bluuebunny/crossref_metadata_2025 huggingface dataset:
Notes on pedal and contrapedal curves of fronts in the Euclidean plane
Authors: Tuncer O. Oğulcan , Ceyhan Hazal , Gök İsmail , Ekmekci F. Nejat
Published: May 2018

A pedal curve (a contrapedal curve) of a regular plane curve is the locus of the feet of the perpendiculars from a point to the tangents (normals) to the curve. These curves can be parametrized by using the Frenet frame of the curve. Yet provided that the curve has some singular points, the Frenet frame at these singular points is not well‐defined. Thus, we cannot use the Frenet frame to examine pedal or contrapedal curves. In this paper, pedal and contrapedal curves of plane curves, which have singular points, are investigated. By using the Legendrian Frenet frame along a front, the pedal and contrapedal curves of a front are introduced and properties of these curves are given. Then, the condition for a pedal (and a contrapedal) curve of a front to be a frontal is obtained. Furthermore, by considering the definitions of the evolute, the involute, and the offset of a front, some relationships are given. Finally, some illustrated examples are presented.
NMR crystallography of zeolites: How far can we go without diffraction data?
Authors: Brouwer Darren H. , Van Huizen Jared
Published: May 2018

Nuclear magnetic resonance (NMR) crystallography—an approach to structure determination that seeks to integrate solid‐state NMR spectroscopy, diffraction, and computation methods—has emerged as an effective strategy to determine structures of difficult‐to‐characterize materials, including zeolites and related network materials. This paper explores how far it is possible to go in determining the structure of a zeolite framework from a minimal amount of input information derived only from solid‐state NMR spectroscopy. It is shown that the framework structure of the fluoride‐containing and tetramethylammonium‐templated octadecasil clathrasil material can be solved from the 1D 29Si NMR spectrum and a single 2D 29Si NMR correlation spectrum alone, without the space group and unit cell parameters normally obtained from diffraction data. The resulting NMR‐solved structure is in excellent agreement with the structures determined previously by diffraction methods. It is anticipated that NMR crystallography strategies like this will be useful for structure determination of other materials, which cannot be solved from diffraction methods alone.
DNA methylation pattern of bovine blastocysts associated with hyperinsulinemia in vitro
Authors: Laskowski Denise , Humblot Patrice , Sirard Marc‐André , Sjunnesson Ylva , Jhamat Naveed , Båge Renée , Andersson Göran
Published: May 2018

Insulin functions as a regulator of metabolism and plays an important role in reproduction. Hyperinsulinemia is often observed in patients with obesity and diabetes type 2 and is known to impair fertility, but the underlying molecular mechanisms are only partly understood. Metabolic programming through epigenetic mechanisms such as DNA methylation during embryonic development can lead to health implications for the offspring later in life. Our aim was to study the potential effect of hyperinsulinemia on gene expression and DNA methylation of embryos by adding insulin (0.1 µg/ml = INS0.1 or 10 µg/ml = INS10) during in vitro oocyte maturation by using the EmbryoGENE DNA methylation array for a study of the bovine epigenome. Our results showed significant differences between blastocysts originating from insulin‐treated oocytes compared with untreated control blastocysts. In total, 13,658 and 12,418 probes were differentially methylated (DM) in INS0.1 and INS10, respectively, with an overlap of 3,233 probes in the DM regions (DMR) for both insulin groups. Genes related to pathways such as lipid metabolism, growth and proliferation, mitochondrial function, and oxidative stress responses were influenced at both the epigenetic and transcriptomic levels. In addition, imprinted genes and genes with functions in the epigenetic machinery were among the DMRs. This study identified DMRs correlated to differential expression of genes involved in metabolic regulation and should help to improve our knowledge of the underlying molecular mechanisms of metabolic imbalance.
An extended reference region model for DCE‐MRI that accounts for plasma volume
Authors: Ahmed Zaki , Levesque Ives R.
Published: May 2018

The reference region model (RRM) for dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) provides pharmacokinetic parameters without requiring the arterial input function. A limitation of the RRM is that it assumes that the blood plasma volume in the tissue of interest is zero, but this is often not true in highly vascularized tissues, such as some tumours. This study proposes an extended reference region model (ERRM) to account for tissue plasma volume. Furthermore, ERRM was combined with a two‐fit approach to reduce the number of fitting parameters, and this was named the constrained ERRM (CERRM). The accuracy and precision of RRM, ERRM and CERRM were evaluated in simulations covering a range of parameters, noise and temporal resolutions. These models were also compared with the extended Tofts model (ETM) on in vivo glioblastoma multiforme data. In simulations, RRM overestimated Ktrans by over 10% at vp = 0.01 under noiseless conditions. In comparison, ERRM and CERRM were both accurate, with CERRM showing better precision when noise was included. On in vivo data, CERRM provided maps that had the highest agreement with ETM, whilst also being robust at temporal resolutions as poor as 30 s. ERRM can provide pharmacokinetic parameters without an arterial input function in tissues with non‐negligible vp where RRM provides inaccurate estimates. The two‐fit approach, named CERRM, further improves on the accuracy and precision of ERRM.
What is known about consumer nutrition environments in Australia? A scoping review of the literature
Authors: Pulker C. E. , Thornton L. E. , Trapp G. S. A.
Published: May 2018

Objective

Food environments can influence food selection and hold the potential to reduce obesity, non‐communicable diseases and their inequalities. ‘Consumer nutrition environments’ describe what consumers encounter within a food retail outlet, including products, price, promotion and placement. This study aimed to summarize the attributes that have been examined in existing peer‐reviewed studies of Australian consumer nutrition environments, identify knowledge gaps and provide recommendations for future research.

Methods

A systematic search of peer‐reviewed literature was conducted. Sixty‐six studies that assessed an aspect of within‐store consumer nutrition environments were included.

Results

Most studies were published from 2011 onwards and were conducted in capital cities and in supermarkets. Studies assessed the domains of product (40/66), price (26/66), promotion (16/66) and placement (6/66). The most common research themes identified were assessment of the impact of area socioeconomic status (13/66), remoteness (9/66) and food outlet type (7/66) on healthy food prices; change in price of healthy foods (6/66); variety of healthy foods (5/66); and prevalence of unhealthy child‐orientated products (5/66).

Conclusions

This scoping review identified a large number of knowledge gaps. Recommended priorities for researchers are as follows: (1) develop consistent observational methodology, (2) consider consumer nutrition environments in rural and remote communities, (3) develop an understanding of food service outlets, (4) build on existing evidence in all four domains of product, price, placement and promotion and (5) determine effective policy and store‐based interventions to increase healthy food selection.
Reverse hydrophobic PDMS surface to hydrophilic by 1‐step hydrolysis reaction
Authors: Zhang Wei , Kalulu Mulenga , Wang Xiao‐Hong , Xia Xue‐Ke , Han Xue‐Lian , Jiang Yong
Published: May 2018

Hydrophilic modification on the surface of polymer polydimethylsiloxane (PDMS) material is a key step for its application in biomaterial, bioengineering, and so on. In this article, a novel and effective method was proposed to reverse hydrophobic surface to hydrophilic by 1‐step hydrolysis of Si―O bond to produce hydrophilic hydroxyl group. The hydrophilizing reagent 2‐(trimethylsiloxy) ethyl methacrylate (TMSEMA) was used during the copolymerization of polydimethylsiloxane prepolymer (DMS U21). The prepared PDMS film was subjected to 1‐step surface hydrophilic reversal treatment using KOH solution to produce hydroxyl groups on the surface. The contact angle, attenuated total reflection Fourier transform infrared spectra, and equilibrium water content (EWC) measurements were conducted on PDMS films. The results showed that TMSEMA content had no obvious impact on the contact angle and EWC value of untreated PDMS. After reversal treatment, the contact angle decreased from 94° to 15°, and the EWC value increases to 10% when the TMSEMA content was 15 wt%. The spectrum proved that the reverse reaction produced hydroxyl and carboxylate on the surface. The hydrophilic stability, surface morphology, and protein adsorption properties of PDMS film were also investigated. This study can provide new ideas and further reference for improving the hydrophilicity of PDMS surface.
Ultrasonic treatment as recent and environmentally friendly route for the synthesis and characterization of polymer nanocomposite having PVA and biosafe BSA‐modified ZnO nanoparticles
Authors: Mallakpour Shadpour , Darvishzadeh Marzieh
Published: May 2018

The present study deals with the immobilization of ZnO nanoparticles (NPs) as nanofiller inside poly(vinyl alcohol) (PVA) by solution casting method which is a low‐cost, environmental‐friendly, and rapid method of sonochemistry. Firstly, the surface of ZnO NPs was treated by bovine serum albumin (BSA) in the phosphate‐buffered solution under ultrasonic cavitation. Three diverse polymeric nanocomposites (NCs) are formed by changing the percentage of ZnO@BSA NPs (3, 6, and 9 wt%) with same amount of PVA. The structure properties, morphology, and thermal stability of prepared NCs were determined through Fourier transform‐infrared spectroscopy, X‐ray diffraction, energy‐dispersive X‐ray spectroscopy (EDX) and optical UV‐Visible spectrum, transmission electron microscopy (TEM), and field emission scanning electron microscopy. The presence and the dispersal of the ZnO@BSA NPs in the PVA matrix were recognized by TEM. In the X‐ray diffraction analysis, the values of mean particle size using Debye‐Scherrer equation were estimated in the range 4 to 6 nm that is almost in agreement with TEM analysis. Increase of 14% in thermal stability and also increase of more than 2‐fold of the tensile strength of PVA/ZnO@BSA NC 9 wt% in respect to the pure PVA showed that the modified NPs well dispersed within PVA and attached to it.
Super macroporous poly(N‐isopropyl acrylamide) cryogel for separation purpose
Authors: Sahiner Nurettin
Published: May 2018

Polymers that can respond reversibly by changing their physical or chemical properties are recognized as stimuli‐responsive polymers. The renowned temperature‐sensitive polymer is poly(N‐isopropyl acrylamide) (p(NIPAM)), and here, homopolymeric supermacroporous p(NIPAM)) cryogel was synthesized via cryopolymerization technique at cryogenic condition (below melting point of solvent, −18°C). Then, the prepared p(NIPAM) cryogel was characterized via scanning electron microscopy, Fourier transform infrared radiation spectrometer, and thermogravimetric analyzer. The lower critical solution temperature (LCST) value of the prepared p(NIPAM) cryogel was determined from % swelling equilibrium swellings at various temperatures, 20, 25, 30, 35, 40, 45, and 50°C, respectively. Furthermore, the pore volume and porosity of p(NIPAM) cryogels were compared below and above the LCST values. Finally, the separation capability of p(NIPAM) cryogels for some molecules such as tannic acid, gallic acid, nicotine (N), and caffeine (C) was investigated at the below and above the LCST values.
Multifunctional curing component for epoxidized novolac resin by grafting poly (amidoamine) on carbon nanotubes using a divergent method
Authors: Pourhosseini‐Pakdel Zohreh , Roghani‐Mamaqani Hossein , Azimi Reza , Gholipour‐Mahmoudalilou Meysam
Published: May 2018

Poly(amidoamine)‐grafted carbon nanotube (CNTD) was synthesized and used as a multi‐component curing agent for epoxidized novolac resin (ENR). This composite and curing agent can improve thermal stability of the resin due to its tubular graphitic core and also dendritic amino‐functionalities. The ENR was cured in the presence of different amounts of CNTD. Then, the thermal degradation temperature and also char content of the products were compared with the ethylenediamine‐cured ENR. Successful functionalization of oxidized carbon nanotubes with poly(amidoamine) was evaluated by Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, X‐ray diffraction, and thermogravimetric analysis. According to the thermogravimetric analysis results, char content of ethylenediamine‐cured ENR is 44.7% which increased to 54.6%, 55.5%, and 56.9% by the addition of 3, 5, and 8 wt% of CNTD into the resin matrix. Also, addition of CNTD content increased thermal stability of the composites. The tubular structure of CNTD was observed by scanning and transmission electron microscopies.
Middle‐Down MS is Ready to Answer Complex Questions in Chromatin Biology
Authors: Sidoli Simone
Published: May 2018

Histones are the most abundant protein family in the cells of complex organisms such as mammals and, together with DNA, they define the backbone of chromatin. Histone PTMs are key players of chromatin biology, as they function as anchors for proteins that bind and modulate chromatin readout, including gene expression. Middle‐down mass spectrometry (MS) has been optimized for about 10 years to study histone N‐terminal tails, but it has been rarely applied to identify the role of coexisting histone marks in biology. In this work, Jiang et al. used middle‐down MS to study the dynamics of coexisting PTMs on histone H4 in two breast cancer cell lines. They found that overall serine 1 phosphorylation (S1ph) is mildly regulated during the cell cycle, but S1ph coexistence frequency with acetylations and methylations on the lysine residues of the N‐terminal tail is remarkably tuned during S phase and G2/M phase. Together, the team placed another benchmark proving that MS analysis of combinatorial histone PTMs provides a more comprehensive view on chromatin state than studying individual marks. We should then constantly question ourselves regarding the limitations of analyzing single PTMs when we attempt to define their effect on protein functions.
Mind‐body interventions for fear of cancer recurrence: A systematic review and meta‐analysis
Authors: Hall Daniel L. , Luberto Christina M. , Philpotts Lisa L. , Song Rhayun , Park Elyse R. , Yeh Gloria Y.
Published: May 2018

Objective

Fear of cancer recurrence (FCR) is a common existential concern and source of distress among adults with a cancer history. Multiple randomized controlled trials (RCTs) have examined mind‐body approaches to mitigating FCR. We summarized characteristics of these trials and calculated their pooled effects on decreasing FCR.

Methods

Six electronic databases were systematically searched from inception to May 2017, using a strategy that included multiple terms for RCTs, cancer, mind‐body medicine, and FCR. Data extraction and reporting followed Cochrane and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Pooled effect sizes on self‐report measures of FCR were computed by using random‐effects models.

Results

Nineteen RCTs (pooled N = 2806) were included. Most studies (53%) were published since 2015 and targeted a single cancer type (84%; mostly breast). Intervention sessions (median = 6, mode = 4) tended to last 120 minutes and occur across 1.5 months. Delivery was predominantly in‐person (63%) to either groups (42%) or individuals (42%). Most interventions incorporated multiple mind‐body components (53%), commonly cognitive‐behavioral skills (58%), or meditative practices (53%). Small‐to‐medium pooled effect sizes were observed postintervention (Hedges' g = −0.36, 95% CI = −0.49, −0.23, P < .001) and at follow‐up assessments (median = 8 months, P < .001). Potential modifiers (control group design, group/individual delivery, use of cognitive‐behavioral or mindfulness skills, number of mind‐body components, cancer treatment status, and number of sessions) did not reach statistical significance.

Conclusions

Mind‐body interventions are efficacious for reducing FCR, with small‐to‐medium effect sizes that persist after intervention delivery ends. Recommendations include testing effects among survivors of various cancers and exploring the optimal integration of mind‐body practices for managing fundamental uncertainties and fears during cancer survivorship.
Statin‐associated myopathy. Assessment of frequency based on data of all statutory health insurance funds in Germany
Authors: Ihle Peter , Dippel Franz‐Werner , Schubert Ingrid
Published: May 2018

Aim of the study was to assess the incidence of statin‐associated myopathy (SAM) under real‐life conditions in Germany. Database: Administrative data (master data, diagnoses, prescriptions) for all individuals in Germany insured with the Statutory Health Insurance. Basic population: individuals 18 years and older who have been insured continually from 2009 to 2011 (52.9 million; 29.9 million men, 23.9 million women). Data access is provided by the German Institute of Medical Documentation and Information, DIMDI) according to the Data Transparency Regulation of 2012. Statins: identification with the ATC–Codes: C10AA, C10BA and C10BX. Study population: incident statin users in 2010 with a diagnosis of lipid disorders (ICD‐10‐GM E78, excluding patients with: E78.1, E78.3, E78.6 in eight quarters before index prescription. Definition of SAM: documentation of myopathy (ICD‐10‐GM G72.0, G72.8; G72.9, M60.8, M60.9, M79.1) in the first statin prescription quarter or in one of the three following quarters. The first event is considered for the incidence estimate. The daily doses included in a package were classified as “days under therapy” (by assuming one DDD) and taken as exposition time. SAM was found in 1.9% of 531 672 incident statin users. The percentage differs according to the patterns of statin use: the lowest incidence is observed in those with only one prescription (1.3%), the highest incidence with 5.0% is observed in those who not only stopped the treatment within 365 days, but who also had their statin changed. Administrative data including diagnoses from ambulatory care provide a realistic estimate of SAM frequency in every day practice.
Decomposition of the acceleration levels distribution of a road transport into a sum of weighted Gaussians: Application to vibration tests
Authors: Bonnin Anne‐Sophie , Nolot Jean‐Baptise , Huart Victor , Pellot Jérôme , Krajka Nicolas , Odof Serge , Erre Damien
Published: May 2018

The usual method to simulate vertical vibrations generated by road transport in laboratory is to use the average power spectral density. With this method, the distribution of the acceleration levels throughout the test is a Gaussian which does not conform to the reality of a transport. This study proposes an improvement of the classical method; this improvement permits to simulate the power spectral density and the distribution of acceleration levels by using a conventional device. The main idea of this method is to decompose the distribution of an actual road transport by using a sum of weighted Gaussians. Then, we apply the power spectral density with the root mean square acceleration (grms) level and duration corresponding to each Gaussian calculated from the weighted sum. We show that the weighting coefficients correspond to the time fraction of the test. Over the total duration of the test, we then retrieve the acceleration levels distribution of the actual transport. This new test method is experimentally validated with 2 examples of actual transports.
A note on GLR charts for monitoring count processes
Authors: Lee Jaeheon , Woodall William H.
Published: May 2018

Various generalized likelihood ratio (GLR) charts have been proposed to monitor count processes such as binomial, Bernoulli, Poisson, and multinomial processes. The advantages of GLR charts are that designing the chart is relatively easy, estimates of the process change‐point and shift size are available for post‐signal diagnosis, and they are effective in detecting a wide range of shifts in the process parameter. However, for some special cases of the observations, such as observing all defective items or all non‐defective items, the GLR chart statistic for monitoring a count process has been said to be undefined. We show that the GLR chart statistic is always well defined.
Gathering society's opinion of the sustainable management and economic value of the coastal zone
Authors: Halkos George , Matsiori Steriani
Published: May 2018

This study explores people's perceptions of marine ecosystem services and sustainable coastal zone management. More specifically, it investigates the relationship between respondents' attitudes and motives for placing economic value on the coastal zone, expressing their intention to pay for coastal zone quality improvement. Primary data were obtained from a sample of 468 people living on the coastline of the Pagasitikos Gulf. Respondents' attitude was measured using questions that include issues related to the marine ecosystem. Our empirical findings reveal that ‘people's responsibility’ and respondents' perception of ‘endangered species’ are the main factors explaining their attitude towards the marine environment. In a second stage, we explore the relationship between people's intention to pay for coastal zone quality improvement in the region and ‘people's responsibility’.
Finance beyond function: Three causal explanations for financialization
Authors: Pitluck Aaron Z. , Mattioli Fabio , Souleles Daniel
Published: May 2018

This article suggests that it is advantageous for social scientists to deliberately depart from functionalist theories seeking to explain the expansion of financial instruments and logics across social life. Rather, we identify three causes of financialization from three extant clusters of scholastic activity: an organic political economy that sees finance expanding as a product or by‐product of larger state‐ and imperial‐level political struggles, a relational sociology that sees the ways that finance expands by becoming another medium for expressing and constraining social relationships, and a cultural analysis that observes the increasing redefinition of discursive and material practices as financial. Across this larger discussion, we introduce and situate the contributions to this journal's special issue on financialization.
Gendered redistribution and family debt: The ambiguities of a cash transfer program in Brazil
Authors: Badue Ana Flavia , Ribeiro Florbela
Published: May 2018

Latin American conditional cash transfer (CCT) programs are usually regarded as policies of social protection that question the neoliberal agenda. This article suggests instead that the Brazilian CCT Bolsa Família (Family Grant) is ambiguous in the sense that it was consolidated in association with policies of expansion of financial markets in the country under the rubric of social rights and female emancipation. To analyze the ambiguities of the program, we first delve into official federal documents and practices, which expose the connections between financialization and cash transfer. Second, we build on ethnographic data investigating the financial lives of Bolsa Família beneficiaries in the city of São Paulo. Our findings suggest that there are two scales at which Bolsa Família is associated with financialization: on the national level, the state‐led policy of cash transfer provides the conditions for the expansion of the banking system, and vice versa; on the local level, among the beneficiaries, Bolsa Família and access to credit tools trigger lateral dependencies and family conflicts.
Financialization of work, value, and social organization among transnational soy farmers in the Brazilian Cerrado
Authors: Ofstehage Andrew L.
Published: May 2018

This article describes the financialization of work, value, and social organization in a transnational community of soy farmers in the Brazilian Cerrado. This community originally migrated from the US Midwest to the Brazilian Cerrado in search of large tracts of cheap and productive land. While these farmers migrated to Brazil in pursuit of the reproduction of farming livelihoods and values, they adopted new forms of work, new values of farming, and new social organization on the farm. Based on fourteen months of ethnographic research on two transnational soy‐farming communities in Brazil, this article analyzes the operations of capital and the emergence of financialized farming. US family farmers purchased massive tracts of Brazilian farmland for soy production, often financed by neighboring farmer‐investors, and transitioned from mid‐scale farmers to large‐scale farm managers. This transition entailed a shift in forms of work from the field to the office and a corporatization of the farm decision‐making process, shifting from family centered to investor centered. Consequently, farmers placed less value on traditional measures of a good farmer, such as yield, and greater value on financialized measures of a good farmer, including return on investment, land acquisition, and accounting practices. This research supports the framework of financialization as a situated process that emerges out of practice and reworks economic and social organization.
Tribological properties of poly(phthalazione ether sulfone ketone) composites reinforced with glass fabric modified by graphene oxide depositing
Authors: Cao Fengxiang , Jiang Pengfei , Wang Jianzhang , Yan Fengyuan
Published: May 2018

In this paper, by electrophoretic deposition of graphene oxide (GO) on the surface of high‐strength glass fabric, a new fabric/poly(phthalazione ether sulfone ketone) (PPESK) composites material was successfully fabricated. The effects of GO on the interfacial adhesion, interlaminar shear strength, and tribological properties of the composites were investigated. Because of the addition of GO, the interlaminar shear strength of the composites was enhanced by 36.04%. Besides, the scanning electron microscope observation revealed that the interfacial adhesion between PPESK matrix and glass fabric was greatly improved. Attributing to the good interfacial adhesion, the wear‐resistance of the fabric/PPESK composite was greatly enhanced. Moreover, it can be found that the failure location transferred from the interface to the matrix after GO deposition.
From Single Atoms to Nanoparticles: Autocatalysis and Metal Aggregation in Atomic Layer Deposition of Pt on TiO2 Nanopowder
Authors: Grillo Fabio , Van Bui Hao , La Zara Damiano , Aarnink Antonius A. I. , Kovalgin Alexey Y. , Kooyman Patricia , Kreutzer Michiel T. , van Ommen Jan Rudolf
Published: May 2018

A fundamental understanding of the interplay between ligand‐removal kinetics and metal aggregation during the formation of platinum nanoparticles (NPs) in atomic layer deposition of Pt on TiO2 nanopowder using trimethyl(methylcyclo‐pentadienyl)platinum(IV) as the precursor and O2 as the coreactant is presented. The growth follows a pathway from single atoms to NPs as a function of the oxygen exposure (PO2 × time). The growth kinetics is modeled by accounting for the autocatalytic combustion of the precursor ligands via a variant of the Finke–Watzky two‐step model. Even at relatively high oxygen exposures (<120 mbar s) little to no Pt is deposited after the first cycle and most of the Pt is atomically dispersed. Increasing the oxygen exposure above 120 mbar s results in a rapid increase in the Pt loading, which saturates at exposures >> 120 mbar s. The deposition of more Pt leads to the formation of NPs that can be as large as 6 nm. Crucially, high PO2 (≥5 mbar) hinders metal aggregation, thus leading to narrow particle size distributions. The results show that ALD of Pt NPs is reproducible across small and large surface areas if the precursor ligands are removed at high PO2.
Selective friends in C++
Authors: Márton Gábor , Porkoláb Zoltán
Published: May 2018

There is a strong prejudice against the friendship access control mechanism in C++. People claim that friendship breaks the encapsulation, reflects bad design, and creates too strong coupling. However, friends appear even in the most carefully designed systems, and if it is used judiciously (like using the attorney‐client idiom), they may be better choice than widening the public interface of the class.

In this paper, we investigate how the friendship mechanism is used in C++ programs. We have made measurements on several open source projects to understand the current use of friends. Our results show various holes and errors in friend usage, like friend functions accessing only public members or not accessing members at all or the class, which declare friends has no private members at all. The results also show that friend functions actually use only a low percentage of the private members they were granted to access, which is a source of errors.

These results have motivated us to propose a selective friend language construct for C++, which can restrict friendship only to well‐defined members. Such a new language element may decrease the degradation of encapsulation and significantly increase the diagnostic capacity of the compiler. We have created a proof‐of‐concept implementation based on the LLVM/Clang compiler infrastructure to show that such constructs can be established with a minimal syntactical and compilation overhead.
Higgs boson pair production at NNLO with top quark mass effects
Authors: Grazzini M. , Heinrich G. , Jones S. , Kallweit S. , Kerner M. , Lindert J. M. , Mazzitelli J.
Published: May 2018

Abstract

We consider QCD radiative corrections to Higgs boson pair production through gluon fusion in proton collisions. We combine the exact next-to-leading order (NLO) contribution, which features two-loop virtual amplitudes with the full dependence on the top quark mass M

t
, with the next-to-next-to-leading order (NNLO) corrections computed in the large-M

t
approximation. The latter are improved with different reweighting techniques in order to account for finite-M

t
effects beyond NLO. Our reference NNLO result is obtained by combining one-loop double-real corrections with full M

t
dependence with suitably reweighted real-virtual and double-virtual contributions evaluated in the large-M

t
approximation. We present predictions for inclusive cross sections in pp collisions at

$$ \sqrt{s} $$

s

= 13, 14, 27 and 100 TeV and we discuss their uncertainties due to missing M

t
effects. Our approximated NNLO corrections increase the NLO result by an amount ranging from +12% at

$$ \sqrt{s}=13 $$

s

=
13

TeV to +7% at

$$ \sqrt{s}=100 $$

s

=
100

TeV, and the residual uncertainty of the inclusive cross section from missing M

t
effects is estimated to be at the few percent level. Our calculation is fully differential in the Higgs boson pair and the associated jet activity: we also present predictions for various differential distributions at

$$ \sqrt{s}=14 $$

s

=
14

and 100 TeV, and discuss the size of the missing M

t
effects, which can be larger, especially in the tails of certain observables. Our results represent the most advanced perturbative prediction available to date for this process.
An economically and environmentally acceptable synthesis of chiral drug intermediate l-pipecolic acid from biomass-derived lysine via artificially engineered microbes
Authors: Cheng Jie , Huang Yuding , Mi Le , Chen Wujiu , Wang Dan , Wang Qinhong
Published: May 2018

Deficiency in petroleum resources and increasing environmental concerns have pushed a bio-based economy to be built, employing a highly reproducible, metal contaminant free, sustainable and green biomanufacturing method. Here, a chiral drug intermediate l-pipecolic acid has been synthesized from biomass-derived lysine. This artificial bioconversion system involves the coexpression of four functional genes, which encode l-lysine α-oxidase from Scomber japonicus, glucose dehydrogenase from Bacillus subtilis, Δ1-piperideine-2-carboxylase reductase from Pseudomonas putida, and lysine permease from Escherichia coli. Besides, a lysine degradation enzyme has been knocked out to strengthen the process in this microbe. The overexpression of LysP improved the l-pipecolic acid titer about 1.6-folds compared to the control. This engineered microbial factory showed the highest l-pipecolic acid production of 46.7 g/L reported to date and a higher productivity of 2.41 g/L h and a yield of 0.89 g/g. This biotechnological l-pipecolic acid production is a simple, economic, and green technology to replace the presently used chemical synthesis.
Sonographic Evaluation of Umbilical Vein
Authors: Shah Deval , Shah Nilpa
Published: May 2018

To evaluate intraabdominal course of umbilical vein, its relation with portal vein and ductus venosus and its anomalies. All pregnant women were examined during midtrimester anomaly scan between January 2015 and December 2017. With evaluation of umbilical vein in its intraabdominal course, size of umbilical vein, its relation to the stomach and the gallbladder and origin of ductus venosus were studied in middle and upper abdominal axial and sagittal planes by two dimensional and colour doppler sonography. Anastomosis of umbilical vein with portal vein and its further course was examined and detailed anatomical survey was made to look for associated anomalies. Fetal and neonatal outcome was assessed after delivery. Twelve cases of umbilical vein abnormalities were evaluated. Of them, there were three cases of umbilical vein varix, four cases of persistent right umbilical vein and five cases of abnormal umbilical–portal–systemic venous shunt were noted. Examination of the intraabdominal course of umbilical vein and ductus venosus should be a part of second trimester anomaly scan. Proper knowledge of umbilical portal venous system is mandatory.
Effects of Antiparkinson Medication on Cognition in Parkinson’s Disease: A Systematic Review
Authors: Roy Marc-André , Doiron Maxime , Talon-Croteau Jessica , Dupré Nicolas , Simard Martine
Published: May 2018

Objective: This study aimed to systematically review the effects of currently prescribed antiparkinson medication on cognition in patients with mild-to-moderate Parkinson’s disease (PD) who were either cognitively intact or mildly impaired. Methods: English- and French-language studies published between 1969 and 2017 were accessed via MedLine, PsychNET, EMBASE and EBSCO databases. Methodological quality (MQ) was evaluated with the quality assessment instrument of the Cochrane Collaboration Depression, Anxiety and Neurosis Review (scores from 0% to 44% indicate very low quality; scores from 45% to 64% indicate low quality; scores from 65% to 84% indicate medium quality; and scores from 85% to 100% indicate high quality). Hedges’ g and Student’s t-test were performed on all cognitive outcome measures reported. Results: In total, 14 studies assessed the cognitive effects of levodopa (L-D), pramipexole (PRX), selegiline (SEL) and rasagiline (RAS) in mild-to-moderate non-demented PD patients. The MQ was overall low, with an average score of 49.1%. Results for L-D showed deleterious effects on a test of cognitive inhibition, as well as benefits on tests of attention/processing speed/working memory, executive functions and episodic memory. Pramipexole was associated with a worsening of episodic memory and impulse control. Results on SEL indicated a deterioration of global cognition over time and of concept formation. Rasagiline had some benefits on working memory and verbal fluency. Conclusion: Antiparkinson medications can have deleterious (L-D; PRX; SEL) and beneficial (L-D; RAS) effects on cognition. However, randomized double-blind placebo-controlled trials with larger sample sizes are required to better elucidate this issue.
2232
Authors: Ferrandino Rocco , Nadkarni Girish , Poojary Priti , Saha Aparna , Ferket Bart , Chauhan Kinsuk , Coca Steven
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: In June 2016, the FDA cautioned against the use of SGLT-2 inhibitors because of increased risk of acute kidney injury (AKI) after 101 cases of AKI were reported between March 2013 and October 2015. This study seeks to determine risk of AKI associated with SGLT-2 inhibitors in a large cohort of type 2 diabetic patients. METHODS/STUDY POPULATION: Retrospective cohort study including SGLT-2 inhibitor users and nonusers in the Mount Sinai Chronic Kidney Disease Registry between January 2013 and September 2016. SGLT-2 inhibitor users and nonusers were type 2 diabetics with new SGLT-2 inhibitor prescription after January 2013 and an outpatient visit between 2013 and 2015, respectively. Subjects were propensity matched by nearest neighbor method based on demographics, comorbidities, laboratory values, medications, estimated glomerular filtration rate (eGFR), and length of follow-up. The primary end point was AKI (defined by KDIGO laboratory algorithm) occurring during the follow-up period. RESULTS/ANTICIPATED RESULTS: In total, 372 SGLT-2 inhibitor users [mean age 63 years; 205 (55%) men] and 372 [mean age 63; 194 (52%) men] nonusers were included in the primary analysis. Proportions of AKI events defined by KDIGO criteria in users and nonusers were 4.0% and 10.0%, respectively. Adjusted odds ratio for AKI was 1.00 (95% CI, 0.28–2.62). Median peak serum creatinine measurements during AKI events for user and nonuser groups were 1.60 (IQR 1.36–1.78) and 1.88 (IQR 1.55–2.44) (p=0.02), respectively. Sensitivity analyses yielded similar results. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that there is no evidence of increased odds of AKI in SGLT-2 inhibitor users compared with propensity-matched nonusers with type 2 diabetes.
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Authors: Weingarten Angela , Clark Daniel E. , Byrne Ryan D. , Chu Patricia Y. , Fish Frank A. , Frischhertz Benjamin P. , Markham Larry W.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The morbidity and mortality in adults with single ventricular hearts who have undergone Fontan palliation is poorly defined. These patients have a high burden of arrhythmia, heart failure, and re-operation. We hypothesized that age and type of Fontan predict occurrence of arrhythmia. METHODS/STUDY POPULATION: In total, 205 patients aged 18 years who had undergone a Fontan procedure were identified. Those with incomplete data were excluded. Demographic, anatomic, pharmacologic, imaging, hemodynamic, and electrophysiologic data were collected. The χ2 and Mann-Whitney U tests were used to test significance defined as p<0.05. RESULTS/ANTICIPATED RESULTS: Of the 205 patients identified, 59 had been lost to follow-up. Of the 146 patients (77, 53% female) actively followed 18 (12%) had died at a median (IQR) age of 27 (21–34.3); in patients alive as of 10/2016 the median age was 26 years (22–34). Fontan types were lateral tunnel (LT) (n=79, 54.1%), extracardiac (EC) (n=32, 22%), right atrial to pulmonary artery (RV-PA) (n=28, 19%), and Fontan with Bjork modification (n=4, 2.7%). Systemic left ventricle (n=96, 66%) was more common than systemic right ventricle (n=43, 30%). Of the 146 patients, 101 (69%) had significant morbidity or mortality: 86 (59%) were diagnosed with arrhythmia, 18 (12%) died, and 11 (8%) underwent heart transplants. Frequent procedures included: Fontan revisions/cryoablation in 28 (19%), electrophysiology studies with ablation in 73 (50%), and pacemakers in 53 (36%). Of the arrhythmia diagnoses, 57 (64%) were atrial tachyarrhythmias. RV-PA Fontan procedures were associated with significantly more atrial arrhythmia than all other Fontan types (70% vs. 30%; p<0.01). There was no statistical difference in occurrence of atrial arrhythmia in adults with LT Versus EC Fontans (p=0.3). While patients who had undergone RV-PA and Bjork Fontans were older with median age 34 years, there was no significant difference in age between LT and EC (median 24.0 and 24.5). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult survivors of the Fontan procedure suffer from significant morbidity and mortality. The single most prevalent morbidity is atrial arrhythmia. We conclude that RV-PA Fontans, now obsolete, have the highest prevalence of arrhythmia and that there is no difference in arrhythmia burden between LT and EC Fontans. Given the high prevalence of morbidity and mortality in this population, it is imperative that they be followed by cardiologists with expertise in congenital heart disease.
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Authors: Ezra Shabason Jacob , Chen Jerry , Apisarnthanarax Smith , Damjanov Nevena , Giantonio Bruce , Loaiza-Bonilla Arturo , O’Dwyer Peter , O’Hara Mark , Reiss Kim , Teitelbaum Ursina , Wissel Paul , Drebin Jeffery , Vollmer Charles , Kochman Michael , Mick Rosemarie , Vergara Norge , Jhala Nirag , Berman Abigail , Dorsey Jay , Evans Sydney M. , Kao Gary , Lukens John N. , Plastaras John P. , Metz James M. , Ben-Josef Edgar
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
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Authors: Azevedo Christina , Cen Steven , Zheng Ling , Amirhossein Jaberzadeh Pelletier
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To identify brain regions with the highest and least variable rate of multiple sclerosis (MS)-specific atrophy using an agnostic approach, and to perform simulation-based sample size calculations for Phase II s using these regions as primary endpoint. METHODS/STUDY POPULATION: In total, 601 subjects (2638 MRI scans) were analyzed; 520 subjects with relapsing forms of MS across the spectrum of disease severity and duration were followed in a single-center prospective cohort study at an academic MS Center between 2005 and 2010 with annual 3 T MRIs and clinical visits for 5 years, including standardized 1 mm3 3D T1-weighted images (3DT1s; 2483 MRIs). Separately, a convenience sample of 81 healthy controls (HC) was recruited from the same center and scanned longitudinally using the same MRI scanner and protocol (155 MRIs). 3DT1s were processed using FreeSurfer’s longitudinal pipeline (software version 5.3). Rates of change in all cortical and subcortical regions (n=119 brain regions) were estimated in MS patients and HC with linear mixed effects models. An effect size was calculated for each region as the difference in change over time between MS patients and HC divided by the standard error of the difference [d=β(MS×time)/SE β(MS×time)]. Regions were ranked according to absolute effect size, and the top regions were chosen for simulation-based sample size calculations to estimate the number of subjects needed to achieve 80% power to detect a slowing of MS atrophy down to normal aging, assuming significance levels of 5% and 10%. Ten percent was included because some have advocated for a more relaxed alpha in Phase II s. RESULTS/ANTICIPATED RESULTS: Four regions (putamen, subcortical grey matter, caudate, and thalamus) yielded the smallest sample sizes. At 80% power, ~50 subjects per arm would be needed with putamen or subcortical grey matter volume, or ~80–85 subjects per arm with caudate or thalamic volume as primary endpoint. For the remaining regions, >140 subjects per arm would be needed. A 20%–30% increase in sample size was observed when α=5% was used. DISCUSSION/SIGNIFICANCE OF IMPACT: Using an agnostic approach considering all brain regions and simulation-based sample size calculations specifically designed for longitudinal studies, putaminal, subcortical grey, caudate, and thalamic volumes are sensitive to change over time and yield feasible sample sizes for Phase II studies in MS. Because the effect size estimates incorporate normal aging, these regions represent the most sensitive outcomes for testing therapeutic interventions that target irreversible, MS-specific brain atrophy. The clinical relevance of these regions is our next focus to help inform which of these regions should be favored as primary endpoint.