Purification and analytical characterization of an anti- CD4 monoclonal antibody for human therapy

A purification process for the monclonal anti-CD4 antibody MAX.16H5 was developed on an analytical scale using (NH&SO, precipitation, anion-exchange chromatography on MonoQ or Q-Sepharose, hydrophobic interaction chromatography on phenyl- Sepharose and gel filtration chromatography on Superdex 200. The purification schedule was scaled up and gram amounts of MAX.16H5 were produced on corresponding BioPilot columns. Studies of the identity, purity and possible contamination by a broad range of methods showed that the product was highly purified and free from contaminants such as mouse DNA, viruses, pyrogens and irritants. Overall, the analytical data confirm that the monoclonal antibody MAX.16H5 prepared by this protocol is suitable for human therapy

Charge Transfer in Partition Theory

The recently proposed Partition Theory (PT) [J.Phys.Chem.A 111, 2229 (2007)] is illustrated on a simple one-dimensional model of a heteronuclear diatomic molecule. It is shown that a sharp definition for the charge of molecular fragments emerges from PT, and that the ensuing population analysis can be used to study how charge redistributes during dissociation and the implications of that redistribution for the dipole moment. Interpreting small differences between the isolated parts' ionization potentials as due to environmental inhomogeneities, we gain insight into how electron localization takes place in H2+ as the molecule dissociates. Furthermore, by studying the preservation of the shapes of the parts as different parameters of the model are varied, we address the issue of transferability of the parts. We find good transferability within the chemically meaningful parameter regime, raising hopes that PT will prove useful in chemical applications.Comment: 12 pages, 16 figure

Pengaruh Karakteristik Pekerjaan, Kompensasi, Dan Kepuasan Kerja Terhadap Produktivitas Kerja Karyawan Pada CV. Ibu Sri “Tilung” Di Boyolali

The purpose of this study is to determine the effect of labor characteristics, compensation, and job satisfaction on employee productivity in CV Ibu Sri Tilung. This study also aims to determine jointly the influence of the three independent variables to the dependent variable. The type of research is quantitative research, with a sample of 35 respondents. Sampling using convinience-purposive sampling technique. Techniques of collecting research data through questionnaires with Likert scale. Data analysis methods used were validity test, reliability test, classical assumption test, and multiple linier regression analysis test. The result showed that both the partial and simultaneous variables influence the characteristics of labor, compensation and job satisfaction have a positive and significant effect on employee work productivity. In the determinant coefficient (R ²), the result is 0.918, it means that the variable of labor characteristics (X1), compensation (X2), and job satisfaction (X3) are able to explain the work productivity (Y) variable of 0.918 or 91.8%, and the rest can be explained variable other outside the research model

Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

*S Supporting Information ABSTRACT: Two nicotinamide adenine dinucleotide (NAD +) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD + (6-N-methyl nicotinamide adenosine 5′-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5′-diphosphoribose, 11), whereas 6-thio NHD + (nicotinamide 6-mercaptopurine 5′-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5′-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5′-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1cIDPR-induced Ca 2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5′-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling

How do changes along the risk chain affect flood risk?

Flood risk is impacted by a range of physical and socio-economic processes. Hence, the quantification of flood risk ideally considers the complete flood risk chain, from atmospheric processes through catchment and river system processes to damage mechanisms in the affected areas. Although it is generally accepted that a multitude of changes along the risk chain can occur and impact flood risk, there is a lack of knowledge of how and to what extent changes in influencing factors propagate through the chain and finally affect flood risk. To fill this gap, we present a comprehensive sensitivity analysis which considers changes in all risk components, i.e. changes in climate, catchment, river system, land use, assets, and vulnerability. The application of this framework to the mesoscale Mulde catchment in Germany shows that flood risk can vary dramatically as a consequence of plausible change scenarios. It further reveals that components that have not received much attention, such as changes in dike systems or in vulnerability, may outweigh changes in often investigated components, such as climate. Although the specific results are conditional on the case study area and the selected assumptions, they emphasize the need for a broader consideration of potential drivers of change in a comprehensive way. Hence, our approach contributes to a better understanding of how the different risk components influence the overall flood risk.</p

Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation

Nicotinic acid adenine dinucleotide phosphate (NAADP) has been implicated as an initial Ca(2+) trigger in T cell Ca(2+) signalling, but its role in formation of the immune synapse in CD4(+) effector T cells has not been analysed. CD4(+) T cells are activated by the interaction with peptide-MHCII complexes on the surface of antigen-presenting cells. Establishing a two-cell system including primary rat CD4(+) T cells specific for myelin basic protein and rat astrocytes enabled us to mirror this activation process in vitro and to analyse Ca(2+) signalling, cell shape changes and motility in T cells during formation and maintenance of the immune synapse. After immune synapse formation, T cells showed strong, antigen-dependent increases in free cytosolic calcium concentration ([Ca(2+)](i)). Analysis of cell shape and motility revealed rounding and immobilization of T cells depending on the amplitude of the Ca(2+) signal. NAADP-antagonist BZ194 effectively blocked Ca(2+) signals in T cells evoked by the interaction with antigen-presenting astrocytes. BZ194 reduced the percentage of T cells showing high Ca(2+) signals thereby supporting the proposed trigger function of NAADP for global Ca(2+) signalling. Taken together, the NAADP signalling pathway is further confirmed as a promising target for specific pharmacological intervention to modulate T cell activation

The 2021 FASEB science research conference on NAD metabolism and signaling

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