238 research outputs found
Computational convergence of the path integral for real dendritic morphologies
No full textNeurons are characterised by a morphological structure unique amongst biological cells, the core of which is the dendritic tree. The vast number of dendritic geometries, combined with heterogeneous properties of the cell membrane, continue to challenge scientists in predicting neuronal input-output relationships, even in the case of sub-threshold dendritic currents. The Green’s function obtained for a given dendritic geometry provides this functional relationship for passive or quasi-active dendrites and can be constructed by a sum-over-trips approach based on a path integral formalism. In this paper, we introduce a number of efficient algorithms for realisation of the sum-over-trips framework and investigate the convergence of these algorithms on different dendritic geometries. We demonstrate that the convergence of the trip sampling methods strongly depends on dendritic morphology as well as the biophysical properties of the cell membrane. For real morphologies, the number of trips to guarantee a small convergence error might become very large and strongly affect computational efficiency. As an alternative, we introduce a highly-efficient matrix method which can be applied to arbitrary branching structures
Reduced intensity conditioning regimen followed by glycosylated G-CSF mobilized PBSCT in patients with solid tumors and malignant lymphomas
No full textThe aim of this pilot study was to exploit the graft-versus-tumor potential of allogeneic transplants while improving safety of the procedure. Twelve patients with advanced hematological malignancies and solid tumors underwent a low intensity conditioning regimen (fludarabine and cyclophosphamide) followed by an allogeneic peripheral blood stem cell transplantation. The median time to achieve an absolute neutrophil count of more than 0.5 x 10(9)/l and an untransfused platelet count of more than 20 x 10(9)/l was 15 and 14 days, respectively. The main extra-hematological toxicities were mucositis and infections. Acute graft-versus-host (GVHD) disease was experienced by 62% of evaluable patients (grade II/B or III/C 80%) responsive to steroids. Extensive chronic GVHD was observed in 62% of patients. Non-relapse transplant-related mortality by day +30 was observed in three patients (25%). Eight out of 12 patients were full donor chimeric by day +100. One patient showed a mixed chimerism at day +37 when he died from progressive disease. One patient was in complete remission (CR) before allogeneic transplantation, and after transplantation four patients achieved CR and four experienced progressive disease. Our study confirms that a low intensity conditioning regimen for allogeneic stem cell transplantation is feasible and effective in heavily pretreated patients
Editorial for special issue on neurodynamics
No full text“Neurodynamics” is an interdisciplinary area of mathematics where dynamical systems theory (deterministic and stochastic) is the primary tool for elucidating the fundamental mechanisms responsible for the behaviour of neural systems (whether biological or synthetic). A meeting on this topic was held at the International Centre for Mathematical Sciences in Edinburgh from March 5–7 in 2012. In this special issue, we have invited seven of the main contributors to this event to expand on their presentations and highlight the use of mathematics in understanding the dynamics of neural systems
B-cell reconstitution recapitulates B-cell lymphopoiesis following haploidentical BM transplantation and post-transplant CY
No full textDesensitization with plasma exchange in a patient with human leukocyte antigen donor-specific antibodies before T-cell-replete haploidentical transplantation
No full textBACKGROUND The presence of human leukocyte antigen donor-specific antibodies (DSAs) increases the risk of graft failure in T-cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) CASE REPORT A 49-year-old female with high-risk acute myeloid leukemia in first complete remission received a haplo-HSCT from her daughter. Pretransplant recipient screening examination showed high DSAs levels against unshared class I leukocyte antigens. RESULTS The patient underwent a desensitization program consisting of plasma exchange (PEX), polyvalent intravenous (IV) immunoglobulins, and IV tacrolimus and mycophenolate mofetil (MMF). This protocol resulted in the disappearance of the DSA anti HLA B41. Engraftment was prompt with stable full donor chimerism. CONCLUSIONS This case report suggests that the adopted scheme is safe for reducing DSA levels and facilitating donor engraftment in patients scheduled for haplo-HSCT
Estrous Cycle Modulation of Feeding and Relaxin-3/Rxfp3 mRNA Expression: Implications for Estradiol Action
No full textIntroduction: Food intake varies during the ovarian hormone/estrous cycle in humans and rodents, an effect mediated mainly by estradiol. A potential mediator of the central anorectic effects of estradiol is the neuropeptide relaxin-3 (RLN3) synthetized in the nucleus incertus (NI) and acting via the relaxin family peptide-3 receptor (RXFP3). Methods: We investigated the relationship between RLN3/RXFP3 signaling and feeding behavior across the female rat estrous cycle. We used in situ hybridization to investigate expression patterns of Rln3 mRNA in NI and Rxfp3 mRNA in the hypothalamic paraventricular nucleus (PVN), lateral hypothalamic area (LHA), medial preoptic area (MPA), and bed nucleus of the stria terminalis (BNST), across the estrous cycle. We identified expression of estrogen receptors (ERs) in the NI using droplet digital PCR and assessed the electrophysiological responsiveness of NI neurons to estradiol in brain slices. Results: Rln3 mRNA reached the lowest levels in the NI pars compacta during proestrus. Rxfp3 mRNA levels varied across the estrous cycle in a region-specific manner, with changes observed in the perifornical LHA, magnocellular PVN, dorsal BNST, and MPA, but not in the parvocellular PVN or lateral LHA. G protein-coupled estrogen receptor 1 (Gper1) mRNA was the most abundant ER transcript in the NI. Estradiol inhibited 33% of type 1 NI neurons, including RLN3-positive cells. Conclusion: These findings demonstrate that the RLN3/RXFP3 system is modulated by the estrous cycle, and although further studies are required to better elucidate the cellular and molecular mechanisms of estradiol signaling, current results implicate the involvement of the RLN3/RXFP3 system in food intake fluctuations observed across the estrous cycle in female rats
Phytochemical composition of Humulus Lupulus L. in ontogeny under different treatments
No full textWild hop (Humulus lupulus L.) is a double-headed perennial climbing plant that belongs to the Cannabaceae family. Hops contain many biologically active compounds possessing powerful antimicrobial, antioxidant and antifungal activity, due to which its original use was for medicinal purposes and only later began to be used in beer production. The aim of the work was to identify the effects of growth regulators (hibbersib and epin-extra) and biofertilizer (powder) on the content of soluble phenolic compounds, flavonoids, tannins, carotenoids, vitamins C and B, protein and sugars in plants of common hop (Humulus lupulus L.) during ontogenesis. Root cuttings of hops were planted in the beginning of May 2022 in protected ground under laboratory conditions. In the second variant rootstock were potted in soil with 10 g/kg powders; in the third variant rootstocks were treated with hibbersib (666.6 µg/l) by spraying; in the fourth variant also, rootstocks were treated with epin-extra (500 µl/l) by spraying. After 4 weeks, all variants were transplanted to the open field. The samples for analysis (leaves) were taken 4, 8, 12 and 16 weeks after planting in the open ground, the average night temperatures were +160C, +240C, +140C and +70C, respectively. Phytochemical composition of leaves was determined by spectrophotometric method. In control plants the content of phenolic compounds and vitamin C reached the highest values in the twelfth week after planting. The synthetic growth regulators (epin-extra and hibbersib) and the biofertilizer (pudrete) were shown to change the phytochemical composition of the hop plants to different extents. Powdertet increased the vitamin and protein content to a greater extent whereas growth regulators increased the content of phenolic compounds and sugars, particularly under the influence of hibbersib
Low Temperature Equilibrium Ageing Under Self-Irradiation in Binary Alloys of Pu with Elements of Group III -B
No full textPhytochemical composition of Humulus Lupulus L. in ontogeny under different treatments
No full textWild hop (Humulus lupulus L.) is a double-headed perennial climbing plant that belongs to the Cannabaceae family. Hops contain many biologically active compounds possessing powerful antimicrobial, antioxidant and antifungal activity, due to which its original use was for medicinal purposes and only later began to be used in beer production. The aim of the work was to identify the effects of growth regulators (hibbersib and epin-extra) and biofertilizer (powder) on the content of soluble phenolic compounds, flavonoids, tannins, carotenoids, vitamins C and B, protein and sugars in plants of common hop (Humulus lupulus L.) during ontogenesis. Root cuttings of hops were planted in the beginning of May 2022 in protected ground under laboratory conditions. In the second variant rootstock were potted in soil with 10 g/kg powders; in the third variant rootstocks were treated with hibbersib (666.6 µg/l) by spraying; in the fourth variant also, rootstocks were treated with epin-extra (500 µl/l) by spraying. After 4 weeks, all variants were transplanted to the open field. The samples for analysis (leaves) were taken 4, 8, 12 and 16 weeks after planting in the open ground, the average night temperatures were +160C, +240C, +140C and +70C, respectively. Phytochemical composition of leaves was determined by spectrophotometric method. In control plants the content of phenolic compounds and vitamin C reached the highest values in the twelfth week after planting. The synthetic growth regulators (epin-extra and hibbersib) and the biofertilizer (pudrete) were shown to change the phytochemical composition of the hop plants to different extents. Powdertet increased the vitamin and protein content to a greater extent whereas growth regulators increased the content of phenolic compounds and sugars, particularly under the influence of hibbersib
Feasibility and efficacy of CD45RA+ depleted donor lymphocytes infusion after haploidentical transplantation with post-transplantation cyclophosphamide in patients with hematological malignancies
No full textAllogeneic stem cell transplantation from haploidentical donor using post-transplantation cyclophosphamide has been used to cure hematological diseases. Because of slow immunological reconstitution, there is an increased incidence of viral infection. The aim of our study was to prospectively evaluate the efficacy and the feasibility of a CD45RA+ depleted donor lymphocytes infusion (DLI) in terms of reduction of viral infection early after haploidentical transplantation. This a prospective single-center study. We enrolled 23 patients, of whom 19 were evaluable. Graft-versus-host disease (GVHD) prophylaxis was the same for all patients. The primary endpoint was 100-day cumulative incidence of viral infections. The primary endpoint was met, because the 100-day cumulative incidence of viral infection was 32%. The median time from transplantation to first CD45RA+ depleted DLI was 55 days (range, 46-63). 28% of patients had cytomegalovirus reactivation, no patients reactivated human herpesvirus-6; 1 patient developed BK virus related hemorrhagic cystitis. Most of the patients received the planned 3 infusions. Only 1 patient had development of grade 2 acute GVHD, and 2 patients had moderate chronic GVHD. All evaluable patients were off immunosuppressive therapy at last follow-up. The median follow-up was 12 months (range, 3-23), the 1-year overall survival and progression-free survival were 79% and 75%, respectively; the 100-day and 1-year non-relapse mortality were 5% and 12%, respectively. CD45RA+ depleted DLI are feasible in patients treated with haploidentical transplantation. The toxic profile is good with a low risk for development of both acute and chronic GVHD
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