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2021 ◽  
Author(s):  
Richard W. Shuai ◽  
Jeffrey A. Ruffolo ◽  
Jeffrey J. Gray

Successful development of monoclonal antibodies (mAbs) for therapeutic applications is hindered by developability issues such as low solubility, low thermal stability, high aggregation, and high immunogenicity. The discovery of more developable mAb candidates relies on high-quality antibody libraries for isolating candidates with desirable properties. We present Immunoglobulin Language Model (IgLM), a deep generative language model for generating synthetic libraries by re-designing variable-length spans of antibody sequences. IgLM formulates antibody design as an autoregressive sequence generation task based on text-infilling in natural language. We trained IgLM on approximately 558M antibody heavy- and light-chain variable sequences, conditioning on each sequence's chain type and species-of-origin. We demonstrate that IgLM can be applied to generate synthetic libraries that may accelerate the discovery of therapeutic antibody candidates


2021 ◽  
Vol 2 (2) ◽  
pp. 390-402
Author(s):  
Mohamed GHONİMY

The mathematical analysis for estimating the performance rate "RP" of chain-type trenching machine was studied. The mathematical analysis ended with an equation for this type. This mathematical equation was checked under different operating conditions. The practical study of the performance rate showed that the deviation of the theoretical performance rate from the actual performance rate ranged from -3.4 to +2% only for the 150.7 cm and 120.7 cm trench depth respectively. The machine field efficiency ranged from 46.7 to 57% for the 150.7 cm and 120.7 cm depth respectively. It also showed an increase in machine field efficiency by decreasing the trench depth.


2021 ◽  
Author(s):  
Adedayo Oke Adelakun

Abstract OPCL Coupling of Integer-order and fractional-order Sprott-A systems using off-shelf components are constructed. Fractance configurations such as chain-type and tree-type were designed using a fractional-order capacitor and fractional-order resistor, respectively. The simulation results of the coupled circuits reveal the transition between complete synchronization (CS) to Anti-synchronization (AS) and vice versa via Amplitude death (AD).


2021 ◽  
Vol 38 (1) ◽  
Author(s):  
Shanshan Zhu ◽  
Chao Yang ◽  
Wei Li ◽  
Meilin Lin

Objectives: To investigate the value of urine immunofixation electrophoresis in prognostic evaluation of hematopoietic stem cell transplantation in patients with myeloma. Methods: Thirty-four patients with multiple myeloma admitted to Affiliated Hospital of Hebei University from November 2013 to December 2014 were included as research subjects. All patients received hematopoietic stem cell transplantation and were followed up for five years. Outcomes were evaluated according to the recovery status: complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), and progression disease (PD). In addition, the overall response rate (CR+VGPR) of patients was observed and their urine immunoglobulin status was measured by immunofixation electrophoresis. The Kaplan-Meier method was utilized to plot the survival curve, and the Log-rank method was adopted to analyze the relationship between CR+VGPR and PR and hematopoietic stem cell transplantation (HSCT) survival in patients with myeloma. Results: The basic clinical type of immunofixation electrophoresis was as follows: 19 cases (55.88%) of IgG, 7 cases (20.59%) of IgA, 6 cases (17.65%) of IgM, and 2 cases (5.88%) of light chain type. Outcomes: 13 cases (38.24%) of CR, 12 cases (35.29%) of VGPR, 9 cases (26.47%) of PR, and 25 cases (73.53%) of the overall response rate (CR+VGPR). Compared with IgG, CR, VGPR and PR of IgA, IgM and light chain had statistically significant differences in outcome (p<0.05), and CR+VGPR of patients with IgG was higher than that of patients with IgA, IgM and light chain type (p<0.05). Two of the 34 patients were lost to follow-up. The log-rank analysis showed that the survival rate of patients with CR+VGPR was higher than that of patients with PR (p<0.05). Patients with IgA, IgM, and light chain type had an increased number of prognostic death compared with those with IgG (p<0.05). Conclusion: Patients with IgG type myeloma are superior to those with IgA, IgM and light chain type in terms of the prognosis of hematopoietic stem cell transplantation, which has a certain clinical reference value. doi: https://doi.org/10.12669/pjms.38.1.4425 How to cite this:Zhu S, Yang C, Li W, Lin M. Application of urine immunofixation electrophoresis in prognostic evaluation of hematopoietic stem cell transplantation in patients with myeloma. Pak J Med Sci. 2022;38(1):315-319. doi: https://doi.org/10.12669/pjms.38.1.4425 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2021 ◽  
Vol 275 ◽  
pp. 119075
Author(s):  
Chao Wang ◽  
Junbin Liao ◽  
Junhua Li ◽  
Quan Chen ◽  
Huimin Ruan ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2706
Author(s):  
Yasuhiro Fuseya ◽  
Kazuhiro Iwai

The ubiquitin system modulates protein functions by decorating target proteins with ubiquitin chains in most cases. Several types of ubiquitin chains exist, and chain type determines the mode of regulation of conjugated proteins. LUBAC is a ubiquitin ligase complex that specifically generates N-terminally Met1-linked linear ubiquitin chains. Although linear ubiquitin chains are much less abundant than other types of ubiquitin chains, they play pivotal roles in cell survival, proliferation, the immune response, and elimination of bacteria by selective autophagy. Because linear ubiquitin chains regulate inflammatory responses by controlling the proinflammatory transcription factor NF-κB and programmed cell death (including apoptosis and necroptosis), abnormal generation of linear chains can result in pathogenesis. LUBAC consists of HOIP, HOIL-1L, and SHARPIN; HOIP is the catalytic center for linear ubiquitination. LUBAC is unique in that it contains two different ubiquitin ligases, HOIP and HOIL-1L, in the same ligase complex. Furthermore, LUBAC constitutively interacts with the deubiquitinating enzymes (DUBs) OTULIN and CYLD, which cleave linear ubiquitin chains generated by LUBAC. In this review, we summarize the current status of linear ubiquitination research, and we discuss the intricate regulation of LUBAC-mediated linear ubiquitination by coordinate function of the HOIP and HOIL-1L ligases and OTULIN. Furthermore, we discuss therapeutic approaches to targeting LUBAC-mediated linear ubiquitin chains.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Lei Hua ◽  
Zhong Yang ◽  
Jiyou Shao ◽  
Dan Jin

In the formation process of innovation networks, the level of preferential attachment between agents has an important impact on the resulting structural and functional characteristics of a network. A simulation model of innovation networks with variable preferential levels of attachment is established to study these impacts. Negative preferences tend to form chain-type structures, while positive preferences tend to form star-type structures. Furthermore, a simulation process of innovation is added to the network model to test the impact of the resulting structures on innovation efficiency. For explorative innovation, the structure with unbiased preference has the fastest innovation speed, but the structures with strong positive preference show lower innovation costs. For exploitive innovation, strong negative preferences generate the fastest innovation speed and relatively low cost, while strong positive preferences show a slightly lower cost than negative preference structures but a much lower innovation speed. Finally, some internal mechanisms of the results are discussed.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2121
Author(s):  
Emma I. Kane ◽  
Kelly L. Waters ◽  
Donald E. Spratt

Neurodegeneration has been predominantly recognized as neuronal breakdown induced by the accumulation of aggregated and/or misfolded proteins and remains a preliminary factor in age-dependent disease. Recently, critical regulating molecular mechanisms and cellular pathways have been shown to induce neurodegeneration long before aggregate accumulation could occur. Although this opens the possibility of identifying biomarkers for early onset diagnosis, many of these pathways vary in their modes of dysfunction while presenting similar clinical phenotypes. With selectivity remaining difficult, it is promising that these neuroprotective pathways are regulated through the ubiquitin-proteasome system (UPS). This essential post-translational modification (PTM) involves the specific attachment of ubiquitin onto a substrate, specifically marking the ubiquitin-tagged protein for its intracellular fate based upon the site of attachment, the ubiquitin chain type built, and isopeptide linkages between different ubiquitin moieties. This review highlights both the direct and indirect impact ubiquitylation has in oxidative stress response and neuroprotection, and how irregularities in these intricate processes lead towards the onset of neurodegenerative disease (NDD).


Author(s):  
Jiacheng Wu ◽  
Haibo Wan ◽  
Shiyuan Zhou ◽  
Peiyang Gu ◽  
Yutao Zhu ◽  
...  
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