Miracle-dz/UniFAR-FTUs huggingface dataset:
Preferential interactions of trehalose, L-arginine.HCl and sodium chloride with therapeutically relevant IgG1 monoclonal antibodies

ABSTRACT Preferential interactions of weakly interacting formulation excipients govern their effect on the equilibrium and kinetics of several reactions of protein molecules in solution. Using vapor pressure osmometry, we characterized the preferential interactions of commonly used excipients trehalose, L-arginine.HCl and NaCl with three therapeutically-relevant, IgG1 monoclonal antibodies that have similar size and shape, but differ in their surface hydrophobicity and net charge. We further characterized the effect of these excipients on the reversible self-association, aggregation and viscosity behavior of these antibody molecules. We report that trehalose, L-arginine.HCl and NaCl are all excluded from the surface of the three IgG1 monoclonal antibodies, and that the exclusion behavior is linearly related to the excipient molality in the case of trehalose and NaCl, whereas a non-linear behavior is observed for L-arginine.HCl. Interestingly, we find that the magnitude of trehalose exclusion depends upon the nature of the protein surface. Such behavior is not observed in case of NaCl and L-arginine.HCl as they are excluded to the same extent from the surface of all three antibody molecules tested in this study. Analysis of data presented in this study provides further insight into the mechanisms governing excipient-mediated stabilization of mAb formulations.
Bed-tree: an all-purpose index structure for string similarity search based on edit distance

Strings are ubiquitous in computer systems and hence string processing has attracted extensive research effort from computer scientists in diverse areas. One of the most important problems in string processing is to efficiently evaluate the similarity between two strings based on a specified similarity measure. String similarity search is a fundamental problem in information retrieval, database cleaning, biological sequence analysis, and more. While a large number of dissimilarity measures on strings have been proposed, edit distance is the most popular choice in a wide spectrum of applications. Existing indexing techniques for similarity search queries based on edit distance, e.g., approximate selection and join queries, rely mostly on n-gram signatures coupled with inverted list structures. These techniques are tailored for specific query types only, and their performance remains unsatisfactory especially in scenarios with strict memory constraints or frequent data updates. In this paper we propose the Bed-tree, a B+-tree based index structure for evaluating all types of similarity queries on edit distance and normalized edit distance. We identify the necessary properties of a mapping from the string space to the integer space for supporting searching and pruning for these queries. Three transformations are proposed that capture different aspects of information inherent in strings, enabling efficient pruning during the search process on the tree. Compared to state-of-the-art methods on string similarity search, the Bed-tree is a complete solution that meets the requirements of all applications, providing high scalability and fast response time.
Stability Analysis of an Unsupervised Competitive Neural Network

Unsupervised competitive neural networks (UCNN) are an established technique in pattern recognition for feature extraction and cluster analysis. A novel model of an unsupervised competitive neural network implementing a multi—time scale dynamics is proposed in this paper. The global asymptotic stability of the equilibrium points of this continuous—time recurrent system whose weights are adapted based on a competitive learning law is mathematically analyzed. The proposed neural network and the derived results are compared with those obtained from other multi—time scale architectures.
Lineage Relationships and Differentiation of Natural Killer (NK) T Cells: Intrathymic Selection and Interleukin (IL)-4 Production in the Absence of NKR-P1 and Ly49 Molecules

In this report, we have assessed the lineage relationships and cytokine dependency of natural killer (NK) T cells compared with mainstream TCR-αβ T cells and NK cells. For this purpose, we studied common γ chain (γc)-deficient mice, which demonstrate a selective defect in CD3− NK cell development relative to conventional TCR-αβ T cells. NK thymocytes differentiate in γc− mice as shown by the normal percentage of TCR Vβ8+ CD4−CD8− cells and the normal quantity of thymic Vα14–Jα281 mRNA that characterize the NK T repertoire. However, γc-deficient NK thymocytes fail to coexpress the NK-associated markers NKR-P1 or Ly49, yet retain characteristic expression of the cytokine receptors interleukin (IL)-7Rα and IL-2Rβ. Despite these phenotypic abnormalities, γc− NK thymocytes could produce normal amounts of IL-4. These results define a maturational progression of NK thymocyte differentiation where intrathymic selection and IL-4–producing capacity can be clearly dissociated from the acquisition of the NK phenotype. Moreover, these data suggest a closer ontogenic relationship of NK T cells to TCR-αβ T cells than to NK cells with respect to cytokine dependency. We also failed to detect peripheral NK T cells in these mice, demonstrating that γc-dependent interactions are required for export and/or survival of NK T cells from the thymus. These results suggest a stepwise pattern of differentiation for thymically derived NK T cells: primary selection via their invariant TCR to confer the IL-4–producing phenotype, followed by acquisition of NK-associated markers and maturation/export to the periphery.
The Relationship Between Big Five Model and Impulsive Buying Behaviour of Middle Income Families In Peninsular Malaysia: A Study on Post GST Implementation.

The introduction of Goods and Services Tax (GST) in Malaysia starting from 1 st April 2015 has become a new concern to every Malaysian. The middle 40 percent of the household income group (M40) as the major contributor to the national economy is widely believed to be influenced by this new taxation policy especially in their spending habits. The goal of this research is to examine the correlation between Big Five Model and impulsive buying behaviour of middle income families from Peninsular Malaysia after the implementation of GST in the country. Big Five Model is classified according to the personality traits taxonomy: openness to experience (O), conscientiousness (O), extraversion (E), agreeableness (A) and neuroticism (N) (OCEAN). A quantitative research design has been selected as the most appropriate method to collect data from the targeted respondents for this study. A response of 371 sets of questionnaire has been collected and received from the middle-income households living across Wilayah Persekutuan Putrajaya, Wilayah Persekutuan Kuala Lumpur, and Selangor. Descriptive tests such as mean, central tendency, standard deviation, frequency and percentage have been conducted to analyze the demographic characteristics of the target respondents. Using Multiple Linear Regression model, this research is useful to examine the relationship between the five independent variables (OCEAN) to one dependent variable (impulsive buying behaviour; IBB) after meeting all the given assumptions successfully.
Sox10 Cooperates with the Mediator Subunit 12 during Terminal Differentiation of Myelinating Glia

Several transcription factors are essential for terminal differentiation of myelinating glia, among them the high-mobility-group-domain-containing protein Sox10. To better understand how these factors exert their effects and shape glial expression programs, we identified and characterized a physical and functional link between Sox10 and the Med12 subunit of the Mediator complex that serves as a conserved multiprotein interphase between transcription factors and the general transcription machinery. We found that Sox10 bound with two of its conserved domains to the C-terminal region of Med12 and its close relative, Med12-like. In contrast to Med12-like, substantial amounts of Med12 were detected in both Schwann cells and oligodendrocytes. Its conditional glia-specific deletion in mice led to terminal differentiation defects that were highly reminiscent of those obtained after Sox10 deletion. In support of a functional cooperation, both proteins were jointly required for Krox20 induction and were physically associated with the critical regulatory region of the Krox20 gene in myelinating Schwann cells. We conclude that Sox10 functions during terminal differentiation of myelinating glia, at least in part by Med12-dependent recruitment of the Mediator complex.
Voltage-Gated K 1 Channel b Subunits : Expression and Distribution of Kv b 1 and Kv b 2 in Adult Rat Brain

Recent cloning of K channel b subunits revealed that these cytoplasmic polypeptides can dramatically alter the kinetics of current inactivation and promote efficient glycosylation and surface expression of the channel-forming a subunits. Here, we examined the expression, distribution, and association of two of these b subunits, Kvb1 and Kvb2, in adult rat brain. In situ hybridization using cRNA probes revealed that these b-subunit genes are heterogeneously expressed, with high densities of Kvb1 mRNA in the striatum, CA1 subfield of the hippocampus, and cerebellar Purkinje cells, and high densities of Kvb2 mRNA in the cerebral cortex, cerebellum, and brainstem. Immunohistochemical staining using subunit-specific monoclonal and affinity-purified polyclonal antibodies revealed that the Kvb1 and Kvb2 polypeptides frequently co-localize and are concentrated in neuronal perikarya, dendrites, and terminal fields, and in the juxtaparanodal region of myelinated axons. Immunoblot and reciprocal co-immunoprecipitation analyses indicated that Kvb2 is the major b subunit present in rat brain membranes, and that most K channel complexes containing Kvb1 also contain Kvb2. Taken together, these data suggest that Kvb2 is a component of almost all K channel complexes containing Kv1 a subunits, and that individual channels may contain two or more biochemically and functionally distinct b-subunit polypeptides.
Correlation between Charge Movement and Ionic Current during Slow Inactivation in Shaker K+ Channels

Prolonged depolarization induces a slow inactivation process in some K+ channels. We have studied ionic and gating currents during long depolarizations in the mutant Shaker H4-Δ(6–46) K+ channel and in the nonconducting mutant (Shaker H4-Δ(6–46)-W434F). These channels lack the amino terminus that confers the fast (N-type) inactivation (Hoshi, T., W.N. Zagotta, and R.W. Aldrich. 1991. Neuron. 7:547–556). Channels were expressed in oocytes and currents were measured with the cut-open-oocyte and patch-clamp techniques. In both clones, the curves describing the voltage dependence of the charge movement were shifted toward more negative potentials when the holding potential was maintained at depolarized potentials. The evidences that this new voltage dependence of the charge movement in the depolarized condition is associated with the process of slow inactivation are the following: (a) the installation of both the slow inactivation of the ionic current and the inactivation of the charge in response to a sustained 1-min depolarization to 0 mV followed the same time course; and (b) the recovery from inactivation of both ionic and gating currents (induced by repolarizations to −90 mV after a 1-min inactivating pulse at 0 mV) also followed a similar time course. Although prolonged depolarizations induce inactivation of the majority of the channels, a small fraction remains non–slow inactivated. The voltage dependence of this fraction of channels remained unaltered, suggesting that their activation pathway was unmodified by prolonged depolarization. The data could be fitted to a sequential model for Shaker K+ channels (Bezanilla, F., E. Perozo, and E. Stefani. 1994. Biophys. J. 66:1011–1021), with the addition of a series of parallel nonconducting (inactivated) states that become populated during prolonged depolarization. The data suggest that prolonged depolarization modifies the conformation of the voltage sensor and that this change can be associated with the process of slow inactivation.
Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins

Leishmaniasis is a significant worldwide health problem for which no vaccine exists. Activation of CD4(+) and CD8(+) T cells is crucial for the generation of protective immunity against parasite. Recent trend in vaccine design has been shifted to epitope-based vaccines that are more specific, safe, and easy to produce. In the present study, four known antigenic Leishmania infantum proteins, cysteine peptidase A (CPA), histone H1, KMP-11, and Leishmania eukaryotic initiation factor (LeIF) were analyzed for the prediction of binding epitopes to H2(d) MHC class I and II molecules, using online available algorithms. Based on in silico analysis, eight peptides including highly scored MHC class I- and II-restricted epitopes were synthesized. Peptide immunogenicity was validated in MHC compatible BALB/c mice immunized with each synthetic peptide emulsified in complete Freund's adjuvant/incomplete Freund's adjuvant. CPA_p2, CPA_p3, H1_p1, and LeIF_p6 induced strong spleen cell proliferation upon in vitro peptide re-stimulation. In addition, the majority of the peptides, except of LeIF_p1 and KMP-11_p1, induced IFN-γ secretion, while KMP-11_p1 indicated a suppressive effect on IL-10 production. CPA_p2, CPA_p3, LeIF_p3, and LeIF_p6 induced IFN-γ-producing CD4(+) T cells indicating a TH1-type response. In addition, CPA_p2, CPA_p3, and H1_p1 induced also the induction of CD8(+) T cells. The induction of peptide-specific IgG in immunized mice designated also the existence of B cell epitopes in peptide sequences. Combining immunoinformatic tools and experimental validation, we demonstrated that CPA_p2, CPA_p3, H1_p1, H1_p3, CPA_p2, LeIF_p3, and LeIF_p6 are likely to include potential epitopes for the induction of protective cytotoxic and/or TH1-type immune responses supporting the feasibility of peptide-based vaccine development for leishmaniasis.
Celiac disease and health-related quality of life

Celiac disease is a particularly common life-long disorder with a prevalence of approximately 1–2% in Western populations. In recent years the health-related quality of life has become an important issue in this context, and most studies carried out so far have shown diminished quality of life in untreated patients compared with healthy controls. Furthermore, there has generally been a beneficial response to treatment with a gluten-free diet. However, the majority of trials have been carried out among adults with gastrointestinal disease, while in fact several extraintestinal and atypical forms of celiac disease might be even more common than the classical disorder. In addition, only a small proportion of these studies have been conducted among children. This article highlights the studies of health-related quality of life and celiac disease conducted to date. Particular attention is paid to the extraintestinal and atypical forms of the disorder.
Probing layer number and stacking order of few-layer graphene by Raman spectroscopy.

Graphene is a two-dimensional material defined as a planar honeycomb lattice of close-packed carbon atoms, where the electrons exhibit a linear dispersion near Dirac K points and behave as massless Dirac fermions. However, the valence and conduction bands in an AB stacked graphene bilayer split into two parabolic branches near the K point originating from the interaction of p electrons, and the electrons are hence described by massive Dirac fermions. Moreover, a graphene bilayer is a tunable-gap semiconductor under electric-field biasing. With a further increase in the number of layers along with AB stacking, the electronic structure reveals stepwise variations that eventually approach that of the three-dimensional counterpart. Considering the close relation between the electronic properties and layer number of few-layer graphene (FLG), the ability to accurately determine the layer number and correlating this with the electronic structure is a prerequisite in understanding the evolution of the electronic properties from twoto threedimensional graphitic materials. In addition to graphene layers with AB stacking, FLG with arbitrary stacking (Figure 1) is considered to possess distinct properties arising from its different crystalline structure and p electron interactions. Experimentally, it has been observed that the electroand magnetotransport properties for folded graphene sheets are different to thoseofAB stackedbilayers. Furthermore,FLG grown on SiC, Ni, and Ru also have non-AB stacking order. Therefore, elucidating the detailed character-
Multishift Variants of the QZ Algorithm with Aggressive Early Deflation

New variants of the QZ algorithm for solving the generalized eigenvalue problem are proposed. An extension of the small-bulge multishift QR algorithm is developed, which chases chains of many small bulges instead of only one bulge in each QZ iteration. This allows the effective use of level 3 BLAS operations, which in turn can provide efficient utilization of high performance computing systems with deep memory hierarchies. Moreover, an extension of the aggressive early deflation strategy is proposed, which can identify and deflate converged eigenvalues long before classic deflation strategies would. Consequently, the number of overall QZ iterations needed until convergence is considerably reduced. As a third ingredient, we reconsider the deflation of infinite eigenvalues and present a new deflation algorithm, which is particularly effective in the presence of a large number of infinite eigenvalues. Combining all these developments, our implementation significantly improves existing implementations of the QZ algorithm. This is demonstrated by numerical experiments with random matrix pairs as well as with matrix pairs arising from various applications.
Energy‐efficient resource allocation for amplify‐and‐forward relaying in OFDM systems

In this paper, we study end‐to‐end energy efficiency of an orthogonal frequency‐division multiplexing relay‐based system under power constraints for the base station and relay node with system circuit power considerations. Using a two‐phase amplify‐and‐forward relaying protocol, we assume that relay has a fixed power constraint and the source power can vary in transmission power interval where the source employs a selective relaying mechanism for each individual subcarrier. Therefore, in our model, the source is able to adaptively select some subcarriers to be relayed. The radio resource allocation is then formulated as an energy‐efficient mixed binary integer programming, and then we propose a heuristic algorithm to find the suboptimal solution. The solution consists of the suboptimal transmit power of the source, the suboptimal set of subcarriers for relaying and the optimal transmit power of each subcarrier at the source and relay in the first and second time slots. The algorithm obtains energy‐efficient transmission power for a given relay transmission power based on a gradient descent method. Then a two‐step iterative scheme is proposed to obtain the subcarriers to be relayed as well as the optimal power allocation at the source and relay in the first and second time slots. To evaluate the efficiency of the proposed method, we compare its efficiency through simulations with the cases without using selective subcarrier relaying and without circuit power consideration in low and high relay transmit power regimes. The simulation results indicate that using our proposed method results in a significant improvement in the energy efficiency. Copyright © 2014 John Wiley & Sons, Ltd.
Holarctic phylogeography of the root vole (Microtus oeconomus): implications for late Quaternary biogeography of high latitudes

A species‐wide phylogeographical study of the root vole (Microtus oeconomus) was performed using the whole 1140 base pair mitochondrial (mt) cytochrome b gene. We examined 83 specimens from 52 localities resulting in 65 unique haplotypes. Our results demonstrate that the root vole is divided into four main mtDNA phylogenetic lineages that seem to have largely allopatric distributions. Net divergence estimates (2.0–3.5%) between phylogroups, as well as relatively high nucleotide diversity estimates within phylogroups, indicate that the distinct phylogeographical structure was initiated by historical events that predated the latest glaciation. European root voles are divided into a Northern and a Central mtDNA phylogroup. The mtDNA data in concert with fossil records imply that root voles remained north of the classical refugial areas in southern Europe during the last glacial period. The currently fragmented populations in central Europe belong to a single mtDNA phylogroup. The Central Asian and the North European lineages are separated by the Ural Mountains, a phylogeographical split also found in collared lemmings (Dicrostonyx) and the common vole (M. arvalis). The Beringian lineage occurs from eastern Russia through Alaska to northwestern Canada. This distribution is congruent with the traditional boundaries of the Beringian refugium and with phylogeographical work on other organisms. In conclusion, similarities between the phylogeographical patterns in the root vole and other rodents, such as Arctic and subarctic lemmings, as well as more temperate vole species, indicate that late Quaternary geological and climatic events played a strong role in structuring northern biotic communities.
Bacterial Cellulose Production and its Industrial Applications

Microbial cellulose has proven to be a remarkably versatile biomaterial and can be used in wide variety of applied scientific endeavors, such as paper product, electronics and biomedical devices. In fact, biomedical devices recently have gained a significant attention owing to increase in tissue-engineering products for both wound care and the regeneration of demand or diseased organs. So, microbial cellulose production, characterization and influence of additives during its production are important to understand the microbial pathway and create new application.
The Phosphoproteome of the Minimal Bacterium Mycoplasma pneumoniae

Mycoplasma pneumoniae belongs to the Mollicutes, the group of organisms with the smallest genomes that are capable of host-independent life. These bacteria show little regulation in gene expression, suggesting an important role for the control of protein activities. We have studied protein phosphorylation in M. pneumoniae to identify phosphorylated proteins. Two-dimensional gel electrophoresis and mass spectrometry allowed the detection of 63 phosphorylated proteins, many of them enzymes of central carbon metabolism and proteins related to host cell adhesion. We identified 16 phosphorylation sites, among them 8 serine and 8 threonine residues, respectively. A phosphoproteome analysis with mutants affected in the two annotated protein kinase genes or in the single known protein phosphatase gene suggested that only one protein (HPr) is phosphorylated by the HPr kinase, HPrK, whereas four adhesion-related or surface proteins were targets of the protein kinase C, PrkC. A comparison with the phosphoproteomes of other bacteria revealed that protein phosphorylation is evolutionarily only poorly conserved. Only one single protein with an identified phosphorylation site, a phosphosugar mutase (ManB in M. pneumoniae), is phosphorylated on a conserved serine residue in all studied organisms from archaea and bacteria to man. We demonstrate that this protein undergoes autophosphorylation. This explains the strong conservation of this phosphorylation event. For most other proteins, even if they are phosphorylated in different species, the actual phosphorylation sites are different. This suggests that protein phosphorylation is a form of adaptation of the bacteria to the specific needs of their particular ecological niche.