bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of platelet transfusion: past, present and future
Authors: Katus M. C. , Szczepiorkowski Z. M. , Dumont L. J. , Dunbar N. M.
Published: March 2014

Platelet components became routinely available to many institutions in the late 1960s and since then utilization has steadily increased. Platelets are produced by three principal methods and their manufacturing process is regulated by multiple agencies. As the field of platelet transfusion has evolved, a broad array of strategies to improve platelet safety has developed. This review will explore the evolution of modern platelet component therapy, highlight the various risks associated with platelet transfusion and describe risk reduction strategies that have been implemented to improve platelet transfusion safety. In closing, the reader will be briefly introduced to select investigational platelet and platelet‐mimetic products that have the potential to enhance platelet transfusion safety in the near future.
Caprine pancreatic islet xenotransplantation into diabetic immunosuppressed BALB/c mice
Authors: Hani Homayoun , Allaudin Zeenathul N. , Mohd‐Lila Mohd‐Azmi , Ibrahim Tengku A. Tengku , Othman Abas M.
Published: March 2014

Background

Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use of caprine (goat) islet cells as xenogeneic grafts in the treatment for diabetes in a mouse model.

Methods

Caprine pancreases were harvested and transported to the laboratory under conditions optimized to prevent ischemia. Islets were isolated, purified, and tested for functionality. Caprine islets (2000 islet equivalent) were transplanted beneath the kidney capsules of diabetic BALB/c mice under thalidomide‐induced immunosuppression. Blood glucose and insulin levels of grafted mice were evaluated by glucometer and enzyme‐linked immunosorbent assay kit, respectively. The functionality and quality of caprine pancreatic islet grafts were assessed by intraperitoneal glucose tolerance tests.

Results

The viability of purified islet cells exceeded 90%. Recipient mice exhibited normoglycemia (<11 mm glucose) for 30 days. In addition, weight gain negatively correlated with blood glucose level. The findings verified diabetes reversal in caprine islet recipient mice. A significant drop in non‐fasting blood glucose level (from 23.3 ± 5.4 to 8.04 ± 0.44 mm) and simultaneous increase in serum insulin level (from 0.01 ± 0.001 to 0.56 ± 0.17 μg/l) and body weights (from 23.64 ± 0.31 to 25.85 ± 0.34 g) were observed (P < 0.05). Immunohistochemical analysis verified insulin production in the transplanted islets.

Conclusions

Purified caprine islets were demonstrated to successfully sustain viability and functionality for controlling blood glucose levels in an immunosuppressed mouse model of diabetes. These results suggest the use of caprine islets as an addition to the supply of xenogeneic islets for diabetes research.
Design and Research of a Robotic Aided System for Retinal Vascular Bypass Surgery
Authors: Jingjing Xiao , Long Huang , Lijun Shen , Yang Yang
Published: March 2014

With reference to the study of the robotic system for ophthalmology microsurgery, a robotic system was presented with the key mechanism design and control subsystem scheme considering the procedures and features of retinal vascular bypass surgery. After discussion of the clinical application, the human-machine cooperated surgical process of the robotic system for retinal vascular bypass surgery was described, and the design of the surgical layout environment was proposed. The intraocular motion planning method was also described and corresponding experiments using a table tennis ball model and an in vitro porcine eye model were performed. Finally, the feasibility analysis and robotic system error analysis were also summarized and future works discussed for further research.
Models and Numerical Solutions of Generalized Oscillator Equations
Authors: Xu Yufeng , Agrawal Om P.
Published: March 2014

In this paper, we use three operators called K-, A-, and B-operators to define the equation of motion of an oscillator. In contrast to fractional integral and derivative operators which use fractional power kernels or their variations in their definitions, the K-, A-, and B-operators allow the kernel to be arbitrary. In the case, when the kernel is a power kernel, these operators reduce to fractional integral and derivative operators. Thus, they are more general than the fractional integral and derivative operators. Because of the general nature of the K-, A-, and B-operators, the harmonic oscillators are called the generalized harmonic oscillators. The equations of motion of a generalized harmonic oscillator are obtained using a generalized Euler–Lagrange equation presented recently. In general, the resulting equations cannot be solved in closed form. A finite difference scheme is presented to solve these equations. To verify the effectiveness of the numerical scheme, a problem is considered for which a closed form solution could be found. Numerical solution for the problem is compared with the analytical solution, which demonstrates that the numerical scheme is convergent.
Fan Noise Control Using Microperforated Splitter Silencers
Authors: Allam Sabry , Åbom Mats
Published: March 2014

Splitter or baffle silencers are commonly used, for example, in heating ventilation and air conditioning (HVAC) systems and as inlet/outlet silencers on gas turbines. Another application is to reduce noise from the cooling fan inlet for large IC-engines. A splitter silencer can be seen as a periodic arrangement of parallel rectangular absorbers, which can be placed in a rectangular duct. The noise reduction afforded by parallel splitters depends not only on the physical properties of the lining but also upon the angle of incidence of the impinging sound waves, and the splitter and duct dimensions. In this paper, the potential of using splitters made of microperforated plates (MPPs) is investigated, with a particular focus on cooling fan inlet/outlet applications.
Modeling of a Steam Turbine Including Partial Arc Admission for Use in a Process Simulation Software Environment
Authors: Liese Eric
Published: March 2014

A dynamic process model of a steam turbine, including partial arc admission operation, is presented. Models were made for the first stage and last stage, with the middle stages assumed to have a constant pressure ratio and efficiency. A condenser model is also presented. The paper discusses the function and importance of the steam turbine's entrance design and the first stage. The results for steam turbines with a partial arc entrance are shown and compare well with experimental data available in the literature; in particular, the “valve loop” behavior as the steam flow rate is reduced. This is important to model correctly since it significantly influences the downstream state variables of the steam, and thus the characteristic of the entire steam turbine, e.g., state conditions at extractions, overall turbine flow, and condenser behavior. The importance of the last stage (the stage just upstream of the condenser) in determining the overall flow rate and exhaust conditions to the condenser is described and shown via results.
Studying the formation of nitrogen δ-doped layers on GaAs(001) using reflection high-energy electron diffraction
Authors: Nishimoto Norihisa , Kondow Masahiko , Ishikawa Fumitaro
Published: March 2014

The authors measured reflection high-energy electron diffraction patterns during the formation of nitrogen δ-doped layers on GaAs(001). The authors investigated the effects of nitrogen coverage, substrate temperature, and growth rate of the GaAs overlayer on the roughness, faceting, and strain state of the surface. During δ-doping, the authors observed coherently grown nitrogen-mediated surface reconstruction. The lattice of the GaAs overlayer expanded and shrank as it grew up to two monolayers, eventually recovering to a smooth surface. When the GaAs overlayer was grown on δ-doped layers with nitrogen coverage greater than 0.3 monolayers, it exhibited characteristic faceting, possibly caused by the presence of excess nitrogen adatoms. These behaviors were mostly identical for layers grown under both As4 and As2 overpressures.
Three‐dimensional liver motion tracking using real‐time two‐dimensional MRI
Authors: Brix Lau , Ringgaard Steffen , Sørensen Thomas Sangild , Poulsen Per Rugaard
Published: March 2014

Purpose:

Combined magnetic resonance imaging (MRI) systems and linear accelerators for radiotherapy (MR‐Linacs) are currently under development. MRI is noninvasive and nonionizing and can produce images with high soft tissue contrast. However, new tracking methods are required to obtain fast real‐time spatial target localization. This study develops and evaluates a method for tracking three‐dimensional (3D) respiratory liver motion in two‐dimensional (2D) real‐time MRI image series with high temporal and spatial resolution.

Methods:

The proposed method for 3D tracking in 2D real‐time MRI series has three steps: (1) Recording of a 3D MRI scan and selection of a blood vessel (or tumor) structure to be tracked in subsequent 2D MRI series. (2) Generation of a library of 2D image templates oriented parallel to the 2D MRI image series by reslicing and resampling the 3D MRI scan. (3) 3D tracking of the selected structure in each real‐time 2D image by finding the template and template position that yield the highest normalized cross correlation coefficient with the image. Since the tracked structure has a known 3D position relative to each template, the selection and 2D localization of a specific template translates into quantification of both the through‐plane and in‐plane position of the structure. As a proof of principle, 3D tracking of liver blood vessel structures was performed in five healthy volunteers in two 5.4 Hz axial, sagittal, and coronal real‐time 2D MRI series of 30 s duration. In each 2D MRI series, the 3D localization was carried out twice, using nonoverlapping template libraries, which resulted in a total of 12 estimated 3D trajectories per volunteer. Validation tests carried out to support the tracking algorithm included quantification of the breathing induced 3D liver motion and liver motion directionality for the volunteers, and comparison of 2D MRI estimated positions of a structure in a watermelon with the actual positions.

Results:

Axial, sagittal, and coronal 2D MRI series yielded 3D respiratory motion curves for all volunteers. The motion directionality and amplitude were very similar when measured directly as in‐plane motion or estimated indirectly as through‐plane motion. The mean peak‐to‐peak breathing amplitude was 1.6 mm (left‐right), 11.0 mm (craniocaudal), and 2.5 mm (anterior‐posterior). The position of the watermelon structure was estimated in 2D MRI images with a root‐mean‐square error of 0.52 mm (in‐plane) and 0.87 mm (through‐plane).

Conclusions:

A method for 3D tracking in 2D MRI series was developed and demonstrated for liver tracking in volunteers. The method would allow real‐time 3D localization with integrated MR‐Linac systems.
Virulence and Pathogenesis of HIV-1 Infection: An Evolutionary Perspective
Authors: Fraser Christophe , Lythgoe Katrina , Leventhal Gabriel E. , Shirreff George , Hollingsworth T. Déirdre , Alizon Samuel , Bonhoeffer Sebastian
Published: March 2014

HIV Virulence

A major focus of research on HIV is on host responses to infection—understandably, because the virus targets the immune system and because of the interest in vaccine development. In reviewing what little research has been done on viral virulence determinants,

Fraser
et al.

(
10.1126/science.1243727
) present evolutionary explanations for some of the poorly understood phenomena that mark HIV infection, including long-term survivorship, latency, rapid within-host evolution, and inheritability of between-host virulence.
Counting the Ways to Decode Dynamic Signals
Authors: Wollman Roy
Published: March 2014

The social amoeba
Dictyostelium discoideum
decodes an oscillatory signal to measure time.

[Also see Research Article by

Cai
et al.

]
Hints of Detente Between NSF and Republicans
Authors: Mervis Jeffrey
Published: March 2014

Congressional Republicans and the National Science Foundation appear to be creeping toward common ground in their yearlong fight over how the agency manages its $7 billion research portfolio.
U.S. and Mexico Unleash a Flood Into Colorado Delta
Authors: Stokstad Erik
Published: March 2014

Hoping for a boost to native vegetation, scientists will study the effects of an experimental flood of the Colorado River delta on trees, soil salinity, and ground water.
Characterization of Reverse Genetics-Derived Cold-Adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants with H5N1 Surface Genes in a Mouse Model
Authors: Isakova-Sivak Irina , Chen Li-Mei , Bourgeois Melissa , Matsuoka Yumiko , Voeten J. Theo M. , Heldens Jacco G. M. , van den Bosch Han , Klimov Alexander , Rudenko Larisa , Cox Nancy J. , Donis Ruben O.
Published: March 2014

Live attenuated influenza vaccines (LAIV) offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing processes and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild-type (wt) A/Leningrad/134/1957 and cold-adapted (ca) A/Leningrad/134/17/1957 (Len17) master donor virus (MDV), we produced and characterized three rg H5N1 reassortant viruses carrying modified HA and intact NA genes from either A/Vietnam/1203/2004 (H5N1, VN1203, clade 1) or A/Egypt/321/2007 (H5N1, EG321, clade 2) virus. A mouse model of infection was used to determine the infectivity and tissue tropism of the parentalwtviruses compared to thecamaster donor viruses as well as the H5N1 reassortants. Allcaviruses showed reduced replication in lungs and enhanced replication in nasal epithelium. In addition, the H5N1 HA and NA enhanced replication in lungs unless it was restricted by the internal genes of thecaMDV. Mice inoculated twice 4 weeks apart with the H5N1 reassortant LAIV candidate viruses developed serum hemagglutination inhibition HI and IgA antibody titers to the homologous and heterologous viruses consistent with protective immunity. These animals remained healthy after challenge inoculation with a lethal dose with homologous or heterologouswtH5N1 highly pathogenic avian influenza (HPAI) viruses. The profiles of viral replication in respiratory tissues and the immunogenicity and protective efficacy characteristics of the twocaH5N1 candidate LAIV viruses warrant further development into a vaccine for human use.
Hsp104 Overexpression Cures Saccharomyces cerevisiae [
PSI
+
] by Causing Dissolution of the Prion Seeds
Authors: Park Yang-Nim , Zhao Xiaohong , Yim Yang-In , Todor Horia , Ellerbrock Robyn , Reidy Michael , Eisenberg Evan , Masison Daniel C. , Greene Lois E.
Published: March 2014

The [
PSI
+
] yeast prion is formed when Sup35 misfolds into amyloid aggregates. [
PSI
+
], like other yeast prions, is dependent on the molecular chaperone Hsp104, which severs the prion seeds so that they pass on as the yeast cells divide. Surprisingly, however, overexpression of Hsp104 also cures [
PSI
+
]. Several models have been proposed to explain this effect: inhibition of severing, asymmetric segregation of the seeds between mother and daughter cells, and dissolution of the prion seeds. First, we found that neither the kinetics of curing nor the heterogeneity in the distribution of the green fluorescent protein (GFP)-labeled Sup35 foci in partially cured yeast cells is compatible with Hsp104 overexpression curing [
PSI
+
] by inhibiting severing. Second, we ruled out the asymmetric segregation model by showing that the extent of curing was essentially the same in mother and daughter cells and that the fluorescent foci did not distribute asymmetrically, but rather, there was marked loss of foci in both mother and daughter cells. These results suggest that Hsp104 overexpression cures [
PSI
+
] by dissolution of the prion seeds in a two-step process. First, trimming of the prion seeds by Hsp104 reduces their size, and second, their amyloid core is eliminated, most likely by proteolysis.
Concordance between Molecular and Phenotypic Testing of Mycobacterium tuberculosis Complex Isolates for Resistance to Rifampin and Isoniazid in the United States
Authors: Yakrus Mitchell A. , Driscoll Jeffrey , Lentz Allison J. , Sikes David , Hartline Denise , Metchock Beverly , Starks Angela M.
Published: March 2014

Multidrug-resistant (MDR) isolates of
Mycobacterium tuberculosis
complex (MTBC) are defined by resistance to at least rifampin (RMP) and isoniazid (INH). Rapid and accurate detection of multidrug resistance is essential for effective treatment and interruption of disease transmission of tuberculosis (TB). Overdiagnosis of MDR TB may result in treatment with second-line drugs that are more costly, less effective, and more poorly tolerated than first-line drugs. CDC offers rapid confirmation of MDR TB by the molecular detection of drug resistance (MDDR) for mutations associated with resistance to RMP and INH along with analysis for resistance to other first-line and second-line drugs. Simultaneously, CDC does growth-based phenotypic drug susceptibility testing (DST) by the indirect agar proportion method for a panel of first-line and second-line antituberculosis drugs. We reviewed discordance between molecular and phenotypic DST for INH and RMP for 285 isolates submitted as MTBC to CDC from September 2009 to February 2011. We compared CDC's results with those from the submitting public health laboratories (PHL). Concordances between molecular and phenotypic testing at CDC were 97.4% for RMP and 92.5% for INH resistance. Concordances between CDC's molecular testing and PHL DST results were 93.9% for RMP and 90.0% for INH. Overall concordance between CDC molecular and PHL DST results was 91.7% for RMP and INH collectively. Discordance was primarily attributable to the absence of known INH resistance mutations in isolates found to be INH resistant by DST and detection of mutations associated with low-level RMP resistance in isolates that were RMP susceptible by phenotypic DST. Both molecular and phenotypic test results should be considered for the diagnosis of MDR TB.
Comparison of Xpert MTB/RIF with Line Probe Assay for Detection of Rifampin-Monoresistant Mycobacterium tuberculosis
Authors: Rufai Syed Beenish , Kumar Parveen , Singh Amit , Prajapati Suneel , Balooni Veena , Singh Sarman
Published: March 2014

The MTBDR
plus
line probe assay (LPA) and Xpert MTB/RIF have been endorsed by the World Health Organization for the rapid diagnosis of drug-resistant tuberculosis. However, there is no clarity regarding the superiority of one over the other. In a double-blinded prospective study, we evaluated the efficacy of the Xpert MTB/RIF on samples that were first tested by LPA under the revised national tuberculosis control program of India. A total of 405 sputum samples from suspected drug-resistant tuberculosis patients were included. Of these, 285 smear-positive samples were subjected to LPA. Seventy-two (25.8%) samples showed multidrug resistance, 62 (22.2%) showed rifampin monoresistance, 29 (10.3%) showed isoniazid monoresistance, and 116 (41.5%) were pan-susceptible. Six (2.1%) of the samples gave invalid results. Of the 62 rifampin-monoresistant samples by LPA, 38 (61.4%) showed rifampin resistance, while 21 (33.8%) were found susceptible to rifampin by Xpert MTB/RIF using cartridge version G4. Three (4.8%) samples gave an error. Of the 116 pan-susceptible samples, only 83 were available for Xpert MTB/RIF testing; 4 (5.1%) were rifampin resistant, 74 (94.8%) were susceptible, and 5 (6.0%) showed an error. The 25 discrepant samples were further subjected to MGIT960 drug susceptibility testing. The MGIT960 results showed 100% agreement with LPA results but only 64.4% agreement with Xpert MTB/RIF results. Sequencing analysis of discrepant samples showed 91.3% concordance with LPA but only 8.7% concordance with the Xpert MTB/RIF assay. These findings indicate that by using Xpert MTB/RIF testing we might be underestimating the burden of drug-resistant tuberculosis and indicate that country-specific probes need to be designed to increase the sensitivity of the Xpert MTB/RIF.
Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years
Authors: Gasparini Roberto , Comanducci Maurizio , Amicizia Daniela , Ansaldi Filippo , Canepa Paola , Orsi Andrea , Icardi Giancarlo , Rizzitelli Emanuela , De Angelis Gabriella , Bambini Stefania , Moschioni Monica , Comandi Sara , Simmini Isabella , Boccadifuoco Giueseppe , Brunelli Brunella , Giuliani Marzia Monica , Pizza Mariagrazia , Panatto Donatella
Published: March 2014

Neisseria meningitidis
is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The
fHbp
and
nhba
genes were present in all isolates, while the
nadA
gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage.
Determinants for Membrane Association of the Hepatitis C Virus NS2 Protease Domain
Authors: Lange Christian M. , Bellecave Pantxika , Dao Thi Viet Loan , Tran Huong T. L. , Penin François , Moradpour Darius , Gouttenoire Jérôme
Published: March 2014

Hepatitis C virus (HCV) nonstructural protein 2 (NS2) is required for HCV polyprotein processing and particle assembly. It comprises an N-terminal membrane domain and a C-terminal, cytosolically oriented protease domain. Here, we demonstrate that the NS2 protease domain itself associates with cellular membranes. A single charged residue in the second α-helix of the NS2 protease domain is required for proper membrane association, NS2 protein stability, and efficient HCV polyprotein processing.
Crystallographic and Glycan Microarray Analysis of Human Polyomavirus 9 VP1 Identifies
N
-Glycolyl Neuraminic Acid as a Receptor Candidate
Authors: Khan Zaigham Mahmood , Liu Yan , Neu Ursula , Gilbert Michel , Ehlers Bernhard , Feizi Ten , Stehle Thilo
Published: March 2014

Human polyomavirus 9 (HPyV9) is a closely related homologue of simian B-lymphotropic polyomavirus (LPyV). In order to define the architecture and receptor binding properties of HPyV9, we solved high-resolution crystal structures of its major capsid protein, VP1, in complex with three putative oligosaccharide receptors identified by glycan microarray screening. Comparison of the properties of HPyV9 VP1 with the known structure and glycan-binding properties of LPyV VP1 revealed that both viruses engage short sialylated oligosaccharides, but small yet important differences in specificity were detected. Surprisingly, HPyV9 VP1 preferentially binds sialyllactosamine compounds terminating in 5-
N
-glycolyl neuraminic acid (Neu5Gc) over those terminating in 5-
N
-acetyl neuraminic acid (Neu5Ac), whereas LPyV does not exhibit such a preference. The structural analysis demonstrated that HPyV9 makes specific contacts, via hydrogen bonds, with the extra hydroxyl group present in Neu5Gc. An equivalent hydrogen bond cannot be formed by LPyV VP1.

IMPORTANCE
The most common sialic acid in humans is 5-
N
-acetyl neuraminic acid (Neu5Ac), but various modifications give rise to more than 50 different sialic acid variants that decorate the cell surface. Unlike most mammals, humans cannot synthesize the sialic acid variant 5-
N
-glycolyl neuraminic acid (Neu5Gc) due to a gene defect. Humans can, however, still acquire this compound from dietary sources. The role of Neu5Gc in receptor engagement and in defining viral tropism is only beginning to emerge, and structural analyses defining the differences in specificity for Neu5Ac and Neu5Gc are still rare. Using glycan microarray screening and high-resolution protein crystallography, we have examined the receptor specificity of a recently discovered human polyomavirus, HPyV9, and compared it to that of the closely related simian polyomavirus LPyV. Our study highlights critical differences in the specificities of both viruses, contributing to an enhanced understanding of the principles that underlie pathogen selectivity for modified sialic acids.
A case of impacted central incisor due to dentigerous cyst associated with impacted compound odontome
Authors: Jayam Cheranjeevi , Bandlapalli Anila , Patel Nikunj , Choudhary Rama Shankar Kashinath
Published: March 2014

Odontomes are hamartomatous growths of odontogenic origin. Odontomes usually do not erupt into oral cavity and can cause several difficulties like swelling, displacement of teeth and adjacent structures, cystic changes and carcinomatous transformation. Odontomes are treated by surgical removal. Dentigerous cysts arise due to accumulation of fluid between reduced enamel epithelium and crown of unerupted tooth. Dentigerous cysts cause several difficulties such as swelling, non-eruption of involved teeth and displacement of adjacent teeth, thus requiring early detection and prompt treatment. Treatment for dentigerous cyst ranges from marsupialisation to enucleation. In children, marsupialisation is more commonly used when compared with enucleation treatment. This study discusses successful treatment of impacted central incisor due to obstruction from dentigerous cyst originating from impacted compound odontome. The paper also throws light into importance to radiography while diagnosing odontome.
Nutritional implications of selective eating in a child with autism spectrum disorder
Authors: Keown Karen , Bothwell Janice , Jain Sonya
Published: March 2014

A 4-year-old boy attending the autism assessment service was identified to have a restricted diet. His food diary documented that he ate a narrow range of foods and consumed excessive quantities of carrot juice (excess 2.5 L daily). Physical examination showed that the boy had a florid orange discolouration of his skin, growth parameters were <91st centile for weight, >50th centile for height and head circumference. Blood investigations showed a raised serum carotene level and vitamin D deficiency. He was referred for urgent specialist input from dietetics and the other disciplines within the autism intervention team.
A case of scrotal venous malformation mimicking a failed varicocelectomy
Authors: Yi Chong K , Derosa Raffaella , Sterbis Joseph R , Ching Brian H
Published: March 2014

A 21-year-old man presented to interventional radiology department with several years of left scrotal pain, which exacerbated by prolonged standing and walking. The patient had undergone a left varicocelectomy at the age of 10, after which he had a persistent scrotal mass. As he grew older, the left scrotal mass continued to increase in size, and symptoms progressively worsened. Physical examination revealed a non-tender, firm left scrotal mass which remained unchanged in size after Valsalva manoeuvres. Initial ultrasound examination revealed an extratesticular, intrascrotal mass with minimal internal flow. MRI revealed a heterogeneously enhancing, low-flow venous malformation centred in the midscrotum involving multiple tissue planes. Two sessions of percutaneous sclerotherapy failed to relieve his pain. Three months after the second sclerotherapy, the patient underwent surgical resection. At the time of his postoperative visit, his left scrotal pain had significantly improved and pain with prolonged standing and walking had resolved completely.
Lactic acidosis in diabetic ketoacidosis
Authors: Feenstra Rieneke A , Kiewiet Mink K P , Boerma E Christiaan , ter Avest Ewoud
Published: March 2014

We describe the case of a 22-year-old man with insulin-dependent diabetes, who was admitted to the emergency department with hypotension, unconsciousness and a severe combined diabetic ketoacidosis (DKA) and lactic acid acidosis. In the discussion, we focus on the pathophysiological mechanisms underlying lactic acidosis in DKA, and we elaborate on the prognostic value of hyperlactataemia on such occasion.
Service improvement system to enhance the safety of patients admitted on long-term warfarin
Authors: Warcel Dana , Johnson Daniel , Shah Neeraj , shreeve Norman
Published: March 2014

It is common for hospital inpatients on warfarin to suffer from fluctuations in their INR (international normalised ratio). Raised INRs are potentially very dangerous and may result in acute life-threatening haemorrhages. Conversely, low INRs may increase the risk for the development of venous thromboembolism. Having observed many deranged INRs among hospital inpatients, we decided to focus our project on identifying the contributing factors to deranged INRs and ways to address this problem. We analysed the warfarin prescriptions on all drug charts and surveyed the junior doctor staff. Our results revealed poor knowledge and confidence levels on warfarin prescribing among junior doctor staff. This is likely to be reflected in the poor completion rate of warfarin prescriptions. We instituted practical changes to resolve the issue: most importantly, a change to the warfarin administration time from 6 pm to 2 pm, supported by a poster campaign to increase awareness of the problem. The objective of these changes was to reduce prescribing errors by reducing warfarin prescriptions out-of-hours, by the on-call doctors. We repeated the audit cycle twice. Although our interventions were successfully introduced as shown in our second audit cycle, the changes that were implemented were not sustained as shown in the third audit cycle. We identified a need for annual intervention to educate new junior doctor staff to ensure that the positive outcomes achieved are maintained in the long term.
Eosinophilic oesophagitis: clinical presentation and pathogenesis
Authors: Bystrom Jonas , O’Shea Nuala R
Published: March 2014

Eosinophilic oesophagitis (EoE) is an inflammatory disorder of the oesophagus which has become increasingly recognised over recent years, although it remains underdiagnosed in many centres. It is characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field), and clinically with features of oesophageal dysfunction such a dysphagia, food impaction, and proton pump inhibitor (PPI) resistant dyspepsia. Fibrosis and oesophageal remodelling may occur and lead to oesophageal strictures. An allergic predisposition is common in the EoE population, which appears to be primarily food antigen driven in children and aeroallergen driven in adults. Evidence suggests that the pathogenesis of EoE is due to a dysregulated immunological response to an environmental allergen, resulting in a T helper type 2 (Th2) inflammatory disease and remodelling of the oesophagus in genetically susceptible individuals. Allergen elimination and anti-inflammatory therapy with corticosteroids are currently the mainstay of treatment; however, an increasing number of studies are now focused on targeting different stages in the disease pathogenesis. A greater understanding of the underlying mechanisms resulting in EoE will allow us to improve the therapeutic options available.
Synthesis and characterization of aza-bridged thiophene–pyrrole dyads and their isomers
Authors: Furuyama Taniyuki , Noguchi Daiki , Suzuki Yuta , Kobayashi Nagao
Published: March 2014

Aza-bridged thiophene-pyrrole dyads were synthesized and characterized. Thiophenes substituted with electron-withdrawing groups (EWGs) were used as building blocks for the framework. However, an unprecedented cyclization occurred, and a thieno[2,3-d]pyrimidine derivative (4) was obtained in the reaction between 2,5-diamino-3,4-dicyanothiophene (1) and 3,5-diiminoisoindoline (3), whereas the reaction between 2,5-diamino-3,4-dicarboxylic acid ethyl ester (2) and 3 produced the desired dyad (5). The structures of 4 and 5 were unambiguously characterized by X-ray diffraction. Compound 5 is the first example of a core-modified azadipyrromethene, and the electronic interaction between the thiophene and pyrrole moieties was estimated with several spectroscopies. Several kinds of aryl groups can be attached at the terminal amino moiety of 4, and their unique absorption properties were also revealed.
Effects of mannan oligosaccharide and virginiamycin on the cecal microbial community and intestinal morphology of chickens raised under suboptimal conditions
Authors: Pourabedin Mohsen , Xu Zhengxin , Baurhoo Bushansingh , Chevaux Eric , Zhao Xin
Published: March 2014

There is an increasing movement against use of antibiotic growth promoters in animal feed. Prebiotic supplementation is a potential alternative to enhance the host’s natural defense through modulation of gut microbiota. In the present study, the effect of mannan oligosaccharide (MOS) and virginiamycin (VIRG) on cecal microbial ecology and intestinal morphology of broiler chickens raised under suboptimal conditions was evaluated. MOS and VIRG induced different bacterial community structures, as revealed by denaturing gradient gel electrophoresis of 16S rDNA. The antibiotic treatment reduced cecal microbial diversity while the community equitability increased. A higher bacterial diversity was observed in the cecum of MOS-supplemented birds. Quantitative polymerase chain reaction results indicated that MOS changed the cecal microbiota in favor of the Firmicutes population but not the Bacteroidetes population. No difference was observed in total bacterial counts among treatments. MOS promoted the growth of Lactobacillus spp. and Bifidobacterium spp. in the cecum and increased villus height and goblet cell numbers in the ileum and jejunum. These results provide a deeper insight into the microbial ecological changes after supplementation of MOS prebiotic in poultry diets.
Milk composition, milk consumption, and growth rate of a captive spotted seal (Phoca largha) pup from Liaodong Bay, China
Authors: Zhang P.J. , Song X.R. , Han J.B. , Wang L.M. , Yang Y.
Published: March 2014

As lactation is commonly very brief in phocid seals, the transfer of sufficient energy between mother and offspring is critical for their reproductive success. In this study, we investigated variation in the pattern of energy transfer and allocation during lactation in the spotted seal (Phoca largha Pallas, 1811). Temporal changes in milk composition, milk consumption, and pup mass gain were analyzed from birth to weaning in a spotted seal pup that was hand-reared on a donor-female’s milk. In addition, growth rates were measured in six pups raised in captivity but nursed naturally. We found that milk fat content increased and water content decreased during lactation. We calculated that spotted seal pup ingest a mean (±SD) daily energy of 39.5 ± 8.6 MJ/day, which corresponded to a daily mass gain of 0.9 kg/day. We found that the growth rates of the hand-reared pup and the six naturally reared pups did not differ, and overall, the mean (±SD) daily growth rate of spotted seal pups was 1.1 ± 0.2 kg/day before weaning and 0.6 ± 0.2 kg/day from birth to molt. Our study provides the first data on lactation patterns in this species.
Universality of phase transition dynamics: Topological defects from symmetry breaking
Authors: del Campo Adolfo , Zurek Wojciech H.
Published: March 2014

In the course of a nonequilibrium continuous phase transition, the dynamics ceases to be adiabatic in the vicinity of the critical point as a result of the critical slowing down (the divergence of the relaxation time in the neighborhood of the critical point). This enforces a local choice of the broken symmetry and can lead to the formation of topological defects. The Kibble–Zurek mechanism (KZM) was developed to describe the associated nonequilibrium dynamics and to estimate the density of defects as a function of the quench rate through the transition. During recent years, several new experiments investigated the formation of defects in phase transitions induced by a quench both in classical and quantum mechanical systems. At the same time, some established results were called into question. We review and analyze the Kibble–Zurek mechanism focusing in particular on this surge of activity, and suggest possible directions for further progress.
MODELING THE COEVOLUTION OF ROAD EXPANSION AND URBAN TRAFFIC GROWTH
Authors: WU JIANJUN , XU MINGTAO , GAO ZIYOU
Published: March 2014

The evolution of road expansion and traffic growth (motor vehicle) of urban system is a quite complex process. To investigate the interaction between them, a coevolution dynamics model is proposed in this paper to capture the relationships among traveler, vehicle and road. Then stability analysis and numerical simulation are conducted. The results show that the coevolution model can be stable under certain conditions and there exists a dynamic equilibrium in the evolution process. In order to verify the proposed model, Beijing as a case study is analyzed. Results show that the proposed model provides a new perspective for capturing the characteristic of road and urban traffic and contributes to the coordinated development of the whole transportation system.
PREPARATION AND ANTI-CORROSION PERFORMANCE OF ZINC PHOSPHATE NANOCRYSTALS BY ULTRASONIC–HYDROTHERMAL SYNERGISTIC ROUTE
Authors: LIU CHANG , XIE HONG-ZHEN , WANG JIAN-DONG , TONG QIN , LIU JIN-KU , YANG XIAO-HONG
Published: March 2014

The zinc phosphate nanocrystals were synthesized by the ultrasonic–hydrothermal synergistic route. The ultrasonic–hydrothermal synergistic route can not only decrease the size of the zinc phosphate material, but also improve the crystallinity of the product. The transmission electron microscopy (TEM) image showed that the needle-like zinc phosphate product was 200–300 nm in length and 70–80 nm in width. The anti-corrosion tests revealed that the salt atmosphere-resistant time about 1056 h was longer than 768 h common zinc phosphate materials in the market. The mechanisms of ultrasonic–hydrothermal synergistic route and anti-corrosion were discussed.
FAILURE PATTERNS OF SHEAR KEYS AND SEISMIC RESISTANCE OF A GRAVITY DAM WITH LONGITUDINAL JOINTS
Authors: ZHANG LIAOJUN , ZHANG HANYUN , HU SHAOWEI
Published: March 2014

In order to thoroughly study the seismic resistance of gravity dams with longitudinal joints, a contact model based on constraint function method is used to simulate the shear keys within the joints and a concrete smeared crack model is selected to present the cracking characteristics of concrete materials. Because of the great size difference between the shear keys and the dam body, a glue mesh is proposed to implement multi-scale modeling. A dam-foundation-reservoir interaction system with longitudinal joints considering the various shear keys is developed and analyzed by nonlinear time-history method. On the basis of actual construction, arrangement and loading features of shear keys, a gravity dam is taken as a test case and a finite element model of the dam is established with triangular or trapezoidal shear keys. The working behaviors and failure patterns of various shear keys under earthquakes are explored. Moreover, the effects of various shear keys on the seismic resistance of the gravity dam are discussed. The results show that the seismic responses of shear keys are resulted in designed forms. The occlusion and dislocation of the shear keys within the longitudinal joints have an impact on seismic resistance of the gravity dams.
The Erdős–Faber–Lovász conjecture is true for n ≤ 12
Authors: Romero David , Alonso-Pecina Federico
Published: March 2014

The unsolved Erdős–Faber–Lovász conjecture states that if a hypergraph has n edges, each of size n, and every pair of edges intersect in at most one vertex, then its vertex chromatic number is equal to n. Hindman proved it for n ≤ 10; here we extend this result up to n ≤ 12.
Stem Cell-Based Tissue Engineering for Regenerative Medicine
Authors: Shi Donglu , Tatu Rigwed , Liu Qing , Hosseinkhani Hossein
Published: March 2014

The applications of stem cells in tissue engineering will show great promise in generating tailor-made tissue/organs for clinical applications. This paper gives a review on a broad spectrum of areas in stem cell-based tissue engineering including neuron repair, cardiac patches, skin regeneration, gene therapy and cartilage tissue engineering. This paper is intended to serve as an informative tutorial for scientists and physicians from fields other than stem cells and tissue engineering. It will shed light on various strategies of target tissue/organ repair involving stem cells.
Comparative Study of Magnetic Properties and Antitumor Effect of Nanocomplexes from Oxides Iron Nanoparticles and Doxorubicin During Radio-Frequency Hyperthermia of the Walker-256 Carcinosarcoma
Authors: Orel Valerii E. , Shevchenko Anatoliy D. , Nikolov Nikolay A. , Romanov Andriy V. , Rykhalskyi Alexander Y. , Burlaka Anatoliy P. , Lukin Sergey N. , Dzyatkovskaya Natalya N. , Shchepotin Igor B.
Published: March 2014

A comparative study of magnetic properties using the method of magnetometry with vibration magnetometer and spectra of electron paramagnetic resonance (EPR) nanocomplexes (NCs) of nanoparticles Fe2O3, Fe3O4and antitumor antibiotic doxorubicin (DOXO) have shown that changes in saturation magnetic moments are similar to changes in integral intensity of EPR spectra. The greatest magnetic moments of saturation and integral intensity of EPR spectra were demonstrated by samples of Fe3O4in NC with doxorubicin, which had the highest antitumor effect in radiofrequency hyperthermia of Walker-256 carcinosarcoma. The presented research provides the evidence of stronger antitumor effect of Fe3O4and DOXO NC in comparison to NC from γ- Fe2O3and DOXO at combined action of constant magnetic field and electromagnetic field. This can be a basis for development of bioengineering technology of magnetic cancer nanotherapy in conditions of moderate hyperthermia (< 39°C).
Hydrocarbon exploration and exploitation West of Shetlands
Authors: Austin J. A. , Cannon S. J. C. , Ellis D.
Published: March 2014

The oil and gas industry has been active in the West of Shetlands area for the last 40 years, but less than 200 wells have been drilled and only four fields have been developed. In the last ten years activity has picked up significantly with very active licensing rounds and increased drilling; however, the challenges of the complex geology and deep-water location, environmental constraints and commercial considerations have also increased at the same time. To fully develop the region successfully an attitude of compromise and collaboration between all the stakeholders must be nurtured, but with the scale of investment required this will remain a challenge for the future.
Ischemic factor-induced increases in cerebral microvascular endothelial cell Na/H exchange activity and abundance: evidence for involvement of ERK1/2 MAP kinase
Authors: Yuen Natalie , Lam Tina I. , Wallace Breanna K. , Klug Nicholas R. , Anderson Steven E. , O'Donnell Martha E.
Published: March 2014

Brain edema forms rapidly in the early hours of ischemic stroke by increased secretion of Na, Cl, and water into the brain across an intact blood-brain barrier (BBB), together with swelling of astrocytes as they take up the ions and water crossing the BBB. Our previous studies provide evidence that luminal BBB Na-K-Cl cotransport (NKCC) and Na/H exchange (NHE) participate in ischemia-induced edema formation. NKCC1 and two NHE isoforms, NHE1 and NHE2, reside predominantly at the luminal BBB membrane. NKCC and NHE activities of cerebral microvascular endothelial cells (CMEC) are rapidly stimulated by the ischemic factors hypoxia, aglycemia, and AVP, and inhibition of NKCC and NHE activities by bumetanide and HOE642, respectively, reduces brain Na uptake and edema in the rat middle cerebral artery occlusion model of stroke. The present study was conducted to further explore BBB NHE responses to ischemia. We examined whether ischemic factor-stimulated NHE activity is sustained over several hours, when the majority of edema forms during stroke. We also examined whether ischemic factors alter NHE1 and/or NHE2 protein abundance. Finally, we conducted initial studies of ERK1/2 MAP kinase involvement in BBB NHE and NKCC responses to ischemic factors. We found that hypoxia, aglycemia, and AVP increase CMEC NHE activity through 5 h and that NHE1, but not NHE2, abundance is increased by 1- to 5-h exposures to these factors. Furthermore, we found that these factors rapidly increase BBB ERK1/2 activity and that ERK1/2 inhibition reduces or abolishes ischemic factor stimulation of NKCC and NHE activities.
Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling
Authors: Sinnett-Smith James , Ni Yang , Wang Jia , Ming Ming , Young Steven H. , Rozengurt Enrique
Published: March 2014

We examined whether class IIa histone deacetylases (HDACs) play a role in mitogenic signaling mediated by protein kinase D1 (PKD1) in IEC-18 intestinal epithelial cells. Our results show that class IIa HDAC4, HDAC5, and HDAC7 are prominently expressed in these cells. Stimulation with ANG II, a potent mitogen for IEC-18 cells, induced a striking increase in phosphorylation of HDAC4 at Ser246 and Ser632, HDAC5 at Ser259 and Ser498, and HDAC7 at Ser155. Treatment with the PKD family inhibitors kb NB 142-70 and CRT0066101 or small interfering RNA-mediated knockdown of PKD1 prevented ANG II-induced phosphorylation of HDAC4, HDAC5, and HDAC7. A variety of PKD1 activators in IEC-18 cells, including vasopressin, lysophosphatidic acid, and phorbol esters, also induced HDAC4, HDAC5, and HDAC7 phosphorylation. Using endogenously and ectopically expressed HDAC5, we show that PKD1-mediated phosphorylation of HDAC5 induces its nuclear extrusion into the cytoplasm. In contrast, HDAC5 with Ser259 and Ser498 mutated to Ala was localized to the nucleus in unstimulated and stimulated cells. Treatment of IEC-18 cells with specific inhibitors of class IIa HDACs, including MC1568 and TMP269, prevented cell cycle progression, DNA synthesis, and proliferation induced in response to G protein-coupled receptor/PKD1 activation. The PKD1-class IIa HDAC axis also functions in intestinal epithelial cells in vivo, since an increase in phosphorylation of HDAC4/5 and HDAC7 was demonstrated in lysates of crypt cells from PKD1 transgenic mice compared with matched nontransgenic littermates. Collectively, our results reveal a PKD1-class IIa HDAC axis in intestinal epithelial cells leading to mitogenic signaling.