Production Cross Research Articles

Tensor of Order Two and Geometric Properties of 2D Metric Space

A 2D metric space has a limited number of properties through which it can be described. This metric space may comprise objects such as a scalar, a vector, and a rank-2 tensor. The paper provides a comprehensive description of relations between objects in 2D space using the matrix product of vectors, geometric product, and dot product of complex numbers. These relations are also an integral part of the Lagrange’s identity. The entire structure of derived theoretical relationships describing properties of 2D space draws on the Lagrange’s identity. The description of how geometric algebra and tensor calculus are interconnected is given here in a comprehensive and essentially clear manner, which is the main contribution of this paper. A new term in this regard is the total geometric and matrix product, which—in a simple manner—predetermines and defines the existence of differential relations such as the gradient, the divergence, and the curl of a vector field. In addition, geometric interpretation of tensors is pointed out, expressed through angular parameters known from the literature as a tensor glyph. This angular interpretation of the tensor has an unequivocal analytical form, and the paper shows how it is linked to the classical tensor denoted by indices.

On Some Examples of Trajectories in R7

In this paper we study the magnetic trajectories as the solutions of the Lorentz equation defined by the cross product corresponding to the 7-dimensional Euclidean space. We find several examples of such trajectories and moreover, we strongly motivate our results making a comparison with the 3-dimensional Euclidean case, ambient space which was among the first ones approached in the study of magnetic trajectories.

Versatile seamless DNA vector production in E. coli using enhanced phage lambda integrase.

Seamless DNA vectors derived from bacterial plasmids are devoid of bacterial genetic elements and represent attractive alternatives for biomedical applications including DNA vaccines. Larger scale production of seamless vectors employs engineered Escherichia coli strains in order to enable tightly regulated expression of site-specific DNA recombinases which precisely delete unwanted sequences from bacterial plasmids. As a novel component of a developing lambda integrase genome editing platform, we describe here strain MG1655-ISC as a means to easily produce different scales of seamless vectors, ranging in size from a few hundred base pairs to more than ten kilo base pairs. Since we employed an engineered lambda integrase that is able to efficiently recombine pairs of DNA crossover sites that differ in sequence, the resulting seamless vectors will be useful for subsequent genome editing in higher eukaryotes to accommodate variations in target site sequences. Future inclusion of single cognate sites for other genome targeting systems could enable modularity. These features, together with the demonstrated simplicity of in vivo seamless vector production, add to their utility in the biomedical space.

Computing high dimensional multiple integrals involving matrix exponentials

This paper deals with the numerical computation of the high dimensional multiple integrals involving matrix exponentials that can be rewritten as the product of a matrix exponential times vector. To this end, in addition to the conventional iterative methods for computing the action of the matrix exponential on a vector, iterative methods for the action of the phi-function over a vector are also considered. This is illustrated with a Krylov–Padé approximation to the product of phi-function times vector, which reveals potential for computing a variety of high dimensional multiple integrals that arise in several areas of applied mathematics, model identification, control engineering and numerical methods.

Keeping things clean The secret to successful vector production for gene therapy

Keeping things clean The secret to successful vector production for gene therapy

Greener Synthesis of Jasminaldehyde via Cross Aldol Condensation Reaction Using Recyclable Phase Transfer Catalysis and its Cosmetic Application

Jasminaldehyde or alpha amyl cinnamic aldehyde is a commonly used aroma molecule in perfume formulationsThe aldol condensation of equimolar n-heptanal and benzaldehyde in NaOH using a surfactant catalyst cetyltrimethylammonium bromide to achieve high cross aldol product Jasminaldehyde selectivity was studied. The process is highly efficient due to the recyclability of the catalyst. The process was studied for four cycles of catalyst reusability. The selectivity of the cross product was dependent on the temperature, surfactant concentration, and mixing. The olfactive profile of Jasminaldehyde obtained with 0.1 M surfactant solution was identical to the standard. Jasminaldehyde formulation was created and applied to in-home care applications.

Bicocycle double cross constructions

We introduce the notion of a bicocycle double cross product (sum) Lie group (algebra), and a bicocycle double cross product bialgebra, generalizing the unified products. On the level of Lie groups the construction yields a Lie group on the product space of two pointed manifolds, none of which being necessarily a subgroup. On the level of Lie algebras, a Lie algebra is obtained on the direct sum of two vector spaces, which are not required to be subalgebras. Finally, on the quantum level a bialgebra is obtained on the tensor product of two (co)algebras that are not necessarily sub-bialgebras.

Mono-γ production of a dark vector at future e + e − colliders* *Supported by the Innovation Capability Support Program of Shaanxi Province (2021KJXX-47), the Double First Class start-up fund (WF220442604), the Shanghai Pujiang Program (20PJ1407800), National Natural Science Foundation of China (12090064), as well as Chinese Academy of Sciences Center for Excellence in Particle Physics (CCEPP)

The associated production of a dark particle and photon, represented as a mono-γ event, is a promising channel to probe particle content and dynamics in the dark sector. In this study, we investigate the properties of the mono-γ production of vector dark matter at future colliders. Photon-like and Pauli operators as well as triple gauge boson interactions involving dark matter are considered in the framework of effective field theory. We show that, in comparison with the Pauli operator, the triple gauge boson couplings are significantly more interesting in high energy colliders. Beam polarization effects are also analyzed, and we show that the experimental sensitivities cannot be significantly enhanced because of the smaller luminosity.

Wobble of a spin stabilized satellite with cross products of inertia and magnetic attitude control

Asymmetrical spin stabilized satellite dynamics in the vicinity of the required motion is considered. The principal axis of the maximum moment of inertia slightly deviates from its assumed direction in the satellite reference frame. This is formalized in the cross products of inertia. This inertial uncertainty results in a wobble, that is undesired angular velocity components perpendicular to the rotation axis, and oscillations of this axis near the required direction. The torque-free motion is investigated first. Expressions that explicitly relate satellite inertia parameters to wobble are provided. Wobble evolution under the action of magnetic damping control is analyzed next. Its amplitude approximate exponential decay behavior and residual unavoidable wobble level are derived. These expressions are compared with numerical simulation results of nonlinear equations of motion including various disturbance sources.

Stabilizing DNA–PEI complexes improves scalability of suspension lentiviral viral vector and AAV processes

Transient transfection is a challenging and time-sensitive upstream unit operation to scale for suspension HEK293 viral vector production. For many transfection reagents, including polyethyleneimine, careful timing of mixing and hold steps is essential to process performance but challenging to maintain at relevant manufacturing scales. We first characterized the process parameters that influence polyethyleneimine transfection reagent performance and then implemented a stabilizing strategy to preserve the activity of transfection complexes when scaling. Generating a transfection complex with an average hydrodynamic diameter between 500 and 700 nm was most predictive of transient transfection productivity, measured by viral vector titer, but is very sensitive to transfection complex concentration and hold time. The addition of human serum albumin as a stabilizing agent maintained the optimal transfection complex size for extended periods of time and improved the process control for both lentiviral vector and adeno-associated viral vector suspension processes at multiple production scales.

Alleviate crucial challenges in scaling up gene therapy manufacturing

How CBM’s modular, decoupled unit operations for vector production drive larger production volumesWhat process mapping from an end-user perspective should impact design strategyHow CBM’s flexible “Partner in Plant” model facilitates in-process development and GMP operations in manufacturing suitesWhat progress needs to be made by the industry to accelerate AAV manufacturing at a large scaleEmily Moran has 16+ years in the biopharmaceutical industry having served most recently as Head of Viral Vector Manufacturing at Lonza Houston, one of the largest viral vector manufacturing operations in the world. At Lonza, managed 20+ viral vector programs resulting in the production of 80+ viral vector batches and subsequent drug product fills at 90%+ success rate including the production of 24+ cell banks and viral banks. Before joining Lonza, Emily spent 14 years focused on GMP Commercial Manufacturing at Sanofi Pasteur, where she oversaw the production of over 1,500 viral and bacterial biologics batches, 5000+ media and buffers, and 600 commercial fills delivering doses to 240M patients. Emily holds a BSc from Ursinus College and an MBA. from the New York Institute of Technology

Arithmetic for closed balls

. Inspired by circular complex interval arithmetic, an arithmetic for closed balls in ℝ n is pursued. In this sense, the properties of certain operations on closed balls in ℝ n , some of which related either to the Hadamard product of vectors or to the 2-fold vector cross product when n ∈ {3,7}, are studied. In particular, known results for operations on closed balls in ℂ, which can be identified with ℝ2, are extended to closed balls in ℝ n .

An Adenoviral Vector as a Versatile Tool for Delivery and Expression of miRNAs.

Only two decades after discovering miRNAs, our understanding of the functional effects of deregulated miRNAs in the development of diseases, particularly cancer, has been rapidly evolving. These observations and functional studies provide the basis for developing miRNA-based diagnostic markers or new therapeutic strategies. Adenoviral (Ad) vectors belong to the most frequently used vector types in gene therapy and are suitable for strong short-term transgene expression in a variety of cells. Here, we report the set-up and functionality of an Ad-based miRNA vector platform that can be employed to deliver and express a high level of miRNAs efficiently. This vector platform allows fast and efficient vector production to high titers and the expression of pri-miRNA precursors under the control of a polymerase II promoter. In contrast to non-viral miRNA delivery systems, this Ad-based miRNA vector platform allows accurate dosing of the delivered miRNAs. Using a two-vector model, we showed that Ad-driven miRNA expression was sufficient in down-regulating the expression of an overexpressed and highly stable protein. Additional data corroborated the downregulation of multiple endogenous target RNAs using the system presented here. Additionally, we report some unanticipated synergistic effects on the transduction efficiencies in vitro when cells were consecutively transduced with two different Ad-vectors. This effect might be taken into consideration for protocols using two or more different Ad vectors simultaneously.

Establishment and Extension of a Fast Descriptor for Point Cloud Registration

Point cloud registration (PCR) is a vital problem in remote sensing and computer vision, which has various important applications, such as 3D reconstruction, object recognition, and simultaneous localization and mapping (SLAM). Although scholars have investigated a variety of methods for PCR, the applications have been limited by low accuracy, high memory footprint, and slow speed, especially for dealing with a large number of point cloud data. To solve these problems, a novel local descriptor is proposed for efficient PCR. We formed a comprehensive description of local geometries with their statistical properties on a normal angle, dot product of query point normal and vector from the point to its neighborhood point, the distance between the query point and its neighborhood point, and curvature variation. Sub-features in descriptors were low-dimensional and computationally efficient. Moreover, we applied the optimized sample consensus (OSAC) algorithm to iteratively estimate the optimum transformation from point correspondences. OSAC is robust and practical for matching highly self-similar features. Experiments and comparisons with the commonly used descriptor were conducted on several synthetic datasets and our real scanned bridge data. The result of the simulation experiments showed that the rotation angle error was below 0.025° and the translation error was below 0.0035 m. The real dataset was terrestrial laser scanning (TLS) data of Sujiaba Bridge in Chongqing, China. The results showed the proposed descriptor successfully registered the practical TLS data with the smallest errors. The experiments demonstrate that the proposed method is fast with high alignment accuracy and achieves a better performance than previous commonly used methods.

Production route analysis of a therapeutic radionuclide 177Lu

177Lu is used in medical research for various radiotheragnostic applications in nuclear medicine because of its various isotope properties. In this paper, we calculated the cross sections and production yields of the Lu isotope from different reactions X+176,174Lu and X+176Lu in energy levels from 0.001 to 100 MeV by using TALYS-1.96 and EMPIRE-3.2.2. Although n, d, and t reactions show an outstanding cross-section performance, α and t reactions show very impactful integral yield data. For the potential outcomes, these estimates are analyzed by comparing them to TENDL-2019 and EMPIRE-3.2.2.

Mammalian cell lines used in bioprocessing

A various number of expressions and host systems are used in biologics manufacturing. The most commonly preferred systems are based on bacteria, yeast, mammalian cells, insect cells, and transgenic animals. A wide range of molecules, including insulin, mAbs, vaccines, and recombinant proteins, are produced using different host systems. Because of several reasons impacting the product quality and yield, mammalian cells are utilized. Moreover, mammalian cells are generally used in virus-based vaccine manufacturing. Chinese Hamster Ovary (CHO) is the most widely used cell line for high yield stable recombinant protein production, while Human Embryonic Kidney (HEK) is favoured for transient transfection low yield protein manufacturing, viral-based vaccine and gene and cell therapy-related vector production. Other mammalian cell lines such as NSO, Sp2.0, Vero, MRC-5 and PerC.6 are also used in both recombinant protein and virus productions. Multiple modifications are carried out on industrial cell lines to make them more suitable for high yield and high-quality protein production. Thanks to these alterations, high productivity and quality levels are achieved in the biotechnology industry.

Computation of NMR shieldings at the CASSCF level using gauge-including atomic orbitals and Cholesky decomposition.

We present an implementation of coupled-perturbed complete active space self-consistent field (CP-CASSCF) theory for the computation of nuclear magnetic resonance chemical shifts using gauge-including atomic orbitals and Cholesky decomposed two-electron integrals. The CP-CASSCF equations are solved using a direct algorithm where the magnetic Hessian matrix-vector product is expressed in terms of one-index transformed quantities. Numerical tests on systems with up to about 1300 basis functions provide information regarding both the computational efficiency and limitations of our implementation.

Effect of alcohol on productivity and quality of adeno-associated virus 2 in HEK293 cells

Investigation of enhancers to improve recombinant adeno-associated virus 2 (rAAV2) productivity by human embryonic kidney 293cells (HEK293) suspension culture showed that the addition of ethanol improved the productivity and packaged genome integrity of rAAV2. Further optimization showed that adding ethanol in the range of 0.09%-1.11% (v/v) during rAAV2 production effectively improved rAAV2 productivity and quality. In addition, ethanol addition improved cell viability. Furthermore, proteome and pathway analysis of the cells during rAAV2 production showed that the addition of ethanol resulted in the upregulation of pathways related to intercellular signaling, gene expression, cell morphology, intercellular maintenance, and others. In contrast, pathways related to cell death, immunity, and reactions to infection were downregulated. These changes in pathway regulation were responsible for the improvement in rAAV2 productivity, packaged genome integrity, and cell viability during rAAV2 production. The results of this study can be applied to the production of viral vectors for invivo gene therapy in an inexpensive and safe manner.

Kinematic analysis of intelligent petrochemical fluid handling arm

In view of the low degree of automation of fluid transfer device in China's petrochemical industry, 
 this paper designs and develops an intelligent fluid transfer operator arm instead of manual 
 operation and draws its three-dimensional model based on the common structure type of 
 land-based fluid loading and unloading arm in the current market. The kinematic model of the 
 arm was developed based on the Denavit-Hartenberg method, and the forward and inverse 
 kinematics were analyzed; then the Jacobi matrix of the arm was obtained based on the 
 chi-square transformation matrix and vector product method. Finally, the positive kinematic 
 simulation was carried out by using the Robotics Toolbox toolkit in Matlab software, and the 
 conclusion that the linkage coordinate system established by the D-H method is consistent with 
 the actual structure of the manipulator arm in this paper.

Achieving better AAV vector productivity and product quality

Transient transfection of plasmids into suspension HEK293 cells is still the most commonly used method for the production of recombinant adeno-associated virus (rAAV) gene therapies – in this episode, Diane Golebiowski and Marissa Stanvick discuss ways to optimize that process.