146 research outputs found
Π ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠΈ ΡΡΠΊΠΎΡΠΈΡΠ΅Π»Π΅ΠΉ Π² ΡΠ»Π΅ΠΊΡΡΠΎΠΏΠ΅ΡΠ΅Π΄Π°ΡΠ΅ ΠΏΠΎΡΡΠΎΡΠ½Π½ΡΠΌ ΡΠΎΠΊΠΎΠΌ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΡ
Π£ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΠΈ ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠΎΡΠ½ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΈ ΡΠ΅Π»Π΅ΠΉΠ½ΠΎΠΉ Π‘ΠΠ ΠΏΡΡΠΊΠΎΠ²ΠΎΠ³ΠΎ ΡΠΎΠΊΠ° ΡΡΠ³ΠΎΠ²ΠΎΠ³ΠΎ ΡΠ»Π΅ΠΊΡΡΠΎΠ΄Π²ΠΈΠ³Π°ΡΠ΅Π»Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π²ΠΎΠ·Π±ΡΠΆΠ΄Π΅Π½ΠΈΡ
Π’Π΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΡΠΉ Π΄ΡΠ΅ΠΉΡ ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΡΡ ΡΠ°ΡΡΠΎΡ ΠΌΠΈΠΊΡΠΎΠΌΠ΅Ρ Π°Π½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π³ΠΈΡΠΎΡΠΊΠΎΠΏΠ°
Π¦Π΅Π»ΡΡ ΡΠ°Π±ΠΎΡΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ Π²Π»ΠΈΡΠ½ΠΈΡΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΠΎΠ³ΠΎ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π½Π° ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΡΠ΅ ΡΠ°ΡΡΠΎΡΡ ΠΌΠΈΠΊΡΠΎΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π³ΠΈΡΠΎΡΠΊΠΎΠΏΠ°, ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΡΠ»Π΅ΠΌΠ΅Π½Ρ ΠΊΠΎΡΠΎΡΠΎΠ³ΠΎ ΡΠ°ΡΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ Π½Π° ΠΊΡΠ΅ΠΌΠ½ΠΈΠ΅Π²ΠΎΠΉ ΠΏΠ»Π°ΡΡΠΈΠ½Π΅ Ρ ΠΊΡΠΈΡΡΠ°Π»Π»ΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΎΡΠΈΠ΅Π½ΡΠ°ΡΠΈΠ΅ΠΉ (111), ΠΈΠΌΠ΅ΡΡΠ΅ΠΉ ΠΈΠ·ΠΎΡΡΠΎΠΏΠΈΡ ΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΡΡ
ΡΠ²ΠΎΠΉΡΡΠ² Π²ΠΎ Π²ΡΠ΅Ρ
Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡΡ
. ΠΠ΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΠΌΠ΅ΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ, Π·Π°Π²ΠΈΡΡΡΠΈΡ
ΠΎΡ ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠ°ΡΡΠΎΡ Π²ΠΎ Π²ΡΠ΅ΠΌ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΠΎΠΌ Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅, ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°Π΅Ρ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ΅ΠΌΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. Π Ρ
ΠΎΠ΄Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π² ΡΡΠ΅Π΄Π΅ ANSYS ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΠΎ-ΠΌΠΎΠ΄Π°Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΌΠΎΠ΄Π΅Π»ΠΈ, ΠΈΠΌΠΈΡΠΈΡΡΡΡΠ΅ΠΉ ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΠ΅ ΠΊΠΎΠ»Π΅Π±Π°Π½ΠΈΡ ΠΌΠΈΠΊΡΠΎΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π³ΠΈΡΠΎΡΠΊΠΎΠΏΠ°. ΠΠΎΠ΄Π΅Π»Ρ ΠΌΠΈΠΊΡΠΎΡΠ΅Π·ΠΎΠ½Π°ΡΠΎΡΠ°, Π²ΡΠ±ΡΠ°Π½Π½Π°Ρ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΈΠΌΠΈΡΠ°ΡΠΎΡΠ° ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΡ
ΠΊΠΎΠ»Π΅Π±Π°Π½ΠΈΠΉ ΠΌΠΈΠΊΡΠΎΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π³ΠΈΡΠΎΡΠΊΠΎΠΏΠ°, Π°Π΄Π΅ΠΊΠ²Π°ΡΠ½ΠΎ ΠΎΡΡΠ°ΠΆΠ°Π΅Ρ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ ΠΊΠΎΠ»Π΅Π±Π°Π½ΠΈΠΉ ΠΌΠ°ΡΡΡ ΠΏΠΎ ΠΎΡΠΈ ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΡ
ΠΊΠΎΠ»Π΅Π±Π°Π½ΠΈΠΉ. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΡΠ΅ Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠ°ΡΡΠΎΡ ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ½ΠΎ-Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠ΅ ΠΌΠΎΠ΄Ρ ΠΊΠΎΠ»Π΅Π±Π°Π½ΠΈΠΉ Π΄Π»Ρ ΠΎΡΡΠΈΠ»Π»ΡΡΠΎΡΠ°, Π²ΡΠΏΠΎΠ»Π½Π΅Π½Π½ΠΎΠ³ΠΎ Π½Π° ΠΊΡΠ΅ΠΌΠ½ΠΈΠ΅Π²ΠΎΠΉ ΠΏΠ»Π°ΡΡΠΈΠ½Π΅ Ρ ΠΊΡΠΈΡΡΠ°Π»Π»ΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΎΡΠΈΠ΅Π½ΡΠ°ΡΠΈΠ΅ΠΉ (111)
ΠΠ½Π°Π»ΠΈΠ· ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΡΡ Π·Π°ΠΊΡΠΏΠΎΠΊ
Π Π°ΡΡΠΌΠΎΡΡΠ΅Π½Π° ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½Π°Ρ ΡΠΈΡΡΠ΅ΠΌΠ° ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½ΠΈΡ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π·Π°ΠΊΠ°Π·Π°, ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ Π΄ΠΎΡΡΠΎΠΈΠ½ΡΡΠ²Π° ΠΈ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠΈ Π΄Π°Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ. ΠΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½ ΠΎΠ±Π·ΠΎΡ Π€Π΅Π΄Π΅ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΡΠ°ΠΊΡΠ½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ
Specific Class I HLA Supertypes but Not HLA Zygosity or Expression Are Associated with Outcomes following HLA-Matched Allogeneic Hematopoietic Cell Transplant: HLA Supertypes Impact Allogeneic HCT Outcomes
Maximizing the probability of antigen presentation to T cells through diversity in HLAs can enhance immune responsiveness and translate into improved clinical outcomes, as evidenced by the association of heterozygosity and supertypes at HLA class I loci with improved survival in patients with advanced solid tumors treated with immune checkpoint inhibitors. We investigated the impact of HLA heterozygosity, supertypes, and surface expression on outcomes in adult and pediatric patients with acute myeloid leukemia (AML), myelodysplastic syndrome, acute lymphoblastic leukemia, and non-Hodgkin lymphoma who underwent 8/8 HLA-matched, T cell replete, unrelated, allogeneic hematopoietic cell transplant (HCT) from 2000 to 2015 using patient data reported to the Center for International Blood and Marrow Transplant Research. HLA class I heterozygosity and HLA expression were not associated with overall survival, relapse, transplant-related mortality (TRM), disease-free survival (DFS), and acute graft-versus-host disease following HCT. The HLA-B62 supertype was associated with decreased TRM in the entire patient cohort (hazard ratio [HR], 0.79; 95% CI, 0.69 to 0.90; P = .00053). The HLA-B27 supertype was associated with worse DFS in patients with AML (HR = 1.21; 95% CI, 1.10 to 1.32; P = .00005). These findings suggest that the survival benefit of HLA heterozygosity seen in solid tumor patients receiving immune checkpoint inhibitors does not extend to patients undergoing allogeneic HCT. Certain HLA supertypes, however, are associated with TRM and DFS, suggesting that similarities in peptide presentation between supertype members play a role in these outcomes. Beyond implications for prognosis following HCT, these findings support the further investigation of these HLA supertypes and the specific immune peptides important for transplant outcomes
Haplotype motif-based models for KIR-genotype informed selection of hematopoietic cell donors fail to predict outcome of patients with Myelodysplastic Syndromes or secondary Acute Myeloid Leukemia
Results from registry studies suggest that harnessing Natural Killer (NK) cell reactivity mediated through Killer cell Immunoglobulin-like Receptors (KIR) could reduce the risk of relapse after allogeneic Hematopoietic Cell Transplantation (HCT). Several competing models have been developed to classify donors as KIR-advantageous or disadvantageous. Basically, these models differ by grouping donors based on distinct KIR-KIR-ligand combinations or by haplotype motif assignment. This study aimed to validate different models for unrelated donor selection for patients with Myelodysplatic Syndromes (MDS) or secondary Acute Myeloid Leukemia (sAML). In a joint retrospective study of the European Society for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) registry data from 1704 patients with secondary AML or MDS were analysed. The cohort consisted mainly of older patients (median age 61 years) with high risk disease who had received chemotherapy-based reduced intensity conditioning and anti-thymocyte globulin prior to allogeneic HCT from well-matched unrelated stem cell donors. The impact of the predictors on Overall Survival (OS) and relapse incidence was tested in Cox regression models adjusted for patient age, a modified disease risk index, performance status, donor age, HLA-match, sex-match, CMV-match, conditioning intensity, type of T-cell depletion and graft type. KIR genes were typed using high-resolution amplicon-based next generation sequencing. In univariable and multivariable analyses none of the models predicted OS and the risk of relapse consistently. Our results do not support the hypothesis that optimizing NK-mediated alloreactivity is possible by KIR-genotype informed selection of HLA-matched unrelated donors. However, in the context of allogeneic transplantation, NK-cell biology is complex and only partly understood. KIR-genes are highly diverse and current assignment of haplotype motifs based on the presence or absence of selected KIR genes is over-simplistic. As a consequence, further research is highly warranted and should integrate cutting edge knowledge on KIR genetics, and NK-cell biology into future studies focused on homogeneous groups of patients and treatment modalities.Development and application of statistical models for medical scientific researc
Transgenic technologies to induce sterility
The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes
Transgenic technologies to induce sterility
The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes
Identification of genes for engineering the male germline of Aedes aegypti and Ceratitis capitata
donor selection for adults and pediatrics
It is known that multiple factors impact on transplantation outcome; the heaviest ones are disease-related (disease refractoriness, phase, clonal abnormalities, etc. in malignancies and disease type and associated rejection risk in non-malignant diseases) and patient-related (age, comorbidities, infectious diseases/colonization, etc.). Moreover, donor-related issues and stem cell source may influence the extent of disease control and transplant-related mortality
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