Spatial and phylodynamic survey on Crimean-Congo hemorrhagic fever virus strains in northeast of Iran

Background: Crimean-Congo hemorrhagic fever (CCHF) is asymptomatic in infected animals, yet the virus poses a serious threat to humans causing a symptomatic, hemorrhagic disease with a high case-fatality rate. Numerous genera of ticks serve as both vectors and reservoirs of the Crimean-Congo hemorrhagic fever virus (CCHFV). Objectives: The aim of the present study is to determine the CCHFV prevalence in ticks from northeast Iran to establish a phylogenetic relationship of the tick-derived CCHFV strains circulating in Iran. Methods: During April to June 2015, a total of 93 hard ticks were collected from different animals in the Damghan district. The Ssegment of positive samples was fully sequenced using the Sanger technique. A total of 142 CCHFV sequences comprised full-length of CCHFV sequences obtained in this study were aligned using the MAFFT algorithm, then phylogenetic tree was constructed using Geneious v 7.1.8. Results: The identified tick species included Hyalomma marginatum (6.5), Hy. dromedarii (21.5), Hy. anatolicum (15.1), Hy. asiaticum (3.2) and Hy. schulzei (2.2), as well as Rhipicephalus sanguineus (47.3). The CCHFV RNA was detected in 4 samples of 93 tick samples (4.3) by RT-PCR. A total of 4 CCHFV sequences were obtained in this study clustered within clade IV (Asia-1 and Asia-2). Conclusions:We demonstrated that 4 species of hard ticks could be a vector forCCHFV in Iran. In addition, our findings indicate the circulation of CCHFV clade IV strain in the northeast of Iran and provide a solid base for more targeted surveillance and prevention programs in Iran. © 2018, Jundishapur Journal of Microbiology

Spatial and phylodynamic survey on Crimean-Congo hemorrhagic fever virus strains in northeast of Iran

Background: Crimean-Congo hemorrhagic fever (CCHF) is asymptomatic in infected animals, yet the virus poses a serious threat to humans causing a symptomatic, hemorrhagic disease with a high case-fatality rate. Numerous genera of ticks serve as both vectors and reservoirs of the Crimean-Congo hemorrhagic fever virus (CCHFV). Objectives: The aim of the present study is to determine the CCHFV prevalence in ticks from northeast Iran to establish a phylogenetic relationship of the tick-derived CCHFV strains circulating in Iran. Methods: During April to June 2015, a total of 93 hard ticks were collected from different animals in the Damghan district. The Ssegment of positive samples was fully sequenced using the Sanger technique. A total of 142 CCHFV sequences comprised full-length of CCHFV sequences obtained in this study were aligned using the MAFFT algorithm, then phylogenetic tree was constructed using Geneious v 7.1.8. Results: The identified tick species included Hyalomma marginatum (6.5), Hy. dromedarii (21.5), Hy. anatolicum (15.1), Hy. asiaticum (3.2) and Hy. schulzei (2.2), as well as Rhipicephalus sanguineus (47.3). The CCHFV RNA was detected in 4 samples of 93 tick samples (4.3) by RT-PCR. A total of 4 CCHFV sequences were obtained in this study clustered within clade IV (Asia-1 and Asia-2). Conclusions:We demonstrated that 4 species of hard ticks could be a vector forCCHFV in Iran. In addition, our findings indicate the circulation of CCHFV clade IV strain in the northeast of Iran and provide a solid base for more targeted surveillance and prevention programs in Iran. © 2018, Jundishapur Journal of Microbiology

Molecular assay on Crimean Congo Hemorrhagic Fever virus in ticks (Ixodidae) collected from Kermanshah Province, Western Iran

Background: Crimean-Congo Hemorrhagic Fever (CCHF) is a feverous and hemorrhagic disease endemic in some parts of Iran and caused by an arbovirus related to Bunyaviridae family and Nairovirusgenus. The main virus reservoir in the nature is ticks, however small vertebrates and a wide range of domestic and wild animals are regarded as reservoir hosts. This study was conducted to determine the infection rate of CCHF virus in hard ticks of Sarpole- Zahab County, Kermanshah province, west of Iran. Methods: From total number of 851 collected ticks from 8 villages, 131 ticks were selected randomlyand investigated for detection of CCHF virus using RT-PCR. Results: The virus was found in 3.8 of the tested ticks. Hyalommaanatolicum, H.asiaticum and Rhipicephalus sanguineus species were found to have viral infection, with the highest infection rate (11.11) in Rh. sanguineus. Conclusion: These findings provide epidemiological evidence for planning control strategies of the disease in the study area

Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3–4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3–4 MAbs completely protected the majority of animals, while administration at 2–3 dpi achieved 50–100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection

Partition pruning: Parallelization-aware pruning for dense neural networks

As recent neural networks are being improved to be more accurate, their model's size is exponentially growing. Thus, a huge number of parameters requires to be loaded and stored from/in memory hierarchy and computed in processors to perform training or inference phase of neural network processing. Increasing the number of parameters causes a big challenge for real-time deployment since the memory bandwidth improvement's trend cannot keep up with models' complexity growing trend. Although some operations in neural networks processing are computational intensive such as convolutional layer computing, computing dense layers face with memory bandwidth bottleneck. To address the issue, the paper has proposed Partition Pruning for dense layers to reduce the required parameters while taking into consideration parallelization. We evaluated the performance and energy consumption of parallel inference of partitioned models, which showed a 7.72x speedup of performance and a 2.73x reduction in the energy used for computing pruned fully connected layers in TinyVGG16 model in comparison to running the unpruned model on a single accelerator. Besides, our method showed a limited reduction in accuracy while partitioning fully connected layers

Development and characterization of a camelid single-domain antibody directed to human CD22 biomarker

CD22 is a B-cell-specific trans-membrane glycoprotein, which is found on the surface of the most B cells and modulates their function, survival, and apoptosis. Recently, targeting this cell surface biomarker in B-cell malignancies and disorders has attracted a lot of attention. The variable domain of camelid single-chain antibodies (VHH, nanobody) is a form of antibodies with novel properties including small size (15-17 kDa), thermal and chemical stability, high affinity and homology to human antibody sequences. In this study, a novel anti-CD22-specific VHH (Nb) has been developed and characterized by the screening of an immunized phage display library and its binding to CD22+ B cells is evaluated. Produced anti-CD22 VHH had a single protein band about 17 kDa of molecular size in Western blotting and its binding affinity was approximately 9 � 10-9 M. Also, this product had high specificity and it was able to recognize the natural CD22 antigen in CD22+ cell lysate as well as on the cell surface (93). This anti-CD22 VHH with both high affinity and specificity recognizes CD22 antigen well and can be used in diagnosis and treatment of B cell disorders and malignancies. © 2018 International Union of Biochemistry and Molecular Biology, Inc

Development and characterization of a camelid single-domain antibody directed to human CD22 biomarker

CD22 is a B-cell-specific trans-membrane glycoprotein, which is found on the surface of the most B cells and modulates their function, survival, and apoptosis. Recently, targeting this cell surface biomarker in B-cell malignancies and disorders has attracted a lot of attention. The variable domain of camelid single-chain antibodies (VHH, nanobody) is a form of antibodies with novel properties including small size (15-17 kDa), thermal and chemical stability, high affinity and homology to human antibody sequences. In this study, a novel anti-CD22-specific VHH (Nb) has been developed and characterized by the screening of an immunized phage display library and its binding to CD22+ B cells is evaluated. Produced anti-CD22 VHH had a single protein band about 17 kDa of molecular size in Western blotting and its binding affinity was approximately 9 � 10-9 M. Also, this product had high specificity and it was able to recognize the natural CD22 antigen in CD22+ cell lysate as well as on the cell surface (93). This anti-CD22 VHH with both high affinity and specificity recognizes CD22 antigen well and can be used in diagnosis and treatment of B cell disorders and malignancies. © 2018 International Union of Biochemistry and Molecular Biology, Inc

Generation and characterization of an anti-delta like ligand-4 Nanobody to induce non-productive angiogenesis

Antibody-based targeting of angiogenesis is a key approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in tumor neovascular development and angiogenesis during tumor progression. It forecasts the prognosis of human malignancies and blocking its signaling can help to inhibit neovascularization and tumor metastasis. Nanobodies are the smallest antigen-binding domains of heavy chain antibodies in camelidae. The aim of this study was to develop a Nanobody against DLL4 and apply binding and functional approaches to target it. In this work, a Nanobody library against human recombinant DLL4 was developed. After panning, the periplasmic-extract (PE) of individual colonies were screened through ELISA. The interactions between Nanobody and DLL4 were assessed using immunohistochemistry and FACS. The functional assessment was carried out via tube formation assay. We selected a Nanobody (3Nb3) with a high binding signal to DLL4, associated with a binding affinity of 3.6 nM. It was demonstrated that 3Nb3 binds to native DLL4 on the surface of MKN cells and gastric carcinoma tissue, and also inhibits the maturation of capillary-like structures in HUVECs. The results were indicative of the potential of Nanobody for DLL4 identification and can broaden the scope for development of cancer diagnosis and treatment techniques. © 2017 Elsevier Inc