Robinson-Foulds Supertrees

Background  

Supertree methods synthesize collections of small phylogenetic trees with incomplete taxon overlap into comprehensive trees, or supertrees, that include all taxa found in the input trees. Supertree methods based on the well established Robinson-Foulds (RF) distance have the potential to build supertrees that retain much information from the input trees. Specifically, the RF supertree problem seeks a binary supertree that minimizes the sum of the RF distances from the supertree to the input trees. Thus, an RF supertree is a supertree that is consistent with the largest number of clusters (or clades) from the input trees.     

Automatic control of finite element models for temperature-controlled radiofrequency ablation

Background  

The finite element method (FEM) has been used to simulate cardiac and hepatic radiofrequency (RF) ablation. The FEM allows modeling of complex geometries that cannot be solved by analytical methods or finite difference models. In both hepatic and cardiac RF ablation a common control mode is temperature-controlled mode. Commercial FEM packages don't support automating temperature control. Most researchers manually control the applied power by trial and error to keep the tip temperature of the electrodes constant.     

The likelihood of persistent arthritis increases with the level of anti-citrullinated peptide antibody and immunoglobulin M rheumatoid factor: a longitudinal study of 376 patients with very early undifferentiated arthritis

Introduction  

We wanted to assess the importance of the levels of anti-citrullinated peptide antibody (anti-CCP) and immunoglobulin M (IgM) rheumatoid factor (RF) in predicting development of persistent arthritis from undifferentiated arthritis (UA), and to investigate whether there is an added predictive value for persistent arthritis in testing for both anti-CCP and IgM RF.     

Diverse bacterial genomes encode an operon of two genes, one of which is an unusual class-I release factor that potentially recognizes atypical mRNA signals other than normal stop codons

Background  

While all codons that specify amino acids are universally recognized by tRNA molecules, codons signaling termination of translation are recognized by proteins known as class-I release factors (RF). In most eukaryotes and archaea a single RF accomplishes termination at all three stop codons. In most bacteria, there are two RFs with overlapping specificity, RF1 recognizes UA(A/G) and RF2 recognizes U(A/G)A.     

Modeling thermal responses in human subjects following extended exposure to radiofrequency energy

Background  

This study examines the use of a simple thermoregulatory model for the human body exposed to extended (45 minute) exposures to radiofrequency/microwave (RF/MW) energy at different frequencies (100, 450, 2450 MHz) and under different environmental conditions. The exposure levels were comparable to or above present limits for human exposure to RF energy.     

Effect of variable heat transfer coefficient on tissue temperature next to a large vessel during radiofrequency tumor ablation

Background  

One of the current shortcomings of radiofrequency (RF) tumor ablation is its limited performance in regions close to large blood vessels, resulting in high recurrence rates at these locations. Computer models have been used to determine tissue temperatures during tumor ablation procedures. To simulate large vessels, either constant wall temperature or constant convective heat transfer coefficient (h) have been assumed at the vessel surface to simulate convection. However, the actual distribution of the temperature on the vessel wall is non-uniform and time-varying, and this feature makes the convective coefficient variable.     

Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor

Introduction  

The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).     

Mannan Binding Lectin (MBL) genotypes coding for high MBL serum levels are associated with rheumatoid factor negative rheumatoid arthritis in never smokers

Introduction  

Previous studies have provided inconsistent results on whether variants in the MBL2 gene, coding for the complement-activating mannan-binding lectin (MBL) protein, associate with rheumatoid arthritis (RA). We re-evaluated this in context of the main environmental and genetic risk factors (smoking, HLA-DRB1 'shared epitope' (SE), PTPN22*620W), which predispose to rheumatoid factor (RF) and/or anti-citrullinated-protein antibody (ACPA)-positive RA.     

Distribution of DNA replication proteins in Drosophila cells

Background  

DNA replication in higher eukaryotic cells is organized in discrete subnuclear sites called replication foci (RF). During the S phase, most replication proteins assemble at the RF by interacting with PCNA via a PCNA binding domain (PBD). This has been shown to occur for many mammalian replication proteins, but it is not known whether this mechanism is conserved in evolution.     

Performance of random forest when SNPs are in linkage disequilibrium

Background  

Single nucleotide polymorphisms (SNPs) may be correlated due to linkage disequilibrium (LD). Association studies look for both direct and indirect associations with disease loci. In a Random Forest (RF) analysis, correlation between a true risk SNP and SNPs in LD may lead to diminished variable importance for the true risk SNP. One approach to address this problem is to select SNPs in linkage equilibrium (LE) for analysis. Here, we explore alternative methods for dealing with SNPs in LD: change the tree-building algorithm by building each tree in an RF only with SNPs in LE, modify the importance measure (IM), and use haplotypes instead of SNPs to build a RF.     

Birdcage volume coils and magnetic resonance imaging: a simple experiment for students

Background

This article explains some simple experiments that can be used in undergraduate or graduate physics or biomedical engineering laboratory classes to learn how birdcage volume radiofrequency (RF) coils and magnetic resonance imaging (MRI) work. For a clear picture, and to do any quantitative MRI analysis, acquiring images with a high signal-to-noise ratio (SNR) is required. With a given MRI system at a given field strength, the only means to change the SNR using hardware is to change the RF coil used to collect the image. RF coils can be designed in many different ways including birdcage volume RF coil designs. The choice of RF coil to give the best SNR for any MRI study is based on the sample being imaged.

Results

The data collected in the simple experiments show that the SNR varies as inverse diameter for the birdcage volume RF coils used in these experiments. The experiments were easily performed by a high school student, an undergraduate student, and a graduate student, in less than 3 h, the time typically allotted for a university laboratory course.

Conclusions

The article describes experiments that students in undergraduate or graduate laboratories can perform to observe how birdcage volume RF coils influence MRI measurements. It is designed for students interested in pursuing careers in the imaging field.

     

M protein typing of Thai group A streptococcal isolates by PCR-Restriction fragment length polymorphism analysis

Background  

Group A streptococcal (GAS) infections can lead to the development of severe post-infectious sequelae, such as rheumatic fever (RF) and rheumatic heart disease (RHD). RF and RHD are a major health concern in developing countries, and in indigenous populations of developed nations. The majority of GAS isolates are M protein-nontypeable (MNT) by standard serotyping. However, GAS typing is a necessary tool in the epidemiologically analysis of GAS and provides useful information for vaccine development. Although DNA sequencing is the most conclusive method for M protein typing, this is not a feasible approach especially in developing countries. To overcome this problem, we have developed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assay for molecular typing the M protein gene (emm) of GAS.     

A Genome-Wide mRNA Expression Profile in Caenorhabditis elegans under Prolonged Exposure to 1750MHz Radiofrequency Fields

Objective

C. elegans has been used as a biomonitor for microwave-induced stress. However, the RF (radiofrequency) fields that have been used in previous studies were weak (≤1.8W/kg), and the bio-effects on C. elegans were mostly negative or ambiguous. Therefore, this study used more intense RF fields (SAR = 3W/kg) and longer time course of exposure (60h at 25°C, L1 stage through adult stage) to investigate the biological consequences of 1750 MHz RF fields in wild-type worms.

Methods

The growth rates and lifespans of RF-exposure group and the control group were carefully recorded. RNA samples were collected at L4 (35h) and gravid adult (50h) stages for further high-throughput sequencing, focusing on differences between the RF-exposure and the sham control groups.

Results

The RF-exposed and sham control groups developed at almost the same rate and had similar longevity curves. In L4 stage worms, 94 up-regulated and 17 down-regulated genes were identified, while 186 up-regulated and 3 down-regulated genes were identified in adult stage worms. GO analysis showed that the differentially expressed genes at 35h were associated with growth, body morphogenesis and collagen and cuticle-based development. Genes that were linked to growth rate and reproductive development were differentially expressed at 50h. Some embryonic and larval development genes in the offspring were also differentially expressed at 50h. Ten genes were differentially expressed at both 35h and 50h, most of which were involved in both embryonic and larval developmental processes. Although prolonged RF fields did not induce significant temperature increase in RF exposure groups, the temperature inside worms during exposure was unknown.

Conclusions

No harmful effects were observed in prolonged exposure to 1750 MHz RF fields at SAR of 3W/kg on development and longevity of C. elegans. Although some differentially expressed genes were found after prolonged RF exposure, these differences were ascribed to oscillating gene expression patterns in L4 and gravid adult worms. It was also difficult to rule out a weak thermal effect caused by prolonged RF exposure inside the worms.     

Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and the effect of rituximab

Introduction  

The purpose of this study was to quantitatively evaluate the contribution of synovial lymphoid aggregates to autoantibody (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) and total immunoglobulin (IgG and IgM) production in rheumatoid arthritis (RA) patients and the effect thereon of the B-cell-depleting antibody, rituximab, in the ARISE (Assessment of Rituximab's Immunomodulatory Synovial Effects) trial.     

Rheumatoid factor and anti-citrullinated protein antibody positivity,but not level,are associated with increased mortality in patients with rheumatoid arthritis: results from two large independent cohorts

Introduction

This study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA).

Methods

Data from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment.

Results

A total of 4962 patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. In NOAR and EAC respectively, 35% and 42% of patients were ACPA/RF positive. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% confidence interval) 1.35 (1.09 to 1.68) and 1.58 (1.16 to 2.15).

Conclusions

Patients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0483-3) contains supplementary material, which is available to authorized users.     

Influence of electrical and thermal properties on RF ablation of breast cancer: is the tumour preferentially heated?

Background  

Techniques based on radio frequency (RF) energy have many applications in medicine, in particular tumour ablation. Today, mammography screening detects many breast cancers at an early stage, facilitating treatment by minimally invasive techniques such as radio frequency ablation (RFA). The breast cancer is mostly surrounded by fat, which during RFA-treatment could result in preferential heating of the tumour due to the substantial differences in electrical parameters. The object of this study was to investigate if this preferential heating existed during experimental in vitro protocols and during computer simulations.     

Impact of 3.0 T Cardiac MR Imaging Using Dual-Source Parallel Radiofrequency Transmission with Patient-Adaptive B1 Shimming

Objectives

To prospectively evaluate the impact of 3.0 T Cardiac MR imaging using dual-source parallel radiofrequency (RF) transmission with patient-adaptive B1 shimming compared with single-source RF transmission in the RF homogeneity, image contrast and image quality.

Methods

The study was approved by the local institutional review board, and all subjects provided written informed consent. Fourteen healthy volunteers were examined at 3.0 T MR, with both the conventional single-source and the new dual-source RF transmission. B1 calibrations (RF shimming) of the heart region were performed to acquire a percent of the prescribed flip angle (FA) of B1 maps, which were used for quantitative assessment of RF homogeneity. Contrast ratios (CRs) between ventricular blood pool and septum were calculated on balanced-turbo field echo (B-TFE) cine images. The off-resonance artifacts of cine images were blindly assessed by two radiologists according to a 4-point grading-scale.

Results

A significantly lower mean coefficients of variance of the achieved FA with dual-source revealed better RF homogeneity compared to single-source (P = 0.0094). Dual-source RF shimming significantly increased the CRs (P<0.05) and reduced the off-resonance artifacts of B-TFE cine images (P<0.05). Inter-observer agreement for the off-resonance artifacts of B-TFE cine images was good to excellent (k >0.65).

Conclusions

Dual-source parallel RF transmission significantly improves the RF homogeneity, increases image contrast and reduces image artifacts of cardiac B-TFE images compared to single-source mode. This may be of value in reducing the observer-dependence of cardiac MR images and enhancing diagnostic confidence for clinical practice using CMR at 3.0 T.     

Therapeutic Efficacy of Combining PEGylated Liposomal Doxorubicin and Radiofrequency (RF) Ablation: Comparison between Slow-Drug-Releasing,Non-Thermosensitive and Fast-Drug-Releasing,Thermosensitive Nano-Liposomes

Aims

To determine how the accumulation of drug in mice bearing an extra-hepatic tumor and its therapeutic efficacy are affected by the type of PEGylated liposomal doxorubicin used, treatment modality, and rate of drug release from the liposomes, when combined with radiofrequency (RF) ablation.

Materials and Methods

Two nano-drugs, both long-circulating PEGylated doxorubicin liposomes, were formulated: (1) PEGylated doxorubicin in thermosensitive liposomes (PLDTS), having a burst-type fast drug release above the liposomes’ solid ordered to liquid disordered phase transition (at 42°C), and (2) non-thermosensitive PEGylated doxorubicin liposomes (PLDs), having a slow and continuous drug release. Both were administered intravenously at 8 mg/kg doxorubicin dose to tumor-bearing mice. Animals were divided into 6 groups: no treatment, PLD, RF, RF+PLD, PLDTS, and PLDTS+RF, for intra-tumor doxorubicin deposition at 1, 24, and 72 h post-injection (in total 41, mice), and 31 mice were used for randomized survival studies.

Results

Non-thermosensitive PLD combined with RF had the least tumor growth and the best end-point survival, better than PLDTS+RF (p<0.005) or all individual therapies (p<0.001). Although at 1 h post-treatment the greatest amount of intra-tumoral doxorubicin was seen following PLDTS+RF (p<0.05), by 24 and 72 h the greatest doxorubicin amount was seen for PLD+RF (p<0.05); in this group the tumor also has the longest exposure to doxorubicin.

Conclusion

Optimizing therapeutic efficacy of PLD requires a better understanding of the relationship between the effect of RF on tumor microenvironment and liposome drug release profile. If drug release is too fast, the benefit of changing the microenvironment by RF on tumor drug localization and therapeutic efficacy may be much smaller than for PLDs having slow and temperature-independent drug release. Thus the much longer circulation time of doxorubicin from PLD than from PLDTS may be beneficial in many therapeutic instances, especially in extra-hepatic tumors.     

Attenuated neuroprotective effect of riboflavin under UV-B irradiation via miR-203/c-Jun signaling pathway in vivo and in vitro

Background

Riboflavin (RF) or vitamin B2 is known to have neuroprotective effects. In the present study, we report the attenuation of the neuroprotective effects of RF under UV-B irradiation. Preconditioning of UV-B irradiated riboflavin (UV-B-RF) showed attenuated neuroprotective effects compared to that of RF in SH-SY5Y neuroblostoma cell line and primary cortical neurons in vitro and a rat model of cerebral ischemia in vivo.

Results

Results indicated that RF pretreatment significantly inhibited cell death and reduced LDH secretion compared to that of the UV-B-RF pretreatment in primary cortical neuron cultures subjected to oxygen glucose deprivation in vitro and cortical brain tissue subjected to ischemic injury in vivo. Further mechanistic studies using cortical neuron cultures revealed that RF treatment induced increased miR-203 expression which in turn inhibited c-Jun expression and increased neuronal cell survival. Functional assays clearly demonstrated that the UV-B-RF preconditioning failed to sustain the increased expression of miR-203 and the decreased levels of c-Jun, mediating the neuroprotective effects of RF. UV-B irradiation attenuated the neuroprotective effects of RF through modulation of the miR-203/c-Jun signaling pathway.

Conclusion

Thus, the ability of UV-B to serve as a modulator of this neuroprotective signaling pathway warrants further studies into its role as a regulator of other cytoprotective/neuroprotective signaling pathways.