A long view of liberal peace and its crisis

The ‘crisis’ of liberal peace has generated considerable debate in International Relations. However, analysis is inhibited by a shared set of spatial, cultural and temporal assumptions that rest on and reproduce a problematic separation between self-evident ‘liberal’ and ‘non-liberal’ worlds, and locates the crisis in presentist terms of the latter’s resistance to the former’s expansion. By contrast, this article argues that efforts to advance liberal rule have always been interwoven with processes of alternative order-making, and in this way are actively integral, not external, to the generation of the subjectivities, contestations, violence and rival social orders that are then apprehended as self-evident obstacles and threats to liberal peace and as characteristic of its periphery. Making visible these intimate relations of co-constitution elided by representations of liberal peace and its crisis requires a long view and an analytical frame that encompasses both liberalism and its others in the world. The argument is developed using a Foucauldian governmentality framework and illustrated with reference to Sri Lanka

A blind accuracy assessment of computer-modeled forensic facial reconstruction using computed tomography data from live subjects.

A computer modeling system for facial reconstruction has been developed that employs a touch-based application to create anatomically accurate facial models focusing on skeletal detail. This article discusses the advantages and disadvantages of the system and illustrates its accuracy and reliability with a blind study using computed tomography (CT) data of living individuals. Three-dimensional models of the skulls of two white North American adults (one male, one female) were imported into the computer system. Facial reconstructions were produced by two practitioners following the Manchester method. Two posters were produced, each including a face pool of five surface model images and the facial reconstruction. The face pool related to the sex, age, and ethnic group of the target individual and included the surface model image of the target individual. Fifty-two volunteers were asked to choose the face from the face pool that most resembled each reconstruction. Both reconstructions received majority percentage hit rates that were at least 50% greater than any other face in the pool. The combined percentage hit rate was 50% above chance (70%). A quantitative comparison of the facial morphology between the facial reconstructions and the CT scan models of the subjects was carried out using Rapidform(™) 2004 PP2-RF4. The majority of the surfaces of the facial reconstructions showed less than 2.5 mm error and 90% of the male face and 75% of the female face showed less than 5 mm error. Many of the differences between the facial reconstructions and the facial scans were probably the result of positional effects caused during the CT scanning procedure, especially on the female subject who had a fatter face than the male subject. The areas of most facial reconstruction error were at the ears and nasal tip

Restoration of disk height through non-surgical spinal decompression is associated with decreased discogenic low back pain: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Because previous studies have suggested that motorized non-surgical spinal decompression can reduce chronic low back pain (LBP) due to disc degeneration (discogenic low back pain) and disc herniation, it has accordingly been hypothesized that the reduction of pressure on affected discs will facilitate their regeneration. The goal of this study was to determine if changes in LBP, as measured on a verbal rating scale, before and after a 6-week treatment period with non-surgical spinal decompression, correlate with changes in lumbar disc height, as measured on computed tomography (CT) scans.</p> <p>Methods</p> <p>A retrospective cohort study of adults with chronic LBP attributed to disc herniation and/or discogenic LBP who underwent a 6-week treatment protocol of motorized non-surgical spinal decompression via the DRX9000 with CT scans before and after treatment. The main outcomes were changes in pain as measured on a verbal rating scale from 0 to 10 during a flexion-extension range of motion evaluation and changes in disc height as measured on CT scans. Paired t-test or linear regression was used as appropriate with p < 0.05 considered to be statistically significant.</p> <p>Results</p> <p>We identified 30 patients with lumbar disc herniation with an average age of 65 years, body mass index of 29 kg/m², 21 females and 9 males, and an average duration of LBP of 12.5 weeks. During treatment, low back pain decreased from 6.2 (SD 2.2) to 1.6 (2.3, p < 0.001) and disc height increased from 7.5 (1.7) mm to 8.8 (1.7) mm (p < 0.001). Increase in disc height and reduction in pain were significantly correlated (r = 0.36, p = 0.044).</p> <p>Conclusions</p> <p>Non-surgical spinal decompression was associated with a reduction in pain and an increase in disc height. The correlation of these variables suggests that pain reduction may be mediated, at least in part, through a restoration of disc height. A randomized controlled trial is needed to confirm these promising results.</p> <p>Clinical trial registration number</p> <p>NCT00828880</p

Nucleoside diphosphate kinase A as a controller of AMP-kinase in airway epithelia

This review integrates recent understanding of a novel role for NDPK-A in two related directions: Firstly, its role in an airway epithelial cell when bound to the luminal (apical) membrane and secondly in the cytosol of many different cells (epithelial and non-epithelial) where an isoform-specific interaction occurs with a regulatory partner, AMPKα1. Thus NDPK-A is present in both a membrane and cytosolic environment but in the apical membrane, its roles are not understood in detail; preliminary data suggest that it co-localises with the cystic fibrosis protein (CFTR). In cytosol, we find that NDPK-A is coupled to the catalytic alpha1 isoform of the AMP-activated protein kinase (AMPKα subunit), which is part of a heterotrimeric protein complex that responds to cellular energy status by switching off ATP-consuming pathways and switching on ATP-generating pathways when ATP is limiting. We find that ATP is located within this complex and ‘fed’ from NDPK to AMPK without ever ‘seeing’ bulk solution. Importantly, the reverse can also happen such that AMPK activity can be made to decline when NDPK-A ‘steals’ ATP from AMPK. Thus we propose a novel paradigm in NDPK-A function by suggesting that AMP-kinase can be regulated by NDPK-A, independently of AMP

Development of an Orthotopic Human Pancreatic Cancer Xenograft Model Using Ultrasound Guided Injection of Cells

Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. In particular, orthotopic tumor xenograft mouse models are emerging as the preference for cancer research due to increased clinical relevance over subcutaneous mouse models. In the current study, we developed orthotopic pancreatic cancer xenograft models in mice by a minimally invasive method, ultrasound guided injection (USGI) comparable to highly invasive surgical orthotopic injection (SOI) methods. This optimized method prevented injection complications such as recoil of cells through the injection canal or leakage of cells out of the pancreas into the peritoneal cavity. Tumor growth was monitored in vivo and quantified by ultrasound imaging weekly, tumors were also detected by in vivo fluorescence imaging using a tumor targeted molecular probe. The mean tumor volumes for the USGI and SOI models after 2 weeks of tumor growth were 205 mm3 and 178 mm3 respectively. By USGI of human pancreatic cancer cell lines, human orthotopic pancreatic cancer xenografts were established. Based on ultrasound imaging, the orthotopic human pancreatic cancer xenograft take rate was 100% for both human pancreatic cancer cell lines used, MiaPaCa-2 and Su86.86, with mean tumor volumes of 28 mm3and 30 mm3. We demonstrated that this USGI method is feasible, reproducible, facile, minimally invasive and improved compared to the highly-invasive SOI method for establishing orthotopic pancreatic tumor xenograft models suitable for molecular imaging

Development of an Orthotopic Human Pancreatic Cancer Xenograft Model Using Ultrasound Guided Injection of Cells

Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. In particular, orthotopic tumor xenograft mouse models are emerging as the preference for cancer research due to increased clinical relevance over subcutaneous mouse models. In the current study, we developed orthotopic pancreatic cancer xenograft models in mice by a minimally invasive method, ultrasound guided injection (USGI) comparable to highly invasive surgical orthotopic injection (SOI) methods. This optimized method prevented injection complications such as recoil of cells through the injection canal or leakage of cells out of the pancreas into the peritoneal cavity. Tumor growth was monitored in vivo and quantified by ultrasound imaging weekly, tumors were also detected by in vivo fluorescence imaging using a tumor targeted molecular probe. The mean tumor volumes for the USGI and SOI models after 2 weeks of tumor growth were 205 mm3 and 178 mm3 respectively. By USGI of human pancreatic cancer cell lines, human orthotopic pancreatic cancer xenografts were established. Based on ultrasound imaging, the orthotopic human pancreatic cancer xenograft take rate was 100% for both human pancreatic cancer cell lines used, MiaPaCa-2 and Su86.86, with mean tumor volumes of 28 mm3and 30 mm3. We demonstrated that this USGI method is feasible, reproducible, facile, minimally invasive and improved compared to the highly-invasive SOI method for establishing orthotopic pancreatic tumor xenograft models suitable for molecular imaging

A theoretical model for template-free synthesis of long DNA sequence

This theoretical scheme is intended to formulate a potential method for high fidelity synthesis of Nucleic Acid molecules towards a few thousand bases using an enzyme system. Terminal Deoxyribonucleotidyl Transferase, which adds a nucleotide to the 3′OH end of a Nucleic Acid molecule, may be used in combination with a controlled method for nucleotide addition and degradation, to synthesize a predefined Nucleic Acid sequence. A pH control system is suggested to regulate the sequential activity switching of different enzymes in the synthetic scheme. Current practice of synthetic biology is cumbersome, expensive and often error prone owing to the dependence on the ligation of short oligonucleotides to fabricate functional genetic parts. The projected scheme is likely to render synthetic genomics appreciably convenient and economic by providing longer DNA molecules to start with

Broader Neutralizing Antibodies against H5N1 Viruses Using Prime-Boost Immunization of Hyperglycosylated Hemagglutinin DNA and Virus-Like Particles

BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 viruses and their transmission capability from birds to humans have raised global concerns about a potential human pandemic. The inherent nature of antigenic changes in influenza viruses has not been sufficiently taken into account in immunogen designs for broadly protective HPAI H5N1 vaccines. METHODS: We designed a hyperglycosylated HA vaccine using N-linked glycan masking on highly variable sequences in the HA1 globular head. Immunization of these hyperglycosylated HA DNA vaccines followed by a flagellin-containing virus-like particle booster in mice was conducted to evaluate neutralizing antibody responses against various clades of HPAI H5N1 viruses. RESULTS: We introduced nine N-X-S/T motifs in five HA1 regions: 83NNT, 86NNT, 94NFT, 127NSS, 138NRT, 156NTT, 161NRS, 182NDT, and 252NAT according to sequence alignment analyses from 163 HPAI H5N1 human isolates. Although no significant differences of anti-HA total IgG titers were found with these hyperglycosyalted HA compared to the wild-type control, the 83NNT and 127NSS mutants elicited significantly potent cross-clade neutralizing antibodies against HPAI H5N1 viruses. CONCLUSIONS: This finding may have value in terms of novel immunogen design for developing cross-protective H5N1 vaccines

Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation with CFTR whereas PKA inhibitors attenuate complex formation. Furthermore, an NDPK-B derived peptide (but not its NDPK-A equivalent) disrupts the NDPK-B/CFTR complex in vitro (19-mers comprising amino acids 36-54 from NDPK-B or NDPK-A). Overlay (Far-Western) and Surface Plasmon Resonance (SPR) analysis both demonstrate that NDPK-B binds CFTR within its first nucleotide binding domain (NBD1, CFTR amino acids 351-727). Analysis of chloride currents reflective of CFTR or outwardly rectifying chloride channels (ORCC, DIDS-sensitive) showed that the 19-mer NDPK-B peptide (but not its NDPK-A equivalent) reduced both chloride conductances. Additionally, the NDPK-B (but not NDPK-A) peptide also attenuated acetylcholine-induced intestinal short circuit currents. In silico analysis of the NBD1/NDPK-B complex reveals an extended interaction surface between the two proteins. This binding zone is also target of the 19-mer NDPK-B peptide, thus confirming its capability to disrupt NDPK-B/CFTR complex. We propose that NDPK-B forms part of the complex that controls chloride currents in epithelia

Insights into the chemical composition of Equisetum hyemale by high resolution Raman imaging

Equisetaceae has been of research interest for decades, as it is one of the oldest living plant families, and also due to its high accumulation of silica up to 25% dry wt. Aspects of silica deposition, its association with other biomolecules, as well as the chemical composition of the outer strengthening tissue still remain unclear. These questions were addressed by using high resolution (<1 μm) Confocal Raman microscopy. Two-dimensional spectral maps were acquired on cross sections of Equisetum hyemale and Raman images calculated by integrating over the intensity of characteristic spectral regions. This enabled direct visualization of differences in chemical composition and extraction of average spectra from defined regions for detailed analyses, including principal component analysis (PCA) and basis analysis (partial least square fit based on model spectra). Accumulation of silica was imaged in the knobs and in a thin layer below the cuticula. In the spectrum extracted from the knob region as main contributions, a broad band below 500 cm−1 attributed to amorphous silica, and a band at 976 cm−1 assigned to silanol groups, were found. From this, we concluded that these protrusions were almost pure amorphous, hydrated silica. No silanol group vibration was detected in the silicified epidermal layer below and association with pectin and hemicelluloses indicated. Pectin and hemicelluloses (glucomannan) were found in high levels in the epidermal layer and in a clearly distinguished outer part of the hypodermal sterome fibers. The inner part of the two-layered cells revealed as almost pure cellulose, oriented parallel along the fiber