bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of multi‐InDels as novel markers to analyze 13 X‐chromosome haplotype loci for forensic purposes
Authors: Fan Guangyao , Ye Yi , Luo Haibo , Hou Yiping
Published: August 2015

Many studies have been proposed to identify insertion/deletion (InDel) polymorphisms in humans for forensic genetic studies. However, the discriminatory power of InDels is limited by the poor polymorphisms of diallelic markers. To improve their discriminatory power, we developed multi‐InDel, a novel autosomal marker comprising more than two InDel loci that are tightly linked by their physical position and combined into a specific marker by a pair of PCR primers. This strategy gives at least three haplotypes for each multi‐InDel marker. Such markers can be potentially very useful in forensic applications. In this study, we focused on multi‐InDel markers located on X chromosome (ChrX). A multiplex system with 13 multi‐InDel markers, including 28 InDel loci in ChrX, was developed. To validate the multi‐InDel panel, the haplotype distribution in a population sample and in a set of pedigrees was investigated. This study demonstrates usefulness of these markers for individual identification and relationship studies. We highlight the fact that the multi‐InDel markers located on ChrX can provide new supporting information for complex kinship testing.
Molecular characterization and first report of Cryptosporidium genotypes in human population in the Slovak Republic
Authors: Petrincová Antónia , Valenčáková Alexandra , Luptáková Lenka , Ondriska František , Kalinová Jana , Halánová Monika , Danišová Oľga , Jarčuška Pavol
Published: August 2015

In our study, we examined 91 fecal samples from five different groups of people containing HIV patients, hemodialysis patients, kidney transplant recipients, immunocompetent humans without clinical signs, and humans with suspected cryptosporidiosis. The purpose of our study was to determine species and genotype composition of representatives of Cryptosporidium spp. using PCR analysis of small subunit ribosomal RNA gene and 60‐kDa glycoprotein gene and examine their phylogenetic relationship. In HIV‐positive/AIDS‐infected group of patients and in hemodialysis patients, no presence of Cryptosporidium species was detected. In two kidney transplant recipients, we detected species/genotypes Cryptosporidium parvum IIaA13G1T1R1 (KT355488) and Cryptosporidium hominis IaA11G2R8 (KT355489) and in two immunocompetent patients with clinical symptoms, we identified Cryptosporidium muris and C. hominis IbA10G2T1 (KT355490). In the group of healthy immunocompetent individuals without clinical signs, we identified species/genotype C. hominis IbA11G2 (KT355491) in one sample.
Natural killer cells regulate T cell immune responses in primary biliary cirrhosis
Authors: Shimoda Shinji , Hisamoto Satomi , Harada Kenichi , Iwasaka Sho , Chong Yong , Nakamura Minoru , Bekki Yuki , Yoshizumi Tomoharu , Shirabe Ken , Ikegami Toru , Maehara Yoshihiko , He Xiao‐Song , Gershwin M. Eric , Akashi Koichi
Published: August 2015

The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T‐ and B‐cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver‐derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)‐γ, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4+ T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN‐γ production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN‐γ secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4+ T cells to become cytopathic. Conclusions: NK cell‐mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen‐specific T cells, essential for progression of disease. (Hepatology 2015;62:1817‐1827)
DNA‐Mediated Copper Nanoparticle Formation on Dispersed Single‐Walled Carbon Nanotubes
Authors: Ursu Elena‐Laura , Clima Lilia , Hejesen Christian , Rotaru Alexandru , Pinteala Mariana
Published: August 2015

A new and facile method for the preparation of single‐walled carbon nanotubes (SWCNTs) decorated with Cu nanoparticles (CuNPs) formed on a double‐stranded DNA template in aqueous solution has been developed. A specially designed synthetic DNA sequence, containing a single‐stranded domain for the dispersion of carbon nanotubes and double‐stranded domains for the selective growth of CuNPs, was utilized. The final SWCNT/CuNP hybrids were characterized using fluorescence spectroscopy and transmission electron microscopy. The analyses clearly demonstrated the selective formation of uniform CuNPs on the carbon nanotube scaffold.
STAT3 polymorphisms may predict an unfavorable response to first‐line platinum‐based therapy for women with advanced serous epithelial ovarian cancer
Authors: Permuth‐Wey Jennifer , Fulp William J. , Reid Brett M. , Chen Zhihua , Georgeades Christina , Cheng Jin Q. , Magliocco Anthony , Chen Dung‐Tsa , Lancaster Johnathan M.
Published: August 2015

Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC‐related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case–control design was used to study 361 women with advanced‐stage serous EOC treated with surgery followed by first‐line platinum‐based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. “Cases” included 102 incomplete responders (IRs) and “controls” included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC‐related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP‐level associations with an IR to therapy were identified for correlated (r2 > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32–3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML = 0.006). rs1053004, a STAT3 SNP in a putative miRNA‐binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high‐risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors.
The Notch pathway in colorectal cancer
Authors: Vinson Kaitlyn E. , George Dennis C. , Fender Alexander W. , Bertrand Fred E. , Sigounas George
Published: August 2015

Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem‐cell‐like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch‐1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.
Increased breast cancer screening and downstaging in Colombian women: A randomized trial of opportunistic breast‐screening
Authors: Murillo Raúl , Díaz Sandra , Perry Fernando , Poveda César , Piñeros Marion , Sánchez Oswaldo , Buitrago Lina , Gamboa Oscar , Lozano Teófilo , Yu Hsiang , Wang Ching‐Yun , Duggan Catherine , Thomas David B. , Anderson Benjamin O.
Published: August 2015

The lack of breast cancer screening in low and middle‐income countries results in later stage diagnosis and worsened outcomes for women. A cluster randomized trial was performed in Bogotá, Colombia between 2008 and 2012 to evaluate effects of opportunistic breast cancer screening. Thirteen clinics were randomized to an intervention arm and 13 to a control arm. Physicians in intervention clinics were instructed to perform clinical breast examination on all women aged 50–69 years attending clinics for non‐breast health issues, and then refer them for mammographic screening. Physicians in control clinics were not explicitly instructed to perform breast screening or mammography referrals, but could do so if they thought it indicated (“usual care”). Women were followed for 2‐years postrandomization. 7,436 women were enrolled and 7,419 (99.8%) screened in intervention clinics, versus 8,419 enrolled and 1,108 (13.1%) screened in control clinics. Incidence ratios (IR) of early, advanced and all breast cancers were 2.9 (95% CI 1.1–9.2), 1.0 (0.3–3.5) and 1.9 (0.9–4.1) in the first (screening) year of the trial, and the cumulative IR for all breast cancers converged to 1.4 (0.7–2.8) by the end of follow‐up (Year 2). Eighteen (69.2%) of 26 women with early stage disease had breast conservation surgery (BCS) versus 6 (42.5%) of 14 women with late‐stage disease (p = 0.02). Fifteen (68.2%) of 22 women with breast cancer in the intervention group had BCS versus nine (50.0%) of 18 women in the control group (p = 0.34). Well‐designed opportunistic clinic‐based breast cancer screening programs may be useful for early breast cancer detection in LMICs.
Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus
Authors: Hung Chao‐Hung , Hu Tsung‐Hui , Lu Sheng‐Nan , Kuo Fang‐Ying , Chen Chien‐Hung , Wang Jing‐Houng , Huang Chao‐Min , Lee Chuan‐Mo , Lin Chih‐Yun , Yen Yi‐Hao , Chiu Yi‐Chun
Published: August 2015

Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age‐ and sex‐matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow‐up. A panel of ten cancer‐associated miRNAs was analyzed by quantitative real‐time reverse‐transcription polymerase chain reaction. Serum levels of miR‐16, miR‐122, miR‐221, let‐7b and miR‐15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR‐122, miR‐let‐7b and miR‐15b levels increased significantly (p = 0.046, 0.043 and 0.044, respectively). As a single marker, α‐fetoprotein (AFP) and miR‐122 as well as let‐7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let‐7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p = 0.001). In conclusion, miR‐122 and let‐7b, which are upregulated in the serum of early‐HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients.
Selenium Flux Effect on Cu(In,Ga)Se2 Thin Films Grown by a 3‐stage Co‐evaporation Process
Authors: Gwak Jihye , Lee MinJi , Yun Jae Ho , Ahn SeJin , Cho Ara , Ahn SeungKyu , Hulme John P. , Shin Kee Shik , Yoon Kyung Hoon
Published: August 2015

An investigation into the effects of Se flux on absorber thin film growth at each step of a 3‐stage co‐evaporation process was conducted to further optimize the performance of CIGS solar cells. In ‘step I’ forming an In‐Ga‐Se precursor thin film during the 3‐stage process, Se flux affected the preferred orientation of the CIGS crystal structure, but not the film morphology. In ‘step II’, no correlation was found between Se flux and the crystal structure, although excessively high Se flux employed throughout the 3‐stage process degraded the solar cell performance. A CIGS thin film, with a (220/204) crystal orientation, minor physical surface defects and ∼20 nm thick MoSe2 at CIGS/Mo interface, was obtained by fine control of Se flux conditions (high Se flux at ‘step I’ and low Se flux at ‘step II’) at optimum substrate temperatures. The solar cell fabricated using the aforementioned CIGS thin film showed the highest conversion efficiency of 20.02 %.
Face 2‐Colorable Embeddings with Faces of Specified Lengths
Authors: Maenhaut Barbara , Smith Benjamin R.
Published: August 2015

Supposeandare arbitrary lists of positive integers. In this article, we determine necessary and sufficient conditions onMandNfor the existence of a simple graphG, which admits a face 2‐colorable planar embedding in which the faces of one color have boundary lengthsand the faces of the other color have boundary lengths. Such a graph is said to have a planar‐biembedding. We also determine necessary and sufficient conditions onMandNfor the existence of a simple graphGwhose edge set can be partitioned intorcycles of lengthsand also intotcycles of lengths. Such a graph is said to be‐decomposable.
The mechanical properties of the systemic and pulmonary arteries of python regius correlate with blood pressures
Authors: van Soldt Benjamin J. , Danielsen Carl Christian , Wang Tobias
Published: August 2015

Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross‐links between fibers will need further study. J. Morphol. 276:1412–1421, 2015. © 2015 Wiley Periodicals, Inc.
Assessment of liver fibrosis by variable flip angle T1 mapping at 3.0T
Authors: Li Zhiming , Sun Jihong , Hu Xi , Huang Ning , Han Guocan , Chen Lumin , Zhou Yurong , Bai Weixian , Yang Xiaoming
Published: August 2015

Purpose

To evaluate the possibility of using a variable flip angle (VFA) T1 mapping technique to diagnose liver fibrosis.

Materials and Methods

Liver fibrosis was induced in rabbits by repetitive administration of carbon tetrachloride (CCl4). T1‐weighted magnetic resonance imaging (MRI) was performed in 29 animals (liver fibrosis, n = 18; control, n = 11) using a series of nonenhanced liver acquisition volume acceleration (LAVA) with VFAs at 3.0T. Hepatic T1 relaxation times were measured via regions of interest, which were correlated with subsequent histologic confirmation. The results of T1 mapping in assessment of liver fibrosis were compared with that of apparent diffusion coefficient (ADC) values.

Results

The mean T1 relaxation time of the control group was the lowest (250.07 ± 88.12 msec), followed by the nonadvanced fibrosis group (387.83 ± 166.58 msec) and the advanced fibrosis group (496.90 ± 291.24 msec). T1 relaxation time measurements differed significantly between the liver fibrosis group and control group (P < 0.05), with a trend of increased mean T1 relaxation times as the fibrotic stage increased. Statistically significant differences were observed between the control group and the nonadvanced fibrosis group (P < 0.05), however with much overlap between the less severe stages. In discriminating between the control group and liver fibrosis group, stage F0‐1 (control and stage F1) and stage F2‐3, stage F0‐2 (control and stage F1‐2) and stage F3, area under the receiver operating characteristic (ROC) curves were 0.803 (cutoff value 273.01 msec), 0.712 (cutoff value 371.54 msec), and 0.696 (cutoff value 276.99 msec), respectively. No difference was found between T1 relaxation times and ADC values in assessment of liver fibrosis in our study.

Conclusion

VFA T1 mapping may become a noninvasive imaging tool for the diagnosis of liver fibrosis. J. MAGN. RESON. IMAGING 2016;43:698–703.
Summer heat waves in southeastern Patagonia: an analysis of the intraseasonal timescale
Authors: Jacques‐Coper Martín , Brönnimann Stefan , Martius Olivia , Vera Carolina , Cerne Bibiana
Published: August 2015

We explore the occurrence of intraseasonal summer heat waves in southeastern Patagonia (SEPG, 46°–52°S; 65°–70°W) since the late 19th century by means of the Twentieth Century Reanalysis version 2 (20CRv2). In total, we identify 201 cases for 1872–2010 using criteria of intensity and persistence. In SEPG, the corresponding intraseasonal temperature signals are centred around the first day of each cluster of days fulfilling those conditions (named day 0). The mean warm deviation lasts for approximately 2 weeks and exhibits a mean temperature peak of 4.3 °C on day 0 (the warmest day in the mean signal). In a regional context, the mean temperature perturbation associated with these heat waves affects a broad area on both sides of the Andes. The warming in SEPG is caused by temperature advection and enhanced radiative heating, following a high pressure system over southern South America (SSA). This atmospheric perturbation is embedded in a wave‐train‐like pattern along the South Pacific. As part of this pattern, a cyclonic anomaly progresses eastward over the Tasman Sea in Oceania, moving from southeastern Australia (day −6, causing a dry anomaly there) over New Zealand (day −3, inducing a wet anomaly on its Southern Island). The anomalous circulation triggered by the wave train leads thus to a teleconnection between SSA and Oceania, documented in a previous work for the interannual scale. Two thirds of the heat wave events are linked to enhanced ascent in the South Atlantic Convergence Zone (SACZ) and around one third of the events within 1957–2010 are associated with extreme absolute maximum temperatures observed at a station‐based record from SEPG. Finally, possible spatial modulations of the wave train pattern at the interannual and interdecadal timescales are discussed.
Influence of increasing construct constraint in the presence of posterolateral deficiency at knee replacement: A biomechanical study
Authors: Ghosh Kanishka M. , Manning William A. , Blain Alasdair P. , Rushton Steve P. , Longstaff Lee M. , Amis Andrew A. , Deehan David J.
Published: August 2015

When faced with posterolateral corner (PLC) deficiency, surgeons must choose a total knee replacement (TKR) construct that provides the appropriate level of constraint. This should match the internal constraint of the device to the soft tissue host laxity pattern. Little guidance is available peroperatively, with factors influencing final component choice remaining ill defined. This study aimed to quantify the effect of PLC insufficiency on the “envelope of laxity” (EoL) after TKR and the effect of increasingly component constraint upon knee behavior through a functional arc of flexion. Using computer navigation, mixed effect modeling and loaded cadaveric legs—laxity was quantified under separate states: the native knee, after implantation of a posterior stabilized (PS)‐TKR, after sectioning the lateral (fibular) collateral ligament and popliteus tendon (PS‐TKR‐PLC), and after re‐implantation with a semi‐constrained “total stabilized” knee replacement (TS‐TKR). Laxity was quantified from 0 to 110° of flexion for anterior draw, varus–valgus, and internal–external rotation. Implantation of the PS‐TKR was consistently associated with increased constraint when compared to the native knee. PLC sectioning led to significantly increased laxity during varus stress from mid to deep flexion. Revision to a TS‐TKR construct restored constraint mimicking that of the primary state but only for the arc of motion 0–90°. In a posterolateral deficient state, a fixed bearing semi‐constrained TS‐TKR restored the knee to near normal kinematics but this was only achieved from an arc of motion 0–90° of flexion. At higher flexion angles, there remained an unfavorable laxity pattern with varus stress opening. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:427–434, 2016.
Effect of repeated tracheostomy tube reprocessing on biofilm formation
Authors: Rodney Jennifer , Ojano‐Dirain Carolyn P. , Antonelli Patrick J. , Silva Rodrigo C.
Published: August 2015

Objectives/Hypothesis

To determine the effect of repeated reprocessing of pediatric tracheostomy tubes (TTs) on biofilm formation.

Study Design

In vitro microbiological study.

Methods

Pediatric, uncuffed, polyvinyl chloride (PVC) TTs from two different manufacturers (Tracoe Mini and Shiley) were reprocessed mechanically with household detergent and soaked in sodium hypochlorite (bleach). Two TTs of each brand were reprocessed 0 (control), 10, or 20 times. Twenty 2‐mm coupons were then obtained from each TT, immersed in human mucus, and cultured with eitherStaphylococcus aureusorPseudomonas aeruginosa. Biofilm formation was evaluated with bacterial counts.

Results

Bacterial counts ofS. aureusfor both brands were significantly higher on the TTs that were reprocessed 20 times compared to those that were not reprocessed (Tracoe:P = .040, Shiley:P  <  .0001) or those that were reprocessed 10 times (Tracoe:P = .022, Shiley:P = .0002). There was no difference between controls and TTs reprocessed 10 times (Tracoe:P = .76, Shiley:P = .24).P. aeuruginosacounts were not significantly different among the varying numbers of reprocessing cycles for either Tracoe or Shiley TTs (P = .08 andP = .97, respectively).

Conclusions

Repeated reprocessing of PVC TTs with detergent and bleach paradoxically promotesS. aureusbiofilm development, possibly due to degradation of the tube surface that facilitates bacterial attachment. Further investigation is needed to determine the optimal technique and limits of reprocessing TTs in clinical practice.

Level of Evidence

NALaryngoscope, 126:996–999, 2016
Biomimicry – An approach to engineering oils into solid fats
Authors: Wang Tzu‐Min , Rogers Michael A.
Published: August 2015

The ability to eliminate trans fats, without incorporating additional saturated fats, is limited by the physico‐chemical properties of the processed food and what role the lipids play in the food structure. To maintain the levels of cardio‐protective unsaturated fats alternative methods to structure them are desperately needed. One such strategy is to utilize oleogels or molecular gels comprised of small molecules. Herein, we illustrate the potential of biomimicking the assemblies formed by the intercellular lipids in stratum corneum using stearic acid, ceramide III and replacing cholesterol with β‐sitosterol.
Novel interactions between iron and n‐3 fatty acids in cognition and immune function
Authors: Baumgartner Jeannine , Malan Linda , Smuts Cornelius M.
Published: August 2015

Many children, particularly from low‐ and middle‐income countries, may suffer from both iron deficiency and inadequate omega‐3 fatty acid intake due to poor quality diets. Both, iron and omega‐3 fatty acids are important for the development and functioning of the brain and immune system. Using a translational research approach, we therefore investigated potential interactive effects of iron and omega‐3 fatty acid deficiencies and supplementation on cognition and immune‐related outcomes. Our results indicate that in children with iron deficiency and poor omega‐3 fatty acid intake, it may be crucial to administer iron in combination with omega‐3 long‐chain polyunsaturated fatty acids to ensure optimal cognition and immune function.
Spatiotemporal closure of fractional laser‐ablated channels imaged by optical coherence tomography and reflectance confocal microscopy
Authors: Banzhaf Christina A. , Wind Bas S. , Mogensen Mette , Meesters Arne A. , Paasch Uwe , Wolkerstorfer Albert , Haedersdal Merete
Published: August 2015

Background and Objective

Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) offer high‐resolution optical imaging of the skin, which may provide benefit in the context of laser‐assisted drug delivery. We aimed to characterize postoperative healing of ablative fractional laser (AFXL)‐induced channels and dynamics in their spatiotemporal closure using in vivo OCT and RCM techniques.

Study design/Materials and Methods

The inner forearm of healthy subjects (n = 6) was exposed to 10,600 nm fractional CO2 laser using 5 and 25% densities, 120 μm beam diameter, 5, 15, and 25 mJ/microbeam. Treatment sites were scanned with OCT to evaluate closure of AFXL‐channels and RCM to evaluate subsequent re‐epithelialization.

Results

OCT and RCM identified laser channels in epidermis and upper dermis as black, ablated tissue defects surrounded by characteristic hyper‐and hyporeflective zones. OCT imaged individual laser channels of the entire laser grid, and RCM imaged epidermal cellular and structural changes around a single laser channel to the depth of the dermoepidermal junction (DEJ) and upper papillary dermis. OCT images visualized a heterogeneous material in the lower part of open laser channels, indicating tissue fluid. By OCT the median percentage of open channels was evaluated at several time points within the first 24 hours and laser channels were found to gradually close, depending on the used energy level. Thus, at 5 mJ/microbeam, 87% (range 73–100%) of channels were open one hour after laser exposure, which declined to 27% (range 20–100%) and 20% (range 7–93%) at 12 and 24 hours after laser exposure, respectively. At 25 mJ/microbeam, 100% (range 100–100%) of channels were open 1 hour after laser exposure while 53% (range 33–100%) and 40% (range 0–100%) remained open at 12 and 24 hours after exposure. Median depth and width of open channels decreased over time depending of applied energy. RCM verified initial re‐epithelialization from day 2 for all energy levels used. Morphology of ablation defects by OCT and RCM corresponded to histological assessments.

Conclusions

OCT and RCM enabled imaging of AFXL‐channels and their spatiotemporal closure. Laser channels remained open up to 24 hours post laser, which may be important for the time perspective to deliver topical substances through AFXL channels. Lasers Surg. Med. 48:157–165, 2016. © 2015 Wiley Periodicals, Inc.
Once‐daily prolonged release tacrolimus in liver transplantation: Experts' literature review and recommendations
Authors: Coilly Audrey , Calmus Yvon , Chermak Faiza , Dumortier Jerome , Duvoux Christophe , Guillaud Olivier , Houssel‐Debry Pauline , Neau‐Cransac Martine , Stocco Jeanick
Published: August 2015

The efficacy and safety of tacrolimus (Tac) twice daily (bid) and once a day (qd) formulations are considered to be similar. However, the available information regarding initiation of Tac qd is sparse, and practical information is lacking. On the basis of a literature review, clinical efficacy, and safety trials, French experts in the liver transplantation field were asked to highlight pharmacokinetic (PK) differences between both formulations to assess efficacy and safety of the qd formulation in the context of de novo initiation or conversion and to provide their recommendations for initiation and day‐to‐day management of Tac qd. The same efficacy and safety profile is found for both immediate‐release and prolonged‐release Tac. PK differences carry on absorption because of the difference in formulations but not on metabolism or excretion. Tac qd offers a better reproducibility in exposure than Tac bid but is associated with an increased risk of disturbed absorption in case of a change in intestinal motility. The same therapeutic drug monitoring with Tac qd and bid could be applied, based on minimal concentration (trough level; Cmin), as there is a similar strong correlation between Cmin and the area under the curve (AUC) for both formulations. Different protocols for Tac qd initiation were described through numerous studies, except for early conversion: initiation on day 0, using 0.10 to 0.20 mg/kg/day as monotherapy, or lower dosages in case of concomitant immunosuppressant treatment or poor graft quality; early conversion from day 5 to 6 months, preferably before hospital discharge, using a 1 to 1.3 mg/kg/day schedule and with first Cmin assessment 48 hours after the conversion; and later conversion (>6 months posttransplantation) using a milligram‐to‐milligram dosage schedule, and with dose adjustment based on weekly Cmin measurement. Experts underline that an increase in treatment adherence was expected using Tac qd in liver recipients. In conclusion, Tac qd has the same efficacy and safety profile as Tac bid. De novo introduction or later conversion are well documented but could differ from day‐to‐day practice. Liver Transpl 21:1312‐1321, 2015. © 2015 AASLD.
Gelatin microgels as a potential corrosion inhibitor carriers for self‐healing coatings: Preparation and codeposition
Authors: Stankiewicz A. , Jagoda Z. , Zielińska K. , Szczygieł I.
Published: August 2015

Co‐deposition of a coating with capsules containing a corrosion inhibitor is one of the methods to protect the material surface against corrosion. This generation of coatings can be regenerated in response to mechanical or chemical damage. The paper presents a method for preparing gelatin microgels that can be eco‐friendly corrosion inhibitor reservoir. The influence of temperature, stirring rate, an addition of surfactants (ionic and non‐ionic) on microgel quality has been studied. It has been found that the microgels obtained at 80 °C from the solution containing non‐ionic surfactant at concentration below its critical micelle concentration are the most stable and less polydisperse one. As a proof of concept, a Ni‐P\gelatin microgels hybrid coating has been obtained by electroless method.
REM sleep behavior disorder and neuropathology in Parkinson's disease
Authors: Postuma Ronald B. , Adler Charles H. , Dugger Brittany N. , Hentz Joseph G. , Shill Holly A. , Driver‐Dunckley Erika , Sabbagh Marwan N. , Jacobson Sandra A. , Belden Christine M. , Sue Lucia I. , Serrano Geidy , Beach Thomas G.
Published: August 2015

Introduction

Rapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with differences in clinical phenotype, including dementia, autonomic loss, and gait dysfunction. The pathological basis for this remains unclear.

Methods

Parkinson's disease subjects in a longitudinal clinicopathologic study were screened for probable RBD with the Mayo Sleep Questionnaire. After death, semiquantitative analyses were conducted for synuclein, amyloid, neurofibrillary tangles, and cerebrovascular lesions.

Results

Forty cases had probable RBD (PD+RBD), and 41 did not (PD‐RBD). Despite similar age at death (∼80 y) and disease duration (∼14.5 y), PD+RBD had increased synuclein deposition in all regions examined, with nine of 10 regions significantly different. The Lewy body 10‐region total score (scale = 0‐40) was 29.5 in PD+RBD versus 24.5 in PD‐RBD (Cohen‐d effect size = 0.79, P = 0.002). Cerebrovascular lesion burden was slightly higher in PD‐RBD.

Conclusions

Although overlap occurs between groups, PD patients with probable RBD may have greater density and range of synuclein pathology on autopsy. © 2015 International Parkinson and Movement Disorder Society
Genetic analysis of nonalcoholic fatty liver disease within a Caribbean–Hispanic population
Authors: Edelman Deborah , Kalia Harmit , Delio Maria , Alani Mustafa , Krishnamurthy Karthik , Abd Mortadha , Auton Adam , Wang Tao , Wolkoff Allan W. , Morrow Bernice E.
Published: August 2015

We explored potential genetic risk factors implicated in nonalcoholic fatty liver disease (NAFLD) within a Caribbean–Hispanic population in New York City. A total of 316 individuals including 40 subjects with biopsy‐proven NAFLD, 24 ethnically matched non‐NAFLD controls, and a 252 ethnically mixed random sampling of Bronx County, New York were analyzed. Genotype analysis was performed to determine allelic frequencies of 74 known single‐nucleotide polymorphisms (SNPs) associated with NAFLD risk based on previous genome‐wide association study (GWAS) and candidate gene studies. Additionally, the entire coding region of PNPLA3, a gene showing the strongest association to NAFLD was subjected to Sanger sequencing. Results suggest that both rare and common DNA variations in PNPLA3 and SAMM50 may be correlated with NAFLD in this small population study, while common DNA variations in CHUK and ERLIN1, may have a protective interaction. Common SNPs in ENPP1 and ABCC2 have suggestive association with fatty liver, but with less compelling significance. In conclusion, Hispanic patients of Caribbean ancestry may have different interactions with NAFLD genetic modifiers; therefore, further investigation with a larger sample size, into this Caribbean–Hispanic population is warranted.
Lycopene reduces cholesterol absorption through the downregulation of Niemann‐Pick C1‐like 1 in Caco‐2 cells
Authors: Zou Jun , Feng Dan
Published: August 2015

Scope

Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Tomato lycopene has been found to have a hypocholesterolemic effect, and the effect was considered to be related to inhibition of cholesterol synthesis. However, since plasma cholesterol levels are also influenced by the absorption of cholesterol in the gut, the present study is to investigate whether lycopene affects cholesterol absorption in the intestinal Caco‐2 cells.

Methods and results

The Caco‐2 cells were pretreated with lycopene at different concentrations for 24 h and then incubated with radioactive micellar cholesterol for 2 h. The absorption of radioactive cholesterol was quantified by liquid scintillation. The expression of Niemann‐Pick C1‐like 1 (NPC1L1) and liver X receptor α (LXRα) was analyzed by Western blot and qPCR. We found that lycopene dose dependently inhibited cholesterol absorption and the expression of NPC1L1 protein and NPC1L1 mRNA. The inhibitory effects of lycopene on cholesterol absorption and NPC1L1 expression could be prevented by blockade of the LXRα pathway.

Conclusion

This study provides the first evidence that lycopene inhibits cholesterol absorption in the intestinal cells and this inhibitory effect of lycopene is mediated, at least in part, by LXRα‐NPC1L1 signaling pathway.
Profiling the metabolome changes caused by cranberry procyanidins in plasma of female rats using 1H NMR and UHPLC‐Q‐Orbitrap‐HRMS global metabolomics approaches
Authors: Liu Haiyan , Garrett Timothy J. , Tayyari Fariba , Gu Liwei
Published: August 2015

Scope

The objective was to investigate the metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) using 1H NMR and UHPLC‐Q‐Orbitrap‐HRMS metabolomics approaches, and to identify the contributing metabolites.

Methods and results

Twenty‐four female Sprague‐Dawley rats were randomly separated into two groups and administered PPCP or partially purified apple procyanidins (PPAP) for three times using a 250 mg extracts/kg body weight dose. Plasma was collected 6 h after the last gavage and analyzed using 1H NMR and UHPLC‐Q‐Orbitrap‐HRMS. No metabolome difference was observed using 1H NMR metabolomics approach. However, LC‐HRMS metabolomics data show that metabolome in the plasma of female rats administered PPCP differed from those gavaged with PPAP. Eleven metabolites were tentatively identified from a total of 36 discriminant metabolic features based on accurate masses and/or product ion spectra. PPCP caused a greater increase of exogenous metabolites including p‐hydroxybenzoic acid, phenol, phenol‐sulphate, catechol sulphate, 3, 4‐dihydroxyphenylvaleric acid, and 4′‐O‐methyl‐(–)‐epicatechin‐3′‐O‐beta‐glucuronide in rat plasma. Furthermore, the plasma level of O‐methyl‐(–)‐epicatechin‐O‐glucuronide, 4‐hydroxy‐5‐(hydroxyphenyl)‐valeric acid‐O‐sulphate, 5‐(hydroxyphenyl)‐ϒ‐valerolactone‐O‐sulphate, 4‐hydroxydiphenylamine, and peonidin‐3‐O‐hexose were higher in female rats administered with PPAP.

Conclusion

The metabolome changes caused by cranberry procyanidins were revealed using an UHPLC‐Q‐Orbitrap‐HRMS global metabolomics approach. Exogenous and microbial metabolites were the major identified discriminate biomarkers.
An anisotropic elastoplastic model for soft clays based on logarithmic contractancy
Authors: Sivasithamparam Nallathamby , Castro Jorge
Published: August 2015

A new constitutive model for soft structured clays is developed based on an existing model called S‐CLAY1S, which is a Cam clay type model that accounts for anisotropy and destructuration. The new model (E‐SCLAY1S) uses the framework of logarithmic contractancy to introduce a new parameter that controls the shape of the yield surface as well as the plastic potential (as an assumed associated flow rule is applied). This new parameter can be used to fit the coefficient of earth pressure at rest, the undrained shear strength or the stiffness under shearing stress paths predicted by the model. The improvement to previous constitutive models that account for soil fabric and bonding is formulated within the contractancy framework such that the model predicts the uniqueness of the critical state line and its slope is independent of the contractancy parameter. Good agreement has been found between the model predictions and published laboratory results for triaxial compression tests. An important finding is that the contractancy parameter, and consequently the shape of the yield surface, seems to change with the degree of anisotropy; however, further study is required to investigate this response. From published data, the yield surface for isotropically consolidated clays seems ‘bullet’ or ‘almond’ shaped, similar to that of the Cam clay model; while for anisotropically consolidated clays, the yield surface is more elliptical, like a rotated and distorted modified Cam clay yield surface. © 2015 The Authors. International Journal for Numerical and Analytical Methods in Geomechanics published by John Wiley & Sons Ltd.
Build a strong program for adult learners by developing adult educators
Authors: Sutton Halley
Published: August 2015

During his 25 years in the United States Air Force, Bill McClure was first exposed to working with adult learners as an adjunct instructor for the University of Maryland, the City Colleges of Chicago, and the Defense Language Institute in Monterey. In addition to teaching and working 40–50 hours a week with the Air Force, he was earning his two graduate degrees.
Conformational stability of the RNP domain controls fibril formation of PABPN1
Authors: Liebold Jens , Winter Reno , Golbik Ralph , Hause Gerd , Parthier Christoph , Schwarz Elisabeth
Published: August 2015

The disease oculopharyngeal muscular dystrophy is caused by alanine codon trinucleotide expansions in the N‐terminal segment of the nuclear poly(A) binding protein PABPN1. As histochemical features of the disease, intranuclear inclusions of PABPN1 have been reported. Whereas the purified N‐terminal domain of PABPN1 forms fibrils in an alanine‐dependent way, fibril formation of the full‐length protein occurs also in the absence of alanines. Here, we addressed the question whether the stability of the RNP domain or domain swapping within the RNP domain may add to fibril formation. A variant of full‐length PABPN1 with a stabilizing disulfide bond at position 185/201 in the RNP domain fibrillized in a redox‐sensitive manner suggesting that the integrity of the RNP domain may contribute to fibril formation. Thermodynamic analysis of the isolated wild‐type and the disulfide‐linked RNP domain showed two state unfolding/refolding characteristics without detectable intermediates. Quantification of the thermodynamic stability of the mutant RNP domain pointed to an inverse correlation between fibril formation of full‐length PABPN1 and the stability of the RNP domain.
Thermodynamics of Aβ16–21 dissociation from a fibril: Enthalpy, entropy, and volumetric properties
Authors: Rao Jampani Srinivasa , Mahmoudinobar Farbod , Su Zhaoqian , Dias Cristiano L.
Published: August 2015

Here, we provide insights into the thermodynamic properties of A
dissociation from an amyloid fibril using all‐atom molecular dynamics simulations in explicit water. An umbrella sampling protocol is used to compute potentials of mean force (PMF) as a function of the distance ξ between centers‐of‐mass of the A
peptide and the preformed fibril at nine temperatures. Changes in the enthalpy and the entropic energy are determined from the temperature dependence of these PMF(s) and the average volume of the simulation box is computed as a function of ξ. We find that the PMF at 310 K is dominated by enthalpy while the entropic energy does not change significantly during dissociation. The volume of the system decreases during dissociation. Moreover, the magnitude of this volume change also decreases with increasing temperature. By defining dock and lock states using the solvent accessible surface area (SASA), we find that the behavior of the electrostatic energy is different in these two states. It increases (unfavorable) and decreases (favorable) during dissociation in lock and dock states, respectively, while the energy due to Lennard‐Jones interactions increases continuously in these states. Our simulations also highlight the importance of hydrophobic interactions in accounting for the stability of A
. Proteins 2015; 83:1963–1972. © 2015 Wiley Periodicals, Inc.
The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis
Authors: Improta Roberto , Vitagliano Luigi , Esposito Luciana
Published: August 2015

The elucidation of the mutual influence between peptide bond geometry and local conformation has important implications for protein structure refinement, validation, and prediction. To gain insights into the structural determinants and the energetic contributions associated with protein/peptide backbone plasticity, we here report an extensive analysis of the variability of the peptide bond angles by combining statistical analyses of protein structures and quantum mechanics calculations on small model peptide systems. Our analyses demonstrate that all the backbone bond angles strongly depend on the peptide conformation and unveil the existence of regular trends as function of ψ and/or φ. The excellent agreement of the quantum mechanics calculations with the statistical surveys of protein structures validates the computational scheme here employed and demonstrates that the valence geometry of protein/peptide backbone is primarily dictated by local interactions. Notably, for the first time we show that the position of the Hα hydrogen atom, which is an important parameter in NMR structural studies, is also dependent on the local conformation. Most of the trends observed may be satisfactorily explained by invoking steric repulsive interactions; in some specific cases the valence bond variability is also influenced by hydrogen‐bond like interactions. Moreover, we can provide a reliable estimate of the energies involved in the interplay between geometry and conformations. Proteins 2015; 83:1973–1986. © 2015 Wiley Periodicals, Inc.
Official Statistics Data Integration for Enhanced Information Quality
Authors: Dalla Valle Luciana , Kenett Ron S.
Published: August 2015

This work is about integrated analysis of data collected as official statistics with administrative data from operational systems in order to increase the quality of information. Information quality, or InfoQ, is ‘the potential of a data set to achieve a specific goal by using a given empirical analysis method’. InfoQ is based on the identification of four interacting components: the analysis goal, the data, the data analysis and the utility, and it is assessed through eight dimensions: data resolution, data structure, data integration, temporal relevance, generalizability, chronology of data and goal, construct operationalization and communication. The paper illustrates, through case studies, a novel strategy to increase InfoQ based on the integration of official statistics with administrative data using copulas and Bayesian Networks. Official statistics are extraordinary sources of information. However, because of temporal relevance and chronology of data and goals, these fundamental sources of information are often not properly leveraged resulting in a poor level of InfoQ in the use of official statistics. This leads to low valued statistical analyses and to the lack of sufficiently informative results. By improving temporal relevance and chronology of data and goals, the use of Bayesian Networks allows us to calibrate official with administrative data, thus strengthening the quality of the information derived from official surveys, and, overall, enhancing InfoQ. We show, with examples, how to design and implement such a calibration strategy. Copyright © 2015 John Wiley & Sons, Ltd.
On the relation between multimarket contact and service quality: Mutual forbearance or network coordination?
Authors: van Reeven Peran , Pennings Enrico
Published: August 2015

Research summary: We reconsider the relationship between multimarket contact and product quality in the airline industry by arguing that multimarket contact has both a negative mutual forbearance effect on quality and a positive network coordination effect on quality. Multimarket contact increases the frequency of contact between firms, and this anticipated future interaction promotes cooperation. In network industries, especially small firms may want to cooperate in order to increase the attractiveness of the composite product. By using size as a moderating variable, we indeed find a consistent positive effect of multimarket contact on product quality for small airlines. We show that this effect can be attributed to network coordination and that this effect generally dominates the negative mutual forbearance effect in a recent period.

Managerial summary: Firms with sales in multiple geographical markets likely encounter each other with mutual respect (i.e., live and let live) because aggressive behavior in one market may lead to retaliatory responses in other markets. Such responses weaken competitive pressures on price and quality. Insofar these firms sell complementary products, they may however also coordinate and improve their joint product offering, resulting in better quality for the consumer. This paper shows that this positive effect of cooperation may dominate the negative competition‐reducing effect, depending on the size distribution of firms. The reason is that small or nondominant firms have a stronger incentive to produce compatible products than large or dominant firms with already a strong position in the (global) market. Copyright © 2015 John Wiley & Sons, Ltd.