bluuebunny/crossref_metadata_2025 huggingface dataset:
Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding
Authors: Kaneko Kenichi , Chuang Victor Tuan Giam , Minomo Ai , Yamasaki Keishi , Bhagavan Nadhipuram V. , Maruyama Toru , Otagiri Masaki
Published: April 2011

Fatty acids are endogenous ligands of human serum albumin (HSA) that induce conformational changes and participate in allosteric ligand binding to HSA. In a previous study, we showed that, when myristate (MYR) is present, the binding of [14C]ketoprofen (KP) to subdomain IA of HSA was increased, indicating that, when MYR binds to HSA, a new binding site in formed in that region. Meanwhile, an N‐B transition has been reported to increase the binding of ligands at alkaline pH when the status of albumin is the B‐conformer. Six histidine single mutants of HSA, H9A, H39A, H67A, H105A, H128A and H146A were produced and photolabeled with [14C]KP at pH 6.5, 7.4 and 8.2 and the role of each histidine in causing the N‐B transition induced allosteric ligand binding was examined. Cyanogen bromide cleavage of the photolabeled native HSA showed that subdomain IA was the site of the allosteric binding of KP at pH 8.2. From the photolabeling results, H146 was found to play a prominent role whilst H128 played little or no role in the allosteric binding. However, the remaining 4 mutants did not show a clear photolabeling pattern that was similar to either native HSA or H146A and, as a result, no firm conclusions can be made. An additional histidine mutant, H146I, was produced to confirm the results for H146A. A similar experiment using H146I showed that a benzene ring‐like structure at position 146 is required for the allosteric ligand binding to occur. © 2011 IUBMB IUBMB Life, 63(4): 277–285, 2011
Calculation of binding free energies of inhibitors to plasmepsin II
Authors: Steiner Denise , Oostenbrink Chris , Diederich François , Zürcher Martina , van Gunsteren Wilfred F.
Published: April 2011

An understanding at the atomic level of the driving forces of inhibitor binding to the protein plasmepsin (PM) II would be of interest to the development of drugs against malaria. To this end, three state of the art computational techniques to compute relative free energies—thermodynamic integration (TI), Hamiltonian replica‐exchange (H‐RE) TI, and comparison of bound versus unbound ligand energy and entropy—were applied to a protein‐ligand system of PM II and several exo‐3‐amino‐7‐azabicyclo[2.2.1]heptanes and the resulting relative free energies were compared with values derived from experimental IC50 values. For this large and flexible protein‐ligand system, the simulations could not properly sample the relevant parts of the conformational space of the bound ligand, resulting in failure to reproduce the experimental data. Yet, the use of Hamiltonian replica exchange in conjunction with thermodynamic integration resulted in enhanced convergence and computational efficiency compared to standard thermodynamic integration calculations. The more approximate method of calculating only energetic and entropic contributions of the ligand in its bound and unbound states from conventional molecular dynamics (MD) simulations reproduced the major trends in the experimental binding free energies, which could be rationalized in terms of energetic and entropic characteristics of the different structural and physico‐chemical properties of the protein and ligands. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Supercritical water oxidation of flammable industrial wastewaters: economic perspectives of an industrial plant
Authors: Vadillo Violeta , García‐Jarana M. Belén , Sánchez‐Oneto Jezabel , Portela Juan Ramón , de la Ossa Enrique J. Martínez
Published: April 2011

BACKGROUND: Supercritical water oxidation (SCWO) is a promising technology that respects the environment, destroys wastes and allows energy recovery. This process has been applied to many model compounds and real wastewaters at laboratory scale. However, SCWO treatments at pilot plant scale of real wastewaters are scarce. The application of this technology to industrial wastewaters has drawbacks such as corrosion, salt deposition and high cost, so industrial scale‐up has been delayed.

RESULTS: In a first stage, for safety reasons the feasibility of SCWO applied to flammable industrial wastewaters was evaluated at laboratory scale in an isothermal plug flow reactor with low concentrations (3–10 g COD L−1), at a constant pressure of 250 bar and at different temperatures in the range 350–500 °C. In a second stage, experiments were conducted with much higher concentrations (20–90 g COD L−1) in a SCWO reactor at pilot plant scale. Experiments at pilot plant scale demonstrated the possibility of working under autothermal conditions and the results were used to estimate the treatment costs for a SCWO plant with a capacity of 1 m3 h−1.

CONCLUSION: Results demonstrated the technical feasibility of using a SCWO process to treat flammable industrial wastewater at pilot plant scale due to the absence of operational drawbacks related to the flammability of this wastewater, such as plugging, pressurization or preheating problems and uncontrolled reactions (explosion, etc.). The economic feasibility was demonstrated, especially bearing in mind the energy recovery optimization. Copyright © 2011 Society of Chemical Industry
Development of histamine‐immunoreactivity in the Central nervous system of the two locust species Schistocerca gregaria and Locusta migratoria
Authors: PÄtschke Arne , Bicker Gerd
Published: April 2011

Locusts are attractive model preparations for cellular investigations of neurodevelopment. In this study, we investigate the immunocytochemical localization of histamine in the developing ventral nerve cord of two locust species, Schistocerca gregaria and Locusta migratoria. Histamine is the fast neurotransmitter of photoreceptor neurons in the compound eye of insects, but it is also synthesized in interneurons of the central nervous system. In the locust ventral nerve cord, the pattern of histamine‐immunoreactive neurons follows a relatively simple bauplan. The histaminergic system comprises a set of single, ascending projection neurons that are segmentally arranged in almost every neuromere. The neurons send out their axons anteriorly, forming branches and varicosities throughout the adjacent ganglia. In the suboesophageal ganglion, the cell bodies lie in a posteriolateral position. The prothoracic ganglion lacks histaminergic neurons. In the posterior ganglia of the ventral nerve cord, the somata of the histaminergic neurons are ventromedially positioned. Histamine‐immunoreactivity starts around 50% of embryonic development in interneurons of the brain. Subsequently, the neurons of the more posterior ganglia of the ventral nerve cord become immunoreactive. From 60% embryonic development, the pattern of soma staining in the nerve cord appears mature. Around 65% of embryonic development, the photoreceptor cells show histamine‐immunoreactivity. The histaminergic innervation of the neuropile develops from the central branches toward the periphery of the ganglia and is completed right before hatching. Microsc. Res. Tech. 2011. © 2011 Wiley‐Liss, Inc.
An efficient one‐pot synthesis of bis‐indolylmethanes containing pyrazolyl catalyzed by Brønsted acidic ionic liquid under solvent‐free conditions
Authors: Liu Chenjiang , Yu Chuanji
Published: April 2011

Brønsted acidic ionic liquid [PyNCH2CO2H][HSO4] was found to be an effective catalyst for the condensation reactions of indoles with various 4‐formylpyrazoles to afford the corresponding bis‐indolylmethanes containing pyrazole under solvent‐free conditions. The satisfactory results were obtained with excellent yields, short reaction time, and simplicity in the experimental procedure. J. Heterocyclic Chem., (2011).
Ontogenetic relationships between cranium and mandible in coyotes and hyenas
Authors: La Croix Suzanne , Holekamp Kay E. , Shivik John A. , Lundrigan Barbara L. , Zelditch Miriam Leah
Published: April 2011

Developing animals must resolve the conflicting demands of survival and growth, ensuring that they can function as infants or juveniles while developing toward their adult form. In the case of the mammalian skull, the cranium and mandible must maintain functional integrity to meet the feeding needs of a juvenile even as the relationship between parts must change to meet the demands imposed on adults. We examine growth and development of the cranium and mandible, using a unique ontogenetic series of known‐age coyotes (Canis latrans), analyzing ontogenetic changes in the shapes of each part, and the relationship between them, relative to key life‐history events. Both cranial and mandibular development conform to general mammalian patterns, but each also exhibits temporally and spatially localized maturational transformations, yielding a complex relationship between growth and development of each part as well as complex patterns of synchronous growth and asynchronous development between parts. One major difference between cranium and mandible is that the cranium changes dramatically in both size and shape over ontogeny, whereas the mandible undergoes only modest shape change. Cranium and mandible are synchronous in growth, reaching adult size at the same life‐history stage; growth and development are synchronous for the cranium but not for the mandible. This synchrony of growth between cranium and mandible, and asynchrony of mandibular development, is also characteristic of a highly specialized carnivore, the spotted hyena (Crocuta crocuta), but coyotes have a much less protracted development, being handicapped relative to adults for a much shorter time. Morphological development does not predict life‐history events in these two carnivores, which is contrary to what has been reported for two rodent species. The changes seen in skull shape in successive life‐history stages suggest that adult functional demands cannot be satisfied by the morphology characterizing earlier life‐history stages. J. Morphol. 2011. © 2011 Wiley‐Liss, Inc.
Mitochondrial dysfunction and nicotinamide dinucleotide catabolism as mechanisms of cell death and promising targets for neuroprotection
Authors: Kristian Tibor , Balan Irina , Schuh Rosemary , Onken Mitch
Published: April 2011

Both acute and chronic neurodegenerative diseases are frequently associated with mitochondrial dysfunction as an essential component of mechanisms leading to brain damage. Although loss of mitochondrial functions resulting from prolonged activation of the mitochondrial permeability transition (MPT) pore has been shown to play a significant role in perturbation of cellular bioenergetics and in cell death, the detailed mechanisms are still elusive. Enzymatic reactions linked to glycolysis, the tricarboxylic acid cycle, and mitochondrial respiration are dependent on the reduced or oxidized form of nicotinamide dinucleotide [NAD(H)] as a cofactor. Loss of mitochondrial NAD+ resulting from MPT pore opening, although transient, allows detrimental depletion of mitochondrial and cellular NAD+ pools by activated NAD+ glycohydrolases. Poly(ADP‐ribose) polymerase (PARP) is considered to be a major NAD+ degrading enzyme, particularly under conditions of extensive DNA damage. We propose that CD38, a main cellular NAD+ level regulator, can significantly contribute to NAD+ catabolism. We discuss NAD+ catabolic and NAD+ synthesis pathways and their role in different strategies to prevent cellular NAD+ degradation in brain, particularly following an ischemic insult. These therapeutic approaches are based on utilizing endogenous intermediates of NAD+ metabolism that feed into the NAD+ salvage pathway and also inhibit CD38 activity. © 2011 Wiley‐Liss, Inc.
Quantitative RT‐PCR and immunoblot analyses reveal acclimated A2 noradrenergic neuron substrate fuel transporter, glucokinase, phospho‐AMPK, and dopamine‐β‐hydroxylase responses to hypoglycemia
Authors: Cherian Ajeesh Koshy , Briski Karen P.
Published: April 2011

Cellular metabolic stasis is monitored in discrete brain sites, including the dorsal vagal complex (DVC), where A2 noradrenergic neurons perform this sensory function. Single‐cell qPCR and high‐sensitivity immunoblotting were used to determine if A2 neurons adapt to chronic hypoglycemia by increasing substrate fuel transporter expression, and whether such adjustments coincide with decreased cellular energy instability during this systemic metabolic stress. Tyrosine hydroxylase‐immunolabeled neurons were laser‐microdissected from the caudal DVC 2 hr after single or serial neutral protamine Hagedorn insulin (NPH) dosing. Preceding hypoglycemia suppressed basal A2 MCT2, GLUT3, and GLUT4 profiles and diminished MCT2, GLUT4, and glucokinase responses to recurring hypoglycemia. Acute NPH caused a robust increase in A2 phospho‐AMPK protein levels; baseline phospho‐AMPK expression was elevated after 3 days of insulin treatment but only slight augmented after a fourth NPH injection. Transcripts encoding the catecholamine biosynthetic enzyme dopamine‐β‐hydroxylase were unaffected by acute NPH but were diminished by serial insulin dosing. This evidence for diminished basal A2 glucose and lactate uptake and attenuated phosopho‐AMPK‐mediated detection of hypoglycemia‐associated energy deficits suggests that these cells acclimate to chronic hypoglycemia by adopting a new metabolic steady state characterized by energy paucity and reduced sensitivity to hypoglycemia. Because dopamine‐β‐hydroxylase mRNA was reduced after serial, but not single NPH dosing, A2 neurotransmitter biosynthesis may be impervious to acute hypoglycemia but inhibited when posthypoglycemic metabolic deficiency is exacerbated by recurring hypoglycemia. This research suggests that chronic hypoglycemia‐associated adjustments in A2‐sensory neurotransmission may reflect cellular energetic debilitation rather than adaptive attenuation of cellular metabolic imbalance. © 2011 Wiley‐Liss, Inc.
Intraneuronal amyloid β oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo
Authors: Umeda Tomohiro , Tomiyama Takami , Sakama Naomi , Tanaka Saya , Lambert Mary P. , Klein William L. , Mori Hiroshi
Published: April 2011

Intraneuronal accumulation of amyloid β (Aβ) is an early pathological change in Alzheimer's disease. Previously, we showed that the E693Δ mutation (referred to as the “Osaka” mutation) of amyloid precursor protein (APP) caused intracellular accumulation of Aβ oligomers and apoptosis in transfected COS‐7 cells. We also showed that transgenic mice expressing APPE693Δ (APPOSK) displayed both an age‐dependent accumulation of intraneuronal Aβ oligomers from 8 months of age and apparent neuronal loss in the hippocampus at 24 months of age. These findings indicate that intraneuronal Aβ oligomers cause cell death, but the mechanism of this process remains unclear. Accordingly, here we investigated the subcellular localization and toxicity of intraneuronal Aβ oligomers in APPOSK‐transgenic mice. We found Aβ oligomer accumulation in the endoplasmic reticulum (ER), endosomes/lysosomes, and mitochondria in hippocampal neurons of 22‐month‐old mice. We also detected up‐regulation of Grp78 and HRD1 (an E3 ubiquitin ligase), leakage of cathepsin D from endosomes/lysosomes into cytoplasm, cytochrome c release from mitochondria, and activation of caspase‐3 in the hippocampi of 18‐month‐old mice. Collectively, our findings suggest that intraneuronal Aβ oligomers cause cell death by inducing ER stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo. © 2011 Wiley‐Liss, Inc.
Mechanical loading affects the energy metabolism of intervertebral disc cells
Authors: Fernando Hanan N. , Czamanski Jessica , Yuan Tai‐Yi , Gu Weiyong , Salahadin Abdi , Huang Chun‐Yuh Charles
Published: April 2011

Research has shown that mechanical loading affects matrix biosynthesis of intervertebral disc (IVD) cells; however, the pathway(s) to this effect is currently unknown. Cellular matrix biosynthesis is an energy demanding process. The objective of this study was to investigate the effects of static and dynamic compressive loading on energy metabolism of IVD cells. Porcine annulus fibrosus (AF) and nucleus pulposus (NP) cells seeded in 2% agarose were used in this experiment. Experimental groups included 15% static compression and 0.1 and 1 Hz dynamic compression at 15% strain magnitude for 4 h. ATP, lactate, glucose, and nitric oxide (NO) contents in culture media, and ATP content in cell–agarose construct were measured using biochemical assays. While the total ATP content of AF cells was promoted by static and dynamic loading, only 1 Hz dynamic loading increased total ATP content of NP cells. Increases in lactate production and glucose consumption of AF cells suggest that ATP production via glycolysis is promoted by dynamic compression. ATP release and NO production of AF and NP cells were significantly increased by dynamic loading. Thus, this study clearly illustrates that static and dynamic compressive loading affect IVD cell energy production while cellular responses to mechanical loading were both cell type and compression type dependent. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1634–1641, 2011
Determination of aflatoxin B1 in cereals by homogeneous liquid–liquid extraction coupled to high performance liquid chromatography‐fluorescence detection
Authors: Sheijooni‐Fumani Neda , Hassan Jalal , Yousefi Seyed R.
Published: April 2011

A simple and rapid method based on homogeneous liquid–liquid extraction coupled to HPLC with fluorescence detection was developed for the determination of aflatoxin B1 (AFB1) in the rice and grain samples after post‐column derivatization. The proposed method eliminated the use of immunoaffinity columns for clean‐up in the determination of AFB1. The parameters affecting recovery and preconcentration such as type and volume of organic solvent, volume ratio of water/methanol, concentration of phase separator reagent and extraction time were optimized. Under the optimized conditions, the calibration graph was linear in the concentration range of 0.01–1.0 ng/g with the detection limit of 0.003 ng/g. This method was successfully applied for the analysis of AFB1 in different cereal samples.
Control of optical properties through photochromism: a promising approach to photonics
Authors: Bianco A. , Perissinotto S. , Garbugli M. , Lanzani G. , Bertarelli C.
Published: April 2011

In this work studies on photochromism for optics and photonics are reviewed. The versatility of organic chemistry gives photochromic materials wide opportunities for several applications that range from tunable filters and gratings, to refractive‐index modulators for optical fibers and communications, to optical memories and sensors. Moreover, novel results on amplified emission efficient modulation in a conjugated polymer/photochromic system are presented.
Nonmotor manifestations of dystonia: A systematic review
Authors: Kuyper Daniel J. , Parra Veronica , Aerts Shanae , Okun Michael S. , Kluger Benzi M.
Published: April 2011

Nonmotor symptoms are increasingly recognized as important determinants of quality of life and disability in a wide range of movement disorders. There is a limited body of research suggesting that many of these symptoms are also commonly associated with primary and other genetic forms of dystonia. However, the significance, etiology, pathophysiology, and treatment of these symptoms remain poorly described. The following is a review of the literature that focuses primarily on the association of these types of dystonia with psychiatric disorders, cognition, sleep, pain, and autonomic symptoms. We will also discuss potential mechanisms and approaches to treatment for nonmotor features of dystonia. © 2011 Movement Disorder Society
Apigetrin induces erythroid differentiation of human leukemia cells K562: Proteomics approach
Authors: Tsolmon Soninkhishig , Nakazaki Eri , Han Junkyu , Isoda Hiroko
Published: April 2011

Scope: Induction of cancer‐cell differentiation is an alternative approach for cancer chemotherapy. There are numerous studies that diets containing an abundance of fruits and vegetables have protection against cancers, and the main agents thought to provide such protective effect are flavonoids. In this study we used apigetrin as a possible cell differentiation inducer and chronic leukemia cells K562 for their pluripotent differentiating potency.

Methods and results: Prolonged treatment with 75 μM apigetrin induced erythroid differentiation of K562 cells with specific marker glycophorin A expression and fetal hemoglobin synthesis in treated cells, which was accompanied with G2/M arrest. Proteomics data revealed the downregulation of several proteins expression involved in cell cycle regulation, protein synthesis and nuclear import and export of signaling molecules.

Conclusion: This is the first evidence that natural compound apigetrin may induce cancer cell differentiation thus could be one of the possible explanations of its antitumor effects.
Origin of far‐field potentials in the ulnar compound muscle action potential
Authors: Sonoo Masahiro , Kurokawa Katsumi , Higashihara Mana , Kurono Hiroko , Hokkoku Keiichi , Hatanaka Yuki , Shimizu Teruo
Published: April 2011

Introduction:

The compound muscle action potential (CMAP) following ulnar nerve stimulation receives a considerable contribution from far‐field potentials (FFPs), although their origin is not entirely clear. We investigated this issue using voluntary contractions.

Methods:

In 7 control subjects, we placed multiple recording electrodes over the motor points of ulnar‐innervated muscles. We asked the subjects to perform a weak movement corresponding to the action of each muscle, and identified the single motor unit potentials (MUPs) from that muscle. We summed the MUPs from each individual muscle and reconstructed the CMAPs.

Results:

The reconstructed CMAPs coincided well with the actual ones. The N1, P1, and early N2 components of the FFPs were generated primarily by palmar, but also by dorsal, interosseous muscles. The abductor digiti minimi muscle usually generated positive–negative biphasic FFPs, and the negative FFP generated the late N2 component.

Conclusions:

These results should prompt a revision of the theory of FFP generation. Muscle Nerve, 2011
Contraction history produces task‐specific variations in spinal excitability in healthy human soleus muscle
Authors: Uematsu Azusa , Sekiguchi Hirofumi , Kobayashi Hirofumi , Hortobágyi Tibor , Suzuki Shuji
Published: April 2011

Introduction: In human movements muscles lengthen and then shorten, or occasionally shorten and then lengthen, but it is unclear whether the nature of neural activation of the initial phase influences the neural state of the subsequent phase. We examined whether contraction history modulates spinal excitability in the healthy human soleus muscle. Methods: Subjects performed six blocks of 10 repetitions of four muscle actions consisting of specific combinations of passive shortening (PAS), and passive lengthening (PAL), shortening contraction (SHO), and lengthening contraction (LEN); that is: (1) SHO+PAL; (2) PAS+LEN; (3) PAS+PAL; and (4) SHO+LEN. Results: Compared with baseline, the H‐reflex increased in the block of 300–400 s after SHO+PAL and decreased in the block of 0–100 s after PAS+LEN and SHO+LEN. Conclusions: Our results suggest that spinal excitability is potentiated during a muscle action preceded by muscle shortening, but it becomes depressed during a muscle action preceded by muscle lengthening. Muscle Nerve, 2010.
Relevance vector machine applied to slope stability analysis
Authors: Zhao Hongbo , Yin Shunde , Ru Zhongliang
Published: April 2011

This paper examines the potential of relevance vector machine (RVM) in slope stability analysis. The nonlinear relationship between slope stability and its influence factors is presented by the relevance vector learning mechanism based on a kernel‐based Bayesian framework. The six input variables used for the RVM for the prediction of stability slope are density (γ), friction angle (C), friction coefficient (ϕ), slope angle (ϕr), slope height (H), and pore water pressure (ru). Comparison of RVM with some other methods is also presented. RVM has been used to compute the error bar. The results presented in this paper clearly highlight that the RVM is a robust tool for the prediction of slope stability. The experimental results show the effectiveness of the proposed approach. Copyright © 2011 John Wiley & Sons, Ltd.
Stroke patients who regain urinary continence in the first week after acute first‐ever stroke have better prognosis than patients with persistent lower urinary tract dysfunction
Authors: Rotar Melita , Blagus Rok , Jeromel Miran , Škrbec Miha , Tršinar Bojan , Vodušek David B.
Published: April 2011

Aims

Urinary incontinence (UI) is a predictor of greater mortality and poor functional recovery; however published studies failed to evaluate lower urinary tract (LUT) function immediately after stroke. The aim of our study was to evaluate the course of LUT function in the first week after stroke, and its impact on prognosis.

Methods

We included 100 consecutively admitted patients suffering first‐ever stroke and evaluated them within 72 hours after stroke, after 7 days, 6 months, and 12 months. For LUT function assessment we used ultrasound measurement. The patients were divided into three groups: (i) patients who remained continent after stroke, (ii) patients who had LUT dysfunction in the acute phase but regained continence in the first week, and (iii) patients who did not regain normal LUT control in the first week. We assessed the influence of variables on death using the multiple logistic regression model.

Results

Immediately after stroke 58 patients had LUT dysfunction. The odds of dying in group with LUT dysfunction were significantly larger than odds in group without LUT dysfunction. Odds for death for patients who regained LUT function in 1 week after stroke were comparable to patients without LUT dysfunction.

Conclusions

We confirmed that post‐stroke UI is a predictor of greater mortality at 1 week, 6 months and 12 months after stroke. However, patients who regain normal bladder control in the first week have a comparable prognosis as the patients who do not have micturition disturbances following stroke. Neurourol. Urodynam. 30:1315–1318, 2011. © 2011 Wiley‐Liss, Inc.
The methodology of normative policy analysis
Authors: Robert Christopher , Zeckhauser Richard
Published: April 2011

Policy analyses frequently clash. Their disagreements stem from many sources, including models, empirical estimates, and values such as who should have standing and how different criteria should be weighted. We provide a simple taxonomy of disagreement, identifying distinct categories within both the positive and values domains of normative policy analysis. Using disagreements in climate policy to illustrate, we demonstrate how illuminating the structure of disagreement helps to clarify the way forward. We conclude by suggesting a structure for policy analysis that can facilitate assessment, comparison, and debate by laying bare the most likely sources of disagreement. © 2011 by the Association for Public Policy Analysis and Management.
‘Missed’ coeliac disease in type 1 diabetes mellitus with fatal consequences
Authors: Talbot F , Neupane S , Gibbons A , Krishnan S , Mathews A
Published: April 2011

Our patient is a 40‐year‐old man with a 22‐year history of type 1 diabetes. His control had been consistently poor but he had minimal end organ damage. There was no significant past medical history or family history. He was a C1 driving licence holder, and the DVLA was aware of his diagnosis of type 1 diabetes.

In January 2007 he unexpectedly lost 8kg in weight and found he required less insulin. He had frequent hypoglycaemic episodes, but did not seek medical attention.

Five months later he was involved in a road traffic accident that was fatal to the other driver. The paramedics found him to be hypoglycaemic. This resulted in a custodial sentence, and lifetime driving ban.

He was subsequently admitted to hospital to investigate his hypoglycaemia. Thyroid function and synacthen tests were normal. Coeliac serology was negative and he was mildly anaemic. His HbA1c was elevated at 10.4% (90mmol/mol). He was discharged without cause found.

A month later he was readmitted with breathlessness. He was severely anaemic with an Hb of 7.8g/dl, and was referred for gastroscopy. This demonstrated hyperplastic gastritis of the stomach, with altered blood present. Duodenal biopsies were taken and showed subtotal villous atrophy with a patchy increase in intraepithelial lymphocytes and crypt hyperplasia. The findings were consistent with coeliac disease. The patient was referred to a dietitian for advice on a gluten‐free diet. His haemoglobin normalised and a DEXA scan excluded osteoporosis. Copyright © 2011 John Wiley & Sons.
Membrane proteomic signatures of karyotypically normal and abnormal human embryonic stem cell lines and derivatives
Authors: Gerwe Brian A. , Angel Peggi M. , West Franklin D. , Hasneen Kowser , Young Amber , Orlando Ron , Stice Steven L.
Published: April 2011

Cultured human embryonic stem cells (hESCs) and derived derivatives contain heterogeneous cell populations with varying degrees of differentiation and karyotypic stability. The inability to isolate homogenous population presents a challenge toward cell‐based applications and therapies. A proteomics approach was utilized to discover novel membrane proteins able to distinguish between the hESC lines BG01, WA09, and abBG02 (trisomy 12, 14, 17 and an extra copy of the X chromosome), along with WA09‐derived human neural progenitor (hNP) cells. Membrane protein signatures were developed using sucrose‐gradient isolation, 1‐D gel electrophoresis followed by in‐gel digestion and analysis by reverse phase chromatography coupled to ion trap‐FT‐ICR. At a ≤1.0% false discovery rate, 1918 proteins were identified; 775 were annotated as membrane proteins and 720 predicted to contain transmembrane spanning regions. Flow cytometry was used to validate cell surface expression of selected proteins. Junctional adhesion molecule 1 expression was shared by BG01, BG02 and abBG02 hESC lines. Dysferlin expression was specific to the WA09 hESC line and not the derived neural or mesenchymal progenitors. Ciliary neurotrophic factor receptor distinguished WA09‐derived human neural progenitor cells from the parent hESC population, and WA09‐derived mesenchymal progenitor cells. This study expands the current membrane protein data set for hESCs.
PecFent: gel‐based nasal fentanyl for breakthrough cancer pain
Authors: Chaplin Steve , Chogle Monica , Campbell William
Published: April 2011

PecFent is a new intranasal formulation of fentanyl licensed for the management of breakthrough pain in cancer patients receiving opioid therapy. In our New products review, Steve Chaplin presents the clinical data relating to its efficacy and adverse effects and Drs Monica Chogle and William Campbell comment on its place in breakthrough pain management. Copyright © 2011 Wiley Interface Ltd
Changes in chemical composition and nanostructure of SiC thin films prepared by PECVD during thermal annealing
Authors: Künle Matthias , Janz Stefan , Nickel Klaus Georg , Eibl Oliver
Published: April 2011

Silicon carbide (SiC) thin films were deposited on silicon (Si) using plasma enhanced chemical vapor deposition (PECVD). Annealing was done in a rapid thermal annealing furnace at a temperature of 1300 °C. As‐deposited and annealed Si‐rich and stoichiometric SiC thin films were investigated by analytical transmission electron microscopy (AEM). TEM‐energy‐dispersive X‐ray spectroscopy was used to quantify the chemical composition of the SiC thin films with high accuracy. The chemical composition of the near stoichiometric SiC thin film changed during annealing from Si0.4C0.6 to Si0.5C0.5 due to diffusion of Si from the Si substrate into the film. The Si‐rich Si1–xCx film had the identical chemical composition of Si0.8C0.2 before and after annealing. As‐deposited films show nanoporosity within the bulk film. During annealing, v‐shaped defect structures were formed at the interface of the stoichiometric SiC thin film to the Si substrate. Diffraction patterns revealed that as‐deposited films were amorphous. During annealing the crystallization of 3C‐SiC occurred in near‐stoichiometric SiC thin films, whereas in Si‐rich Si1–xCx thin films two phases, namely Si and 3C‐SiC, crystallized. Low‐loss and core‐loss electron energy loss spectroscopy (EELS) verified the diffraction results. In the low‐loss spectra of the near stoichiometric SiC thin film, a plasmon peak located at 20.2 eV before and at 22.3 eV after annealing was detected. The low‐loss spectra of the Si‐rich Si1–xCx thin film showed an asymmetric plasmon peak with two maxima located at 18.5 and 25.0 eV in the as‐deposited film and 18.6 and 24.3 eV in the annealed Si‐rich Si1–xCx film. The 18.5 eV plasmon peaks is assigned to Si and the 25 eV plasmon peak is attributed to the SiC phase.
Advanced method for increasing the efficiency of white light quantum dot LEDs
Authors: Duty Chad E. , Bennett Charlee J. C. , Sabau Adrian S. , Jellison Gerald E. , Boudreaux Phillip R. , Walker Steven C. , Ott Ron
Published: April 2011

Covering a light‐emitting diode (LED) with quantum dots (QDs) can produce a broad spectrum of white light. However, current techniques for applying QDs to LEDs suffer from a high density of defects and a non‐uniform distribution of QDs, which, respectively, diminish the efficiency and quality of emitted light. Oak Ridge National Laboratory (ORNL) has the unique capability to thermally anneal QD structures at extremely high power densities for very short durations. This process, called pulse thermal processing (PTP), reduces the number of point defects while maintaining the size and shape of the original QD nanostructure. Therefore, the efficiency of the QD wavelength conversion layer is improved without altering the emission spectrum defined by the size distribution of the QD nanoparticles. The current research uses a thermal model to predict annealing temperatures during PTP and demonstrates up to a 300% increase in photoluminescence for QDs on passive substrates.
First‐principles study on the effect of surface hydrogen coverage on the adsorption process of ammonia on InN(0001) surfaces
Authors: Suzuki Hikari , Togashi Rie , Murakami Hisashi , Kumagai Yoshinao , Koukitu Akinori
Published: April 2011

To examine the effect of hydrogen on the initial growth process of InN, the adsorption processes of group‐V sources commonly used in vapor phase epitaxy (VPE) were investigated using first‐principle calculations based on the density functional theory (DFT). The ideal and reconstructed surfaces with an adsorbed 0.75 monolayer of hydrogen were used as the initial surface structures to examine the influence of surface hydrogen coverage of InN(0001) surfaces on the adsorption processes of group‐V sources including NH3 and NH2 generated by the decomposition of NH3. From the calculations of the adsorption energies for each case, it was revealed that surface hydrogen coverage did not have an effect on the adsorption of NH3, whereas NH2 was significantly affected by the presence of hydrogen on the surface. In comparison with our previous results, it was also shown that the adsorption energies for NH3 and NH2 on InN(0001) surfaces are smaller than those on GaN and AlN(0001) surfaces (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An ultraviolet/infrared matrix‐assisted laser desorption ionization sample stage integrating scanning knife‐edge and slit devices for laser beam analysis
Authors: Soltwisch Jens , Dreisewerd Klaus
Published: April 2011

A sample stage is described that allows the on‐line analysis of laser intensity profiles and spot sizes directly in the ion source of a matrix‐assisted laser desorption ionization (MALDI) mass spectrometer. The detector uses either a scanning knife‐edge or a narrow slit in combination with diffusing disks for scattering of photons and a pyroelectric sensor for recording the light pulses. The setup was integrated into the sample holder of a oMALDI2TM ion source (AB Sciex) and allows parallel analysis of UV‐ and IR‐laser beams at typical UV‐/IR‐MALDI laser fluences. The concept could be especially useful for a precise control of the laser spot size in MALDI imaging applications. Copyright © 2011 John Wiley & Sons, Ltd.
Matrix‐assisted laser desorption/ionization mass spectrometric analysis of aliphatic biodegradable photoluminescent polymers using new ionic liquid matrices
Authors: Serrano Carlos A. , Zhang Yi , Yang Jian , Schug Kevin A.
Published: April 2011

In this study, two novel ionic liquid matrices (ILMs), N,N‐diisopropylethylammonium 3‐oxocoumarate and N,N‐diisopropylethylammonium dihydroxymonooxoacetophenoate, were tested for the structural elucidation of recently developed aliphatic biodegradable polymers by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS). The polymers, formed by a condensation reaction of three components, citric acid, octane diol, and an amino acid, are fluorescent, but the exact mechanism behind their luminescent properties has not been fully elucidated. In the original studies, which introduced the polymer class (J. Yang et al., Proc. Natl. Acad. Sci. USA 2009, 106, 10086–10091), a hyper‐conjugated cyclic structure was proposed as the source for the photoluminescent behavior. With the use of the two new ILMs, we present evidence that supports the presence of the proposed cyclization product. In addition, the new ILMs, when compared with a previously established ILM, N,N‐diisopropylethylammonium α‐cyano‐3‐hydroxycinnimate, provided similar signal intensities and maintained similar spectral profiles. This research also established that the new ILMs provided good spot‐to‐spot reproducibility and high ionization efficiency compared with corresponding crystalline matrix preparations. Many polymer features revealed through the use of the ILMs could not be observed with crystalline matrices. Ultimately, the new ILMs highlighted the composition of the synthetic polymers, as well as the loss of water that was expected for the formation of the proposed cyclic structure on the polymer backbone. Copyright © 2011 John Wiley & Sons, Ltd.
Ultrafast mass spectrometry based bioanalytical method for digoxin supporting an in vitro P‐glycoprotein (P‐gp) inhibition screen
Authors: Wagner Andrew D. , Kolb Janet M. , Özbal Can C. , Herbst John J. , Olah Timothy V. , Weller Harold N. , Zvyaga Tatyana A. , Shou Wilson Z.
Published: April 2011

The evaluation of interactions between drug candidates and transporters such as P‐glycoprotein (P‐gp) has gained considerable interest in drug discovery and development. Inhibition of P‐gp can be assessed by performing bi‐directional permeability studies with in vitro P‐gp‐expressing cellular model systems such as Caco‐2 (human colon carcinoma) cells, using digoxin as a substrate probe. Existing methodologies include either assaying 3H‐digoxin with liquid scintillation counting (LSC) detection or assaying non‐labeled digoxin with liquid chromatography–tandem mass spectrometric (LC‐MS/MS) analysis at a speed of several minutes per sample. However, it is not feasible to achieve a throughput high enough using these approaches to sustain an early liability screen that generates more than a thousand samples on a daily basis. To address this challenge, we developed an ultrafast (9 s per sample) bioanalytical method for digoxin analysis using RapidFire™, an on‐line solid‐phase extraction (SPE) system, with MS/MS detection. A stable isotope labeled analog, d3‐digoxin, was used as internal standard to minimize potential ionization matrix effect during the RF‐MS/MS analysis. The RF‐MS/MS method was more than 16 times faster than the LC‐MS/MS method but demonstrated similar sensitivity, selectivity, reproducibility, linearity and robustness. P‐gp inhibition results of multiple validation compounds obtained with this RF‐MS/MS method were in agreement with those generated by both the LC‐MS/MS method and the 3H‐radiolabel assay. This method has been successfully deployed to assess P‐gp inhibition potential as an important early liability screen for drug–transporter interaction. Copyright © 2011 John Wiley & Sons, Ltd.
Internal standard tracked dilution to overcome challenges in dried blood spots and robotic sample preparation for liquid chromatography/tandem mass spectrometry assays
Authors: Liu Guowen , Snapp Heidi M. , Ji Qin C.
Published: April 2011

Dried blood spot (DBS) technology is an emerging alternative for sample collection in bioanalysis. Dilution for DBS samples is a challenge due to its solid sample format. Currently, DBS samples requiring dilution were first extracted as regular samples and then diluted with extracted blank samples containing internal standard (IS). Since the dilution step is a volume‐critical step, extra care has to be taken to achieve accurate dilution when dealing with limited volume extracted samples. Here, we introduce an alternative sample dilution for liquid chromatography/tandem mass spectrometry (LC/MS/MS) assays using IS to track the dilution step. Dilution factor‐adjusted IS working solution was first added to the sample requiring dilution before sample processing; subsequently, the processed sample was approximately diluted into the assay linear response range before LC/MS/MS analysis. We define this approach as “IS‐tracked dilution”. The advantage of this approach is that the diluting step is tracked by the IS and is no longer a volume‐critical step. Another recognized challenge related to sample dilution is automatic sample dilution using a liquid handler. This “IS‐tracked dilution” may also help address some of the challenges for automatic sample dilution of liquid samples. This new dilution approach was proven to be effective and convenient in both plasma assays and DBS assays using omeprazole as a probe compound. Copyright © 2011 John Wiley & Sons, Ltd.
Efficient address space generation for an OPC UA server
Authors: Girbea Alina , Nechifor Septimiu , Sisak Francisc , Perniu Liviu
Published: April 2011

The new OPC Unified Architecture has been introduced as a replacement for the existing COM‐based specifications. The article describes a generalized algorithm for the automatic generation of the address space structure for an UA server. First, we present the general startup procedure of an OPC UA server, focusing on the address space generation step. Afterwards we introduce specialized algorithms for the generation of the type nodes, of object, variable, method and view nodes. Finally the additional references are added to the fully meshed address space. The basic ideas of the algorithms are: the splitting of the nodes into groups and the sequential addition of the groups to the address space, and the naming of a main reference for every target node. The algorithms have been applied for an aggregating UA server which models the devices of an assembly line. The main advantages are: shorter development time, easier maintenance and the possibility to add nodes to the address space in both online and offline mode. Copyright © 2011 John Wiley & Sons, Ltd.
Impact of nuchal translucency credentialing by the FMF, the NTQR or both on screening distributions and performance
Authors: Evans M. I. , Krantz D. A. , Hallahan T. W. , Sherwin J.
Published: April 2011

Objective

In the USA, both The Fetal Medicine Foundation (FMF) and the Nuchal Translucency Quality Review Program (NTQR) have operated education, review and credentialing for physicians and sonographers for the measurement of nuchal translucency (NT). We sought to assess differences in the distribution of NT measurements based upon the system from which the operator obtained their education, review and credentialing.

Methods

398 311 NT measurements by 1541 sonographers who had performed ≥ 50 exams from July 2008 to June 2010 were grouped by organization. Differences between grouped measurements were assessed using analysis of variance of log10NT multiples of the median (MoM), with sonographer and organization as factors.

Results

MoM values were significantly lower (P⩽0.001) and SD was significantly higher (P < 0.001) for the NTQR group compared with the FMF group or those sonographers credentialed by both. The percentage of individuals with negative bias ≥ 10% was greater for the NTQR group (P < 0.001). The difference was less but still significant (P = 0.009) when bias was adjusted for by the overall median for the organization.

Conclusions

Although NT MoM measurements were significantly lower and had a wider variance when obtained by the NTQR group, our data cannot distinguish between bias in training or the attributes of the participating sonographers in each program. With these large numbers, it is unlikely that patient characteristics could explain the discrepancy in distributions. Ongoing efforts to monitor sonographer performance with remediation for poor performers may reduce discrepancies between organizations. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
An asynchronous low‐power medium access control protocol for wireless sensor networks
Authors: Wang Heping , Zhang Xiaobo , Naït‐Abdesselam Farid , Khokhar Ashfaq
Published: April 2011

Duty cycling is a fundamental approach used in contention‐based medium access control (MAC) protocols for wireless sensor networks (WSNs) to reduce power consumption in sensor nodes. Existing duty cycle‐based MAC protocols use either scheduling or low‐power listening (LPL) to reduce unnecessary energy lost caused by idle listening and overhearing. This paper presents a new asynchronous duty‐cycled MAC protocol for WSN. It introduces a novel dual preamble sampling (DPS) approach to efficiently coordinate channel access among nodes. DPS combines LPL with a short‐strobed preamble approach to significantly reduce the idle‐listening issue in existing asynchronous protocols. We provide detailed analysis of the energy consumption by using well‐known energy models and compare our work with B‐MAC and X‐MAC, two most popular asynchronous duty cycle‐based MAC protocols for WSNs. We also present experimental results based on NS‐2 simulations. We show that depending on the traffic load and preamble length, the proposed MAC protocol improves energy consumption significantly without degrading network performances in terms of delivery ratio and latency. For example, for a traffic rate of 0.1 packets/s and a preamble length of 0.1 s, the average improvement in energy consumption is about 154%. Copyright © 2011 John Wiley & Sons, Ltd.
Stem cell genome‐to‐systems biology
Authors: Chia Na‐Yu , Ng Huck‐Hui
Published: April 2011

Stem cells are capable of extended proliferation and concomitantly differentiating into a plethora of specialized cell types that render them apropos for their usage as a form of regenerative medicine for cell replacement therapies. The molecular processes that underlie the ability for stem cells to self‐renew and differentiate have been intriguing, and elucidating the intricacies within the genome is pertinent to enhance our understanding of stem cells. Systems biology is emerging as a crucial field in the study of the sophisticated nature of stem cells, through the adoption of multidisciplinary approaches which couple high‐throughput experimental techniques with computational and mathematical analysis. This allows for the determination of the molecular constituents that govern stem cell characteristics and conjointly with functional validations via genetic perturbation and protein location binding analysis necessitate the construction of the complex transcriptional regulatory network. With the elucidation of protein–protein interaction, protein–DNA regulation, microRNA involvement as well as the epigenetic modifications, it is possible to comprehend the defining features of stem cells at the system level. WIREs Syst Biol Med 2012, 4:39–49. doi: 10.1002/wsbm.151

This article is categorized under:

Developmental Biology > Stem Cell Biology and Regeneration