bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
Authors: Chiang Chih-Yuan , Uzoma Ijeoma , Moore Richard T. , Gilbert Merle , Duplantier Allen J. , Panchal Rekha G.
Published: March 2018

Increasing incidences of multidrug resistance in pathogenic bacteria threaten our ability to treat and manage bacterial infection. The development and FDA approval of novel antibiotics have slowed over the past decade; therefore, the adoption and improvement of alternative therapeutic strategies are critical for addressing the threat posed by multidrug-resistant bacteria. Host-directed therapies utilize small-molecule drugs and proteins to alter the host response to pathogen infection. Here, we highlight strategies for modulating the host inflammatory response to enhance bacterial clearance, small-molecule potentiation of innate immunity, and targeting of host factors that are exploited by pathogen virulence factors. Application of state-of-the-art “omic” technologies, including proteomics, transcriptomics, and image-omics (image-based high-throughput phenotypic screening), combined with powerful bioinformatics tools will enable the modeling of key signaling pathways in the host-pathogen interplay and aid in the identification of host proteins for therapeutic targeting and the discovery of host-directed small molecules that will regulate bacterial infection. We conclude with an outlook on research needed to overcome the challenges associated with transitioning host-directed therapies into a clinical setting.
UDP-Glucuronic Acid Transport Is Required for Virulence of
Cryptococcus neoformans
Authors: Li Lucy X. , Rautengarten Carsten , Heazlewood Joshua L. , Doering Tamara L.
Published: March 2018

Glycans play diverse biological roles, ranging from structural and regulatory functions to mediating cellular interactions. For pathogens, they are also often required for virulence and survival in the host. In
Cryptococcus neoformans
, an opportunistic pathogen of humans, the acidic monosaccharide glucuronic acid (GlcA) is a critical component of multiple essential glycoconjugates. One of these glycoconjugates is the polysaccharide capsule, a major virulence factor that enables this yeast to modulate the host immune response and resist antimicrobial defenses. This allows cryptococci to colonize the lung and brain, leading to hundreds of thousands of deaths each year worldwide. Synthesis of most glycans, including capsule polysaccharides, occurs in the secretory pathway. However, the activated precursors for this process, nucleotide sugars, are made primarily in the cytosol. This topological problem is resolved by the action of nucleotide sugar transporters (NSTs). We discovered that Uut1 is the sole UDP-GlcA transporter in
C. neoformans
and is unique among NSTs for its narrow substrate range and high affinity for UDP-GlcA. Mutant cells with
UUT1
deleted lack capsule polysaccharides and are highly sensitive to environmental stress. As a result, the deletion mutant is internalized and cleared by phagocytes more readily than wild-type cells are and is completely avirulent in mice. These findings expand our understanding of the requirements for capsule synthesis and cryptococcal virulence and elucidate a critical protein family.

IMPORTANCE
Cryptococcus neoformans
causes lethal meningitis in almost two hundred thousand immunocompromised patients each year. Much of this fungal pathogen’s ability to resist host defenses and cause disease is mediated by carbohydrate structures, including a complex polysaccharide capsule around the cell. Like most eukaryotic glycoconjugates, capsule polysaccharides are made within the secretory pathway, although their precursors are generated in the cytosol. Specific transporters are therefore required to convey these raw materials to the site of synthesis. One precursor of particular interest is UDP-glucuronic acid, which donates glucuronic acid to growing capsule polysaccharides. We discovered a highly specific, high-affinity transporter for this molecule. Deletion of the gene encoding this unusual protein abolishes capsule synthesis, alters stress resistance, and eliminates fungal virulence. In this work, we have identified a novel transporter, elucidated capsule synthesis and thereby aspects of fungal pathogenesis, and opened directions for potential antifungal therapy.
The Who, Why, and How of Small-Molecule Production in Invertebrate Microbiomes: Basic Insights Fueling Drug Discovery
Authors: Kwan Jason C.
Published: March 2018

Bacteria have supplied us with many bioactive molecules for use in medicine and agriculture. However, rates of discovery have decreased as the biosynthetic capacity of the culturable biosphere has been continuously mined for many decades.
On the Road to Strain-Resolved Comparative Metagenomics
Authors: Segata Nicola
Published: March 2018

Metagenomics has transformed microbiology, but its potential has not been fully expressed yet. From computational methods for digging deeper into metagenomes to study designs for addressing specific hypotheses, the Segata Lab is pursuing an integrative metagenomic approach to describe and model human-associated microbial communities as collections of strains.
Factors associated with basic and instrumental activities of daily living in elderly participants of a population-based survey: the Nord-Trøndelag Health Study, Norway
Authors: Storeng Siri Høivik , Sund Erik R , Krokstad Steinar
Published: March 2018

Objectives

To investigate factors associated with the need for assistance in basic and instrumental activities of daily living in Norwegian elderly.

Design

Prospective cohort study.

Setting

The Nord-Trøndelag Health Study (HUNT), a large population-based health survey in Norway.

Participants

5050 individuals aged 60–69 years old at baseline in HUNT2 (1995–1997) who also participated in HUNT3 (2006–2008) were included in the study. 676/693 individuals were excluded in the analyses due to missing outcomes.

Outcomes

Needing assistance in one or more basic or instrumental activities of daily living reported in HUNT3.

Results

In adjusted multinomial logistic regression analyses, poor self-rated health and depression were the strongest risk factors for needing assistance in one or more basic activities of daily living in HUNT3, with ORs of 2.13 (1.35 to 3.38) and 1.58 (0.91 to 2.73). Poor self-rated health and poor life satisfaction were the strongest risk factors for needing assistance in one or more instrumental activities of daily living in HUNT3, with ORs of 2.30 (1.93 to 2.74) and 2.29 (1.86 to 2.81), respectively. Excessive sitting time, short or prolonged sleeping time, and physical inactivity seemed to be the most important lifestyle risk factors for basic/instrumental activities of daily living (ADL/IADL) disability. The studied factors were, in general, greater risk factors for mortality during follow-up than for ADL/IADL disability. Smoking was the strongest risk factor for mortality during follow-up and non-participation in HUNT3. Smoking and low social participation were the strongest risk factors for non-participation in HUNT3.

Conclusions

Subjective health perception, life satisfaction and depression were the strongest risk factors for needing assistance in one or more basic/instrumental activities of daily living later in life. These factors could be possible targets for prevention purposes.
Understanding the role of health information in patients’ experiences: secondary analysis of qualitative narrative interviews with people diagnosed with cancer in Germany
Authors: Blödt Susanne , Kaiser Maleen , Adam Yvonne , Adami Sandra , Schultze Martin , Müller-Nordhorn Jacqueline , Holmberg Christine
Published: March 2018

Objective

To analyse the role and meaning of health information in individuals’ experiences with either breast, colorectal or prostate cancer in order to better understand unmet information needs of people with a cancer diagnosis.

Design

This is a secondary analysis of data from a qualitative interview study including narrative interviews and maximum variation sampling. A thematic analysis was conducted, followed by an in-depth analysis based on the principles of grounded theory.

Setting

Interviewees were sought across Germany through self-help organisations, primary care clinics, rehabilitation facilities, physicians and other healthcare professionals to develop cancer modules for the website krankheitserfahrungen.de (illness experiences.de).

Participants

Women with a diagnosis of breast cancer, individuals with a diagnosis of colorectal cancer and men with a diagnosis of prostate cancer.

Results

The meaning and role of information in the illness experiences were clearly associated with gaining control in a seemingly uncontrollable situation in which others —people, the disease— take over. Four categories characterise the ways in which information helped interviewees to regain a sense of control following a diagnosis of cancer: ‘becoming confident in one’s treatment decision’, ‘taking responsibility for one’s situation’, ‘understanding the consequences of the disease and treatment for one’s life’, and ‘dealing with fear’. There was, however, always a fine line between information seeking and becoming overwhelmed by information.

Conclusions

Information needs to be understood as a management tool for handling the disease and its (potential) consequences. Patients’ unmet needs for information might not be easily solved by a simple increase in the amount of information because emotional support and respect for patient autonomy might also play a role. The evaluation of one’s own information behaviour and the information received is closely linked to how the illness unfolds. This makes it challenging to document unmet information needs and satisfaction with information independent of an individual’s illness trajectory over time.
Effect of noise tolerance on non-restorative sleep: a population-based study in Hong Kong
Authors: Fong Daniel Y T , Wong Janet Y H , Huang Lixi
Published: March 2018

Objective

The aim of this study was to assess the impact of auditory noise tolerance on non-restorative sleep using an objective audiometric test in a representative sample.

Design

A total of 202 Chinese individuals aged 15 years and above were recruited from a population-based household survey. Their non-restorative sleep was assessed by a single item, the degree of feeling refreshed on waking up, on a 0–10 scale, while noise tolerance was measured by the most comfortable level expressed in A-weighted decibels.

Results

The 202 individuals (106 women) had a mean degree of feeling refreshed on waking up of 6.5 on the 0–10 scale and a mean maximum comfortable sound level of 69.2 dB. A multivariable analysis showed that a 1 dB increase in noise tolerance was associated with a 0.1-unit increase in the degree of feeling refreshed after adjusting for age, education, marital status, occupation, exercise, smoking, alcohol consumption, household noise level, stress, anxiety and depression. Moreover, housewives, non-smokers and individuals who were less anxious or stressed felt significantly more refreshed on waking up.

Conclusion

People with higher levels of noise tolerance experienced more refreshing sleep. Additional clinical consideration of enhancing noise tolerance in patients with sleep complaints is needed.
Meta Salud Diabetes study protocol: a cluster-randomised trial to reduce cardiovascular risk among a diabetic population of Mexico
Authors: Sabo Samantha , Denman Champion Catalina , Bell Melanie L , Cornejo Vucovich Elsa , Ingram Maia , Valenica Celina , Castro Vasquez Maria del Carmen , Gonzalez-Fagoaga Eduardo , Geurnsey de Zapien Jill , Rosales Cecilia B
Published: March 2018

Introduction

Northern Mexico has among the highest rates of cardiovascular disease (CVD) and diabetes in the world. This research addresses core gaps in implementation science to develop, test and scale-up CVD risk-reduction interventions in diabetics through a national primary care health system.

Methods and analysis

The Meta Salud Diabetes (MSD) research project is a parallel two-arm cluster-randomised clinical behavioural trial based in 22 (n=22) health centres in Sonora, Mexico. MSD aims to evaluate the effectiveness of the MSD intervention for the secondary prevention of CVD risk factors among a diabetic population (n=320) compared with the study control of usual care. The MSD intervention consists of 2-hour class sessions delivered over a 13-week period providing educational information to encourage sustainable behavioural change to prevent disease complications including the adoption of physical activity. MSD is delivered within the context of Mexico’s national primary care health centre system by health professionals, including nurses, physicians and community health workers via existing social support groups for individuals diagnosed with chronic disease. Mixed models are used to estimate the effect of MSD by comparing cardiovascular risk, as measured by the Framingham Risk Score, between the trial arms. Secondary outcomes include hypertension, behavioural risk factors and psychosocial factors.

Ethics and dissemination

This work is supported by the National Institutes of Health, National Heart Lung and Blood Institute (1R01HL125996-01) and approved by the University of Arizona Research Institutional Review Board (Protocol 1508040144) and the Research Bioethics Committee at the University of Sonora. The first Internal Review Board approval date was 31 August 2015 with five subsequent approved amendments. This article refers to protocol V.0.2, dated 30 January 2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences and will be shared through meetings with health systems officials.

Trial registration number

NCT0280469; Pre-results.
Reliability of single office blood pressure measurements
Authors: Burkard Thilo , Mayr Michael , Winterhalder Clemens , Leonardi Licia , Eckstein Jens , Vischer Annina Salome
Published: March 2018

Objectives

Standard operating procedures for office blood pressure measurement (OBPM) vary greatly between guidelines and studies. We aimed to compare the difference between a single OBPM and the mean of the three following measurements. Further, we studied how many patients with possible hypertension may be missed due to short-term masked hypertension (STMH) and how many might be overdiagnosed due to short-term white coat hypertension (STWCH).

Design and setting

In this cross-sectional, single-centre trial, 1000 adult subjects were enrolled. After 5 min of rest, four sequential standard OBPMs were performed at 2 min intervals in a quiet room in sitting position. We compared the first (fBPM) to the mean of the second to fourth measurement (mBPM). STMH was defined as fBPM <140 mm Hg systolic and <90 mm Hg diastolic and mBPM systolic ≥140 mm Hg or diastolic ≥90 mm Hg. STWCH was defined as fBPM systolic ≥140 mm Hg or diastolic ≥90 mm Hg and mBPM <140 mm Hg systolic and <90 mm Hg diastolic.

Results

Complete measurements were available in 802 subjects. Between fBPM and mBPM, 662 (82.5%), 441 (55%) and 208 (25.9%) subjects showed a difference in systolic and 531 (66.2%), 247 (30.8%) and 51 (6.4%) in diastolic blood pressure (BP) values of >2 mm Hg, >5 mm Hg and >10 mm Hg, respectively. In 3.4% of initially normotensives STMH and in 34.3% of initially hypertensives, STWCH was apparent.

Conclusions

There are significant differences between a single OBPM and the mean of consecutive BP measurements. Our study provides evidence that a single OBPM should not be the preferred method and should be discouraged in future guidelines.

Trial registration number

NCT02552030;Results.
Occupational and educational inequalities in exit from employment at older ages: evidence from seven prospective cohorts
Authors: Carr Ewan , Fleischmann Maria , Goldberg Marcel , Kuh Diana , Murray Emily T , Stafford Mai , Stansfeld Stephen , Vahtera Jussi , Xue Baowen , Zaninotto Paola , Zins Marie , Head Jenny
Published: March 2018

Objectives

Past studies have identified socioeconomic inequalities in the timing and route of labour market exit at older ages. However, few studies have compared these trends cross-nationally and existing evidence focuses on specific institutional outcomes (such as disability pension and sickness absence) in Nordic countries. We examined differences by education level and occupational grade in the risks of work exit and health-related work exit.

Methods

Prospective longitudinal data were drawn from seven studies (n=99 164). Participants were in paid work at least once around age 50. Labour market exit was derived based on reductions in working hours, changes in self-reported employment status or from administrative records. Health-related exit was ascertained by receipt of health-related benefit or pension or from the reported reason for stopping work. Cox regression models were estimated for each study, adjusted for baseline self-rated health and birth cohort.

Results

There were 50 003 work exits during follow-up, of which an average of 14% (range 2–32%) were health related. Low level education and low occupational grade were associated with increased risks of health-related exit in most studies. Low level education and occupational grade were also associated with an increased risk of any exit from work, although with less consistency across studies.

Conclusions

Workers with low socioeconomic position have an increased risk of health-related exit from employment. Policies that extend working life may disadvantage such workers disproportionally, especially where institutional support for those exiting due to poor health is minimal.
The effects of different passive static stretching intensities on recovery from unaccustomed eccentric exercise – a randomized controlled trial
Authors: Apostolopoulos Nikos C. , Lahart Ian M. , Plyley Michael J. , Taunton Jack , Nevill Alan M. , Koutedakis Yiannis , Wyon Matthew , Metsios George S.
Published: March 2018

Effects of passive static stretching intensity on recovery from unaccustomed eccentric exercise of right knee extensors was investigated in 30 recreationally active males randomly allocated into 3 groups: high-intensity (70%–80% maximum perceived stretch), low-intensity (30%–40% maximum perceived stretch), and control. Both stretching groups performed 3 sets of passive static stretching exercises of 60 s each for hamstrings, hip flexors, and quadriceps, over 3 consecutive days, post-unaccustomed eccentric exercise. Muscle function (eccentric and isometric peak torque) and blood biomarkers (creatine kinase and C-reactive protein) were measured before (baseline) and after (24, 48, and 72 h) unaccustomed eccentric exercise. Perceived muscle soreness scores were collected immediately (time 0), and after 24, 48, and 72 h postexercise. Statistical time × condition interactions observed only for eccentric peak torque (p = 0.008). Magnitude-based inference analyses revealed low-intensity stretching had most likely, very likely, or likely beneficial effects on perceived muscle soreness (48–72 h and 0–72 h) and eccentric peak torque (baseline–24 h and baseline–72 h), compared with high-intensity stretching. Compared with control, low-intensity stretching had very likely or likely beneficial effects on perceived muscle soreness (0–24 h and 0–72 h), eccentric peak torque (baseline–48 h and baseline–72 h), and isometric peak torque (baseline–72 h). High-intensity stretching had likely beneficial effects on eccentric peak torque (baseline–48 h), but likely had harmful effects on eccentric peak torque (baseline–24 h) and creatine kinase (baseline–48 h and baseline–72 h), compared with control. Therefore, low-intensity stretching is likely to result in small-to-moderate beneficial effects on perceived muscle soreness and recovery of muscle function post-unaccustomed eccentric exercise, but not markers of muscle damage and inflammation, compared with high-intensity or no stretching.
Interpretation of piezocone penetration and dissipation tests in sensitive Leda clay at Gloucester test site
Authors: Agaiby Shehab S. , Mayne Paul W.
Published: March 2018

A modified piezocone penetration test (CPTu) analytical solution based on spherical cavity expansion and critical state soil mechanics (SCE–CSSM) is employed for assessing yield stress, undrained shear strength, and flow parameters in sensitive Leda clay at the Gloucester test site. For sensitive and structured clays, the formulation relies on the mobilized effective stress friction angle ([Formula: see text]) defined at two parts of the stress–strain curve: (i) peak stress ([Formula: see text]) and (ii) maximum obliquity ([Formula: see text]). Input parameters for assessing the overconsolidation ratio ([Formula: see text], where [Formula: see text] is preconsolidation stress and [Formula: see text] is current effective vertical stress) from CPTu results include: undrained rigidity index (IR= G/su, where G is shear modulus and suis undrained shear strength), plastic volumetric strain potential (Λ = 1 – (Cs/Cc), where Csis swelling index and Ccis virgin compression index), and effective friction angles ([Formula: see text] and [Formula: see text]). A direct CPTu means of assessing the undrained rigidity index in a reliable manner is also developed that gives the Nktcone factor and matches profiles of undrained shear strength from triaxial compression tests (suTC). The modified solution is also implemented on two additional sites: a sensitive-quick clay in Norway and structured varved clay from New England. Interpretations of the coefficient of consolidation and permeability from pore-water pressure dissipation tests at Gloucester are evaluated using the SCE–CSSM formulation and shown to be comparable with independent laboratory and field tests.
K-shell photoionization of Be-like nitrogen from the ground state: energies and Auger widths of the high-lying double-excited states for N IV
Authors: Liang Liang , Zhou Chao
Published: March 2018

The K-shell photoionization cross section of Be-like nitrogen (N IV) from the ground state is studied with the R-matrix and distorted-wave method for photon energies from 5.7 to 41.2 Ry. The close-coupling expansion includes 34 target states of N V with the 13 configurations in the LS-coupling scheme. The resonance energies, quantum defect and widths of 18 series of autoionization are determined from QB method and agree with these by cross sections. Our theoretical resonance energies and widths are compared with the existing experiments on the Auger spectra and other theoretical results. The results show that the calculated resonance energies are in rather good agreement with the experiment on the Auger spectra. For the autoionization width of some resonance states, good agreement is also found with recent theoretical results wherever available obtained using a saddle-point complex-rotation method.
Evaluation of research related to virtual physics laboratory applications
Authors: Mirçik Özden Karagöz , Saka Ahmet Zeki
Published: March 2018

In studies conducted in the last 30 years, different types of virtual labs were applied to different study groups using very different methods and techniques. The aim of this study is to evaluate the virtual labs used in teaching physics in terms of the purpose of use, working groups, methods, and techniques using the content analysis method based on a literature review conducted. The results of the application, which is aimed at the selection and use of virtual physics lab programs that offer very different designs, scopes, and means of application and at the adaptation of such programs to the target audience by educators, as well as at provision of a means for measurement and evaluation, will be analyzed. By examining the data thus obtained in terms of the subject matter, method, and outcome, it will be possible to assist the parties who will utilize the virtual physics laboratory programs in teaching physics to use such programs with expected efficiency.
THE PROPERTIES OF FRACTIONAL ORDER CALCULUS OF FRACTAL INTERPOLATION FUNCTION OF BROKEN LINE SEGMENTS
Authors: PAN XUEZAI , XU RONGFEI , SHANG XUDONG , WANG MINGGANG
Published: March 2018

In order to research the properties of the fractional order calculus of broken line segments’ fractal interpolation function (FIF) generated by the linear iterated function system (IFS), the concepts of the Riemann–Liouville fractional order calculus and the method of the IFS are used to prove the properties of the fractional calculus of the broken line segments’ FIF generated by the linear IFS. There are two conclusions as follows. First, the fractional order integral of the broken line segments’ FIF formed by the linear IFS is continuous and first-order differentiable on the closed interval [Formula: see text]. Second, the broken line segments’ FIF formed by the linear IFS exists with fractional order differential, but the differential function is not continuous.
Convenient Adhesive Strength Evaluation Method in Terms of the Intensity of Singular Stress Field
Authors: Noda Nao-Aki , Li Rong , Miyazaki Tatsujiro , Takaki Rei , Sano Yoshikazu
Published: March 2018

A convenient evaluation method is proposed for the debonding adhesive strength in terms of the intensity of singular stress field (ISSF) appearing at the end of interface. The same FEM mesh pattern is applied to unknown problems and reference problems. It is found that the ISSF is obtained accurately by focussing on the FEM stress at the adhesive corner. Then, the debonding condition can be expressed as a constant value of critical ISSF. The usefulness of the present solution is verified by comparing with the results of the conventional method.
Focus Group: An Optimization Algorithm Inspired by Human Behavior
Authors: Fattahi Edris , Bidar Mahdi , Kanan Hamidreza Rashidy
Published: March 2018

This paper presents a novel optimization algorithm, namely focus group (FG) algorithm, for solving optimization problems. The proposed algorithm is inspired by the behavior of group members to share their ideas (solutions) about a specific subject and trying to improve the solutions based on the cooperation and discussion. In the proposed algorithm, all the members present their solutions about the subject and all the suggested solutions proportional to their fitness, leave impact on the other solutions and incline them towards themselves. While trying to improve the quality of the candidate solutions, they converge to the optimal solution. To improve the performance of the proposed algorithm, two genetic operators are incorporated into the algorithm. The proposed algorithm is evaluated using several constrained and unconstrained benchmark functions commonly used in the area of optimization. Experimental results, in comparison with different well-known evolutionary techniques, confirm the high performance of the proposed algorithm in dealing with the optimization problems.
Finiteness of Brauer groups of K3 surfaces in characteristic 2
Authors: Ito Kazuhiro
Published: March 2018

For a [Formula: see text] surface over a field of characteristic [Formula: see text] which is finitely generated over its prime subfield, we prove that the cokernel of the natural map from the Brauer group of the base field to that of the [Formula: see text] surface is finite modulo the [Formula: see text]-primary torsion subgroup. In characteristic different from [Formula: see text], such results were previously proved by Skorobogatov and Zarhin. We basically follow their methods with an extra care in the case of superspecial [Formula: see text] surfaces using the recent results of Kim and Madapusi Pera on the Kuga-Satake construction and the Tate conjecture for [Formula: see text] surfaces in characteristic [Formula: see text].
Large-Scale Indexing, Discovery, and Ranking for the Internet of Things (IoT)
Authors: Fathy Yasmin , Barnaghi Payam , Tafazolli Rahim
Published: March 2018

Network-enabled sensing and actuation devices are key enablers to connect real-world objects to the cyber world. The Internet of Things (IoT) consists of the network-enabled devices and communication technologies that allow connectivity and integration of physical objects (Things) into the digital world (Internet). Enormous amounts of dynamic IoT data are collected from Internet-connected devices. IoT data are usually multi-variant streams that are heterogeneous, sporadic, multi-modal, and spatio-temporal. IoT data can be disseminated with different granularities and have diverse structures, types, and qualities. Dealing with the data deluge from heterogeneous IoT resources and services imposes new challenges on indexing, discovery, and ranking mechanisms that will allow building applications that require on-line access and retrieval of ad-hoc IoT data. However, the existing IoT data indexing and discovery approaches are complex or centralised, which hinders their scalability. The primary objective of this article is to provide a holistic overview of the state-of-the-art on indexing, discovery, and ranking of IoT data. The article aims to pave the way for researchers to design, develop, implement, and evaluate techniques and approaches for on-line large-scale distributed IoT applications and services.
Survey and Analysis of Kernel and Userspace Tracers on Linux
Authors: Gebai Mohamad , Dagenais Michel R.
Published: March 2018

As applications and operating systems are becoming more complex, the last decade has seen the rise of many tracing tools all across the software stack. This article presents a hands-on comparison of modern tracers on Linux systems, both in user space and kernel space. The authors implement microbenchmarks that not only quantify the overhead of different tracers, but also sample fine-grained metrics that unveil insights into the tracers’ internals and show the cause of each tracer’s overhead. Internal design choices and implementation particularities are discussed, which helps us to understand the challenges of developing tracers. Furthermore, this analysis aims to help users choose and configure their tracers based on their specific requirements to reduce their overhead and get the most of out of them.
Tenets for Social Accessibility
Authors: Shinohara Kristen , Bennett Cynthia L. , Pratt Wanda , Wobbrock Jacob O.
Published: March 2018

Despite years of addressing disability in technology design and advocating user-centered design practices, popular mainstream technologies remain largely inaccessible for people with disabilities. We conducted a design course study investigating how student designers regard disability and explored how designing for multiple disabled and nondisabled users encouraged students to think about accessibility in the design process. Across two university course offerings one year apart, we examined how students focused on a design project while learning user-centered design concepts and techniques, working with people with and without disabilities throughout the project. In addition, we compared how students incorporated disability-focused design approaches within a classroom setting. We found that designing for multiple stakeholders with and without disabilities expanded student understanding of accessible design by demonstrating that people with the same disability could have diverse needs and by aligning such needs with those of nondisabled users. We also found that using approaches targeted toward designing for people with disabilities complemented interactions with users, particularly with regard to managing varying abilities across users, or incorporating social aspects. Our findings contribute to an understanding about how we might incur change in design practice by working with multiple stakeholders with and without disabilities whenever possible. We refined
Design for Social Accessibility
by incorporating these findings into three tenets emphasizing: (1) design for disability ought to incorporate users with and without disabilities, (2) design should address functional and social factors simultaneously, and (3) design should include tools to spur consideration of social factors in accessible design.
Bifurcation Analysis of a Rigid Impact Oscillator with Bilinear Damping
Authors: Zhang Liping , Jiang Haibo , Liu Yang
Published: March 2018

This paper studies a rigid impact oscillator with bilinear damping developed as the mechanical model of an impulsive switched system. The stability and the bifurcation of periodic orbits in the impact oscillator are determined by using the mapping methods. One‐parameter bifurcation analyses under variation of forcing frequency and amplitude of external excitation are carried out. Coexisting attractors and various types of bifurcations, such as grazing, period‐doubling, and saddle‐node, are observed, which show the complex phenomena inhered in this impact oscillator.
Direct Photocoagulation Guided by Merged Retinal Images for the Treatment of Focal Diabetic Macular Edema
Authors: Takamura Yoshihiro , Matsumura Takehiro , Arimura Shogo , Gozawa Makoto , Morioka Masakazu , YutakaYamada  , Inatani Masaru
Published: March 2018

Purpose. To introduce a novel laser photocoagulation (PC) protocol named merged image-guided PC (MIG-PC), which included merging the images of the fundus, optical coherence tomography (OCT) map, and fluorescein angiography (FA). We compared the anatomical and functional results between MIG-PC and FA-guided PC (FG-PC) for the treatment of focal diabetic macular edema (DME). Method. We examined the treatment outcomes in 27 consecutive eyes treated with MIG-PC compared with 28 matched eyes treated with FG-PC. We identified the microaneurysms (MAs) located in the focal edema areas and ablated them using focal PC. Best-corrected visual acuity (BCVA) and retinal thickness (RT) measured using OCT were compared between the groups at baseline and 2, 4, 8, 12, and 24 weeks after treatment. Results. The foveal and perifoveal RT were reduced after treatment in both the groups, and the perifoveal RT in the MIG-PC group was significantly lower than that in the FG-PC group at 4 weeks and thereafter. BCVA in the MIG-PC group was significantly higher than that in the FG-PC group at 12 and 24 weeks. The numbers of laser spots (p=0.0001), additional laser treatments (p=0.0121), and intravitreal injection of ranibizumab (p=0.0012) in the MIG-PC group were significantly lower than those in the FG-PC group (Mann–Whitney test). Conclusion. MIG-PC contributed to the improvement in BCVA and reduction in RT, number of laser shots required, and retreatment rates. Based on our data, MIG-PC can be recommended for the treatment of focal DME. This trial is registered with ID UMIN000030390.
On the Direct Kinematics Problem of Parallel Mechanisms
Authors: Seibel Arthur , Schulz Stefan , Schlattmann Josef
Published: March 2018

The direct kinematics problem of parallel mechanisms, that is, determining the pose of the manipulator platform from the linear actuators’ lengths, is, in general, uniquely not solvable. For this reason, instead of measuring the lengths of the linear actuators, we propose measuring their orientations and, in most cases, also the orientation of the manipulator platform. This allows the design of a low-cost sensor system for parallel mechanisms that completely renounces length measurements and provides a unique solution of their direct kinematics.
Tumor-Shed Antigen Affects Antibody Tumor Targeting: Comparison of Two 89Zr-Labeled Antibodies Directed against Shed or Nonshed Antigens
Authors: Lee Jae-Ho , Kim Heejung , Yao Zhengsheng , Szajek Lawrence P. , Grasso Luigi , Kim Insook , Paik Chang H.
Published: March 2018

We investigated the effect of shed antigen mesothelin on the tumor uptake of amatuximab, a therapeutic anti-mesothelin mAb clinically tested in mesothelioma patients. The B3 mAb targeting a nonshed antigen was also analyzed for comparison. The mouse model implanted with A431/H9 tumor, which expresses both shed mesothelin and nonshed Lewis-Y antigen, provided an ideal system to compare the biodistribution and PET imaging profiles of the two mAbs. Our study demonstrated that the tumor and organ uptakes of 89Zr-B3 were dose-independent when 3 doses, 2, 15, and 60 μg B3, were compared at 24 h after injection. In contrast, tumor and organ uptakes of 89Zr-amatuximab were dose-dependent, whereby a high dose (60 μg) was needed to achieve tumor targeting comparable to the low dose (2 μg) of 89Zr-B3, suggesting that shed mesothelin may affect amatuximab tumor targeting as well as serum half-life. The autoradiography analysis showed that the distribution of 89Zr-B3 was nonuniform with the radioactivity primarily localized at the tumor periphery independent of the B3 dose. However, the autoradiography analysis for 89Zr-amatuximab showed dose-dependent distribution profiles of the radiolabel; at 10 μg dose, the radiolabel penetrated toward the tumor core with its activity comparable to that at the tumor periphery, whereas at 60 μg dose, the distribution profile became similar to those of 89Zr-B3. These results suggest that shed antigen in blood may act as a decoy requiring higher doses of mAb to improve serum half-life as well as tumor targeting. Systemic mAb concentration should be at a severalfold molar excess to the shed Ag in blood to overcome the hepatic processing of mAb-Ag complexes. On the other hand, mAb concentration should remain lower than the shed Ag concentration in the tumor ECS to maximize tumor penetration by passing binding site barriers.
A Midgut Duplication Cyst Lined by Respiratory Epithelium
Authors: Mahendran Balaji , Bracey Tim , Kochupapy Rajesh T.
Published: March 2018

Duplication cysts are an uncommon finding. Majority of these cases are found in the region of the midgut, and many have been reported in literature. However, there has been only one previous case of a midgut duplication cyst lined by respiratory epithelium. This is a rare pathology, of which very little is known about. The pathophysiology of these cases is also difficult to explain. We aim to present a case of a midgut duplication cyst in a paediatric patient, who had other abnormalities as well. We also aim to offer a hypothesis for this case.
Impact of Admission Blood Glucose on Coronary Collateral Flow in Patients with ST-Elevation Myocardial Infarction
Authors: Kurmus Ozge , Aslan Turgay , Ekici Berkay , Baglan Uzunget Sezen , Karaarslan Sukru , Tanindi Asli , Erkan Aycan Fahri , Akgul Ercan Ebru , Kervancıoglu Celal
Published: March 2018

In patients with acute myocardial infarction, glucose metabolism is altered and acute hyperglycemia on admission is common regardless of diabetes status. The development of coronary collateral is heterogeneous among individuals with coronary artery disease. In this study, we aimed to investigate whether glucose value on admission is associated with collateral flow in ST-elevation myocardial infarction (STEMI) patients. We retrospectively evaluated 190 consecutive patients with a diagnosis of first STEMI within 12 hours of onset of chest pain. Coronary collateral development was graded according to Rentrop classification. Rentrop 0-1 was graded as poor collateral development, and Rentrop 2-3 was graded as good collateral development. Admission glucose was measured and compared between two groups. Mean admission glucose level was 173.0 ± 80.1 mg/dl in study population. Forty-five (23.7%) patients had good collateral development, and 145 (76.3%) patients had poor collateral development. There were no statistically significant differences in demographic characteristics between two groups. Three-vessel disease was more common in patients with good collateral development (p=0.026). Mean admission glucose level was higher in patients with poor collateral than good collateral (180.6 ± 84.9 mg/dl versus 148.7 ± 56.6 mg/dl, resp., p=0.008). In univariate analysis, higher admission glucose was associated with poor collateral development, but multivariate logistic regression analysis revealed a borderline result (odds ratio 0.994, 95% CI 0.989–1.000, p=0.049). Our results suggest that elevated glucose on admission may have a role in the attenuation of coronary collateral blood flow in acute myocardial infarction. Further studies are needed to validate our results.
Acupuncture for Acne Vulgaris: A Systematic Review and Meta‐Analysis
Authors: Mansu Suzi S. Y. , Liang Haiying , Parker Shefton , Coyle Meaghan E. , Wang Kaiyi , Zhang Anthony L. , Guo Xinfeng , Lu Chuanjian , Xue Charlie C. L.
Published: March 2018

Purpose. To conduct a systematic review and meta‐analysis to determine the current best available evidence of the efficacy and safety of acupuncture and related therapies for acne vulgaris. Methods. Eleven English and Chinese databases were searched to identify randomized controlled trials (RCTs) of acne vulgaris compared to pharmacotherapies, no treatment, and sham or placebo acupuncture. Methodological quality was assessed using Cochrane Collaboration’s risk of bias tool. Meta‐analysis was conducted using RevMan software. Results. Twelve RCTs were included in the qualitative review and 10 RCTs were included in meta‐analysis. Methodological quality of trials was generally low. The chance of achieving ≥30% change in lesion count in the acupuncture group was no different to the pharmacotherapy group (RR: 1.07 [95% CI 0.98, 1.17]; I2 = 8%) and ≥50% change in lesion count in the acupuncture group was not statistically different to the pharmacotherapy group (RR: 1.07 [95% CI 0.98, 1.17]; I2 = 50%). Conclusions. While caution should be exercised due to quality of the included studies, acupuncture and auricular acupressure were not statistically different to guideline recommended treatments but were with fewer side effects and may be a treatment option. Future trials should address the methodological weaknesses and meet standard reporting requirements stipulated in STRICTA.
Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet
Authors: Ma Xiaoqing , Du Wenhua , Shao Shanshan , Yu Chunxiao , Zhou Lingyan , Jing Fei
Published: March 2018

Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.
Reprogramming of Mouse Calvarial Osteoblasts into Induced Pluripotent Stem Cells
Authors: Wang Yinxiang , Liu Jessica Aijia , Leung Keith K. H. , Sham Mai Har , Chan Danny , Cheah Kathryn S. E. , Cheung Martin
Published: March 2018

Previous studies have demonstrated the ability of reprogramming endochondral bone into induced pluripotent stem (iPS) cells, but whether similar phenomenon occurs in intramembranous bone remains to be determined. Here we adopted fluorescence-activated cell sorting-based strategy to isolate homogenous population of intramembranous calvarial osteoblasts from newborn transgenic mice carrying bothOsx1-GFP::CreandOct4-EGFPtransgenes. Following retroviral transduction of Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc), enriched population of osteoblasts underwent silencing of Osx1-GFP::Cre expression at early stage of reprogramming followed by late activation of Oct4-EGFP expression in the resulting iPS cells. These osteoblast-derived iPS cells exhibited gene expression profiles akin to embryonic stem cells and were pluripotent as demonstrated by their ability to form teratomas comprising tissues from all germ layers and also contribute to tail tissue in chimera embryos. These data demonstrate that iPS cells can be generated from intramembranous osteoblasts.
Structural and Kinetic Hydrogen Sorption Properties of Zr0.8Ti0.2Co Alloy Prepared by Ball Milling
Authors: He Hui , Kou Huaqin , Luo Wenhua , Tang Tao , Huang Zhiyong , Sang Ge , Zhang Guanghui , Ba Jingwen , Liu Meng
Published: March 2018

The effects of ball milling on the hydrogen sorption kinetics and microstructure of Zr0.8Ti0.2Co have been systematically studied. Kinetic measurements show that the hydrogenation rate and amount of Zr0.8Ti0.2Co decrease with increasing the ball milling time. However, the dehydrogenation rate accelerates as the ball milling time increases. Meanwhile, the disproportionation of Zr0.8Ti0.2Co speeds up after ball milling and the disproportionation kinetics is clearly inclined to be linear with time at 500°C. It is found from X-ray powder diffraction (XRD) results that the lattice parameter of Zr0.8Ti0.2Co gradually decreases from 3.164 Å to 3.153 Å when the ball milling time extends from 0 h to 8 h, which is mainly responsible for the hydrogen absorption/desorption behaviors. In addition, scanning electron microscope (SEM) images demonstrate that the morphology of Zr0.8Ti0.2Co has obviously changed after ball milling, which is closely related to the hydrogen absorption kinetics. Besides, high-resolution transmission electron microscopy (HRTEM) images show that a large number of disordered microstructures including amorphous regions and defects exist after ball milling, which also play an important role in hydrogen sorption performances. This work will provide some insights into the principles of how to further improve the hydrogen sorption kinetics and disproportionation property of Zr0.8Ti0.2Co.
Automated Segmentation Methods of Drusen to Diagnose Age-Related Macular Degeneration Screening in Retinal Images
Authors: Kim Young Jae , Kim Kwang Gi
Published: March 2018

Existing drusen measurement is difficult to use in clinic because it requires a lot of time and effort for visual inspection. In order to resolve this problem, we propose an automatic drusen detection method to help clinical diagnosis of age-related macular degeneration. First, we changed the fundus image to a green channel and extracted the ROI of the macular area based on the optic disk. Next, we detected the candidate group using the difference image of the median filter within the ROI. We also segmented vessels and removed them from the image. Finally, we detected the drusen through Renyi’s entropy threshold algorithm. We performed comparisons and statistical analysis between the manual detection results and automatic detection results for 30 cases in order to verify validity. As a result, the average sensitivity was 93.37% (80.95%~100%) and the average DSC was 0.73 (0.3~0.98). In addition, the value of the ICC was 0.984 (CI: 0.967~0.993, p<0.01), showing the high reliability of the proposed automatic method. We expect that the automatic drusen detection helps clinicians to improve the diagnostic performance in the detection of drusen on fundus image.