A morphometric study of nucleolar organiser regions in cervical intraepithelial neoplasia

The study sought a correlation between the number of AgNOR granules and the degree of cervical intraepithelial neoplasia (CIN). Thirty-five sections (5 normal, 10 CIN1, 10 CIN2 and 10 CIN3) were subjected to retrospective analysis. The percentage of cells with 1, 2, 3, 4 and more AgNORs was calculated and the number of granules per 100 cells was counted. The number of cells containing single granules decreases. However, the number increases with CIN level when the cells contain 4 and more AgNORs. The number of granules per 100 cells also increases with the degree of CIN. It can be thus concluded that the number of cells with 4 and more AgNOR granules can serve as a CIN differentiation exponent

Hepatic profile analyses of tipranavir in Phase II and III clinical trials

<p>Abstract</p> <p>Background</p> <p>The risk and course of serum transaminase elevations (TEs) and clinical hepatic serious adverse event (SAE) development in ritonavir-boosted tipranavir (TPV/r) 500/200 mg BID recipients, who also received additional combination antiretroviral treatment agents in clinical trials (TPV/r-based cART), was determined.</p> <p>Methods</p> <p>Aggregated transaminase and hepatic SAE data through 96 weeks of TPV/r-based cART from five Phase IIb/III trials were analyzed. Patients were categorized by the presence or absence of underlying liver disease (+LD or -LD). Kaplan-Meier (K-M) probability estimates for time-to-first US National Institutes of Health, Division of AIDS (DAIDS) Grade 3/4 TE and clinical hepatic SAE were determined and clinical actions/outcomes evaluated. Risk factors for DAIDS Grade 3/4 TE were identified through multivariate Cox regression statistical modeling.</p> <p>Results</p> <p>Grade 3/4 TEs occurred in 144/1299 (11.1%) patients; 123/144 (85%) of these were asymptomatic; 84% of these patients only temporarily interrupted treatment or continued, with transaminase levels returning to Grade ≤ 2. At 96 weeks of study treatment, the incidence of Grade 3/4 TEs was higher among the +LD (16.8%) than among the -LD (10.1%) patients. K-M analysis revealed an incremental risk for developing DAIDS Grade 3/4 TEs; risk was greatest through 24 weeks (6.1%), and decreasing thereafter (>24-48 weeks: 3.4%, >48 weeks-72 weeks: 2.0%, >72-96 weeks: 2.2%), and higher in +LD than -LD patients at each 24-week interval. Treatment with TPV/r, co-infection with hepatitis B and/or C, DAIDS grade >1 TE and CD4⁺> 200 cells/mm³at baseline were found to be independent risk factors for development of DAIDS Grade 3/4 TE; the hazard ratios (HR) were 2.8, 2.0, 2.1 and 1.5, respectively. Four of the 144 (2.7%) patients with Grade 3/4 TEs developed hepatic SAEs; overall, 14/1299 (1.1%) patients had hepatic SAEs including six with hepatic failure (0.5%). The K-M risk of developing hepatic SAEs through 96 weeks was 1.4%; highest risk was observed during the first 24 weeks and decreased thereafter; the risk was similar between +LD and -LD patients for the first 24 weeks (0.6% and 0.5%, respectively) and was higher for +LD patients, thereafter.</p> <p>Conclusion</p> <p>Through 96 weeks of TPV/r-based cART, DAIDS Grade 3/4 TEs and hepatic SAEs occurred in approximately 11% and 1% of TPV/r patients, respectively; most (84%) had no significant clinical implications and were managed without permanent treatment discontinuation. Among the 14 patients with hepatic SAE, 6 experienced hepatic failure (0.5%); these patients had profound immunosuppression and the rate appears higher among hepatitis co-infected patients. The overall probability of experiencing a hepatic SAE in this patient cohort was 1.4% through 96 weeks of treatment. Independent risk factors for DAIDS Grade 3/4 TEs include TPV/r treatment, co-infection with hepatitis B and/or C, DAIDS grade >1 TE and CD4⁺> 200 cells/mm³at baseline.</p> <p>Trial registration</p> <p>US-NIH Trial registration number: NCT00144170</p

Multiple D4-D2-D0 on the Conifold and Wall-crossing with the Flop

We study the wall-crossing phenomena of D4-D2-D0 bound states with two units of D4-brane charge on the resolved conifold. We identify the walls of marginal stability and evaluate the discrete changes of the BPS indices by using the Kontsevich-Soibelman wall-crossing formula. In particular, we find that the field theories on D4-branes in two large radius limits are properly connected by the wall-crossings involving the flop transition of the conifold. We also find that in one of the large radius limits there are stable bound states of two D4-D2-D0 fragments.Comment: 24 pages, 4 figures; v2: typos corrected, minor changes, a reference adde

Penner Type Matrix Model and Seiberg-Witten Theory

We discuss the Penner type matrix model recently proposed by Dijkgraaf and Vafa for a possible explanation of the relation between four-dimensional gauge theory and Liouville theory by making use of the connection of the matrix model to two-dimensional CFT. We first consider the relation of gauge couplings defined in UV and IR regimes of N_f = 4, N = 2 supersymmetric gauge theory being related as $q_{{\rm UV}}={\vartheta_2(q_{{\rm IR}})^4/\vartheta_3(q_{{\rm IR}})^4}$. We then use this relation to discuss the action of modular transformation on the matrix model and determine its spectral curve. We also discuss the decoupling of massive flavors from the N_f = 4 matrix model and derive matrix models describing asymptotically free N = 2 gauge theories. We find that the Penner type matrix theory reproduces correctly the standard results of N = 2 supersymmetric gauge theories.Comment: 22 pages; v2: references added, typos corrected; v3: a version to appear in JHE

Evidence for Duality of Conifold from Fundamental String

We study the spectrum of BPS D5-D3-F1 states in type IIB theory, which are proposed to be dual to D4-D2-D0 states on the resolved conifold in type IIA theory. We evaluate the BPS partition functions for all values of the moduli parameter in the type IIB side, and find them completely agree with the results in the type IIA side which was obtained by using Kontsevich-Soibelman's wall-crossing formula. Our result is a quite strong evidence for string dualities on the conifold.Comment: 24 pages, 13 figures, v2: typos corrected, v3: explanations about wall-crossing improved and figures adde

Quantization of Integrable Systems and a 2d/4d Duality

We present a new duality between the F-terms of supersymmetric field theories defined in two- and four-dimensions respectively. The duality relates N=2 supersymmetric gauge theories in four dimensions, deformed by an Omega-background in one plane, to N=(2,2) gauged linear sigma-models in two dimensions. On the four dimensional side, our main example is N=2 SQCD with gauge group SU(L) and 2L fundamental flavours. Using ideas of Nekrasov and Shatashvili, we argue that the Coulomb branch of this theory provides a quantization of the classical Heisenberg SL(2) spin chain. Agreement with the standard quantization via the Algebraic Bethe Ansatz implies the existence of an isomorphism between the chiral ring of the 4d theory and that of a certain two-dimensional theory. The latter can be understood as the worldvolume theory on a surface operator/vortex string probing the Higgs branch of the same 4d theory. We check the proposed duality by explicit calculation at low orders in the instanton expansion. One striking consequence is that the Seiberg-Witten solution of the 4d theory is captured by a one-loop computation in two dimensions. The duality also has interesting connections with the AGT conjecture, matrix models and topological string theory where it corresponds to a refined version of the geometric transition.Comment: 51 pages, 7 figures. Additional comments, minor improvements and references adde

Fermionic gluing principle of the topological vertex

We will establish the fermionic gluing principle of the topological vertex, that is, provided the framed ADKMV conjecture, the generating functions of the Gromov-Witten invariants of all toric Calabi-Yau threefolds are Bogoliubov transforms of the vacuum.Comment: 24 pages. arXiv admin note: substantial text overlap with arXiv:1201.250

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

A & B model approaches to surface operators and Toda theories

It has recently been argued by Alday et al that the inclusion of surface operators in 4d N=2 SU(2) quiver gauge theories should correspond to insertions of certain degenerate operators in the dual Liouville theory. So far only the insertion of a single surface operator has been treated (in a semi-classical limit). In this paper we study and generalise this proposal. Our approach relies on the use of topological string theory techniques. On the B-model side we show that the effects of multiple surface operator insertions in 4d N=2 gauge theories can be calculated using the B-model topological recursion method, valid beyond the semi-classical limit. On the mirror A-model side we find by explicit computations that the 5d lift of the SU(N) gauge theory partition function in the presence of (one or many) surface operators is equal to an A-model topological string partition function with the insertion of (one or many) toric branes. This is in agreement with an earlier proposal by Gukov. Our A-model results were motivated by and agree with what one obtains by combining the AGT conjecture with the dual interpretation in terms of degenerate operators. The topological string theory approach also opens up new possibilities in the study of 2d Toda field theories.Comment: 43 pages. v2: Added references, including a reference to unpublished work by S.Gukov; minor changes and clarifications