barbara JM , de Vries Carlie JM , Essers Jeroen , de Waard Vivian
Published: July 2017

Marfan syndrome (MFS) is a connective tissue disorder in which aortic rupture is the major cause of death. MFS patients with an aortic diameter below the advised limit for prophylactic surgery (<5 cm) may unexpectedly experience an aortic dissection or rupture, despite yearly monitoring. Hence, there is a clear need for improved prognostic markers to predict such aortic events. We hypothesize that elastin fragments play a causal role in aortic calcification in MFS, and that microcalcification serves as a marker for aortic disease severity. To address this hypothesis, we analysed MFS patient and mouse aortas. MFS patient aortic tissue showed enhanced microcalcification in areas with extensive elastic lamina fragmentation in the media. A causal relationship between medial injury and microcalcification was revealed by studies in vascular smooth muscle cells (SMCs); elastin peptides were shown to increase the activity of the calcification marker alkaline phosphatase (ALP) and reduce the expression of the calcification inhibitor matrix GLA protein in human SMCs. In murine Fbn1C1039G/+ MFS aortic SMCs, Alpl mRNA and activity were upregulated as compared with wild‐type SMCs. The elastin peptide‐induced ALP activity was prevented by incubation with lactose or a neuraminidase inhibitor, which inhibit the elastin receptor complex, and a mitogen‐activated protein kinase kinase‐1/2 inhibitor, indicating downstream involvement of extracellular signal‐regulated kinase‐1/2 (ERK1/2) phosphorylation. Histological analyses in MFS mice revealed macrocalcification in the aortic root, whereas the ascending aorta contained microcalcification, as identified with the near‐infrared fluorescent bisphosphonate probe OsteoSense‐800. Significantly, microcalcification correlated strongly with aortic diameter, distensibility, elastin breaks, and phosphorylated ERK1/2. In conclusion, microcalcification co‐localizes with aortic elastin degradation in MFS aortas of humans and mice, where elastin‐derived peptides induce a calcification process in SMCs via the elastin receptor complex and ERK1/2 activation. We propose microcalcification as a novel imaging marker to monitor local elastin degradation and thus predict aortic events in MFS patients. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Complications preceding early deaths in Black and White children with acute myeloid leukemia
Authors: Winestone Lena E. , Getz Kelly D. , Miller Tamara P. , Li Yimei , Huang Yuan‐Shung , Seif Alix E. , Fisher Brian T. , Aplenc Richard
Published: July 2017

Black patients have a twofold increased risk of induction mortality compared to White patients with acute myeloid leukemia (AML). We reviewed diagnosis and billing data from Pediatric Health Information System for 28 AML Induction I deaths to investigate conditions preceding death in White and Black patients. Half of deaths occurred within 10 days of initial diagnostic admission. Respiratory, cardiac, renal, and infectious complications were common prior to both White and Black deaths. Deaths in White patients were more commonly preceded by intracranial hemorrhage compared to deaths in Black patients. Future studies should assess management approaches of complications by race to identify modifiable processes that reduce mortality.
Outcome after prenatal and postnatal diagnosis of complex congenital heart defects and the influence of genetic anomalies
Authors: De Groote Katya , Vanhie Ellen , Roets Ellen , Ramaekers Paul , De Wilde Hans , Panzer Joseph , Vandekerckhove Kristof , Bove Thierry , François Katrien , Van Herck Koen , De Wolf Daniël
Published: July 2017

Objective

Determine prenatal detection rate, mortality and association with genetic abnormalities in patients with severe CHD.

Method

Single center retrospective study in patients with severe CHD diagnosed prenatally or postnatally (2006 to 2014).

Results

A total of 567 patients were included, 176 (31%) after prenatal diagnosis, with large differences in prenatal detection rate among CHD types. Coarctation (24%), tetralogy of Fallot (21%) and univentricular heart (19%) were the most prevalent CHD. Overall mortality rate was 30% with important contributions of prenatal mortality including termination of pregnancy (40%) and postnatal compassionate care (15%). In the group requiring surgery, mortality rate was 12%. Genetic testing was available in 70%. A genetic cause was present in 140/394 patients tested (36%; 25% in the total group). Mortality was higher in the group with abnormal genetic testing compared with those with normal or no genetic testing (57/141 vs 112/423; p = 0,002).

Conclusion

Only one third of severe CHD are detected; overall mortality remains high (30%) with major contributions of termination of pregnancy and compassionate care. A genetic cause was found in 36% and was associated with a decreased survival. Counseling must include the possibility of associated genetic pathology and its impact on survival. © 2017 John Wiley & Sons, Ltd.
A mixed‐methods study to explore the supportive care needs of breast cancer survivors
Authors: Cheng K.K.F. , Cheng H.L. , Wong W.H. , Koh C.
Published: July 2017

Objective

Needs assessment is the essence of quality cancer survivorship care. The aim of this study was to explore the supportive care needs of breast cancer survivors (BCS) in the first 5 years post treatment.

Methods

A mixed‐methods approach was employed. A quantitative study included a Supportive Care Needs Survey, which was completed by 250 BCS to identify the level of their needs for help. The quantitative data informed semistructured qualitative interviews undertaken with 60 BCS to explore in detail their posttreatment needs and experiences.

Results

32.4% and 16.8% reported 1 to 5 and greater than or equal to 6 needs for help, respectively. The regression analyses revealed that women within 2 years posttreatment and with higher educational level had higher levels of Psychological and Health Care System/Information needs. The qualitative data revealed “continuity of care” and “lifestyle advice and self‐management” as prominent survivorship concerns. It was shown that determination to continue normal life, social support, and feeling overwhelmed by information were all experienced as important influences on survivors' need for help.

Conclusions

Posttreatment needs vary with BCS characteristics and to the domains concerned. The approach to posttreatment care needs to be personalized and viable.
Dielectric screening effect of electronic polarization and intramolecular hydrogen bonding
Authors: Sung Shen‐Shu
Published: July 2017

Recent site‐resolved hydrogen exchange measurements have uncovered significant discrepancies between simulations and experimental data during protein folding, including the excessive intramolecular hydrogen bonds in simulations. This finding indicates a possibility that intramolecular charge–charge interactions have not included sufficient dielectric screening effect of the electronic polarization. Scaling down peptide atomic charges according to the optical dielectric constant is tested in this study. As a result, the number of intramolecular hydrogen bonds is lower than using unscaled atomic charges while reaching the same levels of helical contents or β‐hairpin backbone hydrogen bonds, because van der Waals interactions contribute substantially to peptide folding in water. Reducing intramolecular charge–charge interactions and hydrogen bonding increases conformational search efficiency. In particular, it reduces the equilibrium helical content in simulations using AMBER force field and the energy barrier in folding simulations using CHARMM force field.
Effect of radical prostatectomy on levels of cancer related epitopes in circulating macrophages of patients with clinically localized prostate cancer
Authors: Todenhöfer Tilman , Hennenlotter Jörg , Keller Gabriel , Neumann Tim , Stenzl Arnulf , Bedke Jens
Published: July 2017

Objective

Epitopes of the apoptosis related protein DNaseX (Apo10) and the pentose‐phosphate‐pathway associated protein transketolase‐like 1 (TKTL1) have been shown to be increased in circulating macrophages of patients with different cancer types including prostate cancer (PC). So far, the effect of cancer‐specific therapies on the levels of these markers in blood samples of patients with PC has not been evaluated yet. The aim of the present study was to prospectively assess the effect of surgical removal of the prostate on levels of Apo10 and TKTL1 in blood macrophages using Epitope Detection In Monocytes (EDIM).

Methods

We prospectively enrolled 174 patients with clinically localized PC undergoing radical prostatectomy. Peripheral blood was collected preoperatively in all patients and postoperatively in a subgroup of 72 patients. We separately assessed the proportion of CD14/CD16‐positive monocytes expressing Apo10 and TKTL1 using flow cytometry. The proportion of positive cells was multiplied by ten to generate a score for Apo10 and TKTL1, separately. Pre‐ and postoperative scores of Apo10 and TKTL1 were compared. Moreover, results were correlated with clinicopathologic parameters.

Results

In the total cohort, Median preoperative Apo10 and TKTL1 scores were 136 (Range 101‐254) and 139 (102‐216). In patients who underwent blood collection and testing either pre‐ and postoperatively (n = 72), median pre‐ versus postoperative scores were 132 (101‐215) versus 103 (70‐156) for Apo10 (P < 0.0001) and 140 (102‐212) versus 115 (84‐187) (P < 0.0001) for TKTL1. Following radical prostatectomy, 56 (77.7%) and 59 (81.9%) patients in the cohort of patients with blood collection before and after prostatectomy showed a decrease of Apo10 and TKTL1 expressing monocytes. TKTL1 and Apo10 did not show any correlation with known histopathologic and clinical risk parameters.

Conclusions

The present study demonstrates that surgical removal of the primary tumor leads to a significant decrease of Apo10 and TKTL1 expressing macrophages. This observation further encourages studies assessing the optimal clinical utility of EDIM‐based detection of Apo10 and TKTL1 in patients with PC.
Investigating the role of the IGF axis as a predictor of biochemical recurrence in prostate cancer patients post‐surgery
Authors: Breen Kieran J. , O'Neill Amanda , Murphy Lisa , Fan Yue , Boyce Susie , Fitzgerald Noel , Dorris Emma , Brady Lauren , Finn Stephen P. , Hayes Brian D. , Treacy Ann , Barrett Ciara , Aziz Mardiana Abdul , Kay Elaine W. , Fitzpatrick John M. , Watson R. William G.
Published: July 2017

Background

Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin‐like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF‐1 receptor (IGF‐1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post‐surgery.

Methods

Tissue microarrays (TMA) of 130 patients post‐radical prostatectomy (65 = BCR, 65 = non‐BCR) were stained by immunohistochemistry for INSR, IGF‐1R, PTEN, and AKT using optimized antibody protocols. INSR, IGF1‐R, PTEN, and AKT expression between benign and cancerous tissue, and different Gleason grades was assessed. Kaplan‐Meier survival curves were used to examine the relationship between proteins expression and BCR.

Results

INSR (P < 0.001), IGF‐1R (P < 0.001), and AKT (P < 0.05) expression was significantly increased and PTEN (P < 0.001) was significantly decreased in cancerous versus benign tissue. There was no significant difference in INSR, IGF‐1R, or AKT expression in the cancerous tissue of non‐BCR versus BCR patients (P = 0.149, P = 0.990, P = 0.399, respectively). There was a significant decrease in PTEN expression in the malignant tissue of BCR versus non‐BCR patients (P = 0.011). Combinational analysis of the tissue proteins identified a combination of decreased PTEN and increased AKT or increased INSR was associated with worst outcome. We found that in each case, our hypothesized worst group was most likely to experience BCR and this was significant for combinations of PTEN+INSR and PTEN+AKT but not PTEN+IGF‐1R (P = 0.023, P = 0.028, P = 0.078, respectively).

Conclusions

Low PTEN is associated with BCR and this association is strongly modified by high INSR and high AKT expression. Measurement of these proteins could help inform appropriate patient selection for postoperative adjuvant therapy and prevent BCR.
Geometry of X‐ray based measurement of residual strain at desired penetration depth
Authors: Morawiec A.
Published: July 2017

X‐ray based measurement of residual lattice strains at chosen penetration depth is one of the methods for investigating strain inhomogeneities in near‐surface layers of polycrystalline materials. The measurement relies on determining shifts of Bragg peaks for various directions of the scattering vector with respect to the specimen. At each of these directions, to reach a given the penetration depth, a proper specimen orientation is required. The task of determining such orientations, albeit elementary, is quite intricate. The existing literature describes only partial solutions with unspecified domains of application, which fail if applied to beyond the domains. Therefore, geometric aspects of the measurement are analyzed in details. Explicit bounds on measurement parameters are given. The equation fundamental for the procedure is solved with respect to specimen orientations. For a given direction of the scattering vector, there are generally four different specimen orientations leading to the same penetration depth. This simple fact (overlooked in previous analyses) can be used for improving reliability of measurement results. Analytical formulas for goniometer angles representing these orientations are provided.
A long‐lived supercell over mountainous terrain
Authors: Scheffknecht Phillip , Serafin Stefano , Grubišić Vanda
Published: July 2017

The life cycle of a convective storm forming over highly complex topography on the northern side of the Alps is studied. Moist convection began ahead of a cold front in the late morning of 2 August 2007 in eastern Switzerland. It developed into a supercell storm that moved along the Alpine main crest for more than 8 h, passed over several 2000 m high ridges and ultimately dissipated over eastern Austria. This study analyzes the impact of topography on the pre‐storm environment and on the storm development using several simulations with the Weather Research and Forecasting (WRF) model at a minimum horizontal grid spacing of 833 m. A hindcast simulation of the event features a convective system evolving in good agreement with observations. Variations in the simulated storm intensity appear to be related to the topography below the storm. Two idealized simulations help understand how the Alpine topography affected storm initiation and development. North of the Alps, relatively strong shear between southwesterly synoptic flow aloft and thermally induced plain‐to‐mountain flow near the ground created favourable conditions for supercell development. Small‐scale terrain features supported the upward transport of moisture via slope circulations, locally reducing CIN and increasing CAPE, and ultimately enhancing the storm longevity.
Observer‐based tracking control for switched stochastic systems based on a hybrid 2‐D model
Authors: Rathinasamy Sakthivel , Karimi Hamid Reza , K Raajananthini , Selvaraj P , Ren Yong
Published: July 2017

This paper is concerned with the observer‐based output tracking problem for a class of linear switched stochastic systems with time delay and disturbance by using repetitive control approach. More precisely, a two‐dimensional hybrid model is incorporated to obtain and optimize the repetitive controller. In particular, the repetitive controller is used to improve the tracking performance through its continuous learning actions. In addition, an equivalent‐input‐disturbance estimator is incorporated into the repetitive control design approach to reduce the effect of the external disturbances. The main aim of the control design is to track the periodic reference signal with the measured output of the system under consideration even in the presence of an unknown bounded disturbance. By constructing a suitable Lyapunov‐Krasovskii functional and using average dwell time approach and Jensen inequality, sufficient conditions are obtained in terms of linear matrix inequalities to guarantee the mean‐square exponential stability of the considered system. Eventually, a numerical example is provided to demonstrate the effectiveness of the developed method.
Participative Modelling of Socio‐Technical Transitions: Why and How Should We Look Beyond the Case‐Specific Energy Transition Challenge?
Authors: Ulli‐Beer Silvia , Kubli Merla , Zapata Juliana , Wurzinger Michael , Musiolik Jörg , Furrer Bettina
Published: July 2017

Participative modelling (PM) is a promising approach to mutual learning about causal mechanisms and dynamics in socio‐technical transitions. However, case‐specific PM initiatives often fail to generate insights that inform related cases. We address this methodical limitation in a case study on the Swiss energy transition. The central question is as follows: How can a PM workshop series be designed to create insights that go beyond the single socio‐technical transition case? Based on theorizing literature, we develop a process framework for generic PM based on system dynamics modelling and socio‐technical transition frameworks. The framework differentiates the steps in theorizing and explains how to integrate different levels of theorizing into the PM process. We illustrate how we applied the framework in our PM workshop series. Our experiences show that workshop participants employ various conceptual tools (e.g. socio‐technical frameworks or causal loop diagrams) to classify and clarify their own experience in general terms. Copyright © 2017 John Wiley & Sons, Ltd.
Dreams, agency, and judgement
Authors: Soteriou Matthew
Published: July 2017

Sosa (Proc Addresses Am Philos Assoc 79(2): 7–18, 2005) argues that we should reject the orthodox conception of dreaming—the view that dream states and waking states are “intrinsically alike, though different in their causes and effects” (2005: p. 7). The alternative he proposes is that “to dream is to imagine” (2005: p. 7). According to this imagination model of dreaming, our dreamt conscious beliefs, experiences, affirmations, decisions and intentions are not “real” insofar as they are all merely imagined beliefs, experiences, affirmations, decisions and intentions. This paper assesses the epistemic implications of Sosa’s imagination model of dreaming. Section 1 outlines and assesses the reasons Sosa gives for thinking that his imagination model of dreaming introduces a new dimension to debates about dream scepticism. Sosa argues that his imagination model of dreaming invites a more radical version of dream scepticism, and also makes available a novel and more powerful response to dream scepticism. Objections are raised to both of those claims. This leads to a challenge to Sosa’s imagination model of dreaming. This is the concern that Sosa’s imagination model of dreaming lacks the resources to accommodate the intuition that there is something illusory or misleading about one’s situation when one is dreaming, and as a result his account of dreams fails to accommodate the common intuition that there is a sceptical problem about dreaming but not about dreamless sleep. Section 2 of the paper elaborates a version of the imagination model of dreaming that can overcome that challenge. This version of the imagination model of dreaming goes beyond what Sosa explicitly commits to when he outlines his view of dreams, however, it exploits ideas that are integral to a key theme in Sosa’s recent writings on virtue reliabilism—namely his proposal that epistemic agency should be accorded a central place in that approach to knowledge, and his related proposal that agency is exercised in conscious judgement. An implication of this version of the imagination model of dreaming is that an elucidation of a connection between the wakeful condition and our capacity to exercise agency over our mental lives should be central to an account of the nature, and epistemic significance of, wakeful consciousness. The final section of the paper considers whether this version of the imagination model of dreaming has anything novel to contribute to debates about dream scepticism.
Geological Evaluation of EIGEN-6C4 and GOCE Derived Gravity Models in and around Karakoram Shear Zone, Leh, India
Authors: Roy Priyom , Krishnaveni A. Sai , Kumar K. Vinod
Published: July 2017

New generation high resolution gravity models derived from space-borne gravity data, integrated with land based surveys, have enabled understanding of regional gravity field over regions, which are till date considered to be inaccessible for land surveys, especially in mountainous terrains. In this study, we evaluate two high resolution gravity models EIGEN-6C4 and GO_CONS_GCF_2_TIM_R5 in order to understand its usability in identification of meso-scale regional geological features and lithological boundaries around the Karakoram shear zone, in Leh, India. The EIGEN-6C4 is a “hybrid” model integrating data from space-borne sensors and terrestrial data, whereas GO_CONS_GCF_2_TIM_R5 is a model derived from the latest space-borne GOCE sensor. Bouguer gravity anomaly has been derived for both the models and compared. It is seen that, the GOCE derived model pertains to the regional gravity field of the region and compares well with the regional derivative of the EIGEN-6C4 model. Further, the EIGEN-6C4 has been analyzed using horizontal derivatives (dx, dy), analytical signal (ANS) and tilt derivative (TDR) techniques. These, derived maps are then overlain on published geological map of the area to understand the correlation between sub-surface geology vis a vis gravitational signal. The major and distinct geological signatures as derived from the various derivative maps correlate well with the existing geological map. The source boundaries derived from the TDR map agrees reasonably well with the lithological boundaries. Further, the anomaly and derivative maps from EIGEN-6C4 indicates towards a possible continuation of the Shyok suture zone in the region. Therefore, for the given spatial extent of the area under consideration, the GOCE derived model represents the regional field, whereas the EIGEN-6C4 data and derivatives are of sufficient resolution for understanding the geological variability in and around the Karakoram shear zone.
Extension of Kelvin’s minimum energy theorem to incompressible fluid domains with open regions
Authors: Saad Tony , Majdalani Joseph
Published: July 2017

Kelvin’s minimum energy theorem predicts that the irrotational motion of a homogeneously incompressible fluid in a simply connected region will carry less kinetic energy than any other profile that shares the same normal velocity conditions on the domain’s boundary. In this work, Kelvin’s analysis is extended to regions with boundaries on which the normal velocity requirements are relaxed. Given the ubiquity of practical configurations in which such boundaries exist, the question of whether Kelvin’s theorem continues to hold is one of significant interest. In reconstructing Kelvin’s proof, we find it useful to define a net rotational velocity as the difference between the generally rotational flow and the corresponding potential motion. In Kelvin’s classic theorem, the normal component of the net rotational velocity at all domain boundaries is zero. In contrast, the present analysis derives a sufficient condition for ensuring the validity of Kelvin’s theorem in a domain where the normal component of net rotational velocity at some or all of the boundaries is not zero. The corresponding criterion requires the evaluation of a simple surface integral over the boundary.
Before 1962: The Case for 1950s China-India History
Authors: Ghosh Arunabh
Published: July 2017

China-India history of the 1950s remains mired in concerns related to border demarcations and a teleological focus on the causes, course, and consequences of the war of 1962. The result is an overt emphasis on diplomatic and international history of a rather narrow form. In critiquing this narrowness, this article offers an alternate chronology accompanied by two substantive case studies. Taken together, they demonstrate that an approach that takes seriously cultural, scientific, and economic life leads to different sources and different historical arguments than an approach focused on political (and especially high political) life. Such a shift in emphasis, away from conflict and onto moments of contact, comparison, cooperation, and competition, can contribute fresh perspectives not just on the histories of China and India, but also on the histories of the Global South.