I\u27m Simply Crazy Over You

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Monoclonal Antibody Production and Purification

Monoclonal antibody (mAb) therapy is a form of immunotherapy that uses mAbs to bind mono-specifically to certain cells or proteins. This may then stimulate the patient\u27s immune system to attack those cells. MAbs are currently used to treat medical conditions such as cancer, diabetes, arthritis, psoriasis, and Crohn’s Disease, but have the potential to treat countless diseases and disorders. In 2015, the mAb market was valued at $85.4 billion, and is expected to reach$138.6 billion by 2024.1 In manufacturing, mAbs are typically produced in suspension in a series of fed-batch bioreactors using genetically engineered cells originally obtained from Chinese Hamster Ovaries (CHO).2 In this proposal, two upstream bioreactor designs were analyzed for economic comparison given an annual production goal of 100 kg of mAb, with the first design culminating in a 20,000 L volume at low mAb titer and the second design culminating with a 2,000 L volume at high mAb titer. Following upstream mAb production, the protein was purified to meet clinical FDA standards using a series of downstream purification techniques, including centrifugation, filtration, and chromatography. The two designs can be modeled for both an on-patent and off-patent mAb in order to ensure long-term economic viability. In this project, the drug was modeled based on Ocrevus (ocrelizumab), a humanized therapeutic mAb brought to market in 2017 that targets a CD20-positive B cell to treat the symptoms of both primary progressive and relapsing Multiple Sclerosis.3 For an off-patent drug, it is recommended that the mAb be priced at $35,000 per 1200 mg annual treatment in order to earn a 15$65,000 per 1200 mg treatment should be used to recover the R&D costs of developing a new drug and sunk cost of past unsuccessful drugs. After analyzing both designs, it was concluded that the second, smaller design scheme is more scalable, less risky, and more cost effective for the production of both the on- and off-patent drugs

Fortran 90 implementation of the Hartree-Fock approach within the CNDO/2 and INDO models

Despite the tremendous advances made by the ab initio theory of electronic structure of atoms and molecules, its applications are still not possible for very large systems. Therefore, semi-empirical model Hamiltonians based on the zero-differential overlap (ZDO) approach such as the Pariser-Parr-Pople, CNDO, INDO, etc. provide attractive, and computationally tractable, alternatives to the ab initio treatment of large systems. In this paper we describe a Fortran 90 computer program developed by us, that uses CNDO/2 and INDO methods to solve Hartree-Fock(HF) equation for molecular systems. The INDO method can be used for the molecules containing the first-row atoms, while the CNDO/2 method is applicable to those containing both the first-, and the second-row, atoms. We have paid particular attention to computational efficiency while developing the code, and, therefore, it allows us to perform calculations on large molecules such as C_60 on small computers within a matter of seconds. Besides being able to compute the molecular orbitals and total energies, our code is also able to compute properties such as the electric dipole moment, Mulliken population analysis, and linear optical absorption spectrum of the system. We also demonstrate how the program can be used to compute the total energy per unit cell of a polymer. The applications presented in this paper include small organic and inorganic molecules, fullerene C_60, and model polymeric systems, viz., chains containing alternating boron and nitrogen atoms (BN chain), and carbon atoms (C chain).Comment: 29 pages, 3 figures, to appear in Computer Physics Communication

When Reintroductions are Augmentations: The Genetic Legacy of Fishers (Martes Pennanti) in Montana

Fishers (Martes pennanti) were purportedly extirpated from Montana by 1930 and extant populations are assumed to be descended from translocated fishers. To determine the lineage of fisher populations, we sequenced 2 regions of the mitochondrial DNA genome from 207 tissue samples from British Columbia, Minnesota, Wisconsin, and Montana. In northwestern Montana, fishers share haplotypes with samples from the upper Midwest and British Columbia; in west-central Montana, we detected haplotypes found in British Columbia samples, but also detected a control region and cytochrome-b haplotype not found in source populations. Based on the unique haplotypes found in west-central Montana, we propose that individuals with these haplotypes are descended from a relic population. Fishers in northwestern Montana are likely descended from fishers from the Midwest and British Columbia

The Lower Critical Dimension of the XY Spin Glass

We investigate the XY spin-glass model in two and three dimensions using the domain-wall renormalization-group method. The results for systems of linear sizes up to L=12 (2D) and L=8 (3D) strongly suggest that the lower critical dimension for spin-glass ordering may be $d_{c}\approx 3$ rather than four as is commonly believed. Our 3D data favor the scenario of a low but finite spin-glass ordering temperature below the chiral transition but they are also compatible with the system being at or slightly below its lower critical dimension.Comment: 4 pages, 3 ps figures. Typos have been corrected, one reference has been added and the concluding paragraph has been expanded. To appear in Phys. Rev. Let

1-(5-Carboxy­pent­yl)-2,3,3-trimethyl-3H-indol-1-ium bromide monohydrate

In the title compound, C17H24NO2 +·Br−·H2O, the pentyl group chain in the cation extends nearly perpendicular [N—C—C—C = −64.4 (3)°] to the mean plane of the indole ring with the carboxyl end group twisted such that the dihedral angle between the mean planes of the indole and carb­oxy groups measures 43.2 (4)°. Both ions in the salt form inter­molecular hydrogen bonds (O—H⋯Br and O—H⋯O) with the water mol­ecule. As a result of the Br⋯H—O—H⋯Br inter­actions, a zigzag chain is formed in the c-axis direction. The crystal packing is influenced by the collective action of the O—H⋯O and O—H⋯Br inter­molecular inter­actions as well as π–π stacking inter­molecular inter­actions between adjacent benzyl rings of the indole group [centroid–centroid distance = 3.721 (13) Å] and inter­molecular C—H⋯π inter­actions between a methyl hydrogen and the benzyl ring of the indole group. The O—H⋯Br inter­actions form a distorted tetra­hedral array about the central Br atom. A MOPAC AM1 calculation provides support to these observations

Numerical Study of Spin and Chiral Order in a Two-Dimensional XY Spin Glass

The two dimensional XY spin glass is studied numerically by a finite size scaling method at T=0 in the vortex representation which allows us to compute the exact (in principle) spin and chiral domain wall energies. We confirm earlier predictions that there is no glass phase at any finite T. Our results strongly support the conjecture that both spin and chiral order have the same correlation length exponent $\nu \approx 2.70$. We obtain preliminary results in 3d.Comment: 4 pages, 2 figures, revte