bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical analysis of constitutive pigmentation of human epidermis reveals constant eumelanin to pheomelanin ratio
Authors: Del Bino Sandra , Ito Shosuke , Sok Juliette , Nakanishi Yukiko , Bastien Philippe , Wakamatsu Kazumasa , Bernerd Françoise
Published: August 2015

The skin constitutive pigmentation is given by the amount of melanin pigment, its relative composition (eu/pheomelanin) and distribution within the epidermis, and is largely responsible for the sensitivity to UV exposure. Nevertheless, a precise knowledge of melanins in human skin is lacking. We characterized the melanin content of human breast skin samples with variable pigmentations rigorously classified through the Individual Typology Angle (ITA) by image analysis, spectrophotometry after solubilization with Soluene‐350 and high‐performance liquid chromatography (HPLC) after chemical degradation. ITA and total melanin content were found correlated, ITA and PTCA (degradation product of DHICA melanin), and TTCA (degradation product of benzothiazole‐type pheomelanin) as well but not 4‐AHP (degradation product of benzothiazine‐type pheomelanin). Results revealed that human epidermis comprises approximately 74% of eumelanin and 26% pheomelanin, regardless of the degree of pigmentation. They also confirm the low content of photoprotective eumelanin among lighter skins thereby explaining the higher sensitivity toward UV exposure.
Cytokine profile of food‐allergic post‐liver transplant children is identified by high levels of IL‐5 and low IL‐10 secretion from patients' peripheral blood mononuclear cells
Authors: Nahum Amit , Brener Avivit , Granot Ettie
Published: August 2015

Severe allergic reaction to food following liver transplantation is a well‐known phenomenon. However, the mechanisms underlying this phenomenon are not yet elucidated. This study aimed to reveal the nature of the immune response in post‐transplanted allergic patients and compare them to non‐allergic transplanted as well as allergic and non‐allergic control subjects, with focus on cytokine milieu. Post‐liver transplant patients with and without allergic reactions as well as food‐allergic but otherwise healthy and healthy non‐allergic control patients were recruited. We reviewed patient records and routine laboratory tests and assayed subjects' PBMCs, studying cytokine secretion profile in response to different stimuli. Post‐transplant patients with food allergy showed a unique cytokine profile in response to various stimuli, with extremely elevated IL‐5, low IL‐10 secretion, and somewhat higher IFN‐γ. T regulatory cell number was not significantly different among the groups of patients and controls. Immune response of food‐allergic post‐liver transplant patients is identified by a unique cytokine profile when compared to allergic but otherwise healthy individuals.
Treatment of localized mycosis fungoides with digital UV photochemotherapy
Authors: Reidel Ulrich , Bechstein Sarah , Lange‐Asschenfeldt Bernhard , Beyer Marc , Vandersee Staffan
Published: August 2015

Background/Purpose

Photochemochemotherapy with 8‐methoxypsoralen and UV‐A light (PUVA) is a well‐established treatment for mycosis fungoides (MF), although evidence for this therapy by means of prospective studies is scarce. However, long‐term risks of PUVA are premature skin aging and development of nonmelanoma skin cancer. We therefore evaluated a device for targeted UV therapy, which reduces irradiation of unaffected skin in MF patients.

Methods

Ten patients with patch‐ or plaque‐type MF affecting less than 10% body surface area were included in a prospective study. A total of 14 lesions were treated with cream PUVA using the digital phototherapy device skintrek® PT3.

Results

Seven of ten patients showed response to treatment. Complete clinical remission was achieved in four of ten patients (complete remission of seven of fourteen treated lesions) after an average of 13.4 weeks and an average cumulative UV dose of 42.6 J/cm2 in a mean of 31.2 treatment sessions. Adverse events were rare and of mild severity.

Conclusions

This study is the first prospective trial demonstrating efficacy and safety of cream PUVA in MF patients. As healthy adjacent skin remains unaffected, the potential to reduce the carcinogenic risk of PUVA treatment makes this new method a promising therapeutic option for localized MF.
Enhanced sensitization to animal, interpersonal, and intergroup fear‐relevant stimuli (but no evidence for selective one‐trial fear learning)
Authors: Lipp Ottmar V. , Cronin Sophie L. , Alhadad Sakinah S. J. , Luck Camilla C.
Published: August 2015

Selective sensitization has been proposed as an alternative explanation for enhanced responding to animal fear‐relevant stimuli—snakes and spiders—during extinction of Pavlovian fear conditioning. The current study sought to replicate the phenomenon using a shock workup procedure as the sensitizing manipulation and to extend it to interpersonal and intergroup fear‐relevant stimuli—angry faces and other‐race faces. Assessment of selective sensitization was followed by a one‐trial fear learning procedure. Selective sensitization, larger electrodermal responses to fear‐relevant than to control stimuli after sensitization, or a larger increase in electrodermal responding to fear‐relevant than to control stimuli after sensitization was observed across stimulus domains. However, the one‐trial fear learning procedure failed to provide evidence for enhanced fear conditioning to fear‐relevant stimuli. One‐trial fear learning was either absent or present for fear‐relevant and nonfear‐relevant stimuli. The current study confirms that electrodermal responses to fear‐relevant stimuli across stimulus domains are subject to selective sensitization.
The Impact of Performance Management on Performance in Public Organizations: A Meta‐Analysis
Authors: Gerrish Ed
Published: August 2015

Performance‐based management is pervasive in public organizations; countless governments have implemented performance management systems with the hope that they will improve organizational effectiveness. However, there has been little comprehensive review of their impact. This article conducts a meta‐analysis on the impact of performance management on performance in public organizations. It contributes to the current literature in three ways. First, it examines the effect of the “average” performance management system. Second, it examines the influence of management: whether beneficial performance management practices moderate the average effect. Third, it examines the effect of “time” on performance management. Using 2,188 effects from 49 studies, the analysis finds that performance management has a small average effect. However, the effect is substantially larger when indicators of best practices in high‐quality studies are included, indicating that management practices have an important impact on the effectiveness of performance management systems. Evidence for the effect of time is mixed.
Reproductive Patterns in the Non‐Breeding Season in Asinina de Miranda Jennies
Authors: Quaresma M , Silva SR , Payan‐Carreira R
Published: August 2015

Contents

This study aims to characterize the reproductive patterns in Asinina de Miranda jennies during the non‐breeding season. Reproductive activity was surveyed in 12 females, aged between 3 and 18 years old, using ultrasound and teasing with a jack. The animals were monitored from September to April, six in each consecutive year. Of these 12 females, nine showed disruption to the normal pattern of ovarian activity during the non‐breeding season. Loss of normal cyclicity included anoestrus (41.7%), silent ovulatory oestrus (25%), and persistence of corpus luteum (8.3%). Only three females maintained a regular cyclic pattern with oestrous behaviour during the non‐breeding season. Anoestrus began in early November and lasted for an average of 147 ± 28 days (113–191 days), ending near to the spring equinox. Onset of silent oestrous cycles began more erratically, between October and February. In both groups the first behavioural ovulation of the year occurred around the time of the spring equinox. Disrupted reproductive activity was preceded by a shorter oestrous cycle only in females entering anoestrus. The mean follicle size in the first ovulation of the year was larger than in the reproductive season (44.7 ± 2.45 mm vs 39.2 ± 3.60 mm) in anoestrous jennies with protracted oestrus. Though age and body condition score (BCS) were associated, changes in BCS below a threshold of four points (for anoestrus) and five points (for silent oestrus) contributed greatly to disruption of reproductive cycles. BCS in females with regular oestrous cycles during the winter season remained unchanged or exceeded five points prior to the winter solstice.
The Concepts of Risk, Safety, and Security: Applications in Everyday Language
Authors: Boholm Max , Möller Niklas , Hansson Sven Ove
Published: August 2015

The concepts of risk, safety, and security have received substantial academic interest. Several assumptions exist about their nature and relation. Besides academic use, the words risk, safety, and security are frequent in ordinary language, for example, in media reporting. In this article, we analyze the concepts of risk, safety, and security, and their relation, based on empirical observation of their actual everyday use. The “behavioral profiles” of the nouns risk, safety, and security and the adjectives risky, safe, and secure are coded and compared regarding lexical and grammatical contexts. The main findings are: (1) the three nouns risk, safety, and security, and the two adjectives safe and secure, have widespread use in different senses, which will make any attempt to define them in a single unified manner extremely difficult; (2) the relationship between the central risk terms is complex and only partially confirms the distinctions commonly made between the terms in specialized terminology; (3) whereas most attempts to define risk in specialized terminology have taken the term to have a quantitative meaning, nonquantitative meanings dominate in everyday language, and numerical meanings are rare; and (4) the three adjectives safe, secure, and risky are frequently used in comparative form. This speaks against interpretations that would take them as absolute, all‐or‐nothing concepts.
The Impact of Inheritance on the Distribution of Wealth: Evidence from Great Britain
Authors: Karagiannaki Eleni
Published: August 2015

Using the British Household Panel Survey, we investigate the role of inheritance in shaping the distribution of household wealth in Great Britain during 1995–2005a period characterized by a substantial increase in wealth and an equally important decrease in wealth inequality. Abstracting from behavioral effects, we find that inheritances received during this period accounted for 30 percent of the increase in wealth of inheritors. Regression estimates of the effect of inheritance on wealth accumulation suggest that households spend 30 percent of their inheritances on average, and that there is substantial heterogeneity in household responses. Households that accumulated more wealth saved a larger share of their inheritances, as did middle aged households and those with lower initial wealth. Although inheritances are highly unequal they had a small impact on overall wealth inequality. This mainly reflected the fact that their size relative to other sources of wealth was very small.
Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy
Authors: Nilsen T. S. , Thorsen L. , Fosså S. D. , Wiig M. , Kirkegaard C. , Skovlund E. , Benestad H. B. , Raastad T.
Published: August 2015

Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross‐sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 μm2, P = 0.04), with the only significant increase observed in type II fibers (1076 μm2, P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.
The Influence of Goal Value on Persistence in Exuberant Chinese Children
Authors: He Jie , Guo Dong , Zhang Qing , Liu Yuxia , Lou Liyue , Shen Mowei
Published: August 2015

With regard to the study of temperament and motivation in young children, exuberance, an important temperamental characteristic of the approach motivational system, has been relatively understudied in comparison with behavioral inhibition. However, due to the relationship between exuberance and behavioral regulation (e.g., problem behavior, task persistence), it is an important topic of study. Accordingly, this study examined whether the incentive value of goals moderated the relationship between exuberance and persistence in 109 Chinese preschoolers. Children's temperamental exuberance was assessed by behavioral observation and parental report. Their persistence was measured in two goal‐blocked contexts (tower‐building [TB] and locked box [LB]). In each task, children were randomly assigned to either a high‐ or low‐incentive condition designed to vary the incentive value of a given goal. Results suggested that exuberance was positively associated with persistence in the high‐incentive condition of TB and in both conditions of LB. The results highlight the incentive value of goals as an important factor for behavioral regulation development in exuberant Chinese children.
Reciprocal Relations across Time between Basic Values and Value‐expressive Behaviors: A Longitudinal Study among Children
Authors: Vecchione Michele , Döring Anna K. , Alessandri Guido , Marsicano Gilda , Bardi Anat
Published: August 2015

The current study examines the reciprocal relations between children's values and value‐expressive behavior over a sixth‐month period. Three hundred and ten sixth‐grade students in Italy completed value and value‐expressive behavior questionnaires three times in three‐month intervals during the scholastic year. We assessed Schwartz's (1992) higher‐order values of conservation, openness to change, self‐enhancement, and self‐transcendence, as well as their respective expressive behaviors. Reciprocal relations over time between values and behaviors were examined using a cross‐lagged longitudinal design. Results showed that values and behaviors had reciprocal longitudinal effects on one another, after the stability of the variables was taken into account (i.e., values predicted change in behaviors, but also behaviors predicted change in values). Our findings also revealed that: (1) values were more stable over time than behaviors and (2) the longitudinal effect of values on behaviors tended to be stronger than the longitudinal effect of behaviors on values. Findings are discussed in light of the recent developmental literature on value change.
Mother Emotion, Child Temperament, and Young Children's Helpless Responses to Failure
Authors: Smiley Patricia A. , Tan Sherylle J. , Goldstein Alison , Sweda Jennifer
Published: August 2015

Young children differ in their responses to failure, displaying mastery or helpless behavior patterns. We examine the moderating role of child temperament on the association between parent warmth/negativity and children's helpless responses to failure. Regarding temperament, we focus on tendencies to experience interest and sadness because they entail task engagement and withdrawal, respectively. We measured mother (n=150) expressions of positive and negative emotion during a teaching task, assessed temperament using LabTAB‐Preschool episodes, and coded helplessness during an impossible puzzle task. Maternal negative emotion during teaching was positively associated with helplessness, but only for children low in interest. Maternal warmth was negatively associated with helplessness, but only for children high in sadness; sadness did not moderate the relation between maternal negativity and helplessness. Findings provide support for parenting by temperament goodness‐of‐fit models and for a discrete emotions approach to temperament.
Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients
Authors: Swartling L. , Allard A. , Törlen J. , Ljungman P. , Mattsson J. , Sparrelid E.
Published: August 2015

Background

An outbreak of human adenovirus (HAdV) A31 occurred from December 2011 to March 2012 at the Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital in Sweden. We analyzed the outbreak, the routes of transmission, and report the medical consequences.

Methods

The medical records of all patients admitted to CAST during the outbreak period were studied. Phylogenetic analysis of the patient HAdV strains was performed by sequencing the hexon gene and the more variable E3 gene.

Results

We identified 9 cases of HAdV A31. Hygiene measures were implemented, but transmission continued for 2 months. All 9 patients had been admitted to the ward, but 2 had no connection in time to other known HAdV A31 cases. DNA sequencing of the patient strains strongly suggested nosocomial transmission. Transplantation was postponed and then cancelled in 1 patient, and 5 patients were treated with cidofovir because of high levels of viremia. In 7 patients, concomitant graft‐versus‐host disease (GVHD) grade II–V complicated the clinical picture, as it was difficult to distinguish symptoms of GVHD from those of HAdV infection.

Conclusion

An outbreak of HAdV in HSCT recipients can be difficult to control. Although none of the patients had severe disease, the medical consequences were significant. It is possible that unidentified cases with mild symptoms may have caused continuous transmission at the unit. Regular testing of all patients several weeks beyond the last case identified may be an important measure to control transmission.
Effect of feeding on the pharmacokinetics of oral minocycline in healthy research dogs
Authors: Hnot Melanie L. , Cole Lynette K. , Lorch Gwendolen , Rajala‐Schultz Paivi J. , Papich Mark G.
Published: August 2015

Background

The effect of food on minocycline oral absorption in dogs is unknown.

Objective

The objective was to determine the pharmacokinetics of minocycline after administration of a single oral dose in fed and fasted dogs.

Methods

Ten research hounds were administered oral minocycline (approximately 5 mg/kg) with and without food, in a crossover study, with a one‐week wash‐out between treatments. Blood samples were collected immediately prior to minocycline administration and over 24 h. Minocycline plasma drug concentrations were measured using high‐performance liquid chromatography using ultraviolet detection and were analysed with compartmental modelling to determine primary pharmacokinetic parameters. Each dog was analysed independently, followed by calculation of means and variation of the dogs. The Wilcoxon signed–rank test [analysing secondary pharmacokinetic parameters – peak concentration (CMAX), area under the concentration versus time curve (AUC)] was used to compare the two groups. A population pharmacokinetic modelling approach was performed using nonlinear mixed effects modelling of primary parameters for the population as fixed effects and the difference between subjects as a random effect. Covariate analysis was used to identify the source of variability in the population.

Results

No significant difference was found between treatments forAUC(P = 0.0645), althoughAUCwas higher in fasted dogs. A significant difference was found forCMAX(P = 0.0059), with fasted dogs attaining a higherCMAX. The covariate of fed versus fasted accounted for a significant variation in the pharmacokinetics.

Conclusions and clinical importance

Because feeding was a significant source of variation for the population's primary pharmacokinetic parameters and fasted dogs had higher minocycline concentrations, we recommend administering minocycline without food.
Refined curve counting with tropical geometry
Authors: Block Florian , Göttsche Lothar
Published: August 2015

The Severi degree is the degree of the Severi variety parametrizing plane curves of degree $d$ with ${\it\delta}$ nodes. Recently, Göttsche and Shende gave two refinements of Severi degrees, polynomials in a variable $y$, which are conjecturally equal, for large $d$. At $y=1$, one of the refinements, the relative Severi degree, specializes to the (non-relative) Severi degree. We give a tropical description of the refined Severi degrees, in terms of a refined tropical curve count for all toric surfaces. We also refine the equivalent count of floor diagrams for Hirzebruch and rational ruled surfaces. Our description implies that, for fixed ${\it\delta}$, the refined Severi degrees are polynomials in $d$ and $y$, for large $d$. As a consequence, we show that, for ${\it\delta}\leqslant 10$ and all $d\geqslant {\it\delta}/2+1$, both refinements of Göttsche and Shende agree and equal our refined counts of tropical curves and floor diagrams.
Caloric restriction in lean and obese strains of laboratory rat: effects on body composition, metabolism, growth and overall health
Authors: Aydin C. , Jarema K. A. , Phillips P. M. , Gordon C. J.
Published: August 2015

New Findings

What is the central question of this study?

How do lean and obese rats respond physiologically to caloric restriction?

What is the main finding and its importance?

Obese rats show marked benefits compared with lean animals.

Reduced body fat is associated with improved longevity with caloric restriction (CR) in rodents. Little is known regarding effects of CR in genetically lean versus obese strains. Long–Evans (LE) and Brown Norway (BN) rats make an ideal comparison for a CR study because the percentage body fat of young adult LE rats is double that of BN rats. Male LE and BN rats were either fed ad libitum (AL) or were calorically restricted to 80 or 90% of their AL weight. The percentages of fat, lean and fluid mass were measured non‐invasively at 2‐ to 4‐week intervals. Metabolic rate and respiratory quotient were measured after 3, 6, 9 and 12 months of CR. Overall health was scored monthly. The percentage of fat of the LE strain decreased with CR, whereas the percentage of fat of the BN strain remained above the AL group for several months. The percentage of lean mass increased above the AL for both strains subjected to CR. The percentage of fluid was unaffected by CR. The average metabolic rate over 22 h of the BN rats subjected to CR was reduced, whereas that of LE rats was increased slightly above the AL group. The respiratory quotient of BN rats was decreased with CR. Overall health of the CR LE group was significantly improved compared with that of the AL group, whereas health of the CR BN rats was impaired compared with the AL group. Overall, the lean BN and obese LE strains differ markedly in fat utilization and metabolic response to prolonged CR. There appears to be little benefit of CR in the lean strain.
Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training
Authors: Montero David , Cathomen Adrian , Jacobs Robert A. , Flück Daniela , de Leur Jeroen , Keiser Stefanie , Bonne Thomas , Kirk Niels , Lundby Anne‐Kristine , Lundby Carsten
Published: August 2015

Key points

This study assessed the respective contributions of haematological and skeletal muscle adaptations to any observed improvement in peak oxygen uptake () induced by endurance training (ET).

, peak cardiac output (), blood volumes and skeletal muscle biopsies were assessed prior (pre) to and after (post) 6 weeks of ET. Following the post‐ET assessment, red blood cell volume (RBCV) reverted to the pre‐ET level following phlebotomy and and were determined again.

We speculated that the contribution of skeletal muscle adaptations to an ET‐induced increase in could be identified when offsetting the ET‐induced increase in RBCV.

, , blood volumes, skeletal muscle mitochondrial volume density and capillarization were increased after ET. Following RBCV normalization, and reverted to pre‐ET levels.

These results demonstrate the predominant contribution of haematological adaptations to any increase in induced by ET.

It remains unclear whether improvements in peak oxygen uptake () following endurance training (ET) are primarily determined by central and/or peripheral adaptations. Herein, we tested the hypothesis that the improvement in following 6 weeks of ET is mainly determined by haematological rather than skeletal muscle adaptations. Sixteen untrained healthy male volunteers (age = 25 ± 4 years,  = 3.5 ± 0.5 l min−1) underwent supervised ET (6 weeks, 3–4 sessions per week). , peak cardiac output (), haemoglobin mass (Hbmass) and blood volumes were assessed prior to and following ET. Skeletal muscle biopsies were analysed for mitochondrial volume density (MitoVD), capillarity, fibre types and respiratory capacity (OXPHOS). After the post‐ET assessment, red blood cell volume (RBCV) was re‐established at the pre‐ET level by phlebotomy and and were measured again. We speculated that the contribution of skeletal muscle adaptations to the ET‐induced increase in would be revealed when controlling for haematological adaptations. and were increased (P < 0.05) following ET (9 ± 8 and 7 ± 6%, respectively) and decreased (P < 0.05) after phlebotomy (−7 ± 7 and −10 ± 7%). RBCV, plasma volume and Hbmass all increased (P < 0.05) after ET (8 ± 4, 4 ± 6 and 6 ± 5%). As for skeletal muscle adaptations, capillary‐to‐fibre ratio and total MitoVD increased (P < 0.05) following ET (18 ± 16 and 43 ± 30%), but OXPHOS remained unaltered. Through stepwise multiple regression analysis, , RBCV and Hbmass were found to be independent predictors of . In conclusion, the improvement in following 6 weeks of ET is primarily attributed to increases in and oxygen‐carrying capacity of blood in untrained healthy young subjects.
Effect of proton irradiation energy on AlGaN/GaN metal-oxide semiconductor high electron mobility transistors
Authors: Ahn Shihyun , Dong Chen , Zhu Weidi , Kim Byung-Jae , Hwang Ya-Hsi , Ren Fan , Pearton Stephen J. , Yang Gwangseok , Kim Jihyun , Patrick Erin , Tracy Brian , Smith David J. , Kravchenko Ivan I.
Published: August 2015

The effects of proton irradiation energy on dc characteristics of AlGaN/GaN metal-oxide semiconductor high electron mobility transistors (MOSHEMTs) using Al2O3 as the gate dielectric were studied. Al2O3/AlGaN/GaN MOSHEMTs were irradiated with a fixed proton dose of 5 × 1015 cm−2 at different energies of 5, 10, or 15 MeV. More degradation of the device dc characteristics was observed for lower irradiation energy due to the larger amount of nonionizing energy loss in the active region of the MOSHEMTs under these conditions. The reductions in saturation current were 95.3%, 68.3%, and 59.8% and reductions in maximum transconductance were 88%, 54.4%, and 40.7% after 5, 10, and 15 MeV proton irradiation, respectively. Both forward and reverse gate leakage current were reduced more than one order of magnitude after irradiation. The carrier removal rates for the irradiation energies employed in this study were in the range of 127–289 cm−1. These are similar to the values reported for conventional metal-gate high-electron mobility transistors under the same conditions and show that the gate dielectric does not affect the response to proton irradiation for these energies.
Dosimetric commissioning and quality assurance of scanned ion beams at the Italian National Center for Oncological Hadrontherapy
Authors: Mirandola Alfredo , Molinelli S. , Vilches Freixas G. , Mairani A. , Gallio E. , Panizza D. , Russo S. , Ciocca M. , Donetti M. , Magro G. , Giordanengo S. , Orecchia R.
Published: August 2015

Purpose:

To describe the dosimetric commissioning and quality assurance (QA) of the actively scanned proton and carbon ion beams at the Italian National Center for Oncological Hadrontherapy.

Methods:

The laterally integrated depth‐dose‐distributions (IDDs) were acquired with the PTW Peakfinder, a variable depth water column, equipped with two Bragg peak ionization chambers. fluka Monte Carlo code was used to generate the energy libraries, the IDDs in water, and the fragment spectra for carbon beams. EBT3 films were used for spot size measurements, beam position over the scan field, and homogeneity in 2D‐fields. Beam monitor calibration was performed in terms of number of particles per monitor unit using both a Farmer‐type and an Advanced Markus ionization chamber. The beam position at the isocenter, beam monitor calibration curve, dose constancy in the center of the spread‐out‐Bragg‐peak, dose homogeneity in 2D‐fields, beam energy, spot size, and spot position over the scan field are all checked on a daily basis for both protons and carbon ions and on all beam lines.

Results:

The simulated IDDs showed an excellent agreement with the measured experimental curves. The measured full width at half maximum (FWHM) of the pencil beam in air at the isocenter was energy‐dependent for both particle species: in particular, for protons, the spot size ranged from 0.7 to 2.2 cm. For carbon ions, two sets of spot size are available: FWHM ranged from 0.4 to 0.8 cm (for the smaller spot size) and from 0.8 to 1.1 cm (for the larger one). The spot position was accurate to within ±1 mm over the whole 20 × 20 cm2 scan field; homogeneity in a uniform squared field was within ±5% for both particle types at any energy. QA results exceeding tolerance levels were rarely found. In the reporting period, the machine downtime was around 6%, of which 4.5% was due to planned maintenance shutdowns.

Conclusions:

After successful dosimetric beam commissioning, quality assurance measurements performed during a 24‐month period show very stable beam characteristics, which are therefore suitable for performing safe and accurate patient treatments.
Prediction of standard‐dose brain PET image by using MRI and low‐dose brain [18F]FDG PET images
Authors: Kang Jiayin , Gao Yaozong , Shi Feng , Lalush David S. , Lin Weili , Shen Dinggang
Published: August 2015

Purpose:

Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High‐quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high‐quality PET images, a standard‐dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient's exposure to radiation. One solution to solve this problem is predicting standard‐dose PET images using low‐dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard‐dose brain [18F]FDG PET image by using a low‐dose brain [18F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image.

Methods:

The authors employ a regression forest for predicting the standard‐dose brain [18F]FDG PET image by low‐dose brain [18F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low‐dose PET and MRI images to build tissue‐specific models that can be used to initially predict standard‐dose brain [18F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy.

Results:

The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low‐dose PET, and standard‐dose PET images, using leave‐one‐out cross‐validations. The proposed algorithm gives promising results with well‐estimated standard‐dose brain [18F]FDG PET image and substantially enhanced image quality of low‐dose brain [18F]FDG PET image.

Conclusions:

In this paper, the authors propose a framework to generate standard‐dose brain [18F]FDG PET image using low‐dose brain [18F]FDG PET and MRI images. Both the visual and quantitative results indicate that the standard‐dose brain [18F]FDG PET can be well‐predicted using MRI and low‐dose brain [18F]FDG PET.
A multimodality segmentation framework for automatic target delineation in head and neck radiotherapy
Authors: Yang Jinzhong , Beadle Beth M. , Garden Adam S. , Schwartz David L. , Aristophanous Michalis
Published: August 2015

Purpose:

To develop an automatic segmentation algorithm integrating imaging information from computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) to delineate target volume in head and neck cancer radiotherapy.

Methods:

Eleven patients with unresectable disease at the tonsil or base of tongue who underwent MRI, CT, and PET/CT within two months before the start of radiotherapy or chemoradiotherapy were recruited for the study. For each patient, PET/CT and T1‐weighted contrast MRI scans were first registered to the planning CT using deformable and rigid registration, respectively, to resample the PET and magnetic resonance (MR) images to the planning CT space. A binary mask was manually defined to identify the tumor area. The resampled PET and MR images, the planning CT image, and the binary mask were fed into the automatic segmentation algorithm for target delineation. The algorithm was based on a multichannel Gaussian mixture model and solved using an expectation–maximization algorithm with Markov random fields. To evaluate the algorithm, we compared the multichannel autosegmentation with an autosegmentation method using only PET images. The physician‐defined gross tumor volume (GTV) was used as the “ground truth” for quantitative evaluation.

Results:

The median multichannel segmented GTV of the primary tumor was 15.7 cm3 (range, 6.6–44.3 cm3), while the PET segmented GTV was 10.2 cm3 (range, 2.8–45.1 cm3). The median physician‐defined GTV was 22.1 cm3 (range, 4.2–38.4 cm3). The median difference between the multichannel segmented and physician‐defined GTVs was −10.7%, not showing a statistically significant difference (p‐value = 0.43). However, the median difference between the PET segmented and physician‐defined GTVs was −19.2%, showing a statistically significant difference (p‐value =0.0037). The median Dice similarity coefficient between the multichannel segmented and physician‐defined GTVs was 0.75 (range, 0.55–0.84), and the median sensitivity and positive predictive value between them were 0.76 and 0.81, respectively.

Conclusions:

The authors developed an automated multimodality segmentation algorithm for tumor volume delineation and validated this algorithm for head and neck cancer radiotherapy. The multichannel segmented GTV agreed well with the physician‐defined GTV. The authors expect that their algorithm will improve the accuracy and consistency in target definition for radiotherapy.
Presence of 1/f noise in the temporal structure of psychoacoustic parameters of natural and urban sounds
Authors: Yang Ming , De Coensel Bert , Kang Jian
Published: August 2015

1/f noise or pink noise, which has been shown to be universal in nature, has also been observed in the temporal envelope of music, speech, and environmental sound. Moreover, the slope of the spectral density of the temporal envelope of music has been shown to correlate well to its pleasing, dull, or chaotic character. In this paper, the temporal structure of a number of instantaneous psychoacoustic parameters of environmental sound is examined in order to investigate whether a 1/f temporal structure appears in various types of sound that are generally preferred by people in everyday life. The results show, to some extent, that different categories of environmental sounds have different temporal structure characteristics. Only a number of urban sounds considered and birdsong, generally, exhibit 1/f behavior on short to medium duration time scales, i.e., from 0.1 s to 10 s, in instantaneous loudness and sharpness, whereas a more chaotic variation is found in birdsong at longer time scales, i.e., of 10 s–200 s. The other sound categories considered exhibit random or monotonic variations in the different time scales. In general, this study shows that a 1/f temporal structure is not necessarily present in environmental sounds that are commonly perceived as pleasant.
Stromal cell–derived factor 2 is critical for Hsp90-dependent eNOS activation
Authors: Siragusa Mauro , Fröhlich Florian , Park Eon Joo , Schleicher Michael , Walther Tobias C. , Sessa William C.
Published: August 2015

SDF2 promotes the activation of the enzymes that produce the gasotransmitter nitric oxide.
The transcription cofactor c-JUN mediates phenotype switching and BRAF inhibitor resistance in melanoma
Authors: Ramsdale Rachel , Jorissen Robert N. , Li Frederic Z. , Al-Obaidi Sheren , Ward Teresa , Sheppard Karen E. , Bukczynska Patricia E. , Young Richard J. , Boyle Samantha E. , Shackleton Mark , Bollag Gideon , Long Georgina V. , Tulchinsky Eugene , Rizos Helen , Pearson Richard B. , McArthur Grant A. , Dhillon Amardeep S. , Ferrao Petranel T.
Published: August 2015

The transcriptional regulator c-JUN is a key mediator of the metastatic potential and drug resistance in melanoma.
Disrupting protein trafficking to reduce hepatic lipogenesis
Authors: VanHook Annalisa M.
Published: August 2015

The transcriptional coactivator CRTC2 functions at the endoplasmic reticulum to reduce activation of the transcription factor SREBP1, which promotes hepatic lipogenesis.
Active but not oncogenic
Authors: Prabakaran Sudhakaran
Published: August 2015

Disrupting ERK dimerization rather than catalytic activity may reduce cancer progression while limiting negative side effects.
Taking the STING out of infection
Authors: Gough Nancy R.
Published: August 2015

Analysis of how
Shigella
inhibits STING activity reveals that STING becomes activated upon reaching the Golgi membranes.
Darunavir and Ritonavir Total and Unbound Plasmatic Concentrations in HIV-HCV-Coinfected Patients with Hepatic Cirrhosis Compared to Those in HIV-Monoinfected Patients
Authors: Curran Adrian , Martí Ramon , López Rosa María , Pérez Mercè , Crespo Manel , Melià María Jesús , Navarro Jordi , Burgos Joaquín , Falcó Vicenç , Ocaña Inma , Ribera Esteban
Published: August 2015

Our objective was to describe the pharmacokinetic (PK) parameters of total and unbound darunavir and ritonavir concentrations in HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis, as ritonavir-boosted darunavir is mainly metabolized in the liver, and hepatic cirrhosis might modify darunavir-ritonavir concentrations. This was a prospective, case-control, and unicenter study. HIV-HCV-coinfected patients with compensated cirrhosis (cases) and HIV-monoinfected patients with normal liver function (controls) were included. Darunavir-ritonavir was given at 800/100 mg once daily. Patients were followed for 24 weeks to assess safety and efficacy. A steady-state 12-h PK study was performed. Total and unbound concentrations were determined by liquid chromatography-tandem mass spectrometry. The unbound fraction was obtained by ultrafiltration. The plasma area under the concentration-time curve (AUC) and oral clearance (CL/F) were assessed by noncompartmental models. Thirty patients (20 cases and 10 controls) were included. Among cirrhotic patients, the Child-Pugh score was C in 4 cases, B in 1 case, and A in 15 cases; the median (interquartile range) transient elastography values were 20 kPa (14 to 26 kPa), and 5 patients had prior clinical decompensations. There were no significant differences in the darunavir PK parameters between cases and controls except for longer time to maximum plasma concentrations (
T
max
) and half-lives in the cirrhotic patients. There were no significant differences in ritonavir total concentrations, but the unbound concentrations were higher in cirrhotic patients. There were significant correlations between the darunavir total and unbound concentrations in both cirrhotic patients and controls. There were no differences in PK parameters based on Child-Pugh score, liver elasticity, gender, or use of concomitant medications. In conclusion, in HIV-HCV-coinfected patients with clinically compensated cirrhosis receiving darunavir-ritonavir at 800/100 mg once daily, the darunavir total and unbound concentrations are similar to those observed in noncirrhotic patients, and dose adjustments are not necessary.
Emergence of Raoultella ornithinolytica Coproducing IMP-4 and KPC-2 Carbapenemases in China
Authors: Zheng Beiwen , Zhang Jing , Ji Jinru , Fang Yunhui , Shen Ping , Ying Chaoqun , Lv Jifang , Xiao Yonghong , Li Lanjuan
Published: August 2015

We report here the emergence of seven IMP-4-producing
Raoultella ornithinolytica
isolates obtained from one patient. All isolates carried the
bla
IMP-4
carbapenemase gene, five isolates also carried
bla
SHV-12
, four contained
bla
TEM-1
, and one contained
bla
OXA-1
. Notably, the
R. ornithinolytica
isolate Ro25724 also expressed
Klebsiella pneumoniae
carbapenemase (KPC)-2. The
bla
KPC-2
gene was located on a Tn
3
-Tn
4401
integration structure on a plasmid of ∼450 kb. This is the first description of the coexistence of
bla
KPC-2
and
bla
IMP-4
from the genus
Raoultella
.
HIV Drug Resistance Testing by High-Multiplex “Wide” Sequencing on the MiSeq Instrument
Authors: Lapointe H. R. , Dong W. , Lee G. Q. , Bangsberg D. R. , Martin J. N. , Mocello A. R. , Boum Y. , Karakas A. , Kirkby D. , Poon A. F. Y. , Harrigan P. R. , Brumme C. J.
Published: August 2015

Limited access to HIV drug resistance testing in low- and middle-income countries impedes clinical decision-making at the individual patient level. An efficient protocol to address this issue must be established to minimize negative therapeutic outcomes for HIV-1-infected individuals in such settings. This is an observational study to ascertain the potential of newer genomic sequencing platforms, such as the Illumina MiSeq instrument, to provide accurate HIV drug resistance genotypes for hundreds of samples simultaneously. Plasma samples were collected from Canadian patients during routine drug resistance testing (n= 759) and from a Ugandan study cohort (n= 349). Amplicons spanning HIV reverse transcriptase codons 90 to 234 were sequenced with both MiSeq sequencing and conventional Sanger sequencing methods. Sequences were evaluated for nucleotide concordance between methods, using coverage and mixture parameters for quality control. Consensus sequences were also analyzed for disparities in the identification of drug resistance mutations. Sanger and MiSeq sequencing was successful for 881 samples (80%) and 892 samples (81%), respectively, with 832 samples having results from both methods. Most failures were for samples with viral loads of <3.0 log10HIV RNA copies/ml. Overall, 99.3% nucleotide concordance between methods was observed. MiSeq sequencing achieved 97.4% sensitivity and 99.3% specificity in detecting resistance mutations identified by Sanger sequencing. Findings suggest that the Illumina MiSeq platform can yield high-quality data with a high-multiplex “wide” sequencing approach. This strategy can be used for multiple HIV subtypes, demonstrating the potential for widespread individual testing and annual population surveillance in resource-limited settings.
The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin
Authors: Garcia De Gonzalo C. V. , Denham E. L. , Mars R. A. T. , Stülke J. , van der Donk W. A. , van Dijl J. M.
Published: August 2015

The mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) ofBacillusspecies as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such asBacillusspecies andStaphylococcus aureus, including methicillin-resistantS. aureus(MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin.
Functional Analysis of a Bacitracin Resistance Determinant Located on ICE
Cp1
, a Novel Tn
916
-Like Element from a Conjugative Plasmid in Clostridium perfringens
Authors: Han Xiaoyan , Du Xiang-Dang , Southey Luke , Bulach Dieter M. , Seemann Torsten , Yan Xu-Xia , Bannam Trudi L. , Rood Julian I.
Published: August 2015

Bacitracins are mixtures of structurally related cyclic polypeptides with antibiotic properties. They act by interfering with the biosynthesis of the bacterial cell wall. In this study, we analyzed an avian necrotic enteritis strain of
Clostridium perfringens
that was resistant to bacitracin and produced NetB toxin. We identified a bacitracin resistance locus that resembled a bacitracin resistance determinant from
Enterococcus faecalis
. It contained the structural genes
bcrABD
and a putative regulatory gene,
bcrR
. Mutagenesis studies provided evidence that both
bcrA
and
bcrB
are essential for bacitracin resistance, and that evidence was supported by the results of experiments in which the introduction of both the
bcrA
and
bcrB
genes into a bacitracin-susceptible
C. perfringens
strain was required to confer bacitracin resistance. The wild-type strain was shown to contain at least three large, putatively conjugative plasmids, and the
bcrRABD
locus was localized to an 89.7-kb plasmid, pJIR4150. This plasmid was experimentally shown to be conjugative and was sequenced. The sequence revealed that it also carries a
tpeL
toxin gene and is related to the pCW3 family of conjugative antibiotic resistance and toxin plasmids from
C. perfringens
. The
bcr
genes were located on a genetic element, ICE
Cp1
, which is related to the Tn
916
family of integrative conjugative elements (ICEs). ICE
Cp1
appears to be the first Tn
916
-like element shown to confer bacitracin resistance. In summary, we identified in a toxin-producing
C. perfringens
strain a novel mobile bacitracin resistance element which was experimentally shown to be essential for bacitracin resistance and is carried by a putative ICE located on a conjugative plasmid.