T cell renewal rates, telomerase, and telomere length shortening

Measurements on the average telomere lengths of normal human naive and memory T cells suggested that 1) naive and memory human T cells have similar division rates, and 2) that the difference between naive and memory cells reflects the degree of clonal expansion during normal immune reactions. Here we develop mathematic models describing how the population average of telomere length depends on the cell division rates of naive and memory T cells during clonal expansion and normal renewal. The results show that 1) telomeres shorten with twice the cell division rate, 2) that the conventional approach of estimating telomere length shortening per mean population doubling gives rise to estimates that are 39% larger than the "true" loss per cell division, 3) that naive and memory T cells are expected to shorten their telomeres at rates set by the division rate of the naive T cells only, i.e., irrespective of the division rate of memory T cells, 4) that the measured difference in the average telomere length between naive and memory T cells may largely reflect the difference in renewal rates between these subpopulations rather than the clonal expansion, and 5) that full telomerase compensation during clonal expansion is consistent with all data on the shortening of telomere length in, and between, naive and memory T cells. Thus we reconcile the apparent contradictions between the demonstrated difference in division rates between human naive and memory T cells and their similar rates of telomere shortening, and the demonstrated telomere shortening in the presence of telomerase activity

How Specific Should Immunological Memory Be?

Protection against infection hinges on a close interplay between the innate immune system and the adaptive immune system. Depending on the type and context of a pathogen, the innate system instructs the adaptive immune system to induce an appropriate immune response. Here, we hypothesize that the adaptive immune system stores these instructions by changing from a naive to an appropriate memory phenotype. In a secondary immune reaction, memory lymphocytes adhere to their instructed phenotype. Because cross-reactions with unrelated Ags can be detrimental, such a qualitative form of memory requires a sufficient degree of specificity of the adaptive immune system. For example, lymphocytes instructed to clear a particular pathogen may cause autoimmunity when cross-reacting with ignored self molecules. Alternatively, memory cells may induce an immune response of the wrong mode when cross-reacting with subsequent pathogens. To maximize the likelihood of responding to a wide variety of pathogens, it is also required that the immune system be sufficiently cross-reactive. By means of a probabilistic model, we show that these conflicting requirements are met optimally by a highly specific memory lymphocyte repertoire. This explains why the lymphocyte system that was built on a preserved functional innate immune system has such a high degree of specificity. Our analysis suggests that 1) memory lymphocytes should be more specific than naive lymphocytes and 2) species with small lymphocyte repertoires should be more vulnerable to both infection and autoimmune diseases

Износостойкость высокохромистых чугунов при ударном помоле абразива в присутствии коррозионно-активной среды

Представлены результаты испытаний чугунов, содержащих 2,24-2,59 % С, 2,07-3,13 % Mn и 9,7-28,4 % Cr, в условиях ударно-абразивного изнашивания в присутствии водных растворов щелочи и кислоты с варьированием рН от 14 до 1. Показано, что износ чугунов меняется в зависимости от рН раствора немонотонно, а характер влияния хрома на износ зависит от типа пульпы. Установлено, что чугуны с 20–28 % Cr в данных условиях изнашивания не имеют преимущества перед менее легированными хромом чугунами. В пульпе с резко кислой средой (рН=1) износ чугунов растет прямо пропорционально содержанию в них хрома.Представлено результати випробувань чавунів, що містять 2,24-2,59 % С, 2,07-3,13 % Mn і 9,7-28,4 % Cr, в умовах ударно-абразивного зношування в присутності водяних розчинів луги і кислоти з варіюванням рН від 14 до 1. Показано, що знос чавунів змінюється в залежності від рН розчину немонотонно, а характер впливу хрому на знос залежить від типу пульпи. Встановлено, що чавуни з 20-28 % Cr у даних умовах зношування не мають переваги перед менш легованими хромом чавунами. У пульпі з різко кислим середовищем (рН=1) знос чавунів зростає прямо пропорційно вмісту в них хрому.The results of the test cast iron, containing 2,24-2,59 % С, 2,07-3,13 % Mn and 9,7-28,4 % Cr, in condition is striking-abrasive wear in water solutions of alkali and acids with variation pH from 14 to 1 are presented. It is shown that wear of cast irons is changing depending on pH solution nonmonotonic, but nature of the influence of chromium on wear depends on type of the pulp. It is determined that cast irons with 20-28 % Cr in wear condition mentioned above has no advantage over cast irons with 10-12 % Cr. In pulp with sharply tart ambience (pH=1) wear of cast irons grows straight pro rata contents of chromium

Diversity of Human αβ T Cell Receptors

(a = alpha) Arstila et al. (1) estimated an average diversity of 9 * 10^5 different b chains and 4.5 * 10^5 different a chains in the human nai¨ve T cell repertoire. To calculate the total T cell repertoire diversity, the b-chain diversity was estimated within a certain variable (V) gene family, Va12^+, comprising 2.5% of the total a-chain repertoire. Finding in this particular family an estimated total of 6 * 105 different ß chains (i.e., two-thirds of the total ß-chain repertoire), Arstila et al. suggested that the total T cell receptor (TCR) diversity comprises at least (6 * 105) * 40 = 2.4 * 10^7 different aß combinations (1). The authors acknowledge that this is only a lower bound, because the calculation assumes that the ß chains that do bind at least one Va12 chain bind only one of the 4.5 * 10^5 different a chains in the Va12^+ family. If each ß chain found within the Va12^+ family were to bind an average of n different Va12 chains instead, the total estimated TCR diversity would be n-fold higher than this lower bound

Fabrication scheme for dense aquatic flow sensor arrays

A fabrication scheme to realize dense arrays of flexible, closed membranes with a small gap separating them from the substrate is presented. These membranes are the first step towards aquatic hair based flow sensors biomimicking fish lateral line. Electrodes are integrated underneath the membrane to avoid contact with the liquid. Arrays of membranes with a diameter of 100 μm, gap height of 3 μm, and mutual distance of 200 μm have been successfully fabricated