bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Soliton Resolution for Equivariant Wave Maps to the Sphere
Authors: Côte Raphaël
Published: October 2014

We consider finite energy corotational wave maps with target manifold . We prove that for a sequence of times, they decompose as a sum of decoupled harmonic maps in the light cone, and a smooth wave map (in the blowup case) or a linear scattering term (in the global case), up to an error which tends to 0 in the energy space. © 2015 Wiley Periodicals, Inc.
Improving the user experience of the rCUDA remote GPU virtualization framework
Authors: Reaño Carlos , Silla Federico , Castelló Adrián , Peña Antonio J. , Mayo Rafael , Quintana‐Ortí Enrique S. , Duato José
Published: October 2014

Graphics processing units (GPUs) are being increasingly embraced by the high‐performance computing community as an effective way to reduce execution time by accelerating parts of their applications. remote CUDA (rCUDA) was recently introduced as a software solution to address the high acquisition costs and energy consumption of GPUs that constrain further adoption of this technology. Specifically, rCUDA is a middleware that allows a reduced number of GPUs to be transparently shared among the nodes in a cluster. Although the initial prototype versions of rCUDA demonstrated its functionality, they also revealed concerns with respect to usability, performance, and support for new CUDA features. In response, in this paper, we present a new rCUDA version that (1) improves usability by including a new component that allows an automatic transformation of any CUDA source code so that it conforms to the needs of the rCUDA framework, (2) consistently features low overhead when using remote GPUs thanks to an improved new communication architecture, and (3) supports multithreaded applications and CUDA libraries. As a result, for any CUDA‐compatible program, rCUDA now allows the use of remote GPUs within a cluster with low overhead, so that a single application running in one node can use all GPUs available across the cluster, thereby extending the single‐node capability of CUDA. Copyright © 2014 John Wiley & Sons, Ltd.
Evaluating automatically parallelized versions of the support vector machine
Authors: Codreanu Valeriu , Dröge Bob , Williams David , Yasar Burhan , Yang Po , Liu Baoquan , Dong Feng , Surinta Olarik , Schomaker Lambert R.B. , Roerdink Jos B.T.M. , Wiering Marco A.
Published: October 2014

The support vector machine (SVM) is a supervised learning algorithm used for recognizing patterns in data. It is a very popular technique in machine learning and has been successfully used in applications such as image classification, protein classification, and handwriting recognition. However, the computational complexity of the kernelized version of the algorithm grows quadratically with the number of training examples. To tackle this high computational complexity, we have developed a directive‐based approach that converts a gradient‐ascent based training algorithm for the CPU to an efficient graphics processing unit (GPU) implementation. We compare our GPU‐based SVM training algorithm to the standard LibSVM CPU implementation, a highly optimized GPU‐LibSVM implementation, as well as to a directive‐based OpenACC implementation. The results on different handwritten digit classification datasets demonstrate an important speed‐up for the current approach when compared to the CPU and OpenACC versions. Furthermore, our solution is almost as fast and sometimes even faster than the highly optimized CUBLAS‐based GPU‐LibSVM implementation, without sacrificing the algorithm's accuracy. Copyright © 2014 John Wiley & Sons, Ltd.
Efficient Production and Separation of Biodegradable Surfactants from Cellulose in 1‐Butyl‐3‐Methylimidazolium Chloride
Authors: Puga Alberto V. , Corma Avelino
Published: October 2014

Alkyl glycoside biodegradable surfactants were produced from cellulose and 1‐octanol or 1‐dodecanol in a one‐pot, two‐step (hydrolysis–glycosidation) process in 1‐butyl‐3‐methylimidazolium chloride. Both surfactant productivity and separation efficiencies have been strikingly enhanced compared to other previously reported ionic liquid processes. Production temperatures were decreased to limit the extent of glucose dehydration and further degradation processes, but the conversions remained high. Surfactant molar yields up to 72 % were achieved by operating at 70 °C. Several separation procedures were tested to achieve high recoveries of both surfactant and ionic liquid. The use of a silica stationary phase was useful for isolation of the surfactant, whereas crystallization of the ionic liquid improved its separation efficiency. Finally, the precipitation of dodecyl glycosides in aqueous media was highly efficient for their isolation and for the recovery (>99 %) of the ionic liquid by using only water as the solvent for separation.
Path Integral Formalism for Line Broadening in Plasmas: Lyman‐α case
Authors: Bedida N. , Meftah M. T. , Difallah M.
Published: October 2014

Using the path integral formalism, the fine structure and dynamics effects are taken into account for the study of the spectral line broadening in plasmas. A compact expression of the dipolar autocorrelation function (DAF) for an emitter in the plasma is derived for Lyman alpha lines with fine structure. The expression of the DAF takes into account the dynamics effects, which are represented by the time autocorrelation function of the electric microfield. The spectral line for the Lyman‐alpha case has been obtained in a compact form and plotted in the quasi‐static approximation and compared to a line obtained by a simulation. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ion Drift Measurements Around a Grounded Sphere in Magnetized Sub‐Sonic Plasma Flows
Authors: Brunner K. J. , Grulke O. , Niemczyk D. , Klinger T.
Published: October 2014

The ion kinetics around a spherical object immersed in a sub‐sonic flowing plasma has been investigated by non‐invasive laser induced fluorescence for direct measurement of the ion velocity distribution function. The measurements are compared to Langmuir probe and emissive probe measurements. Indications for ion focusing as observed by previous works were observed. The plasma under observation was varied in magnetization and mean parallel plasma drift. The experiments were conducted in the linear plasma device VINETA at the Max‐Planck‐Institute for Plasma Physics in Greifswald. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On a possible evolutionary link of the stomochord of hemichordates to pharyngeal organs of chordates
Authors: Satoh Noriyuki , Tagawa Kunifumi , Lowe Christopher J. , Yu Jr‐Kai , Kawashima Takeshi , Takahashi Hiroki , Ogasawara Michio , Kirschner Marc , Hisata Kanako , Su Yi‐Hsien , Gerhart John
Published: October 2014

As a group closely related to chordates, hemichordate acorn worms are in a key phylogenic position for addressing hypotheses of chordate origins. The stomochord of acorn worms is an anterior outgrowth of the pharynx endoderm into the proboscis. In 1886 Bateson proposed homology of this organ to the chordate notochord, crowning this animal group “hemichordates.” Although this proposal has been debated for over a century, the question still remains unresolved. Here we review recent progress related to this question. First, the developmental mode of the stomochord completely differs from that of the notochord. Second, comparison of expression profiles of genes including Brachyury, a key regulator of notochord formation in chordates, does not support the stomochord/notochord homology. Third, FoxE that is expressed in the stomochord‐forming region in acorn worm juveniles is expressed in the club‐shaped gland and in the endostyle of amphioxus, in the endostyle of ascidians, and in the thyroid gland of vertebrates. Based on these findings, together with the anterior endodermal location of the stomochord, we propose that the stomochord has evolutionary relatedness to chordate organs deriving from the anterior pharynx rather than to the notochord. genesis 52:925–934, 2014. © 2014 Wiley Periodicals, Inc.
Palladium(II) and Platinum(II) Complexes Containing Six‐Membered N‐Heterocyclic Ligands: Synthesis, Characterization, Interaction with DNA, DFT Calculation, and Cytotoxicity
Authors: Sun Ya‐guang , Guo Ying , Sun Di , Zhu Ming‐chang , Ding Fu , Liu Yi‐nan , Gao En‐jun , Wang Shu‐ju , Xiong Gang , Dragutan Ileana , Dragutan Valerian
Published: October 2014

Four novel complexes based on the ligand piperazine (Pip) in a chair conformation have been synthesized, namely [Pd(5,5′‐dcbpy)Pip]·4H2O (1), [Pt(5,5′‐dcbpy)Pip]·3H2O (2), [Pd(4,4′‐dcbpy)Pip]·4H2O (3), and [Pt(4,4′‐dcbpy)Pip]·2H2O (4; 4,4′‐dcbpy = 2,2′‐bipyridyl‐4,4′‐dicarboxylate, 5,5′‐dcbpy = 2,2′‐bipyridyl‐5,5′‐dicarboxylate). The four complexes were characterized by elemental analysis, FTIR spectroscopy, 1H and 13C NMR spectroscopy, and single‐crystal X‐ray diffraction analysis. In addition, gel electrophoresis was performed on the four complexes and further insight into these complexes was gained by quantum chemistry calculations. The interaction of these complexes with fish sperm DNA (FS‐DNA) was studied by UV/Vis and fluorescence spectroscopy, which revealed that they have the ability to bind to FS‐DNA. The IC50 values of the four complexes range from 8.3 to 32.5 μM. Finally, we studied the cytotoxic activities of complexes 1–4 against two different cancer cell lines.
Unprecedented Borylene Insertion into a C–N Bond
Authors: Ghadwal Rajendra S. , Schürmann Christian J. , Engelhardt Felix , Steinmetzger Christian
Published: October 2014

Invited for the cover of this issue is the group of Rajendra S. Ghadwal at Georg‐August‐Universität Göttingen, Germany. The cover image shows insertion of a borylene into a C–N bond with an N‐heterocyclic olefin (NHO) ligand.
Di‐tert‐butylneopentylphosphine (DTBNpP): An Efficient Ligand in the Palladium‐Catalyzed α‐Arylation of Ketones
Authors: Raders Steven M. , Jones Jessica M. , Semmes Jeffrey G. , Kelley Steven P. , Rogers Robin D. , Shaughnessy Kevin H.
Published: October 2014

Di‐tert‐butylneopentylphosphine (DTBNpP) and palladium(II) acetate provide an efficient catalytic system for the α‐arylation of ketones. Aryl bromides were coupled with ketones using 0.25–0.5 mol‐% Pd(OAc)2/DTBNpP in toluene at 50 °C, whereas aryl chlorides required a higher catalyst loading (0.5–2.0 mol‐%) and a higher temperature (80 °C). Coupling of 2‐bromophenol with ketones using the Pd/DTBNpP system provides an efficient route for the synthesis of benzofurans.
Modified Gold Surfaces with Gold Nanoparticles and 6‐(Ferrocenyl)hexanethiol: Design of a Mediated Microbial Sensor
Authors: Yildirim Nimet , Demirkol Dilek Odaci , Timur Suna
Published: October 2014

Herein, a mediated Gluconobacter oxydans biosensor was constructed by immobilizing the intact cells on the modified gold electrode. The surface was initially modified with gold nanoparticles and then, self‐assembled monolayers were formed by using 6‐(ferrocenyl) hexanethiol. Finally, G. oxydans cells were adsorbed onto the surfaces and the bio‐active layer was covered with a dialysis membrane. As well as the response characteristics, stabilities and substrate specificities ere investigated.
The scent of human diseases: a review on specific volatile organic compounds as diagnostic biomarkers
Authors: Buljubasic Fanis , Buchbauer Gerhard
Published: October 2014

The use of body odours, emitted in the form of volatile organic compounds (VOCs), has become the focus of scientific research in recent years.

Diseases such as cancer, metabolic disorders, infections and some other diseases can change the components of daily VOCs, often leading to the production of disease‐specific VOCs that might be used as diagnostic biomarkers if detected early enough. We summarize here scientific publications (2003–2013) related to the study of VOCs in human diseases. Copyright © 2014 John Wiley & Sons, Ltd.
Putting the Patient in Patient Reported Outcomes: A Robust Methodology for Health Outcomes Assessment
Authors: McCarthy Ian M.
Published: October 2014

When analyzing many health‐related quality‐of‐life (HRQoL) outcomes, statistical inference is often based on the summary score formed by combining the individual domains of the HRQoL profile into a single measure. Through a series of Monte Carlo simulations, this paper illustrates that reliance solely on the summary score may lead to biased estimates of incremental effects, and I propose a novel two‐stage approach that allows for unbiased estimation of incremental effects. The proposed methodology essentially reverses the order of the analysis, from one of ‘aggregate, then estimate’ to one of ‘estimate, then aggregate’. Compared to relying solely on the summary score, the approach also offers a more patient‐centered interpretation of results by estimating regression coefficients and incremental effects in each of the HRQoL domains, while still providing estimated effects in terms of the overall summary score. I provide an application to the estimation of incremental effects of demographic and clinical variables on HRQoL following surgical treatment for adult scoliosis and spinal deformity. Copyright © 2014 John Wiley & Sons, Ltd.
Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition
Authors: Ibarrola‐Villava Maider , Kumar Rajiv , Nagore Eduardo , Benfodda Meriem , Guedj Mickael , Gazal Steven , Hu Hui‐Han , Guan Jian , Rachkonda P. Sivaramakishna , Descamps Vincent , Basset‐Seguin Nicole , Bensussan Armand , Bagot Martine , Saiag Philippe , Schadendorf Dirk , Martin‐Gonzalez Manuel , Mayor Matias , Grandchamp Bernard , Ribas Gloria , Nadem Soufir
Published: October 2014

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high‐risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta‐analysis (3940 melanoma cases and 3620 controls) with two‐side p values of 0.002, (OR = 0.86) and 4.07 × 10−10 (OR = 0.80), respectively. Exome sequencing revealed a non‐synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma.
Genetic delivery of an immunoRNase by an oncolytic adenovirus enhances anticancer activity
Authors: Fernández‐Ulibarri Inés , Hammer Katharina , Arndt Michaela A.E. , Kaufmann Johanna K. , Dorer Dominik , Engelhardt Sarah , Kontermann Roland E. , Hess Jochen , Allgayer Heike , Krauss Jürgen , Nettelbeck Dirk M.
Published: October 2014

Antibody therapy of solid cancers is well established, but suffers from unsatisfactory tumor penetration of large immunoglobulins or from low serum retention of antibody fragments. Oncolytic viruses are in advanced clinical development showing excellent safety, but suboptimal potency due to limited virus spread within tumors. Here, by developing an immunoRNase‐encoding oncolytic adenovirus, we combine viral oncolysis with intratumoral genetic delivery of a small antibody‐fusion protein for targeted bystander killing of tumor cells (viro‐antibody therapy). Specifically, we explore genetic delivery of a small immunoRNase consisting of an EGFR‐binding scFv antibody fragment fused to the RNase Onconase (ONCEGFR) that induces tumor cell death by RNA degradation after cellular internalization. Onconase is a frog RNase that combines lack of immunogenicity and excellent safety in patients with high tumor killing potency due to its resistance to the human cytosolic RNase inhibitor. We show that ONCEGFR expression by oncolytic adenoviruses is feasible with an optimized, replication‐dependent gene expression strategy. Virus‐encoded ONCEGFR induces potent and EGFR‐dependent bystander killing of tumor cells. Importantly, the ONCEGFR‐encoding oncolytic adenovirus showed dramatically increased cytotoxicity specifically to EGFR‐positive tumor cells in vitro and significantly enhanced therapeutic activity in a mouse xenograft tumor model. The latter demonstrates that ONCEGFR is expressed at levels sufficient to trigger tumor cell killing in vivo. The established ONCEGFR‐encoding oncolytic adenovirus represents a novel agent for treatment of EGFR‐positive tumors. This viro‐antibody therapy platform can be further developed for targeted/personalized cancer therapy by exploiting antibody diversity to target further established or emerging tumor markers or combinations thereof.
High S100A8 and S100A12 protein expression is a favorable prognostic factor for survival of oropharyngeal squamous cell carcinoma
Authors: Funk Sonja , Mark Regina , Bayo Pilar , Flechtenmacher Christa , Grabe Niels , Angel Peter , Plinkert Peter K. , Hess Jochen
Published: October 2014

S100/calgranulins (S100A8, S100A9 and S100A12) are key players of innate immune function and elevated levels are a characteristic feature of acute and chronic inflammation, and inflammation‐associated carcinogenesis. However, reduced S100A8 and S100A9 expression has been detected for squamous cell carcinoma, including the head and neck region (HNSCC), which originate from mucosal epithelia with abundant expression of both proteins under physiological conditions. In contrast to S100A8 and S100A9, only sparse information is available for S100A12 and a comparative study of all three S100/calgranulins in HNSCC is still missing. We analyzed S100/calgranulin protein levels in a retrospective patient cohort (n = 131) of oropharyngeal squamous cell carcinoma (OPSCC) by immunohistochemical staining of tissue microarrays. Common characteristics of all three S100/calgranulins were: (i) abundant expression in supra‐basal keratinocytes of normal mucosa with predominant nuclear staining, (ii) low expression in 30.4–51.9% of primary OPSCCs and (iii) variable accumulation of S100/calgranulin‐positive immune cells in the tumor stroma. These features were associated with histopathological characteristics, such as tumor grade, lymph node metastasis and tumor stage. Furthermore, univariate and multivariate analysis revealed worse overall survival of OPSCC patients with simultaneous reduction of S100A8 and S100A12 expression, while expression of S100A9 or presence of the S100A8/S100A9 heterodimer had no impact, suggesting distinct regulation and function of individual S100/calgranulins in the pathogenesis of HNSCCs.
New therapeutic perspectives in CCDC6 deficient lung cancer cells
Authors: Morra Francesco , Luise Chiara , Visconti Roberta , Staibano Stefania , Merolla Francesco , Ilardi Gennaro , Guggino Gianluca , Paladino Simona , Sarnataro Daniela , Franco Renato , Monaco Roberto , Zitomarino Federica , Pacelli Roberto , Monaco Guglielmo , Rocco Gaetano , Cerrato Aniello , Linardopoulos Spiros , Muller Mark T. , Celetti Angela
Published: October 2014

Non‐small cell lung cancer (NSCLC) is the main cause of cancer‐related death worldwide and new therapeutic strategies are urgently needed. In this study, we have characterized a panel of NSC lung cancer cell lines for the expression of coiled‐coil‐domain containing 6 (CCDC6), a tumor suppressor gene involved in apoptosis and DNA damage response. We show that low CCDC6 protein levels are associated with a weak response to DNA damage and a low number of Rad51 positive foci. Moreover, CCDC6 deficient lung cancer cells show defects in DNA repair via homologous recombination. In accordance with its role in the DNA damage response, CCDC6 attenuation confers resistance to cisplatinum, the current treatment of choice for NSCLC, but sensitizes the cells to olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. Remarkably, the combination of the two drugs is more effective than each agent individually, as demonstrated by a combination index <1. Finally, CCDC6 is expressed at low levels in about 30% of the NSCL tumors we analyzed by TMA immunostaining. The weak CCDC6 protein staining is significatively correlated with the presence of lymph node metastasis (p ≤ 0.02) and negatively correlated to the disease free survival (p ≤ 0.01) and the overall survival (p ≤ 0.05). Collectively, the data indicate that CCDC6 levels provide valuable insight for OS. CCDC6 could represent a predictive biomarker of resistance to conventional single mode therapy and yield insight on tumor sensitivity to PARP inhibitors in NSCLC.
Active cigarette smoking and risk of breast cancer
Authors: Catsburg Chelsea , Miller Anthony B. , Rohan Thomas E.
Published: October 2014

Although epidemiological evidence on the role of active cigarette smoking in breast cancer risk has been inconsistent, recent literature supports a modest association between smoking and breast cancer. This association is particularly observed in women who smoke for a long duration, or who smoke for a long time prior to their first pregnancy. Here, we provide updated results on cigarette smoking and breast cancer risk in the Canadian National Breast Screening Study (NBSS). The NBSS is a large cohort of 89,835 women, aged 40–59, who were followed for a mean of 22.1 years, resulting in the ascertainment of 6,549 incident cases of breast cancer. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cigarette smoking variables with breast cancer risk. We found breast cancer to be associated with duration (40 years vs. 0: HR = 1.57; 95%CI = 1.29–1.92), intensity (40 cigarettes per day vs. 0: HR = 1.21; 95%CI = 1.04–1.40), cumulative exposure (40 pack‐years vs. 0: HR = 1.19; 95%CI = 1.06–1.13) and latency (40 years since initiation vs. 0: HR = 1.19; 95%CI = 1.10–1.53) of cigarette smoking. Number of years smoked prior to first full‐term pregnancy was associated with higher risk of breast cancer than comparative years smoked post‐pregnancy (among parous women, 5 years pre pregnancy vs. 0: HR = 1.18; 95%CI = 1.10–1.26). These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.
HOME ENVIRONMENTS OF INFANTS FROM IMMIGRANT FAMILIES IN THE UNITED STATES: FINDINGS FROM THE NEW IMMIGRANT SURVEY
Authors: Bradley Robert H. , Pennar Amy , Glick Jennifer
Published: October 2014

Data from the New Immigrant Survey were used to describe the home environments of 638 children ages birth to 3 years whose parents legally immigrated to the United States. Thirty‐two indicators of home conditions were clustered into four domains: discipline and socioemotional in support, learning materials, enriching experiences, and family activities. Results revealed variation in how frequently infants from every country (Mexico, El Salvador, India, Philippines) and region (East Asia, Europe, Caribbean, Africa) studied experienced each home environmental condition. There were differences between countries and regions on many indicators as well as differences based on parents’ level of education. The experiences documented for children of recent legal immigrants were similar to those documented for children of native‐born families in other studies.
An evaluation of response prompts for teaching behavior chains
Authors: Seaver Jessica L. , Bourret Jason C.
Published: October 2014

Individuals who have been diagnosed with autism spectrum disorders can have difficulty acquiring new skills, and teaching procedures found to be efficient with 1 individual may not be efficient with others. However, relatively little research has evaluated methods to identify efficient, individualized response‐prompt and prompt‐fading procedures. We evaluated an assessment of multiple response prompts and prompt‐fading procedures with 10 individuals with an autism spectrum disorder. The prompt types assessed were verbal and gestural, model, and physical. Prompt‐fading procedures assessed were least to most, most to least, and a progressive delay. Each assessment was conducted at least twice, and the findings of both prompt‐type and prompt‐fading assessments were generally reliable. A final validity test showed the assessment outcomes to have generality that may extend to other clinically significant responses.
A comparison of methods for teaching receptive language to toddlers with autism
Authors: Vedora Joseph , Grandelski Katrina
Published: October 2014

The use of a simple‐conditional discrimination training procedure, in which stimuli are initially taught in isolation with no other comparison stimuli, is common in early intensive behavioral intervention programs. Researchers have suggested that this procedure may encourage the development of faulty stimulus control during training. The current study replicated previous work that compared the simple‐conditional and the conditional‐only methods to teach receptive labeling of pictures to young children with autism spectrum disorder. Both methods were effective, but the conditional‐only method required fewer sessions to mastery.
Pre‐existing immunity to adeno‐associated virus (AAV)2 limits transgene expression following intracerebral AAV2‐based gene delivery in a 6‐hydroxydopamine model of Parkinson's disease
Authors: Janelidze Shorena , Nordström Ulrika , Kügler Sebastian , Brundin Patrik
Published: October 2014

Background

Adeno‐associated virus (AAV) vectors are used to deliver potentially therapeutic genes in clinical trials in Parkinson's disease (PD). Pre‐existing immunity to AAV and a local neuroinflammatory response might negatively affect the efficacy of such AAV‐mediated gene delivery.

Methods

We pre‐immunized rats with wild‐type AAV‐2. Three months later, we created PD‐like lesions by intrastriatal injections of 6‐hydroxydopamine (6‐OHDA) in 50% of the animals. One month later, we injected AAV2 vector expressing enhanced green fluorescent protein (eGFP) in the striatum. Using immunohistochemistry, we assessed eGFP expression, microglia activation and CD8 T cell infiltration. We also measured AAV‐2 specific neutralizing antibody titers in the serum.

Results

The number of striatal cells transduced with AAV2 vector expressing eGFP was reduced by 71% in rats pre‐immunized with wild‐type AAV2 compared to non‐immunized animals. We detected elevated numbers of OX6+ activated microglia in the striatum and circulating AAV2‐specific neutralizing antibodies in pre‐immunized rats. We also observed that the intrastriatal 6‐OHDA injection promoted CD8+ T cell infiltration and enhanced microglia activation. Nevertheless, the 6‐OHDA lesion did not alter AAV2‐mediated expression of eGFP in either pre‐immunized or non‐immunized rats.

Conclusions

Our findings indicate that intracerebral AAV2‐based gene therapy is compromised in rats with pre‐existing immunity to AAV2. By contrast, a local neuroinflammatory response, caused by intrastriatal a 6‐OHDA injection, does not affect viral vector‐mediated transgene expression. Our results emphasize the importance of monitoring circulating AAV‐specific neutralizing antibodies in patients undergoing intracerebral gene therapy using AAV vectors. Copyright © 2014 John Wiley & Sons, Ltd.
Peptides derivatized with bicyclic quaternary ammonium ionization tags. Sequencing via tandem mass spectrometry
Authors: Setner Bartosz , Rudowska Magdalena , Klem Ewelina , Cebrat Marek , Szewczuk Zbigniew
Published: October 2014

Improving the sensitivity of detection and fragmentation of peptides to provide reliable sequencing of peptides is an important goal of mass spectrometric analysis. Peptides derivatized by bicyclic quaternary ammonium ionization tags: 1‐azabicyclo[2.2.2]octane (ABCO) or 1,4‐diazabicyclo[2.2.2]octane (DABCO), are characterized by an increased detection sensitivity in electrospray ionization mass spectrometry (ESI‐MS) and longer retention times on the reverse‐phase (RP) chromatography columns. The improvement of the detection limit was observed even for peptides dissolved in 10 mM NaCl. Collision‐induced dissociation tandem mass spectrometry of quaternary ammonium salts derivatives of peptides showed dominant a‐ and b‐type ions, allowing facile sequencing of peptides. The bicyclic ionization tags are stable in collision‐induced dissociation experiments, and the resulted fragmentation pattern is not significantly influenced by either acidic or basic amino acid residues in the peptide sequence. Obtained results indicate the general usefulness of the bicyclic quaternary ammonium ionization tags for ESI‐MS/MS sequencing of peptides. Copyright © 2014 John Wiley & Sons, Ltd.
Mass spectrometric study of gas‐phase ions of acid β‐glucosidase (Cerezyme) and iminosugar pharmacological chaperones
Authors: Rajabi Khadijeh
Published: October 2014

The effect on the conformations and stability of gas‐phase ions of Cerezyme, a glycoprotein, when bound to three small‐molecule chaperones has been studied using intact ESI MS, collision cross section and MS/MS measurements. To distinguish between the peaks from apo and small‐molecule complex ions, Cerezyme is deglycosylated (dg‐Cer). ESI MS of dg‐Cer reveals that glycosylation accounts for 8.5% of the molecular weight. When excess chaperone, either covalent (2FGF) or noncovalent (A and B iminosugars), is added to solutions of dg‐Cer, mass spectra show peaks from 1:1 chaperone–enzyme complexes as well as free enzyme. On average, ions of the apoenzyme have 1.6 times higher cross sections when activated in the source region of the mass spectrometer. For a given charge state, ions of complexes of 2FGF and B have about 30% and 8.4% lower cross sections, respectively, compared to the apoenzyme. Thus, binding the chaperones causes the gas‐phase protein to adopt more compact conformations. The noncovalent complex ions dissociate by the loss of charged chaperones. In the gas phase, the relative stability of dg‐Cer with B is higher than that with the A, whereas in solution A binds enzyme more strongly than B. Nevertheless, the disagreement is explained based on the greater number of contacts between the B and dg‐Cer than the A and dg‐Cer (13 vs. 8), indicating the importance of noncovalent interactions within the protein–chaperone complex in the absence of solvent. Findings in this work suggest a hypothesis towards predicting a consistent correlation between gas‐phase properties to solution binding properties. Copyright © 2014 John Wiley & Sons, Ltd.
Ultra performance liquid chromatography – mass spectrometry studies of formalin‐induced alterations of human brain lipidome
Authors: Gaudin Mathieu , Panchal Maï , Ayciriex Sophie , Werner Erwan , Brunelle Alain , Touboul David , Boursier‐Neyret Claire , Auzeil Nicolas , Walther Bernard , Duyckaerts Charles , Laprévote Olivier
Published: October 2014

The development of ‘omics’ sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post‐mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin‐fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time‐of‐flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin‐fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin‐induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N‐methylation and N‐formylation of amine‐containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin‐fixed samples. Copyright © 2014 John Wiley & Sons, Ltd.
Evaluation and determination of the cyclofructans–amino acid complex binding pattern by electrospray ionization mass spectrometry
Authors: Wang Lin , Li Yikun , Yao Liqing , Sun Cuirong , Zeng Su , Pan Yuanjiang
Published: October 2014

The noncovalent complex interactions between cyclofructans, a new class of cyclic oligosaccharide hosts, and various amino acids have been characterized by means of electrospray ionization mass spectrometry and nuclear magnetic resonance. The 1 : 1 stoichiometry of cyclofructans and amino acid complexes was confirmed by their mass‐to‐charge ratio in positive mode. Cyclofructans (CFs)–amino acid complexes and cyclodextrin–amino acid complexes exhibited distinctive different fragment behaviors in collision‐induced dissociation experiments. Coupled with the results of 1H NMR and nuclear overhauser effect spectroscopy, cyclofructan–amino acid complexes were deduced to be rim complexes via formation hydrogen bonding and ion–dipole forces. The interaction pattern could be controlled by changing the pH condition. In neutral solution, amino acids are located on the positive side of CFs, although moved to the negative side pocket constructed by 3‐OH oxygen of furanose ring and the crown ether oxygen in acid condition. In addition, theory calculation for geometry optimization of Trp and CFs was performed, which was in good agreement with the experimental results. Copyright © 2014 John Wiley & Sons, Ltd.
Substitution pattern elucidation of hydroxypropyl Pinus pinaster (Ait.) bark polyflavonoid derivatives by ESI(−)‐MS/MS
Authors: García Marrero Danny E. , Glasser Wolfgang G. , Pizzi Antonio , Paczkowski Sebastian , Laborie Marie‐Pierre G.
Published: October 2014

The structure of condensed tannins (CTs) from Pinus pinaster bark extract and their hydroxypropylated derivatives with four degrees of substitution (DS 1, 2, 3 and 4) has been characterized for the first time using negative‐ion mode electrospray ionization tandem mass spectrometry (ESI(−)‐MS/MS). The results showed that P. pinaster bark CTs possess structural homogeneity in terms of monomeric units (C15, catechin). The oligomer sizes were detected to be dimers to heptamers. The derivatives showed typical phenyl‐propyl ether mass fragmentation by substituent elimination (58 amu) and inherent C15 flavonoid fissions. The relative abundance of the product ions revealed a preferential triple, tetra‐/penta‐ and octa‐ hydroxypropylation substitution pattern in the monomer, dimer and trimer derivatives, respectively. A defined order of –OH reactivity towards propylene oxide was established by means of multistage experiments (A‐ring ≥ B‐ring > C‐ring). A high structural heterogeneity of the modified oligomers was detected. Copyright © 2014 John Wiley & Sons, Ltd.
Seasonal prediction of East African rainfall
Authors: Chen Chia‐Jeng , Georgakakos Aris P.
Published: October 2014

The detrimental impacts of climate variability on water, agriculture, and food resources in East Africa underscore the importance of reliable seasonal climate predictions. This study compares several forecasting methods using sea surface temperature (SST) anomalies to predict East African rains with various lead times. It is shown that the forecasts can explain more than 50% of the short rains (boreal autumn) variance across large regions of Ethiopia, Somalia, and Kenya, and reaffirm the importance of the Walker‐like circulation over the Indian Ocean. The forecasts also explain more than 50% of the long rains (boreal spring) over Uganda, Lake Victoria, and western Kenya, and demonstrate the strong connection of the long rains to the SSTs in the southern Atlantic Ocean, Mediterranean Sea, southwestern Indian Ocean, and Arabian Sea. For the unimodal rains in Tanzania, the forecasts explain more than 40% of the rainfall variance over northwestern Tanzania based on SST predictors in the southwestern Indian Ocean and the subtropical North Atlantic. For the South Sudan and Ethiopian Kiremt rains, the forecast skill is less pronounced. The predictor regions (dipoles) for a recently developed method are validated through composite maps of surface and atmospheric reanalysis variables. Lastly, 2010–2011 forecasts for both the long and short rains demonstrate skill in predicting the recent drought suggesting that seasonal climate forecasts can inform natural disaster preparedness and water resources planning in East Africa.
An assessment of real‐time extended range forecast of 2013 Indian summer monsoon
Authors: Borah N. , Sahai A. K. , Abhilash S. , Chattopadhyay R. , Joseph S. , Sharmila S. , Kumar A.
Published: October 2014

Several aspects of real‐time forecast of Indian summer monsoon (ISM) in 3–4 pentad lead time (extended range) are discussed in this study to explore the operational capability of the Climate Forecast System model version 2 (CFSv2) developed by National Centre for Environmental Prediction (NCEP). 2013 summer monsoon was a near excess monsoon year in terms of seasonal mean and was a result of rich diversity of phenomena including strong intraseasonal variations and intense northward propagations over the Indian region. Eleven‐member forecasts were made at every 5‐day interval during the June–September monsoon season which included monsoon onset and withdrawal phases. The ensemble members were created by perturbing the initial conditions at each start time. In addition to the CFSv2 forecasts, we also carried out forecasts using the atmospheric‐only component (GFSv2) forced with CFSv2‐derived sea surface temperature (SST) subjected to a bias correction based on historical observations (GFSbc runs).

Both the CFSv2 and GFSbc runs were able to predict the progression of ISM over the Indian region and the subsequent intraseasonal oscillations (active and break phases). The analysis for an extreme event (Uttarakhand flood) and monsoon revival (MR) towards the end of the season was also performed. Comparison between the two runs shows that active and break spells were predicted with good fidelity over the Indian region, though GFSbc outperforms CFSv2 on several occasions. Thus, improvement of the operational monsoon forecast over Indian region using NCEP CFSv2 requires better representation of air–sea interaction and mean states of ocean.
Optimized conditions for determination of total soil organic matter in diverse samples by mass loss on ignition
Authors: Ghabbour Elham A. , Davies Geoffrey , Cuozzo Nicolas P. , Miller Robert O.
Published: October 2014

Reliable measurement of soil organic matter (SOM) contents is crucial to assessment of soil health, productive longevity and the effects of climate change. In this study, the loss‐on‐ignition (LOI) method has been used to determine the SOM of dried soil samples with a wide range of clay, sand and silt contents from the Agricultural Laboratory Proficiency (ALP) program. Regressions of ALP participant data against LOI measurements at 350–650°C indicate that the extent of SOM oxidation depends more on the ignition temperature and time than on the sample compositions. Thus, LOI data from ignition at 350–550°C for 12 h relative to ignition at 650°C for 12 h converge at 650°C and the average coefficient of variance decreases to ≈ 4% at 650°C. Also examined are regressions of soil organic C from direct dry combustion as standards with LOI measured at 360°C for 2 h, LOI measured at 650°C for 12 h and with the Walkley‐Black procedure used in the ALP program.
A Middle Palaeolithic site in the southern North Sea: investigating the archaeology and palaeogeography of Area 240
Authors: TIZZARD L. , BICKET A. R. , BENJAMIN J. , LOECKER D. DE
Published: October 2014

The potential for Middle Palaeolithic sites to survive beneath the sea in northern latitudes has been established by intensive investigation within Area 240, a marine aggregate licence area situated in the North Sea, 11 km off the coast of Norfolk, England. The fortuitous discovery of bifacial handaxes, and Levallois flakes and cores, led to a major programme of fieldwork and analysis between 2008 and 2013. The artefacts were primarily recovered from Marine Isotope Stage 8/7 floodplain sediments deposited between 250 and 200 ka. It is considered that the hand axes and Levallois products are contemporaneous in geological terms with taphonomically complex sedimentary contexts, as observed in several north‐west European sites. The Early Middle Palaeolithic (EMP) lithics have survived multiple phases of glaciation and marine transgression. The investigations confirm that the artefacts are not a ‘chance’ find, but indicate clear relationships to submerged and buried landscapes that, although complex, can be examined in detail using a variety of existing fieldwork and analytical methods. The palaeogeographical context of the finds also offers expanded interpretations of the distribution of EMP hominins in the southern North Sea, not predictable from onshore archaeological records.
Biochronological data inferred from the Early Pleistocene small mammals of the Barranc de la Boella site (Tarragona, north‐eastern Spain)
Authors: LOZANO‐FERNÁNDEZ IVÁN , BAÑULS‐CARDONA SANDRA , BLAIN HUGUES‐ALEXANDRE , LÓPEZ‐GARCÍA JUAN MANUEL , VALLVERDÚ JOSEP , AGUSTÍ JORDI , CUENCA‐BESCÓS GLORIA
Published: October 2014

In 2007, remains of Mammuthus meridionalis and 334 lithic artefacts were recovered in level 2 of Barranc de la Boella. The presence of M. meridionalis allows us to assign an age older than 700 ka to this level, which represents one of the few sites of this age with palaeontological remains associated with lithic industry. It also enables us to shed light on questions pertaining to the chronology and the biogeography of the earliest European human settlements. In this paper, the small mammals from the Barranc de la Boella site are described for the first time, with special emphasis on the arvicolines. The presence of Victoriamys chalinei and Mimomys savini allows us to estimate the age of level 2. Level 2 of the Barranc de la Boella site ranges between the top of the Jaramillo subchron (0.99 Ma) and shortly after the Brunhes–Matuyama transition at 0.78 Ma, thus covering a time span of great importance for our knowledge of the earliest human occupations in Western Europe.
Vasculobiliary complications following adult right lobe split liver transplantation from the perspective of reconstruction techniques
Authors: Mabrouk Mourad Moustafa , Liossis Christos , Kumar Senthil , Gunson Bridget K. , Mergental Hynek , Isaac John , Bramhall Simon R. , Muiesan Paolo , Mirza Darius F. , Thamara P. R. Perera M.
Published: October 2014

Split liver transplantation (SLT) compensates for the organ shortage and provides an alternative solution for recipients disadvantaged by a smaller body size. Variations in the hepatic arterial anatomy and reconstructive techniques may lead to more technical complications, and we sought to analyze the incidence and risk factors of vasculobiliary complications with respect to reconstructive techniques. We identified 171 adult right lobe SLT procedures and 1412 whole liver transplantation (WLT) procedures between January 2000 and June 2012 and compared the results of these 2 groups. In the SLT group, arterial reconstruction techniques were classified into 4 subgroups (I‐IV), and biliary reconstruction was classified into 2 groups [duct‐to‐duct (DD) anastomosis and Roux‐en‐Y hepaticojejunostomy (RH)]. Specific surgical complications were analyzed against reconstruction techniques. The overall incidence of vascular and biliary complications in the SLT group was greater than that in the WLT group (P = 0.009 and P = 0.001, respectively). There was no difference in hepatic artery thrombosis (HAT), but we saw a tendency toward early HAT in the presence of multiple hepatic arteries supplying the right lobe graft (group IV; 20%) in comparison with the other arterial reconstruction groups (P = 0.052). No difference was noticed in the overall incidence of biliary complications in either DD or RH recipients across 4 arterial reconstruction groups. When the arterial reconstruction involved a right hepatic artery (groups II and III) combined with a DD biliary anastomosis, there was a significant preponderance of biliary complications (P = 0.04 and P = 0.01, respectively). There was no survival difference between SLT and WLT grafts. In conclusion, the complications of SLT are directly related to arterial and biliary reconstruction techniques, and this classification helps to identify high‐risk reconstructive techniques. Liver Transpl 21:63‐71, 2015. © 2014 AASLD.
Comprehensive, Multidisciplinary Deep Brain Stimulation Screening for Parkinson Patients: No Room for “Short Cuts”
Authors: Abboud Hesham , Mehanna Raja , Machado Andre , Ahmed Anwar , Gostkowski Michal , Cooper Scott , Itin Ilia , Sweeney Patrick , Pandya Mayur , Kubu Cynthia , Floden Darlene , Ford Paul J. , Fernandez Hubert H.
Published: October 2014

Careful, often cumbersome, screening is a fundamental part of DBS evaluation in Parkinson's disease (PD). It often involves a brain MRI, neuropsychological testing, neurological, surgical, and psychiatric evaluation, and “ON/OFF” motor testing. Given that DBS has now been a standard treatment for advanced PD, with clinicians’ improved comfort and confidence in screening and referring patients for DBS, we wondered whether we can now streamline our lengthy evaluation process. We reviewed all PD patients evaluated for DBS at our center between 2006 and 2011 and analyzed the reasons for exclusion and for dropping out despite passing the screening process. A total of 223 PD patients who underwent DBS evaluation had complete charting. Only 131 (58.7%) patients were successfully implanted. Sixty‐one (27.3%) patients were excluded after screening because of significant cognitive decline (32.7%), early disease with room for medication adjustment (29.5%), behavioral dysfunction (21.3%), suspected secondary parkinsonism or atypical parkinsonism syndrome (13.1%), PD, but with poor levodopa response (11.4%), unrealistic goals (9.8%), PD with predominant axial symptoms (6.5%), significant comorbidities (6.5%), or abnormal brain imaging (3.2%). In addition, 31 (13.9%) patients were cleared for surgery, but either chose not have it (18 patients), were lost to follow‐up (12 patients), or were denied by medical insurance (1 patient). Through careful screening, a significant percentage of surgical candidates continue to be identified as less suitable because of a variety of reasons. This underscores the continued need for a comprehensive, multidisciplinary screening process.