bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent fusion transcripts detected by whole‐transcriptome sequencing of 120 primary breast cancer samples
Authors: Kim Jisun , Kim Sehwan , Ko Seyoon , In Yong‐ho , Moon Hyeong‐Gon , Ahn Soo Kyung , Kim Min Kyoon , Lee Minju , Hwang Jin‐Ha , Ju Young Seok , Kim Jong‐Il , Noh Dong‐Young , Kim Sun , Park Jung‐Hoon , Rhee Hwanseok , Kim Sunghoon , Han Wonshik
Published: July 2015

Relatively few recurrent gene fusion events have been associated with breast cancer to date. In an effort to uncover novel fusion transcripts, we performed whole‐transcriptome sequencing of 120 fresh‐frozen primary breast cancer samples and five adjacent normal breast tissues using the Illumina HiSeq2000 platform. Three different fusion‐detecting tools (deFuse, Chimerascan, and TopHatFusion) were used, and the results were compared. These tools detected 3,831, 6,630 and 516 fusion transcripts (FTs) overall. We primarily focused on the results obtained using the deFuse software. More FTs were identified from HER2 subtype breast cancer samples than from the luminal or triple‐negative subtypes (P < 0.05). Seventy fusion candidates were selected for validation, and 32 (45.7%) were confirmed by RT‐PCR and Sanger sequencing. Of the validated fusions, six were recurrent (found in 2 or more samples), three were in‐frame (PRDX1‐AKR1A1, TACSTD2‐OMA1, and C2CD2‐TFF1) and three were off‐frame (CEACAM7‐CEACAM6, CYP4X1‐CYP4Z2P, and EEF1DP3‐FRY). Notably, the novel read‐through fusion, EEF1DP3‐FRY, was identified and validated in 6.7% (8/120) of the breast cancer samples. This off‐frame fusion results in early truncation of the FRY gene, which plays a key role in the structural integrity during mitosis. Three previously reported fusions, PPP1R1B‐STARD3, MFGE8‐HAPL, and ETV6‐NTRK3, were detected in 8.3, 3.3, and 0.8% of the 120 samples, respectively, by both deFuse and Chimerascan. The recently reported MAGI3‐AKT3 fusion was not detected in our analysis. Although future work will be needed to examine the biological significance of our new findings, we identified a number of novel fusions and confirmed some previously reported fusions. © 2015 Wiley Periodicals, Inc.
The UK‐PBC risk scores: Derivation and validation of a scoring system for long‐term prediction of end‐stage liver disease in primary biliary cholangitis
Authors: Carbone Marco , Sharp Stephen J. , Flack Steve , Paximadas Dimitrios , Spiess Kelly , Adgey Carolyn , Griffiths Laura , Lim Reyna , Trembling Paul , Williamson Kate , Wareham Nick J. , Aldersley Mark , Bathgate Andrew , Burroughs Andrew K. , Heneghan Michael A. , Neuberger James M. , Thorburn Douglas , Hirschfield Gideon M. , Cordell Heather J. , Alexander Graeme J. , Jones David E.J. , Sandford Richard N. , Mells George F. ,   and the members of the UK‐PBC Consortium
Published: July 2015

The biochemical response to ursodeoxycholic acid (UDCA)—so‐called “treatment response”—strongly predicts long‐term outcome in primary biliary cholangitis (PBC). Several long‐term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long‐term prognostic models of PBC using data from the UK‐PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA‐treated participants. We used nonautomatic backward selection to derive the best‐fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver‐related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA‐treated participants. The best‐fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5‐, 10‐, and 15‐year risk scores were highly accurate (areas under the curve: >0.90). Conclusions: The prognosis of PBC patients can be accurately evaluated using the UK‐PBC risk scores. They may be used to identify high‐risk patients for closer monitoring and second‐line therapies, as well as low‐risk patients who could potentially be followed up in primary care. (Hepatology 2016;63:930–950)
The nephridial hypothesis of the gill slit origin
Authors: Ezhova Olga V. , Malakhov Vladimir V.
Published: July 2015

Metameric gill slits are mysterious structures, unique for Chordata and Hemichordata, and also, perhaps, for the extinct Cambrian Calcichordata. There is a discussed hypothesis of the gill slits origin from the metameric nephridia. According to the hypothesis, the hypothetical metameric deuterostome ancestor had in each segment a pair of coelomoducts and a pair of intestinal pockets. In the anterior segments, the coelomoducts have fused with the intestinal pockets. As a result, each nephridium opened both into the gut and into the environment. Then the dissepiments and funnels reduced in all segments except the collar one. Thus, in recent enteropneusts, only the first pair of gill slits keeps the ancestral arrangement communicating at the same time with the gut, with the environment, and with the coelom of the preceding (collar) segment. In the anterior part of the branchio‐genital trunk region of enteropneusts, the metameric intestinal pockets remained, as well as the metameric coelomoducts functioning as the ducts of the metameric gonads, i.e., as the gonoducts. The consequence of the hypothesis is that the metameric gill pores originate from the metameric excreting pores, and the metameric branchial sacs originate from the metameric endodermal pockets of the gut fused with the coelomoducts. The metameric gill slits by themselves correspond with metameric openings connecting the gut with metameric intestinal pockets. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 647–652, 2015. © 2015 Wiley Periodicals, Inc.
DAG‐Width and Circumference of Digraphs
Authors: Bang‐Jensen Jørgen , Larsen Tilde My
Published: July 2015

We prove that every digraph of circumference l has DAG‐width at most l. This is best possible and solves a recent conjecture from S. Kintali (ArXiv:1401.2662v1 [math.CO], January 2014).1 As a consequence of this result we deduce that the k‐linkage problem is polynomially solvable for every fixed k in the class of digraphs with bounded circumference. This answers a question posed in J. Bang‐Jensen, F. Havet, and A. K. Maia (Theor Comput Sci 562 (2014), 283–303). We also prove that the weak k‐linkage problem (where we ask for arc‐disjoint paths) is polynomially solvable for every fixed k in the class of digraphs with circumference 2 as well as for digraphs with a bounded number of disjoint cycles each of length at least 3. The case of bounded circumference digraphs is still open. Finally, we prove that the minimum spanning strong subdigraph problem is NP‐hard on digraphs of DAG‐width at most 5.
Pulmonary high‐resolution ultrashort TE MR imaging: Comparison with thin‐section standard‐ and low‐dose computed tomography for the assessment of pulmonary parenchyma diseases
Authors: Ohno Yoshiharu , Koyama Hisanobu , Yoshikawa Takeshi , Seki Shinichiro , Takenaka Daisuke , Yui Masao , Lu Aiming , Miyazaki Mitsue , Sugimura Kazuro
Published: July 2015

Background

To determine the accuracy of pulmonary MR imaging with ultrashort echo time (UTE) for lung and mediastinum assessments using computed tomography (CT) as the reference standard, for various pulmonary parenchyma diseases.

Methods

Eight‐five consecutive patients (46 males: mean age, 69 years and 39 females: mean age, 69 years) with various pulmonary parenchyma diseases were examined with chest standard‐ and low‐dose CTs and pulmonary MR imaging with UTE. This was followed by visual assessment using a 5‐point system of the presence of nodules or masses, ground‐glass opacity, micronodules, nodules, patchy shadow or consolidation, emphysema or bullae, bronchiectasis, reticular opacity, and honeycomb and traction bronchiectasis. Presence of aneurysms, pleural or pericardial effusions, pleural thickening or tumor, and lymph adenopathy was also evaluated using a 5‐point system. To compare the capability of the methods for lung parenchyma and mediastinum evaluation, intermethod agreement was evaluated by means of kappa statistics and χ2 test. Receiver operating characteristic analyses were used to compare diagnostic performance of all methods.

Results

Intermethod agreements between pulmonary MR imaging and standard‐dose and low‐dose CT were significant and either substantial or almost perfect (0.67 ≤ κ ≤ 0.98; P < 0.0001). Areas under the curve for emphysema or bullae, bronchiectasis or traction bronchiectasis and reticular opacity on standard‐dose CT were significantly larger than those on low‐dose CT (emphysema or bullae: P = 0.0002; reticular opacity: P < 0.0001) and pulmonary MR imaging (emphysema or bullae: P < 0.0001; bronchiectasis: P = 0.008; reticular opacity: P < 0.0001).

Conclusion

Pulmonary MR imaging with UTE is useful for lung and mediastinum assessment and evaluation of radiological findings for patients with various pulmonary parenchyma diseases. J. Magn. Reson. Imaging 2016;43:512–532.
Zinc uptake and distribution in tomato plants in response to foliar supply of Zn hydroxide‐nitrate nanocrystal suspension with controlled Zn solubility
Authors: Du Yumei , Li Peng , Nguyen Anh V , Xu Zhi Ping , Mulligan David , Huang Longbin
Published: July 2015

The present study investigated the foliar uptake rate, distribution, and retranslocation patterns of novel, synthesized zinc hydroxide‐nitrate nanocrystals (ZnHN; solubility 30–50 mg Zn L−1) applied on to the adaxial surface of tomato leaves (Solanum lycopersicum L. cv. Roma). The total Zn absorption from ZnHN suspension positively increased with ZnHN application rates, but the relative efficacy started to decline at > 400 mg Zn L−1. Within the 3 weeks, total Zn recovery in the ZnHN‐treated plants was 16% of the total ZnHN‐Zn applied, compared to the near 90% total Zn recovery in the Zn(NO3)2‐plants at the same Zn rate. Foliar‐absorbed ZnHN‐Zn was distributed from the treated leaves into other plant parts and preferentially translocated into the roots. Distribution of Zn from ZnHN‐treated leaves to apical parts was not limited by Zn deficiency. These results demonstrate that ZnHN crystals with controlled solubility provided some sort of slow‐release Zn over a certain growth period at a rate slower (but quantitatively effective) than the soluble Zn(NO3)2. The efficacy of the prolonged foliar Zn supply could be enhanced if the ZnHN suspension is sprayed over a large leaf surface area at the peak vegetative or early flowering stage.
Diurnal patterns of methane emissions from paddy rice fields in the Philippines
Authors: Weller Sebastian , Kraus David , Butterbach‐Bahl Klaus , Wassmann Reiner , Tirol‐Padre Agnes , Kiese Ralf
Published: July 2015

Methane (CH4) emissions from rice paddies often show significant diurnal variations, most likely driven by diurnal changes of radiation and temperature in air, floodwater, and soil. Field measurements, however, are often scheduled at a fixed time of a given measuring day, thereby neglecting sub‐daily variations of CH4 emissions. Here we evaluated diurnal patterns of CH4 emissions from traditional paddy rice production as observed during field measurements in the Philippines. Field emissions were measured during three consecutive cropping seasons using an automated chamber and gas sampling system with fluxes being obtained every 4 h. Methane fluxes were monitored with a total of nine chambers during the dry seasons in 2012 and 2013 and 27 chambers during the wet season in 2012. Significant and consistent diurnal patterns of CH4 emissions were mainly observed from the start of field flooding until the middle of cropping periods, i.e., periods with low leaf area of the rice crop. Our data show that disregarding the diurnal variability of fluxes results in an average overestimation of seasonal CH4 emissions of 22% (16–31%) if measurements were conducted only around noon. Scheduling manual sampling either at early morning (7:00–9:00) or evening (17:00–19:00) results in estimations of seasonal emissions within 94–101% of the “true” value as calculated from multiple daily flux measurements. Alternatively, uncertainties of seasonal emissions can be reduced to an average of ≤3% by applying sinus function or Gauss function‐based correction factors. Application of correction factors allows the performance of flux measurements at any time of day. We also investigated N2O emissions from rice paddies with respect to diurnal variations, but did not find, as in the case of CH4, any significant and persistent diurnal pattern.
Results of pediatric tympanoplasty on short‐term surgical missions
Authors: Isaacson Glenn , Melaku Abebe
Published: July 2015

Objectives/Hypothesis

To determine the safety and effectiveness of pediatric tympanoplasty performed on short‐term international medical missions.

Study Design

Prospective observational study.

Methods

Ethiopian children who had dry or nearly dry tympanic perforations and bilateral conductive hearing losses underwent postauricular tympanoplasties with underlain temporalis fascia grafts. Pre‐ and postoperative air and bone audiometry was performed. Complications, graft success, hearing improvement, and dry ear at 6‐month follow‐up were evaluated.

Results

Patients were 7 to 25 years old (24 female ears, 20 male ears). The majority had subtotal perforations. Operative findings included ossicular erosions and fixation by hypertrophic mucosa. There were no major medical complications or deaths in this series.

Of 44 ears, 27 had complete pre‐ and postoperative audiometric data. Twenty‐four of 44 surgeries resulted in an intact tympanic membrane. Twelve of 44 markedly reduced the perforation. Eight of 44 grafts failed. The mean improvement in PTA was 14 dB (range = −6–45 dB). Human immunodeficiency virus (HIV)+ patients had a high rate of graft failure (3/4) and comprised 38% (3/8) of complete graft failures (P = .015). Among the 20 ears with residual perforations, 14 were dry at 6‐month follow‐up. Of the six ears with drainage, three were HIV+ (P = .019).

Conclusions

Pediatric tympanoplasty is a safe procedure in a short‐term surgical mission setting when high anesthetic and surgical standards are maintained. Surgical results were similar to those found in developing‐world university hospitals, but were worse than in United States or European series. HIV+ children did worse than their HIV−/unknown peers, with a high rate of graft failure and persistent otorrhea.

Level of Evidence

4. Laryngoscope, 126:1464–1469, 2016
Clinical relevance of quality of life in laryngomalacia
Authors: Thottam Prasad John , Simons Jeffrey P. , Choi Sukgi , Maguire Raymond , Mehta Deepak K.
Published: July 2015

Objectives/Hypothesis

To examine aspects of laryngomalacia and correlate findings with quality of life (QOL).

Study Design

Prospective cross‐sectional study.

Methods

Seventy‐two patients with laryngomalacia were examined; the mean age was 8.8 weeks. Parents answered questions from the Infant and Toddler Quality of Life Questionnaire–47 (ITQOL‐SF47). Fiberoptic laryngoscopy and endoscopic examination of swallowing (FEES) were performed. The presence of laryngomalacia‐associated characteristics and swallowing status were recorded. Patient age, sex, presence of reflux, clinical severity, anatomical findings, and swallowing results were evaluated through logistic regression. Independent sample t tests were used to compare responses on the ITQOL‐SF47. Overall laryngomalacia ITQOL‐SF47 scores were compared to the scores of a large healthy sample population.

Results

Forty‐three (60%) patients had mild laryngomalacia, and 61 (85%) patients had findings suggesting gastroesophageal reflux disease. The most common abnormality was shortened aryepiglottic folds. Ten patients failed FEES. Patients with moderate laryngomalacia (χ = 7.62; P = .006) or prolapsing cuneiforms (χ = 4.79; P = .029) were more likely to fail FEES. Laryngomalacia severity impacted parental perception of their child's health (P < .05). Parents of children who demonstrated aspiration or penetration reported significant emotional impact (mean = 56.9; t = 2.74; P = .008). The mean ITQOL‐SF47 scores of patients were significantly lower in certain sections than the reported general sample population.

Conclusions

Epiglottal prolapse correlated with severity of laryngomalacia and cuneiform prolapse with swallowing dysfunction. Perceptions of worsening health and physical ability were related to severity of disease. Swallowing dysfunction had a significant emotional impact on parental daily life. Infants with laryngomalacia have a lower QOL

Level of Evidence

3 Laryngoscope, 126:1232–1235, 2016
Therapeutic advances in Huntington's Disease
Authors: Shannon Kathleen M. , Fraint Avram
Published: July 2015

Huntington's disease is a rare hereditary degenerative disease with a wide variety of symptoms that encompass movement, cognition, and behavior. The genetic mutation that causes the disease has been known for more than 20 y, and animal models have illuminated a host of intracellular derangements that occur downstream of protein translation. A number of clinical trials targeting these metabolic consequences have failed to produce a single effective therapy, although clinical trials continue. New strategies targeting the protein at the level of transcription, translation, and posttranslational modification and aggregation engender new hope that a successful strategy will emerge, but there is much work ahead. Some of the clinical manifestations of the illness, particularly chorea, affective symptoms, and irritability, are amenable to palliative strategies, but physicians have a poor evidence base on which to select the best agents. Clinical trials since 2013 have dashed hopes that coenzyme Q10 or creatine might have disease‐modifying properties but suggested other agents were safe or hinted at efficacy (cysteamine, selisistat, hydroxyquinoline) and could proceed into later‐stage disease modification trials. The hunt for effective symptom relief suggested that pridopidine might be shown effective given the right outcome measure. This review summarizes recent progress in HD and highlights promising new strategies for slowing disease progression and relieving suffering in HD. © 2015 International Parkinson and Movement Disorder Society
Time‐domain Galerkin method for dynamic load identification
Authors: Liu Jie , Meng Xianghua , Jiang Chao , Han Xu , Zhang Dequan
Published: July 2015

This paper proposes a new method called time‐domain Galerkin method (TDGM) for investigating the structural dynamic load identification problems. Firstly, the shape functions are adopted to approximate three parameters, such as the dynamic load, kernel function response, and measured structural response Secondly, defining a residual function could be expressed as the difference of the measured response and the computational response. Thirdly, select an appropriate weighting function to multiply the defined residual function and make integral operation with respect to time to be zero. Finally, when the shape functions are chosen as the weighting function, it establishes the forward model called TDGM. Furthermore, the regularization method could have effectiveness in solving the ill‐posed matrix of load reconstruction and obtaining the accurate identified results of the dynamic load. Compared with the traditional Green kernel function method (GKFM), TDGM can effectively overcome the influences of noise and improve the accuracy of the dynamic load identification. Three numerical examples are provided to demonstrate the correctness and advantages of TDGM. Copyright © 2015 John Wiley & Sons, Ltd.
Raman study of insulating and conductive ZnO:(Al, Mn) thin films
Authors: Cerqueira M. F. , Viseu T. , Ayres de Campos J. , Rolo A. G. , de Lacerda‐Aroso T. , Oliveira F. , Bogdanovic‐Radovic I. , Alves E. , Vasilevskiy M. I.
Published: July 2015

Raman spectroscopy results obtained for undoped and Al‐ and/or Mn‐doped ZnO thin films produced by RF‐sputtering are reported. The effect of the doping method (either co‐sputtering or ion implantation), the dopant type, and its concentration on the Raman‐active vibrational modes in these films were studied in detail. The results are discussed with focus on the peak shifts and broadening, and on the doping‐induced relaxation of the symmetry selection rules. A particular attention is paid to the 520–530 cm−1 Raman band observed in all Mn containing samples and a simple theoretical model and arguments are presented in support of its relation to the local (gap) phonon mode produced by Mn atoms substituting Zn in the cationic sublattice of the ZnO crystal.
Influence of side groups on the performance of infrared absorbing aza‐BODIPY organic solar cells
Authors: Kraner Stefan , Widmer Johannes , Benduhn Johannes , Hieckmann Ellen , Jägeler‐Hoheisel Till , Ullbrich Sascha , Schütze Daniel , Sebastian Radke K. , Cuniberti Gianaurelio , Ortmann Frank , Lorenz‐Rothe Melanie , Meerheim Rico , Spoltore Donato , Vandewal Koen , Koerner Christian , Leo Karl
Published: July 2015

Abstractauthoren Organic solar cells are a promising technology for a large area conversion of sunlight into electricity. In particular for solar cells based on oligomers (small molecules), efficient donor materials absorbing wavelengths larger than 780 nm are still rare. Here, we investigate three aza‐BODIPY dyes absorbing in the infrared. The addition of side groups leads to a red shift of the optical gap from 802 to 818 nm. In optimized devices using these donors in a bulk heterojunction with , we observe a higher charge carrier mobility and a higher power conversion efficiency for the molecules without a methyl or methoxy side group lowering the molecular reorganization energy. Surprisingly, the donor–acceptor blend with the lowest energy loss during the electron transfer to the yields the highest short circuit current. With increasing size of the attached side chain, the devices exhibit a larger trap density, measured by impedance spectroscopy. Based on the investigation of different blend ratios, we conclude that these traps are mainly present in the donor phase.
The Clinician's Toolbox: Assessing the Sexual Impacts of Cancer on Adolescents and Young Adults with Cancer (AYAC)
Authors: Aubin Sylvie , Perez Samara
Published: July 2015

Introduction

Adolescents and young adults aged 15-39 years who have been diagnosed with cancer (AYAC) have unique medical and psychosocial needs. Following their cancer treatments, AYAC must learn to manage the sometimes irreversible general side effects of cancer treatments including side effects that impact their sexuality. These side effects include but are not limited to: infertility, altered body/physical appearance, and sexual dysfunction. Such effects may hinder AYAC efforts to date and experiment sexually, limiting sexual maturation and confidence, as well as the formation or maintenance of meaningful couple and sexual relationships. It is clear that we need to tailor our clinical approaches to ensure that we assess the unique needs and concerns faced by AYAC.

Aims

Based on consistent study findings substantiating the distinctive needs of AYAC, the main objective of this article is to present the core clinical components involved in assessing sexuality among AYAC.

Methods

The clinical recommendations are based on the authors and experts' clinical experiences coupled with a thorough examination of the literature related to AYAC sexuality.

Main Outcome Measures

This article first describes the three components (clinical interview, review of chart notes, and self-report questionnaires) of a sexuality assessment and the seven core domains that highlight target areas of focus.

Results

A detailed outline of each of the core domains of assessment (socio-demographics; medical history; fertility and sexually transmitted infection; sexual functioning; sexual coping style; body and self-image; and sexual history and dating/couple experience) is presented. A “toolbox” table containing useful resources for clinicians (e.g., questionnaires and red flags) and direct resources for AYAC patients are included.

Conclusion

Cancer can have a significant impact on numerous domains of AYAC sexuality. The assessment of and attention to the impact of sexuality on AYAC is crucial in order to provide effective and comprehensive quality patient cancer care.
The creation of a comprehensive metocean data set for offshore wind turbine simulations
Authors: Stewart Gordon M. , Robertson Amy , Jonkman Jason , Lackner Matthew A.
Published: July 2015

A database of meteorological and ocean conditions is presented for use in offshore wind energy research and design. The original data are from 23 ocean sites around the USA and were obtained from the National Data Buoy Center run by the National Oceanic and Atmospheric Administration. The data are presented in a processed form that includes the variables of interest for offshore wind energy design: wind speed, significant wave height, wave peak‐spectral period, wind direction and wave direction. For each site, a binning process is conducted to create conditional probability functions for each of these variables. The sites are then grouped according to geographic location and combined to create three representative sites, including a West Coast site, an East Coast site and a Gulf of Mexico site. Both the processed data and the probability distribution parameters for the individual and representative sites are being hosted on a publicly available domain by the National Renewable Energy Laboratory, with the intent of providing a standard basis of comparison for meteorological and ocean conditions for offshore wind energy research worldwide. Copyright © 2015 John Wiley & Sons, Ltd.
Chromosom 14-assoziierte Imprintingsyndrome – Temple- und Kagami-Ogata-Syndrome
Authors: Elbracht Miriam , Buiting Karin , Bens Susanne , Siebert Reiner , Horsthemke Bernhard , Gillessen-Kaesbach Gabriele , Eggermann Thomas
Published: July 2015

In Analogie zu den bekannten Imprintingstörungen der elterlich geprägten Regionen auf Chromosom 15 (Prader-Willi-/Angelman-Syndrom) und Chromosom 11 (Beckwith-Wiedemann-/Silver-Russell-Syndrom) existieren auch für die Imprintingregion 14q32 zwei molekular gegensätzliche syndromale Störungen. Aufgrund der ersten klinischen Beschreibungen und des häufigsten molekularen Basismechanismus dieser Störungen erfolgte die Namensgebung zunächst als upd(14)mat- bzw. upd(14)pat-Syndrom (upd, uniparentale Disomie). Da das klinische Bild aber auch durch chromosomale Imbalancen und Epimutationen der Region 14q32 hervorgerufen wird, wurden die Bezeichnungen Temple-Syndrom (TS14, upd(14)mat) und Kagami-Ogata-Syndrom (KOS14, upd(14)pat) vorgeschlagen.

Das KOS14 zeichnet sich durch ein charakteristisches klinisches Bild aus, welches bereits intrauterin durch das Auftreten eines Polyhydramnions, eines glockenförmigen Thorax (bell-shaped thorax) mit „Kleiderbügel ähnlichen“ Rippen (coathanger rips) und einer kritischen Perinatalperiode gekennzeichnet ist. Der faziale Phänotyp mit vollen Wangen, eingesunkener Nasenwurzel, vorstehendem Philtrum, Mikrognathie und einem kurzen, breiten Nacken ist wiedererkennbar. Es liegen erste Hinweise auf ein erhöhtes Risiko für das Auftreten eines Hepatoblastoms vor. Hingegen handelt es sich beim TS14 um eine weniger spezifische und variablere Störung, die vor allem durch einen prä- und postnatalen Kleinwuchs und eine vorzeitige Pubertätsentwicklung gekennzeichnet ist. Es bestehen sowohl Übereinstimmungen mit dem PWS als auch Parallelen zu Patienten mit SRS. Nach neueren Erkenntnissen ist die mentale Retardierung kein konstantes Merkmal des TS14.

In den meisten Fällen ist das Wiederholungsrisiko für das Auftreten eines TS14 oder eines KOS14 bei Geschwistern eines betroffenen Kindes klein. Es kann aber in Abhängigkeit des zugrunde liegenden molekularen Defektes bis zu 50 % betragen, sodass eine entsprechende Diagnostik im Rahmen einer genetischen Beratung erfolgen sollte.
Cloaking in shallow-water waves via nonlinear medium transformation
Authors: Zareei Ahmad , Alam Mohammad-Reza
Published: July 2015

A major obstacle in designing a perfect cloak for objects in shallow-water waves is that the linear transformation media scheme (also known as transformation optics) requires spatial variations of two independent medium properties. In the Maxwell’s equation and for the well-studied problem of electromagnetic cloaking, these two properties are permittivity and permeability. Designing an anisotropic material with both variable permittivity and variable permeability, while challenging, is achievable. On the other hand, for long gravity waves, whose governing equation maps one-to-one to the single polarization Maxwell’s equations, the two required spatially variable properties are the water depth and the gravitational acceleration; in this case changing the gravitational acceleration is simply impossible. Here we present a nonlinear transformation that only requires the change in one of the medium properties, which, in the case of shallow-water waves, is the water depth, while keeping the gravitational acceleration constant. This transformation keeps the governing equation perfectly intact and, if the cloak is large enough, asymptotically satisfies the necessary boundary conditions. We show that with this nonlinear transformation an object can be cloaked from any wave that merely satisfies the long-wave assumption. The presented transformation can be applied as well for the design of non-magnetic optical cloaks for electromagnetic waves.
Oscillatory motion and wake of a bubble rising in a thin-gap cell
Authors: Filella Audrey , Ern Patricia , Roig Véronique
Published: July 2015

We investigate the characteristics of the oscillatory motion and wake of confined bubbles freely rising in a thin-gap cell ($h=3.1~\text{mm}$ width). Once the diameter $d$ of the bubble in the plane of the cell is known, the mean vertical velocity of the bubble $V_{b}$ is proportional to the gravitational velocity $(h/d)^{1/6}\sqrt{gd}$, where $g$ is the gravitational acceleration. This velocity is used to build the Reynolds number $Re=V_{b}d/{\it\nu}$ that characterizes the flow induced by the bubble in the surrounding liquid (of kinematic viscosity ${\it\nu}$), and which determines at leading order the mean deformation of the bubble given by the aspect ratio ${\it\chi}$ of the ellipse equivalent to the bubble contour. We then show that in the reference frame associated with the bubble (having a fixed origin and axes corresponding to the minor and major axes of the equivalent ellipse) the characteristics of its oscillatory motion in the plane of the cell display remarkable properties in the range $1200<Re<3000$ and $h/d<0.4$. In particular, the velocity of the bubble presents along its path an almost constant component along its minor axis (fluctuations in time of approximately 5 %), given by $V_{a}/V_{b}\simeq 0.92$ for all $Re$. The dimensionless amplitude of oscillation of the angular velocity is also constant for all $Re$, $\tilde{r}d/V_{b}\simeq 0.75$, while that of the transverse velocity of the bubble (along its major axis) is given by $\tilde{V}_{t}/V_{b}\simeq 0.32{\it\chi}$, reaching values comparable to those of the axial velocity $V_{a}$ for the most deformed bubbles (${\it\chi}\approx 3$). Furthermore, the frequency $f$ of oscillation scales with the inertial time scale based on the transverse velocity of the bubble $\tilde{V}_{t}$, corresponding to a constant Strouhal number $St^{\ast }=fd/\tilde{V}_{t}\simeq 0.27$. Using high-frequency particle image velocimetry, we investigate in detail the properties of the wake associated with the oscillatory motion of sufficiently confined bubbles. We observe that vortex shedding occurs for a maximal transverse velocity $V_{t}$ of the bubble, corresponding to a maximal drift angle of the bubble. Furthermore, the measured vorticity of the vortex at detachment corresponds to the estimation $V_{b}{\it\chi}^{3/2}/d$ of the vorticity produced at the bubble surface. Three stages then emerge concerning the evolution in time of the wake generated by the bubble. For one to two periods of oscillation $T_{x}$ following the release of a vortex, a rapid decay of the vorticity of the released vortex is observed. Meanwhile, the released vortex located initially at a distance of approximately one diameter from the bubble centre moves outwards from the bubble path and expands. At intermediate times, the vortex street undergoes vortex pairing. When viscous effects become predominant at a time of the order of the viscous time scale ${\it\tau}_{{\it\nu}}=h^{2}/(4{\it\nu})$, the vortex street becomes frozen and decays exponentially in place.
Steady and unsteady modelling of the float height of a rotating air hockey disk
Authors: Weidman Patrick D. , Sprague Michael A.
Published: July 2015

A similarity reduction of the Navier–Stokes equations for the motion of an infinite rotating disk above an air-bearing table yields a coupled pair of ordinary differential equations governed by a Reynolds number $Re=Wh/{\it\nu}$ and a rotation parameter $S=\sqrt{2}h{\it\Omega}/W$, where $h$ is the float height, $W$ is the air levitation velocity, ${\it\Omega}$ is the disk rotation rate, and ${\it\nu}$ is the kinematic viscosity of air. After deriving the small- and large-Reynolds-number behaviour of solutions, the equations are numerically integrated over a wide range of $Re{-}S$ parameter space. Zero-lift boundaries are computed as well as the boundaries separating pure outward flow from counter-flow in the gap. The theory is used to model the steady float height of a finite-radius air hockey disk under the assumption that the float height is small relative to the diameter of the disk and the flow is everywhere laminar. The steady results are tested against direct numerical simulation (DNS) of the unsteady axisymmetric Navier–Stokes equations for the cases where the disk rotates at constant angular velocity but is either at a fixed height or free to move axially. While a constant shift in the gap pressure conforms closely to that found using steady theory, the interaction of the radial jet emanating from the gap with a vertical transpiration field produces vortex rings which themselves propagate around to interact with the jet. Although these structures diffuse as they propagate up and away from the gap, they induce a departure from the steady-flow assumption of atmospheric pressure at the gap exit, thus inducing small irregular axial oscillations of the floating disk.
Soliton-like solutions and chaotic motions for a forced and damped Zakharov–Kuznetsov equation in a magnetized electron–positron–ion plasma
Authors: Zhen Hui-Ling , Tian Bo , Liu De-Yin , Liu Lei , Jiang Yan
Published: July 2015

A forced and damped Zakharov–Kuznetsov equation for a magnetized electron–positron–ion plasma affected by an external force is studied in this paper. Via the Hirota method, the soliton-like solutions are given. The soliton’s amplitude gets enhanced with the phase velocity${\it\lambda}$decreasing or ion-to-electron density ratio${\it\beta}$increasing. With the damped coefficient increasing, when the external force$g(t)$is periodic, the two solitons are always parallel during the propagation and background of the two solitons drops on the$x{-}y$plane, and amplitudes of the two solitons increase on the$x{-}t$and$y{-}t$planes, with$(x,y)$as the coordinates of the propagation plane and$t$as the time. When$g(t)$is exponentially decreasing, the two solitons merge into a single one and the background rises on the$x{-}y$plane, and amplitudes of the two solitons decrease on the$x{-}t$and$y{-}t$planes. Further, associated chaotic motions are obtained when$g(t)$is periodic. Using the phase projections and Poincaré sections, we find that the chaotic motions can be weakened with${\it\alpha}_{1}$, the amplitude of$g(t)$, decreasing. With${\it\alpha}_{2}$, the frequency of$g(t)$, decreasing, a three-dimensional attractor with stretching-and-folding structure is found, indicating that the weak chaos is transformed into the developed chaos. Chaotic motions can also be weakened with${\it\lambda}$, the phase velocity, decreasing, but strengthened with${\it\beta}$, the ion-to-electron density ratio, and${\it\alpha}_{2}$decreasing.
Ibn Khaldun (1332–1406): A Precursor of Intercivilizational Discourse
Authors: GAMARRA YOLANDA
Published: July 2015

This article shows how the political, historical, sociological, and economic narrative of Ibn Khaldun influenced the conjunction of elements that were essential to the civilizing language promoted by European and American liberals in the nineteenth and twentieth centuries. The ‘standard of civilization’ has experienced a revival among critical legal scholars. These authors have reconstructed a historical process of ‘rise, fall, and rise’ of the ‘standard of civilization’, identifying its reappearance in an era of globalization and global governance with the current existence of a (neo-)colonial paradigm in international law and a (neo-)liberal global economy. This study is divided into three parts intended to examine in depth the precursory role of this Islamic thinker in the shaping of civilizing language. The first part examines Ibn Khaldun's life as a way of understanding his thinking on civilization. The second part explores the influence of Ibn Khaldun's work on the discourse surrounding the standard of civilization, by reintroducing the interpretation of Rafael Altamira (1866–1951). The third starts with Ibn Khaldun's writings on economic science and Joseph Spengler's (1902–1991) approach to his works. Several Islamic economic institutions and their influence on the state and concept of international society are examined. The revival of Ibn Khaldun's thinking is partly intended to fill an existing gap in the studies of medieval Islamic theorists. By examining his ideas about the socio-political and economic viability of a dynasty (or a civilization or a state), this article attempts to shed light on the intercultural origins of international law.
Whatever Happened to Gramsci? Some Reflections on New Legal Realism
Authors: KLABBERS JAN
Published: July 2015

This article responds to five pieces published in the previous issue of theLeiden Journal of International Law, extolling the virtues of a new legal realism. I first express some doubts as to whether an awful lot can and should be expected from yet another new approach to the study of international law; earlier approaches widely heralded have quietly disappeared from sight, sometimes without leaving much trace. Subsequently, I discuss the extent to which the new international legal realism conceptualizes its notion of empirical reality, followed by a discussion on which interests the new insights spawned by new legal realism are to serve.
SIRT1 is involved in oncogenic signaling mediated by GPER in breast cancer
Authors: Santolla M F , Avino S , Pellegrino M , De Francesco E M , De Marco P , Lappano R , Vivacqua A , Cirillo F , Rigiracciolo D C , Scarpelli A , Abonante S , Maggiolini M
Published: July 2015

A number of tumors exhibit an altered expression of sirtuins, including NAD+-dependent histone deacetylase silent information regulator 1 (SIRT1) that may act as a tumor suppressor or tumor promoter mainly depending on the tumor types. For instance, in breast cancer cells SIRT1 was shown to exert an essential role toward the oncogenic signaling mediated by the estrogen receptor-α (ERα). In accordance with these findings, the suppression of SIRT1 led to the inhibition of the transduction pathway triggered by ERα. As the regulation of SIRT1 has not been investigated in cancer cells lacking ER, in the present study we ascertained the expression and function of SIRT1 by estrogens in ER-negative breast cancer cells and cancer-associated fibroblasts obtained from breast cancer patients. Our results show that 17β-estradiol (E2) and the selective ligand of GPER, namely G-1, induce the expression of SIRT1 through GPER and the subsequent activation of the EGFR/ERK/c-fos/AP-1 transduction pathway. Moreover, we demonstrate that SIRT1 is involved in the pro-survival effects elicited by E2 through GPER, like the prevention of cell cycle arrest and cell death induced by the DNA damaging agent etoposide. Interestingly, the aforementioned actions of estrogens were abolished silencing GPER or SIRT1, as well as using the SIRT1 inhibitor Sirtinol. In addition, we provide evidence regarding the involvement of SIRT1 in tumor growth stimulated by GPER ligands in breast cancer cells and xenograft models. Altogether, our data suggest that SIRT1 may be included in the transduction network activated by estrogens through GPER toward the breast cancer progression.
Rapid Column-Free Enrichment of Mononuclear Cells from Solid Tissues
Authors: Scoville Steven D. , Keller Karen A. , Cheng Stephanie , Zhang Michael , Zhang Xiaoli , Caligiuri Michael A. , Freud Aharon G.
Published: July 2015

We have developed a rapid negative selection method to enrich rare mononuclear cells from human tissues. Unwanted and antibody-tethered cells are selectively depleted during a Ficoll separation step and there is no need for magnetic-based reagents and equipment. The new method is fast, customizable, inexpensive, remarkably efficient and easy to perform and per sample the overall cost is less than one-tenth the cost associated with a magnetic column-based method.
Activation of TRESK channels by the inflammatory mediator lysophosphatidic acid balances nociceptive signalling
Authors: Kollert Sina , Dombert Benjamin , Döring Frank , Wischmeyer Erhard
Published: July 2015

In dorsal root ganglia (DRG) neurons TRESK channels constitute a major current component of the standing outward current IKSO. A prominent physiological role of TRESK has been attributed to pain sensation. During inflammation mediators of pain e.g. lysophosphatidic acid (LPA) are released and modulate nociception. We demonstrate co-expression of TRESK and LPA receptors in DRG neurons. Heterologous expression of TRESK and LPA receptors in Xenopus oocytes revealed augmentation of basal K+ currents upon LPA application. In DRG neurons nociception can result from TRPV1 activation by capsaicin or LPA. Upon co-expression in Xenopus oocytes LPA simultaneously increased both depolarising TRPV1 and hyperpolarising TRESK currents. Patch-clamp recordings in cultured DRG neurons from TRESK[wt] mice displayed increased IKSO after application of LPA whereas under these conditions IKSO in neurons from TRESK[ko] mice remained unaltered. Under current-clamp conditions LPA application differentially modulated excitability in these genotypes upon depolarising pulses. Spike frequency was attenuated in TRESK[wt] neurons and, in contrast, augmented in TRESK[ko] neurons. Accordingly, excitation of nociceptive neurons by LPA is balanced by co-activation of TRESK channels. Hence excitation of sensory neurons is strongly controlled by the activity of TRESK channels, which therefore are good candidates for the treatment of pain disorders.
Orexin receptors exert a neuroprotective effect in Alzheimer’s disease (AD) via heterodimerization with GPR103
Authors: Davies Julie , Chen Jing , Pink Ryan , Carter David , Saunders Nigel , Sotiriadis Georgios , Bai Bo , Pan Yanyou , Howlett David , Payne Annette , Randeva Harpal , Karteris Emmanouil
Published: July 2015

Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimer’s disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways.
Nuclear volume effects in equilibrium stable isotope fractionations of mercury, thallium and lead
Authors: Yang Sha , Liu Yun
Published: July 2015

The nuclear volume effects (NVEs) of Hg, Tl and Pb isotope systems are investigated with careful evaluation on quantum relativistic effects via the Dirac’s formalism of full-electron wave function. Equilibrium 202Hg/198Hg, 205Tl/203Tl, 207Pb/206Pb and 208Pb/206Pb isotope fractionations are found can be up to 3.61‰, 2.54‰, 1.48‰ and 3.72‰ at room temperature, respectively, larger than fractionations predicted by classical mass-dependent isotope fractionations theory. Moreover, the NVE can cause mass-independent fractionations (MIF) for odd-mass isotopes and even-mass isotopes. The plot of "Equation missing"vs. "Equation missing" for Hg-bearing species falls into a straight line with the slope of 1.66, which is close to previous experimental results. For the first time, Pb4+-bearing species are found can enrich heavier Pb isotopes than Pb2+-bearing species to a surprising extent, e.g., the enrichment can be up to 4.34‰ in terms of 208Pb/206Pb at room temperature, due to their NVEs are in opposite directions. In contrast, fractionations among Pb2+-bearing species are trivial. Therefore, the large Pb fractionation changes provide a potential new tracer for redox conditions in young and closed geologic systems. The magnitudes of NVE-driven even-mass MIFs of Pb isotopes (i.e., "Equation missing") and odd-mass MIFs (i.e., "Equation missing") are almost the same but with opposite signs.
Mutant p53 promotes ovarian cancer cell adhesion to mesothelial cells via integrin β4 and Akt signals
Authors: Lee Jong-Gyu , Ahn Ji-Hye , Jin Kim Tae , Ho Lee Jae , Choi Jung-Hye
Published: July 2015

Missense mutations in the TP53 gene resulting in the accumulation of mutant proteins are extremely common in advanced ovarian cancer, which is characterised by peritoneal metastasis. Attachment of cancer cells to the peritoneal mesothelium is regarded as an initial, key step for the metastatic spread of ovarian cancer. In the present study, we investigated the possible role of a p53 mutant in the mesothelial adhesion of ovarian cancer cells. We found that OVCAR-3 cells with the R248 TP53 mutation (p53R248) were more adhesive to mesothelial Met5A cells than were A2780 cells expressing wild-type p53. In addition, ectopic expression of p53R248 in p53-null SKOV-3 cells significantly increased adhesion to Met5A cells. Knockdown of mutant p53 significantly compromised p53R248-induced cell adhesion to Met5A cells. Microarray analysis revealed that several adhesion-related genes, including integrin β4, were markedly up-regulated and certain signalling pathways, including PI3K/Akt, were activated in p53R248 transfectants of SKOV-3 cells. Inhibition of integrin β4 and Akt signalling using blocking antibody and the inhibitor LY294002, respectively, significantly attenuated p53R248-mediated ovarian cancer-mesothelial adhesion. These data suggest that the p53R248 mutant endows ovarian cancer cells with increased adhesiveness and that integrin β4 and Akt signalling are associated with the mutation-enhanced ovarian cancer-mesothelial cell adhesion.