Magnetic resonance imaging of tumor-associated-macrophages (TAMs) with a nanoparticle contrast agent.

In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells in vitro. We evaluate the effect of degree of sulfation on uptake by primary cultured bone marrow derived macrophages (BMDM) and found that a higher degree of sulfation led to higher uptake, but there were no differences across the subtypes. Further analysis of the BMDM showed similar SR-A expression across stimulation conditions, suggesting that this classic model for macrophage subtypes may not be ideal for definitive M2 subtype marker expression, especially SR-A. We further examine the localization of SDIO in TAMs in vivo, in the mammary fat pad mouse model of breast cancer. We demonstrate that uptake by TAMs expressing SR-A scales with degree of sulfation, consistent with the in vitro studies. The TAMs demonstrate M2-like function and secrete Arg-1 but not iNOS. Uptake by these M2-like TAMs is validated by immunohistochemistry. SDIO show promise as a valuable addition to the toolkit of imaging probes targeted to different biomarkers for TAMs.

Analysis of the therapeutic effect of artificial leather embedding combined with fascial sleeve flap transplantation on chronic wounds of lower limbs with bone and plate exposure.

BACKGROUND: After severe trauma of lower limbs, bone, tendon or plate graft exposure is common. The traditional repair method is to use a variety of skin flap transplantation to cover the exposed part, but the wound often can not heal after operation, or the wound is cracked, ulcer, sinus, bone and steel plate are exposed again after wound healing. The reason for this result is that when the flap is covered, the space around the bone plate is not well closed, forming a dead cavity, blood and exudate accumulation, hematoma formation or infection, and finally the wound ruptures again. In addition, due to the swelling and contracture of the flap after operation, the suture tension between the flap and the receiving area becomes larger, the skin becomes thinner and broken, and then the wound is formed. In order to solve the above problems, we carried out the study of artificial true skin embedding combined with fascial sleeve flap transplantation in the treatment of chronic bone plate exposed wounds of lower limbs. METHODS: In this paper, 11 cases of chronic wounds with bone exposure and skin necrosis after steel plate implantation were selected. First stage is the wound bed preparation including primary wound expansion, removal of necrotic tissue and incision of sinus wall, removal of deep necrotic bone and fibrotic scarred skin on the outer wall of steel plate to normal tissue on the outer edge of the wound, removal of precipitated peptone and purulent fur in the hole, periphery and bone space of the steel plate, and removal of tendon tissue with basal necrosis and disintegration of the wound. After vacuum sealing drainage (VSD) 1-2 weeks, the peritraumatic basal granulation tissue grew well and there was no necrotic tissue in the wound. In the second stage, the exposed bone was covered with artificial dermis, the steel plate hole or the periphery and the basal space were filled, and the exposed steel plate was completely embedded, and then the fascia sleeve flap was transplanted to cover the wound. The sural neurovascular flap was performed in nine cases and the lateral superior malleolar artery perforator flap in two case. RESULTS: The flap survived well in all 11 cases. During the follow-up of 6 months to the removal of the plate, there was no case of rupture, exposure and sinus formation. CONCLUSIONS: Artificial dermal covering combined with fascial sleeve flap transplantation can effectively avoid wound dehiscence or sinus formation caused by foreign body retention, infection and flap contracture. It has good effect in repairing chronic wounds with bone plate exposure after severe trauma of lower limbs.

NMUR1 in the NMU-Mediated Regulation of Bone Remodeling.

Neuromedin-U (NMU) is an evolutionarily conserved peptide that regulates varying physiologic effects including blood pressure, stress and allergic responses, metabolic and feeding behavior, pain perception, and neuroendocrine functions. Recently, several lines of investigation implicate NMU in regulating bone remodeling. For instance, global loss of NMU expression in male and female mice leads to high bone mass due to elevated bone formation rate with no alteration in bone resorption rate or observable defect in skeletal patterning. Additionally, NMU treatment regulates the activity of osteoblasts in vitro. The downstream pathway utilized by NMU to carry out these effects is unknown as NMU signals via two G-protein-coupled receptors (GPCRs), NMU receptor 1 (NMUR1), and NMU receptor 2 (NMUR2), and both are expressed in the postnatal skeleton. Here, we sought to address this open question and build a better understanding of the downstream pathway utilized by NMU. Our approach involved the knockdown of Nmur1 in MC3T3-E1 cells in vitro and a global knockout of Nmur1 in vivo. We detail specific cell signaling events (e.g., mTOR phosphorylation) that are deficient in the absence of NMUR1 expression yet trabecular bone volume in femora and tibiae of 12-week-old male Nmur1 knockout mice are unchanged, compared to controls. These results suggest that NMUR1 is required for NMU-dependent signaling in MC3T3-E1 cells, but it is not required for the NMU-mediated effects on bone remodeling in vivo. Future studies examining the role of NMUR2 are required to determine the downstream pathway utilized by NMU to regulate bone remodeling in vivo.

A bioactive multi-functional heparin-grafted aligned poly(lactide-co-glycolide)/curcumin nanofiber membrane to accelerate diabetic wound healing.

Curcumin is reported to possess excellent efficacy to treat wounds that exhibit impaired healing. Heparin shows high affinity for many growth factors that are key biological mediators during the wound healing process. In this study, we aimed to prepare wound dressing membranes, for sustained release of an exogenous factor curcumin as well as sequestering endogenous growth factors at the wound site, to promote wound healing in diabetic rats. Toward this end, we prepared aligned curcumin-loaded poly(lactide-co-glycolide) (PLGA) nanofiber membranes (PC NFMs), followed by high density surface grafting of heparin to fabricate PLGA/curcumin (PCH) NFMs. Both PC and PCH NFMs show high tensile strength, low cytotoxicity and suitable water vapor transmission rate for application as wound dressings. Nonetheless, the PCH NFM shows higher curcumin release rate than PC due to enhanced hydrophilicity, which leads to higher cell migration rate and induced oxidative stress protection of HS68 fibroblast cells in vitro. In vivo study indicated the PCH exhibits the fastest wound closure rate among all membranes with accelerated re-epithelization rate, higher angiogenesis rate and more collagen deposition at the wound site. The accelerated and better skin tissue regeneration could be suggested to correlate with the multi-functionality of nanofibers, where grafted heparin attracting and stabilizing the growth factors important for wound healing in situ, together with relieving the high oxidative stress and the inflammatory cascade from released curcumin during diabetic wound healing.

Silence of Binary Kerr Black Holes.

A nontrivial S matrix generally implies a production of entanglement: starting with an incoming pure state, the scattering generally returns an outgoing state with nonvanishing entanglement entropy. It is then interesting to ask if there exists a nontrivial S matrix that generates no entanglement. In this Letter, we argue that the answer is the S-matrix for the scattering of classical black holes. We study the spin entanglement in the scattering of arbitrary spinning particles. Augmenting the S-matrix with Thomas-Wigner rotation factors, we derive the entanglement entropy from the gravitational induced 2→2 amplitude. In the Eikonal limit, we find that the relative entanglement entropy, defined here as the difference between the entanglement entropy of the in and out states, is nearly zero for minimal coupling irrespective of the in state and increases significantly for any nonvanishing spin multipole moments. This finding suggests that minimal couplings of spinning particles, whose classical limit corresponds to a Kerr black hole, have the unique feature of generating near zero entanglement.

Neuromedin U (NMU) regulates osteoblast differentiation and activity.

Osteoporosis is a disease of low bone mass that places individuals at enhanced risk for fracture, disability, and death. Osteoporosis rates are expected to rise significantly in the coming decades yet there are limited pharmacological treatment options, particularly for long-term management of this chronic condition. The drug development pipeline is relatively bereft of new strategies, causing an urgent and unmet need for developing new strategies and targets for treating osteoporosis. Here, we examine a lesser-studied bone remodeling pathway, Neuromedin U (NMU), which is expressed in the bone microenvironment along with its cognate receptors NMU receptor 1 (NMUR1) and 2 (NMUR2). We independently corroborate a prior report that global loss of NMU expression leads to high bone mass and test the hypothesis that NMU negatively regulates osteoblast differentiation. Consistent with this, in vitro studies reveal NMU represses osteoblastic differentiation of osteogenic precursors but, in contrast, promotes osteoblastic marker expression, proliferation and activity of osteoblast-like cells. Phospho-profiling arrays were used to detail differential signaling outcomes that may underlie the opposite responses of these cell types. Collectively, our findings indicate that NMU exerts cell-type-specific responses to regulate osteoblast differentiation and activity.

Synthetic α5ß1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke.

Ischemic stroke is the leading cause of disability and death worldwide. An effective therapeutic approach is urgently needed. Stroke-induced angiogenesis and neurogenesis are essential mechanisms in the long-term repair. Extracellular matrix proteins are also involved in tissue self-repair. Recently, a PHSRN (Pro-His-Ser-Arg-Asn) peptide from the fibronectin synergistic motif that can promote wound healing in epithelia and induce endothelial proliferation and cancer cell migration was identified. The therapeutic potential of this peptide in stroke is unknown. Here, we examined the potential of PHSRN in stroke therapy using an ischemic rat model of middle cerebral artery occlusion (MCAO). PHSRN reduced the infarct volume in MCAO rats, improved neurological function, and alleviated motor function impairment. PHSRN targeted the damaged brain region and distributed to endothelial cells after intraperitoneal injection. PHSRN significantly promoted angiogenesis and vascular endothelial growth factor secretion through activation of integrin α5ß1 and its downstream intracellular signals, e.g., focal adhesion kinase, Ras, cRaf, and extracellular-signal-regulated kinase. PHSRN treatment also stimulated neurogenesis in MCAO rats, and maintained neuronal survival and neuronal morphologic complexity via induction of VEGF secretion. Together, these results provide insights into the role of integrin α5ß1 following ischemia and support the feasibility of using PHSRN peptide in stroke therapy.

Dualities for Ising Networks.

In this Letter, we study the equivalence between planar Ising networks and cells in the positive orthogonal Grassmannian. We present a microscopic construction based on amalgamation, which establishes the correspondence for any planar Ising network. The equivalence allows us to introduce two recursive methods for computing correlators of Ising networks. The first is based on duality moves, which generate networks belonging to the same cell in the Grassmannian. This leads to fractal lattices where the recursion formulas become the exact renormalization group equations of the effective couplings. The second, we use an amalgamation in which each iteration doubles the size of the seed lattice. This leads to an efficient way of computing the correlator where the complexity scales logarithmically with respect to the number of spin sites.

Correction: Induction of Connective Tissue Growth Factor Expression by Hypoxia in Human Lung Fibroblasts via the MEKK1/MEK1/ERK1/GLI-1/GLI-2 and AP-1 Pathways.

[This corrects the article DOI: 10.1371/journal.pone.0160593.].

Analysis of phenolic acids by ionic liquid-in-water microemulsion liquid chromatography coupled with ultraviolet and electrochemical detector.

An environmentally friendly ionic liquid-in-water (IL/W) microemulsion was established and applied as mobile phase in microemulsion liquid chromatography (MELC) with ultraviolet (UV) detection or electrochemical detector (ECD) for analysis of phenolic compounds in real samples. The optimal condition of the method was using the best composition of microemulsion (0.2% w/v [HMIM]PF6, 1.0% w/v SDS, 3.0% w/v n-butanol, 95.8% v/v water, pH 2.5) with UV detection. The validation results indicated that the method provided high degree of sensitivity, precision and accuracy with the low limit of detections ranged from 17.9-238ng/mL, satisfactory mean recovery values in the range of 80.1-105% and good linearity (r2>0.9994). Additionally, this method exhibited high selectivity and resolution for the analytes and was more eco-friendly compared with traditional MELC method. Consequently, the established IL/W MELC method was successfully applied to simultaneously separate and determine target compounds in Danshen sample and its preparation.

Induction of Connective Tissue Growth Factor Expression by Hypoxia in Human Lung Fibroblasts via the MEKK1/MEK1/ERK1/GLI-1/GLI-2 and AP-1 Pathways.

Several reports have indicated that hypoxia, GLI, and connective tissue growth factor (CTGF) contribute to pulmonary fibrosis in idiopathic pulmonary fibrosis. We investigated the participation of mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1)/MEK1/ERK1/GLI-1/2 and activator protein-1 (AP-1) signaling in hypoxia-induced CTGF expression in human lung fibroblasts. Hypoxia time-dependently increased CTGF expression, which was attenuated by the small interfering RNA (siRNA) of GLI-1 (GLI-1 siRNA) and GLI-2 (GLI-2 siRNA) in both human lung fibroblast cell line (WI-38) and primary human lung fibroblasts (NHLFs). Moreover, GLI-1 siRNA and GLI-2 siRNA attenuated hypoxia-induced CTGF-luciferase activity, and the treatment of cells with hypoxia induced GLI-1 and GLI-2 translocation. Furthermore, hypoxia-induced CTGF expression was reduced by an MEK inhibitor (PD98059), MEK1 siRNA, ERK inhibitor (U0126), ERK1 siRNA, and MEKK1 siRNA. Both PD98059 and U0126 significantly attenuated hypoxia-induced CTGF-luciferase activity. Hypoxia time-dependently increased MEKK1, ERK, and p38 MAPK phosphorylation. Moreover, SB203580 (a p38 MAPK inhibitor) also apparently inhibited hypoxia-induced CTGF expression. The treatment of cells with hypoxia induced ERK, GLI-1, or GLI-2 complex formation. Hypoxia-induced GLI-1 and GLI-2 translocation into the nucleus was significantly attenuated by U0126. In addition, hypoxia-induced ERK Tyr204 phosphorylation was impeded by MEKK1 siRNA. Moreover, hypoxia-induced CTGF-luciferase activity was attenuated by cells transfected with AP-1 site mutation in a CTGF construct. Exposure to hypoxia caused a time-dependent phosphorylation of c-Jun, but not of c-Fos. Chromatin immunoprecipitation (ChIP) revealed that hypoxia induced the recruitment of c-Jun, GLI-1, and GLI-2 to the AP-1 promoter region of CTGF. Hypoxia-treated cells exhibited an increase in α-smooth muscle actin (α-SMA) and collagen production, which was blocked by GLI-1 siRNA and GLI-2 siRNA. Overall, these data implied that the MEKK1/MEK1/ERK1/GLI-1/GLI-2, and AP-1 pathways mediated hypoxia-induced CTGF expression in human lung fibroblasts. Furthermore, GLI-1 and GLI-2 found to be involved in hypoxia-induced α-SMA and collagen expression.

The stimuli-responsive multiphase behavior of core-shell nanogels with opposite charges and their potential application in in situ gelling system.

Concentrated p(N-isopropylacrylamide) (PNIPAM) nanogel dispersions exhibited rich temperature-sensitive sol-gel phase transition behavior. In the present work, the influence of electrostatic forces between nanogel particles, including attraction and repulsion, on the sol-gel phase transition behavior of PNIPAM nanogel dispersions has been studied. Both oppositely charged nanogels with core-shell structures (NIA and PND nanogels) were synthesized, and their shell charges were calculated to -0.33 and 0.082 mmol/g by potentiometric titration method. When mixed with various ratio of negative and positive charge (NC value), the resultant mixture dispersions of NIA and PND nanogel (OCNs) exhibited different aggregating behavior from NIA and PND nanogels. OCN-e aggregates (NC value=1/4), which exhibited temperature-independence of electric neutrality, had the maximum size, about 1.9-2.2 times larger than NIA or PND nanogels. Concentrated OCN-e dispersions exhibited stronger ability to form shrunken gel. Its CGC was about 2.0 wt%, 4-times lower than that of NIA and PND nanogels (about 8.0 wt%). In vitro and in vivo gelling results indicated that OCN-e aggregates could form free-standing gel with good mechanical strength, and were promising to be developed as new in situ gelling system.

New Fermionic Soft Theorems for Supergravity Amplitudes.

Soft limits of a massless S matrix are known to reflect the symmetries of the theory. In particular, for theories with Goldstone bosons, the double-soft limit of scalars reveals the coset structure of the vacuum manifold. In this Letter, we propose that such universal double-soft behavior is not only true for scalars, but also for spin-1/2 particles in four dimensions and fermions in three dimensions. We first consider the Akulov-Volkov theory and demonstrate that the double-soft limit of Goldstinos yields the supersymmetry algebra. More surprisingly, we also find that amplitudes in 4≤N≤8 supergravity theories in four dimensions as well as N=16 supergravity in three dimensions behave universally in the double-soft-fermion limit, analogous to the scalar ones. The validity of the new soft theorems at loop level is also studied. The results for supergravity are beyond what is implied by supersymmetry Ward identities and may impose nontrivial constraints on the possible counterterms for supergravity theories.

A novel sound-blocking structure based on the muffler principle for rib-sparing transcostal high-intensity focused ultrasound treatment.

The main challenge in transcostal high-intensity focused ultrasound therapy is minimising heat deposition in the ribs while ensuring that a sufficient dose is delivered to the target region. Current approaches rely on expensive multichannel phased-array systems to turn the individual transducer on and off according to either geometrical arrangements or complicated wave calculations. To protect the ribs from heating, the ultrasound energy must not only not reach the ribs, but must also not accumulate in front of the ribs. The research in this paper proposes a different approach, of attaching a sound-blocking structure in front of the rib cage with similar effects to those of an engine exhaust muffler. The sound-blocking structure is based on the muffler principle to prevent ultrasound energy from reaching the ribs and reduce the amount of energy reflected back to the applicator. Finite element simulations with a 0.5-MHz transducer of the overall sound fields and temperature distribution showed that the ultrasound pressure and energy level would decrease behind the novel sound-blocking structures, thereby resulting in a lower temperature at the ribs than at the tumour. Without the protecting structure, the rib temperature reached 104.19 °C whereas with the structure it reached only 37.86 °C. An experimental set-up using porcine ribs with a phantom was also developed to validate the concept, which showed that the rib temperature reached 73 °C without protection within 1 min of ablation time whereas it reached 36.5 °C with the device. The tumour region in the tests reached 51 °C and 49 °C with and without protection, respectively.

Ecological genomics in Xanthomonas: the nature of genetic adaptation with homologous recombination and host shifts.

BACKGROUND: Comparative genomics provides insights into the diversification of bacterial species. Bacterial speciation usually takes place with lasting homologous recombination, which not only acts as a cohering force between diverging lineages but brings advantageous alleles favored by natural selection, and results in ecologically distinct species, e.g., frequent host shift in Xanthomonas pathogenic to various plants. RESULTS: Using whole-genome sequences, we examined the genetic divergence in Xanthomonas campestris that infected Brassicaceae, and X. citri, pathogenic to a wider host range. Genetic differentiation between two incipient races of X. citri pv. mangiferaeindicae was attributable to a DNA fragment introduced by phages. In contrast to most portions of the genome that had nearly equivalent levels of genetic divergence between subspecies as a result of the accumulation of point mutations, 10% of the core genome involving with homologous recombination contributed to the diversification in Xanthomonas, as revealed by the correlation between homologous recombination and genomic divergence. Interestingly, 179 genes were under positive selection; 98 (54.7%) of these genes were involved in homologous recombination, indicating that foreign genetic fragments may have caused the adaptive diversification, especially in lineages with nutritional transitions. Homologous recombination may have provided genetic materials for the natural selection, and host shifts likely triggered ecological adaptation in Xanthomonas. To a certain extent, we observed positive selection nevertheless contributed to ecological divergence beyond host shifting. CONCLUSION: Altogether, mediated with lasting gene flow, species formation in Xanthomonas was likely governed by natural selection that played a key role in helping the deviating populations to explore novel niches (hosts) or respond to environmental cues, subsequently triggering species diversification.

Protective effects of bifidobacterial adhesin on intestinal mucosa of stressed male rats via modulation of inflammation.

This study aimed to assess BA impact on inflammation markers and repair of intestinal mucosa. Forty-eight rats were randomly divided into stress (n = 24) and BA (n = 24) groups. Stress was induced by fettering in all animals, fed enterally with 125.4 kJ/kg/d and 0.2 g/kg/d nitrogen. Then, rats were treated for 8 days with 5 mg/kg/d BA (BA group) or 5 mg/kg/d saline (Stress group). Levels of NF-κB, IL-10, TNF-α, and IFN-γ were measured at different time points, in plasma and intestinal mucosa samples. Changes in intestinal mucosa morphology were observed by electron microscopy. Plasma and/or mucosal levels of NF-κB, TNF-α, and IFN-γ were significantly higher in both groups after stress induction (P < 0.05). These high levels persisted in control animals throughout the experiment, and were significantly reduced in the BA group, 3 and 8 days after stress induction (P < 0.05). Interestingly, IL-10 levels were increased after BA treatment (P < 0.05). At day 8, ileal mucosal villi and crypt structure were significantly restored in the BA group. Bifidobacterial adhesin plays a role in repairing intestinal mucosa injury after stress by regulating the release of inflammatory mediators in the intestinal mucosa.

Consistency conditions for gauge theory S matrices from requirements of generalized unitarity.

In the modern on-shell approach, the perturbative S matrix is constructed iteratively using on-shell building blocks with manifest unitarity. As only gauge invariant quantities enter in the intermediate steps, the notion of a gauge anomaly is absent. In this Letter, we rephrase the anomaly cancellation conditions in a purely on-shell language. We demonstrate that while the unitarity methods automatically lead to a unitary S matrix, the rational terms that are required to enforce locality, invariably give rise to inconsistent factorization channels in chiral theories. In four dimensions, the absence of such inconsistencies implies the vanishing of the symmetric trace of three generators. In six dimensions, if the symmetric trace of four generators does not vanish, the rational term develops a factorization channel revealing a new particle in the spectrum: the 2-form of the Green-Schwarz mechanism. Thus, in the purely on-shell construction, the notion of a gauge anomaly is replaced by the difficulty to consistently impose locality on the unitary S matrix.

The depletion of securin enhances butein-induced apoptosis and tumor inhibition in human colorectal cancer.

Butein (3,4,2',4'-tetrahydroxychalcone) is a promising natural polyphenolic compound that shows the growth inhibitory activity in human cancer cells; however, the precise mechanism is still unclear. Securin plays pivotal role in cancer cell proliferation and tumorigenesis. Here, we report the presence of securin that could modulate apoptosis and tumor growth ability in the butein-treated human colorectal cancer. Butein induced caspase-3 activation and PARP protein cleavage for apoptosis induction in human colorectal cancer cells. Interestingly, butein reduced the securin protein levels but conversely increased the phospho-histone H3 proteins, mitotic arrest and abnormal chromosomes segregation in cancer cells. The securin-null colorectal cancer cells were more sensitive on the reduction of cell viability than the securin-wild type cancer cells following butein treatment. The loss of securin in human colorectal cancer cells decreased tumor growth ability in nude mice. Moreover, butein reduced the tumor size of xenografted human colorectal tumors of nude mice. Taken together, this study demonstrates for the first time that the depletion of securin mediates the butein-induced apoptosis and colorectal tumor inhibition.

HaplotypeCN: copy number haplotype inference with Hidden Markov Model and localized haplotype clustering.

Copy number variation (CNV) has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states.

Equivalent D = 3 supergravity amplitudes from double copies of three-algebra and two-algebra gauge theories.

We show that three-dimensional supergravity amplitudes can be obtained as double copies of either three-algebra super-Chern-Simons matter theory or two-algebra super-Yang-Mills theory when either theory is organized to display the color-kinematics duality. We prove that only helicity-conserving four-dimensional gravity amplitudes have nonvanishing descendants when reduced to three dimensions, implying the vanishing of odd-multiplicity S-matrix elements, in agreement with Chern-Simons matter theory. We explicitly verify the double-copy correspondence at four and six points for N = 12,10,8 supergravity theories and discuss its validity for all multiplicity.