Закономерности накопления водорода в титановом сплаве ВТ1-0 при электролитическом и газофазном наводороживании

В настоящем исследовании я изучил макроскопические свойства титанового сплава (BT1-0) и его свойства в субмикронной структуре, а также способы определения количества, распределения и состояния накопленного водорода для разработки методов предотвращения водородного охрупчивания.In the present study, I studied the macroscopic properties of titanium alloy (BT1-0) and its properties under submicron structure, and how to determine the quantity, distribution and state of accumulated hydrogen to develop methods for preventing hydrogen embrittlement

Pre-emptive Allogeneic Hematopoietic Stem Cell Transplantation in Ataxia Telangiectasia

Ataxia telangiectasia (A-T) is a primary immunodeficiency with mutations in the gene encoding the A-T mutated (ATM) protein that interacts with immune, hematopoietic, and endocrine targets resulting in broad multi-systemic clinical manifestations with a devastating outcome. Apart from a progressive neurodegenerative disorder, A-T leads to significantly increased susceptibility to malignancies. It is a matter of discussion whether pre-emptive allogeneic hematopoietic stem cell transplantation (alloHSCT) using a reduced intensity conditioning regimen would be an option to restore immune-competence and prevent malignancy, as shown in animal models, because conventional treatment protocols of malignant diseases using radio- and/or chemotherapy have a high rate of therapy-related morbidity and mortality in these patients. We present the course of the disease, including immune reconstitution and neurological outcome following pre-emptive alloHSCT in a 4-year-old boy with A-T on a 6 year follow-up. Our manuscript provides a proof-of-concept of alloHSCT as an individual pre-emptive treatment strategy from which some A-T patients might benefit

IL-2 Stimulated but Not Unstimulated NK Cells Induce Selective Disappearance of Peripheral Blood Cells: Concomitant Results to a Phase I/II Study

In an ongoing clinical phase I/II study, 16 pediatric patients suffering from high risk leukemia/tumors received highly purified donor natural killer (NK) cell immunotherapy (NK-DLI) at day (+3) +40 and +100 post haploidentical stem cell transplantation. However, literature about the influence of NK-DLI on recipient's immune system is scarce. Here we present concomitant results of a noninvasive in vivo monitoring approach of recipient's peripheral blood (PB) cells after transfer of either unstimulated (NK-DLI(unstim)) or IL-2 (1000 U/ml, 9–14 days) activated NK cells (NK-DLI(IL-2 stim)) along with their ex vivo secreted cytokine/chemokines. We performed phenotypical and functional characterizations of the NK-DLIs, detailed flow cytometric analyses of various PB cells and comprehensive cytokine/chemokine arrays before and after NK-DLI. Patients of both groups were comparable with regard to remission status, immune reconstitution, donor chimerism, KIR mismatching, stem cell and NK-DLI dose. Only after NK-DLI(IL-2 stim) was a rapid, almost complete loss of CD56(bright)CD16(dim/−) immune regulatory and CD56(dim)CD16(+) cytotoxic NK cells, monocytes, dendritic cells and eosinophils from PB circulation seen 10 min after infusion, while neutrophils significantly increased. The reduction of NK cells was due to both, a decrease in patients' own CD69(−) NCR(low)CD62L(+) NK cells as well as to a diminishing of the transferred cells from the NK-DLI(IL-2 stim) with the CD56(bright)CD16(+/−)CD69(+)NCR(high)CD62L(−) phenotype. All cell counts recovered within the next 24 h. Transfer of NK-DLI(IL-2 stim) translated into significantly increased levels of various cytokines/chemokines (i.e. IFN-γ, IL-6, MIP-1β) in patients' PB. Those remained stable for at least 1 h, presumably leading to endothelial activation, leukocyte adhesion and/or extravasation. In contrast, NK-DLI(unstim) did not cause any of the observed effects. In conclusion, we assume that the adoptive transfer of NK-DLI(IL-2 stim) under the influence of ex vivo and in vivo secreted cytokines/chemokines may promote NK cell trafficking and therefore might enhance efficacy of immunotherapy

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future

Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes

<p>Abstract</p> <p>Background</p> <p>Congenital nephrogenic diabetes insipidus (NDI) is characterised by an inability to concentrate urine despite normal or elevated plasma levels of the antidiuretic hormone arginine vasopressin. We report a Japanese extended family with NDI caused by an 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>Rho GTPase-activating protein 4 </it>(<it>ARHGAP4</it>) locus. ARHGAP4 belongs to the RhoGAP family, Rho GTPases are critical regulators of many cellular activities, such as motility and proliferation which enhances intrinsic GTPase activity.</p> <p>ARHGAP4 is expressed at high levels in hematopoietic cells, and it has been reported that an NDI patient lacking <it>AVPR2 </it>and all of <it>ARHGAP4 </it>showed immunodeficiency characterised by a marked reduction in the number of circulating CD3+ cells and almost complete absence of CD8+ cells.</p> <p>Methods</p> <p>PCR and sequencing were performed to identify the deleted region in the Japanese NDI patients. Immunological profiles of the NDI patients were analysed by flow cytometry. We also investigated the gene expression profiles of peripheral blood mononuclear cells (PBMC) from NDI patients and healthy controls in microarray technique.</p> <p>Results</p> <p>We evaluated subjects (one child and two adults) with 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>ARHGAP4</it>. Hematologic tests showed a reduction of CD4+ cells in one adult patient, a reduction in CD8+ cells in the paediatric patient, and a slight reduction in the serum IgG levels in the adult patients, but none of them showed susceptibility to infection. Gene expression profiling of PBMC lacking <it>ARHGAP4 </it>revealed that expression of RhoGAP family genes was not influenced greatly by the lack of <it>ARHGAP4</it>.</p> <p>Conclusion</p> <p>These results suggest that loss of <it>ARHGAP4 </it>expression is not compensated for by other family members. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of <it>ARHGAP4 </it>does not result in clinical immunodeficiency.</p

Joint Modeling of Immune Reconstitution Post Haploidentical Stem Cell Transplantation in Pediatric Patients With Acute Leukemia Comparing CD34+-Selected to CD3/CD19-Depleted Grafts in a Retrospective Multicenter Study

Rapid immune reconstitution (IR) following stem cell transplantation (SCT) is essential for a favorable outcome. The optimization of graft composition should not only enable a sufficient IR but also improve graft vs. leukemia/tumor effects, overcome infectious complications and, finally, improve patient survival. Especially in haploidentical SCT, the optimization of graft composition is controversial. Therefore, we analyzed the influence of graft manipulation on IR in 40 patients with acute leukemia in remission. We examined the cell recovery post haploidentical SCT in patients receiving a CD34+-selected or CD3/CD19-depleted graft, considering the applied conditioning regimen. We used joint model analysis for overall survival (OS) and analyzed the dynamics of age-adjusted leukocytes; lymphocytes; monocytes; CD3+, CD3+CD4+, and CD3+CD8+ T cells; natural killer (NK) cells; and B cells over the course of time after SCT. Lymphocytes, NK cells, and B cells expanded more rapidly after SCT with CD34+-selected grafts (P = 0.036, P = 0.002, and P &lt; 0.001, respectively). Contrarily, CD3+CD4+ helper T cells recovered delayer in the CD34 selected group (P = 0.026). Furthermore, reduced intensity conditioning facilitated faster immune recovery of lymphocytes and T cells and their subsets (P &lt; 0.001). However, the immune recovery for NK cells and B cells was comparable for patients who received reduced-intensity or full preparative regimens. Dynamics of all cell types had a significant influence on OS, which did not differ between patients receiving CD34+-selected and those receiving CD3/CD19-depleted grafts. In conclusion, cell reconstitution dynamics showed complex diversity with regard to the graft manufacturing procedure and conditioning regimen

Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents—the HELENA study

Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5–17.5 years, n = 405, 48.9 % boys), considering age, sex, puberty and body mass index (BMI). CD3+ (mature T cells), CD4+ (T helper), CD8+ (T cytotoxic), CD16+56+ (natural killer), CD19+ (B cells), CD3+CD45RA+, CD4+CD45RA+, CD8+CD45RA+ (naïve), CD3+CD45RO+, CD4+CD45RO+ and CD8+CD45RO+ (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3+CD45RO+ and CD4+CD45RO+ cell counts and CD3+/CD19+ ratio, and lower CD3+CD45RA+ and CD4+CD45RA+ counts than boys. Age was associated with higher neutrophil counts and CD3+/CD19+, and lower CD19+ counts; in boys, with lower CD3+CD45RA+, CD4+CD45RA+ and CD8+CD45RA+ counts as well; in girls, with higher WBC, CD3+CD45RO+ and CD4+CD45RO+ counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3+CD45RO+ and CD4+CD45RO+ values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4+, CD3+CD45RO+ and CD4+CD45RO+ counts. Conclusion: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations

Huenecke, Dorothy, What is Curriculum Theorizing? What Are Its Implications for Practice? Educational Leadership, 39(January, 1982), 290-294.*

Distinguishes between structural, generic, and substantive theorizing in curriculum

The influence of perceived academic effort on the social acceptance of low-achieving children

Includes bibliographical references (pages [72]-75)The present study examined children's perceptions of low-achieving peers in light of Attributional Theory, which predicts that perception of effort influences subsequent attributional beliefs, affective responses, and pro-social intentions. Second-, fifth-, and eighth/ninth-grade children listened to short descriptions of two low-achieving hypothetical peers who demonstrated high or low academic effort. Participants rated their attributional beliefs about and affective responses toward the target peers. Participants also rated their intentions toward the peers in both academic and non-academic settings, as well as their estimates of the peers' cognitive ability. Finally, participants completed a recognition task for information presented about the peer. Analyses indicted that the amount of academic effort a low-achieving child demonstrated had significant effects on participants' beliefs, as well as affective and behavioral intentions toward the peer. Specifically, ratings of responsibility were discrepant between the two peers, with the low-effort peer viewed as most responsible for the negative outcome. The low-effort peer provoked the greatest anger, and the least pity and liking. Furthermore, the low-effort peer was less likely to be helped or accepted by participants. The converse was partially true for the high-effort peer, who was not disliked, received more pity, and was more likely to receive help and acceptance. Additionally, these basic outcomes were apparent in varying degrees across genders and grades. Girls indicated greater feelings of pity and intentions of helping and acceptance, whereas fifth graders in general, and fifth-grade boys in particular, were most negative in their attributions, affective responses, and intentions of helping and accepting the low-effort peer.M.A. (Master of Arts