Reproducibilty of partial weight bearing

Objectives: To find out whether partial weight bearing can be reproduced and retained. Design: In vivo experiment in normal subjects. Intervention: Training for partial weight bearing (25% of body weight) using bathroom scales. Main outcome measurement: Reproducibility on force platform immediately after training and after 60 min. Results: Twelve subjects were asked to reproduce 25% of their body weight through either the dominant or non-dominant limb on force platform after three practice attempts on bathroom scales with concurrent visual feedback. No feedback was provided after the measurements on force plate. The process was repeated after 1 h without any practice sessions in the interim period to find out if the weight practised could be retained. The mean 0-min reading was found to be 25.9% of body weight while the mean 60-min reading was found to be 24.4%. The p-value for the difference between the two means was found to be 0.3841. Conclusions: This study indicates that partial weight bearing instructions can be quantified and graded. Simple bathroom scales are sufficient to educate the patients and this can be practised at home after an initial period of supervision

Frequency-interleaved SDM transmission over multicore fiber for next generation short-reach optical interconnect systems

Space division multiplexing (SDM) technique is proposed to overcome the bandwidth density drives of short-reach optical transmission systems by utilizing 8-core multicore fiber (MCF). Intercore crosstalk (XT) and higher order modulation format are the most challenging impairments of SDM based optical interconnect (OI) systems. To satisfy the exponential growth of the Internet traffic a frequency interleaving scheme is applied to short-reach MCF OI transmission systems. The negative effects of spectral overlap and intercore XT is reduced by shifting channel frequencies between adjacent cores. To exploit the full potential of SDM power efficient binary phase shift keying (BPSK) modulation format and digital signal processing such as multiple input multiple output (MIMO) equalization are used

A novel 18F-labelled high affinity agent for PET imaging of the translocator protein

The translocator protein (TSPO) is an important target for imaging focal neuroinflammation in diseases such as brain cancer, stroke and neurodegeneration, but current tracers for non-invasive imaging of TSPO have important limitations. We present the synthesis and evaluation of a novel 3-fluoromethylquinoline-2-carboxamide, AB5186, which was prepared in eight steps using a one-pot two component indium(III)-catalysed reaction for the rapid and efficient assembly of the 4-phenylquinoline core. Biological assessment and the implementation of a physicochemical study showed AB5186 to have low nanomolar affinity for TSPO, as well as optimal plasma protein binding and membrane permeability properties. Generation of [18F]-AB5186 through 18F incorporation was achieved in good radiochemical yield and subsequent in vitro and ex vivo autoradiography revealed the ability of this compound to bind with specificity to TSPO in mouse glioblastoma xenografts. Initial positron emission tomography imaging of a glioma bearing mouse and a healthy baboon support the potential for [18F]-AB5186 use as a radiotracer for non-invasive TSPO imaging in vivo

Synthesis and evaluation of a radioiodinated tracer with specificity for poly(ADP-ribose) polymerase-1 (PARP-1) in vivo

Interest in nuclear imaging of poly(ADP-ribose) polymerase-1 (PARP-1) has grown in recent years due to the ability of PARP-1 to act as a biomarker for glioblastoma and increased clinical use of PARP-1 inhibitors. This study reports the identification of a lead iodinated analog 5 of the clinical PARP-1 inhibitor olaparib as a potential single-photon emission computed tomography (SPECT) imaging agent. Compound 5 was shown to be a potent PARP-1 inhibitor in cell-free and cellular assays, and it exhibited mouse plasma stability but approximately 3-fold greater intrinsic clearance when compared to olaparib. An (123)I-labeled version of 5 was generated using solid state halogen exchange methodology. Ex vivo biodistribution studies of [(123)I]-5 in mice bearing subcutaneous glioblastoma xenografts revealed that the tracer had the ability to be retained in tumour tissue and bind to PARP-1 with specificity. These findings support further investigations of [(123)I]-5 as a non-invasive PARP-1 SPECT imaging agent

An 18F-labeled poly(ADP-ribose) polymerase positron emission tomography imaging agent

Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for positron emission tomography (PET) and single photon emission computed tomography imaging. Consequently, over the past decade, there has been a drive to develop nuclear imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based on the potent PARP inhibitor olaparib (1). Our lead PET tracer candidate, [18F]20, was synthesized and evaluated as a potential PARP PET radiotracer in mice bearing subcutaneous glioblastoma xenografts using ex vivo biodistribution and PET−magnetic resonance imaging techniques. Results showed that [18F]20 could be produced in a good radioactivity yield and exhibited specific PARP binding allowing visualization of tumors overexpressing PARP. [18F]20 is therefore a potential candidate radiotracer for in vivo PARP PET imaging

Radiopharmaceuticals for imaging chronic lymphocytic inflammation

In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the preclinical diagnosis of chronic inflammatory processes, even before anatomical and functional changes occur in affected tissues. Moreover, the introduction of radiolabelled monoclonal antibodies and sophisticated technique like PET/CT now make the field of inflammation imaging highly specific and accurate. In this review, different approaches of the established and experimental radiopharmaceuticals for imaging of chronic inflammation are discussed.Nas últimas décadas, foram propostos vários radiofármacos para obtenção de imagens de sítios de inflamação, diferindo em suas especificidades e mecanismos de captação quando comparados aos tradicionais agentes utilizados para essa finalidade. Citocinas radiomarcadas representam uma ferramenta confiável para o diagnóstico pré-clinico precoce de processos inflamatórios crônicos, anterior às alterações anatômicas e funcionais, em tecidos afetados. Além disso, a introdução de anticorpos monoclonais radiomarcados e técnicas sofisticadas, como PET/CT, tornaram a obtenção de imagens de focos de inflamação altamente específica e apurada. Nesta revisão, diferentes abordagens com radiofármacos já bem estabelecidos e com outros em nível experimental para a obtenção de imagens de sítios de inflamação crônica são discutidas

Colocalization of different neurotransmitter transporters on synaptic vesicles is sparse except for VGLUT1 and ZnT3

Vesicular transporters (VTs) define the type of neurotransmitter that synaptic vesicles (SVs) store and release. While certain mammalian neurons release multiple transmitters, it is not clear whether the release occurs from the same or distinct vesicle pools at the synapse. Using quantitative single-vesicle imaging, we show that a vast majority of SVs in the rodent brain contain only one type of VT, indicating specificity for a single neurotransmitter. Interestingly, SVs containing dual transporters are highly diverse (27 types) but small in proportion (2% of all SVs), excluding the largest pool that carries VGLUT1 and ZnT3 (34%). Using VGLUT1-ZnT3 SVs, we demonstrate that the transporter colocalization influences the SV content and synaptic quantal size. Thus, the presence of diverse transporters on the same vesicle is bona fide, and depending on the VT types, this may act to regulate neurotransmitter type, content, and release in space and time

Towards Enriching Genomic Resources in Legumes

Food legumes, mainly comprising dry beans, dry peas, soybean, chickpea, pigeonpea, groundnut, greengram, blackgram, cowpea, lentil and lathyrus, have considerable area under cultivation globally and these are important constituents of cereal-based vegetarian diets. Keeping in view their tremendous importance for diversification and intensification of contemporary agriculture, systematic efforts towards their genetic improvement have been undertaken with classical breeding tools, lately complemented by the use of genomic tools. These genomic tools provide comprehensive information on genes involved in biochemical pathways leading upto nutritional compounds and can be used to understand the genetics of traits of interest and consequently, helping in marker assisted breeding. During the last two decades powerful genetic and genomic tools such as establishment of genetic and physical maps, expressed sequence tags, bioinformatic tools, genome-wide sequence data, genomic and metabolomic platforms, etc. have been developed for many legume species. These efforts have led to development of large scale molecular markers, identification of various marker trait associations, construction of genetic and linkage maps, expressed sequence tags database, partial or whole genome sequences, physical and molecular maps, DNA chips and bacterial artificial chromosome (BAC) libraries. After the genome sequencing of three model species, Medicago, Lotus and Glycine, draft genome sequences have recently been made available in agronomically important food legumes, pigeonpea and chickpea while similar efforts are underway in groundnut and greengram. The new generation sequencing (NGS) and genotyping platforms such as 454/FLX sequencing and Illumina GoldenGate/Solexa have revolutionized plant genomic research as these generate millions of ESTs per run. With the increased amount of genomic resources, there are now tremendous opportunities to integrate these with the genetic resources for their widespread use in routine legume improvement programmes by integrating them with conventional breeding tools. As a result, the genomics assisted breeding (GAB) can now be successfully used in legume improvement and development of improved genotypes having improved agronomic and quality traits and resistance to biotic and abiotic stresses. This chapter discusses the developments made in development of legume genomics and their role in overall improvement of food legumes