bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical Advance: Function and efficacy of an α4-integrin antagonist using bioluminescence imaging to detect leukocyte trafficking in murine experimental colitis
Authors: Murphy Carola T , Moloney Gerard , MacSharry John , Haynes Andrea , Faivre Emilie , Quinlan Aoife , McLean Peter G , Lee Kevin , OˈMahony Liam , Shanahan Fergus , Melgar Silvia , Nally Kenneth 
Published: August 2010

Abstract
Method for in vivo bioluminescence imaging as a valuable strategy for pre-clinical evaluation of leukocyte trafficking as shown here for small molecule α4-integrin antagonists as a promising therapeutic for IBD.
Leukocyte trafficking is a therapeutic target in IBD. The integrins α4β7 and α4β1 regulate leukocyte migration into tissues and lymphoid organs. Current strategies rely on biologics, such as mAb, to inhibit leukocyte recruitment. Here we show the in vivo therapeutic effects of a small molecule α4-integrin antagonist (GSK223618A) in a leukocyte-trafficking model and a murine model of colitis. Leukocytes isolated from MLNs of transgenic β-actin-luc+ mice were injected i.v. into recipients with DSS-induced colitis. Recipient mice were orally gavaged with vehicle or an α4-integrin antagonist 1 h pre-adoptive transfer, followed by bioluminescence whole body and ex vivo organ imaging 4 h post-transfer. To confirm its therapeutic effect, the α4-integrin antagonist was given orally twice daily for 6 days to mice with DSS-induced colitis, starting on Day 3. Clinical, macroscopic, and histological signs of inflammation were assessed and gene-expression profiles analyzed. Using bioluminescence imaging, we tracked and quantified leukocyte migration to the inflamed gut and demonstrated its inhibition by a small molecule α4-integrin antagonist. Additionally, the therapeutic effect of the antagonist was confirmed in DSS-induced colitis in terms of clinical, macroscopic, and histological signs of inflammation. Gene expression analysis suggested enhancement of tissue healing in compound-treated animals. Inhibition of leukocyte trafficking using small molecule integrin antagonists is a promising alternative to large molecule biologics. Furthermore, in vivo bioluminescence imaging is a valuable strategy for preclinical evaluation of potential therapeutics that target leukocyte trafficking in inflammatory diseases.
Parathyroid Hormone Treatment Improves Pain and Fracture Healing in Adult Hypophosphatasia
Authors: Schalin-Jäntti Camilla , Mornet Etienne , Lamminen Antti , Välimäki Matti J. 
Published: August 2010

Introduction: Adult hypophosphatasia (HPP) is characterized by low serum alkaline phosphatase (S-ALP) and poorly healing fractures due to ALPL gene mutations. Increased S-ALP and fracture repair were reported in two patients treated with teriparatide, PTH 1-34. The effects of full-length PTH 1-84 have not been studied.
Methods: Two 56- and 64-yr-old sisters (patients 1 and 2) with HPP and with long-standing, painful femur fractures received PTH 1-84 (Preotact, 100 μg/d sc) for 7 and 18 months, respectively. Patient 1 had another treatment 8 months later because of new femur fractures. We characterized the underlying mutation(s) and treatment effects according to S-ALP, bone markers, serum ionized calcium, plasma phosphate (P-Pi), pain, mobility, and fracture healing.
Results: Both patients were compound heterozygotes for a p.G339R and p.E191K ALPL mutation. S-ALP increased significantly, 4.9- and 6.8-fold in patient 1 and 2.7-fold in patient 2. Responses decreased at 6 months but remained higher than basal activity. Serum N-terminal propeptide of type I procollagen and urinary N-telopeptide of type I collagen increased 14- to 19-fold and 9–5-fold in patient 1, respectively, and 9- and 3-fold in patient 2. P-Pi fluctuated in patient 1 and increased in patient 2. Pain and mobility improved promptly. Fractures healed after 7–8 months of treatment in patient 1 and at 15 months in patient 2.
Conclusion: PTH 1-84 improves pain, mobility, and fracture repair in adult HPP, even after repeat treatment. Residual activity of the p.E191K ALPL gene mutation could explain why PTH can stimulate S-ALP. P-Pi concentrations may modulate the response.
The Thyroid Hormone Receptor α1 Protein Is Expressed in Embryonic Postmitotic Neurons and Persists in Most Adult Neurons
Authors: Wallis Karin , Dudazy Susi , Hogerlinden Max van , Nordström Kristina , Mittag Jens , Vennström Björn 
Published: August 2010

AbstractThyroid hormone is essential for brain development where it acts mainly through the thyroid hormone receptor α1 (TRα1) isoform. However, the potential for the hormone to act in adult neurons has remained undefined due to difficulties in reliably determining the expression pattern of TR proteins in vivo. We therefore created a mouse strain that expresses TRα1 and green fluorescent protein as a chimeric protein from the Thra locus, allowing examination of TRα1 expression during fetal and postnatal development and in the adult. Furthermore, the use of antibodies against other markers enabled identification of TRα1 expression in subtypes of neurons and during specific stages of their maturation. TRα1 expression was first detected in postmitotic cells of the cortical plate in the embryonic telencephalon and preceded the expression of the mature neuronal protein NeuN. In the cerebellum, TRα1 expression was absent in proliferating cells of the external granular layer, but switched on as the cells migrated towards the internal granular layer. In addition, TRα1 was expressed transiently in developing Purkinje cells, but not in mature cells. Glial expression was found in tanycytes in the hypothalamus and in the cerebellum. In the adult brain, TRα1 expression was detected in essentially all neurons. Our data demonstrate that thyroid hormone, unexpectedly, has the capacity to play an important role in virtually all developing and adult neurons. Because the role of TRα1 in most neuronal cell types in vivo is largely unknown, our findings suggest that novel functions for thyroid hormone remain to be identified in the brain.
Synthesis of Novel Photochromic Calix[4]arene Ligand Bearing a Spirobenzopyran and Three Ethyl-Ester Moieties and Photocontrol of Its Alkali Metal Ion Extractability
Authors: Machitani Koji , Saeda Megumi , Nakahara Yoshio , Kimura Keiichi 
Published: August 2010

Abstract
A novel photochromic calix[4]arene ligand bearing a spirobenzopyran and three ethyl-ester moieties (compound 1) was synthesized, and photocontrol of its alkali metal ion extractability was studied. In the dark, compound 1 showed the largest changes of absorption spectra for Na+ among alkali metal ions. When Na+ was gradually added to the solution of compound 1, its complexation behavior was evaluated by 1H NMR, which suggests that Na+ was taken into the cavity formed by four carbonyl oxygens and four ether oxygens, and that compound 1 formed a 1:1 complex with Na+. The proton signals originating from the spirobenzopyran moiety were slightly changed by metal-ion complexation. This means that the spirobenzopyran moiety was not very close to Na+ under dark conditions. Liquid–liquid extraction experiments with alkali metal ion using compound 1 made it clear that the extractability of Na+ was enhanced under UV-light irradiation, compared with that under visible-light irradiation. This suggests that the electrostatic interaction between a phenolate anion of the merocyanine moiety generated by UV-light irradiation and Na+ promotes the extractability to some extent.
Construction of Two- or Three-Component Low Molecular Weight Gel Systems
Authors: Yamanaka Masamichi , Aoyama Ryohei 
Published: August 2010

Abstract
Pyridyl group-bound tris-urea 2, whose structure is similar to the tris-urea low molecular weight gelator (LMWG) 1, was synthesized. Addition of a trace amount of 2 and Pd(OAc)2 to 1 resulted in a reduction in the critical gelation concentration (CGC) in acetone. Metal–ligand interaction between Pd(OAc)2 and the pyridyl group of 2 assist the gelation. Assistance by intermolecular hydrogen bonding was also effective for gelation of acetone. An acetone gel of 1 was formed at half the value of the CGC of 1 alone by adding a trace amount of 2 and isophthalic acid. Scanning electron microscopy (SEM) measurements of these aggregates showed structural alterations caused by the additive. A mixture of 1 and a trace amount of 2 in EtOAc gave a gel. Addition of 2 was essential to form the gel, because 1 alone did not gel EtOAc. SEM measurements indicated that 2 produced extension of the fibrous aggregates.
Comparative outcome of oesophagogastric cancer in younger patients
Authors: Mehta Samir P , Bailey Diana , Davies Nick 
Published: August 2010

INTRODUCTION The incidence of oesophageal and gastric cardia adenocarcinoma has increased rapidly over the previous two decades. There has been a rise in the number of younger patients affected, and the disease may be more aggressive and have a worse prognosis in these individuals. Current UK guidelines for urgent cancer referral focus on patients who are over 55 years. This study prospectively compares the referral times and outcome in a cohort of patients diagnosed with oesophagogastric cancer under the age of 55 years with a matched cohort over 55 of age. PATIENTS AND METHODS Every patient diagnosed with oesophageal, junctional or gastric cancer under the age of 55 years and every subsequent patient over the age of 55 years was accepted into this study. In all, 17 hospitals participated over a 12-month period. The following data were recorded: duration of symptoms, number of fast-track referrals, duration from GP referral to first hospital visit and stage at presentation. A survival analysis between the two groups was conducted at 2 years after the end of recruitment. RESULTS In total, 102 patients under the age of 55 years were diagnosed with oesophagogastric cancer during the study period. There were fewer fast-track referrals from GPs in this group compared to the over 55-year matched cases (29.4% vs 40.2%). Duration of time from GP referral to first hospital visit was significantly longer in the under 55-year group (median 14 days vs 11 days; P = 0.045 Mann-Whitney). Stage at presentation was similar between groups, but a higher proportion of patients under 55 years were offered a curative treatment plan compared to those over 55 years (P < 0.01). Survival analysis conducted at 2 years after the end of recruitment demonstrated a longer median survival in the under 55-year group (348 days vs 248 days; P = 0.03 log rank). CONCLUSIONS Although there was a longer referral time in patients under the age of 55 years, this had no effect on disease stage at presentation. Patients under the age of 55 years diagnosed with oesophageal or gastric cancer appear to have a better prognosis than those aged over 55 years.
Nailbed repair and patient satisfaction in children
Authors: Pearce S , Colville RJI 
Published: August 2010

INTRODUCTION We performed an audit to assess frequency of injury to the nail bed and outcomes after repair in a busy paedi-atric hand trauma clinic. SUBJECTS AND METHODS This retrospective study examines 46 consecutive nail bed repairs over a 6-month period. All notes were reviewed for patient demographics, details of the injury including the operation and aftercare. Telephone interviews were used to assess patient/parent satisfaction and complications. RESULTS The commonest mechanism of injury was trapping a finger in a door. The accident usually occurred indoors and most frequently affected the middle finger. The majority of repairs were carried out under general anaesthetic, by registrars, using absorbable synthetic sutures, within 24 h of the injury as a day-case. Outcome data with a minimum of 15 months follow-up, showed a high satisfaction rate (8.9/10) and low complication rate (7%), none of which required further surgery. There was a high failure rate of attendance in the follow-up clinic whilst the outcomes of those attending were good. CONCLUSIONS Outcomes and patient satisfaction were good with a low complication rate resulting in a change of practice in our unit to an ‘opt-in’ system for follow-up.
Mechanisms of recurrence of Ta/T1 bladder cancer
Authors: Bryan Richard T , Collins Stuart I , Daykin Mark C , Zeegers Maurice P , Cheng KK , Wallace D Michael A , Sole Graham M 
Published: August 2010

INTRODUCTION Bladder cancer recurrence occurs via four mechanisms - incomplete resection, tumour cell re-implantation, growth of microscopic tumours, and new tumour formation. The first two mechanisms are influenced by clinicians before and immediately after resection; the remaining mechanisms have the potential to be influenced by chemopreventive agents. However, the relative importance and timing of these mechanisms is currently unknown. Our objective was to postulate the incidence and timing of these mechanisms by investigating the location of bladder cancer recurrences over time. PATIENTS AND METHODS The topographical locations of tumours and their recurrences were analysed retrospectively for 169 patients newly-diagnosed with Ta/T1 bladder cancer, with median follow-up of 33.8 months. Tumours were assigned to one or more of six bladder sectors, and time to recurrence and location of recurrences were recorded. RESULTS Median time to first tumour recurrence was 40 months. Median times between subsequent recurrences were 6.6, 7.9, 8.0 and 6.6 months for recurrences 1 to 2, 2 to 3, 3 to 4, and 4 to 5, respectively. The risk of first tumour recurrence in any given bladder sector increased by nearly 4-fold if the primary tumour was resected from that sector (P < 0.001); this association was not significant for subsequent recurrences. The proportion of tumour recurrences in multiple bladder sectors increased from 13% for the first recurrence to 100% for recurrence seven onwards. CONCLUSIONS First tumour recurrence appears different to subsequent recurrences; incomplete resection and tumour cell re-implantation may dominate at this time-point. Only later does genuine new tumour formation appear to increase in importance. This has important implications for clinical trials, especially those involving chemopreventive agents.
Plasma Renin Activity by LC-MS/MS: Development of a Prototypical Clinical Assay Reveals a Subpopulation of Human Plasma Samples with Substantial Peptidase Activity
Authors: Bystrom Cory E , Salameh Wael , Reitz Richard , Clarke Nigel J 
Published: August 2010

BACKGROUND
For management and treatment of secondary hypertension, plasma renin activity (PRA) assay is considered an essential diagnostic tool. We developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based approach to PRA offering improvements in laboratory workflow and throughput. During development, we observed a substantial number of clinical samples that have strong degradation activity toward angiotensin (Ang) I during generation. A preliminary characterization of this degradation activity was performed, and we provide here a method by which this degradation can be monitored via the addition of an isotope-labeled degradation standard.

METHODS
Automated online sample extraction coupled with HPLC was used to isolate Ang I and internal standard from plasma. The effluent from the analytical column was directed to a triple quadrupole MS operated in selected reaction monitoring mode, monitoring the a5 and b5 product ions from the [M+3H]+3 precursors. Routine analysis could be achieved with as little as 150 μL plasma.

RESULTS
We identified both C-terminal and N-terminal degradation products of Ang I using isotope-labeled peptides as controls and substrates. In 2%–5% of patient samples, the degradation essentially eliminated any Ang I produced during generation.

CONCLUSIONS
Our method requires reduced sample handling when compared with an RIA and eliminates the need for extended generation times for samples with low renin activity. Degradation of Ang I during generation appears to be a confounding variable in the interpretation of results from some clinical samples. Samples with profound degradation activity can be identified using a degradation standard that is added at the start of generation.
Analytical Characterization of Sediment Formed in Soy Oil-Based B20 Biodiesel
Authors: McGinnis Timothy P. , Peyton Kim B. 
Published: August 2010

Abstract
A thick, gel-like precipitate, which separated from a B20 blend, has been characterized using a variety of analytical techniques. The sediment formed in a blend of soy-based fatty acid methyl ester (FAME) and ultra low sulfur diesel (ULSD), which had been stored under ASTM D4625 conditions without the presence of antioxidant. Analysis indicates that the majority of the sediment consists of a wide variety of polar oxygenated compounds. These vary considerably in molecular weight. The lower molecular weight species arise due to oxidative cleavage of the methyl esters. Also present are free fatty acids formed due to hydrolysis of FAME. The highest molecular weight compounds are oxidized FAME that have not undergone cleavage and oligomers of the oxidized FAME. Monoglycerides and steryl glucosides are not significant components in this sediment. The sediment does contain some diesel fuel, intact FAME, and impurities, which are inherent to the FAME. A proposed scenario for the formation of this type of sediment is as follows: As free radical formation, oxidation, and hydrolysis occur in unsaturated methyl esters, there are numerous polar organic compounds formed. These vary widely in molecular weight and include carboxylic acids, alcohols, aldehydes, and ketones, as well as compounds containing combinations of these functional groups. All of these reaction products undergo aggregation due to their polarity differences with the bulk matrix. Included in these aggregates are the trace components present as impurities in the FAME, such as water, glycerol, glycerides, plant sterols, and steryl glucosides. Eventually, a level of thermodynamic instability is reached and phase separation occurs. While the aggregates and sediment contain significant polar functionality, they still maintain a very high degree of alkyl and olefinic character. As a result, intact FAME and diesel fuel components have a certain degree of solubility in the aggregated mixture and make up part of the precipitated sediment.
Stress Crack Protocol for Finished Product Testing of Corrugated High Density Polyethylene Pipe
Authors: Kurdziel John M. 
Published: August 2010

Abstract
The primary load bearing component of a dual wall corrugated high density polyethylene pipe is the annular corrugated wall. It is this area that necessitates engineering evaluation with regard to the maximum permissible strains and the associated stress crack resistance of this thermoplastic material. This paper presents the protocol for evaluating the stresses in these critical structural members with new testing methods for determining the long-term stress capacity or service life for these members. This test method provides an alternate long-term stress crack evaluation protocol that will allow the user to design piping systems for a desired service life with more accuracy than simply specifying hydrostatic design basis rated resins.
General polyhedra, virus structure and mutation
Authors: Andersson Sten 
Published: August 2010

Abstract
We describe how mutations of viruses can be understood, organized and described as truncation and chiral operations on the shape of the capsids described by a summations taking into account the pentagonal symmetry. This gives an unlimited number of possible variations and serves as a mathematical description of a new concept of polyhedra. E.g., the HK97 structure is n = 8 in the Blue tongue series.
The crystal structure and the disorder behaviour of NO[NbCl6]
Authors: Henke Henning 
Published: August 2010

Abstract
NO[NbCl6] crystallizes in the noncentrosym metric space group P212121 with a = 6.630(1), b = 6.746(1), c = 39.23(1) Å at 150 K and Z = 8; i.e. there are two formu la units in the asymmetric unit. X-ray data have been re corded by means of an imaging plate system.
The interaction between the nitrosonium cations and the hexachloridoniobate anions polarizes the latter such that the niobium atoms are displaced from the centre of their chlorine polyhedra by 0.17 and 0.16 Å, respectively. The NO+ ions develop disorder, in both cases with preference for one out of two possible orientations.
Trends in Food Photography: A Prop Stylist's View
Authors: matalon-degni francine 
Published: August 2010

This article traces the evolution of food photography through the lens of its political context. The ways in which prop stylists and food stylists defined food photography trends was guided by more than their unique interpretation of assigned art direction. The political zeitgeist was also a guiding force. From the socially conservative leadership during the Reagan/Bush years to the promises of hope and change defining the Obama presidency——the tenor of each administration left its mark on food photography.
During the Reagan/Bush years, legislation favored the moneyed classes; food photography reflected the tastes of a culture rife with opulent excess. Food was presented in fantastical sets propped with precious accoutrements, some having hardly anything at all to do with the eating or serving of food. The Clinton administration's pro-family domestic agenda set the cultural tone for Martha Stewart's ascendency and for her magazine's visual message to endure. Both Clinton and Stewart brought us back to the real world. Food sets became whiter and brighter as prop stylists jettisoned intricately detailed props for those with cleaner, simpler lines. The muddled disinformation fed to us during the George W. Bush years played out in the confusing, tumultuous compositions proliferating Gourmet's food photography during his presidency. Yellow, the color of hope and promise, cast its hue on the food pages of magazines at the onset of Obama's presidency; but just as he chose to address policymaking by embracing a myriad of viewpoints, so too did magazines embrace a mix of visual viewpoints to please their readers. What we were left with, on both fronts, was an all-over-the-place quality lacking clear definition.
Photographs from Gourmet, Food & Wine, Bon Apetit, Weight Watcher's Magazine, Woman's Day and Fine Cooking serve as visual reference points.
Estimating the Per Capita Rate of Population Change: How Well Do Life-History Surrogates Perform?
Authors: Chmielewski M W , Khatchikian C , Livdahl T 
Published: August 2010

Abstract
A method of estimating per capita rate of change for experimental populations in the absence of adult survival and fecundity schedules (r′) was proposed previously (J. Anim. Ecol. 53: 573–580; 1984). The method has been used repeatedly, although there has been no attempt to verify the relationship between r′ and the per capita growth rate in populations. This method was tested with laboratory populations of the mosquito Aedes albopictus (Skuse) (Diptera: Culicidae) growing at three larval densities. Survival and fecundity schedules enabled calculation of per capita growth rate, r, for each population, whereas measuring emergent females enabled the calculation r′. The capacity of r′ to predict r was significant, although a substantial amount of variation in r remained unaccounted for, and r′ overestimated r. The degree of overestimation of r by r′ was consistent across the three densities, and the regressions off and r′ versus density were similar. Overestimation of per capita rate of change by r′ is attributed largely to extensive adult longevity in laboratory conditions for this species, coupled with a lengthy reproductive period, in combination with prereproductive adult mortality, both of which are assumed to be negligible with the r′ method. Separate indicators of larval success were also tested for their predictions of r; only first day emergence and average development time were significant predictors although neither performed as well as r′. The r′ index accounted for the largest fraction of variation in r. Implications of overestimating r by r′ to estimating other population parameters are discussed.