bluuebunny/crossref_metadata_2025 huggingface dataset:
A Location Aware Mobile Tool for Direct and Indirect Climate Data Sensors
Authors: Ramos Francisco , Monfort Aida , Huerta Joaquin
Published: June 2014

Access to GIS data from mobile platforms continues to be a challenge and there is a wide range of fields where it is extremely useful. In this work, we combined three key aspects: climate data sensors, mobile platforms and spatial proximity operations. We published and made use of a web 2.0 network of climate data, where content is user‐collected, by means of their meteorological stations, and exposed as available information for the virtual community. Moreover, we enriched this data by giving the users the opportunity to directly inform the system with different climate measures. In general, management of this type of information from a mobile application could result in an important decision tool, as it enables us to provide climate‐related data according to a context and a geographical location. Therefore, we implemented a native mobile application for iPhone and iPad platforms by using ArcGIS SDK for iOS and by integrating a series of ArcGIS webmaps, which allows us to perform geospatial queries based on the user's location, offering, at the same time, access to all the data provided by the climate data sensor network and from direct users.
The BEL1‐type homeobox gene SH5 induces seed shattering by enhancing abscission‐zone development and inhibiting lignin biosynthesis
Authors: Yoon Jinmi , Cho Lae‐Hyeon , Kim Song Lim , Choi Heebak , Koh Hee‐Jong , An Gynheung
Published: June 2014

Seed shattering is an important trait that influences grain yield. A major controlling quantitative trait locus in rice is qSH1. Although the degree of shattering is correlated with the level of expression of qSH1, some qSH1‐defective cultivars display moderate shattering while others show a non‐shattering phenotype. Os05 g38120 (SH5) on chromosome 5 is highly homologous to qSH1. Although we detected SH5 transcripts in various organs, this gene was highly expressed at the abscission zone (AZ) in the pedicels. When expression of this gene was suppressed in easy‐shattering ‘Kasalath’, development of the AZ was reduced and thereby so was seed loss. By contrast, the extent of shattering, as well as AZ development, was greatly enhanced in moderate‐shattering ‘Dongjin’ rice when SH5 was overexpressed. Likewise, overexpression of SH5 in the non‐shattering ‘Ilpum’ led to an increase in seed shattering because lignin levels were decreased in the basal region of spikelets in the absence of development of an AZ. We also determined that two shattering‐related genes, SHAT1 and Sh4, which are necessary for proper formation of an AZ, were induced by SH5. Based on these observations, we propose that SH5 modulates seed shattering by enhancing AZ development and inhibiting lignin biosynthesis.
Cloning of theArabidopsisrwm1gene for resistance toWatermelon mosaic viruspoints to a new function for natural virus resistance genes
Authors: Ouibrahim Laurence , Mazier Marianne , Estevan Joan , Pagny Gaëlle , Decroocq Véronique , Desbiez Cécile , Moretti André , Gallois Jean‐Luc , Caranta Carole
Published: June 2014

Arabidopsis thalianarepresents a valuable and efficient model to understand mechanisms underlying plant susceptibility to viral diseases. Here, we describe the identification and molecular cloning of a new gene responsible for recessive resistance to several isolates ofWatermelon mosaic virus(WMV, genusPotyvirus) in the Arabidopsis Cvi‐0 accession.rwm1acts at an early stage of infection by impairing viral accumulation in initially infected leaf tissues. Map‐based cloning delimitedrwm1on chromosome 1 in a 114‐kb region containing 30 annotated genes. Positional and functional candidate gene analysis suggested thatrwm1encodescPGK2 (At1g56190), an evolutionary conserved nucleus‐encoded chloroplast phosphoglycerate kinase with a key role in cell metabolism. Comparative sequence analysis indicates that a single amino acid substitution (S78G) in the N‐terminal domain ofcPGK2 is involved inrwm1‐mediated resistance. This mutation may have functional consequences because it targets a highly conserved residue, affects a putative phosphorylation site and occurs within a predicted nuclear localization signal. Transgenic complementation in Arabidopsis together with virus‐induced gene silencing inNicotiana benthamianaconfirmed thatcPGK2corresponds torwm1and that the protein is required for efficient WMV infection. This work uncovers new insight into natural plant resistance mechanisms that may provide interesting opportunities for the genetic control of plant virus diseases.
Two CCAAT‐box‐binding transcription factors redundantly regulate early steps of the legume‐rhizobia endosymbiosis
Authors: Laloum Tom , Baudin Maël , Frances Lisa , Lepage Agnes , Billault‐Penneteau Benjamin , Cerri Marion R. , Ariel Federico , Jardinaud Marie‐Françoise , Gamas Pascal , de Carvalho‐Niebel Fernanda , Niebel Andreas
Published: June 2014

During endosymbiotic interactions between legume plants and nitrogen‐fixing rhizobia, successful root infection by bacteria and nodule organogenesis requires the perception and transduction of bacterial lipo‐chitooligosaccharidic signal called Nod factor (NF). NF perception in legume roots leads to the activation of an early signaling pathway and of a set of symbiotic genes which is controlled by specific early transcription factors (TFs) including CYCLOPS/IPD3, NSP1, NSP2, ERN1 and NIN. In this study, we bring convincing evidence that the Medicago truncatula CCAAT‐box‐binding NF‐YA1 TF, previously associated with later stages of rhizobial infection and nodule meristem formation is, together with its closest homolog NF‐YA2, also an essential positive regulator of the NF‐signaling pathway. Here we show that NF‐YA1 and NF‐YA2 are both expressed in epidermal cells responding to NFs and their knock‐down by reverse genetic approaches severely affects the NF‐induced expression of symbiotic genes and rhizobial infection. Further over‐expression, transactivation and ChIP‐PCR approaches indicate that NF‐YA1 and NF‐YA2 function, at least in part, via the direct activation of ERN1. We thus propose a model in which NF‐YA1 and NF‐YA2 appear as early symbiotic regulators acting downstream of DMI3 and NIN and possibly within the same regulatory complexes as NSP1/2 to directly activate the expression of ERN1.
Improved oxidation resistance of organic/inorganic composite atomic layer deposition coated cellulose nanocrystal aerogels
Authors: Smith Sean W. , Buesch Christian , Matthews David J. , Simonsen John , Conley John F.
Published: June 2014

Cellulose nanocrystal (CNC) aerogels are coated with thin conformal layers of Al2O3 using atomic layer deposition to form hybrid organic/inorganic nanocomposites. Electron probe microanalysis and scanning electron microscopy analysis indicated the Al2O3 penetrated more than 1500 μm into the aerogel for extended precursor pulse and exposure/purge times. The measured profile of coated fiber radius versus depth from the aerogel surface agrees well with simulations of precursor penetration depth in modeled aerogel structures. Thermogravimetric analysis shows that Al2O3 coated CNC aerogel nanocomposites do not show significant thermal degradation below 295 °C as compared with 175 °C for uncoated CNC aerogels, an improvement of over 100 °C.
Structure and electrical properties of Nb-Ge-C nanocomposite coatings
Authors: Tengstrand Olof , Nedfors Nils , Fast Lars , Flink Axel , Jansson Ulf , Eklund Per , Hultman Lars
Published: June 2014

Nb-Ge-C nanocomposite thin films were deposited by dc magnetron sputtering using three elemental targets. The films consist of substoichiometric NbCx in a nanometer-thick matrix of amorphous C and Ge. Films with no Ge contain grains that are elongated in the growth direction with a (111) preferred crystallographic orientation. With the addition of ∼12 at. % Ge, the grains are more equiaxed and exhibit a more random orientation. At even higher Ge contents, the structure also becomes denser. The porous structure of the low Ge content films result in O uptake from the ambient. With higher C content in the films both the amount of amorphous C and C/Nb-ratio increases. The contact resistance was measured by four-point technique as a function of contact force between 0 and 10 N. The lowest contact resistance (1.7 mΩ) is obtained at 10 N. The resistivity varies between 470 and 1700 μΩ·cm depending on porosity and O content.
High density and taper-free boron doped Si1−xGex nanowire via two-step growth process
Authors: Periwal Priyanka , Salem Bassem , Bassani Franck , Baron Thierry , Barnes Jean-Paul
Published: June 2014

The authors study Au catalyzed chemical vapor growth of Si1−xGex alloyed nanowires in the presence of diborane, serving as a dopant precursor. Our experiments reveal that introduction of diborane has a significant effect on doping and morphology. Boron exposure poisons the Au catalyst surface, suppresses catalyst activity, and causes significantly tapered wires, as a result of conformal growth. The authors develop here a two-step method to obtain high density and taper-free boron doped Si1−xGex alloy nanowires. The two-step process consists of: (1) growth of a small undoped Si1−xGex section and (2) introduction of diborane to form a boron doped Si1−xGex section. The catalyst preparation step remarkably influences wire yield, quality and morphology. The authors show that dopant-ratio influences wire resistivity and morphology. Resistivity for high boron doped Si1−xGex nanowire is 6 mΩ-cm. Four probe measurements show that it is possible to dope Si1−xGex alloy nanowires with diborane.
Parasympathetic ganglia derive from Schwann cell precursors
Authors: Espinosa-Medina I. , Outin E. , Picard C. A. , Chettouh Z. , Dymecki S. , Consalez G. G. , Coppola E. , Brunet J.-F.
Published: June 2014

Exploiting nervous paths already traveled

The parasympathetic nervous system helps regulate the functions of many tissues and organs, including the salivary glands and the esophagus. To do so, it needs to reach throughout the body, connecting central systems to peripheral ones. Dyachuk
et al.
and Espinosa-Medina
et al.
explored how these connections are established in mice (see the Perspective by Kalcheim and Rohrer). Progenitor cells that travel along with the developing nerves can give rise to both myelinforming Schwann cells and to parasympathetic neurons. That means the interacting nerves do not have to find each other. Instead, the beginnings of the connections are laid down as the nervous system develops.

Science
, this issue p.
82
, p.
87
; see also p.
32
Quantum computations on a topologically encoded qubit
Authors: Nigg D. , Müller M. , Martinez E. A. , Schindler P. , Hennrich M. , Monz T. , Martin-Delgado M. A. , Blatt R.
Published: June 2014

Fault-tolerant quantum computing

Quantum states can be delicate. Attempts to process and manipulate quantum states can destroy the encoded information. Nigg
et al.
encoded the quantum state of a single qubit (in this case, a trapped ion) over the global properties of a series of trapped ions. These so-called stabilizers protected the information against noise sources that can degrade the single qubit. The protocol provides a route to fault-tolerant quantum computing.

Science
, this issue p.
302
Draft Genome Sequences of Two Clinical Isolates of Streptococcus mutans
Authors: Zheng Hui , Guo Lihong , Du Ning , Lin Jiuxiang , Song Lai , Liu Guiming , Chen Feng
Published: June 2014

We report the draft genome sequences of PKUSS-HG01 and PKUSS-LG01, two clinical isolates of
Streptococcus mutans
from human dental plaque. The genomics information will facilitate the study of the mechanisms of pathogenicity and evolution of
S. mutans
.
Genome Sequences of Porcine Epidemic Diarrhea Virus:
In Vivo
and
In Vitro
Phenotypes
Authors: Lawrence Paulraj K. , Bumgardner Eric , Bey Russell F. , Stine Douglas , Bumgarner Roger E.
Published: June 2014

Since the outbreak of porcine epidemic diarrhea virus (PEDV) in May 2013, U.S. swine producers have lost almost five million baby pigs. In an attempt to understand the evolution of PEDV in the United States and possibly develop a control strategy, we compared the genome sequences of a PEDV strain isolated from an infected piglet against its
in vitro
adapted version. The original PEDV strain was grown in Vero cells and passed 10 times serially in a MARC145 cell line. The sequence analysis of the native PEDV strain and
in vitro
passaged virus shows that the cell culture adaptation specifically modifies PEDV spike protein whereas the open reading frame 1a/b (ORF1a/b)-encoded polyprotein, the nucleoprotein, NS3B (ORF3), and membrane and envelope proteins remain unchanged.
Genome Sequence of SCB34, a Sequence Type 131 Multidrug-Resistant Escherichia coli Isolate Causing Neonatal Early-Onset Sepsis
Authors: Chavez-Bueno Susana , Day Michael W. , Toby Inimary T. , Akins Darrin R. , Dyer David W.
Published: June 2014

SCB34 is a sequence type 131, highly invasive, multidrug-resistant
Escherichia coli
isolate that produced neonatal bacteremia. Whole-genome sequencing was performed using a 250-bp library on the Illumina MiSeq platform; 5,910,264 reads were assembled
de novo
using the A5 assembly pipeline. The total contig length was 5,227,742 bp; the RAST server was used for annotation.
Genetic Characterization of HIV-1 Subtype D Near-Full-Length Proviral Genomes by Illumina Massively Parallel Sequencing Technology
Authors: Pessôa Rodrigo , Lopes Maria Esther , Sanabani Sabri S.
Published: June 2014

This study describes the near-full-length genome deep sequencing of two HIV-1 subtype D strains identified in blood donors in Rio de Janeiro, Brazil, in what seems to have been a small restricted subtype D epidemic in the country.
Acupuncture for Treatment of Secondary Osteoporosis in Patients with Spinal Cord Injury: A Controlled Study
Authors: Meng Qingxi , Liu Xin , Shan Qunqun , Yu Peng , Mao Zhaohu , Zhang Fan , Li Jian , Zhao Tingbao
Published: June 2014

Objective

We explored the effect of adjunctive acupuncture on secondary osteoporosis in patients with spinal cord injury (SCI).

Methods

Patients with subacute SCI were recruited and divided into two groups by patient choice: group 1 patients received standard combination therapy and group 2 patients received combination therapy plus acupuncture for 3 months. The concentrations of IgG, IgM and tumour necrosis factor α (TNFα) in serum and the bone mineral density were measured before and after treatment.

Result

The decrease in the concentration of TNFα and IgM in patients in group 2 compared with those in group 1 was statistically significant. The IgG level showed no significant change in either group. Bone mineral density increased more after adjunctive acupuncture, but the difference was not significant.

Conclusions

Further research is needed to determine whether acupuncture as an adjunct to combination therapy can reduce osteoporosis in patients with subacute SCI.

Trial Registration Number

P153-2008-36
Phytobezoar leading to gastric outlet obstruction in a patient with diabetes
Authors: Dhakal Om Prakash , Dhakal Mona , Bhandari Dhurba
Published: June 2014

Gastroparesis is a condition which results in delayed gastric emptying without gastric outflow tract obstruction. Gastrointestinal involvement in diabetes can present in various forms such as oesophageal dysmotility, gastro-oesophageal reflux disease, gastroparesis, enteropathy, non-alcoholic fatty liver disease and glycogenic hepatopathy. Gastroparesis is the most common gastric motility disorder complicating long-standing diabetes. It can sometimes lead to mechanical obstruction as a result of formation of bezoars. Phytobezoars are the most common type of bezoar and are composed of indigestible food, vegetable fibre or seeds. Poor pyloric function and decreased acid formation predisposes phytobezoars formation in patients with diabetic gastroparesis. An 80-year-old patient with diabetes in our presentation developed gastric outlet obstruction due to impaction of phytobezoar over the pylorus.
The child with spontaneous recurrent bleeding in the eye
Authors: Rao Aparna , Padhy Debanand
Published: June 2014

Juvenile xanthogranuloma is a self-limiting dermatological condition characterised by spontaneous hyphaema due to uveal involvement causing neovascularisation. Recurrent hyphaema in a child should alert the clinician towards this rare diagnosis. Appropriate investigations and treatment should be directed towards treating this possible diagnosis associated with neovascular glaucoma where routine filtering surgeries may be associated with several complications.
Transient acute adrenal insufficiency associated with adenovirus serotype 40 infection
Authors: Rai Birendra , Ali Muhammad , Kumar Varun , Krebit Ibraheem
Published: June 2014

We present an instance of a 6-year-old boy who was admitted with adenovirus infection and developed transient acute adrenal insufficiency, which required supplementation with glucocorticoids and mineralocorticoids for 8 weeks. Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We could not find any similar reported case in medical literature. We hope our case would add to the existing knowledge of adenoviral complications in paediatric patients.
Peritoneal inclusion cysts in pregnancy, a diagnostic challenge
Authors: Hitzerd Emilie , Jeurgens-Borst Anneke J C M , Pijnenborg Johanna M A
Published: June 2014

A cystic pelvic mass detected during pregnancy is not uncommon, but can be a diagnostic challenge. Most of these pelvic masses are benign ovarian cysts and resolve spontaneously. However, rare non-ovarian causes can complicate the diagnostic and therapeutic management. In this report an unusual case is presented of a 27-year-old pregnant woman with an atypical multicystic lesion in the pelvis, seen on routine first trimester ultrasound. A laparoscopic exploration was performed to rule out ovarian malignancy, and after histological analysis she was diagnosed with peritoneal inclusion cysts. The diagnostic and therapeutic challenges inherent to this rare non-ovarian disease are addressed in this case report.
The effect of neuropeptide Y on cell survival and neurotrophin expression in in-vitro models of Alzheimer’s disease
Authors: Angelucci Francesco , Gelfo Francesca , Fiore Marco , Croce Nicoletta , Mathé Aleksander A. , Bernardini Sergio , Caltagirone Carlo
Published: June 2014

Alzheimer’s disease (AD) is a disorder characterized by the accumulation of abnormally folded protein fragments in neurons, i.e., β-amyloid (Aβ) and tau protein, leading to cell death. Several neuropeptides present in the central nervous system (CNS) are believed to be involved in the pathophysiology of AD. Among them, neuropeptide Y (NPY), a small peptide widely distributed throughout the brain, has generated interest because of its role in neuroprotection against excitotoxicity in animal models of AD. In addition, it has been shown that NPY modulates neurogenesis. Interestingly, these latter effects are similar to those elicited by neurotrophins, which are critical molecules for the function and survival of neurons that degenerate during the course of AD. In this review we summarize the evidence for the involvement of NPY and neurotrophins in AD pathogenesis, and the similarity between them in CNS neurons. Finally, we recapitulate our recent in-vitro evidence for the involvement of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the neuroprotective effect elicited by NPY in AD neuron-like models (neuroblastoma cells or primary cultures exposed to toxic concentrations of Aβ’s pathogenic fragment 25–35), and propose a putative mechanism based on NPY-induced inhibition of voltage-dependent Ca2+ influx in pre- and post-synaptic neurons.
Heterochromatin and sibling species ofSimulium praelargums.l. (Diptera: Simuliidae)
Authors: Thapa Sachin , Procunier William , Henry Willie , Chhetri Shailika
Published: June 2014

Cytological descriptions are given for two sympatric sibling species, Simulium praelargum IIIL-st and Simulium praelargum IIIL-1.2, from Darjeeling, West Bengal, India. Sibling IIIL-1.2 differs from IIIL-st by a two step fixed included inversion (IIIL-1.2) found on the long arm of chromosome III. Both siblings possess heterochromatinized IIIS polytene chromosome ends, while IIIL-1.2 is unique within the Simuliidae in that it exhibits a very large enhanced chromocentre that persists in normal somatic tissue, contrary to other chromocentre-containing taxa. In IIIL-1.2, the chromocentre occurs as a positively allocyclic heteropycnotic body in normal mitotic interphase cells of neuroblast ganglia, oogonia, and spermatogonia. In mitotic metaphase chromosomes, the chromocentre forms large pronounced primary (centromere) constrictions and appears to be associated with nonhomologous pairing. Initial cytological studies on taxa within the feuerborni group have revealed heterochromatic chromosomal polymorphisms. Progressive fixation of these polymorphisms in different taxa within the group opens up the possibility of using comparative molecular or genomic approaches to begin to define the functional and structural aspects of the epigenome and to further characterize mitosis and meiosis in S. praelargum IIIL-1.2.
Area spectrum of extremal black holes with warped AdS near-horizon geometry
Authors: Wen Wen-Yu
Published: June 2014

In this paper, we provide an alternative method to study the area spectrum of certain classes of extremal black holes which have near-horizon geometry as warped AdS. We argue that previous methods which are based on the existence of quasinormal modes may not be applicable in the extremal limit. The topology difference of the near-horizon geometry between non-extremal and extremal black holes implies a separate treatment is needed to study the area discreteness in the extremal limit. To be specific, we will study area spectrum of supersymmetric BMPV black holes/black rings and Reissner–Nordström (RN) black holes at the extremal limit. Inspired by the recently established Kerr/CFT and RN/CFT correspondence, we propose a new way to quantize the area regardless of the (non-)existence of quasinormal modes or zero Hawking temperature. At last, we propose a dilute gas model and harmonic oscillator model which have same degrees of freedom as the dual CFT.
Electron cloud in accelerators
Authors: Cimino Roberto , Demma Theo
Published: June 2014

Low energy electrons in accelerators are known to interact with the circulating beam, giving rise to the formation of a so-called e-cloud. Such e-cloud may induce detrimental effects on the accelerated beam quality and stability. Those effects have been observed in most accelerators of positively charged particles. A longstanding effort has been so far devoted to understand in detail the physical origin of such e-cloud, its build-up and its interaction with the circulating beam. We will first describe the origin and the basic features causing e-cloud formation in accelerators, then we review some of the theoretical work produced to simulate and analyze such phenomenon. In selected cases, theoretical expectations and experimental observations will be compared, to address the importance of benchmarking codes versus observations to reach the required predictive capability. To this scope, codes need realistic input parameters which correctly describe material and surface properties at the basis of such e-cloud formation and build-up. The experimental efforts, performed worldwide in many surface and material science laboratories, to measure such essential parameters will then be presented and critically reviewed. Finally, we will describe some of the e-cloud mitigation strategies adopted so far and draw some conclusions.
Process Flexibility in Service Orchestration: A Systematic Literature Review
Authors: Murguzur Aitor , Intxausti Karmele , Urbieta Aitor , Trujillo Salvador , Sagardui Goiuria
Published: June 2014

In dynamic environments, changes are often unpredictable and complex. Process models cannot be fully specified up-front and process flexibility becomes a key issue. Enterprise applications and systems supporting such processes are increasingly being architected in a service-oriented style. In this light, our goal is to analyze service orchestration approaches from a process flexibility perspective. Through a systematic literature review, we evaluate 17 service orchestration approaches and analyze their support for: (i) variability, support for large collections of process variants, (ii) adaptation, need for instance changes during runtime, (iii) evolution, need for schema changes during runtime, and (iv) looseness, need for loosely-specified models. The review findings provide a clearer understanding of process flexibility requirements and service orchestration mechanisms that support them, helping us to understand the limitations and shed light on future research areas.
Asymptotics of linear recurrences
Authors: Wong R.
Published: June 2014

In this paper, we review the asymptotic results that are now available for second-order linear difference equations containing a parameter (or, equivalently, three-term recurrence relations). These include asymptotic expansions for solutions to these equations when the parameter is fixed or varying in an interval containing a turning point or a transition point. Also presented is a method for deriving asymptotic approximations for solutions when the initial values are given. These results are particularly useful when a given system of orthogonal polynomials (i) does not satisfy any second-order differential equation, (ii) does not have any integral representation, and (iii) is not even associated with a unique (or any) weight function.
Synthesis and properties of rhenium(I) bridged boron-dipyrromethene dyad
Authors: Madhu Sheri , Hinge Vijaya Kumar , Ravikanth Mangalampalli
Published: June 2014

We synthesized the hexa-coordinated Re ( I ) bridged BODIPY dyad 1 in decent yield by thermal reaction of benzimidazole substituted BODIPY 2 with Re ( CO )5 Cl . The dyad 1 was characterized by 1 H , 13 C , 11 B , 19 F NMR, ESI-MS, FTIR, UV-vis, and electrochemical techniques. In Re ( I ) bridged dyad 1, the Re ( I ) ion is hexa-coordinated and coordinates with nitrogen atoms of two benzimidazole units, three axial carbonyl ligands and one chloride atom. The presence of three carbonyl groups in dyad 1 was verified by 13 C NMR and IR spectroscopy. The absorption and steady-state fluorescence spectra of Re ( I ) bridged BODIPY dyad showed a slightly broad and hypsochromically shifted absorption and emission bands compared to BODIPY 2. The electrochemical studies indicated that, the Re ( I ) bridge BODIPY dyad 1 was easy to reduce compared to BODIPY 2 supporting the electron deficient nature dyad upon Re ( I ) ion binding. The molecular structure of dyad 1 was further elucidated by DFT computational studies.
Different oral sensitivities to and sensations of short-, medium-, and long-chain fatty acids in humans
Authors: Running Cordelia A. , Mattes Richard D.
Published: June 2014

Fatty acids that vary in chain length and degree of unsaturation have different effects on metabolism and human health. As evidence for a “taste” of nonesterified fatty acids (NEFA) accumulates, it may be hypothesized that fatty acid structures will also influence oral sensations. The present study examined oral sensitivity to caproic (C6), lauric (C12), and oleic (C18:1) acids over repeated visits. Analyses were also conducted on textural properties of NEFA emulsions and blank solutions. Oral thresholds for caproic acid were lower compared with oleic acid. Lauric acid thresholds were intermediate but not significantly different from either, likely due to lingering irritating sensations that prevented accurate discrimination. From particle size analysis, larger droplets were observed in blank solutions when mineral oil was used, leading to instability of the emulsion, which was not observed when emulsions contained NEFA or when mineral oil was removed from the blank. Rheological data showed no differences in viscosity among samples except for a slightly higher viscosity with oleic acid concentrations above 58 mM. Thus, texture was unlikely to be the property used to distinguish between the samples. Differences in oral detection and sensation of caproic, lauric, and oleic acids may be due to different properties of the fatty acid alkyl chains.
Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury
Authors: Weerasinghe Sujith V. W. , Jang You-Jin , Fontana Robert J. , Omary M. Bishr
Published: June 2014

Several serum markers are used to assess hepatocyte damage, but they have limitations related to etiology specificity and prognostication. Identification of novel hepatocyte-specific biomarkers could provide important prognostic information and better pathogenesis classification. We tested the hypothesis that hepatocyte-selective biomarkers are released after subjecting isolated mouse hepatocytes to Fas-ligand-mediated apoptosis. Proteomic analysis of hepatocyte culture medium identified the mitochondrial matrix protein carbamoyl phosphate synthetase-1 (CPS1) among the most readily detected proteins that are released by apoptotic hepatocytes. CPS1 was also detected in mouse serum upon acute challenge with Fas-ligand or acetaminophen and in hepatocytes upon hypoosmotic stress, independent of hepatocyte caspase activation. Furthermore, CPS1 was observed in sera of mice chronically fed the hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Mouse CPS1 detectability was similar in serum and plasma, and its half-life was 126 ± 9 min. Immune staining showed that CPS1 localized to mouse hepatocytes but not ductal cells. Analysis of a few serum samples from patients with acute liver failure (ALF) due to acetaminophen, Wilson disease, or ischemia showed readily detectable CPS1 that was not observed in several patients with chronic viral hepatitis or in control donors. Notably, CPS1 rapidly decreased to undetectable levels in sera of patients with acetaminophen-related ALF who ultimately recovered, while alanine aminotransferase levels remained elevated. Therefore, CPS1 becomes readily detectable upon hepatocyte apoptotic and necrotic death in culture or in vivo. Its abundance and short serum half-life, compared with alanine aminotransferase, suggest that it may be a useful prognostic biomarker in human and mouse liver injury.
Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis
Authors: Weijenborg Pim W. , Smout André J. P. M. , Verseijden Caroline , van Veen Henk A. , Verheij Joanne , de Jonge Wouter J. , Bredenoord Albert J.
Published: June 2014

Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus is associated with the expression of filaggrin.
Autonomic dysfunction affects dynamic cerebral autoregulation during Valsalva maneuver: comparison between healthy and autonomic dysfunction subjects
Authors: Castro Pedro M. , Santos Rosa , Freitas João , Panerai Ronney B. , Azevedo Elsa
Published: June 2014

The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial blood pressure (ABP) fluctuations [cerebral autoregulation (CA)] is still controversial. We aimed to study the repercussion of autonomic failure (AF) on dynamic CA during the Valsalva maneuver (VM). Eight AF subjects with familial amyloidotic polineuropahty (FAP) were compared with eight healthy controls. ABP and CBF velocity (CBFV) were measured continuously with Finapres and transcranial Doppler, respectively. Cerebrovascular response was evaluated by cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance-area product (RAP) changes. Dynamic CA was derived from continuous estimates of autoregulatory index (ARI) [ARI( t)]. During phase II of VM, FAP subjects showed a more pronounced decrease in normalized CBFV (78 ± 19 and 111 ± 16%; P = 0.002), ABP (78 ± 19 and 124 ± 12%; P = 0.0003), and RAP (67 ± 17 and 89 ± 17%; P = 0.019) compared with controls. CrCP and CVRi increased similarly in both groups during strain. ARI( t) showed a biphasic variation in controls with initial increase followed by a decrease during phase II but in FAP this response was blunted (5.4 ± 3.0 and 2.0 ± 2.9; P = 0.033). Our data suggest that dynamic cerebral autoregulatory response is a time-varying phenomena during VM and that it is disturbed by autonomic dysfunction. This study also emphasizes the fact that RAP + CrCP model allowed additional insights into understanding of cerebral hemodynamics, showing a higher vasodilatory response expressed by RAP in AF and an equal CrCP response in both groups during the increased intracranial and intrathoracic pressure, while classical CVRi paradoxically suggests a cerebral vasoconstriction.
The Early Detection of Pancreatic Cancer: What Will It Take to Diagnose and Treat Curable Pancreatic Neoplasia?
Authors: Lennon Anne Marie , Wolfgang Christopher L. , Canto Marcia Irene , Klein Alison P. , Herman Joseph M. , Goggins Michael , Fishman Elliot K. , Kamel Ihab , Weiss Matthew J. , Diaz Luis A. , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Hruban Ralph H.
Published: June 2014

Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease, such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific approaches for screening of curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. Cancer Res; 74(13); 3381–9. ©2014 AACR.
Validation of Plasma Proneurotensin as a Novel Biomarker for the Prediction of Incident Breast Cancer
Authors: Melander Olle , Belting Mattias , Manjer Jonas , Maisel Alan S. , Hedblad Bo , Engström Gunnar , Nilsson Peter , Struck Joachim , Hartmann Oliver , Bergmann Andreas , Orho-Melander Marju
Published: June 2014

Background: High fasting plasma proneurotensin concentration was associated with the development of breast cancer in the Malmö Diet and Cancer Study (MDCS). Here, we aimed at replicating the initial finding in an independent second cohort.

Methods: The Malmö Preventive Project (MPP) is a population study and comprised 18,240 subjects when examined in 2002–2006. Of women without history of breast cancer at examination, we included all who developed breast cancer during follow-up (n = 130) until December 31, 2010, and a random sample of women without breast cancer until the end of follow-up (n = 1,439) for baseline plasma proneurotensin assessment (mean age, 70.0 ± 4.4 years). Proneurotensin was measured in fasting plasma samples and was related to the risk of later breast cancer development using multivariate logistic regression.

Results: Proneurotensin [odds ratio (OR) per standard deviation (SD) increment of LN-transformed proneurotensin] was significantly related to incident breast cancer [OR, 2.09; 95% confidence interval (CI), 1.79–2.44; P < 0.001; adjusted for age, body mass index (BMI), smoking, and hormone replacement therapy]. The effect estimate in the MPP was larger than in the discovery cohort (MDCS), with the main difference between the two cohorts being that women of the MPP study were on the average about 10 years older and follow-up time was shorter than that of the MDCS.

Conclusion: As initially found in the MDCS, fasting plasma proneurotensin was significantly associated with the development of breast cancer in the MPP study as well.

Impact: Measurement of plasma proneurotensin warrants further investigation as a blood-based marker for early breast cancer detection. Cancer Epidemiol Biomarkers Prev; 23(8); 1672–6. ©2014 AACR.
Chloroquine Inhibits Autophagy to Potentiate Antiestrogen Responsiveness in ER+ Breast Cancer
Authors: Cook Katherine L. , Wärri Anni , Soto-Pantoja David R. , Clarke Pamela AG. , Cruz M. Idalia , Zwart Alan , Clarke Robert
Published: June 2014

Purpose: Estrogen receptor-α (ERα)-targeted therapies including tamoxifen (TAM) or Faslodex (ICI) are used to treat ER+ breast cancers. Up to 50% of tumors will acquire resistance to these interventions. Autophagy has been implicated as a major driver of antiestrogen resistance. We have explored the ability of chloroquine (CQ), which inhibits autophagy, to affect antiestrogen responsiveness.

Experimental Design: TAM-resistant MCF7-RR and ICI-resistant/TAM cross-resistant LCC9 ER+ breast cancer cells were injected into mammary fat pads of female athymic mice and treated with TAM and/or ICI in combination with oral low-dose CQ.

Results: We show that CQ can increase antiestrogen responsiveness in MCF7-RR and LCC9 cells and tumors, likely through the inhibition of autophagy. However, the combination of ICI+CQ was less effective than CQ alone in vivo, unlike the TAM+CQ combination. Antiestrogen treatment stimulated angiogenesis in tumors but did not prevent CQ effectiveness. The lower efficacy of ICI+CQ was associated with ICI effects on cell-mediated immunity within the tumor microenvironment. The mouse chemokine KC (CXCL1) and IFNγ were differentially regulated by both TAM and ICI treatments, suggesting a possible effect on macrophage development/activity. Consistent with these observations, TAM+CQ treatment increased tumor CD68+ cells infiltration, whereas ICI and ICI+CQ reduced peripheral tumor macrophage content. Moreover, macrophage elimination of breast cancer target cells in vitro was reduced following exposure to ICI.

Conclusion: CQ restores antiestrogen sensitivity to resistant tumors. Moreover, the beneficial combination of TAM+CQ suggests a positive outcome for ongoing neoadjuvant clinical trials using this combination for the treatment of ER+ ductal carcinoma in situ lesions. Clin Cancer Res; 20(12); 3222–32. ©2014 AACR.
Receptor Tyrosine Kinases Endocytosis in Endothelium
Authors: Zhang Xi , Simons Michael
Published: June 2014

Receptor tyrosine kinases are involved in regulation of key processes in endothelial biology, including proliferation, migration, and angiogenesis. It is now generally accepted that receptor tyrosine kinase signaling occurs intracellularly and on the plasma membrane, although many important details remain to be worked out. Endocytosis and subsequent intracellular trafficking spatiotemporally regulate receptor tyrosine kinase signaling, whereas signaling endosomes provide a platform for the compartmentalization of signaling events. This review summarizes recent advances in our understanding of endothelial receptor tyrosine kinase endocytosis and signaling using vascular endothelial growth factor receptor-2 as a paradigm.
Strategic Planning to Reduce the Burden of Stroke Among Veterans
Authors: Lich Kristen Hassmiller , Tian Yuan , Beadles Christopher A. , Williams Linda S. , Bravata Dawn M. , Cheng Eric M. , Bosworth Hayden B. , Homer Jack B. , Matchar David B.
Published: June 2014

Background and Purpose—

Reducing the burden of stroke is a priority for the Veterans Affairs Health System, reflected by the creation of the Veterans Affairs Stroke Quality Enhancement Research Initiative. To inform the initiative’s strategic planning, we estimated the relative population-level impact and efficiency of distinct approaches to improving stroke care in the US Veteran population to inform policy and practice.

Methods—

A System Dynamics stroke model of the Veteran population was constructed to evaluate the relative impact of 15 intervention scenarios including both broad and targeted primary and secondary prevention and acute care/rehabilitation on cumulative (20 years) outcomes including quality-adjusted life years (QALYs) gained, strokes prevented, stroke fatalities prevented, and the number-needed-to-treat per QALY gained.

Results—

At the population level, a broad hypertension control effort yielded the largest increase in QALYs (35 517), followed by targeted prevention addressing hypertension and anticoagulation among Veterans with prior cardiovascular disease (27 856) and hypertension control among diabetics (23 100). Adjusting QALYs gained by the number of Veterans needed to treat, thrombolytic therapy with tissue-type plasminogen activator was most efficient, needing 3.1 Veterans to be treated per QALY gained. This was followed by rehabilitation (3.9) and targeted prevention addressing hypertension and anticoagulation among those with prior cardiovascular disease (5.1). Probabilistic sensitivity analysis showed that the ranking of interventions was robust to uncertainty in input parameter values.

Conclusions—

Prevention strategies tend to have larger population impacts, though interventions targeting specific high-risk groups tend to be more efficient in terms of number-needed-to-treat per QALY gained.
Incidental Magnetic Resonance Diffusion-Weighted Imaging–Positive Lesions Are Rare in Neurologically Asymptomatic Community-Dwelling Adults
Authors: Batool Saima , O’Donnell Martin , Sharma Mukul , Islam Shofiqul , Dagenais Gilles R. , Poirier Paul , Lear Scott A. , Wielgosz Andreas , Teo Koon , Stotts Grant , McCreary Cheryl R. , Frayne Richard , DeJesus Jane , Rangarajan Sumathy , Yusuf Salim , Smith Eric E.
Published: June 2014

Background and Purpose—

Incidental magnetic resonance diffusion-weighted imaging (DWI)–positive lesions, considered to represent small acute infarcts, have been detected in patients with cerebral small vessel diseases or cognitive impairment, but the prevalence in the community population is unknown.

Methods—

DWI sequences collected in 793 participants in the Prospective Urban Rural Epidemiological (PURE) study were reviewed for DWI lesions consistent with small acute infarcts.

Results—

No DWI-positive lesions were detected (0%, 95% confidence interval, 0–0.5).

Conclusions—

DWI-positive lesions are rare in an asymptomatic community population. The prevalence of DWI-positive lesions in the community seems to be lower than in patients with cerebral amyloid angiopathy, intracerebral hemorrhage, or cognitive impairment.
Randomized Controlled Trial on Hemifield Eye Patching and Optokinetic Stimulation in Acute Spatial Neglect
Authors: Machner Björn , Könemund Inga , Sprenger Andreas , von der Gablentz Janina , Helmchen Christoph
Published: June 2014

Background and Purpose—

Right hemisphere stroke patients frequently experience spatial neglect, a severe lack of awareness for contralesional hemispace. Although neglect counts among the strongest predictors for poor functional outcome after stroke, there is no established therapy, particularly not for the acute stage.

Methods—

In a randomized controlled trial, we compared the combined treatment of hemifield eye patching and repetitive optokinetic stimulation in acute stroke patients with neglect to the spontaneous course. Outcome measures were a neuropsychological test battery for neglect as well as scales of functional independence and clinical impairment. Outcomes were assessed at baseline (day 1), post treatment (day 8), and at 1-month follow-up (day 30).

Results—

Final analysis included 21 acute right hemisphere stroke patients with neglect (23 enrolled, 2 lost to follow-up) allocated either to the treatment (1 week hemifield eye patching and daily sessions of optokinetic stimulation, n=11) or the control group (no neglect-specific treatment, n=10). At baseline, both groups did not differ in neuropsychological test performance, clinical impairment, or functional disability. At the post treatment session, both groups had improved in all these measures, and results were stable or further improved at follow-up. However, there was no significant difference in this change between the treatment and the control group.

Conclusions—

An early intervention of combined hemifield eye patching and optokinetic stimulation in acute stroke patients with spatial neglect has no additive effect to the spontaneous remitting course of the disorder.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01617343.
Illegal, Unreported and Unregulated Fishing on the High Seas: The Port State Measures Agreement in Context
Authors: Witbooi Emma
Published: June 2014

Despite stepped-up efforts to tackle illegal, unreported and unregulated (iuu) fishing on the high seas, it is flourishing. The threats that it poses, ranging from adverse effects on fish stocks to the destabilisation of coastal communities, warrant renewed urgent concern about its proliferation. There is general agreement amongst commentators, regulators and those on the ground alike that a multi-pronged approach to tackling iuu fishing is required which creatively employs the complementary legal tools currently available. The potential power of port state controls, as a relatively simple and economic means of hitting at the profitability of iuu fishing has recently received attention, in part due to the adoption of the 2009 fao Agreement on Port State Measures. This article provides input into the potential of this Agreement to meaningfully advance current efforts in tackling iuu fishing, particularly from an enforcement perspective, in combination with other existing regulatory efforts towards this end.
Musa cylindrica, a new species of Musa (Musaceae) from North-East India
Authors: JOE ALFRED , SREEJITH PURAVANNOOR EDAKKATILLUM , SABU MAMIYIL
Published: June 2014

A new species of Musa belonging to the Sect. Musa from Meghalaya, North-East India is described as Musa cylindrica. A detailed description, distribution, ecology, phenology and key to the related species are provided.
Taxonomic notes on Chinese Lilium L. (Liliaceae) with proposal of three nomenclatural revisions
Authors: Gao Yun-Dong , Gao Xin-Fen
Published: June 2014

In this revision, we treat Lilium wenshanense L.J. Peng & F.X. Li, L. jinfushanense L.J. Peng & B.N. Wang and L. huidongense J.M. Xu from China as synonyms of L. brownii F.E. Brown ex Miellez, L. taliense Franchet and L. lijiangense L.J. Peng, respectively. We justify the synonymy by demonstrating the existence of continuous morphological variation, which we observed in the field and among herbarium specimens.