bluuebunny/crossref_metadata_2025 huggingface dataset:
LOSS of Mrp1 alters detoxification enzyme expression in a tissue‐ and hormonal‐status‐specific manner
Authors: Sivils Jeffrey C. , Ancrum Tiffany M. , Bain Lisa J.
Published: April 2012

The multidrug resistance‐associated protein1 (MRP1/ABCC1) is a member of the ABCC transporter subfamily that mediates the efflux of pharmaceuticals, xenobiotics and steroid hormones, typically as glutathione, glucuronide or sulfate conjugates. Since loss of one transporter can be compensated by increasing the expression of other transporters and conjugation enzymes, we sought to examine compensatory changes in phase I, II and III enzyme expression in extrahepatic tissues, including the kidney, lungs and small intestine of intact or castrated Mrp1−/− male mice. In the kidney, the expression of several P450s, sulfotransferase 1a1 (Sult), glucuronosyltransferases (Ugt) and Mrps2–4, were significantly changed owing to castration alone. The only time genotype mattered was between the castrated FVB and Mrp1 knockout mice. In contrast, expression of the Ugts, Sult 1a1 and Mrp3 in the lungs was significantly downregulated in the Mrp1 knockout mice, so based exclusively on genotype. In the small intestine, there were interactions between steroid hormone levels and genotype, as the expression differences were only found in mice lacking Mrp1, and were changed between intact and castrated animals. The mechanism behind this pattern of expression may be to due to Nrf2 regulation, as its expression mirrors that of the phase II and phase III enzymes. These results indicate that compensatory responses owing to the loss of Mrp1 vary dramatically, depending on the particular tissue. This information will aid in the understanding of how drug uptake, disposition and elimination can be influenced by both hormone status and the presence and magnitude of transporter expression. Copyright © 2012 John Wiley & Sons, Ltd.
Link analysis for fraud detection
Authors: Tackett James A. , Wolf Fran
Published: April 2012

The past ten years have witnessed a remarkable transformation in the way companies and customers interact with one another. Almost every office and household has an Internet connection along with some type of wireless capability. But everything comes at a price, and we pay for our increased computer speed and efficiency with new opportunities for fraudsters.

However, people conducting routine digital activities do leave an information trail. Under the right circumstances, this digital library of automatically generated data can be used to detect fraud or misuse of company resources. So, many companies are using Link Analysis (LA) as an effective tool for organizing this digital information when looking for fraud or employee misconduct.

This article presents an overview of LA—and explains how your company can use it to detect possible fraud. © 2012 Wiley Periodicals, Inc.
Identifying and recovering vendor credits: A bigger problem than you imagine
Authors: Schaeffer Mary S.
Published: April 2012

Identifying and recovering vendor credits is a much bigger problem than you might imagine. Most JCAF readers are well versed in accounting issues, and probably believe they are recovering all the vendor credits their company or their clients are entitled to. Unfortunately, says the author of this article, the data shows something entirely different. Vendor credits are evaporating at an alarming rate, and their rightful owners are not even aware of it.

What can you do to audit and recover these credits? The author has some answers. © 2012 Mary S. Schaeffer.
Why most audit ethics courses don't work
Authors: Goldberg Stephen R. , Centers David P.
Published: April 2012

Ethics training and education usually assume that people recognize when they encounter ethical situations—and that a better understanding of ethics results in better ethical decisions. But these assumptions are false! Instead, the authors suggest other approaches to improve ethical decision making by auditors. And although this article focuses on auditing, it also applies to other business and nonbusiness situations. © 2012 Wiley Periodicals, Inc.
Comparative physicochemical analysis of suspended and immobilized cultivation of Chlorella sp.
Authors: Zeng Xianhai , Danquah Michael K. , Halim Ronald , Yang Shuyu , Chen Xiao Dong , Lu Yinghua
Published: April 2012

BACKGROUND: Immobilized cultivation of microorganisms is gaining interest in the microalgae industry. In this study, a novel microalgae polymeric carrier, sodium cellulose sulphate/poly‐dimethyl‐diallyl‐ammonium chloride (NaCS‐PDMDAAC) capsule system, was employed to immobilize Chlorella sp. Microalgae cultivation was performed under immobilized and suspended conditions, and the resulting cells were characterized biochemically and physically.

RESULTS: Experimental results indicated that microalgae cells cultivated under NaCS‐PDMDAAC immobilized conditions have a robust morphology, a smaller average cell size of 2.92 µm and a higher Zeta potential of − 17.10 mV than the suspended cells with a cell size of 6.81 µm and Zeta potential of − 32.90 mV. The immobilized microalgae cells displayed a total lipid content of 14.85%, and a chlorophyll content of 3.36%, slightly higher than those obtained from the suspended cells.

CONCLUSION: These differences are critical to further explore the impact of immobilized microalgae cultivation systems for specific biotechnological applications. © 2012 Society of Chemical Industry
Ultrastructural features of the myotendinous junction of the sternomastoid muscle in Wistar rats: From newborn to aging
Authors: Ciena Adriano Polican , De Almeida Sonia Regina Yokomizo , De Sousa Bolina Cristina , De Sousa Bolina‐Matos Regina , Grassi Rici Rose Eli , Da Silva Marcelo Cavenaghi Pereira , Miglino Maria Angélica , Watanabe Ii‐Sei
Published: April 2012

The myotendinous junction (MTJ) is a major area for transmitting force from the skeletal muscle system and acts in joint position and stabilization. This study aimed to use transmission electron microscopy to describe the ultrastructural features of the MTJ of the sternomastoid muscle in Wistar rats from newborn to formation during adulthood and possible changes with aging. Ultrastructural features of the MTJ from the newborn group revealed pattern during development with interactions between muscle cells and extracellular matrix elements with thin folds in the sarcolemma and high cellular activity evidenced through numerous oval mitochondria groupings. The adult group had classical morphological features of the MTJ, with folds in the sarcolemma forming long projections called “finger‐like processes” and sarcoplasmic invaginations. Sarcomeres were aligned in series, showing mitochondria near the Z line in groupings between collagen fiber bundles. The old group had altered “finger‐like processes,” thickened in both levels of sarcoplasmic invaginations and in central connections with the lateral junctions. We conclude that the MTJ undergoes intense activity from newborn to its formation during adulthood. With increasing age, changes to the MTJ were observed in the shapes of the invaginations and “finger‐like processes” due to hypoactivity, potentially compromising force transmission and joint stability. Microsc. Res. Tech. 75:1292–1296, 2012. © 2012 Wiley Periodicals, Inc.
Morphology of immature stages of Megaselia spiracularis Schmitz (Diptera: Phoridae)
Authors: Dian‐Xing Feng , Guang‐Chun Liu
Published: April 2012

In addition to causing myiasis in humans, Megaselia spiracularis Schmitz has also been reported as a forensically important fly. In this study, we presented the morphology of all larval instars and puparium of M. spiracularis using scanning electron microscopy. The first instar larva was composed of 12 segments. Antennae and maxillary palp complex were visible. Two spiracular slits could be seen at the posterior spiracle. The branch of posterior spiracular hairs was approximately equal to the palm‐formed base in length. Second and third larval instars were very similar to first instar, except for the presence of anterior spiracle. The labium of the second instar larva was triangular and ventrally curved, whereas it was a bilobed structure and the tip forked in the first instar. The bubble membrance comprised of ≈40 globules presented at the third instar larvae. Puparia showed a retracted cephalic region and a pair of pupal respiratory horns on the dorsum. A comparison of the morphological features between immature stages of M. spiracularis and M. scalaris, a forensically important fly indoors in Germany, Malaysia, and China, was discussed. Microsc. Res. Tech. 75:1297–1303, 2012. © 2012 Wiley Periodicals, Inc.
Finding our way together on the journey to zero
Authors: Hilliard Mary Anne
Published: April 2012

Remember that classic scene from The Wizard of Oz when Dorothy's house is being hurled into the sky and her world and worries are rotating around her in a great tornado? Ever feel that way at work? To be sure, the modern risk manager and safety professional are facing new challenges and expectations: value‐based services, mandatory reporting, pay for performance, new compliance standards, and so on. Sometimes it's disorienting, perhaps similar to how Dorothy must have felt when she realized she was not in Kansas anymore.
Perspectives on healthcare reform: High Court to decide constitutionality of individual mandate
Authors: Groszkruger Dan
Published: April 2012

The US Supreme Court soon will decide a number of issues regarding the constitutionality of the Patient Protection and Affordable Care Act(1) (PPACA), pursuant to an order published on November 14, 2011. This article will identify four issues (Commerce Clause power, severability, Medicaid expansion, and Anti‐Injunction Act) coming before the Court for argument in the spring of 2012. Also, this article identifies and discusses the pro and con arguments pertaining to each issue. Readers who wish to refresh their memories about all the events leading up to the Supreme Court review may refer to the December 2010 monograph of the American Society for Healthcare Risk Management (ASHRM).(2).
Risk management and legal issues with the use of social media in the healthcare setting
Authors: Lambert Kristen M. , Barry Pauline , Stokes Gwen
Published: April 2012

Social media have infiltrated all of our lives, both personally and professionally. Most of us could never have envisioned the impact that social media have had on us, particularly in the healthcare arena. Who would have thought even five years ago that a discussion on the ASHRM exchange would involve the use of Twitter in the operating room or that a physician would be reprimanded by a state medical board and have her privileges revoked due to posting information online about a trauma patient? In the coming years, social media use will only increase, causing concern for risk managers across the continuum. Furthermore, although case law and statutory regulations addressing the use of social media are minimal today, it is anticipated that we will see legal challenges to this evolving medium in the future.
Synthesis of a carbon‐11 labelled agonist of the α7 nicotinic acetylcholine receptors
Authors: Dollé F. , Hinnen F. , Valette H. , Demphel S. , Coulon C. , Ottaviani M. , Bottlaender M. , Crouzel C.
Published: April 2012

The lead compound of a new series of azabicyclic carbamates, described by Astra Laboratories, namely Astra‐255082 (N‐(4‐bromophenyl)carbamic acid quinuclidin‐3‐yl ester) has been labelled with carbon‐11 using no‐carrier‐added [11C]phosgene.
The development of additional radioligands of varying pharmacokinetics for the 5‐HT1A receptor
Authors: Lang L. , Jagoda E. M. , Eckelman W. C.
Published: April 2012

Six compounds have been prepared to further probe the structure activity relationships based on the 5‐HT1A receptor ligand, WAY 100635. The goal is to obtain a series of radiotracers with varying pharmacokinetic properties. Substitution of a pyrimidine for a pyridine moiety, increased the specific binding ratio in the phenylcarboxamide series, but decreased the ratio in the cyclohexanecarboxamide series. A series of compounds with varying pharmacokinetic properties are now available to study a range of properties involving 5‐HT1A receptor binding.
Carbon‐11 labelling of a half mustard prodrug by reductive alkylation using [11C]acetaldehyde. A potential tracer for evaluation of adept or gdept using pet
Authors: Khanum N. , Luthra S. K. , Zhao Y. , Aboagye E. , Price P. M. , Burke P. , Brady F.
Published: April 2012

A half mustard anticancer prodrug carrying N‐chloroethyl and N′‐ethyl groups was labelled in the N′‐ethyl group by reductive alkylation using [11C]acetaldehyde.
Synthesis of 2, 16α‐ and 4, 16α‐[16α‐18F]difluoroestradiols and their 11β‐methoxy derivatives for estrogen receptor imaging
Authors: Seimbille Y. , Rousseau J. , Bénard F. , Ali H. , Van Lier J. E.
Published: April 2012

We have prepared the 2‐ and 4‐fluoro derivatives of 16α‐[18F]fluoroestradiol (FES) (4a, b) and 11β‐OMe‐FES (4c, d). Electrophilic substitution of estrone or 11β‐OMe‐estrone with N‐fluoropyridinium salt gave the 2‐and 4‐F derivatives 1, which were converted to the triols 2 and subsequently to the reactive 16β, 17β‐cyclic sulfates 3. Stereoselective opening of the cyclic sulfates via nucleophilic fluorination with Me4NF or [18F]F‐ and removal of the protecting ether and sulfate groups via rapid acid hydrolysis gave 4a‐d or [16α‐18F]‐(4a‐d).
Radiolabelling of the potential anti‐cancer agent, 5‐fluoro‐2‐(4‐amino‐3‐methylphenyl)benzothiazole (5F203) with fluorine‐18
Authors: Brown G. D. , Wilson H. K. , Westwell A. D. , Hutchinson I. , Stevens M. F. G. , Price P. M. , Aboagye E. , Luthra S. K. , Brady F.
Published: April 2012

The novel potential antitumour agent 5‐fluoro‐2‐(4‐amino‐3‐methylphenyl)benzothiazole (5F203) has been radiolabelled with fluorine‐18 by reaction of an amino protected trimethyltin precursor with molecular fluorine (18F‐F) followed by alkaline deprotection of the amino group. [18F]5F203 was obtained in ca 10% radiochemical yield in ca. 60 mins from end of bombardment.
FDG‐2‐nitroimidazole: A new potential hypoxia tracer using glucose transport
Authors: Patt M. , Sorger D. , Scheunemann M. , Stöcklin G.
Published: April 2012

A promising new radiotracer for the detection of hypoxic tissue in vivo with PET has been synthesized in good yields starting from tetra‐O‐acetyl‐2‐[18F]FDG available in high amounts in 2‐[18F]FDG synthesis. The new tracer representing an adduct of 2‐nitroimidazole and 2‐[18F]FDG is not phosphorylated in vitro by hexokinase thus excluding a second non‐hypoxia dependent trapping mechanism. Furthermore it has been shown to interfere with glucose transport proteins since it inhibits the cellular uptake of [18F]FDG in a concentration‐dependent manner.
Synthesis and first evaluation of new 18F‐labelled sulfonylureas for the determination of the beta‐cell status in vivo
Authors: Schirrmacher R. , Shiue G. , Shiue S. J. , Alavi A. , Feilen P. J. , Schneider S. , Beyer J. , Rösch F.
Published: April 2012

The syntheses and first in vitro evaluations for two fluoride bearing sulfonylurea derivatives are reported. Firstly, the tolbutamide derivative 1‐[4‐(2‐[18F]fluoroethoxy)benzenesulfonyl]‐3‐butyl urea (2‐[18F]fluoroethyl‐tolbutamide) could be labeled efficiently with [18F]fluoride. Subsequently, the glibenclamid derivative N‐(2‐(4‐(N‐((cyclohexylamino)carbonyl)sulfonylamino)phenyl)ethyl) 2‐(5‐chloro‐2‐[18F]fluorethoxy)phenyl) formamide (2‐[18F]fluoroethyl‐glibenclamide) was labeled with [18F]fluoride in high yields. Its ability to induce insuline secretion from rat beta‐cells in relation to the original glibenclamide was determined.
Cyclopentadienyl tricarbonyl technetium‐99m octanoic acid: A novel radiotracer for evaluation of fatty acid metabolism in the liver
Authors: Lee B. C. , Choe Y. S. , Lee K.‐H. , Chi D. Y. , Kim S. E. , Choi Y. , Kim B.‐T.
Published: April 2012

Cyclopentadienyl tricarbonyl 99mTc octanoic acid (99mTc‐CpTOA; 1) was prepared in high radiochemical yield (40–63%) and shown to be stable (90% at 6 h) in human serum. Biological studies demonstrated longer retention and slower metabolism of 99mTc‐CpTOA in CCl4‐treated mice than in normal mice, possibly due to impaired β‐oxidation. These results along with good water solubility of the radioactive extracts from the liver indicated that this radiotracer was mainly metabolized via β‐oxidation in the liver. This study thus suggests that 99mTc‐CpTOA 1 holds promise for evaluation of fatty acid metabolism in the liver.
Chemical modifications of 99mTc tricarbonyl labeled single chain antibody fragments for improved in vivo behavior in tumor targeting
Authors: Stichelberger A. , Jager H. , Waibel R. , Novak‐Hofer I. , Chester K. , Schubiger P. A.
Published: April 2012

One of the major limitations of using intact immunoglobulins for targeting tumors is the poor penetration into tissues. Although small single chain Fv (scFv) antibody fragments have been used because of their improved kinetics, some exhibit high renal accumulation. In this study we show a significant reduction of renal accumulation of His‐tagged scFv's directly labelled with 99mTc‐tricarbonyl by use of succinic anhydride. Further decrease of renal uptake will make this approach hopefully suitable for therapeutic application, using 188/186Re(I)‐tricarbonyl.
Metabolism and localization properties of 99mTc labeled synthetic neurotensin analogs
Authors: Nock B. , Maina T. , Nikolopoulou A. , Tsipra C. , Poppe M. , Conrath P. , Tourwé D. , Chiotellis E.
Published: April 2012

Recent reports have demonstrated that neurotensin (NT) receptors are overexpressed at high density in such devastating human neoplasms like exocrine ductal pancreatic carcinomas. Consequently, radiolabeled NT analogs can be used in the early diagnosis or even treatment of such tumors. In the present study we report on the synthesis and preclinical evaluation of four 99mTc labeled synthetic NT analogs based on the NT(8–13) sequence, known to specifically interact with the NTR1 subtype found in neoplastic cells. The biological half life of these analogs has been increased by strategic reduction of amide bonds, replacement of amino acid residues and coupling of a tetramine bifunctional chelator at the N‐terminal of resulting peptides. The affinity for the NTR1 subtype was found high in competition binding assays in WiDr cell membrane preparations. Labeling with 99mTc was quantitative under mild conditions leading to single radioactive species in high specific activities. The stability of labeled peptides in plasma, urine and kidney homogenates was found dependent on the above described modifications. The rate of internalization in WiDr cells was very high for all radiolabeled peptides, with >90% of the radioactivity accumulating in the cells within 30 min. In vivo distribution of the two most stable 99mTc NT analogs in mice xenografts revealed a specific accumulation of radioactivity in NTR1 subtype — rich cancer tissue combined with a very rapid clearance of background activity through the kidneys and the urinary system.
Effect of increased temperature on labelling efficiency of some 99mTc‐radiopharmaceuticals
Authors: Maksin T. , Djokić D. , Janković D.
Published: April 2012

The influence of increased temperature on the labelling efficiency with 99mTc for some compounds: pyrophosphate (PyP), dicarboxypropane diphosphonate (DPD), dimercaptosuccinate (DMS) and Sn‐colloid was investigated. The samples were exposed at 37°C for different time intervals and after that each of them was labelled with 99mTc (pertechnetate were simply injected into vials with samples). The radiochemical analyses were performed by paper and TL chromatography using different chromatography papers (Whatman N°1, SG, Schleicher&Schull) and proper mobile phases (80% methanol, 1N NaCl, acetone). Those results indicate the increases of impurity in the case of 99mTc‐PyP. In the case of 99mTc‐DPD and 99mTc‐DMS unsuitable complexes for bone and kidney image respectively were formed. There were no changes in results of quality control for 99mTc‐Sn colloid. Therefore it is very important for producer and also user of Tc‐radiopharmaceuticals to know the possible effect of bed storage and transportation condition on their quality.
Rutin labeled with technetium‐99M and its biodistribution inwistarrats
Authors: Bernardo L. C. , Oliveira M. B. N. , da Silva C. R. , Moura R. S. , Bernardo‐Filho M.
Published: April 2012

The use of natural products as medicines is growing along the years in the world. The rutin, a compound isolated fromRuta graveolens, is a flavonoid which has been suggested to have the capacity to protect the capillary endothelium and to reduce the triacylglycerol levels. Besides, it seems to present antioxidant characteristics and to be a great free radical scavenger. The use of technetium‐99m (99mTc) can be justified for its physical and chemistry properties. The aim of this study is to label rutin with 99mTc and to study its biodistribution inWistarrats. Firstly, rutin was dissolved in ethyl alcohol, and later incubated with stannous chloride. After that, 99mTc, as sodium pertechnetate, was added. The labeling efficiency was determined through the instant thin layer chromatography (ITLC‐SG). The biodistribution study of the rutin labeled with 99mTc was performed withWistarrats and the highest uptake was found in kidneys (0.535±0.09 % ID/g). It is possible to conclude that the rutin was successfully labeled with 99mTc.
[111In]‐DOTA‐Lys8‐Vasotocin: A new promising peptide for oxytocin receptor expressing tumors
Authors: Chinol M. , Nacca A. , Bussolati G. , Cassoni P. , Paganelli G.
Published: April 2012

Oxytocin receptors (OTR) are expressed by a large variety of human tumors. We have developed a new reagent specifically designed to transfer radionuclides to OTR‐expressing tumors. We selected Lys8‐vasotocin (LVT), an analogue of oxytocin (OT), with high affinity for OTR and coupled the chelating agent DOTA. The new reagent (DOTA‐LVT) was radiolabeled with 111In and showed specific binding to OTR positive cell lines. In vivo experiments demonstrated the receptor mediated binding of 111In‐DOTA‐LVT to OTR expressing tumors. The present study has shown that the new reagent may be promising to convey radioisotopes to OTR positive tumors although further improvements are warranted.
Synthesis and peptide coupling of a new DOTA‐based prochelator, forming neutral complexes with yttrium‐90 and indium‐111
Authors: Eisenwiener Klaus‐Peter , Reubi Jean‐Claude , Wenger Sandra , Mäcke Helmut R.
Published: April 2012

As a result of positive effects of the chelators DOTA and DOTAGA, when coupled to Tyr3‐octreotide, we designed a new potential chelator, DOTAtaGA, which combines these effects. DOTAtaGA has a spacer between the pharmacophoric part of the peptide and the chelator and forms neutral complexes with Yiii and InIII, as in the case of Y‐DOTA‐Tyr3‐octreotide. The corresponding prochelator DOTAtaGA(tBu)3 (1, 4, 7, 10‐tetraazacyclododecane‐1‐(1‐carboxy‐3‐carbo‐tertbutoxypropyl)‐4, 10 (carbotertbutoxymethyl)‐7‐acetamide) was synthesized in 3 steps with an overall yield of 16.5%. It was coupled to Tyr3‐octreotide, and the resulting peptide DOTAtaGA‐Tyr3‐octreotide has a ten times higher binding affinity to the somatostatin receptor subtype 2 than DOTA‐TOC.
Syntheses of new derivatives of amino acids and peptides and studies of their radioprotective activity
Authors: Kazaryan S. H. , Grigoryan K. P. , Gevondyan A. I. , Minasyan S. H. , Tonoyan V. J. , Bajinyan S. A. , Poghosyan A. S. , Malakyan M. H. , Sorenson J. R. S.
Published: April 2012

The synthesis of ethyl esters of 2‐salicylidene derivatives of tyrosine, γ‐amino butyric acid (GABA), and glycyl‐glycine was carried out. These Schiff base ligands present themselves as pale‐yellow crystals. These Schiff bases have been used to prepare Mn (II) complexes by allowing them to react with Mn (II) ion. Their possible structures were determined using several analytical and physical‐chemical techniques. These Mn (II) complexes are obtained as gray crystals.

Cytogenetic studies of bone marrow cells from whole‐body 4.2 Gy (0.42 Gy/min dose rate) irradiated white inbred rats revealed that prior administration of 10mg/kg of the Mn chelate of the ethyl ester of the 2‐salicylidene derivative of tyrosine was radioprotective. Compared to two control groups: (I) — animals exposed to irradiation only and (II) — animals treated with vehicle before irradiation, there was a 7‐fold decrease in number of chromosome aberrations. Mn‐chelates of 2‐salicylidene GABA and glycyl‐glycine were less radioprotective.

The studies compounds have just as superoxide scavanging activity.
Cellular processing of indirectly astatinated and iodinated mAb A33 in SW1222 cultured cells
Authors: Orlova A. , Sjöström A. , Ericson A. , Lebeda O. , Lundqvist H. , Carlsson J. , Tolmachev V.
Published: April 2012

In principle, alpha‐emitting radionuclides, such as 211At, are more efficient than beta‐emitters to inactive single disseminated cancer cells. However, cellular processing of astatinated proteins has not yet been studied in detail. In this study an anti‐colorectal cancer monoclonal antibody (mAb) A33 was indirectly labeled with 211At and for comparison with 125I. Binding and retention of radioactivity was studied in the colorectal cancer cell‐line SW1222. A similar pattern of binding and retention of the two radiohalogens was seen. The main difference found, that the retention time of astatinated mAb in SW1222 was almost two times longer, might be of advantage in radionuclide therapy.
The analogs of acetyl choline: Choline and thiocholine esters of amino acids and peptides
Authors: Kazaryan S. H. , Grigoryan K. P. , Gevondyan A. I. , Bajinyan S. A. , Malakyan M. H.
Published: April 2012

The synthesis was carried out to obtain choline and thiocholine esters of N‐protected and non‐protected amino acids and peptides.

As the N‐protecting group the benzyloxycarbonyl group was applied, which was then removed by CH3COOH/HBr after the synthesis of β‐amino esters. Choline and thiocholine esters are obtained by the interaction of the corresponding β‐ amino esters with iodic methyl.

The pharmacological studies have indicated that choline esters of both N‐protected amino acids and peptides, and non‐protected derivatives possess slight radioprotective activity.
Production of 103Pd by proton irradiation of silver
Authors: Mausner L. F. , Kolsky K. L. , Awasthi V. , Srivastava S. C.
Published: April 2012

Brachytherapy with 103Pd (t1/2= 16.97 d) has shown significant success in treating prostate cancer. We have investigated a new high‐energy accelerator route with the Ag(p, 2pxn)103Pd reaction. Natural Ag foils were irradiated at energies from 75 to 140 MeV at the Brookhaven Linac Isotope Producer (BLIP). Radiochemical separation of Pd from the Ag target utilized chromatography with Chelex‐100TM. A thick target (0.63cm) irradiation at 140 MeV, (45_A current, 24d) produced 751GBq of 103Pd and 259 GBq of 100Pd at EOB and useful quantities of 95mTc (3.3 GBq) and 97Ru (377 GBq). A 20d decay time is required to reduce the 100Pd (t1/2 = 3.6 d) and its daughter 100Rh (t1/2 = 20.8h) to less than 2%. The radiochemical process gave a Pd chemical recovery of ∼99%, specific activity at EOB 514MBq/_g, but some Rh isotope remained. Practical production of 850 GBq per run will be possible with thick targets.
The micro‐imager — a real‐time radio‐imaging system
Authors: Filthuth Heinz
Published: April 2012

The Micro‐Imager (1), a new technology allows to perform quantitative analysis in real‐time on radio‐ and luminescence labelled tissue and plant sections, bacteria and cell cultures, high density micro‐arrays of DNA, on geological samples and other 2‐dimensional objects.

The unique features of the instrument are very high spatial resolution (10–15 μm) and high detection sensitivity, 60% for 3H and 55Fe and 90% for all typical β‐emitters such as 14C, 35S, 1251, 1311, 33P, 32P, 99mTc.

Due to the high sensitivity short living positron emitters can be very well detected such as 18F, 11C, 15O and α‐emitters as 213Bi.
An improved enantioselective synthesis of no‐carrier‐added (NCA) 6‐[18F]FLUORO‐L‐DOPA
Authors: Wang Y. X. , Zhang L. , Tang G. H. , Yin D. Z.
Published: April 2012

6‐[18F]Fluoro‐L‐Dopa (6‐FDOPA) is the analogue of L‐Dopa, the biosynthesis precursor for dopamine. As a PET tracer, it was widely applied for the presynaptic dopamine function in cerebral studies in humans. The synthesis routes to this radiopharmaceutical could be divided into two main groups, that is, electrophilic and nucleophilic route. Lemaire et al reported a new nucleophilic synthesis procedure using a chiral phase‐transfer catalyst. A similar procedure with some improvements was described in this study. A trimethylammonium veratraldehyde triflate was synthesized and used as a precurser for the synthesis of 6‐[18F]Fluoro‐L‐Dopa by using the chiral phase‐transfer catalyst, O‐Allyl‐N‐(9)‐anthracenylcinchonidinium Bromide which was also synthesized in this study. The nca Fluorine‐18F‐fluoride was produced by the 18O(p, n) 18F nuclear reaction on enriched water. First the 6‐[19F]Fluoro‐L‐Dopa was synthesized to test the chemical structure of the synthesized end product and whole prcedure. Then the synthesis of 6‐[18F]Fluoro‐L‐Dopa was completed and identified by HPLC, TLC and MS(only the case of the 6‐[19F]Fluoro‐L‐Dopa).
An improved synthesis of 3′‐DEOXY‐3′‐[18F]fluorothymidine ([18F]FLT) and the fate of the precursor, 2, 3′‐anhydro‐5′‐O‐(4, 4′‐dimethoxytrityl)‐thymidine
Authors: Cleij M. C. , Steel C. J. , Brady F. , Ell P. J. , Pike V. W. , Luthra S. K.
Published: April 2012

Summary

The fate of the precursor, 2, 3′‐anhydro‐5′‐O‐(4, 4′‐dimethoxytrityl)‐thymidine was investigated during the synthesis of [18F]FLT with the aim of improving the radiochemical yield. This precursor was shown to undergo a rapid base catalysed elimination reaction and to be consumed within 5–10 min. The by‐product was identified. Modification of the synthesis has produced between 1.85–3.70 GBq (50–100 mCi) of [18F]FLT in 60 min using an automated synthesis system.
Radiolabeling of unprotected octreotide with F‐18
Authors: Panico M. , Lang L. , Sassaman M. B. , Eckelman W. C.
Published: April 2012

Octreotide can be labeled with fluorine‐18 as a potential radiopharmaceutical for quantitative in vivo mapping of somatostatin receptors in cancer patients. A one step synthesis that does not involve blocking and unblocking of the ε‐lysine amine would prevent preparation of the blocked starting material and would eliminate the need for hydrolysis after radiolabeling. The effect of labeling the ε‐amino of lysine versus the α‐amino moiety of D‐phenylalanine has been studied previously. In general, at high pH the ε‐amine of lysine is labeled when using reactive reagents, e.g. the Bolton Hunter reagent. At lower pH values, the α‐amino moiety is labeled, but never quantitatively (1). We found that using octreotide and the N‐succinimidyl 4‐fluorobenzoate, we could obtain radiolabeling yields of >15% for the α‐amino moiety at neutral pH. The radioligand was easily separated and did not require the blocked precursor. This yield is sufficient for carrying out experiments in large animals and human subjects.
A versatile, commercially available automated synthesizer for the development and production of pet radiotracers
Authors: Hostetler E. D. , Hamill T. G. , Francis B. E. , Burns H. D.
Published: April 2012

The automation of routinely produced radiotracers is an important process for any PET center. Automation allows frequent, highly reproducible syntheses with large amounts of radioactivity while minimizing exposure to the radiochemist in comparison with manual radiotracer synthesis. We found the Gilson SK233 Work Station, coupled with Gilson's 735 Sampler Software and a Gilson SPE (solid phase extraction) module, to be a versatile, user‐friendly, and cost‐effective solution to our need for automation in the development and routine synthesis of radiotracers.
Production, processing and uses of 94mTc
Authors: Bigott H. M. , Mccarthy D. W. , Wüst F. R. , Dahlheimer J. L. , Piwnica‐Worms D. R. , Welch M. J.
Published: April 2012

Technetium‐99m is a widely used radioisotope in nuclear medicine. The characteristics of this generator‐produced radionuclide (T1/2 = 6 h, Eγ = 140.5 keV, Iγ = 87.2 %) make it an ideal isotope for single photon emission computed tomography (SPECT). Technetium‐94m has a half‐life of 52 minutes and a positron branching ratio of 72 %, with Eβ+max of 2.44 MeV. Technetium‐94m undergoes the same chemistry as 99mTc, but has characteristics suitable for imaging using positron emission tomography (PET), with which more quantitative measurements of radiopharmaceutical uptake, biodistribution and clearance can be made.
Synthesis and in vivo evaluation (PIG) of the selective seretonin reuptake inhibitor [11C]NS 2456
Authors: Smith D. F. , Bender D. , Marthi K. , Cumming P. , Hansen S. B. , Peters D. , Nielsen E. ØStergaard , Scheel‐Krüger J. , Gjedde A.
Published: April 2012

We evaluated a new selective serotonin reuptake inhibitor, NS 2456, to determine whether it is suited for use in PET. Racemic NS 2456 [(1RS, 5SR)‐8‐methyl‐3‐[4‐trifluoromethoxy phenyl]‐8‐azabicyclo [3.2.1]oct‐2‐ene] and its N‐demethylated analogue, racemic NS 2463, selectively inhibit serotonin uptake in rat brain synaptosomes. For uses in PET of the living porcine brain, racemic [11C]NS2463 as well as its radiolabelled enantiomers were used. The compounds crossed the blood‐brain‐barrier rapidly and accumulated preferentially in regions rich in serotonin uptake sites. However their binding potentials were relatively low and no stereoselectivity was found. Thus, neither [11C]NS 2456 nor [11C]‐labelled enantiomers are ideal for PET neuroimaging of neuronal serotonin uptake sites.
Human plasma kinetics and metabolites of [123I]CNS‐1261 — a novel NMDA receptor radioligand for spet
Authors: Mulligan R. S. , Erlandsson K. , Bressan R. A. , Owens J. , Ell P. J. , Pike V. W. , Pilowsky L. S.
Published: April 2012

This study reports on the pharmacokinetics and metabolism of [123I]CNS‐1261 as part of the validation of this radioligand for imaging the activated NMDA ion channel in humans with SPET. After injection of [123I]CNS‐1261, radioactivity is cleared rapidly from plasma. Parent radioligand is metabolised to three, more polar radioactive metabolites. Arterial and venous plasma radioactivity has also been measured and compared. Arterial data is required for biomathematical modelling.
Radiosynthesis of [4‐O‐methyl‐11C]KF18446 as a potential ligand for the central adenosine a2A receptor and comparison with [4‐O‐methyl‐11C]KW6002 in rats
Authors: Turton D. R. , Hirani E. , Osman S. , Poole K. , Falokun G. , Brady F. , Karasawa A. , Shimada J. , Brooks D. J. , Hume S. , Luthra S. K.
Published: April 2012

The adenosine A2A antagonist, KF18446 was labelled in the aromatic O‐methyl position using [11C]iodomethane. [4‐O‐methyl‐11C]KF18446 and [4‐O‐methyl‐11C]KW‐6002, an adenosine A2A antagonist that we radiolabelled previously, were evaluated in rats. In brain, both [4‐O‐methyl‐11C]KW‐6002 and [4‐O‐methyl‐11C]KF18446 showed the highest uptake in striata and lowest in frontal cortex. For [4‐O‐methyl‐11C]KW‐6002 maximal striata: frontal cortex ratio was 1.7 from 60 to 120 min. For [4‐O‐methyl‐11C]KF18446 maximal striata: frontal cortex ratio was 2.4 from 30 to 90 min. The amount of unchanged [4‐O‐methyl‐11C]KW‐6002 was > 98 % in striata and cerebellum at 75 min post‐injection.
Significance of circulating endothelial progenitor cells in patients with fracture healing process
Authors: Ma Xin‐Long , Sun Xiao‐Lei , Wan Chun‐You , Ma Jian‐Xiong , Tian Peng
Published: April 2012

Fracture healing is a complex bone formation process, and neovascularization may contribute to new bone regeneration. The circulating endothelial progenitor cell (EPC) mobilization and homing could involve in neovascularization and vasculogenesis. In this study, we investigate the changes of circulating EPC during bone fracture healing, and the possible contribution of EPCs to increased neovascularization and fracture healing. The number of circulating EPCs was monitored in twenty‐four patients with long bone traumatic fracture within the first 48 h and at 3, 5, 10, and 14 days post‐fracture. The mononuclear cells which isolated from peripheral blood were analyzed by flow cytometry. Peripheral blood counts of leukocytes and platelets were measured by hematology analyzer. The amount of peripheral EPCs significantly increased in patients with fracture compared to age‐matched healthy control subjects within the first 48 h after injury, and peaked at 3 days post‐fracture. There was no significant difference in the change trend of early EPCs between male and female, but the number of early EPCs was significantly greater in younger patients compared to older patients. A comparison of the EPCs levels between patients with severe injury (ISS > 16) and patients with mild injury (ISS ≤ 16) revealed no statistically significant difference. The level of early EPCs was inverse correlation with the level of plate after fracture, but no correlation with the level of peripheral leucocytes. These findings suggest traumatic fracture may induce the mobilization of EPCs into the peripheral circulation. The increased EPCs may contribute to neovascularization and involve in fracture healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1860–1866, 2012
Effects of seeding rate, nitrogen rate and cultivar on barley malt quality
Authors: Edney Michael J , O'Donovan John T , Turkington T Kelly , Clayton George W , McKenzie Ross , Juskiw Pat , Lafond Guy P , Brandt Stewart , Grant Cynthia A , Harker K Neil , Johnson Eric , May William
Published: April 2012

BACKGROUND:Crop management tools have been shown to affect barley kernel size and grain protein content, but the direct effect on malt quality is not well understood. The present study investigated the effect of seeding rate, nitrogen fertilisation and cultivar on malt quality.

RESULTS:Higher seeding rates produced barley with less grain protein and smaller, more uniformly sized kernels. The small, uniformly sized kernels modified more completely, leading to malt with higher extract and lower wort β‐glucan than malt from low‐seeding‐rate barley. Increasing rates of nitrogen fertilisation caused grain protein levels to increase, which limited endosperm modification and reduced malt extract levels. AC Metcalfe showed better modification and higher malt extract than CDC Copeland, but CDC Copeland had better protein modification at higher fertilisation rates, which resulted in less reduction of malt extract as nitrogen rate increased.

CONCLUSION:Higher seeding rates reduced kernel size and grain protein levels without compromising malt extract owing to better endosperm modification of the more uniformly sized kernels. Negative effects of higher nitrogen rates on malt quality can be reduced through development of cultivars with improved ability to modify protein during malting. © 2012 Her Majesty the Queen in Right of Canada
Naked and Self‐Clickable Propargylic‐Decorated Single‐Chain Nanoparticle Precursors via Redox‐Initiated RAFT Polymerization
Authors: Sanchez‐Sanchez Ana , Asenjo‐Sanz Isabel , Buruaga Lorea , Pomposo José A.
Published: April 2012

Protection of acetylenic monomers is a common practice to avoid parasitic side reactions during polymerization. Herein, we report that redox‐initiated RAFT polymerization allows the direct, room temperature synthesis of a variety of single‐chain nanoparticle precursors (displaying narrow molecular weight dispersity, $\overline{M}_{\rm w}$/$\overline{M}_{\rm n}$ = 1.12 –1.37 up to $\overline{M}_{\rm w}$ = 100 kDa) containing well‐defined amounts of naked, unprotected acetylenic functional groups available for rapid and quantitative intrachain cross‐linking via metal‐catalyzed carbon–carbon coupling (i.e., C–C “click” chemistry). To illustrate the useful “self‐clickable” character of the new unprotected acetylenic precursors, single‐chain nanoparticles have been prepared for the first time in a facile and highly efficient manner by copper‐catalyzed alkyne homocoupling (i.e., Glaser–Hay coupling) at room temperature under normal air atmosphere.
Fabrication of Arrays of Polymer Gradients Using Inkjet Printing
Authors: Hansen Anne , Zhang Rong , Bradley Mark
Published: April 2012

Arrays of 84 polymer gradients, fabricated on a single glass microscope slide, were generated by inkjet printing, allowing a combination of high‐throughput and true combinatorial methods. The gradual change of composition within the polymer gradients, consisting of two different monomers and a cross‐linker, was validated by XPS and fluorescence analysis. Cellular screening of the gradients allowed the rapid identification of optimal polymer compositions for binding of the suspension cell line K562 and the adherent cell line HeLa. The polymers identified were identical to those identified by previous microarray data, providing proof of concept for the successful application of the polymer gradient arrays as a screening tool. In addition, the polymer gradients could be readily modified by conjugation enabling the generation of bio‐molecule gradients.
Highly undersampled phase‐contrast flow measurements using compartment‐based k–t principal component analysis
Authors: Giese Daniel , Schaeffter Tobias , Kozerke Sebastian
Published: April 2012

The applicability of cine blood flow measurements in a clinical setting is often compromised by the long scan times associated with phase‐contrast imaging. In this work, we propose an extension to the k–t principal component analysis method and demonstrate that by definition of spatial compartment‐dependent temporal basis functions, significant improvements in reconstruction accuracy can be achieved relative to the original k–t principal component analysis and k–t SENSE formulations. Using this method, it is shown that prospective nominal undersampling of up to 16 corresponding to a net acceleration factor of 8 including training data acquisition can be realized while keeping the error in stroke volume below 5%. As a practical application, the acquisition of cine flow data in the aorta is demonstrated permitting assessment of two‐dimensional velocity images and pulse wave velocities at 100 frames per second in a single breathhold per slice. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Improved partial volume correction for single inversion time arterial spin labeling data
Authors: Liang Xiaoyun , Connelly Alan , Calamante Fernando
Published: April 2012

Arterial spin labeling has relatively low spatial resolution, which affects cerebral blood flow measurements by partial volume effect occurring at tissue interfaces, e.g., between gray matter, white matter, and cerebrospinal fluid. This can be an important source of cerebral blood flow quantification error. To correct for partial volume effect in arterial spin labeling, a linear regression method was recently proposed. Because this method assumes that tissue magnetization and cerebral blood flow are constant over an n2 × 1 regression kernel, an inherent spatial blurring is introduced. In this study, a modified least trimmed squares algorithm is proposed for partial volume effect correction. It is demonstrated using simulations that the modified least trimmed square method can correct for partial volume effect and produce less blurring than the linear regression method. This is achieved without either acquiring additional datasets or increasing the computation burden. These capabilities were further demonstrated in vivo. The modified least trimmed square method should, therefore, play an important role in arterial spin labeling studies. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Measurement of vibration‐induced volumetric strain in the human lung
Authors: Hirsch Sebastian , Posnansky Oleg , Papazoglou Sebastian , Elgeti Thomas , Braun Jürgen , Sack Ingolf
Published: April 2012

Noninvasive image‐based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase‐contrast MRI to measure three‐dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three‐dimensional vector fields of 50‐Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective‐medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression‐sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence‐sensitive MRI may serve as a noninvasive marker sensitive to disease‐related alterations of regional elastic recoil pressure in the lungs. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Russian lobbying in the United States: stages of evolution
Authors: Kostyaev Sergey Sergeevich
Published: April 2012

The article examines Russian lobbying in the US. The endogenous and exogenous factors of Russian lobbying are analyzed as well as its qualitative and quantitative characteristics. The article depicts stages of Russian lobbying development: (i) from government to private entities; (ii) nongovernmental lobbying; and (iii) a return to government. Additionally, occasional attempts by Russian entities to secure funding from the US budget are mentioned. Two case studies are studied to show the nature of current Russian lobbying in the US: lobbying campaigns by Techsnabexport, state‐owned corporation, and GML, a private business concern. The article concludes that Russian lobbying in the US is weak. At the beginning, it was mostly about investment consulting, and with the rise in oil prices and the decrease in political freedom, the need for and availability of lobbying diminished. Some private corporations were nationalized under President Putin and, as a result, lost control over their international expansion strategies, with the remaining private corporations being afraid of independent lobbying campaigns abroad. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of plasma treatment on greenhouse polyethylene cover aged under sub‐Saharan conditions
Authors: Dobbi Abdelmadjid , Bouabdallah Ahcene , Bouchama Mohamed , Meghoufel Faiza Zahira , Hassini Noureddine
Published: April 2012

The effects of natural ageing, in sub‐Saharan regions, on treated low density polyethylene by cold plasma are presented in this work. The data analysis is performed by comparing the changes of physical, mechanical and structural effects on the material surface induced by plasma treatment with regard to the natural abrasion effect due to sand wind. Plasma treatments for short durations are applied to neutral LDPE (low density polyethylene) films. Few seconds suffice to observe chemical changes on the samples. The treated samples are then subjected to natural ageing in the region of Ouargla (south of Algeria), characterized by very frequent sand wind. The characterization of the effects of plasma treatment and its combination with sand wind is performed using XPS (X‐ray Photoelectron Spectroscopy), FTIR (Fourier Transform Infrared spectrometry), and mechanical tensile testing. The results led to conclude a synthesis of new materials on the surface that significantly change the material surface properties and physico‐chemical properties of material, more particularly, optical, and mechanical properties are thus strongly affected. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers