1,653 research outputs found
Why are tumour blood vessels abnormal and why is it important to know?
Tumour blood vessels differ from their normal counterparts for reasons that have received little attention. We report here that they are of at least six distinct types, we describe how each forms, and, looking forward, encourage the targeting of tumour vessel subsets that have lost their vascular endothelial growth factor-A (VEGF-A) dependency and so are likely unresponsive to anti-VEGF-A therapies
Scattering AMplitudes from Unitarity-based Reduction Algorithm at the Integrand-level
SAMURAI is a tool for the automated numerical evaluation of one-loop
corrections to any scattering amplitudes within the dimensional-regularization
scheme. It is based on the decomposition of the integrand according to the
OPP-approach, extended to accommodate an implementation of the generalized
d-dimensional unitarity-cuts technique, and uses a polynomial interpolation
exploiting the Discrete Fourier Transform. SAMURAI can process integrands
written either as numerator of Feynman diagrams or as product of tree-level
amplitudes. We discuss some applications, among which the 6- and 8-photon
scattering in QED, and the 6-quark scattering in QCD. SAMURAI has been
implemented as a Fortran90 library, publicly available, and it could be a
useful module for the systematic evaluation of the virtual corrections oriented
towards automating next-to-leading order calculations relevant for the LHC
phenomenology.Comment: 35 pages, 7 figure
Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics
DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to ‘sloppy’ transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences
Polymorphisms and their Haplotype Combinations in the Lysozyme Gene Associated with the Production Traits of a Chinese Native Chicken Breed
RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord
ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients
Large scale analytic calculations in quantum field theories
We present a survey on the mathematical structure of zero- and single scale
quantities and the associated calculation methods and function spaces in higher
order perturbative calculations in relativistic renormalizable quantum field
theories.Comment: 25 pages Latex, 1 style fil
Diet of the lizard Liolaemus occipitalis in the coastal sand dunes of southern Brazil (Squamata-Liolaemidae)
On the Integrand-Reduction Method for Two-Loop Scattering Amplitudes
We propose a first implementation of the integrand-reduction method for
two-loop scattering amplitudes. We show that the residues of the amplitudes on
multi-particle cuts are polynomials in the irreducible scalar products
involving the loop momenta, and that the reduction of the amplitudes in terms
of master integrals can be realized through polynomial fitting of the
integrand, without any apriori knowledge of the integral basis. We discuss how
the polynomial shapes of the residues determine the basis of master integrals
appearing in the final result. We present a four-dimensional constructive
algorithm that we apply to planar and non-planar contributions to the 4- and
5-point MHV amplitudes in N=4 SYM. The technique hereby discussed extends the
well-established analogous method holding for one-loop amplitudes, and can be
considered a preliminary study towards the systematic reduction at the
integrand-level of two-loop amplitudes in any gauge theory, suitable for their
automated semianalytic evaluation.Comment: 26 pages, 11 figure
Recommended from our members
A small molecule that mitigates bacterial infection disrupts Gram-negative cell membranes and is inhibited by cholesterol and neutral lipids
Infections caused by Gram-negative bacteria are difficult to fight because these pathogens exclude or expel many clinical antibiotics and host defense molecules. However, mammals have evolved a substantial immune arsenal that weakens pathogen defenses, suggesting the feasibility of developing therapies that work in concert with innate immunity to kill Gram-negative bacteria. Using chemical genetics, we recently identified a small molecule, JD1, that kills Salmonella enterica serovar Typhimurium (S. Typhimurium) residing within macrophages. JD1 is not antibacterial in standard microbiological media, but rapidly inhibits growth and curtails bacterial survival under broth conditions that compromise the outer membrane or reduce efflux pump activity. Using a combination of cellular indicators and super resolution microscopy, we found that JD1 damaged bacterial cytoplasmic membranes by increasing fluidity, disrupting barrier function, and causing the formation of membrane distortions. We quantified macrophage cell membrane integrity and mitochondrial membrane potential and found that disruption of eukaryotic cell membranes required approximately 30-fold more JD1 than was needed to kill bacteria in macrophages. Moreover, JD1 preferentially damaged liposomes with compositions similar to E. coli inner membranes versus mammalian cell membranes. Cholesterol, a component of mammalian cell membranes, was protective in the presence of neutral lipids. In mice, intraperitoneal administration of JD1 reduced tissue colonization by S. Typhimurium. These observations indicate that during infection, JD1 gains access to and disrupts the cytoplasmic membrane of Gram-negative bacteria, and that neutral lipids and cholesterol protect mammalian membranes from JD1-mediated damage. Thus, it may be possible to develop therapeutics that exploit host innate immunity to gain access to Gram-negative bacteria and then preferentially damage the bacterial cell membrane over host membranes.</p
- …