bluuebunny/crossref_metadata_2025 huggingface dataset:
The valley of the fallen: a new El Escorial for Spain
Authors: Solé Queralt
Published: May 2017

Since the beginning of the twenty-first century, Spain has experienced a cycle of
exhumations of the mass graves of the Spanish Civil War (1936–39) and has rediscovered
that the largest mass grave of the state is the monument that glorifies the Franco regime:
the Valley of the Fallen. Building work in the Sierra de Guadarrama, near Madrid, was
begun in 1940 and was not completed until 1958. This article analyses for the first time
the regimes wish, from the start of the works, for the construction of the Valley of the
Fallen to outdo the monument of El Escorial. At the same time the regime sought to create
a new location to sanctify the dictatorship through the vast transfer to its crypts of the
remains of the dead of the opposing sides of the war.
Efficacy of β-lactam/β-lactamase inhibitor combination is linked to WhiB4-mediated changes in redox physiology of Mycobacterium tuberculosis
Authors: Mishra Saurabh , Shukla Prashant , Bhaskar Ashima , Anand Kushi , Baloni Priyanka , Jha Rajiv Kumar , Mohan Abhilash , Rajmani Raju S , Nagaraja Valakunja , Chandra Nagasuma , Singh Amit
Published: May 2017

Mycobacterium tuberculosis (Mtb) expresses a broad-spectrum β-lactamase (BlaC) that mediates resistance to one of the highly effective antibacterials, β-lactams. Nonetheless, β-lactams showed mycobactericidal activity in combination with β-lactamase inhibitor, clavulanate (Clav). However, the mechanistic aspects of how Mtb responds to β-lactams such as Amoxicillin in combination with Clav (referred as Augmentin [AG]) are not clear. Here, we identified cytoplasmic redox potential and intracellular redox sensor, WhiB4, as key determinants of mycobacterial resistance against AG. Using computer-based, biochemical, redox-biosensor, and genetic strategies, we uncovered a functional linkage between specific determinants of β-lactam resistance (e.g. β-lactamase) and redox potential in Mtb. We also describe the role of WhiB4 in coordinating the activity of β-lactamase in a redox-dependent manner to tolerate AG. Disruption of WhiB4 enhances AG tolerance, whereas overexpression potentiates AG activity against drug-resistant Mtb. Our findings suggest that AG can be exploited to diminish drug-resistance in Mtb through redox-based interventions.
miR‐203a‐3p.1 targets IL‐24 to modulate hepatocellular carcinoma cell growth and metastasis
Authors: Huo Wei , Du Min , Pan Xinyan , Zhu Xiaomin , Gao Yu , Li Zhimin
Published: May 2017

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer‐related death. Cytokines, including interleukin 24 (IL‐24), play an important role in HCC. IL‐24 inhibits HCC metastasis but the molecular mechanism by which this occurs is still unknown. MicroRNAs (miRNAs) are regulators of cancers including hepatocellular carcinoma (HCC). However, the role that miRNAs play in the regulation of IL‐24 in HCC is unclear. The aim of this study was to investigate the effects of regulation of IL‐24 by miR‐203a‐3p.1 on liver cancer cell proliferation and metastasis. IL‐24 mRNA and miR‐203a‐3p.1 were detected by real‐time RT‐PCR, and IL‐24 protein in the cell growth medium was measured by ELISA. A luciferase assay was used to verify that the IL‐24 gene was the target of miR‐203a‐3p.1. Cell survival ability was detected by the MTT assay and colony formation. Cell metastasis was assayed by the Transwell system. The results showed that IL‐24 could be down‐regulated by miR‐203a‐3p.1 in HCC cells and that miR‐203a‐3p.1 acted as an onco‐miRNA by targeting IL‐24. Inhibition of miR‐203a‐3p.1 in cells could lead to the reversal of HCC cell proliferation and metastasis. The study highlights a novel molecular interaction between miR‐203a‐3p.1 and IL‐24, which indicates that IL‐24 and miR‐203a‐3p.1 may constitute potential therapeutic targets for HCC.
Your act is worse than mine: Perception bias in revenge situations
Authors: Elshout Maartje , Nelissen Rob M. A. , van Beest Ilja
Published: May 2017

Theoretical reflections suggest that avengers and targets of revenge have self‐serving perception biases when judging the severity of revenge acts and preceding offenses. Empirical research investigating such biases has so far focused on either the offense or the revenge act and may have confounded a perception bias with a situational selection bias (i.e., avengers and targets selecting different events in self‐serving ways, so that there may be actual, as opposed to perceptual, differences in severity). The current research circumvents this shortcoming by empirically investigating this perception bias by assessing avengers’ and targets’ severity scores of both the offense and the revenge act, and comparing these scores with severity scores of independent raters. Results show that although there is a situational selection bias, there is also a perception bias for both avengers and targets: Both avengers and targets believe that the other person's act is worse than their own act. This perception bias may explain the existence of perpetuating revenge cycles.
AAPM Medical Physics Practice Guideline 8.a.: Linear accelerator performance tests
Authors: Smith Koren , Balter Peter , Duhon John , White Gerald A. , Vassy David L. , Miller Robin A. , Serago Christopher F. , Fairobent Lynne A.
Published: May 2017

Purpose

The purpose of this guideline is to provide a list of critical performance tests in order to assist the Qualified Medical Physicist (QMP) in establishing and maintaining a safe and effective quality assurance (QA) program. The performance tests on a linear accelerator (linac) should be selected to fit the clinical patterns of use of the accelerator and care should be given to perform tests which are relevant to detecting errors related to the specific use of the accelerator.

Methods

A risk assessment was performed on tests from current task group reports on linac QA to highlight those tests that are most effective at maintaining safety and quality for the patient. Recommendations are made on the acquisition of reference or baseline data, the establishment of machine isocenter on a routine basis, basing performance tests on clinical use of the linac, working with vendors to establish QA tests and performing tests after maintenance.

Results

The recommended tests proposed in this guideline were chosen based on the results from the risk analysis and the consensus of the guideline's committee. The tests are grouped together by class of test (e.g., dosimetry, mechanical, etc.) and clinical parameter tested. Implementation notes are included for each test so that the QMP can understand the overall goal of each test.

Conclusion

This guideline will assist the QMP in developing a comprehensive QA program for linacs in the external beam radiation therapy setting. The committee sought to prioritize tests by their implication on quality and patient safety. The QMP is ultimately responsible for implementing appropriate tests. In the spirit of the report from American Association of Physicists in Medicine Task Group 100, individual institutions are encouraged to analyze the risks involved in their own clinical practice and determine which performance tests are relevant in their own radiotherapy clinics.
Conductive Metal–Organic Framework Nanowire Array Electrodes for High‐Performance Solid‐State Supercapacitors
Authors: Li Wen‐Hua , Ding Kui , Tian Han‐Rui , Yao Ming‐Shui , Nath Bhaskar , Deng Wei‐Hua , Wang Yaobing , Xu Gang
Published: May 2017

The application of conventional metal–organic frameworks (MOFs) as electrode materials in supercapacitors is largely hindered by their conventionally poor electrical conductivity. This study reports the fabrication of conductive MOF nanowire arrays (NWAs) and the application of them as the sole electrode material for solid‐state supercapacitors. By taking advantage of the nanostructure and making full use of the high porosity and excellent conductivity, the MOF NWAs in solid‐state supercapacitor show the highest areal capacitance and best rate performance of all reported MOF materials for supercapacitors, which is even comparable to most carbon materials.
Reduced Interface‐Mediated Recombination for High Open‐Circuit Voltages in CH3NH3PbI3 Solar Cells
Authors: Wolff Christian M. , Zu Fengshuo , Paulke Andreas , Toro Lorena Perdigón , Koch Norbert , Neher Dieter
Published: May 2017

Perovskite solar cells with all‐organic transport layers exhibit efficiencies rivaling their counterparts that employ inorganic transport layers, while avoiding high‐temperature processing. Herein, it is investigated how the choice of the fullerene derivative employed in the electron‐transporting layer of inverted perovskite cells affects the open‐circuit voltage (VOC). It is shown that nonradiative recombination mediated by the electron‐transporting layer is the limiting factor for the VOC in the cells. By inserting an ultrathin layer of an insulating polymer between the active CH3NH3PbI3 perovskite and the fullerene, an external radiative efficiency of up to 0.3%, a VOC as high as 1.16 V, and a power conversion efficiency of 19.4% are realized. The results show that the reduction of nonradiative recombination due to charge‐blocking at the perovskite/organic interface is more important than proper level alignment in the search for ideal selective contacts toward high VOC and efficiency.
Optical Properties of Plasmonic Ultrathin TiN Films
Authors: Shah Deesha , Reddy Harsha , Kinsey Nathaniel , Shalaev Vladimir M. , Boltasseva Alexandra
Published: May 2017

Overcoming the challenge of growing ultrathin metallic films is of great importance for practical applications of nanoplasmonic structures. In the present work, epitaxial, ultrathin (<10 nm) films of plasmonic TiN are grown on MgO using DC reactive magnetron sputtering. The optical properties of the films are studied through variable angle spectroscopic ellipsometry and Hall measurements. As the film thickness decreases, they become less metallic and exhibit higher loss while still remaining plasmonic in the optical range. These trends are related to the decreasing carrier concentration in the thinner films and increased scattering, respectively. However, all films tested (2, 4, 6, 8, and 10 nm) still remain highly metallic with a carrier concentration on the order of 1022 cm−3. Based on the relationship between the plasma frequency, carrier concentration, and effective mass, it is determined that the reduction in carrier concentration plays the main role in defining the film's optical properties, as variations in the effective mass are found to be minimal for thicknesses above 4 nm. However, for the 2 nm film and below, theoretical calculations begin to deviate from experimental values.
Development of a Global Health Milestones Tool for Learners in Emergency Medicine: A Pilot Project
Authors: Douglass Katherine A. , Jacquet Gabrielle A. , Hayward Alison S. , Dreifuss Bradley A. , Tupesis Janis P.
Published: May 2017

Objectives

In medical education and training, increasing numbers of institutions and learners are participating in global health experiences. Within the context of competency‐based education and assessment methodologies, a standardized assessment tool may prove valuable to all of the aforementioned stakeholders. Milestones are now used as the standard for trainee assessment in graduate medical education. Thus, the development of a similar, milestone‐based tool was undertaken, with learners in emergency medicine (EM) and global health in mind.

Methods

The Global Emergency Medicine Think Tank Education Working Group convened at the 2016 Society for Academic Medicine Annual Meeting in New Orleans, Louisiana. Using the Interprofessional Global Health Competencies published by the Consortium of Universities for Global Health's Education Committee as a foundation, the working group developed individual milestones based on the 11 stated domains. An iterative review process was implemented by teams focused on each domain to develop a final product.

Results

Milestones were developed in each of the 11 domains, with five competency levels for each domain. Specific learning resources were identified for each competency level and assessment methodologies were aligned with the milestones framework. The Global Health Milestones Tool for learners in EM is designed for continuous usage by learners and mentors across a career.

Conclusions

This Global Health Milestones Tool for learners in EM may prove valuable to numerous stakeholders. The next steps include a formalized pilot program for testing the tool's validity and usability across training programs, as well as an assessment of perceived utility and applicability by collaborating colleagues working in training sites abroad.
Marine Fungi Against Aquaculture Pathogens and Induction of the Activity via Co‐Culture
Authors: Özkaya Ferhat Can , Peker Zerife , Camas Mustafa , Sazak Camas Anil , Altunok Muhammet
Published: May 2017

Ethyl acetate extracts from 70 strains of marine‐derived fungi, isolated from sponges, were screened against four fish pathogenic bacteria. Sixteen of the fungal isolates exhibited antibacterial activity against at least one pathogen. All the strains showed antibacterial activity against Vagococcus salmoninarum. Three isolates showed strong inhibition against all test pathogens and they may therefore be remarkable as a broad‐spectrum antimicrobial. Nine isolates showed antibacterial activity against Lactococcus garvieae, six were against Vibrio anguillarum, and four isolates inhibited the growth of Yersinia ruckeri. Co‐culture of the fungus with the mix of the pathogen bacteria led to the induction of bioactivity in two isolates. Aspergillus iizukae produced strong and broad‐spectrum antibacterial activity against pathogens with minimum inhibitory concentrations of 0.8–406 μg mL−1. The screening results confirmed the sponge associated fungi as a source of environmentally friendly antimicrobials that may contribute the sustainable development of aquaculture. In addition, co‐culture technique is a promising strategy to increase antimicrobial activity that can stimulate the production of novel compounds, and increases the antimicrobial activities of marine derived fungi.
Pharmacometric Modeling of Naloxegol Efficacy and Safety: Impact on Dose and Label
Authors: Al‐Huniti N , Zhou D , Xu H , Aksenov S , Bui KH , Fox R , Helmlinger G , Stanski D
Published: May 2017

Naloxegol is a peripherally acting μ‐opioid receptor antagonist that was developed for the treatment of opioid‐induced constipation. Modeling and simulation of naloxegol efficacy and tolerability informed selection of doses for phase III studies and provided comprehensive dosage recommendations for the naloxegol US package insert.
Improving inference for aerial surveys of bears: The importance of assumptions and the cost of unnecessary complexity
Authors: Schmidt Joshua H. , Wilson Tammy L. , Thompson William L. , Reynolds Joel H.
Published: May 2017

Obtaining useful estimates of wildlife abundance or density requires thoughtful attention to potential sources of bias and precision, and it is widely understood that addressing incomplete detection is critical to appropriate inference. When the underlying assumptions of sampling approaches are violated, both increased bias and reduced precision of the population estimator may result. Bear (Ursusspp.) populations can be difficult to sample and are often monitored using mark‐recapture distance sampling (MRDS) methods, although obtaining adequate sample sizes can be cost prohibitive. With the goal of improving inference, we examined the underlying methodological assumptions and estimator efficiency of three datasets collected under anMRDSprotocol designed specifically for bears. We analyzed these data usingMRDS, conventional distance sampling (CDS), and open‐distance sampling approaches to evaluate the apparent bias‐precision tradeoff relative to the assumptions inherent under each approach. We also evaluated the incorporation of informative priors on detection parameters within a Bayesian context. We found that theCDSestimator had low apparent bias and was more efficient than the more complexMRDSestimator. When combined with informative priors on the detection process, precision was increased by >50% compared to theMRDSapproach with little apparent bias. In addition, open‐distance sampling models revealed a serious violation of the assumption that all bears were available to be sampled. Inference is directly related to the underlying assumptions of the survey design and the analytical tools employed. We show that for aerial surveys of bears, avoidance of unnecessary model complexity, use of prior information, and the application of open population models can be used to greatly improve estimator performance and simplify field protocols. Although we focused on distance sampling‐based aerial surveys for bears, the general concepts we addressed apply to a variety of wildlife survey contexts.
Local scale processes drive long‐term change in biodiversity of sandy beach ecosystems
Authors: Schooler Nicholas K. , Dugan Jenifer E. , Hubbard David M. , Straughan Dale
Published: May 2017

Evaluating impacts to biodiversity requires ecologically informed comparisons over sufficient time spans. The vulnerability of coastal ecosystems to anthropogenic and climate change‐related impacts makes them potentially valuable indicators of biodiversity change. To evaluate multidecadal change in biodiversity, we compared results from intertidal surveys of 13 sandy beaches conducted in the 1970s and 2009–11 along 500 km of coast (California, USA). Using a novel extrapolation approach to adjust species richness for sampling effort allowed us to address data gaps and has promise for application to other data‐limited biodiversity comparisons. Long‐term changes in species richness varied in direction and magnitude among beaches and with human impacts but showed no regional patterns. Observed long‐term changes in richness differed markedly among functional groups of intertidal invertebrates. At the majority (77%) of beaches, changes in richness were most evident for wrack‐associated invertebrates suggesting they have disproportionate vulnerability to impacts. Reduced diversity of this group was consistent with long‐term habitat loss from erosion and sea level rise at one beach. Wrack‐associated species richness declined over time at impacted beaches (beach fill and grooming), despite observed increases in overall intertidal richness. In contrast richness of these taxa increased at more than half (53%) of the beaches including two beaches recovering from decades of off‐road vehicle impacts. Over more than three decades, our results suggest that local scale processes exerted a stronger influence on intertidal biodiversity on beaches than regional processes and highlight the role of human impacts for local spatial scales. Our results illustrate how comparisons of overall biodiversity may mask ecologically important changes and stress the value of evaluating biodiversity change in the context of functional groups. The long‐term loss of wrack‐associated species, a key component of sandy beach ecosystems, documented here represents a significant threat to the biodiversity and function of coastal ecosystems.
The effect of interpregnancy interval on obesity/overweight among women in the first trimester of pregnancy
Authors: Ali Elrazi A. , Almugabil Abdelmageed , Salim Ala , Rayis Duria A. , Adam Ishag
Published: May 2017

Objective

To determine the effect of interpregnancy interval (IPI) on obesity/overweight among pregnant Sudanese women in early pregnancy.

Methods

A cross‐sectional study was conducted at Saad Abu‐Alela Hospital, Khartoum, Sudan, from January to December 2015. Women with a singleton pregnancy and at least one previous pregnancy were enrolled in the first trimester. A questionnaire was used to collect clinical and sociodemographic data from the participants, and current body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters.

Results

Among 1045 participants, 344 (32.9%), 424 (40.6%), and 277 (26.5%) women had short (<18 months), normal (18–30 months), and long IPIs (>30 months), respectively. BMI indicated 18 (1.7%), 408 (39.0%), 381 (36.5%), and 238 (22.8%) women were underweight (<18.5), normal weight (18.5–24.9), overweight (25.0–29.9), and obese (≥30.0), respectively. Age and proportion using contraceptives were increased among women with long IPI (both P<0.001). When compared with women of normal weight, overweight women and obese women were more likely to have a long IPI (odds ratio 1.72, 95% confidence interval 1.08–2.93; and 1.71, 1.05–2.94, respectively).

Conclusion

Long IPI was associated with obesity and overweight, which were prevalent among pregnant Sudanese women.
Microwave‐assisted Synthesis of Thioesters from Aldehydes and Thiols in Water
Authors: Jhuang Huei‐Shu , Liu Yi‐Wei , Reddy Daggula Mallikarjuna , Tzeng Yong‐Ze , Lin Wei‐Yu , Lee Chin‐Fa
Published: May 2017

We describe the synthesis of thioesters via copper‐ or iron‐catalyzed coupling of thiols with aldehydes on application of microwave irradiation. In this protocol, a variety of aliphatic and aromatic aldehydes and thiols were used, and the products were obtained in good to excellent yields.
High‐grade dysplasia/carcinoma in situ of the bile duct margin in patients with surgically resected node‐negative perihilar cholangiocarcinoma is associated with poor survival: a retrospective study
Authors: Higuchi Ryota , Yazawa Takehisa , Uemura Shuichiro , Izumo Wataru , Furukawa Toru , Yamamoto Masakazu
Published: May 2017

Background

The clinical relevance of a high‐grade dysplasia/carcinoma in situ (HD/CIS)‐positive bile duct margin in perihilar cholangiocarcinoma (PHC) is unclear. We evaluated the surgical outcomes of PHC patients with HD/CIS.

Methods

Clinicopathological data of 163 consecutive patients who underwent resection of PHC between 2004 and 2013 were analyzed retrospectively.

Results

Postoperative states included curative resection (R0) with free margins in 113 patients, non‐curative resection with HD/CIS (R1‐HD/CIS) in 22 patients, and non‐curative resection with any invasive carcinoma margin in 28 patients. Multivariate analyses in the entire cohort showed that lymph node metastasis (hazard ratio [HR] 1.91), distant metastasis (HR 3.87), and non‐curative resection with any invasive carcinoma margin (vs. R0; HR 2.06) were significant independent prognosticators. However, in node‐negative and distant metastasis‐negative PHC patients, histology (HR 2.97), R1‐HD/CIS (vs. R0; HR 2.31), and non‐curative resection with any invasive carcinoma margin (vs. R0; HR 5.33) were significant independent prognosticators. The 2‐ and 5‐year disease‐specific survival rates in node‐negative and distant metastasis‐negative PHC patients with R1‐HD/CIS margins were lower compared with those in patients with R0 margins (2‐year, 76.7% vs. 84.3%; 5‐year, 37.5% vs. 69.3%; P = 0.026).

Conclusions

R1‐HD/CIS should be avoided in patients undergoing surgery for node‐negative and distant metastasis‐negative PHC.
The possible role of CCR5Δ32 mutation in Crimean‐Congo hemorrhagic fever infection
Authors: Rustemoglu Aydin , Ekinci Duygu , Nursal Ayşe F. , Barut Sener , Duygu Fazilet , Günal Özgür
Published: May 2017

Crimean‐Congo hemorrhagic fever infection (CCHF) is a viral zoonosis. The pathogenesis of this disease has not been established so far, however, cytokines account for its progression and outcome. The aim of the present study is to investigate the association between chemokine receptor 5 (CCR5) gene Δ32 mutation and pathogenity, severity, and mortality of CCHF. This case‐control study included 133 CCHF patients diagnosed by detection of CCHV RNA positivity and 97 healthy control subjects. CCR5 gene Δ32 mutation analyzed by polymerase chain reaction (PCR) method. The results were compared by using SPSS 16.0 and WINPEPI software's. The genotype distribution and allele frequency of the CCR5Δ32 were statistically different between the patients and the control group (P = 0.017; OR: 4.98 95% CI = 1.65‐14.99 and P = 0.019; OR:4.76 95%CI = 1.30‐17.50, respectively). CCR5/CCR5 (W/W) genotype and W allele of CCR5 gene were more common in patient group than in controls. There was no significant difference in severe and mild cases with regard to genotype distribution and allele distribution of CCR5Δ32 mutation (P >0.05). These results suggest that the CCR5 gene and its product might play a role in the pathogenesis of CCHF disease. Future studies will help us to uncover the exact role of CCR5 in the pathogenesis and prognosis of CCHF and to treat the disease.
Can freshwater phytoplankton access cadmium bound to low‐molecular‐weight thiols?
Authors: Liu Fengjie , Fortin Claude , Campbell Peter G. C.
Published: May 2017

Recent studies have suggested that low‐molecular‐weight (LMW) ligands can enhance trace metal uptake by marine diatoms. We have extended this work to freshwater phytoplankton and have investigated Cd bioavailability in the presence of LMW thiols, with two green algae (Chlamydomonas reinhardtii and Pseudokirchneriella subcapitata) and a cyanobacterium (Anabaena flos‐aquae). Using nitrilotriacetic acid (NTA) to hold the free Cd2+ concentration constant, we progressively added cysteine to the exposure medium and determined short‐term Cd uptake rates for each organism; the Cd uptake rates remained constant and were unaffected even when the concentrations of the Cd‐cysteine complexes exceeded that of the free Cd2+. Similar results were obtained with algae pre‐acclimated to different nitrogen sources or low zinc concentrations, even though such treatments affect their ability to utilize amino acids or take up Cd. A lack of effect was also observed for the two green algae with penicillamine, mercaptosuccinic acid, dithiothreitol and glutathione. These results suggest that the Cd‐thiol complexes do not contribute to Cd uptake. However, when the experiments were repeated with cysteine in the absence of NTA, at the same Cd2+ concentration, a significantly higher Cd uptake rate was observed in the presence of the L‐ or D‐cysteine stereoisomers than in the presence of NTA. This enhancement of Cd uptake in the presence of cysteine alone was sensitive to the nitrogen nutrition of these microorganisms, and we suggest that the enhancement likely results from biologically‐induced chemical oxidation of cysteine in the boundary layer adjacent to the algal cell.
Photocontrolled Living Polymerization Systems with Reversible Deactivations through Electron and Energy Transfer
Authors: Shanmugam Sivaprakash , Xu Jiangtao , Boyer Cyrille
Published: May 2017

Recently, visible‐light‐regulated polymerization has been gaining popularity, as it opens a range of new opportunities for the synthesis of functional polymers and materials. Here, the most recent developments in this field are summarized, which is the use of photocatalysts and catalyst‐free approaches to mediate polymerization upon photoexcitation. These catalysts can transfer an electron or energy to activate an initiator. The recent achievements in light‐regulated atom‐transfer radical polymerization, reversible addition‐fragmentation chain‐transfer polymerization, ring‐opening metathesis polymerization, cobalt‐mediated radical polymerization, iodine‐mediated radical polymerization, and living cationic polymerization are reviewed. Recent development in these fields have solved important challenges in polymer chemistry, such as the development of oxygen‐tolerant polymerization, polymerization mediated by near‐infrared, metal‐free polymerization, and spatial‐, temporal‐, and sequence‐controlled polymerization. Some applications of these techniques will be discussed, such as adapting the current photocatalytic systems to synthesize heterogeneous photocatalysts that act as recyclable photocatalysts and novel light‐mediated approaches for surface functionalization of hybrid materials and living cells. Finally, the existing challenges in polymer chemistry that could be overcome by further development of light‐mediated polymerization techniques are highlighted along with the future directions of this field.

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Contract design in dynamic agency: An experimental analysis
Authors: Lukas Christian
Published: May 2017

This paper reports results from an experiment studying contract design in a dynamic 2‐period agency relationship with unobservable effort. A deferred compensation contract is theoretically optimal—it places all incentives on the outcomes in the second period. Observed contract choices offer a substantial part of the incentives for the high outcome in the first period suggesting a strong preference for timely rewards. Information about theoretically optimal bonuses and effort decisions shifts contract choices towards a deferred compensation contract. This contract structure is more profitable for principal participants.
Future of medical physics: Real‐time MRI‐guided proton therapy
Authors: Oborn Bradley M. , Dowdell Stephen , Metcalfe Peter E. , Crozier Stuart , Mohan Radhe , Keall Paul J.
Published: May 2017

With the recent clinical implementation of real‐time MRI‐guided x‐ray beam therapy (MRXT), attention is turning to the concept of combining real‐time MRI guidance with proton beam therapy; MRI‐guided proton beam therapy (MRPT). MRI guidance for proton beam therapy is expected to offer a compelling improvement to the current treatment workflow which is warranted arguably more than for x‐ray beam therapy. This argument is born out of the fact that proton therapy toxicity outcomes are similar to that of the most advanced IMRT treatments, despite being a fundamentally superior particle for cancer treatment.

In this Future of Medical Physics article, we describe the various software and hardware aspects of potential MRPT systems and the corresponding treatment workflow. Significant software developments, particularly focused around adaptive MRI‐based planning will be required. The magnetic interaction between the MRI and the proton beamline components will be a key area of focus. For example, the modeling and potential redesign of a magnetically compatible gantry to allow for beam delivery from multiple angles towards a patient located within the bore of an MRI scanner. Further to this, the accuracy of pencil beam scanning and beam monitoring in the presence of an MRI fringe field will require modeling, testing, and potential further development to ensure that the highly targeted radiotherapy is maintained.

Looking forward we envisage a clear and accelerated path for hardware development, leveraging from lessons learnt from MRXT development. Within few years, simple prototype systems will likely exist, and in a decade, we could envisage coupled systems with integrated gantries. Such milestones will be key in the development of a more efficient, more accurate, and more successful form of proton beam therapy for many common cancer sites.
Metastatic angiosarcoma arising in malignant peripheral nerve sheath tumor in a young patient with neurofibromatosis type 1
Authors: Winters Amanda C. , Black Jennifer O. , Cost Carrye R.
Published: May 2017

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of approximately one in 3,000 and a lifetime risk of malignancy estimated at 8–13%. Here, we report the case of a patient with NF1 who developed synchronous malignant peripheral nerve sheath tumors, one with a focus of angiosarcoma. He succumbed to metastatic angiosarcoma despite local resection and adjuvant chemotherapy. This case highlights the need for monitoring for malignancy in NF1 patients, the risks of sampling error during tumor biopsy, and the clinical decision ‐ making involved in choosing a therapeutic plan for a patient with multiple simultaneous malignancies.
Analysis of electrical and dynamic mechanical response of conductive elastomeric composites subjected to cyclic deformations and temperature
Authors: Sethi Deepak , Ram Ranvijai , Khastgir Dipak
Published: May 2017

Effects of different mechanical deformations such as cyclic bending and compressive flexing and temperature on electrical and dynamic mechanical properties of elastomeric composites have been investigated. Conductive elastomeric composites were prepared by incorporating different carbon blacks in an insulating polychloroprene (CR) rubber matrix. The filler loading was varied between 10 and 110 phr (parts per hundred rubber) i/r/o different carbon blacks to assess the percolation threshold of different composites. Due to the spatial arrangement of conductive filler particles at certain critical concentration, some conducting networks are formed leading to abrupt increase in conductivity of polymer composites. This critical concentration is known as percolation threshold. The increase in conductivity well below and above percolation threshold is relatively less compared to that around percolation. The variation of electrical conductivity and dynamic mechanical modulus due to bending and compressive flexing are found to be similar, that is, both characteristics show a drop in magnitude with increase in number of flex cycles. The conductivity of system changes when composites are subjected to changes in temperature. This is mainly due to the destruction of existing conducting networks as well as formation of some new conducting networks. The net change depends on the degree of formation or destruction of networks. It is interesting to see that conductivity does not follow the same path during heating–cooling cycles thereby causing electrical hysteresis. POLYM. COMPOS., 39:3912–3923, 2018. © 2017 Society of Plastics Engineers
Comparison between chaotropic and detergent‐based sample preparation workflow in tendon for mass spectrometry analysis
Authors: Ashraf Kharaz Yalda , Zamboulis Danae , Sanders Karen , Comerford Eithne , Clegg Peter , Peffers Mandy
Published: May 2017

Exploring the tendon proteome is a challenging but important task for understanding the mechanisms of physiological/pathological processes during ageing and disease and for the development of new treatments. Several extraction methods have been utilised for tendon mass spectrometry, however different extraction methods have not been simultaneously compared. In the present study we compared protein extraction in tendon with two chaotropic agents, guanidine hydrochloride (GnHCl) and urea, a detergent, RapiGest™, and their combinations for shotgun mass spectrometry. An initial proteomic analysis was performed following urea, GnHCl, and RapiGest™ extraction of equine superficial digital flexor tendon (SDFT) tissue. Subsequently, another proteomic analysis was performed following extraction with GnHCl, Rapigest™, and their combinations. Between the two chaotropic agents, GnHCl extracted more proteins, whilst a greater number of proteins were solely identified after Rapigest™ extraction. Protein extraction with a combination of GnHCl followed by RapiGest™ on the insoluble pellet demonstrated, after label‐free quantification, increased abundance of identified collagen proteins and low sample to sample variability. In contrast, GnHCl extraction on its own showed increased abundance of identified proteoglycans and cellular proteins. Therefore, the selection of protein extraction method for tendon tissue for mass spectrometry analysis should reflect the focus of the study.
Monitoring bivariate and trivariate mean vectors with a Shewhart chart
Authors: Leoni Roberto Campos , Costa Antonio Fernando Branco
Published: May 2017

In this article, we propose the use of the mean chart to control multivariate processes. The basic idea is to control the mean vector of bivariate (X, Y) and trivariate (X, Y, Z) processes by alternating the charting statistic of the Shewhart chart. If the mean of X observations was the charting statistic to obtain the current sample point, then the mean of Y observations will be the charting statistic to obtain the next sample point (for the trivariate case, the mean of Z observations will be the charting statistic to obtain the sample point subsequent to the next one). As a Shewhart chart, the signal is given anytime a sample point is plotted beyond the control limits, independent of the charting statistic in use. A fair comparison between the proposed chart and the Hotelling chart is based on an equal number of measurements per sample. The Shewhart chart with alternated charting statistic (ACS) always outperforms the Hotelling chart, except for specific types of disturbances in quality characteristics highly correlated (ρ = 0.7). The ACS chart is substantially easier to operate and faster than the Hotelling chart in signaling changes in the mean vector of bivariate and trivariate processes. Even with fewer measurements per sample, the trivariate ACS chart outperforms the Hotelling chart.
Zanthoxylum avicennae extract enhances GSK‐3β to attenuate β‐catenin via phosphatase 2A to block metastatic effects of HA22T cells and hepatocellular carcinoma xenografted nude mice
Authors: Wu Hsi‐Chin , Lay Ing‐Shiow , Shibu Marthandam Asokan , Ho Tsung‐Jung , Cheng Shiu‐Min , Lin Chih‐Hao , Dung Tran Duc , Jeng Long‐Bin , Viswanadha Vijaya Padma , Huang Chih‐Yang
Published: May 2017

Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/β‐catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on β‐catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock‐down assays and co‐immunoprecipitation assay. Additionally, the HA22T‐implanted xenograft nude mice were used to confirm the assessed cellular effects. Mice treated with YBBEs showed a strong increasing trend in PP2Acα, GSK‐3β, APC, and β‐TrCP/HOS levels, however the expression of β‐catenin, p‐GSK‐3β, TBX 3, and IL8 proteins showed a decreasing trend. YBBE significantly downregulated the nuclear and cytosolic β‐catenin levels by facilitating the proteosomal degradation of β‐catenin. Moreover, as observed by co‐immunoprecipitation assay, YBBE directly promoted the protein interactions between GSK‐3β, β‐TrCP, APC, PP2A, and β‐catenin. In conclusion, both in vitro and in vivo models clearly demonstrated that YBBE inhibits β‐catenin involved metastatic signaling in highly metastatic HA22T cells through PP2A activation.
Predictive Business Process Monitoring Considering Reliability Estimates
Authors: Metzger Andreas , Föcker Felix
Published: May 2017

Predictive business process monitoring aims at predicting potential problems during process execution so that these problems can be proactively managed and mitigated. Compared to aggregate prediction accuracy indicators (e.g., precision or recall), prediction reliability estimates provide additional information about the prediction error for an individual business process. Intuitively, it appears appealing to consider reliability estimates when deciding on whether to adapt a running process instance or not. However, we lack empirical evidence to support this intuition, as research on predictive business process monitoring focused on aggregate prediction accuracy. We experimentally analyze the effect of considering prediction reliability estimates for proactive business process adaptation. We use ensemble prediction techniques, which we apply to an industry data set from the transport and logistics domain. In our experiments, proactive business process adaptation in general had a positive effect on cost in 52.5% of the situations. In 82.9% of these situations, considering reliability estimates increased the positive effect, leading to cost savings of up to 54%, with 14% savings on average.
Translating theLife of Antichristinto German and Czech in the Early Modern Period
Authors: Fidlerová Alena A.
Published: May 2017

Based on a sociocultural and functional approach to the history of translation, this article introduces theLeben Antichristiby the German Capuchin and famous preacher Dionysius of Luxemburg, first published in 1682 at Frankfurt am Main, as an example of the transmission of formerly elite content to a popular readership via its translation into simple vernacular prose. It then discusses possible reasons why three Czech translations of the book, created independently during the eighteenth century and preserved in manuscript, were never printed, although the German version went through twelve editions and similar works by Dionysius's fellow brother Martin of Cochem were among the most often printed books of the Czech Baroque.
Und was ist mit dem Patienten?
Authors: Sigg Babette
Published: May 2017

Zusammenfassung. Die Frage nach den Bedürfnissen und Erwartungen der Schweizer Konsumenten im Gesundheitswesen ist durchaus berechtigt. Nicht zuletzt, weil sie sich nicht eindeutig beantworten lässt. Konsumenten gibt es viele, nicht jeder Konsument ist Patient und Bedürfnisse und Erwartungen sind individuell. Dennoch hält die Literatur fest: Am wichtigsten sind den Konsumenten in der Schweiz tiefe Prämien und Selbstzahlungsbeiträge. Für den Patienten ist die Kommunikation und die gemeinsame Entscheidungsfindung zwischen Arzt und Patient das A und O einer guten Gesundheitsversorgung. Was, wenn die Beziehungskontinuität zwischen Arzt und Patient in einer Zeit der sich wandelnden Gesundheitsversorgung nicht mehr gewährleistet werden kann? Sowohl chronische Krankheiten als auch neue Versorgungskonzepte durch Einbezug neuer Berufsgruppen werden die Behandlung von morgen fragmentieren. Nebst verschiedenster Entwicklungen im Bereich der Informationskontinuität und Digitalisierung ist das Gesundheitswesen immer mehr auf engagierte Patienten angewiesen. Ein Patient ist dann engagiert, wenn er sich Gesundheitskompetenzen aneignet und in der Lage ist, Missstände auszusprechen. Und um sich in der Gesellschaft Gehör zu verschaffen, muss es dem Patienten gelingen, Koalitionen einzugehen.
Human IgG2‐ and IgG4‐expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age
Authors: de Jong Britt G , IJspeert Hanna , Marques Lemelinda , van der Burg Mirjam , van Dongen Jacques JM , Loos Bruno G , van Zelm Menno C
Published: May 2017

The mechanisms involved in sequential immunoglobulin G (IgG) class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on blood mononuclear cells from young children and adults as models for primary and secondary immunological memory. Additional sequencing and detailed immunophenotyping with IgG subclass‐specific antibodies was performed on purified IgG+ memory B‐cell subsets. In both children and adults, SHM levels were higher in transcripts involving more downstream‐located IGHG genes (esp. IGHG2 and IGHG4). In adults, SHM levels were significantly higher than in children, and downstream IGHG genes were more frequently utilized. This was associated with increased frequencies of CD27+IgG+ memory B cells, which contained higher levels of SHM, more IGHG2 usage, and higher expression levels of activation markers than CD27−IgG+ memory B cells. We conclude that secondary immunological memory accumulates with age and these memory B cells express CD27, high levels of activation markers, and carry high SHM levels and frequent usage of IGHG2. These new insights contribute to our understanding of sequential IgG subclass switching and show a potential relevance of using serum IgG2 levels or numbers of IgG2‐expressing B cells as markers for efficient generation of memory responses.
Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations
Authors: Chang Jiang , Tan Wenle , Ling Zhiqiang , Xi Ruibin , Shao Mingming , Chen Mengjie , Luo Yingying , Zhao Yanjie , Liu Yun , Huang Xiancong , Xia Yuchao , Hu Jinlin , Parker Joel S. , Marron David , Cui Qionghua , Peng Linna , Chu Jiahui , Li Hongmin , Du Zhongli , Han Yaling , Tan Wen , Liu Zhihua , Zhan Qimin , Li Yun , Mao Weimin , Wu Chen , Lin Dongxin
Published: May 2017

Approximately half of the world’s 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy
Authors: Cabral Maria P. , García Patricia , Beceiro Alejandro , Rumbo Carlos , Pérez Astrid , Moscoso Miriam , Bou Germán
Published: May 2017

Vaccine development is a priority for global health due to the growing multidrug resistance in bacteria. D-glutamate synthesis is essential for bacterial cell wall formation. Here we present a strategy for generating effective bacterial whole-cell vaccines auxotrophic for D-glutamate. We apply this strategy to generate D-glutamate auxotrophic vaccines for three major pathogens, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. These bacterial vaccines show virulence attenuation and self-limited growth in mice, and elicit functional and cross-reactive antibodies, and cellular immunity. These responses correlate with protection against acute lethal infection with other strains of the same species, including multidrug resistant, virulent and/or high-risk clones such as A. baumannii AbH12O-A2 and Ab307-0294, P. aeruginosa PA14, and community-acquired methicillin-resistant S. aureus USA300LAC. This approach can potentially be applied for the development of live-attenuated vaccines for virtually any other bacterial pathogens, and does not require the identification of virulence determinants, which are often pathogen-specific.
All pure bipartite entangled states can be self-tested
Authors: Coladangelo Andrea , Goh Koon Tong , Scarani Valerio
Published: May 2017

Quantum technologies promise advantages over their classical counterparts in the fields of computation, security and sensing. It is thus desirable that classical users are able to obtain guarantees on quantum devices, even without any knowledge of their inner workings. That such classical certification is possible at all is remarkable: it is a consequence of the violation of Bell inequalities by entangled quantum systems. Device-independent self-testing refers to the most complete such certification: it enables a classical user to uniquely identify the quantum state shared by uncharacterized devices by simply inspecting the correlations of measurement outcomes. Self-testing was first demonstrated for the singlet state and a few other examples of self-testable states were reported in recent years. Here, we address the long-standing open question of whether every pure bipartite entangled state is self-testable. We answer it affirmatively by providing explicit self-testing correlations for all such states.