Miracle-dz/UniFAR-FTUs huggingface dataset:
Methods for Evaluating Cell-Specific, Cell-Internalizing RNA Aptamers

Recent clinical trials of small interfering RNAs (siRNAs) highlight the need for robust delivery technologies that will facilitate the successful application of these therapeutics to humans. Arguably, cell targeting by conjugation to cell-specific ligands provides a viable solution to this problem. Synthetic RNA ligands (aptamers) represent an emerging class of pharmaceuticals with great potential for targeted therapeutic applications. For targeted delivery of siRNAs with aptamers, the aptamer-siRNA conjugate must be taken up by cells and reach the cytoplasm. To this end, we have developed cell-based selection approaches to isolate aptamers that internalize upon binding to their cognate receptor on the cell surface. Here we describe methods to monitor for cellular uptake of aptamers. These include: (1) antibody amplification microscopy, (2) microplate-based fluorescence assay, (3) a quantitative and ultrasensitive internalization method (“QUSIM”) and (4) a way to monitor for cytoplasmic delivery using the ribosome inactivating protein-based (RNA-RIP) assay. Collectively, these methods provide a toolset that can expedite the development of aptamer ligands to target and deliver therapeutic siRNAs in vivo.
Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host

Since 2003, H5N1 influenza viruses have caused over 400 known cases of human infection with a mortality rate greater than 60%. Most of these cases resulted from direct contact with virus-contaminated poultry or poultry products. Although only limited human-to-human transmission has been reported to date, it is feared that efficient human-to-human transmission of H5N1 viruses has the potential to cause a pandemic of disastrous proportions. The genetic basis for H5N1 viral transmission among humans is largely unknown. In this study, we used guinea pigs as a mammalian model to study the transmission of six different H5N1 avian influenza viruses. We found that two viruses, A/duck/Guangxi/35/2001 (DKGX/35) and A/bar-headed goose/Qinghai/3/2005(BHGQH/05), were transmitted from inoculated animals to naïve contact animals. Our mutagenesis analysis revealed that the amino acid asparagine (Asn) at position 701 in the PB2 protein was a prerequisite for DKGX/35 transmission in guinea pigs. In addition, an amino acid change in the hemagglutinin (HA) protein (Thr160Ala), resulting in the loss of glycosylation at 158–160, was responsible for HA binding to sialylated glycans and was critical for H5N1 virus transmission in guinea pigs. These amino acids changes in PB2 and HA could serve as important molecular markers for assessing the pandemic potential of H5N1 field isolates.
Discovery of Molecular Markers to Discriminate Corneal Endothelial Cells in the Human Body

The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro.
International Journal of Pure and Applied Sciences and Technology Techniques for Evolving Non-functional Properties of Software

Software systems find themselves working in an environment that forces them to be undergoing rapid change, and with each change to provide better services. In some systems, the functional requirements are easy to provide, it is the non-functional ones that are difficult. Yet with the ever changing requirements comes the demands for better quality and performance. For software system to achieve its goal, there is need for a technique which will allow it to change while improving its performance. This paper surveys some techniques for evolving non-functional properties of software. These techniques use different features of the software system to support software evolution. Based on the techniques surveyed, we recommended some features that techniques for evolving software properties should have.
Battling Corruption: Has NREGA Reached India's Rural Poor?

In an attempt to respond to the needs of the country's poor, the Indian government launched an ambitious workfare scheme, the National Rural Employment Guarantee Act (NREGA) in 2005, which guaranteed hundred days of employment in unskilled manual labour at a minimum wage to every rural household each year. The book assesses the effectiveness of formal and informal mechanisms-political representation, community social audits, access to information, membership in networks, political competition-in reducing corrupt practices and enabling NREGA to reach its intended beneficiaries in Andhra Pradesh, Tamil Nadu, Madhya Pradesh, and Rajasthan. The book tests several intuitions and finds that, among other things, political representation for scheduled castes and tribes, and women has produced dividends in the form of higher participation and higher earnings in the scheme by these groups. Low access to information, on the other hand, has hindered the effective functioning of these mechanisms. Written in non-technical language, it is one of the few studies of its kind that blends econometric and ethnographic analyses towards a better understanding of the effective implementation of the scheme. Available in OSO:
Modulation of Major Histocompatibility Complex Protein Expression by Human Gamma Interferon Mediated by Cysteine Proteinase-Adhesin Polyproteins of Porphyromonas gingivalis

ABSTRACT Cysteine proteinases have been emphasized in the virulence ofPorphyromonas gingivalis in chronic periodontitis. These hydrolases may promote the degradation of extracellular matrix proteins and disrupt components of the immune system. In this study it was shown that purified Arg-gingipain and Lys-gingipain inhibited expression of class II major histocompatibility complex (MHC) proteins in response to the stimulation of endothelial cells with human gamma interferon (IFN-γ). Treatment with the cysteine proteinases resulted in a rapid shift in the apparent molecular size of IFN-γ from 17 to 15 kDa, as shown by Western blot analysis, a response which also occurred in the presence of serum. Further, glycosylated natural IFN-γ from human leukocytes and unglycosylated recombinant IFN-γ from Escherichia coli were both digested by the cysteine proteinases. Immunoblot analysis indicated that cleavage within the carboxyl terminus of recombinant IFN-γ correlated with the loss of induction of MHC class II expression as monitored by analytical flow cytometry. No hydrolysis of MHC class II molecules or human IFN-γ receptor by these proteinases was detected by Western blot analysis. These findings suggest that P. gingivalis cysteine proteinases may alter the cytokine network at the point of infection through the cleavage of IFN-γ. Degradation of IFN-γ could have important consequences for the recruitment and activation of leukocytes and therefore may contribute significantly to the destruction of the periodontal attachment.
Relation-Aware Isosurface Extraction in Multifield Data

We introduce a variation density function that profiles the relationship between multiple scalar fields over isosurfaces of a given scalar field. This profile serves as a valuable tool for multifield data exploration because it provides the user with cues to identify interesting isovalues of scalar fields. Existing isosurface-based techniques for scalar data exploration like Reeb graphs, contour spectra, isosurface statistics, etc., study a scalar field in isolation. We argue that the identification of interesting isovalues in a multifield data set should necessarily be based on the interaction between the different fields. We demonstrate the effectiveness of our approach by applying it to explore data from a wide variety of applications.
Coronary vein tracking from MSCT using a minimum cost path approach

In this paper, we deal with the problem of tracking the coronary venous tree from Multi-Slice Computed Tomography (MSCT) angiography. Contrast inhomogeneities are a major issue. The proposed tracking procedure is based on minimum-cost path computation and makes use of ‘Fast-Marching’ technique. The algorithm aims at propagating a front inside a vascular structure and extracting a centered path. To achieve this goal, a specific cost function which combines the vessel local orientation to a vesselness measure is designed. Experiments on synthetic data and real data have been performed. Coronary veins with contrast difficulties are extracted with a low computing time.
An improved nucleic acid parameter set for the GROMOS force field

Over the past decades, the GROMOS force field for biomolecular simulation has primarily been developed for performing molecular dynamics (MD) simulations of polypeptides and, to a lesser extent, sugars. When applied to DNA, the 43A1 and 45A3 parameter sets of the years 1996 and 2001 produced rather flexible double‐helical structures, in which the Watson–Crick hydrogen‐bonding content was more limited than expected. To improve on the currently available parameter sets, the nucleotide backbone torsional‐angle parameters and the charge distribution of the nucleotide bases are reconsidered based on quantum‐chemical data. The new 45A4 parameter set resulting from this refinement appears to perform well in terms of reproducing solution NMR data and canonical hydrogen bonding. The deviation between simulated and experimental observables is now of the same order of magnitude as the uncertainty in the experimental values themselves. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 725–737, 2005
The challenges of innovating for sustainable development

Over the past decade, companies have become increasingly aware of the social and environmental pressures facing business. Many management scholars and consultants have argued that these new demands offer terrific opportunities for progressive organizations, and innovation is one of the primary means by which companies can achieve sustainable growth. But, say the authors, the reality is that managers have had considerable difficulty dealing with sustainable-development pressures. Specifically, their innovation strategies are often inadequate to accommodate the highly complex and uncertain nature of these new demands. In response, the authors propose the concept of sustainable-development innovation, or SDI. In contrast to conventional, market-driven innovation, SDI considers the added constraints of social and environmental pressures. SDI is therefore usually more complex, because there is typically a wider range of stakeholders, and more ambiguous, as many of the parties have contradictory demands. Furthermore, sustainable-development pressures can be driven by science that has yet to be accepted fully by the scientific, political and managerial communities. Organizations that fail to understand such issues could well find themselves making costly mistakes in bringing new technologies to market.
Nonlinear relaxation dynamics in elastic networks and design principles of molecular machines

Analyzing nonlinear conformational relaxation dynamics in elastic networks corresponding to two classical motor proteins, we find that they respond by well defined internal mechanical motions to various initial deformations and that these motions are robust against external perturbations. We show that this behavior is not characteristic for random elastic networks. However, special network architectures with such properties can be designed by evolutionary optimization methods. Using them, an example of an artificial elastic network, operating as a cyclic machine powered by ligand binding, is constructed.
Identification and Expression Analysis of a Novel HbCIPK2-Interacting Ferredoxin from Halophyte H. brevisubulatum

Ferredoxin is a small iron-sulfer protein involved in various one-eletron transfer pathways. Little is known about how ferredoxin is regulated to distribute electron under abiotic stress. Our previous study has showed that HbCIPK2 conferred salinity and drought tolerance. Thus, we hypothesized that HbCIPK2 could mediate the activities of interacting partners as a signal transducer. In this report, we identified a novel HbCIPK2-interacting ferredoxin (HbFd1) from halophyte Hordeum brevisubulatum by yeast two-hybrid screens, confirmed this interaction by BiFC in vivo and CoIP in vitro, and presented the expression pattern of HbFd1. HbFd1 was down-regulated under salinity and cold stress but up-regulated under PEG stress, its expression showed tissue-specific, mainly in shoot chloroplast, belonging to leaf-type subgroup. Moreover, HbCIPK2 could recruit HbFd1 to the nucleus for their interaction. The C-terminal segment in HbFd1 protein was involved in the interaction with HbCIPK2. These results provided insight into the connection between CBL-CIPK signaling network and Fd-dependent metabolic pathways.
Supermassive black hole masses of AGNs with elliptical hosts

The recently discovered tight correlation between supermassive black hole mass and central velocity dispersion for both inactive and active galaxies suggests a possibility to estimate the black hole mass from the measured central velocity dispersion. However, for most AGNs it is difficult to measure the central velocity dispersions of their host galaxies directly with spectroscopic studies. In this paper we adopt the fundamental plane for ellipticals to estimate the central velocity dispersion and black hole mass for a number of AGNs with morphology parameters of their elliptical host galaxies obtained by the Hubble Space Telescope imaging observations. The estimated black hole masses of 63 BL Lac objects, 10 radio galaxies, 10 radio-loud quasars and 9 radio-quiet quasars are mostly in the range of $10^{7.5}~M_\odot$ to $10^{9}~ M_\odot$. No significant difference in black hole mass is found for high-frequency peaked BL Lacs and low-frequency peaked BL Lacs, as well as for radio galaxies and radio-loud quasars. The Eddington ratios of radio galaxies are substantially smaller than those of quasars. This suggests that the different observational features of these radio-loud AGNs may be mainly dominated by different accretion rate rather than by the black hole mass, which is in agreement with some evolutionary scenarios recently proposed for radio-loud AGNs. Different to some previous claims, we found that the derived mean black hole mass for radio-loud quasars is only slightly larger than that of radio-quiet quasars. Though the black hole mass distributions between radio-loud and radio-quiet quasars are statistically different, their Eddington ratio distributions are probably from the same population. In addition, we noted that the relation between black hole mass and host galaxy luminosity we obtained using the fundamental plane provides further arguments for a nonlinear scaling law between supermassive black hole mass and galactic bulge mass.
N‐methyl‐D‐aspartate receptor agonists modulate homocysteine‐induced developmental abnormalities

We showed previously that the induction of neural crest (NC) and neural tube (NT) defects is a general property of N‐methyl‐D‐aspartate receptor (NMDAR) antagonists. Since homocysteine induces NC and NT defects and can also act as an NMDAR antagonist, we hypothesized that the mechanism of homocysteine‐induced developmental defects is mediated by competitive inhibition of the NMDAR by homocysteine. If this hypothesis is correct, homocysteine‐induced defects will be reduced by NMDAR agonists. To test the hypothesis, we treated chicken embryos during the process of neural tube closure with sufficient homocysteine thiolactone to induce NC and NT defects in ∼40% of survivors or with homocysteine thiolactone in combination with each of a selected set of NMDAR agonists in 0.05–5000 nmol doses. Glutamate site agonists selected were L‐glutamate and N‐methyl‐D‐aspartate. Glycine site agonists were glycine, D‐cycloserine, and aminocyclopropane‐carboxylic acid. Glycine was the most effective overall, reducing defects significantly at two different doses (each P<0.001). These results support the hypothesis that homocysteine may affect NC and NT development by its ability to inhibit the NMDAR. One potentially important consequence of this putative mechanism is that homocysteine may interact synergistically with other NMDAR antagonists to enhance its effect on development. —Rosenquist, T. H. , Schneider, A. M. , and Monaghan, D. T. N‐methyl‐D‐aspartate receptor agonists modulate homocysteine‐induced developmental abnormalities. FASEB J. 13, 1523–1531 (1999)
Prospect of Fine Grain Dynamic Memory Access Control with Profiling

Attacks often exploit vulnerabilities in memory to compromise a system or get classified information. In spite of extensive research, attackers are still able to find security holes. In order to address the attacks exploiting vulnerabilities in memory, we propose fine grain dynamic memory access control with profiling. This technique builds profile data for memory accesses with training, and this data is referenced later to check if an access is an allowed legitimate one. To facilitate the fine grain memory access control at a reasonable overhead, instructions and memory words form access group to represent allowed accesses: within one access group, one instruction is accessing at least two memory words or one memory word is accessed by at least two instructions. One access group is assigned with its unique color, and this color is referenced to verify legitimacy of a memory access. In order to handle memory accesses to run-time generated object, we suggest an efficient addressing methods and identifier for associating group information with the object in profiling procedure. To verify its feasibility in statistical point of view, we have implemented our idea in Bochs simulator and results show that memory access control with profiling data can be reliable.
The Morphological Features and Mitochondrial Oxidative Stress Mechanism of the Retinal Neurons Apoptosis in Early Diabetic Rats

This paper aims to explore the relationship of retinal neuron apoptosis and manganese superoxidase dismutase (MnSOD) at early phase of diabetic retinopathy. Sprague-Dawley rats were grouped into normal controls and diabetics. Data were collected after 4, 8, and 12 weeks (n = 12). The pathological changes and ultrastructure of the retina, the apoptosis rate of retinal neurons by TdT-mediated dUTP nick end label (TUNEL), mRNA expressions of MnSOD and copper-zinc superoxide dismutase (Cu–Zn SOD), and the activities of total SOD (T-SOD) and subtypes of SOD were tested. For the controls, there was no abnormal structure or apoptosis of retinal neurons at any time. There was no change of structure for rats with diabetes at 4 or 8 weeks, but there was a decrease of retinal ganglion cells (RGCs) number and thinner inner nuclear layer (INL) at 12 weeks. The apoptosis ratio of RGCs was higher than that of the controls at 8 and 12 weeks (P < 0.001). The activity and mRNA levels of MnSOD were lower in diabetics at 4, 8, and 12 weeks (P < 0.05). In summary, the apoptosis of the retinal neurons occurred at 8 weeks after the onset of diabetes. Retinal neuron apoptosis in early diabetic rats may be associated with the decreased activity and mRNA of MnSOD.
A Priority-driven ACO Algorithm for DAG Task Scheduling in Cloud Environment

Task scheduling in cloud environment is a key technical problem on how to allocate available cloud resources to cloud users. Usually, a task in cloud environment can be cut into a serials of subtasks, which have precedence and dependency relationships among themselves. We describe the problem by means of a DAG (Directed Acyclic Graph) model. Then, we propose a priority algorithm for DAG task scheduling, and a priority-driven ACO (Ant Colony Optimization) algorithm for DAG task scheduling on the basis of the DAG model. Finally, we compare these two algorithms with the greedy algorithm through simulation in the CloudSim platform. The simulation results show that the priority-driven ACO algorithm is effective to solve DAG task scheduling problem in cloud environment.
Impact of an ABCDE team triage process combined with public guidance on the division of work in an emergency department

Abstract Objective. To study the effects of applying an emergency department (ED) triage system, combined with extensive publicity in local media about the “right” use of emergency services, on the division of work between ED nurses and general practitioners (GPs). Design. An observational and quasi-experimental study based on before–after comparisons. Setting. Implementation of the ABCDE triage system in a Finnish combined ED where secondary care is adjacent, and in a traditional primary care ED where secondary care is located elsewhere. Subjects. GPs and nurses from two different primary care EDs. Main outcome measures. Numbers of monthly visits to different professional groups before and after intervention in the studied primary care EDs and numbers of monthly visits to doctors in the local secondary care ED. Results. The beginning of the triage process increased temporarily the number of independent consultations and patient record entries by ED nurses in both types of studied primary care EDs and reduced the number of patient visits to a doctor compared with previous years but had no effect on doctor visits in the adjacent secondary care ED. No further decrease in the number of nurse or GP visits was observed by inhibiting the entrance of non-urgent patients. Conclusion. The ABCDE triage system combined with public guidance may reduce non-urgent patient visits to doctors in different kinds of primary care EDs without increasing visits in the secondary care ED. However, the additional work to implement the ABCDE system is mainly directed to nurses, which may pose a challenge for staffing.