Diamines prevent thermal aggregation and inactivation of lysozyme

Protein aggregation is a major obstacle in both biological applications and biomedical fields involving proteins. In this study, we investigated the essential structure of small additives that function as chemical chaperones. Aggregation-suppressing competent additives were 1,3-diaminopropane, 1,4-diaminobutane, and 1,5-diaminopentane, which suppressed aggregation in the given order; whereas no diols or monoamines prevented the thermal aggregation and the inactivation of lysozyme. The heat-inactivation rate of lysozyme with 1,3-diaminopropane was almost identical to that of lysozyme with spermine and arginine ethylester, which are the most prominent additives reported yet.     

Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.     

Constrained Load Flow Using Recursive Quadratic Programming

The present paper will discuss the efficient, practical and definitive algorithm for dealing with constrained load flow problems. Algorithms based on mathematical programming and algorithms based on the load flow calculation methods have been studied since earlier days. However, on account of numerous control variables to be determined and of inadequate calculating efficiency, the guarantee of unfailing solution is yet to be achieved. In the calculating procedure herein described the extents of adjustments are not determined simultaneously for all the control variables ; the control variables considered likely to produce greater adjusting effect are selected one by one and are adjusted successively. This adjustment method, as a consequence, is useful not only for on-line power system operation but also as simulator software for training system operators.     

Contribution of protein-surface ion pairs of a hyperthermophilic protein on thermal and thermodynamic stability

Hyperthermophilic proteins possess many ion pairs on their surface. To reveal the role of the ion pairs, O6-methylguanine-DNA methyltransferase from Thermococcus kodakaraensis KOD1 (Tk-MGMT) was studied as a model protein. The maximum free-energy changes of the protein in 0.1 and 0.5 M NaCl at pH 7.0 were 61.7 kJ mol(-1) at 31.5 degrees C and 77.4 kJ mol(-1) at 39.7 degrees C, respectively. On the other hand, mid points of the thermal unfolding temperatures in 0.1 and 0.5 M NaCl at pH 7.0 were 94.8 degrees C and 90.1 degrees C, respectively. The results suggest that the protein-surface ion pairs contribute to thermal stability (Tm), rather than thermodynamic stability (DeltaG).     

Biophysical analysis of heat-induced structural maturation of glutamate dehydrogenase from a hyperthermophilic archaeon

Tertiary structure of the recombinant glutamate dehydrogenase from Thermococcus kodakaraensis KOD1 (Tk-rGDH) converts into an intact form induced by the heat treatment. This phenomenon, heat-induced structural maturation, means that high temperature plays an important role in the proper folding and oligomerization of Tk-rGDH. In this work, we analyzed the heat-induced structural maturation of Tk-rGDH by differential scanning microcalorimetry (DSC), circular dichroism (CD), and activity measurements. In DSC measurements, the peak of adsorption of non-heated Tk-rGDH (nh-Tk-rGDH) was two times smaller than that of Tk-rGDH heated at 70 degrees C for 30 min (h-Tk-rGDH). The transition temperature (T(m)) of h-Tk-rGDH was 115 degrees C, which was about 3 degrees C higher than that of nh-Tk-rGDH. In the presence of 0.5 M NaCl, the nh-Tk-rGDH showed two peaks at 107 degrees C and 114 degrees C, while the h-Tk-rGDH showed a single peak at 115.7 degrees C. The heat-induced conformational change process was monitored by changes in CD intensity at 222 nm, and the result showed that heat-induced structural maturation is irreversible. The heat treatment at 70 degrees C showed the highest enhancement in activity, which was 15% larger than that of heat-treated Tk-rGDH at 40 degrees C. The results indicate that heat-induced structural maturation involves an irreversible process, transforming the non-heated form to the stable and active form.     

Extended Study of the Classification of Dopamine Receptor Agonists and Antagonists using a TFS-based Support Vector Machine

We previously investigated the classification and prediction of dopamine D1 receptor agonists and antagonists using a topological fragment spectra (TFS)-based support vector machine (SVM), in which the dataset contained noise compounds that had no D1 receptor activity. This work extended the dataset to seven activity classes (dopamine D1, D2, and auto-receptor agonists, and D1, D2, D3, and D4 antagonists) and increased the noise ratio to ten times that of active compounds. In total, this study used 16,008 compounds for training and 1,779 compounds for prediction. The TFS-based SVM gave good, stable results for both classification and prediction, even in the case that included ten times the noise data. The resulting model correctly predicted 97.6% of the prediction set of 1,779 compounds.     

An algorithm for discrete optimal power flow

This paper presents a new algorithm to solve an optimal power flow problem which can take into consideration the discrete nature of some facilities in power systems. The optimal power flow problem is formulated as a nonlinear mixed-integer programming problem in which the number of transformer taps and the number of shunt capacitor units and reactor units are treated as discrete variables. This paper attempts to solve such a large-scale nonlinar mixed-integer programming problem by some effective programming techniques. The optimization procedure of the algorithm is that the nonlinear mixed-integer programming problem is linearized iteratively and solved by an approximation method for linear mixed-integer programming. A fundamental feature of the algorithm is that it can guarantee a solution which is discrete, feasible and near-optimal. The validity and efficiency of the algorithm is demonstrated by the numerical results of real-scale optimal power flow problems.     

Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy (IPL), a disease presenting with polyclonal hypergammaglobulinemia and a sheet-like proliferation of mature plasma cells in the lymph nodes. Some researchers consider IPL to be a part of iMCD-NOS, although it has not been clearly defined to date. This is the first paper to analyze iMCD-NOS clinicopathologically, to examine whether IPL forms a uniform disease unit in iMCD. Histologically, the IPL group showed prominent plasmacytosis and the hyperplasia of germinal centers, while the non-IPL group showed prominent vascularity. Clinically, the IPL group showed significant thrombocytosis and elevated serum IgG levels compared to the non-IPL group (p = 0.007, p < 0.001, respectively). Pleural effusion and ascites were less common in the IPL group (p < 0.001). The IPL group was more likely to have an indolent clinical course and a good response to the anti-IL-6 receptor antibody, while the non-IPL counterpart frequently required more aggressive medical interventions. Thus, the IPL group is a clinicopathologically uniform entity that forms an independent subtype of iMCD.     

A VAR planning method with multiple power-flow states

The goal of reactive power (VAR) planning is to find the minimum cost installation plan of new reactive power sources so that the system voltage is maintained within an acceptable level. The consideration of multiple contingency states, together with the discrete nature of VAR facilities, creates a large-scale nonlinear mixed-integer programming (MIP) problem. To overcome the discrete nature of VAR facilities, an approximate method for the MIP problem is employed since the method is linear-programming based and thus efficient for large-scale problems. To treat the multiple contingencies, a resource directive decomposition approach is used in the proposed algorithm. If the number of installed VAR sources is fixed, the overall problem can be reduced to independent subproblems. Then subproblems are coordinated to give a VAR installation pattern in which installation cost becomes less than before. The algorithm proposed is tested for a 135-node real-size system and the results show the validity and effectiveness of the algorithm.