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Exact Solutions For The Longitudinal And Transverse impedances Of An Off centered Beam In A Rectangular Beam Pipe
In storage rings and accumulators, some sections of the beampipe may be rectangular in cross section and the beam may not be at the center of the beampipe. In this note, through conformal mapping, we try to compute exactly the longitudinal, vertical and horizontal transverse impedances for the beam under these circumstances. For simplicity, we restrict the beam to the horizontal symmetry axis of the beampipe. Both the effects due to the resistivity of the beampipe's wall and space-charge are considered
Anti-neurofascin antibodies
Neurofascin (NF) is a cell-adhesion molecule that is found at the nodes of Ranvier. The 186
kDa isoform of neurofascin (NF186) is expressed on the axon in the exposed node, and the
155 kDa isoform (NF155) is expressed on myelinating glia at the paranode. NF186 is essential
for clustering of sodium channels to the nodes while NF155 is needed for close paranodal interactions
between myelinating glia and axons. The neurofascins are found in both the peripheral
and central nervous system (PNS and CNS).
NF-specific autoantibodies were identified in serum of multiple sclerosis (MS) patients using
a proteomics approach with two-dimensional Western blotting of human myelin glycoproteins.
A monoclonal antibody (mAb) specific for NF was shown to induce axonal injury in an animal
model of MS, experimental autoimmune encephalomyelitis. This indicated that NF is a relevant
autoantibody target in patients with inflammatory diseases of the nervous system (central and
peripheral), but actual abundance of anti-NF autoantibodies is unknown.
The objectives of the thesis were the following: 1) Develop assays to detect autoantibodies
against human NF. 2) Determine the prevalence in patients with MS and with inflammatory
diseases of the PNS. 3) Characterize the reactivity by immunoglobulin isotyping, serial dilution,
epitope mapping, and staining of nodal structures in tissue sections. 4) Affinity purify anti-NF
antibodies from plasma exchange material. 5) Determine possible in vivo effects of anti-NF
antibodies in the PNS using a neuritis animal model.
First, we expressed the complete human NF155 and NF186 on the surface of stable human cell
lines, produced the complete extracellular portion of the NFs in HEK293 cells, and expressed
truncated variants of the NFs in E. coli. With these reagents, we set up three antibody detection
assays: cell-based assay by flow cytometry, ELISA, and Western blot. These assays were
validated using NF-specific monoclonal and polyclonal antibodies, and optimized with a test
cohort of serum samples.
We screened 687 serum and 48 plasma exchange samples from patients with MS (n = 233),
inflammatory diseases in the PNS (n = 294), and controls (n = 208). From serum analysis,
we observed low prevalence of anti-NF reactivity (3%) by flow cytometry and/or ELISA despite
broad reactivity in almost half of the serum samples analyzed by Western blot. Reactivity observed
by flow cytometry and by ELISA were congruent only in the patients with the highest
reactivities. The anti-NF antibodies were NF-isoform specific, mainly IgG subclasses, and at
high titres in some cases. Using truncated variants of NF fused to super green fluorescence
protein (sGFP), we showed that reactivity of anti-NF Abs was largely directed towards the membrane
proximal extracellular domains that are unique to each isoform, while the membrane
distal immunoglobulin-like domains and fibronectin domains were not recognized.
A small proportion (3%; 8/254) of patients with GBS and CIDP showed reactivity to human NF
by ELISA. A few showed a particularly high reactivity (up to 1:10 000 dilution) to NF. Two CIDP
patients showed a particularly high (up to 1:10 000 dilution) anti-NF155 reactivity by FACS and
ELISA, recognized paranodes in tissue sections, and exhibited dominant IgG4 subclass usage.
Another CIDP patient who benefited from plasma exchange had a persistent anti-NF155
reactivity by ELISA in serum, and after affinity purification, anti-NF186 and -NF155 reactivity by
FACS and ELISA were detected in addition. These antibodies were mainly IgG3, with minor
contribution of IgM and IgA. To investigate possible functions of anti-NF antibodies in inflammatory
PNS diseases, we injected two different monoclonal antibodies (mAbs) into a P2-peptide
induced experimental autoimmune neuritis (EAN) animal model at disease onset. We found
that while the anti-NF mAbs prolonged and exacerbated clinical disease in these animals, they
could not induce disease on their own.
We detected NF-reactivity in a small proportion of MS samples (3%; 7/225) by ELISA and flow
cytometry. We obtained follow-up material from two NF-reactive patients and saw a persistent
NF reactivity in one of them. To increase detection sensitivity, we affinity purified anti-NF antibodies
from plasma exchange material of patients with MS (n = 8). IgG, IgM, and IgA were
isolated from most of the samples; they were found to recognize NF155 and to a lower extent
NF186 by ELISA and in a few also by flow cytometry. This indicates that low levels of anti-NF
antibodies exist in a proportion of MS patients.
In conclusion, 3% of serum samples from patients with PNS inflammatory neuropathies (GBS
and CIDP) showed reactivity by ELISA and none of the controls. In an animal model of autoimmune
peripheral nerve inflammation, we showed, using two anti-NF mAbs, that antibody
targeting of NF can enhance and prolong disease course. This suggests that antibodies to NF
may be relevant for a small group of patients with peripheral inflammatory neuropathies. In MS
patients, 3% showed anti-NF reactivity by flow cytometry and ELISA. Furthermore, low levels of
anti-NF antibodies that could be detected by ELISA and flow cytometry after affinity purification
were additionally found in some MS patient samples that were unreactive by serum screening.
This raises the possibility that low levels of antibodies to NF are present in some MS patients
and may contribute to the pathogenesis of this chronic disease
Direct Liability and Veil-Piercing: When One Door Closes, Another Opens
Piercing the corporate veil has been substantially limited in English law since Prest v. Petrodel. This contraction coincides with the development of the direct liability doctrine which attaches liability directly on the parent company. The authors argue that the shift from using piercing the corporate veil to direct liability is a positive development as it gives English courts a better tool to combat the abuse of separate legal personality. However, compared the English doctrines with their counterparts under the U.S. laws, it is argued that the much broader U.S. piercing doctrine makes the expansion of direct liability doctrine unnecessary in the United States
Differential Geometry of Ice Flow
Flowlines on ice sheets and glaciers form complex patterns. To explore their role in ice routing and extend the language for studying such patterns, we develop a theory of flow convergence and curvature in plan view. These geometric quantities respectively equal the negative divergence of the vector field of ice-flow direction and the curl of this field. From the first of these two fundamental results, we show that flow in individual catchments of an ice sheet can converge (despite its overall spreading) because ice divides are loci of strong divergence, and that a sign bifurcation in convergence occurs during ice-sheet “symmetry breaking” (the transition from near-radial spreading to spreading with substantial azimuthal velocities) and during the formation of ice-stream tributary networks. We also uncover the topological control behind balance-flux distributions across ice masses. Notably, convergence participates in mass conservation along flowlines to amplify ice flux via a positive feedback; thus the convergence field governs the form of ice-stream networks simulated by balance-velocity models. The theory provides a roadmap for understanding the tower-shaped plot of flow speed versus convergence for the Antarctic Ice Sheet
Sequence variability of Campylobacter temperate bacteriophages
<p>Abstract</p> <p>Background</p> <p>Prophages integrated within the chromosomes of <it>Campylobacter jejuni </it>isolates have been demonstrated very recently. Prior work with <it>Campylobacter </it>temperate bacteriophages, as well as evidence from prophages in other enteric bacteria, suggests these prophages might have a role in the biology and virulence of the organism. However, very little is known about the genetic variability of <it>Campylobacter </it>prophages which, if present, could lead to differential phenotypes in isolates carrying the phages versus those that do not. As a first step in the characterization of <it>C. jejuni </it>prophages, we investigated the distribution of prophage DNA within a <it>C. jejuni </it>population assessed the DNA and protein sequence variability within a subset of the putative prophages found.</p> <p>Results</p> <p>Southern blotting of <it>C. jejuni </it>DNA using probes from genes within the three putative prophages of the <it>C. jejuni </it>sequenced strain RM 1221 demonstrated the presence of at least one prophage gene in a large proportion (27/35) of isolates tested. Of these, 15 were positive for 5 or more of the 7 <it>Campylobacter </it>Mu-like phage 1 (CMLP 1, also designated <it>Campylobacter jejuni </it>integrated element 1, or CJIE 1) genes tested. Twelve of these putative prophages were chosen for further analysis. DNA sequencing of a 9,000 to 11,000 nucleotide region of each prophage demonstrated a close homology with CMLP 1 in both gene order and nucleotide sequence. Structural and sequence variability, including short insertions, deletions, and allele replacements, were found within the prophage genomes, some of which would alter the protein products of the ORFs involved. No insertions of novel genes were detected within the sequenced regions. The 12 prophages and RM 1221 had a % G+C very similar to <it>C. jejuni </it>sequenced strains, as well as promoter regions characteristic of <it>C. jejuni</it>. None of the putative prophages were successfully induced and propagated, so it is not known if they were functional or if they represented remnant prophage DNA in the bacterial chromosomes.</p> <p>Conclusion</p> <p>These putative prophages form a family of phages with conserved sequences, and appear to be adapted to <it>Campylobacter</it>. There was evidence for recombination among groups of prophages, suggesting that the prophages had a mosaic structure. In many of these properties, the Mu-like CMLP 1 homologs characterized in this study resemble temperate bacteriophages of enteric bacteria that are responsible for contributions to virulence and host adaptation.</p
3/2 Firefighters are not enough
The firefighter problem is a monotone dynamic process in graphs that can be
viewed as modeling the use of a limited supply of vaccinations to stop the
spread of an epidemic. In more detail, a fire spreads through a graph, from
burning vertices to their unprotected neighbors. In every round, a small amount
of unburnt vertices can be protected by firefighters. How many firefighters per
turn, on average, are needed to stop the fire from advancing? We prove tight
lower and upper bounds on the amount of firefighters needed to control a fire
in the Cartesian planar grid and in the strong planar grid, resolving two
conjectures of Ng and Raff.Comment: 8 page
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