bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Novel 1,2,3‐Triazole/Isoxazole‐Functionalized Imidazo[4,5‐b]pyridin‐2(3H)‐one Derivatives, Their Antimicrobial and Anticancer Activity
Authors: Banda Veeraswamy , Gautham Santhosh Kumar , Pillalamarri Sambasiva Rao , Chavva Kurumurthy , Banda Narsaiah
Published: July 2015

A series of novel 1,2,3‐triazole/isoxazole‐functionalized imidazo[4,5‐b]pyridine‐2(3H)‐one derivatives7and8were prepared starting from pyridin‐2(1H)‐one1in a series of steps. Initially, compound1was converted into imidazo[4,5‐b]pyridine‐2(3H)‐one5via formation of 2‐alkylamino/amino‐6‐phenyl‐4‐(trifluoromethyl)nicotinonitrile3followed by hydrolysis4and Hoffman type rearrangement5. Compound5was further reacted with propargyl bromide to form exclusivelyN‐propargylated derivatives6. Compounds6were cyclized with arylazides/aryloximes in the presence of CuI and sodium hypochlorite, respectively, and obtained title products7and8. All the final products7and8were screened for antimicrobial and anticancer activity.
Synthesis of stable isotopically labelled 3‐methylfuran‐2(5H)‐one and the corresponding strigolactones
Authors: Cheng Yun , Ding Wen‐hui , Long Qin , Zhao Min , Yang Jun , Li Xiao‐qiang
Published: July 2015

Conventional synthetic procedures of strigolactones (SLs) involve the independent synthesis of ring ABC and ring D, followed by a coupling of the two fragments. Here we prepared three kinds of stable, isotopically labelled D‐ring analogues productively using a facile protocol. Then, a coupling of the D‐rings to ring ABC produced three isotope‐labelled SL derivatives. Moreover, (+)‐D3‐2′‐epi‐1A and (−)‐ent‐D3‐2′‐epi‐1A with high enantiomeric purity were obtained via chiral resolution.
Detection of early changes after growth plate injury using MRI
Authors: Nakase Masashi , Kim Wook‐Cheol , Oka Yoshinobu , Hosokawa Motoo , Yoshida Takashi , Yamada Naotake , Nishida Atsushi , Yokozeki Kouichi , Ikoma Kazuya , Kawata Mitsuhiro , Kubo Toshikazu
Published: July 2015

Background

To elucidate the association between growth plate injury size and the beginning of physeal growth disturbance by MRI.

Methods

Thirty‐two 5‐week‐old male Japanese white rabbits were used. Injuries were made to the right tibial proximal growth plate central region with a 3.0‐mm and a 1.2‐mm drill. The left tibia was used as a control. MRI (7.04 Tesla [T], gradient echo: repetition time [TR], 71.68 ms; echo time [TE], 3.60 ms; proton‐density weighted imaging: TR, 2000 ms; TE, 12 ms) of the growth plates was performed at 1, 4, 8, 10, and 12 weeks postinjury. Tibia length, histology, radiography, and microcomputed tomography (µCT) were studied.

Results

MRI showed that at 10 and 12 weeks postinjury in the 3.0‐mm group, the medial and lateral growth plates in the noninjured regions were significantly reduced compared with the controls (P < 0.05). At 12 weeks postinjury in the 1.2‐mm group, medial and lateral growth plates in the noninjured regions were significantly reduced (P < 0.05). Tibia length and histological growth plate height of injured side in both groups were significantly shorter than controls at 12 weeks postinjury (P < 0.05). Comparison with the controls showed no significant difference at any of the time periods in either the 3.0‐ or 1.2‐mm group according to the radiographic studies (P > 0.05). Bony bridges developed in all the subjects of the 3.0‐mm group and in five of eight subjects of the 1.2‐mm group, as shown by µCT images.

Conclusion

This study suggested that growth plate injury size was associated with the timing of the beginning of physeal growth disturbance. J. MAGN. RESON. IMAGING 2015;42:1698–1704.
Performance of an efficient image‐registration algorithm in processing MR renography data
Authors: Conlin Christopher C. , Zhang Jeff L. , Rousset Florian , Vachet Clement , Zhao Yangyang , Morton Kathryn A. , Carlston Kristi , Gerig Guido , Lee Vivian S.
Published: July 2015

Purpose

To evaluate the performance of an edge‐based registration technique in correcting for respiratory motion artifacts in magnetic resonance renographic (MRR) data and to examine the efficiency of a semiautomatic software package in processing renographic data from a cohort of clinical patients.

Materials and Methods

The developed software incorporates an image‐registration algorithm based on the generalized Hough transform of edge maps. It was used to estimate glomerular filtration rate (GFR), renal plasma flow (RPF), and mean transit time (MTT) from 36 patients who underwent free‐breathing MRR at 3T using saturation‐recovery turbo‐FLASH. The processing time required for each patient was recorded. Renal parameter estimates and model‐fitting residues from the software were compared to those from a previously reported technique. Interreader variability in the software was quantified by the standard deviation of parameter estimates among three readers. GFR estimates from our software were also compared to a reference standard from nuclear medicine.

Results

The time taken to process one patient's data with the software averaged 12 ± 4 minutes. The applied image registration effectively reduced motion artifacts in dynamic images by providing renal tracer‐retention curves with significantly smaller fitting residues (P < 0.01) than unregistered data or data registered by the previously reported technique. Interreader variability was less than 10% for all parameters. GFR estimates from the proposed method showed greater concordance with reference values (P < 0.05).

Conclusion

These results suggest that the proposed software can process MRR data efficiently and accurately. Its incorporated registration technique based on the generalized Hough transform effectively reduces respiratory motion artifacts in free‐breathing renographic acquisitions. J. Magn. Reson. Imaging 2016;43:391–397.
The effect of beam arrangements and the impact of non‐coplanar beams on the treatment planning of stereotactic ablative radiation therapy for early stage lung cancer
Authors: Fitzgerald Rhys , Owen Rebecca , Barry Tamara , Hargrave Cathy , Pryor David , Bernard Anne , Lehman Margot , Mai Tao , Fielding Andrew
Published: July 2015

Introduction

The aim of this study was to compare various coplanar and non‐coplanar 3‐dimensional conformal radiation therapy (3DCRT) beam arrangements for the delivery of stereotactic ablative radiation therapy (SABR) to patients with early stage lung cancer, based on the dosimetric criteria from the Radiation Therapy Oncology Group (RTOG) 1021 protocol.

Methods

Ten medically inoperable lung cancer patients eligible for SABR were re‐planned using three different coplanar and three different non‐coplanar beam arrangements. The plans were compared by assessing planning target volume (PTV) coverage, doses to normal tissues, the high‐dose conformity (conformity index) and intermediate dose spillage as defined by the D2cm, (the dose at any point 2 cm away from the PTV), and the R50% (the ratio of the volume of half the prescription dose to the volume of the PTV).

Results

Sixty plans in total were assessed. Mean PTV coverage with the prescription isodose was similar between coplanar (95.14%) and non‐coplanar (95.26%) techniques (P = 0.47). There was significant difference between all coplanar and all non‐coplanar fields for the R50% (P < 0.0001) but none for the D2cm (P = 0.19). The seven and nine field beam arrangements with two non‐coplanar fields had less unacceptable protocol deviations (10 and 7) than the seven and nine field plans with only coplanar fields (13 and 8). The 13 field coplanar fields did not improve protocol compliance with eight unacceptable deviations. The 10 field non‐coplanar beam arrangement achieved best compliance with the RTOG 1021 dose criteria with only one unacceptable deviation (maximum rib dose).

Conclusion

A 3DCRT planning technique using 10 fields with ≥6 non‐coplanar beams best satisfied high and intermediate dose constraints stipulated in the RTOG 1021 trial. Further investigations are required to determine if minor protocol deviations should be balanced against efficiency with the extended treatment times required to deliver non‐coplanar fields and if treatment times can be improved using novel intensity modulated techniques.
Characterization of VP1 gene of coxsackievirus A16 prevalent among hand foot mouth disease suffered children in Taizhou, P. R. China, between 2010 and 2013
Authors: Ma Zhilong , Zha Jie
Published: July 2015

A total of 453 strains of Coxsackievirus A16 (CV‐A16) were screened out of 1,509 hand‐foot‐mouth disease (HFMD) samples collected in Taizhou during the period from 2010 to 2013. And between first quarter of 2011 and first quarter of 2013, an outbreak of CV‐A16 was found among the HFMD sufferers in Taizhou. Phylogenic analysis of VP1 sequences indicated a major CV‐A16 sub‐group in Taizhou, whose change pattern of effective population sizes was found to be similar to the pattern of the actual percentage changes of CV‐A16 during the outbreak over the same period. More importantly, the sub‐group all displayed a Leu (L) to Met (M) mutation at site‐23 of capsid VP1 which might be correlated with the outbreak of CV‐A16 in Taizhou. J. Med. Virol. 88:202–210, 2016. © 2015 Wiley Periodicals, Inc.
Genetic diversity of HHV8 subtypes in South Africa: A5 subtype is associated with extensive disease in AIDS‐KS
Authors: Isaacs Thuraya , Abera Aron B. , Muloiwa Rudzani , Katz Arieh A. , Todd Gail
Published: July 2015

Human herpes virus 8 (HHV8) is the etiological agent of all forms of Kaposi's sarcoma (KS). Six major subtypes (A‐F), based on genetic variability of open reading frame (ORF)‐K1, have been identified. Numerous studies point to differing tumorigenic and pathogenic properties of the HHV8 subtypes. The study objectives were to determine the HHV8 subtypes and their prevalence in a cohort of clinical and histologically confirmed KS in Cape Town, South Africa, and analyze associations between the different subtypes and clinical presentation of KS. Clinical records were prospectively reviewed to extract clinical presentation; demographic data were retrospectively collected and tissue biopsies were taken for ORF‐K1 subtyping. Eighty six patients were subtyped; 81 AIDS (acquired immune deficiency syndrome)‐KS and 5 African endemic‐KS. Subtype A5 (42/86) and B2 (16/86) predominated. B1, B3, A1 and A4 subtypes were identified in 10/86, 9/86, 4/86 and 1/86 patients, respectively. A5 and B subtypes were found in African blacks and individuals of mixed ancestry, while subtypes A1 and A4 were found only in whites and individuals of mixed ancestry. Subtype A5 was associated with >10 KS lesions at presentation in the AIDS cohort (adjusted OR: 3.13; CI: 1.02–9.58). Subtypes A1 and A4 combined were less likely to be associated with poor risk tumor extension (P = 0.031) and A1 was associated with lower likelihood of lower limb involvement (P = 0.019). In conclusion, these results indicate that subtype A5 and B predominate in South Africa and A5 may be associated with more extensive disease. J. Med. Virol. 88:292–303, 2016. © 2015 Wiley Periodicals, Inc.
Guidance for representing uncertainty on global temperature change maps
Authors: Retchless David P. , Brewer Cynthia A.
Published: July 2015

Uncertainty in the spatial distribution of projected climate changes can be represented along with the magnitudes of those changes using coincident‐bivariate maps. While these maps are popular in climate change assessment reports, limited empirical research has tested which combinations of colour (including variation in the visual variables of hue, lightness, and saturation) and pattern (including variation in the visual variables of size, shape, spacing, orientation, and arrangement) are best suited to mapping projected changes coincident with uncertainty. We evaluate eight coincident‐bivariate techniques for mapping global temperature (CMIP5 ensemble using RCP8.5 and RCP4.5 scenarios) and its uncertainty, each using 20‐classes: five temperature change classes combined with four uncertainty classes. Subjects ranked rectangular map regions by overall amounts of temperature change and uncertainty; response accuracy was evaluated using Kendall's Tau Distance. Maps using colour for representing temperature change and pattern for uncertainty appear most suitable for retaining separability of temperature and uncertainty information. Spot symbols for uncertainty (combining arrangement and lightness) overlaid on hue/lightness for temperature performed best for uncertainty ranking, second best for temperature ranking, and were map users' preferred representation. If colour alone must be used for both variables, then a classed overlay of lightness/saturation differences for uncertainty with hue/lightness for temperature change was preferred; such maps were strong performers on the uncertainty‐ranking task but interfered with map users' ability to rank temperature change. Such a masking approach may be the best choice if the goal is to actively prevent map users from making erroneous inferences based on highly uncertain model output for climate change.
Regional climate simulations of the changes in the components of the moisture budget over South America
Authors: Coutinho Maytê Duarte Leal , Lima Kellen Carla , Santos e Silva Cláudio Moisés
Published: July 2015

The moisture transport over South America (SA) was investigated through the vertically integrated moisture flux of three regions: the Amazon (AMZ), Northeastern Brazil (NEB) and the La Plata Basin (LPB), in different climates, past (1961–1990) and future (2071–2100), in the summer (DJF) and winter (JJA) seasons. For this, we used the results of the simulations of four regional climate models (RCMs) of the Regional Climate Change Assessment for the La Plata Basin (CLARIS‐LPB) project. The capacity and limitations of the models to simulate seasonal precipitation for the past period is discussed. In general, the RCMs tended to overestimate the observed precipitation during DJF in the NEB and underestimate it during JJA in the LPB. In relation to change in precipitation (future minus past), the RCMs indicated a decrease in precipitation over northern SA. The average fluxes of the AMZ and NEB regions provided most of the water vapour through the east and north edges, which indicates that the contributions of the North and South Atlantic trade winds are equally important for the entry of moisture during JJA and DJF. This configuration was observed in all models and climates. By comparing past and future climates, the moisture flux convergence during the past was lower relative to the future in different regions and seasons, with statistically significant differences at the 5% level considering the Student's t‐test. In the same study, we compared the simulated (RCMs) and reanalysis moisture flux (ERA‐40) in the past climate. The result indicated that the CLARIS project's RCMs are capable of simulating values similar or equal to the observed ones, providing high quality data for SA that can be useful in the analysis of changes in future moisture fluxes.
Enhanced expression of Wnt9a in the flexor tenosynovium in idiopathic carpal tunnel syndrome
Authors: Yamanaka Yoshiaki , Menuki Kunitaka , Zenke Yukichi , Hirasawa Hideyuki , Sakai Akinori
Published: July 2015

This study aimed to clarify the association between abnormal Wnt signaling and the cause of idiopathic carpal tunnel syndrome (ICTS) and whether an association exists between Wnt signaling and cell proliferation in the flexor tenosynovium. The subjects included nine patients with ICTS; the controls were nine patients with distal radius fractures without any symptoms of carpal tunnel syndrome. We extracted mRNA from the flexor tenosynovium and compared the expression levels of genes encoding 17 types of Wnt in both subjects and controls via quantitative real‐time polymerase chain reaction (PCR). Expression levels of factors involved in cell proliferation, such as estrogen‐responsive finger protein, epidermal growth factor receptor, heparin binding‐epidermal growth factor‐like growth factor, insulin‐like growth factor‐1, and vascular endothelial growth factor (VEGF) were also measured using quantitative real‐time PCR. In addition, we compared the Wnt and MIB‐1 protein expression levels to clarify the effect of Wnt on cell proliferation. Quantitative real‐time PCR revealed significantly greater expression of the gene encoding Wnt9a in subjects with ICTS than in controls and also revealed a positive correlation between the expression of genes encoding Wnt9a and VEGF in subjects with ICTS. Quantitative evaluation using immunohistochemical staining also indicated more marked Wnt9a expression in subjects than in controls. However, there was no relationship between the expression of Wnt9a and the cell proliferation index MIB‐1. These results indicate that Wnt9a expression is enhanced in ICTS and that Wnt9a may be involved in VEGF expression in ICTS. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1531–1536, 2015.
Screening anti‐tumor compounds from Ligusticum wallichii using cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry
Authors: Zhang Tao , Ding Yuanyuan , An Hongli , Feng Liuxin , Wang Sicen
Published: July 2015

Tyrosine 367 Cysteine‐fibroblast growth factor receptor 4 cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry was developed. Tyrosine 367 Cysteine‐HEK293 cells were used as the cell membrane stationary phase. The specificity and reproducibility of the cell membrane chromatography was evaluated using 1‐tert‐butyl‐3‐{2‐[4‐(diethylamino)butylamino]‐6‐(3,5‐dimethoxyphenyl)pyrido[2,3‐d]pyrimidin‐7‐yl}urea, nimodipine and dexamethasone acetate. Then, anti‐tumor components acting on Tyrosine 367 Cysteine‐fibroblast growth factor receptor 4 were screened and identified from extracts of Ligusticum wallichii. Components from the extract were retained on the cell membrane chromatographic column. The retained fraction was directly eluted into high‐performance liquid chromatography with mass spectrometry system for separation and identification. Finally, Levistolide A was identified as an active component from Ligusticum wallichii extracts. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide‐formazan colorimetric assay revealed that Levistolide A inhibits proliferation of overexpressing the mutated receptor cells with dose‐dependent manner. Phosphorylation of fibroblast growth factor receptor 4 was also decrease under Levistolide A treatment. Flex dock simulation verified that Levistolide A could bind with the tyrosine kinase domain of fibroblast growth factor receptor 4. Therefore, Levistolide A screened by the cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry can arrest cell growth. In conclusion, the two‐dimensional high‐performance liquid chromatography method can screen and identify potential anti‐tumor ingredients that specifically act on the tyrosine kinase domain of the mutated fibroblast growth factor receptor 4.
Traumatic Brain Injury and Suicidal Ideation Among U.S. Operation Enduring Freedom and Operation Iraqi Freedom Veterans
Authors: Gradus Jaimie L. , Wisco Blair E. , Luciano Matthew T. , Iverson Katherine M. , Marx Brian P. , Street Amy E.
Published: July 2015

Traumatic brain injury (TBI) is associated with suicidal behavior among veterans, and gender differences in the strength of associations may exist. Almost all research has been limited to Veterans Health Administration (VHA) patients, and it is unclear if findings generalize to veterans who do not use VHA services. We examined gender‐ and VHA‐user‐specific associations between TBI related to deployment and postdeployment suicidal ideation in a U.S. national sample of 1,041 female and 880 male Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans. Path analysis was used to estimate TBI and suicidal ideation association, and examine PTSD and depression symptomatology in these associations. TBI was associated with suicidal ideation among male VHA users, OR = 3.64, 95% CI [2.21, 6.01]; and male and female nonusers, OR = 2.24, 95% CI [1.14, 4.44] and OR = 2.65, 95% CI [1.26, 5.58], respectively, in unadjusted analyses. This association was explained by depression symptoms among male and female nonusers. Among male VHA users an association between TBI and suicidal ideation remained when accounting for depression symptoms, OR = 2.50, 95% CI [1.33, 4.71]. Our findings offered evidence of an association between TBI and suicidal ideation among male OEF/OIF VHA users.
A novel dual‐wavelength, Nd:YAG, picosecond‐domain laser safely and effectively removes multicolor tattoos
Authors: Bernstein Eric F. , Schomacker Kevin T. , Basilavecchio Lisa D. , Plugis Jessica M. , Bhawalkar Jayant D.
Published: July 2015

Background and Objectives

Although nanosecond‐domain lasers have been the mainstay of laser tattoo removal for decades, recent disruptive innovations in laser design have introduced a new class of commercial Q‐switched lasers that generate picosecond‐domain pulses.

Study

A picosecond‐domain, Nd:YAG laser with a KTP frequency‐doubling crystal was used to treat 31 decorative tattoos in 21 subjects. Safety and effectiveness were determined by blinded evaluation of digital images in this prospective clinical study.

Results

The average clearance overall as evaluated by blinded observers evaluating randomized digital photographs was 79 ± 0.9% (mean ± sem) after an average of 6.5 treatments. Of the 31 tattoos completing treatment, 6 had evidence of mild hyper‐ or hypo‐pigmentation by evaluation of photographs.

Conclusion

The 350 picosecond, 532 nm, and 450 picosecond 1,064 nm Nd:YAG laser is safe and effective for removing decorative tattoos. Lasers Surg. Med. 47:542–548, 2015. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
Fluorescent Phosphorus Dendrimer as a Spectral Nanosensor for Macrophage Polarization and Fate Tracking in Spinal Cord Injury
Authors: Shakhbazau Antos , Mishra Manoj , Chu Tak‐Ho , Brideau Craig , Cummins Karen , Tsutsui Shigeki , Shcharbin Dzmitry , Majoral Jean‐Pierre , Mignani Serge , Blanchard‐Desce Mireille , Bryszewska Maria , Yong V. Wee , Stys Peter K. , van Minnen Jan
Published: July 2015

Dendrimers and dendriplexes, highly branched synthetic macromolecules, have gained popularity as new tools for a variety of nanomedicine strategies due to their unique structure and properties. We show that fluorescent phosphorus dendrimers are well retained by bone marrow‐derived macrophages and exhibit robust spectral shift in its emission in response to polarization conditions. Fluorescence properties of this marker can also assist in identifying macrophage presence and phenotype status at different time points after spinal cord injury. Potential use of a single dendrimer compound as a drug/siRNA carrier and phenotype‐specific cell tracer offers new avenues for enhanced cell therapies combined with monitoring of cell fate and function in spinal cord injury.
Acid‐Sensitive Nanogels for Synergistic Chemo‐Photodynamic Therapy
Authors: Chen Xiaofei , Yao Xuemei , Chen Li , Chen Xuesi
Published: July 2015

Herein, a novel kind of intelligent nanogels have been designed, which can spatiotemporally control the release of drug (doxorubicin) and photosensitizers (porphyrins) to combine chemo‐therapy and photodynamic therapy. Further, the fluorescing properties of porphyrins make it possible to be used as a kind of diagnostic bio‐imaging agents. In vitro release assays confirm that DOX‐loaded nanogels show obvious intracellular pH‐sensitive property. The intracellular experiments further prove that drug‐loaded nanogels has the significantly antitumor efficacy due to the combination of chemotherapy and photodynamic therapy, which made this drug delivery system hold great potential applications for further cancer treatment.
Development of Layered Multiscale Porous Thin Films by Tuning Deposition Time and Molecular Weight of Polyelectrolytes
Authors: Yu Jing , Sanyal Oishi , Izbicki Andrew P. , Lee Ilsoon
Published: July 2015

This work focuses on the design of porous polymeric films with nano‐ and micro‐sized pores existing in distinct zones. The porous thin films are fabricated by the post‐treatment of layer‐by‐layer assembled poly(allylamine hydrochloride) (PAH)/poly(acrylic acid) (PAA) multilayers. In order to improve the processing efficiency, the deposition time is shortened to ≈10 s. It is found that fine porous structures can be created even by significantly reducing the processing time. The effect of using polyelectrolytes with widely different molecular weights is also studied. The pore size is increased by using high molecular weight PAH, while high molecular weight PAA minimizes the pore size to nanometer scale. Having gained a precise control over the pore size, layered multiscale porous thin films are further built up with either a microsized porous zone on top of a nanosized porous zone or vice versa.

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Elucidating the Morphological Complexities of Linear Symmetric Triblock Polymers Confined Between Two Parallel Plates: A Self‐Consistent Field Theoretic Approach
Authors: Mohagheghi Mouge , Khomami Bamin
Published: July 2015

Three dimensional self‐consistent field theoretic simulations have been performed to determine the equilibrium morphologies formed by linear ABC triblock polymer melts confined between two parallel plates that favor the middle block. Our primary goal is to elucidate the conditions under which the perpendicular lamella is stabilized, since this morphology plays a central role in many nanotechnology applications. Key factors, namely, the chain architecture, surface energy and the mismatch between the film thickness d and the bulk lamella period, L0, determine the final morphologies, e.g., perpendicular and parallel lamella, perforated lamella and wet substrate with parallel cylinders in the core, have been identified. Overall, our findings are fully consistent with the results of limited experimental studies focused on morphology development in thin films of triblock polymer melts. Finally, we have clearly demonstrated that ABC triblocks hold technological advantages over diblocks for nano‐lithographic fabrications.
In vivo role of Candida albicans β‐hexosaminidase (HEX1) in carbon scavenging
Authors: Ruhela Deepa , Kamthan Mohan , Saha Paramita , Majumdar Subeer S. , Datta Kasturi , Abdin Malik Zainul , Datta Asis
Published: July 2015

The capability to utilize of N‐acetylglucosamine (GlcNAc) as a carbon source is an important virulence attribute of Candida albicans. But there is a lack of information about the in vivo source of GlcNAc for the pathogen within the host environment. Here, we have characterized the GlcNAc‐inducible β‐hexosaminidase gene (HEX1) of C. albicans showing a role in carbon scavenging. In contrast to earlier studies, we have reported HEX1 to be a nonessential gene as shown by homozygous trisomy test. Virulence study in the systemic mouse murine model showed that Δhex1 strain is significantly less virulent in comparison to the wild‐type strain. Moreover, Δhex1 strain also showed a higher susceptibility to peritoneal macrophages. In an attempt to determine possible substrates of Hex1, hyaluronic acid (HA) was treated with purified Hex1 enzyme. A significant release of GlcNAc was observed by gas chromatography‐mass spectrometry analysis analysis suggesting HA degradation. Interestingly, immunohistochemistry analysis showed significant accumulation of HA in the mice kidney infected with the wild‐type strain of C. albicans. Northern blot analysis showed that C. albicans HEX1 is expressed during mice renal colonization. Thus, C. albicans can obtain GlcNAc during organ colonization by secreting Hex1 via degradation of host HA.
Impact of Depression on Progression of Impairment and Disability in Early Parkinson's Disease
Authors: Bega Danny , Luo Sheng , Fernandez Hubert , Chou Kelvin , Aminoff Michael , Parashos Sotirios , Walker Harrison , Russell David S. , Christine Chadwick W. , Dhall Rohit , Singer Carlos , Bodis‐Wollner Ivan , Hamill Robert , Truong Daniel , Mari Zoltan , Glazmann Sofya , Huang Meilin , Houston Emily , Simuni Tanya ,   the NET PD LS1 investigators
Published: July 2015

Background

Depression is one of the most common nonmotor symptoms associated with Parkinson's disease (PD), yet the impact of depression on progression of disease is unclear.

Objective

The aim of this study was to prospectively characterize the relationship between depressive symptoms and measures of disease progression in a large sample of patients with early, medically treated PD.

Methods

Baseline and longitudinal Beck Depression Inventory (BDI) scores from participants in the NINDS Exploratory Trials in PD Long Term Study 1 were correlated with changes in multiple measures of disease severity over 5 years. Multivariate analysis of predictors of change in BDI was performed.

Results

Of 1,741 participants, 746 completed 5‐year assessments and were included. Mean age was 62.00 years (standard deviation [SD]: 9.22) and mean disease duration was 1.69 years (SD, 1.16). Mean BDI score was 6.24 (SD, 5.02) at baseline and 8.57 (SD, 6.60) at 5 years. Baseline BDI score was strongly associated with rate of change in all examined measures of disease severity. In multivariate analysis, BDI 5‐year change was associated with change in UPDRS Part I (excluding depression item; P < 0.01), 33‐item Parkinson's Disease Questionnaire (P < 0.01), EuroQOL Five Dimensional Questionnaire (P = 0.02), and Total Functional Capacity (P < 0.01), but was not associated with motor or cognitive measures. This model explained 68.8% of the variance 5‐year change of the BDI score.

Conclusions

Worse baseline BDI scores are associated with a decline in multiple measures of disease severity in PD. Worsening of BDI at 5 years was associated with worsening in UPDRS Part I and quality‐of‐life measures, but not with motor or cognitive measures.
Delineating nonmotor symptoms in early Parkinson's disease and first‐degree relatives
Authors: Baig Fahd , Lawton Michael , Rolinski Michal , Ruffmann Claudio , Nithi Kannan , Evetts Samuel G. , Fernandes Hugo R. , Ben‐Shlomo Yoav , Hu Michele T.M
Published: July 2015

Nonmotor symptoms (NMS) are an important prodromal feature of Parkinson's disease (PD). However, their frequency, treatment rates, and impact on health‐related quality of life (HRQoL) in the early motor phase is unclear. Rates of NMS in enriched at‐risk populations, such as first‐degree PD relatives, have not been delineated. We assessed NMS in an early cohort of PD, first‐degree PD relatives and control subjects to address these questions. In total, 769 population‐ascertained PD subjects within 3.5 years of diagnosis, 98 first‐degree PD relatives, and 287 control subjects were assessed at baseline across the following NMS domains: (1) neuropsychiatric; (2) gastrointestinal; (3) sleep; (4) sensory; (5) autonomic; and (6) sexual. NMS were much more common in PD, compared to control subjects. More than half of the PD cases had hyposmia, pain, fatigue, sleep disturbance, or urinary dysfunction. NMS were more frequent in those with the postural instability gait difficulty phenotype, compared to the tremor dominant (mean total number of NMS 7.8 vs. 6.2; P < 0.001). PD cases had worse HRQoL scores than controls (odds ratio: 4.1; P < 0.001), with depression, anxiety, and pain being stronger drivers than motor scores. NMS were rarely treated in routine clinical practice. First‐degree PD relatives did not significantly differ in NMS, compared to controls, in this baseline study. NMS are common in early PD and more common in those with postural instability gait difficulty phenotype or on treatment. Despite their major impact on quality of life, NMS are usually under‐recognized and untreated. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Ethyl‐eicosapentaenoic acid treatment in Huntington's disease: A placebo‐controlled clinical trial
Authors: Ferreira Joaquim J. , Rosser Anne , Craufurd David , Squitieri Ferdinando , Mallard Nicholas , Landwehrmeyer Bernhard
Published: July 2015

Background

It has been suggested that treatment with ethyl‐eicosapentaenoic acid (EPA) may improve motor function in patients with Huntington's disease (HD) with cytosine‐adenine‐guanine repeat numbers of <45.

Methods

This multicenter, randomized, double‐blind, placebo‐controlled 6‐month trial compared the effects of ethyl‐EPA versus placebo on 290 subjects with mild‐to‐moderate HD. The primary endpoint was the change from baseline to 6 months in the Total Motor Score 4 (TMS‐4) component of the Unified Huntington's Disease Rating Scale (UHDRS). Secondary endpoints included change from baseline in UHDRS subscores and Clinical Global Impression (CGI).

Results

No significant differences in TMS‐4 scores were noted between treatment groups. Similarly, there were no significant differences between groups on any of the UHDRS subscores or CGI scores.

Conclusion

Ethyl‐EPA was not beneficial in patients with HD during 6 months of placebo‐controlled evaluation. © 2015 International Parkinson and Movement Disorder Society
L‐dopa increases α‐synuclein DNA methylation in Parkinson's disease patients in vivo and in vitro
Authors: Schmitt Ina , Kaut Oliver , Khazneh Hassan , deBoni Laura , Ahmad Ashar , Berg Daniela , Klein Christine , Fröhlich Holger , Wüllner Ullrich
Published: July 2015

Background

Increasing gene dosages of α‐synuclein induce familial Parkinson's disease (PD); thus, the hypothesis has been put forward that regulation of gene expression, in particular altered α‐synuclein gene methylation, might be associated with sporadic PD and could be used as a biological marker.

Methods

We performed a thorough analysis of α‐synuclein methylation in bisulfite‐treated DNA from peripheral blood of 490 sporadic PD patients and 485 healthy controls and in addition analyzed the effect of levodopa (l‐dopa) on α‐synuclein methylation and expression in cultured mononuclear cells.

Results

α‐Synuclein was hypomethylated in sporadic PD patients, correlated with sex, age, and a polymorphism in the analyzed sequence stretch (rs3756063). α‐Synuclein methylation separated healthy individuals from sporadic PD with a specificity of 74% (male) and 78% (female), respectively. α‐Synuclein methylation was increased in sporadic PD patients with higher l‐dopa dosage, and l‐dopa specifically induced methylation of α‐synuclein intron 1 in cultured mononuclear cells.

Conclusions

α‐Synuclein methylation levels depended on disease status, sex, age, and the genotype of rs3756063. The pharmacological action of l‐dopa was not limited to the dopamine precursor function but included epigenetic off‐target effects. The hypomethylation of α‐synuclein in sporadic PD patients' blood already observed in previous studies was probably underestimated because of effect of l‐dopa, which was not known previously. The analysis of α‐synuclein methylation can help to identify nonparkinsonian individuals with reasonable specificity, which offers a valuable tool for researchers and clinicians. © 2015 International Parkinson and Movement Disorder Society
Challenges and Opportunities in Continuous Production of Emulsion Polymers: a Review
Authors: Asua José M.
Published: July 2015

Profit margin reduction and global competition are pushing latex producers to consider process intensification that relies on the replacement of semicontinuous reactors by continuous ones. The challenges involved and ways in which the challenges can be transformed into opportunities are discussed for: (i) production of branched polymers in CSTRs; (ii) minimization of the grade transition product in the production of a portfolio of pressure sensitive adhesives (PSA) in CSTRs; (iii) synthesis of flocculants by inverse microemulsion polymerization in CSTRs and in tubular and Couette–Taylor reactors; and (iv) production of polyurethane‐acrylic PSAs by miniemulsion polymerization in a tubular reactor.

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Prevalence and phenotypes of congenital myopathy due to α‐actin 1 gene mutations
Authors: Witting Nanna , Werlauff Ulla , Duno Morten , Vissing John
Published: July 2015

Introduction

Congenital myopathy due to mutations in the α‐actin 1 gene (ACTA1) was identified in 1999, but knowledge of prevalence and phenotype in patients who survive 5 years is lacking.

Methods

A national cohort of 91 patients aged ≥5 years and diagnosed with congenital myopathy was assessed for ACTA1 mutations and investigated clinically.

Results

Four patients with ACTA1 mutations were identified, yielding a prevalence of 4.4%. Patients were 10–23 years of age, and all but 1 were ambulatory. Vital capacity ranged from 47% to 70% predicted, and 1 patient needed nocturnal bi‐level positive airway pressure. Limb flexor/extensor muscles and upper and lower extremities were affected equally. Pronounced neck flexor weakness was noted.

Conclusions

Congenital myopathy caused by ACTA1 mutations is fatal in infancy in most cases. This study shows that the prevalence of α‐actin myopathy in older patients with congenital myopathy is not negligible and that phenotypes can be quite mild. Muscle Nerve 53: 388–393, 2016
Relative risks for comorbidities associated with myotonic dystrophy: A population‐based analysis
Authors: Johnson Nicholas E. , Abbott Diana , Cannon‐Albright Lisa A.
Published: July 2015

Introduction: A population‐level relative risk assessment for comorbidities associated with myotonic dystrophy has not been performed. Methods: In this study we utilized the Utah Population Database to identify patients with myotonic dystrophy in Utah according to ICD‐9 coding. Comorbidity cases listed in the medical record were compared with those of the Utah population. Results: Individuals with myotonic dystrophy were found to possess an increased risk of central and obstructive sleep apnea, hypothyroidism, and intellectual disability. The risk of cardiac conduction disorder is 60 times the population risk. Conclusions: This study provides a population‐level relative risk assessment of comorbidities in myotonic dystrophy. This allows for improved counseling of patients regarding these increased risks. Muscle Nerve 52: 659–661, 2015
Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): A randomized, controlled trial
Authors: Benatar Michael , Mcdermott Michael P. , Sanders Donald B. , Wolfe Gil I. , Barohn Richard J. , Nowak Richard J. , Hehir Michael , Juel Vern , Katzberg Hans , Tawil Rabi ,   Muscle Study Group (MSG)
Published: July 2015

Introduction: In this study we evaluated the safety, tolerability, and efficacy of prednisone in patients with ocular myasthenia gravis (OMG) concurrently treated with pyridostigmine. Methods: This investigation was a randomized, double‐blind, placebo‐controlled trial. Participants whose symptoms failed to remit on pyridostigmine were randomized to receive placebo or prednisone, initiated at 10 mg every other day, and titrated to a maximum of 40 mg/day over 16 weeks. The primary outcome measure was treatment failure. Results: Fewer subjects were randomized than the 88 planned. Of the 11 randomized, 9 completed 16 weeks of double‐blind therapy. Treatment failure incidence was 100% (95% CI 48%–100%) in the placebo group (n = 5) vs. 17% (95% CI 0%–64%) in the prednisone group, P = 0.02 (n = 6). Median time to sustained minimal manifestation status (MMS) was 14 weeks, requiring an average prednisone dose of 15 mg/day. Adverse events were infrequent and generally mild in both groups. Conclusions: A strategy of low‐dose prednisone with gradual escalation appears to be safe, well‐tolerated, and effective in treating OMG. Muscle Nerve 53: 363–369, 2016
Deformation of a poroelastic layer overlying an elastic half‐space due to dip‐slip faulting
Authors: Verma R. C. , Rani S. , Singh S. J.
Published: July 2015

An analytical solution of the plane strain problem of the deformation of a homogeneous, isotropic, poroelastic layer of uniform thickness overlying a homogeneous, isotropic, elastic half‐space due to two‐dimensional seismic sources buried in the elastic half‐space has been obtained. The integral expressions for the displacements, stresses and pore pressure have been obtained using the stress function approach by applying suitable boundary conditions at the free surface and the interface. The solution obtained is in the Laplace–Fourier transform domain. The case of a vertical dip‐slip line dislocation for the oceanic crust model of Earth is studied in detail. Schapery's formula is used for the Laplace inversion and the extended Simpson's formula for the Fourier inversion. Diffusion of pore pressure in the layer is studied numerically. Contour maps showing the pore pressure in the poroelastic layer have been plotted. The effect of the compressibility of the solid and fluid constituents on pore pressure has also been studied. Copyright © 2015 John Wiley & Sons, Ltd.
Inventory models with nonlinear shortage costs and stochastic lead times; applications of shape properties of randomly stopped counting processes
Authors: Badía F. G. , Sangüesa C.
Published: July 2015

In this article, we study generalizations of some of the inventory models with nonlinear costs considered by Rosling in (Oper. Res. 50 (2002) 797–809). In particular, we extend the study of both the periodic review and the compound renewal demand processes from a constant lead time to a random lead time. We find that the quasiconvexity properties of the cost function (and therefore the existence of optimal (s, S) policies), holds true when the lead time has suitable log‐concavity properties. The results are derived by structural properties of renewal delayed processes stopped at an independent random time and by the study of log‐concavity properties of compound distributions. © 2015 Wiley Periodicals, Inc. Naval Research Logistics 62: 345–356, 2015
Amide proton transfer of carnosine in aqueous solution studied in vitro by WEX and CEST experiments
Authors: Bodet Olga , Goerke Steffen , Behl Nicolas G. R. , Roeloffs Volkert , Zaiss Moritz , Bachert Peter
Published: July 2015

Amide protons of peptide bonds induce an important chemical exchange saturation transfer (CEST) contrast in vivo. As a simple in vitro model for a peptide amide proton CEST effect, we suggest herein the dipeptide carnosine. We show that the metabolite carnosine creates a CEST effect and we study the properties of the exchange of the amide proton (–NH) of the carnosine peptide bond (NHCPB) in model solutions for a pH range from 6 to 8.3 and a temperature range from T = 5 °C to 43 °C by means of CEST and water exchange spectroscopy (WEX) experiments on a 3 T whole‐body MR tomograph. The dependence of the NHCPB chemical exchange rate ksw on pH and temperature T was determined using WEX. For physiological conditions (T = 37 °C, pH = 7.10) we obtained ksw = (47.07 ± 7.90)/s. With similar chemical shift and exchange properties to amide protons in vivo, carnosine forms a simple model system for optimization of CEST pulse sequences in vitro. The potential for direct detection of the metabolite carnosine in vivo is discussed. Copyright © 2015 John Wiley & Sons, Ltd.
On SSOR‐like preconditioners for non‐Hermitian positive definite matrices
Authors: Bai Zhong‐Zhi
Published: July 2015

We construct, analyze, and implement SSOR‐like preconditioners for non‐Hermitian positive definite system of linear equations when its coefficient matrix possesses either a dominant Hermitian part or a dominant skew‐Hermitian part. We derive tight bounds for eigenvalues of the preconditioned matrices and obtain convergence rates of the corresponding SSOR‐like iteration methods as well as the corresponding preconditioned GMRES iteration methods. Numerical implementations show that Krylov subspace iteration methods such as GMRES, when accelerated by the SSOR‐like preconditioners, are efficient solvers for these classes of non‐Hermitian positive definite linear systems. Copyright © 2015 John Wiley & Sons, Ltd.
Discrete Lagrangian mechanics for nonseparable nonsmooth systems
Authors: Pekarek David , Murphey Todd D.
Published: July 2015

We consider event‐driven schemes for the simulation of nonseparable mechanical systems subject to holonomic unilateral constraints. Systems are modeled in discrete time using variational integrator (VI) theory, by which equations of motion follow from discrete variational principles. For smooth dynamics, VIs are known to exactly conserve a discrete symplectic form and a modified Hamiltonian function. The latter of these conservation laws can play a pivotal role in stabilizing the energy behavior of collision simulations. Previous efforts to leverage modified Hamiltonian conservation have been limited to integrators using the Störmer–Verlet method on separable, nonsmooth Hamiltonian mechanical systems. We generalize the existing approach to the family of all VIs applied to nonseparable, potentially nonconservative Lagrangian mechanical systems. We examine the properties of the resulting integrators relative to other structured collision simulation methods in terms of conserved quantities, trajectory errors as a function of initial condition, and required computation time. Interestingly, we find that the modified collision Verlet algorithm (MCVA) using the Störmer–Verlet integrator defined as a composition method leads to the best accuracy. Although relative to this method, the VI‐based generalized MCVA method offers computational savings when collisions are particularly sparse. Copyright © 2015 John Wiley & Sons, Ltd.
The Effects of Individual Risk Propensity on Volunteering
Authors: Dong Hsiang‐Kai (Dennis)
Published: July 2015

Serving as a volunteer is gratifying and rewarding, but by nature it is also considered a risky decision. Volunteering risk may come from the lack of sufficient training, asymmetric information between volunteers and managers, and the lack of support and protection from nonprofit organizations. Abundant studies discuss volunteering behaviors based on demographics. However, people's decisions are mainly determined by their own preferences rather than demographic differences. Accordingly, this study hypothesizes that individual risk propensity is an important predictor for volunteering behaviors. Using a nationally representative data set, this study finds that risk‐accepting individuals are more likely to volunteer than their risk‐averse peers. Also, the former tend to volunteer more frequently than the latter once they decide to be part of the volunteer labor force. Several managerial implications and volunteer recruitment strategies for nonprofit organizations are discussed.
Viewing as little as 1 hour of TV daily is associated with higher change in BMI between kindergarten and first grade
Authors: Peck Travis , Scharf Rebecca J. , Conaway Mark R. , DeBoer Mark D.
Published: July 2015

Objective

Evaluate associations between TV viewing and weight status in children from kindergarten to first grade.

Methods

Linear and logistic regression was used to evaluate associations of TV‐viewing time on BMI‐z‐score cross‐sectionally at kindergarten and first grade and longitudinally in between, among a nationally representative sample of 14,645 children from the Early Childhood Longitudinal Study‐Kindergarten Cohort 2011. All analyses were adjusted for sex, race/ethnicity, parental education, and household income.

Results

Weekday TV‐viewing time was correlated with BMI‐z‐score (P < 0.01) at kindergarten and first grade and with change in BMI‐z‐score in between (P < 0.05). Compared with children watching <1 h of TV daily, children watching ≥1 h in kindergarten and first grade had a greater odds of overweight (1.50‐1.60) and obesity (1.58‐1.73). Children watching 1‐<2 h and ≥2 h daily had higher BMI‐z‐scores (P < 0.0001) and less favorable changes in BMI‐z‐score between time points (P < 0.05). Children who were not overweight or obese in kindergarten and watched ≥1 h of TV had a greater odds of becoming overweight (1.39) and obese (1.86) between evaluations.

Conclusions

Children watching as little as 1‐<2 h of TV daily were more likely to become overweight and obese over time. Physicians should encourage families to restrict TV‐viewing time to reduce weight gain.