Developmental and Anatomical Patterns Of IL-2 Gene Expression in Vivo in The Murine Thymus

Interleukin-2 (IL-2) is a potent growth factor that mature T lymphocytes synthesize and use as a proliferation signal. Much controversy has arisen concerning whether it is used to drive the extensive proliferation of immature pre-T cells in the thymus. Immature thymocytes acquire the competence to express IL-2 at an early stage, but it has remained uncertain whether they are activated to exercise this competence in vivo. Therefore, we have used in situ hybridization and immunohistochemistry on serial sections obtained from fetal and adult thymuses of normal C57BL/6 mice and of mice bearing the scid defect to determine where, when, and whether IL-2 is expressed in vivo. Our results show a striking spatial and temporal pattern of IL-2 expression in the normal fetal thymus. We detected a burst of IL-2 mRNA accumulation at day 14.5 of gestation, which rapidly decreased by day 15. At day 15, we observed maximal IL-2 protein production that subsequently decreased by day 16 of gestation. Both in situ hybridization and immunohistochemical staining revealed an unexpectedly strict localization of IL-2 expressing cells to patches around the periphery of the fetal thymus, creating a previously unrecognized compartment of high IL-2 protein content. IL-2 production in the day-15 fetal thymus appeared to be unaffected by the scid mutation, indicating that this response is likely to be T-cell receptor (TcR)-independent. Several features distinguish the IL-2 induction pattern in the adult thymus from that in the fetal thymus. In the normal adult thymus, IL-2-expressing cells are extremely rare (found at a frequency of 10^(-7)), but they are reproducibly detectable as isolated cells in the outer cortex and subcapsular region of the thymus. Unlike the fetal thymic IL-2 producers, the IL-2 producers in the adult thymus are completely eliminated in mice homozygous for the scid mutation. This suggests that the IL-2-expressing cells in the normal adult thymus are of a more mature phenotype than the immature, TcR-negative cells that accumulate in the scid adult thymus. Thus, our work demonstrates that two developmentally distinct types of cell interactions induce IL-2 expression in vivo: one, a broadly localized interaction in day 14-15 fetal thymus that is unaffected by the scid mutation; the other, a rare event that occurs asynchronously from late fetal through adult life, but which is completely eliminated by the scid defect. These results imply that significant differences exist between the physiological processing of thymocytes in the fetal and postnatal thymic microenvironments

Spontaneous Expression of Interleukin-2 In Vivo in Specific Tissues of Young Mice

In situ hybridization and immunohistochemistry were used to determine the spectrum of tissues in which interleukin-2 (IL-2) mRNA and protein are found in healthy, normal young mice. In neonatal animals, IL-2 is expressed specifically by distinct, isolated cells at three major sites: the thymus, skin, and gut. Based on morphology and distribution, the IL-2-expressing cells resemble CD3ε + T cells that are also present in all these locations. Within the thymus of postweanling animals, both TcRαβ and TcRγδ lineage cells secrete "haloes" of the cytokine that diffuse over many cell diameters. Within the skin, isolated cells expressing IL-2 are seen at birth in the mesenchyme, and large numbers of IL-2-expressing cells are localized around hair follicles in the epidermis in 3-week-old animals. At this age, a substantial subset of CD3ε + cells is similarly localized in the skin. Significantly, by 5 weeks of age and later when the CD3ε + cells are evenly distributed throughout the epidermis, IL-2 RNA and protein expression are no longer detectable. Finally, within the intestine, IL-2 protein is first detected in association with a few discrete, isolated cells at day 16 of gestation and the number of IL-2 reactive cells increases in frequency through El9 and remains abundant in adult life. In postnatal animals, the frequency of IL- 2-positive cells in villi exceeds by greater than fivefold that found in mesenteric lymph node or Peyer's patches. Overall, these temporal and spatial patterns of expression provide insight into the regulation of IL-2 in vivo and suggest a role for IL-2 expression distinct from immunological responses to antigen

Effective thermal conductivity of polycrystalline materials with randomly oriented superlattice grains

A model has been established for the effective thermal conductivity of a bulk polycrystal made of randomly oriented superlattice grains with anisotropic thermal conductivity. The in-plane and cross-plane thermal conductivities of each superlattice grain are combined using an analytical averaging rule that is verified using finite element methods. The superlattice conductivities are calculated using frequency dependent solutions of the Boltzmann transport equation, which capture greater thermal conductivity reductions as compared to the simpler gray medium approximation. The model is applied to a PbTe/Sb_2Te_3 nanobulk material to investigate the effects of period, specularity, and temperature. The calculations show that the effective thermal conductivity of the polycrystal is most sensitive to the in-plane conductivity of each superlattice grain, which is generally four to five times larger than the cross-plane conductivity of a grain. The model is compared to experimental measurements of the same system for periods ranging from 287 to 1590 nm and temperatures from 300 to 500 K. The comparison suggests that the effective specularity increases with increasing annealing temperature and shows that these samples are in a mixed regime where both Umklapp and boundary scattering are important

Integrated electroplated heat spreaders for high power semiconductor lasers

Thermal management of high power semiconductor lasers is challenging due to the low thermal conductivity of the laser substrate and the active device layers. In this work, we demonstrate the use of a microfabricated laser test device to study the thermal management of edge emitting semiconductor lasers. In this device, metallic heat spreaders of high thermal conductivity are directly electroplated on structures that mimic edge-emitting semiconductor lasers. The effects of various structural parameters of the heat spreader on the reduction of the thermal resistance of the laser test device are demonstrated both experimentally and theoretically. Without resolving to computational costive simulations, we developed two independent analytical models to verify the experimental data and further utilized them to identify the dominant thermal resistance under different laser mounting configurations. We believe our approach here of using microfabricated devices to mimic thermal characteristics of lasers as well as the developed analytical models for calculating the laser thermal resistance under different mounting configurations can potentially become valuable tools for thermal management of high power semiconductor lasers

Vorticity cutoff in nonlinear photonic crystals

Using group theory arguments, we demonstrate that, unlike in homogeneous media, no symmetric vortices of arbitrary order can be generated in two-dimensional (2D) nonlinear systems possessing a discrete-point symmetry. The only condition needed is that the non-linearity term exclusively depends on the modulus of the field. In the particular case of 2D periodic systems, such as nonlinear photonic crystals or Bose-Einstein condensates in periodic potentials, it is shown that the realization of discrete symmetry forbids the existence of symmetric vortex solutions with vorticity higher than two.Comment: 4 pages, 5 figures; minor changes in address and reference

The Area Quantum and Snyder Space

We show that in the Snyder space the area of the disc and of the sphere can be quantized. It is also shown that the area spectrum of the sphere can be related to the Bekenstein conjecture for the area spectrum of a black hole horizon.Comment: 7 pages, in Press, Physics Letters

Tensor extension of the Poincar\'e algebra

A tensor extension of the Poincar\'e algebra is proposed for the arbitrary dimensions. Casimir operators of the extension are constructed. A possible supersymmetric generalization of this extension is also found in the dimensions $D=2,3,4$.Comment: 1+7 pages, LaTe