Increased Frequency of CD4 and CD8 Regulatory T Cells in Individuals under 15 Years with Multibacillary Leprosy

Background: Leprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceara state, Brazil, reflects the difficulty of its control. the spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4(+)/CD8(+)CD25(high)FOXP3(+) and CD4(+)/CD8(+)CD25(high)FOXP3(high) cells in leprosy patients and household contacts, in both cases under 15 years old.Methodology/Principal Findings: PBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4(+)/CD8(+) Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4(+)FOXP3(+) (21.93 +/- 8.43 vs. 13.79 +/- 8.19%, p = 0.0500), CD4(+)FOXP3(high) (10.33 +/- 5.69 vs. 5.57 +/- 4.03%, p = 0.0362), CD8(+)FOXP3(+) (13.88 +/- 9.19 vs. 6.18 +/- 5.56%, p = 0.0230) and CD8(+)FOXP3(high) (5.36 +/- 4.17 vs. 2.23 +/- 2.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients.Conclusions/Significance: We have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4(+) and CD8(+) Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection.Fundacao Cearense de Apoio ao Desenvolvimento Cientifico e TecnologicoPost-Graduation Program in Medical MicrobiologyUniv Fed Ceara, Dept Pathol & Legal Med, Med Lab Immunol, Fortaleza, Ceara, BrazilDermatol Ctr Dona Libania, Fortaleza, Ceara, BrazilWalter Cantidio Univ Hosp, Fortaleza, Ceara, BrazilUniv Fortaleza, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilWeb of Scienc

Holomorphic variables in magnetized brane models with continuous Wilson lines

We analyze the action of the target-space modular group in toroidal type IIB orientifold compactifications with magnetized D-branes and continuous Wilson lines. The transformation of matter fields agree with that of twisted fields in heterotic compactifications, constituting a check of type I/heterotic duality. We identify the holomorphic N = 1 variables for these compactifications. Matter fields and closed string moduli are both redefined by open string moduli. The redefinition of matter fields can be read directly from the perturbative Yukawa couplings, whereas closed string moduli redefinitions are obtained from D-brane instanton superpotential couplings. The resulting expressions reproduce and generalize, in the presence of internal magnetic fields, previous results in the literature.Comment: 9 pages, no figures; v2: conventions for Wilson lines changed, major simplifications in expressions, discussions extended, typos corrected, some references adde

Non-Abelian discrete gauge symmetries in 4d string models

We study the realization of non-Abelian discrete gauge symmetries in 4d field theory and string theory compactifications. The underlying structure generalizes the Abelian case, and follows from the interplay between gaugings of non-Abelian isometries of the scalar manifold and field identifications making axion-like fields periodic. We present several classes of string constructions realizing non-Abelian discrete gauge symmetries. In particular, compactifications with torsion homology classes, where non-Abelianity arises microscopically from the Hanany-Witten effect, or compactifications with non-Abelian discrete isometry groups, like twisted tori. We finally focus on the more interesting case of magnetized branes in toroidal compactifications and quotients thereof (and their heterotic and intersecting duals), in which the non-Abelian discrete gauge symmetries imply powerful selection rules for Yukawa couplings of charged matter fields. In particular, in MSSM-like models they correspond to discrete flavour symmetries constraining the quark and lepton mass matrices, as we show in specific examples.Comment: 58 pages; minor typos corrected and references adde

Adénome Pléomorphe Géant à Localisation Submandibulaire: À Propos d’un Cas

Introduction: The pleomorphic adenoma is a benign tumor of the salivary glands. Its extra parotid locations are rare. The aim of this study is to describe the particular management of the pleomorphic adenoma in its unusual location. Observation: This patient was a 35 - year - old patient referred from Zinder Hospital for the management of tumefaction in the mandibular region that had been undergoing surgery for 10 years. The clinical and paraclinical examinations led to the conclusion of a pleomorphic adenoma of the submandibular gland, by imaging and confirmed by the anatomo-pathological examination of the surgical specimen, which measured 15x12x8cm following submandibulectomy with complete tumor resection. The follow-up was simple and no recurrence or malignant transformation was reported after a mean follow-up of one year. Conclusion: The extra-parotid localization of the pleomorphic adenoma is dominated by the submandibular gland. This localization stands out in its clinical and therapeutic peculiarities. Introduction: L’adénome pléomorphe est une tumeur bénigne des glandes salivaires. Ses localisations extra parotidiennes sont rares. L’objectif de ce travail est de décrire la prise en charge particulière de l’adénome pléomorphe dans sa localisation inhabituelle. Observation: Ils’agissait d’un patient de 35 ans, référé de l’Hôpital National de Zinder pour la prise en charge d’une tumeur de la région mandibulaire évoluant depuis 10 ans. Les examens cliniques et paracliniques avaient permis de conclure à un adénome pléomorphe de la glande submandibulaire, par l’imagerie et confirmé par l’examen anatomo-pathologique de la pièce opératoire qui mesurait 15x12x 8cm suite à la submandibulectomie avec résection tumorale complète. Les suites opératoires étaient simples et aucune récidive ni transformation maligne n’a été rapportée après un recul d’un an. Conclusion: La localisation extra-parotidienne de l’adénome pléomorphe est dominée par la glande submandibulaire. Cette localisation se distingue dans ses particularités cliniques et thérapeutiques

Non-perturbative Vacuum Destabilization and D-brane Dynamics

We analyze the process of string vacuum destabilization due to instanton induced superpotential couplings which depend linearly on charged fields. These non-perturbative instabilities result in potentials for the D-brane moduli and lead to processes of D-brane recombination, motion and partial moduli stabilization at the non-perturbative vacuum. By using techniques of D-brane instanton calculus, we explicitly compute this scalar potential in toroidal orbifold compactifications with magnetized D-branes by summing over the possible discrete instanton configurations. We illustrate explicitly the resulting dynamics in globally consistent models. These instabilities can have phenomenological applications to breaking hidden sector gauge groups, open string moduli stabilization and supersymmetry breaking. Our results suggest that breaking supersymmetry by Polonyi-like models in string theory is more difficult than expected.Comment: 61 pages, 6 figures, 5 tables; Minor corrections, version published in JHE

Yukawa couplings and masses of non-chiral states for the Standard Model on D6-branes on T6/Z6'

The perturbative leading order open string three-point couplings for the Standard Model with hidden USp(6) on fractional D6-branes on T6/Z6' from arXiv:0806.3039 [hep-th], arXiv:0910.0843 [hep-th] are computed. Physical Yukawa couplings consisting of holomorphic Wilsonian superpotential terms times a non-holomorphic prefactor involving the corresponding classical open string Kaehler metrics are given, and mass terms for all non-chiral matter states are derived. The lepton Yukawa interactions are at leading order flavour diagonal, while the quark sector displays a more intricate pattern of mixings. While N=2 supersymmetric sectors acquire masses via only two D6-brane displacements - which also provide the hierarchies between up- and down-type Yukawas within one quark or lepton generation -, the remaining vector-like states receive masses via perturbative three-point couplings to some Standard Model singlet fields with vevs along flat directions. Couplings to the hidden sector and messengers for supersymmetry breaking are briefly discussed.Comment: 52 pages (including 8p. appendix); 5 figures; 14 tables; v2: discussion in section 4.1.3 extended, footnote 5 added, typos corrected, accepted by JHE

Clinical outcome of endonasal KTP laser assisted dacryocystorhinostomy

BACKGROUND: To evaluate the clinical outcome of primary endonasal laser assisted dacryocystorhinostomy (ENL-DCR) using the potassium-titanyl-phosphate laser. METHODS: We retrospectively reviewed all primary ENL-DCRs performed within a period of twelve months by the same combined Ophthalmology and Otorhinolaringology team in Freeman Hospital, Newcastle upon Tyne, UK. The main outcome measure for success was resolution or significant improvement of epiphora. Details of surgery, intraoperative and postoperative complications, as well as pathology associated with failure were also studied. Patients were followed up for at least 12 months. RESULTS: A total of 41 consecutive ENL-DCRs on 29 patients (22 females, 7 males, mean age 75 years) were analysed. All patients had bicanalicular silicone intubation for at least 4 months. The success rate at 12 months postoperatively was 78.1%. Pathology associated with failure included: intranasal pathology (12.2%), mucocele (7.3%), and systemic sarcoidosis (2.4%). No significant intra-operative complications were recorded. CONCLUSION: The ENL-DCR with potassium-titanyl-phosphate laser can be considered as a safe and efficient primary procedure for the treatment of nasolacrimal duct obstruction

Flux and Instanton Effects in Local F-theory Models and Hierarchical Fermion Masses

We study the deformation induced by fluxes and instanton effects on Yukawa couplings involving 7-brane intersections in local F-theory constructions. In the absence of non-perturbative effects, holomorphic Yukawa couplings do not depend on open string fluxes. On the other hand instanton effects (or gaugino condensation on distant 7-branes) do induce corrections to the Yukawas. The leading order effect may also be captured by the presence of closed string (1,2) IASD fluxes, which give rise to a non-commutative structure. We check that even in the presence of these non-perturbative effects the holomorphic Yukawas remain independent of magnetic fluxes. Although fermion mass hierarchies may be obtained from these non-perturbative effects, they would give identical Yukawa couplings for D-quark and Lepton masses in SU(5) F-theory GUT's, in contradiction with experiment. We point out that this problem may be solved by appropriately normalizing the wavefunctions. We show in a simple toy model how the presence of hypercharge flux may then be responsible for the difference between D-quarks and Lepton masses in local SU(5) GUT's.Comment: 84 pages, 1 figure. v2: minor corrections and references adde

Filtration analysis of pedestrian-vehicle interactions for autonomous vehicle control

Interacting with humans remains a challenge for autonomousvehicles (AVs). When a pedestrian wishes to cross the road in front of thevehicle at an unmarked crossing, the pedestrian and AV must competefor the space, which may be considered as a game-theoretic interaction inwhich one agent must yield to the other. To inform development of newreal-time AV controllers in this setting, this study collects and analy-ses detailed, manually-annotated, temporal data from real-world humanroad crossings as they interact with manual drive vehicles. It studies thetemporal orderings (filtrations) in which features are revealed to the ve-hicle and their informativeness over time. It presents a new frameworksuggesting how optimal stopping controllers may then use such data toenable an AV to decide when to act (by speeding up, slowing down, orotherwise signalling intent to the pedestrian) or alternatively, to continueat its current speed in order to gather additional information from newfeatures, including signals from that pedestrian, before acting itself