Efficient human-like antibody repertoire and hybridoma production in trans-chromosomic mice carrying megabase-sized human immunoglobulin loci

Abstract Trans-chromosomic (Tc) mice carrying mini-chromosomes with human immunoglobulin (Ig) loci have contributed to the development of fully human therapeutic monoclonal antibodies (Abs); however, we previously observed that mitotic instability of human mini-chromosomes in mice has limited the efficiency of hybridoma production. Here, we established a new generation of human Ab producing Tc mice (TC-mAb mice), which stably maintain a mouse-derived engineered chromosome containing the entire human Ig heavy and kappa chain loci in a mouse Ig knockout background. Comprehensive, high-throughput DNA sequencing revealed that the human Ig repertoire, including variable gene use, was well recapitulated in TC-mAb mice. Despite slightly altered B cell development and a delayed immune response, immunized TC-mAb mice exhibited more subsets of antigen-specific plasmablast and plasma cells compared with wild-type mice, leading to high efficiency hybridoma production. Thus, TC-mAb mice offer a valuable platform to obtain fully human therapeutic Abs and to elucidate the regulation of human Ig repertoire formation.

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Recent Advancements in Polythiophene-Based Materials and Their Biomedical, Geno Sensor and DNA Detection

International Journal of Molecular Sciences ◽

10.3390/ijms22136850 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6850

Author(s):

Seyyed Mojtaba Mousavi ◽

Seyyed Alireza Hashemi ◽

Sonia Bahrani ◽

Khadije Yousefi ◽

Gity Behbudi ◽

...

Keyword(s):

Biomedical Engineering ◽

High Efficiency ◽

Polymeric Materials ◽

The Novel ◽

Electrode Coating ◽

Effective Response ◽

Hiv Drugs ◽

New Generation ◽

New Compounds ◽

Anti Hiv

In this review, the unique properties of intrinsically conducting polymer (ICP) in biomedical engineering fields are summarized. Polythiophene and its valuable derivatives are known as potent materials that can broadly be applied in biosensors, DNA, and gene delivery applications. Moreover, this material plays a basic role in curing and promoting anti-HIV drugs. Some of the thiophene’s derivatives were chosen for different experiments and investigations to study their behavior and effects while binding with different materials and establishing new compounds. Many methods were considered for electrode coating and the conversion of thiophene to different monomers to improve their functions and to use them for a new generation of novel medical usages. It is believed that polythiophenes and their derivatives can be used in the future as a substitute for many old-fashioned ways of creating chemical biosensors polymeric materials and also drugs with lower side effects yet having a more effective response. It can be noted that syncing biochemistry with biomedical engineering will lead to a new generation of science, especially one that involves high-efficiency polymers. Therefore, since polythiophene can be customized with many derivatives, some of the novel combinations are covered in this review.

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The Bacterial Enzyme Cas13 Interferes with Neurite Outgrowth from Cultured Cortical Neurons

Toxins ◽

10.3390/toxins13040262 ◽

2021 ◽

Vol 13 (4) ◽

pp. 262

Author(s):

Qin-Wei Wu ◽

Josef P. Kapfhammer

Keyword(s):

Rna Editing ◽

Cortical Neurons ◽

High Efficiency ◽

Primary Cultures ◽

Cultured Neurons ◽

Therapeutic Tool ◽

Bacterial Enzyme ◽

Rna Targeting ◽

Cultured Cortical Neurons ◽

New Generation

The CRISPR-Cas13 system based on a bacterial enzyme has been explored as a powerful new method for RNA manipulation. Due to the high efficiency and specificity of RNA editing/interference achieved by this system, it is currently being developed as a new therapeutic tool for the treatment of neurological and other diseases. However, the safety of this new generation of RNA therapies is still unclear. In this study, we constructed a vector expressing CRISPR-Cas13 under a constitutive neuron-specific promoter. CRISPR-Cas13 from Leptotrichia wadei was expressed in primary cultures of mouse cortical neurons. We found that the presence of CRISPR-Cas13 impedes the development of cultured neurons. These results show a neurotoxic action of Cas13 and call for more studies to test for and possibly mitigate the toxic effects of Cas13 enzymes in order to improve CRISPR-Cas13-based tools for RNA targeting.

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Industrial Sewing Machine Design and Development of Digital Design and Simulation Platform

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.365-366.917 ◽

2013 ◽

Vol 365-366 ◽

pp. 917-920

Author(s):

De Fa Zhang ◽

Yi Cong Gao

Keyword(s):

Energy Saving ◽

High Performance ◽

High Efficiency ◽

Machine Intelligence ◽

Digital Design ◽

Machine Design ◽

Design And Development ◽

Sewing Machine ◽

Great Leap Forward ◽

New Generation

In recent years, industrial sewing machine intelligence can be increased. Compared with the traditional equipment, the new generation of domestic equipment in the "high efficiency, energy saving, special" has realized great-leap-forward development. In the performance, will towards high precision, high efficiency, high performance, intelligent direction; in function, to the miniaturization, multi-function direction; in the program, to the systematic, integrated direction. The design and development of industrial sewing machine digitization design packaging platform are discussed.

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Efficiency Evaluation of the Ejector Cooling Cycle using a New Generation of HFO/HCFO Refrigerant as a R134a Replacement

Energies ◽

10.3390/en11082136 ◽

2018 ◽

Vol 11 (8) ◽

pp. 2136 ◽

Cited By ~ 11

Author(s):

Bartosz Gil ◽

Jacek Kasperski

Keyword(s):

High Efficiency ◽

Coefficient Of Performance ◽

Condensation Temperature ◽

Evaporation And Condensation ◽

Wide Range ◽

Theoretical Investigations ◽

Maximum Coefficient ◽

C 30 ◽

New Generation ◽

And Control

Theoretical investigations of the ejector refrigeration system using hydrofluoroolefins (HFOs) and hydrochlorofluoroolefin (HCFO) refrigerants are presented and discussed. A comparative study for eight olefins and R134a as the reference fluid was made on the basis of a one-dimensional model. To facilitate and extend the possibility of comparing our results, three different levels of evaporation and condensation temperature were adopted. The generator temperature for each refrigerant was changed in the range from 60 °C to the critical temperature for a given substance. The performed analysis shown that hydrofluoroolefins obtain a high efficiency of the ejector system at low primary vapor temperatures. For the three analyzed sets of evaporation and condensation temperatures (te and tc equal to 0 °C/25 °C, 6 °C/30 °C, and 9 °C/40 °C) the maximum Coefficient of Performance (COP) was 0.35, 0.365, and 0.22, respectively. The best performance was received for HFO-1243zf and HFO-1234ze(E). However, they do not allow operation in a wide range of generator temperatures, and, therefore, it is necessary to correctly select and control the operating parameters of the ejector.

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MEs in Nano-Medicine

Mechanical Engineering ◽

10.1115/1.2012-jun-3 ◽

2012 ◽

Vol 134 (06) ◽

pp. 36-41

Author(s):

Guy M. Genin ◽

Ram V. Devireddy

Keyword(s):

Tissue Engineering ◽

Regenerative Medicine ◽

Osteogenesis Imperfecta ◽

High Efficiency ◽

Medical Diagnostics ◽

Imperial College ◽

Current Generation ◽

The Core ◽

Nano Medicine ◽

New Generation

This article reviews the use of mechanical engineering techniques in the field of nano-engineered medicines. Nano-engineered solutions now exist for a range of medical diagnostics, therapeutics, and imaging, and are at the core of many of the current generation of regenerative medicine and tissue engineering strategies. Nanoparticles can be developed to absorb energy with high efficiency from photons of certain frequency ranges. The ability to understand specific diseases such as osteogenesis imperfecta based upon such fundamental analyses has been demonstrated by ASME member Sandra Shefelbine of Imperial College London in collaboration with the Buehler group. The tools of nanotechnology have enabled mechanical engineers to engineer the beginnings of an entirely new generation of cures and therapies, and this article has discussed just a sample. In order to serve as a forum for discussion of these advances ASME is recommissioning the Journal of Nanotechnology in Engineering and Medicine.

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Functional role of carbohydrate residues in human immunoglobulin G and therapeutic monoclonal antibodies

Biochemistry (Moscow) ◽

10.1134/s0006297916080058 ◽

2016 ◽

Vol 81 (8) ◽

pp. 835-857 ◽

Cited By ~ 7

Author(s):

Y. L. Dorokhov ◽

E. V. Sheshukova ◽

E. N. Kosobokova ◽

A. V. Shindyapina ◽

V. S. Kosorukov ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Immunoglobulin G ◽

Functional Role ◽

Human Immunoglobulin ◽

Human Immunoglobulin G ◽

Therapeutic Monoclonal Antibodies

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Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Cancers ◽

10.3390/cancers12010015 ◽

2019 ◽

Vol 12 (1) ◽

pp. 15 ◽

Cited By ~ 9

Author(s):

Francesca Bonello ◽

Roberto Mina ◽

Mario Boccadoro ◽

Francesca Gay

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Monoclonal Antibodies ◽

T Cell ◽

Plasma Cells ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Promising Target ◽

Therapeutic Monoclonal Antibodies ◽

Antibody Drug

Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs®), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.

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Gas Turbine Exhaust Expansion Joints, Diverter and Damper Designs for the New Generation of Higher Temperature, High Efficiency Gas Turbines

Volume 4: Heat Transfer; Electric Power; Industrial and Cogeneration ◽

10.1115/89-gt-173 ◽

1989 ◽

Author(s):

Lothar Bachmann ◽

W. Fred Koch

Keyword(s):

Gas Turbine ◽

Gas Turbines ◽

High Efficiency ◽

Combined Cycle ◽

Operating Conditions ◽

High Mass ◽

Expansion Joints ◽

Gas Turbine Exhaust ◽

New Generation ◽

Turbine Exhaust

The purpose of this paper is to update the industry on the evolutionary steps that have been taken to address higher requirements imposed on the new generation combined cycle gas turbine exhaust ducting expansion joints, diverter and damper systems. Since the more challenging applications are in the larger systems, we shall concentrate on sizes from nine (9) square meters up to forty (40) square meters in ducting cross sections. (Reference: General Electric Frame 5 through Frame 9 sizes.) Severe problems encountered in gas turbine applications for the subject equipment are mostly traceable to stress buckling caused by differential expansion of components, improper insulation, unsuitable or incompatible mechanical design of features, components or materials, or poor workmanship. Conventional power plant expansion joints or dampers are designed for entirely different operating conditions and should not be applied in gas turbine applications. The sharp transients during gas turbine start-up as well as the very high temperature and high mass-flow operation conditions require specific designs for gas turbine application.

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