Miracle-dz/UniFAR-FTUs huggingface dataset:
A Hybrid Cationic Peptide Composed of Human β-Defensin-1 and Humanized θ-Defensin Sequences Exhibits Salt-Resistant Antimicrobial Activity

ABSTRACT We have designed a hybrid peptide by combining sequences of human β-defensin-1 (HBD-1) and θ-defensin, in an attempt to generate a molecule that combines the diversity in structure and biological activity of two different peptides to yield a promising therapeutic candidate. HBD-1 was chosen as it is a natural defensin of humans that is constitutively expressed, but its antibacterial activity is considerably impaired by elevated ionic strength. θ-Defensins are expressed in human bone marrow as a pseudogene and are homologous to rhesus monkey circular minidefensins. Retrocyclins are synthetic human θ-defensins. The cyclic nature of the θ-defensin peptides makes them salt resistant, nonhemolytic, and virtually noncytotoxic in vitro. However, a nonhuman circular molecule developed for clinical use would be less viable than a linear molecule. In this study, we have fused the C-terminal region of HBD-1 to the nonapeptide sequence of a synthetic retrocyclin. Cyclization was achieved by joining the terminal ends of the hybrid peptide by a disulfide bridge. The hybrid peptide with or without the disulfide bridge exhibited enhanced antimicrobial activity against both Gram-negative and Gram-positive bacteria as well as against fungi, including clinical bacterial isolates from eye infections. The peptide retained activity in the presence of NaCl and serum and was nonhemolytic in vitro. Thus, the hybrid peptide generated holds potential as a new class of antibiotics.
kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome

UNLABELLED We announce the release of kSNP3.0, a program for SNP identification and phylogenetic analysis without genome alignment or the requirement for reference genomes. kSNP3.0 is a significantly improved version of kSNP v2. AVAILABILITY AND IMPLEMENTATION kSNP3.0 is implemented as a package of stand-alone executables for Linux and Mac OS X under the open-source BSD license. The executable packages, source code and a full User Guide are freely available at https://sourceforge.net/projects/ksnp/files/ CONTACT barryghall@gmail.com.
Dead Time Compensation in CMOS Single Photon Avalanche Diodes With Active Quenching and External Reset

Single photon avalanche diodes (SPADs) in CMOS are becoming increasingly interesting devices for timing applications, such as fluorescence lifetime imaging, positron emission tomography, and time of flight mass spectroscopy. The CMOS allows integration of functionalities like time-to-digital converters within the same pixel, and the manufacturing of large format arrays. Dead time has to be taken into account in order to correctly interpret SPAD measurements. In this paper, we derive and test a model for dead time in real SPADs where reset is generated off-pixel. We test the model using our own custom designed devices made in a low-voltage 180-nm CMOS image sensor process with full custom implants. A Monte Carlo simulation is implemented to compare with experimental results. Using a fitting method, higher values of the photon detection efficiency (PDE) can be extracted than with a simple linear fit. The resulting PDE corrections are significant, up to 100% depending on the conditions. The limitations are approximated, and it is found that accurate predictions of the true count rate are possible over a control range of 0.25-1.0 MHz.
High performance PL/SQL programming

Performance engineering is a vital aspect in PL/SQL programming, as most of the Database associated applications are built with PL/SQL Code. There subsists many ways of writing PL/SQL statement to retrieve same result set, but the approach which levies minimum impact on DBMS engine is always esteemed. Most commercial transaction scripts are written using PL/SQL code. The proposed idea(s) are envisioned to oblige as tuning utility and benchmark for tuning PL/SQL queries. This paper enunciates different techniques that can reduce time and space complexity of a native SQL query and PL/SQL script. Our analysis reduced the rate of Context switching (an overhead) among SQL engine and PL/SQL engine.
Removal of Lead and Cadmium Ions from Water
Using Cladophora Biomass

Cladophora biomass has been treated and used for the removal of Lead and Cadmium ions from water, and the characterization of Cladophora biomass by Fourier transform infrared (FTIR) and energydispersive x-ray analysis (EDS) indicate the presence of functional groups of different components such as polysaccharides, amino acids, fatty acids and others. Scanning electron microscopy (SEM) and surface area analysis (BET) confirm nonporous algal biomass with small surface area. The parameters affecting metal ions removal from water such as adsorbent-solution contact time, pH of metal ion solution, algal biomass dose and mesh sizes have been studied. Isothermal study has been applied using Freundlich and
Expanding the Range of Protein Function at the Far End of the Order-Structure Continuum*

The traditional view of the structure-function paradigm is that a protein's function is inextricably linked to a well defined, three-dimensional structure, which is determined by the protein's primary amino acid sequence. However, it is now accepted that a number of proteins do not adopt a unique tertiary structure in solution and that some degree of disorder is required for many proteins to perform their prescribed functions. In this review, we highlight how a number of protein functions are facilitated by intrinsic disorder and introduce a new protein structure taxonomy that is based on quantifiable metrics of a protein's disorder.
Latest developments in molecular docking: 2010–2011 in review

The aim of docking is to accurately predict the structure of a ligand within the constraints of a receptor binding site and to correctly estimate the strength of binding. We discuss, in detail, methodological developments that occurred in the docking field in 2010 and 2011, with a particular focus on the more difficult, and sometimes controversial, aspects of this promising computational discipline. The main developments in docking in this period, covered in this review, are receptor flexibility, solvation, fragment docking, postprocessing, docking into homology models, and docking comparisons. Several new, or at least newly invigorated, advances occurred in areas such as nonlinear scoring functions, using machine‐learning approaches. This review is strongly focused on docking advances in the context of drug design, specifically in virtual screening and fragment‐based drug design. Where appropriate, we refer readers to exemplar case studies. Copyright © 2013 John Wiley & Sons, Ltd.
Tissue engineering of cardiac valve prostheses I: development and histological characterization of an acellular porcine scaffold.

BACKGROUND AND AIMS OF THE STUDY Several deficiencies in current heart valve prostheses make them problematic for use in younger patients. Tissue valve substitutes are non-viable with a life expectancy of only 10-15 years, while mechanical valves require long-term anti-coagulation therapy. A solution to these problems would be to develop a tissue-engineered heart valve containing autologous cells, enabling the valve to maintain its biochemical and mechanical properties, yet grow with the patient. The study aim was to optimize a protocol to produce a porcine acellular matrix scaffold for use in developing a tissue-engineered heart valve. METHODS Fresh porcine aortic valve leaflets were treated with Triton X-100, sodium dodecyl sulfate (SDS), sodium deoxycholate, MEGA 10, TnBP, CHAPS, and Tween 20, over a range of concentrations, in the presence of protease inhibitors for up to 72 h. Histological analysis was used to detect the major structural proteins of the heart valve, collagen I, elastin and glycosaminoglycans. RESULTS After 72 h, most protocols resulted in the retention of large numbers of whole cells and cell fragments. Only SDS (0.03-1%) or sodium deoxycholate (0.5-2%) resulted in total decellularization at 24 h. Histological analysis of acellular matrices showed that the major structural proteins had been retained and appeared to be intact. CONCLUSION Protocols utilizing SDS or sodium deoxycholate were successful for leaflet decellularization, and histological analysis showed that the major structural components of the valve matrix had been maintained. These methods are being developed further with a view to reseeding with autologous cells to produce tissue-engineered solutions for clinical implantation.
A survey on optimal consensus of multi-agent systems

This paper provides a review of some main works and research progress in distributed optimal consensus problems of multi-agent systems. Classical and common methods in this area are summarized, such as Riccati design, adaptive dynamic programming and inverse optimal control. This paper detailedly addresses the design schemes of optimal consensus protocols by reviewing several typical literatures. Furthermore, the difficulties and challenges for solving distributed optimal consensus to multi-agent systems are pointed out and future research directions are also proposed.
C‐type natriuretic peptide for reduction of restenosis: gene transfer is superior over single peptide administration

Restenosis is still a significant clinical problem limiting the long‐term therapeutic success following balloon dilation or stent implantation. New approaches are necessary inhibiting neointima formation and simultaneously promoting re‐endothelialization. Therefore, long‐term therapeutic effects of adventitial liposome‐mediated C‐type natriuretic protein (CNP) gene and CNP peptide applications in a porcine model for restenosis post‐angioplasty were investigated.
Compensation for Decreased Expression of B7 Molecules on Leishmania infantum-Infected Canine Macrophages Results in Restoration of Parasite-Specific T-Cell Proliferation and Gamma Interferon Production

ABSTRACT Infection of humans and dogs by Leishmania infantum may result in visceral leishmaniasis, which is characterized by impaired T-cell-mediated immune responses to parasite antigens. Dogs are natural hosts of Leishmania parasites and play an important role in the transmission of the parasites to humans. In an effort to characterize the immune response in dogs infected with this intracellular pathogen, we examined how infection with L. infantum affects canine macrophages and the consequences for T-cell activation in vitro. We showed that the proliferation of T-cell lines to cognate antigen decreases to background levels when infected autologous monocyte-derived macrophages are used as antigen-presenting cells (APC). The observed reduction of antigen-specific T-cell proliferation was shown to be dependent on the parasite load and to require cell-to-cell interaction of T cells with the infected APC. In addition, we observed a decreased expression of costimulatory B7 molecules on infected monocyte-derived macrophages. The expression of other surface molecules involved in T-cell activation, such as major histocompatibility complex class I and class II, on these cells did not change upon infection, whereas the expression of intracellular adhesion molecule 1 was marginally increased. Compensation for the decreased expression of B7 molecules by the addition of B7-transfected cells resulted in the restoration of cell proliferation and gamma interferon (IFN-γ) production by a Leishmania-specific T-cell line. These results showed that for the activation of parasite-specific canine T cells producing IFN-γ, which are most likely involved in protective immunity, sufficient expression of B7 molecules on infected macrophages is required. Provision of costimulatory molecules may be an approach for immunotherapy of leishmaniaisis as well as for vaccine development.
Potentiation of erythroid abnormalities following macrophage depletion in aged rats

Objectives: The effects of prolonged macrophage depletion on haematological parameters were investigated in aged rats and compared with those in young ones. Methods: Four weekly i.v. injections of dichloromethylene diphosphonate‐containing liposomes (Cl2MDP‐CL) were employed to achieve a prolonged depletion of bone marrow (BM) and spleen macrophages. The number of BM macrophages was then assessed by flow cytometry, whereas the spleen clearance function was judged by the elimination of oxidised red blood cells (RBC). Haematological parameters and signs of RBC ageing (reduced MCV, increased density and augmented 4.1a/4.1b membrane protein ratio) were determined. Finally, the recovery from phlebotomy‐induced acute anaemia was investigated. Results: Following the Cl2MDP‐CL treatment, in comparison with young rats, the aged animals showed: (i) reduced numbers of BM macrophages; (ii) greater impairment of spleen clearance function; (iii) similar anaemic condition and signs of RBC ageing; (iv) greater increase in white blood cell (WBC) numbers (mainly neutrophils). In addition, whereas aged control rats showed a recovery from phlebotomy‐induced acute anaemia which was similar to that of the untreated young animals, in the aged‐treated rats, a significantly diminished/delayed restoration of RBC, Hb and reticulocyte to normal values was observed, accompanied by a significantly higher increase in WBC numbers than in the other groups of animals. Conclusion: Haematological abnormalities because of Cl2MDP‐CL‐induced macrophage depletion are potentiated in aged rats in which the BM regenerative potential of the erythroid lineage as well as the clearance function of the spleen appear compromised. Thus, in aged rats, macrophage dysfunction is likely to interfere with erythroid homeostasis particularly during haemopoietic stress.
Error Analysis of MRI and Leksell Stereotactic Frame Target Localization in Deep Brain Stimulation Surgery

Stereotactic deep brain stimulation (DBS) is the surgical treatment of choice for medication-refractory patients with Parkinson’s disease and essential tremor. The subthalamic nucleus and ventral intermediate nucleus of the thalamus appear to be effective targets for electrode placement. Because these targets are small and encased in fiber tracts, their localization can be exceedingly difficult. However, the precision of electrode placement is crucial for obtaining successful results. Currently, surgeons rely on preoperative MRI or CT images to derive stereotactic coordinates for targeting sites such as the subthalamic nucleus and ventral intermediate nucleus of the thalamus coupled with microelectrode recordings during surgery for proper electrode placement. However, it has been argued that the stereotactic head frame produces detrimental artifacts during MRI. We examined MRI images taken from 11 patients undergoing repeat DBS surgery, and determined the coordinates of the previously placed electrode. We then set the Leksell G stereotactic frame to these coordinates and obtained fluoroscope-localizing images. Using MATLAB image analysis tools, we were able to quantify the 3-dimensional error in target localization by measuring the distance from the electrode tip to the targeted coordinate. The mean errors were 0.09 ± 0.34 mm perpendicular, lateral to medial, 0.01 ± 0.32 perpendicular, posterior to anterior, and –0.08 ± 0.33 mm parallel to the electrode, superior to inferior. According to statistical analysis, the error was random and did not seem to move in any predictable fashion. Therefore, we conclude that preoperative MRI images can be safely used in DBS surgery, and they do not negatively affect its accuracy.
Genome Sequences of Beak and Feather Disease Virus in Urban Rainbow Lorikeets (Trichoglossus haematodus)

ABSTRACT Beak and feather disease viral genomes were recovered from two deceased juvenile urban rainbow lorikeets (Trichoglossus haematodus) that lacked tail feathers. These genomes share ~95% pairwise identity with two beak and feather disease virus (BFDV) genomes identified in wild and captive Australian T. haematodus birds and ~92% identity to those in wild New Caledonian T. haematodus deplanchii birds.
Large-scale taxonomy induction using entity and word embeddings

Taxonomies are an important ingredient of knowledge organization, and serve as a backbone for more sophisticated knowledge representations in intelligent systems, such as formal ontologies. However, building taxonomies manually is a costly endeavor, and hence, automatic methods for taxonomy induction are a good alternative to build large-scale taxonomies. In this paper, we propose TIEmb, an approach for automatic unsupervised class subsumption axiom extraction from knowledge bases using entity and text embeddings. We apply the approach on the WebIsA database, a database of subsumption relations extracted from the large portion of the World Wide Web, to extract class hierarchies in the Person and Place domain.
Primary cutaneous B-cell lymphomas – Clinicopathological, prognostic and therapeutic characterisation of 54 cases according to the WHO-EORTC classification and the ISCL/EORTC TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome

Clinical, prognostic and therapeutic features of 54 primary cutaneous marginal zone B-cell lymphoma (pcMZL), follicle centre lymphoma (pcFCL) and diffuse large B-cell lymphoma, leg type (pcDLBL) were analysed applying the WHO-EORTC classification for cutaneous lymphomas and the new TNM staging scheme of the International Society of Cutaneous Lymphomas. Solitary (T1) or regionally clustered (T2) tumors were observed in pcMZL and pcFCL. Disseminated tumors (T3 stage) were found in 26% of patients with pcMZL and in one patient with pcDLBL. A complete remission was achieved in 41% of the patients. Three of 7 patients (43%) with pcDLBL died due to lymphoma. The new TNM staging system is easily applicable for disease documentation, but our relatively small number of patients in each T stage does not allow the assessment of its prognostic value. Surgical excision or radiotherapy is highly effective in pcMZL and pcFCL.
An integrated framework for geospatial data discovering and standardized processing

This paper propose a solution to discover geospatial data from multiple distributed data center in the Web environment. There are two-level of data discovering defined in the paper: dataset discovery and data granule discovery. To find the dataset of interest, multiple dataset clearinghouses were integrated under a dataset catalog federation. Based on the returned dataset information, an integrated catalog was implemented to find data granule from remote data providers. OGC Catalog Service for Web specification was adopted as the interface of catalog federation. The mediator-wrapper architecture was proposed to solve the query language translation and metadata conversion. For the returned data granule, a standardized data processing service, Web Coverage Service was designed and implemented to process heterogeneous data through a universal interface. Overall, the proposed solution in this paper was demonstrated to be effective to find dataset and data granule of interest from multiple sources, and process acquired heterogamous data through standardized interface.
Polyclonal antibodies to chlorosome proteins as probes for green sulfur bacteria

We found that polyclonal antibodies raised against chlorosome polypeptides from green sulfur bacteria reacted to Chlorobium tepidum, Chlorobium limicola, and Chlorobium phaeobacteroides but not to Chloroflexus aurantiacus. These antibodies successfully labeled only green sulfur species in marine microbial mat samples. Our results suggest that these antibodies may be useful as immunohistochemical probes.
MT119, a new planar‐structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation

Microtubule‐targeted drugs are now indispensable for the therapy of various cancer types worldwide. In this article, we report MT119 [6‐[2‐(4‐methoxyphenyl) ‐ethyl]‐9‐[(pyridine‐3‐ylmethyl)amino]pyrido[2′,1′:2,3]imida‐zo[4,5‐c]isoquinolin‐5(6H)‐one] as a new microtubule‐targeted agent. MT119 inhibited tubulin polymerization significantly both in tumor cells and in cell‐free systems, which was followed by the disruption of mitotic spindle assembly. Surface plasmon resonance‐based analyses showed that MT119 bound to purified tubulin directly, with the KD value of 10.6 μM. The binding of MT119 in turn caused tubulin conformational changes as evidenced by the quenched tryptophan fluorescence, the reduction of the bis‐ANS reactivity and the decreased DTNB‐sulfhydryl reaction rate. Competitive binding assays further revealed that MT119 bound to tubulin at its colchicine site. Consequently, by inhibiting tubulin polymerization, MT119 arrested different tumor cells at mitotic phase, which contributed to its potent antitumor activity in vitro. MT119 was also similarly cytotoxic to vincristine‐, adriamycin‐ or mitoxantrone‐resistant cancer cells and to their corresponding parental cells. Together, these data indicate that MT119 represents a new class of colchicine‐site‐targeted inhibitors against tubulin polymerization, which might be a promising starting point for future cancer therapeutics.
Transcriptional and post‐transcriptional limitations of high‐yielding, PEI‐mediated transient transfection with CHO and HEK‐293E cells

Transient gene expression (TGE) in human embryonic kidney (HEK‐293) and Chinese hamster ovary (CHO) cells is a well‐established technology for the rapid generation of recombinant proteins. Although the maximum TGE yields have reached 1 g/L or more, the amount of plasmid DNA (pDNA) required for transfection remains high. Although greater than 103 copies of pDNA are present per transfected cell, protein yields are still lower than those achieved in recombinant cell lines with only one or a few copies of the transgene. This indicates a clear limitation to TGE in terms of the maximum level of recombinant protein production. In this study, we investigated the limitations to high‐yielding TGE processes with CHO and HEK‐293E cells using a monoclonal antibody as a model protein. For either cell host, both the intracellular and intranuclear pDNA levels increased linearly with the amount of pDNA added to the culture. In contrast, transgene mRNA accumulation reached a plateau as the intranuclear pDNA amount increased, suggesting a limitation in pDNA transcription. A post‐transcriptional limitation to TGE yields was revealed by calculating the amount of antibody produced per transgene mRNA (mRNA utilization). For both hosts the transgene mRNA utilization decreased dramatically when transfected pDNA amounts increased beyond the level giving the maximum protein yield. The post‐transcriptional limitation did not appear to be due to bottlenecks in antibody assembly or secretion, suggesting that transgene mRNA translation may be limiting. The results show that TGE yields are not limited by pDNA delivery into the nuclei, but in pDNA and transgene mRNA utilization. © 2014 American Institute of Chemical Engineers Biotechnol. Prog. , 31:541–549, 2015