bluuebunny/crossref_metadata_2025 huggingface dataset:
High throughput fabrication of disposable nanofluidic lab-on-chip devices for single molecule studies
Authors: van Kan Jeroen A. , Zhang Ce , Perumal Malar Piravi , van der Maarel Johan R. C.
Published: July 2012

An easy method is introduced allowing fast polydimethylsiloxane (PDMS) replication of nanofluidic lab-on-chip devices using accurately fabricated molds featuring cross-sections down to 60 nm. A high quality master is obtained through proton beam writing and UV lithography. This master can be used more than 200 times to replicate nanofluidic devices capable of handling single DNA molecules. This method allows to fabricate nanofluidic devices through simple PDMS casting. The extensions of YOYO-1 stained bacteriophage T4 and λ−DNA inside these nanochannels have been investigated using fluorescence microscopy and follow the scaling prediction of a large, locally coiled polymer chain confined in nanochannels.
A rapid, inexpensive surface treatment for enhanced functionality of polydimethylsiloxane microfluidic channels
Authors: Beal John H. L. , Bubendorfer Andrea , Kemmitt Tim , Hoek Ingrid , Mike Arnold W.
Published: July 2012

A rapid, inexpensive method using alkoxysilanes has been developed to selectively coat the interior of polydimethylsiloxane (PDMS) microfluidic channels with an integral silicaceous layer. This method combines the rapid prototyping capabilities of PDMS with the desirable wetting and electroosmotic properties of glass. The procedure can be carried out on the open faces of PDMS blocks prior to enclosure of the channels, or by flowing the reagents through the preformed channels. Therefore, this methodology allows for high-throughput processing of entire microfluidic devices or selective modification of specific areas of a device. Modification of PDMS with tetraethoxysilane generated a stable surface layer, with enhanced wettability and a more stable electroosmotic flow rate than native PDMS. Modification of PDMS with 3-aminopropyltriethoxysilane generated a surface layer bearing amine functionalities allowing for further chemical derivatization of the PDMS surface.
Martensitic transformation and magnetic domains in Mn50Ni40Sn10 studied by in-situ transmission electron microscopy
Authors: Tian H. F. , Lu J. B. , Ma L. , Shi H. L. , Yang H. X. , Wu G. H. , Li J. Q.
Published: August 2012

The structural features, martensitic transformation, and magnetic domains in the Mn50Ni40Sn10 Heusler alloy are investigated by in-situ transmission electron microscopy and Lorentz microscopy. A rich variety of microstructural phenomena arising from structural and magnetic transitions are demonstrated at low temperatures. The “5M” or “6M” superstructure modulations and needle-shaped martensites have been clearly observed in the martensitic phase. Structural evolutions of magnetic domains are revealed under in-situ applied magnetic fields using Lorentz microscopy. The structural domains and reversibility of the phase transitions are analyzed based on our experimental observations and discussed in comparison with results of low-temperature magnetization.
Tuning direct current streaming dielectrophoresis of proteins
Authors: Nakano Asuka , Camacho-Alanis Fernanda , Chao Tzu-Chiao , Ros Alexandra
Published: August 2012

Dielectrophoresis (DEP) of biomolecules has large potential to serve as a novel selectivity parameter for bioanalytical methods such as (pre)concentration, fractionation, and separation. However, in contrast to well-characterized biological cells and (nano)particles, the mechanism of protein DEP is poorly understood, limiting bioanalytical applications for proteins. Here, we demonstrate a detailed investigation of factors influencing DEP of diagnostically relevant immunoglobulin G (IgG) molecules using insulator-based DEP (iDEP) under DC conditions. We found that the pH range in which concentration of IgG due to streaming iDEP occurs without aggregate formation matches the pH range suitable for immunoreactions. Numerical simulations of the electrokinetic factors pertaining to DEP streaming in this range further suggested that the protein charge and electroosmotic flow significantly influence iDEP streaming. These predictions are in accordance with the experimentally observed pH-dependent iDEP streaming profiles as well as the determined IgG molecular properties. Moreover, we observed a transition in the streaming behavior caused by a change from positive to negative DEP induced through micelle formation for the first time experimentally, which is in excellent qualitative agreement with numerical simulations. Our study thus relates molecular immunoglobulin properties to observed iDEP, which will be useful for the future development of protein (pre)concentration or separation methods based on DEP.
Synthesis of Poly(2-Hydroxyethyl Methacrylate) Sponges via Activators Regenerated by Electron-transfer Atom-transfer Radical Polymerization
Authors: Paterson Stefan M. , Brown David H. , Shaw Jeremy A. , Chirila Traian V. , Baker Murray V.
Published: August 2012

Activators regenerated by electron-transfer atom-transfer radical polymerization, catalyzed by tris(2-pyridylmethyl)amine/CuBr2 and Na{Cu(Gly3)}, was used to synthesize poly(2-hydroxyethyl methacrylate) sponges from 80 : 20 H2O/2-hydroxyethyl methacrylate mixtures. Polymerization-induced phase separations resulted in sponges having morphologies based on agglomerated polymer droplets. During the synthesis of poly(2-hydroxyethyl methacrylate) sponges, first-order kinetics were observed up to a maximum of ~50 % conversion regardless of the catalyst used. The morphologies of the sponges were dependent on the rate of polymerization, slower polymerization rates resulting in polymers with larger morphological features (pores and polymer droplets).
Novel Semiconducting Biomaterials Derived from a Proline Ester and Tetracyanoquinodimethane Identified by Handpicked Selection of Individual Crystals
Authors: Martin Lisandra L. , Lu Jinzhen , Nafady Ayman , Le Thanh Hai , Siriwardana Amal I. , Qu Xiaohu , Traore Daouda A. K. , Wilce Matthew , Bond Alan M.
Published: August 2012

Complex mixtures of cation : anion stoichometries often result from the syntheses of tetracyanoquinodimethane (TCNQ) salts, and often these cannot be easily separated. In this study, the reaction of N,N-dimethyl-d-proline-methylester (Pro(CH3)3+) with LiTCNQ resulted in a mixture of crystals. Hand selection and characterisation of each crystal type by X-ray, infrared, Raman and electrochemistry has provided two stoichometries, 1 : 1 [Pro(CH3)3TCNQ] and 2 : 3 ([(Pro(CH3)3)2(TCNQ)3]). A detailed comparison of these structures is provided. The electrochemical method provides an exceptionally sensitive method of distinguishing differences in stoichiometry. The room temperature conductivity of the mixture is 3.1 × 10–2 S cm–1, which lies in the semiconducting range.
A decision-making framework for wildfire suppression
Authors: Petrovic N. , Carlson J. M.
Published: August 2012

This paper addresses two fundamental issues that arise broadly in human response to natural hazards: the effect on overall costs of the high variability (power laws) in event size statistics and complexities associated with combining disparate sources of information in decision-making. To address these issues in a series of concrete scenarios, we analyse data for California wildfires. We also develop a modelling framework that projects costs based on the combination of a dynamic fire spread model, an economic cost model and population data. Our study uses model-generated fire catalogues to estimate the effect of suppression strategies on fire size, and our cost function incorporates both suppression costs and loss of assets. Together, these yield statistical estimates of the average economic impact of fire response policies. Tradeoffs between resource costs and assets at risk determine the optimal response for an individual fire. We also compare the costs of different policies for division of limited resources between multiple fires using scenarios motivated by the 2003 and 2007 California wildfire seasons.
Early forest fire detection by vision-enabled wireless sensor networks
Authors: Fernández-Berni Jorge , Carmona-Galán Ricardo , Martínez-Carmona Juan F. , Rodríguez-Vázquez Ángel
Published: July 2012

Wireless sensor networks constitute a powerful technology particularly suitable for environmental monitoring. With regard to wildfires, they enable low-cost fine-grained surveillance of hazardous locations like wildland–urban interfaces. This paper presents work developed during the last 4 years targeting a vision-enabled wireless sensor network node for the reliable, early on-site detection of forest fires. The tasks carried out ranged from devising a robust vision algorithm for smoke detection to the design and physical implementation of a power-efficient smart imager tailored to the characteristics of such an algorithm. By integrating this smart imager with a commercial wireless platform, we endowed the resulting system with vision capabilities and radio communication. Numerous tests were arranged in different natural scenarios in order to progressively tune all the parameters involved in the autonomous operation of this prototype node. The last test carried out, involving the prescribed burning of a 95 × 20-m shrub plot, confirmed the high degree of reliability of our approach in terms of both successful early detection and a very low false-alarm rate.
Deletion of the
p27
Kip1
gene restores normal development in cyclin D1-deficient mice
Authors: Geng Yan , Yu Qunyan , Sicinska Ewa , Das Manjusri , Bronson Roderick T. , Sicinski Piotr
Published: July 2012

D-type cyclins (cyclins D1, D2, and D3) are key components of cell
cycle machinery in mammalian cells. These proteins are believed to
drive cell cycle progression by associating with their kinase partners,
cyclin-dependent kinases, and by directing phosphorylation of critical
cellular substrates. In addition, D-cyclins play a kinase-independent
role by sequestering cell cycle inhibitors p27
Kip1
and
p21
Cip1
. In the past, we and others generated cyclin
D1-deficient mice and have shown that these mice display developmental
abnormalities, hypoplastic retinas, and pregnancy-insensitive mammary
glands. To test the significance of cyclin D1–p27
Kip1
interaction within a living mouse, we crossed cyclin D1-deficient mice
with mice lacking p27
Kip1
, and we generated double-mutant
cyclin D1
−/−
p27
−/−
animals. Here we report
that ablation of
p27
Kip1
restores
essentially normal development in cyclin D1-deficient mice. Our results
provide genetic evidence that p27
Kip1
functions downstream
of cyclin D1.
Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naïve CD4+T cells
Authors: Ragazzo Jennifer L. , Ozaki Minette E. , Karlsson Lars , Peterson Per A. , Webb Susan R.
Published: July 2012

The mechanisms controlling induction of anergy at the level of naïve CD4+T cells are poorly understood but thought to reflect limited contact with costimulatory molecules during T cell antigen receptor (TCR) ligation. To clarify this question, naïve TCR transgenic CD4+cells were exposed to specific peptide presented by transfected antigen-presenting cells (APC) expressing MHC class II molecules with defined accessory molecules. Significantly, culturing CD4+cells with APC expressing MHC II plus peptide alone elicited early TCR signaling but failed to induce either proliferation or anergy. Culture with APC expressing MHC II plus B7 molecules led to strong proliferation and T cell priming but no anergy. In marked contrast, conspicuous induction of anergy occurred after T cell culture with APC expressing MHC class II and intercellular adhesion molecule-1 (ICAM-1). Thus, at the level of naïve CD4+cells, anergy induction appears to reflect selective contact with APC expressing ICAM-1 in the absence of B7.
A mouse model of familial porphyria cutanea tarda
Authors: Phillips John D. , Jackson Laurie K. , Bunting Michaeline , Franklin Michael R. , Thomas Kirk R. , Levy Joanne E. , Andrews Nancy C. , Kushner James P.
Published: July 2012

Approximately one-third of patients with porphyria cutanea tarda
(PCT), the most common porphyria in humans, inherit a single mutant
allele of the uroporphyrinogen decarboxylase (
URO-D
)
gene. PCT associated with
URO-D
mutations is designated
familial PCT. The phenotype is characterized by a photosensitive
dermatosis with hepatic accumulation and urinary excretion of
uroporphyrin and hepta-carboxylic porphyrins. Most heterozygotes for
URO-D
mutations do not express a porphyric phenotype
unless hepatic siderosis is present. Hemochromatosis gene
(
HFE
) mutations are frequently found when the phenotype
is expressed. We used homologous recombination to disrupt one allele of
murine
URO-D
.
URO-D
+/−
mice
had half-wild type (wt) URO-D protein and enzymatic activity in all
tissues but did not accumulate hepatic porphyrins, indicating that
half-normal URO-D activity is not rate limiting. When
URO-D
+/−
mice were injected with
iron-dextran and given drinking water containing δ-aminolevulinic
acid for 21 days, hepatic porphyrins accumulated, and hepatic URO-D
activity was reduced to 20% of wt. We bred mice homozygous for an
HFE
gene disruption
(
HFE
−/−
) to
URO-D
+/−
mice, generating mice with the
URO-D
+/−
/HFE
−/−
genotype. These animals developed a porphyric phenotype by 14 weeks of
age without ALA supplementation, and URO-D activity was reduced to 14%
of wt. These data indicate that iron overload alone is sufficient to
reduce URO-D activity to rate-limiting levels in
URO-D
+/−
mice. The
URO-D
+/−
mouse serves as an excellent model
of familial PCT and affords the opportunity to define the mechanism by
which iron influences URO-D activity.
Cerebellar neurons lacking complex gangliosides degenerate in the presence of depolarizing levels of potassium
Authors: Wu Gusheng , Xie Xin , Lu Zi-Hua , Ledeen Robert W.
Published: July 2012

Mice engineered to lack GM2/GD2 synthase (GalNAc-T), with resultant deficit of GM2, GD2, and all gangliotetraose gangliosides, were originally described as showing a relatively normal phenotype with only a slight reduction in nerve conduction. However, a subsequent study showed that similar animals suffer axonal degeneration, myelination defects, and impaired motor coordination. We have examined the behavior of cerebellar granule neurons from these neonatal knockouts in culture and have found evidence of impaired capacity for Ca2+regulation. These cells showed relatively normal behavior when grown in the presence of physiological or moderately elevated K+but gradually degenerated in the presence of high K+. This degeneration in depolarizing medium was accompanied by progressive elevation of intracellular calcium and onset of apoptosis, phenomena not observed with normal cells. No differences were detected in cells from normal vs. heterozygous mice. These findings suggest that neurons from GalNAc-T knockout mice are lacking a calcium regulatory mechanism that is modulated by one or more of the deleted gangliosides, and they support the hypothesis that maintenance of calcium homeostasis is one function of complex gangliosides during, and perhaps subsequent to, neuronal development.
Preferential potentiation of fast-releasing synaptic vesicles by cAMP at the calyx of Held
Authors: Sakaba Takeshi , Neher Erwin
Published: July 2012

We have studied the effects of cAMP on synaptic transmission at the
calyx of Held and found that forskolin (an activator of adenylate
cyclase) and 8-Br-cAMP (a membrane-permeable analog of cAMP)
potentiated excitatory postsynaptic currents (EPSCs). Direct sampling
of miniature EPSCs (mEPSCs) and nonstationary fluctuation analysis
showed that mEPSCs were not modulated by cAMP, suggesting that the
locus of modulation is presynaptic. Deconvolution was used to examine
effects of cAMP on quantal-release rates. By using this method, it was
shown recently that release probabilities of readily releasable
vesicles are heterogeneous. Here, we show that cAMP selectively
increases the number of vesicles with higher release probabilities,
whereas a slow component of the EPSC, representing vesicles that fuse
more slowly, is unchanged. cAMP increases the apparent Ca
2+
sensitivity for secretion, but this increase does not reflect an
increase in release probability necessarily but rather an increase in
the number of highly sensitive vesicles.
Three distinct types of GnRH receptor characterized in the bullfrog
Authors: Wang Li , Bogerd Jan , Choi Hueng S. , Seong Jae Y. , Soh Jae M. , Chun Sang Y. , Blomenröhr Marion , Troskie Brigitte E. , Millar Robert P. , Yu Wen H. , McCann Samuel M. , Kwon Hyuk B.
Published: July 2012

It has been proposed recently that two types of GnRH receptors
(GnRHR) exist in a particular species. Here we present data
demonstrating that at least three types of GnRHR are expressed in a
single diploid species, the bullfrog. Three different cDNAs, encoding
distinct types of bullfrog GnRHR (bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3),
were isolated from pituitary and hindbrain of the bullfrog. BfGnRHR-1
mRNA was expressed predominantly in pituitary, whereas bfGnRHR-2 and -3
mRNAs were expressed in brain. The bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3
proteins have an amino acid identity of ≈30% to ≈35% with
mammalian GnRHRs and ≈40% to ≈50% with nonmammalian GnRHRs.
Interestingly, bfGnRHR-2 has an 85% amino acid homology with
Xenopus
GnRHR. Less than 53% amino acid identity
was observed among the three bfGnRHRs. All isolated cDNAs encode
functional receptors because their transient expression in COS-7 cells
resulted in a ligand-dependent increase in inositol phosphate
production. Notably, all three receptors exhibited a differential
ligand selectivity. For all receptors, cGnRH-II has a higher potency
than mGnRH. In addition, salmon GnRH also has a strikingly high potency
to stimulate all three receptors. In conclusion, we demonstrated the
presence of three GnRHRs in the bullfrog. Their expression in pituitary
and brain suggests that bfGnRHRs play an important role in the
regulation of reproductive functions in the bullfrog.
Task complexity and interaction
Authors: Michel Marije C. , Kuiken Folkert , Vedder Ineke
Published: July 2012

This paper presents the overarching conclusions of three consecutive investigations into task-based L2 performance. It aims at giving a better understanding of how changes in the number of elements referred to in a task affect L2 production, and how this relates to cognitive task complexity. Furthermore, it evaluates differences between monologic and dialogic tasks, and searches for combined effects of the factors ‘± elements’ and ‘± monologic’. Analyses examined the oral task performances of 152 participants by using global measures of linguistic complexity, accuracy, and fluency as well as a task specific measure. Results revealed hardly any effects of the manipulation of the number of elements. Dialogic tasks, however, consistently guided L2 performers towards greater accuracy, lexical complexity, and fluency. The discussion compares these findings to native speaker baseline data, reviews the results in light of Robinson’s (2005) Cognition Hypothesis, and highlights the cognitive impact of the factor ‘± monologic’.
Collocations and semantic profiles
Authors: Stubbs Michael
Published: July 2012

Current work on lexical collocations uses two ideas: (i) words have distinctive semantic profiles or "prosodies"; and (ii) the strength of association between words can be measured in quantitative terms. These ideas can be combined to provide comparative semantic profiles of words, which show the frequent and characteristic collocates of node words, and make explicit the semantic relations between the collocates.
Using data from corpora of up to 120 million words, it is shown that the lemma CAUSE occurs in predominantly "unpleasant" collocations, such as cause of the trouble and cause of death. A case study of this lemma is used to illustrate quantitative methods for investigating collocations. Various methods proposed in the literature are of great practical value in establishing collocational sets, but their theoretical basis is less clear. Brief comparative semantic profiles are given for related lemmas, e.g. REASON and CONSEQUENCE. Implications for the relation between system and use are discussed.
Haskalah scientific knowledge in Hebrew garment
Authors: Kogman Tal
Published: July 2012

Scientific texts for Jewish children and youth were produced within the German-Jewish culture from the end of the 18th century and throughout the 19th century. The intention was to fill in the gap in the Judaic literature in Hebrew vis-à-vis the German-Christian literary and educational systems as part of modernization processes. Two case studies of German-Hebrew scientific translations (in natural history and astronomy) are described in an attempt to illustrate the strategies applied by the Jewish translators, which in their turn reﬂect the cultural constraints they faced and the creative ways they chose to deal with them, taking into account the models already available to the target system and the types of target audience the translated texts were intended for.
Resonant tunnelling diodes based on graphene/h-BN heterostructure
Authors: Nguyen V Hung , Mazzamuto F , Bournel A , Dollfus P
Published: July 2012

In this work, we propose a resonant tunnelling diode (RTD) based on a double-barrier graphene/boron nitride (BN) heterostructure as a device suitable to take advantage of the elaboration of atomic sheets containing different domains of BN and C phases within a hexagonal lattice. The device operation and performance are investigated by means of a self-consistent solution within the non-equilibrium Green's function formalism on a tight-binding Hamiltonian. This RTD exhibits a negative differential conductance effect, which involves the resonant tunnelling through both the electron and hole bound states in the graphene quantum well. It is shown that the peak-to-valley ratio reaches a value of ∼4 at room temperature even for zero bandgap and can be higher than 10 when a finite gap opens in the graphene channel.
Effect of nanoparticles on an rf discharge afterglow
Authors: Schweigert I V , Alexandrov A L
Published: July 2012

The influence of nanoparticles on a discharge plasma afterglow in argon is studied using particle-in-cell Monte Carlo collision simulations. The anomalous electron density increase observed in the experiment (Berndt et al 2006 Plasma Sources Sci. Technol.
15 18) is analysed on the basis of the electron and ion distribution functions. It is shown that the departure of fast electrons to the electrodes in the early afterglow is responsible for the rapid increase in the electron density. When the fast electrons escape from the discharge volume, the balance of the electron and ion currents on the dust surface is disturbed, and the magnitude of the dust floating potential drops. The electrons released from the dust surface contribute to the anomalous growth of the electron density. The additional production of electrons due to metastable–metastable ionization enhances the effect of electron density increase provided by dust discharging.
Twisted geometric Satake equivalence via gerbes on the factorizable grassmannian
Authors: Reich Ryan
Published: August 2012

The geometric Satake equivalence of Ginzburg and Mirković- Vilonen, for a complex reductive group

G
G

, is a realization of the tensor category of representations of its Langlands dual group

L

G

{}^L G

as a category of “spherical” perverse sheaves on the affine grassmannian
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper G r Subscript upper G Baseline equals upper G left-parenthesis double-struck upper C left-parenthesis left-parenthesis t right-parenthesis right-parenthesis slash upper G left-parenthesis double-struck upper C left-bracket left-bracket t right-bracket right-bracket right-parenthesis">

Gr
G

=
G
(

C

(

(
t
)

)

/

G
(

C

[

[
t
]

]
)

\operatorname {Gr}_G = G(\mathbb {C}(\mspace {-3.5mu}(t)\mspace {-3.5mu})/G(\mathbb {C}[\mspace {-2mu}[t]\mspace {-2mu}])

. Since its original statement it has been generalized in two directions: first, by Gaitsgory, to the Beilinson–Drinfeld or factorizable grassmannian, which for a smooth complex curve

X
X

is a collection of spaces over the powers

X
n

X^n

whose general fiber is isomorphic to

Gr
G
n

\operatorname {Gr}_G^n

but with the factors “fusing” as they approach points with equal coordinates, allowing a more natural description of the structures and properties even of the Mirković–Vilonen equivalence. The second generalization, due recently to Finkelberg–Lysenko, considers perverse sheaves twisted in a suitable sense by a root of unity, and obtains the category of representations of a group other than the Langlands dual. This latter result can be considered as part of “Langlands duality for quantum groups”.

In this work we obtain a result simultaneously generalizing all of the above. We consider the general notion of twisting by a gerbe and define the natural class of “factorizable” gerbes by which one can twist in the context of the Satake equivalence. These gerbes are almost entirely described by the quadratic forms on the weight lattice of

G
G

. We show that a suitable formalism exists such that the methods of Mirković–Vilonen can be applied directly in this general context virtually without change and obtain a Satake equivalence for twisted perverse sheaves. In addition, we present new proofs of the properties of their structure as an abelian tensor category.
Management of the Febrile Child
Authors: Glew Simon , Finch Joanna
Published: August 2012

Between 20% and 40% of young children suffer a feverish illness each year and many of these will present to their general practitioner. Although the majority of these children have benign, self-limiting illness, infection remains the leading cause of death in children under the age of 5 years. Appropriate assessment, management and referral of the febrile child are important skills to acquire for doctors working in primary care. This article outlines the signs and symptoms of serious infective illness in children under 5 years of age and describes current National Institute for Health and Clinical Excellence (NICE) guidelines for feverish illness in children and the use of the ‘traffic-light’ risk score in the context of face-to-face and remote assessment.
Design of a Novel Antimicrobial Peptide Activated by Virulent Proteases
Authors: Aoki Wataru , Kitahara Nao , Miura Natsuko , Morisaka Hironobu , Kuroda Kouichi , Ueda Mitsuyoshi
Published: August 2012

Antimicrobial peptides are promising antibiotics as they possess strong antimicrobial activity and very broad spectra of activity. However, administration of an antibiotic with a very broad spectrum of activity disrupts normal microflora and increases the risks of other fatal infections. To solve the problem, we designed a novel antimicrobial peptide that is activated by virulent proteases of pathogenic organisms. We constructed a peptide composed of three domains, namely an antimicrobial peptide (lactoferricin) as the active center, a protective peptide (magainin intervening sequence) that suppresses antimicrobial activity, and a specific linker that joins these two components and is efficiently cleaved by virulent proteases. We utilized Candida albicans as a model organism that produces secreted aspartic proteases as a virulence attribute. We screened for a peptide sequence efficiently cleaved by secreted aspartic proteases isozymes and identified a GFIKAFPK peptide as the most favorable substrate. Subsequently, we chemically synthesized a peptide containing the GFIKAFPK sequence. The designed peptide possessed no antimicrobial activity until it was activated by secreted aspartic proteases isozymes. Furthermore, it demonstrated selective antimicrobial activity against C. albicans, but not against Saccharomyces cerevisiae. A designed peptide like the one described in this study may protect normal microflora, resulting in enhanced safety as a therapeutic.
Individual cow's milk allergens as prognostic markers for tolerance development?
Authors: Ahrens B. , Lopes de Oliveira L. C. , Grabenhenrich L. , Schulz G. , Niggemann B. , Wahn U. , Beyer K.
Published: August 2012

Background

Cow's milk allergy (CMA) is one of the most common causes of food allergy in the first years of life. Fortunately, the majority of children with CMA develop clinical tolerance with time. However, no good individual markers exist to predict whether this will occur. Therefore, a prognosis to identify children with persistent CMA at diagnosis would be helpful.

Objective

In this study, we sought to assess whether measurement of IgE to individual allergens of cow's milk (CM) would separate patients with persistent CMA from those who became clinically tolerant to CM over time.

Methods

A total of 52 patients ranging from 3 months to 114 months of age with proven CMA by DBPCFC were followed over time. From these 52 patients, 32 (61.5%) patients became tolerant in the analysed time period. All patients were rechallenged at least once, some were rechallenged two or three times. Serum was analysed prior to each challenge for specific IgE, IgG and IgG4 binding to crude CM protein as well as to individual allergens of CM.

Results

The individual likelihood of outgrowing CMA significantly correlates with a low level of CM‐specific IgE as well as a low level of specific IgE to α‐lactalbumin, β‐lactoglobulin (Bos d5.0102), κ‐casein and αs1‐casein. No significant correlation was found for IgE levels to total casein, lactoferrin, β‐casein and β‐lactoglobulin (Bos d5.0101) as well as IgG and IgG4 levels to α‐lactalbumin, β‐lactoglobulin and total casein.

Conclusions

CM‐specific IgE is a good prognostic marker for persistence of CMA. In addition, component‐resolved diagnostic showed similar results. However, in our view, the rising laboratory costs do not justify a measurement on a daily basis. Additional determination of specific IgG or IgG4 levels was not useful in predicting tolerance development in our study population.
Ligand activation of peroxisome proliferator‐activated receptor delta suppresses cathepsin B expression in human endothelial cells in a posttranslational manner
Authors: Reichenbach Gabi , Starzinski‐Powitz Anna , Doll Monika , Hrgovic Igor , Maria Valesky Eva , Kippenberger Stefan , Bernd August , Kaufmann Roland , Meissner Markus
Published: July 2012

Peroxisome proliferator‐activated receptor (PPAR) delta agonists are known to have distinct anti‐inflammatory and antitumor effects; though, the knowledge regarding their mode of action has thus far been limited. Different cathepsins have been shown to be upregulated in a broad range of pathological events, such as rheumatoid arthritis, psoriasis, atherosclerosis and diverse tumor entities, for example melanoma. Recent work demonstrated that cathepsin B in particular is an important pro‐angiogenic protease in various pathological conditions. We therefore analysed whether cathepsins are a valid target for PPARδ agonists. This study reveals an inhibitory effect of two commonly used PPARδ agonists, GW501516 and L‐165,041, on the protein expression and enzyme activity of cathepsin B in human endothelial cells. In contrast, no inhibitory effects were observed on cathepsin L and cathepsin D protein expression after treatment with PPARδ agonists. Furthermore, the results substantiate that PPARδ activators mediate their inhibitory action in a PPARδ‐dependent manner and that the underlying regulatory mechanism is not based on a transcriptional but rather on a posttranslational mode of action, via the reduction in the cathepsin B protein half‐life. Mechanisms conveying the suppressive effect by 5′‐alternative splicing, a 3′‐UTR‐dependent way or by miRNA could be excluded. The data of this study explore cathepsin B as a new valid target for PPARδ agonists in endothelial cells. The results bolster other studies demonstrating PPARδ agonists as anti‐inflammatory and anticarcinogenic agents and thus might have the potential to help to develop new pharmaceutical drugs.
Comparison of transcript profiles in different life stages of the nematode Globodera pallida under different host potato genotypes
Authors: Palomares‐Rius Juan E. , Hedley Pete E. , Cock Peter J. A. , Morris Jenny A. , Jones John T. , Vovlas Nikos , Blok Vivian
Published: August 2012

The potato cyst nematodes (PCNs) Globodera pallida and Globodera rostochiensis are important parasites of potato. PCNs undergo complex biotrophic interactions with their hosts that involve gene expression changes in both the nematode and the host plant. The aim of this study was to determine key genes that are differentially expressed in Globodera pallida life cycle stages and during the initiation of the feeding site in susceptible and partially resistant potato genotypes. For this purpose, two microarray experiments were designed: (i) a comparison of eggs, infective second‐stage juveniles (J2s) and sedentary parasitic‐stage J2s (SJ2); (ii) a comparison of SJ2s at 8 days after inoculation (DAI) in the susceptible cultivar (Desirée) and two partially resistant lines. The results showed differential expression of G. pallida genes during the stages studied, including previously characterized effectors. In addition, a large number of genes changed their expression between SJ2s in the susceptible cultivar and those infecting partially resistant lines; the number of genes with modified expression was lower when the two partially resistant lines were compared. Moreover, a histopathological study was performed at several time points (7, 14 and 30 DAI) and showed the similarities between both partially resistant lines with a delay and degeneration in the formation of the syncytia in comparison with the susceptible cultivar. Females at 30 DAI in partially resistant lines showed a delay in their development in comparison with those in the susceptible cultivar.
US Hemophilia Treatment Center population trends 1990–2010: patient diagnoses, demographics, health services utilization
Authors: Baker J. R. , Riske B. , Drake J. H. , Forsberg A. D. , Atwood R. , Voutsis M. , Shearer R.
Published: July 2012

For several decades, US government agencies have partially supported regional networks of Hemophilia Treatment Centers (HTC). HTC multidisciplinary teams provide comprehensive and coordinated diagnosis, treatment, prevention, education, outreach and surveillance services to improve the health of people with genetic bleeding disorders. However, national data are scarce on HTC‐patient population trends and services. The aim of the study was to examine national trends over the past 20 years in patient diagnoses, demographics and health services utilization among the Health Resources and Services Administration (HRSA) and Centers for Disease Control and Prevention (CDC)‐supported HTC network. Diagnoses, demographics and health services utilization data from 1990 to 2010 were aggregated from all HTCs using the Hemophilia Data Set (HDS). From 1990 to 2010, the HTC population grew 90% from 17 177 to 32 612. HTC patients with von Willebrand's disease increased by 148%, females by 346%, Hispanic patients by 236% and African Americans by 104%. Four thousand and seventy‐five deaths were reported. From 2002 to 2010, annual comprehensive evaluations grew 38%, and persons with severe haemophilia on a home intravenous therapy programme rose 37%. In 2010, 46% of patients were less than 18 years vs. 24% for the general US population. The Hemophilia Data Set documents the growth and diversity of the US Hemophilia Treatment Center Network's patient population and services. Despite disproportionate deaths due to HIV, the HTC patient base grew faster than the general US population. The HDS is a vital national public health registry for this rare‐disorder population.
Management of factor VII‐deficient patients undergoing joint surgeries – preliminary results of locally developed treatment regimen
Authors: Windyga J. , Zbikowski P. , Ambroziak P. , Baran B. , Kotela I. , Stefanska‐Windyga E.
Published: July 2012

Inherited factor VII (FVII) deficiency is a rare coagulation disorder with variable haemorrhagic manifestations. In severely affected cases spontaneous haemarthroses leading to advanced arthropathy have been observed. Such cases may require surgery. Therapeutic options for bleeding prevention in FVII deficient patients undergoing surgery comprise various FVII preparations but the use of recombinant activated factor VII (rFVIIa) seems to be the treatment of choice. To present the outcome of orthopaedic surgery under haemostatic coverage of rFVIIa administered according to the locally established treatment regimen in five adult patients with FVII baseline plasma levels below 10 IU dL−1. Two patients required total hip replacement (THR); three had various arthroscopic procedures. Recombinant activated factor VII was administered every 8 h on day of surgery (D0) followed by every 12–24 h for the subsequent 9–14 days, depending on the type of surgery. Factor VII plasma coagulation activity (FVII:C) was determined daily with no predefined therapeutic target levels. Doses of rFVIIa on D0 ranged from 18 to 37 μg kg−1 b.w. and on the subsequent days – from 13 to 30 μg kg−1 b.w. Total rFVIIa dose per procedure ranged from 16 to 37.5 mg, and the total number of doses per procedure was 16–31. None of our patients developed excessive bleeding including those in whom FVII:C trough levels returned nearly to the baseline level on the first post‐op day. Preliminary results demonstrate that rFVIIa administered according to our treatment regimen is an effective and safe haemostatic agent for hypoproconvertinaemia patients undergoing orthopaedic surgery.
New genotypes of table olives: profile of bioactive compounds
Authors: Medina Eduardo , Morales‐Sillero Ana , Ramírez Eva Mª , Rallo Pilar , Brenes Manuel , Romero Concepción
Published: August 2012

New table olive genotypes (48) coming from a cross‐breeding programme were evaluated. Most of the fruit traits covered a wide range of variability on the set of genotypes, fruit weight (1.1–9.7 g), pulp‐to‐pit ratio (1.7–10.0), fruit shape (1.0–1.6) and oil content (1.3–15.2%). This is the first time that healthy compounds such as triterpenic acids and phenolic compounds have also been evaluated in olive progenies. Genotypes were stored for 2 months in sterilised brine (5% NaCl and 0.5% acetic acid). A high amount of maslinic (685.0–1394.2 mg kg−1 olive flesh) and oleanolic acids (275.3–817.9 mg kg−1 olive flesh) was found in the flesh of olives stored. The main oleosidic and phenolic compounds evaluated in brines were hydroxytyrosol (1.9–8.4 mmol L−1), hydroxytyrosol glucosides (0.4–19.8 mmol L−1), oleuropein (0.0–4.7 mmol L−1) and the antimicrobial compounds, dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol (0.0–3.4 mmol L−1) and decarboxymethyl elenolic acid (0.0–1.7 mmol L−1), the latter two being observed in only ten genotypes. The wide range of variation observed for most compounds indicates that the contents of these healthy compounds may be used as selection criteria in table olive breeding programmes.
Use of HS‐SPME‐GC‐MS for the classification of Italian lemon, orange and citrus spp. honeys
Authors: Papotti Giulia , Bertelli Davide , Plessi Maria
Published: August 2012

Volatile compounds from 90 Italian citrus honeys of different varieties (lemon, Citrus limon (L.) Burm., orange, Citrus sinensis (L.) Osbeck, and citrus, Citrus spp.), 30 provided by CRA‐API (Consiglio per la Ricerca e la Sperimentazione in Agricoltura‐Unità di ricerca di apicoltura e bachicoltura) (Bologna, Italy) and 60 purchased on the markets, were analysed to classify them according to the characteristic aroma profiles. A HS‐SPME‐GC method previously developed and validated was applied. Factor analysis and general discriminant analysis (GDA) were carried out on peaks and intensity data. Statistical analyses revealed a good separation between samples; the best model based on peaks data shows 66.5% and 33.5% of total variance explained by the first and the second canonical functions and a predictive capacity of 78.9%. Regarding the intensity data, the CFs of the GDA model explain 53.8% and 46.2% of the total variance and the crossvalidation shows a predictive capacity of 96.7%.
Effect of y‐radiation on chives safety and quality
Authors: Junqueira‐Gonçalves Maria Paula , Zuñiga Gustavo E. , Zárate Herman , Arcos Karina , Ganga Angélica , Miltz Joseph
Published: August 2012

The effect of γ‐irradiation on the quality of chives was evaluated. The samples were irradiated at 1.0 and 2.0 kGy, stored at 4 °C for 10 days and used for microbiological (aerobic mesophilic, moulds and yeasts, E. coli and Salmonella sp), biochemical (vitamin C and lipoperoxide (MDA) contents and superoxide dismutase (SOD) and guaiacol peroxidase (POX) activity) and sensorial evaluation. For irradiated samples, the total counts of aerobic mesophilic and moulds and yeasts showed a reduction of 6 log cycles during storage, and colour analysis showed no significant difference (P > 0.05) for the b*‐value. The contents of vitamin C were not significantly affected by irradiation and storage time. The MDA contents and SOD activity changed insignificantly at both γ‐irradiation levels after storage, while POX was significantly increased (P ≤ 0.05) at 1 kGy. Samples irradiated at 2.0 kGy presented sensorial acceptance after the storage. These results show that γ‐irradiation increases the shelf life of chives without significant changes in their quality.
A practical educational tool for teaching child‐care hospital professionals attending evidence‐based practice courses for continuing medical education to appraise internal validity in systematic reviews
Authors: Rosati Paola , Porzsolt Franz
Published: July 2012

Rationale, aims and objectives

Having a quick, practical, educational tool designed for busy child‐care professionals to check whether systematic reviews (SRs) contain valid information would help them regularly update their evidence‐based knowledge and apply it to their patients. Continuing our annual workshop courses encouraging paediatric hospital professionals to use evidence‐based information, in a preliminary study, we compared the commonly used Critical Appraisal Skill Programme (CASP) questionnaire for appraising overall internal validity in SRs with a new, practical tool designed to check internal validity quickly.

Method

During a course in 2010, two ‘teacher‐brokers’ taught experienced paediatric hospital professionals to use and compare the CASP and the new practical tool to appraise a Cochrane SR on beclomethasone for asthma in children by assessing internal validity only from the two most weighted randomized controlled trials in the forest plot. At 15 days and 6 months, participants then answered questionnaires designed to assess qualitative data including feelings about working together, memorization and possibly provide feedback for Cochrane reviewers.

Results

Using the CASP, participants agreed that the Cochrane SR analysed contained overall valid results. Conversely, using the new quick tool, they found poor internal validity. Participants worked well together in a group, took less time to apply the new tool than the CASP (1 vs. 2.5 hours) and provided Cochrane feedback.

Conclusions

Our quick practical tool for teaching critical appraisal encourages busy child‐care hospital professionals to work together, carefully check validity in SRs, apply the findings in clinical practice and provide useful feedback for Cochrane reviewers.
Methods for the bias adjustment of meta‐analyses of published observational studies
Authors: Doi Suhail A. R. , Barendregt Jan J. , Onitilo Adedayo A.
Published: July 2012

Background

A unique challenge in meta‐analysis of observational studies is bias adjustment. Two different approaches have been proposed for doing this – using summary scores versus component scores. The prevailing view on this matter is that summary quality scores are inaccurate because information from its components can cancel each other out.

Methods

A head‐to‐head comparison of the component score adjustment with our method using summary scores is undertaken, using data reported by the authors of the component method.

Results

It is demonstrated that the consideration of components or of aggregate scores does indeed lead to the same conclusions. Yet, the latter does not require imputation of the direction and magnitude of changes to effect sizes.

Conclusions

The summary quality score used for bias adjustment within the context of an appropriate model may be most expedient. Implications for the bias adjustment of meta‐analyses of observational studies are discussed.
Control beliefs are related to smoking prevention in prenatal care
Authors: Lemola Sakari , Meyer‐Leu Yvonne , Samochowiec Jakub , Grob Alexander
Published: July 2012

Background

Smoking during pregnancy is one of the most important avoidable health risks for the unborn child. Gynaecologists and midwives play a fundamental role in the prevention of smoking during pregnancy. However, a large number of health care practitioners still do not address smoking in pregnant patients.

Objectives

We examined whether gynaecologists and midwives engage in screening and counselling of pregnant women and conducting interventions to prevent smoking during pregnancy. Further, we examined the role of gynaecologists’ and midwives’ control beliefs. Control beliefs involve efficacy expectations – the practitioner's confidence in his capacity to conduct prevention efforts adequately – and outcome expectations – the practitioner's expectation that such prevention efforts are successful in general.

Methods

A total of 486 gynaecologists and 366 midwives completed a questionnaire on screening of smoking, counselling and other interventions they conduct to prevent smoking during pregnancy. Moreover, gynaecologists and midwives rated their control beliefs regarding their influence on pregnant patients’ smoking habits.

Results

The majority of gynaecologists and midwives reported screening all pregnant patients regarding smoking, explaining the risks and recommending smoking cessation. By contrast, only a minority engages in more extensive prevention efforts. Strong control beliefs were predictive of a higher likelihood of screening and counselling, as well as of engaging in more extensive interventions.

Conclusions

The findings point to the importance of strengthening gynaecologists’ and midwives’ control beliefs by professional education and training on smoking prevention.