| 1. |
- Ahmad, Sajjad, et al.
(författare)
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Novel mutations in genes of the IL-12/IFN-γ axis cause susceptibility to tuberculosis
- 2023
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Ingår i: Journal of Infection and Public Health. - : Elsevier. - 1876-0341 .- 1876-035X. ; 16:9, s. 1368-1378
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Tidskriftsartikel (refereegranskat)abstract
- Background: The IL-12/23/ISG15-IFN-γ pathway is the main immunological pathway for controlling intra-macrophagic microorganisms such as Mycobacteria, Salmonella, and Leishmania spp. Consequently, upon mutations in genes of the IL-12/23/ISG15-IFN-γ pathway cause increased susceptibility to intra-macrophagic pathogens, particularly to Mycobacteria. Therefore, the purpose of this study was to characterize the mutations in genes of the IL-12/23/ISG15-IFN-γ pathway in severe tuberculosis (TB) patients.Methods: Clinically suspected TB was initially confirmed in four patients (P) (P1, P2, P3, and P4) using the GeneXpert MTB/RIF and culturing techniques. The patients' Peripheral blood mononuclear cells (PBMCs) were then subjected to ELISA to measure Interleukin 12 (IL-12) and interferon gamma (IFN-γ). Flow cytometry was used to detect the surface expressions of IFN-γR1 and IFN-γR2 as well as IL-12Rβ1and IL-12Rβ2 on monocytes and T lymphocytes, respectively.The phosphorylation of signal transducer and activator of transcription 1(STAT1) on monocytes and STAT4 on T lymphocytes were also detected by flow cytometry. Sanger sequencing was used to identify mutations in the IL-12Rβ1, STAT1, NEMO, and CYBB genes.Results: P1's PBMCs exhibited reduced IFN-γ production, while P2's and P3's PBMCs exhibited impaired IL-12 induction. Low IL-12Rβ1 surface expression and reduced STAT4 phosphorylation were demonstrated by P1's T lymphocytes, while impaired STAT1 phosphorylation was detected in P2's monocytes. The impaired IκB-α degradation and abolished H2O2 production in monocytes and neutrophils of P3 and P4 were observed, respectively. Sanger sequencing revealed novel nonsense homozygous mutation: c.191 G>A/p.W64 * in exon 3 of the IL-12Rβ1 gene in P1, novel missense homozygous mutation: c.107 A>T/p.Q36L in exon 3 of the STAT1 gene in P2, missense hemizygous mutation:: c.950 A>C/p.Q317P in exon 8 of the NEMO gene in P3, and nonsense hemizygous mutation: c.868 C>T/p.R290X in exon 8 of CYBB gene in P4.Conclusion: Our findings broaden the clinical and genetic spectra associated with IL-12/23/ISG15-IFN-γ axis anomalies. Additionally, our data suggest that TB patients in Pakistan should be investigated for potential genetic defects due to high prevalence of parental consanguinity and increased incidence of TB in the country.
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| 2. |
- Ahmed, Sairah, et al.
(författare)
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Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma
- 2020
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Ingår i: British Journal of Haematology. - : WILEY. - 0007-1048 .- 1365-2141. ; 190:4, s. 573-582
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Tidskriftsartikel (refereegranskat)abstract
- Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0 center dot 01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0 center dot 54), relapse/progression (P = 0 center dot 02) or progression-free survival (PFS) (P = 0 center dot 14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0 center dot 28; 95% CI = 0 center dot 10-0 center dot 73; P = 0 center dot 009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2 center dot 46; 95% CI = 0 center dot 1.32-4 center dot 61; P = 0 center dot 005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0 center dot 64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).
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| 3. |
- Badshah, Munair, et al.
(författare)
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Development and Evaluation of Drug Loaded Regenerated Bacterial Cellulose-Based Matrices as a Potential Dosage Form
- 2020
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial cellulose (BC) is a highly pure form of cellulose and possesses superior physico-mechanical properties with wide range of applications. These properties of BC can further be improved by various modifications, including its regeneration from the BC solution. In the current research work, regenerated BC (R-BC) matrices were prepared using N-methyl-morpholine-oxide (NMMO; 50% w/w solution in water) and loaded with model drugs, i.e., famotidine or tizanidine. The characterization of drug loaded regenerated BC (R-BC-drug) matrices was carried out using Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA), which revealed the stability of matrices and successful drug loading. Results of dissolution studies showed immediate (i.e., >90%) drug release in 30 min. The drugs release data was found to best fit into first order kinetics model having R2 values >0.99 for all the formulations. These results indicated that regenerated BC-based matrices had the ability to be used for delivery of orally administered drugs.
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| 4. |
- Casulo, Carla, et al.
(författare)
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Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure : A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis
- 2018
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:6, s. 1163-1171
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Tidskriftsartikel (refereegranskat)abstract
- Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within 2 years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup. ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within 2 years of frontline chemoimmunotherapy. We identified 2 groups: the non-autoHCT cohort (patients from the NLCS with ETF not undergoing autoHCT) and the autoHCT cohort (CIBMTR patients with ETF undergoing autoHCT). All patients received rituximab-based chemotherapy as frontline treatment; 174 non-autoHCT patients and 175 autoHCT patients were identified and analyzed. There was no difference in 5-year OS between the 2 groups (60% versus 67%, respectively; P = .16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5-year OS than those without autoHCT (73% versus 60%, P = .05). On multivariate analysis, early use of autoHCT was associated with significantly reduced mortality (hazard ratio, .63; 95% confidence interval, .42 to .94; P = .02). Patients with FL experiencing ETF after frontline chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in select FL patients experiencing ETF.
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| 5. |
- Chauhan, Shakti, et al.
(författare)
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Designing peptide-based vaccine candidates for Plasmodium falciparum erythrocyte binding antigen 175
- 2020
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Ingår i: Biologicals (Print). - : Elsevier. - 1045-1056 .- 1095-8320. ; 67, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- Plasmodium falciparum leads to a virulent form of malaria. Progress has been achieved in understanding the mechanisms involved in the malarial infection, still there is no effective vaccine to prevent severe infection. An effective vaccine against malaria should be one which can induce immune responses against multiple epitopes in the context of predominantly occurring HLA alleles. In this study, an integrated approach was employed to identify promiscuous peptides of a well-defined sequence of erythrocyte binding antigen-175 and promiscuous peptides for HLA alleles were designed using bioinformatics tools. A peptide with 15 amino acids (ILAIAIYESRILKRK) was selected based on its high binding affinity score and synthesized. This promiscuous peptide was used as stimulating antigen in lymphoproliferative responses to evaluate the cellular immune response. It was observed this peptide evokes lymphoproliferative and cytokine responses in individuals naturally exposed to the malaria parasite. The intensity of PBMCs proliferation was observed to be higher in sera obtained from P. falciparum exposed as compared to unexposed healthy individuals, suggesting earlier recognition of peptide of this region by T cells. Furthermore, the binding mode of HLA–peptide complex and their interaction may lead to a rational and selective peptide-based vaccine candidate design approach which can be used as a malaria prophylaxis.
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| 6. |
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| 7. |
- Farooq, Muhammad Umar, 1973, et al.
(författare)
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EBSD characterization of carbide-carbide boundaries in WC-Co
- 2004
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Ingår i: Journal of Microscopy. ; 213:March, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- A sample of WC-6wt%Co was investigated for grain boundary character distribution and occurence of coincidence site lattice (CSL) boundaries on a statistical basis. For this purpose orientation measurements of the grains were carried out using electron back-scattered diffraction (EBSD). The dominant misorientation relationships were determined by complementary EBSD data representation tools such as orientatin maps, misorientation angle distribution histograms and the sectioned three-dimensional misorientation space. It was found that the grain boundary character distribution of the material is nearly random and the CSL boundaries are not present in statistically significant amounts. It was also found that the amount of binder phase does not play a role in the formation of special boundaries. The paper focuses on the methodology of characterizing grain boundaries in a hexagonal material using EBSD.
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| 8. |
- Farooq, Muhammad Umar, et al.
(författare)
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Improving the Thresholds of Generalized LDPC Codes with Convolutional Code Constraints
- 2023
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Ingår i: IEEE Communications Letters. - 1558-2558 .- 1089-7798. ; 27:7, s. 1679-1683
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Tidskriftsartikel (refereegranskat)abstract
- CC-GLPDC codes are a class of generalized low-density parity-check (GLDPC) codes where the constraint nodes (CNs) represent convolutional codes. This allows for efficient decoding in the trellis with the forward-backward algorithm, and the strength of the component codes easily can be controlled by the encoder memory without changing the graph structure. In this letter, we extend the class of CC-GLDPC codes by introducing different types of irregularity at the CNs and investigating their effect on the BP and MAP decoding thresholds for the binary erasure channel (BEC). For the considered class of codes, an exhaustive grid search is performed to find the BP-optimized and MAP-optimized ensembles and compare their thresholds with the regular ensemble of the same design rate. The results show that irregularity can significantly improve the BP thresholds, whereas the thresholds of the MAP-optimized ensembles are only slightly different from the regular ensembles. Simulation results for the AWGN channel are presented as well and compared to the corresponding thresholds.
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| 9. |
- Farooq, Muhammad Umar, 1973, et al.
(författare)
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Microstructual investigation of Co-Cr clad applied on railway wheels
- 2004
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Ingår i: Proceedings of the Channel User Meeting 2004, Ribe, Denmark.. ; , s. 25-30
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Laser cladding is applied to locally improve the functional surface properties of parts such as wear resistance (increased surface hardness) and corrosion resistance. In the present study the EBSD technique was used to investigate microstructure and textur of a Co-Cr-clad applied on railway wheels. The investigations showed that the clad consists of elongated grains that grow perpendicular to the clad surface with a [001] fibre texture. The investigations also revealed that no dominant orientation relationship (angle/axis pair) occurs between the alpha-Co grains of the clad. The relative orientation between the alpha-Co (high temperature) and gamma-Co (low temperature) phase is determined by comparing the pole figures of the respective phases. Different reasons of aprupt changes in the colors of the orientation maps are also discussed.
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| 10. |
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