Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Diagnosis of Familial Prion Diseases Supports the β2-α2 Loop as a Universal Interference Target

Background Mutations in the cellular prion protein associated to familial prion disorders severely increase the likelihood of its misfolding into pathogenic conformers. Despite their postulation as incompatible elements with the native fold, these mutations rarely modify the native state structure. However they variably have impact on the thermodynamic stability and metabolism of PrPC and on the properties of PrPSc aggregates. To investigate whether the pathogenic mutations affect the dynamic properties of the HuPrP(125-229) α-fold and find possible common patterns of effects that could help in prophylaxis we performed a dynamic diagnosis of ten point substitutions. Methodology/Principal Findings Using all-atom molecular dynamics simulations and novel analytical tools we have explored the effect of D178N, V180I, T183A, T188K, E196K, F198S, E200K, R208H, V210I and E211Q mutations on the dynamics of HuPrP(125-228) α-fold. We have found that while preserving the native state, all mutations produce dynamic changes which perturb the coordination of the α2-α3 hairpin to the rest of the molecule and cause the reorganization of the patches for intermolecular recognition, as the disappearance of those for conversion inhibitors and the emergence of an interaction site at the β2-α2 loop region. Conclusions/Significance Our results suggest that pathogenic mutations share a common pattern of dynamical alterations that converge to the conversion of the β2-α2 loop into an interacting region that can be used as target for interference treatments in genetic diseases.
A scFv Phage Display Mini Library Generated from the Immunoglobulin Repertoire of Breast Medullary Carcinoma Infiltrating B Lymphocytes

The detection and characterization of antigens expressed during the progression of carcinogenesis is still a major goal for tumour immunology. We describe a possible new way for defining human tumour specific antigens with the use of scFv phage display technology [1]. An attractive hypothesis is that tumour infiltrating lymphocytes (TIL) are accumulated in the tumour tissue because of their unique capacity for recognizing tumour cells [2]. This has been proved in the case of tumour infiltrating T lymphocytes (TIL-T) [3, 4]. In contrast, knowledge about tumour infiltrating B lymphocytes (TIL-B) is very limited [5–7]. In this work we show data on the immunoglobulin repertoire expressed by TIL-B cells from medullary breast carcinoma (MBC). A detailed DNA sequence analysis of immunoglobulin heavy (VH) and light chain
miRGator v2.0 : an integrated system for functional investigation of microRNAs

miRGator is an integrated database of microRNA (miRNA)-associated gene expression, target prediction, disease association and genomic annotation, which aims to facilitate functional investigation of miRNAs. The recent version of miRGator v2.0 contains information about (i) human miRNA expression profiles under various experimental conditions, (ii) paired expression profiles of both mRNAs and miRNAs, (iii) gene expression profiles under miRNA-perturbation (e.g. miRNA knockout and overexpression), (iv) known/predicted miRNA targets and (v) miRNA-disease associations. In total, >8000 miRNA expression profiles, ∼300 miRNA-perturbed gene expression profiles and ∼2000 mRNA expression profiles are compiled with manually curated annotations on disease, tissue type and perturbation. By integrating these data sets, a series of novel associations (miRNA–miRNA, miRNA–disease and miRNA–target) is extracted via shared features. For example, differentially expressed genes (DEGs) after miRNA knockout were systematically compared against miRNA targets. Likewise, differentially expressed miRNAs (DEmiRs) were compared with disease-associated miRNAs. Additionally, miRNA expression and disease-phenotype profiles revealed miRNA pairs whose expression was regulated in parallel in various experimental and disease conditions. Complex associations are readily accessible using an interactive network visualization interface. The miRGator v2.0 serves as a reference database to investigate miRNA expression and function (http://miRGator.kobic.re.kr).
An Ensemble Based Nonlinear Orthogonal Matching Pursuit Algorithm for Sparse History Matching of Reservoir Models

A nonlinear orthogonal matching pursuit (NOMP) for sparse calibration of reservoir models is presented. Sparse calibration is a challenging problem as the unknowns are both the non-zero components of the solution and their associated weights. NOMP is a greedy algorithm that discovers at each iteration the most correlated components of the basis functions with the residual. The discovered basis (aka support) is augmented across the nonlinear iterations. Once the basis functions are selected from the dictionary, the solution is obtained by applying Tikhonov regularization. The proposed algorithm relies on approximate gradient estimation using an iterative stochastic ensemble method (ISEM). ISEM utilizes an ensemble of directional derivatives to efficiently approximate gradients. In the current study, the search space is parameterized using an overcomplete dictionary of basis functions built using the K-SVD algorithm.
twitter Try out # Grabeeter to Export , Archive and Search Your Tweets

The microblogging platform Twitter is beside Facebook the fastest growing social networking application of the last years. It is used in different ways, e.g. to enhance events (conferences) by sending updates, hyperlinks or other data as a news-stream to a broader public. Until now the stream ends with the end of the event. In this publication a new application is introduced that allows information retrieval and knowledge discovery by searching through local stored tweets related to a corresponding event. The architecture of the prototype is described as well as how the data is being accessed by a web application and a local client. It can be stated that making tweets available after the end of an event, enhances the way we deal with information in future.
Carbohydrate-mimetic peptides: structural aspects of mimicry and therapeutic implications

Introduction: The existence of specific carbohydrates on the surface of a wide range of cells provides the opportunity for the development of highly targeted therapeutic agents. The potential applications of such agents are diverse, and include vaccines against pathogenic microorganisms, cancer and HIV, and anti-rejection agents for organ transplantation. However, the use of carbohydrates as either therapeutic agents or immunogens is frequently problematic, as they are often rapidly metabolized and poorly immunogenic. Therefore, the search for carbohydrate-mimetic agents is of considerable therapeutic value, for the potential of such agents to both interfere with carbohydrate–protein interactions and to generate carbohydrate-specific immune responses. Areas covered: The review discusses recent examples of carbohydrate-mimetic peptides with regard to the structural and functional aspects of mimicry and the implications of peptide mimicry for application in therapeutics. The reader will gain knowledge of the various mechanisms of peptide carbohydrate mimicry, and the potential importance of these mechanisms in targeted therapeutic design. Expert opinion: Peptide carbohydrate mimicry is manifested by distinct mechanisms, any one of which may be relevant to specific protein targets. As structural information becomes available for a wider variety of systems, the questions about mimicry will be more effectively addressed.
History-Based Harvesting of Spare Cycles and Storage in Large-Scale Datacenters

An effective way to increase utilization and reduce costs in datacenters is to co-locate their latency-critical services and batch workloads. In this paper, we describe systems that harvest spare compute cycles and storage space for co-location purposes. The main challenge is minimizing the performance impact on the services, while accounting for their utilization and management patterns. To overcome this challenge, we propose techniques for giving the services priority over the resources, and leveraging historical information about them. Based on this information, we schedule related batch tasks on servers that exhibit similar patterns and will likely have enough available resources for the tasks' durations, and place data replicas at servers that exhibit diverse patterns. We characterize the dynamics of how services are utilized and managed in ten large-scale production datacenters. Using real experiments and simulations, we show that our techniques eliminate data loss and unavailability in many scenarios, while protecting the co-located services and improving batch job execution time.
Fabrication and examination of oxidation resistance of zinc coated copper and brass components by chemical deposition

In this work, the structure and the oxidation resistance of Zn deposited Cu and brass metallic components are examined. The deposition was accomplished with pack cementation chemical deposition. The examination of the samples was performed with electron microscopy and X-ray diffraction analysis. It was found that coatings on Cu substrate consist of two layers with different Zn concentrations, while coatings on brass were single layered with almost constant Zn concentration. The presence of distinct Zn–Cu phases was revealed in both cases. The subjection of the as coated samples together with the uncoated substrates in air at 400°C showed that both Zn coated samples have enhanced resistivity in such atmospheres, as most of the coating remained mostly unoxidised, and the substrates were fully protected. On the contrary, the bare substrates appear to have undergone severe damage as brittle oxides were formed on their surface.
Domain Knowledge as Corporate Resource of Financial Firms

It is almost a cliche to say that we live in a knowledge society and that knowledge is an important resource of firms in their production of goods and provision of services to their clients. However it is not so easy to find many examples showing the use of domain knowledge in financial companies. This paper reports the case of how a vehicle lease company in the Netherlands combines the use of domain knowledge and information technology into an expert system to automate the control of vehicle maintenance activity. The results benefit all parties concerned. The lease company can control the vehicle repair and maintenance works more efficiently. For the customers, it is higher rate of vehicle utilisation, greater safety and lower costs. The dealers who carry out the repairs and maintenance can do their work faster, and are paid immediately and automatically via the banks, resulting in lower administrative costs. The case story suggests that domain knowledge can be perceived as a corporate resource and its utilisation can produce values for the stakeholders. We propose that financial firms (1) see themselves as knowledge system, as a network of knowledge nodes serving their customers, (2) consider knowledge intensive firms as their role models. We draw on an idea of Friedrich Hayek who perceives the economic problem of society as a
XNPro: Low-Impact Hypervisor-Based Execution Prevention on ARM

As virtually all smartphones today run general purpose operating systems, they have to consider malware attacks, with rootkits being among the most hideous ones. Since rootkits execute with the same privileges as the OS kernel, traditional countermeasures are inherently fragile. While virtualization-based technologies have proven themselves capable means to see off rootkit attacks, being especially effective when used to foil code injection attacks, the approach has been dismissed so far as impractical for mobile devices on grounds of constrained resources. In this paper we make the case for using virtualization to counter kernel code injection on mobile devices. To that end, we designed EXecute Never Protection (XNPro), a small Type-I hypervisor that ensures that only authorized code is executed by the guest OS kernel even in the case that an adversary gains unfettered control over the guest. Our design emphasizes a small size of the hypervisor, ease of porting guests, and good runtime performance. To validate our design, we implemented a prototype on a ARM Cortex A7 platform. Various benchmark measurements of the prototype prove the feasibility of our approach.
Simultaneous localization, calibration, and tracking in an ad hoc sensor network

We introduce simultaneous localization and tracking, called SLAT, the problem of tracking a target in a sensor network while simultaneously localizing and calibrating the nodes of the network. Our proposed solution, LaSLAT, is a Bayesian filter that provides on-line probabilistic estimates of sensor locations and target tracks. It does not require globally accessible beacon signals or accurate ranging between the nodes. Real hardware experiments are presented for 2D and 3D, indoor and outdoor, and ultrasound and audible ranging-hardware-based deployments. Results demonstrate rapid convergence and high positioning accuracy
Perforinopathy: A Spectrum of Human Immune Disease Caused by Defective Perforin Delivery or Function

Congenital perforin deficiency is considered a rare cause of human immunopathology and immune dysregulation, and classically presents as a fatal illness early in infancy. However, we propose that a group of related disorders in which killer lymphocytes deliver only partially active perforin or a reduced quantum of wild-type perforin to the immune synapse should be considered part of an extended syndrome with overlapping but more variable clinical features. Apart from the many rare mutations scattered over the coding sequences, up to 10% of Caucasians carry the severely hypomorphic PRF1 allele C272 > T (leading to A91V mutation) and the overall prevalence of the homozygous state for A91V is around 1 in 600 individuals. We therefore postulate that the partial loss of perforin function and its clinical consequences may be more common then currently suspected. An acute clinical presentation is infrequent in A91V heterozygous individuals, but we postulate that the partial loss of perforin function may potentially be manifested in childhood or early adulthood as “idiopathic” inflammatory disease, or through increased cancer susceptibility – either hematological malignancy or multiple, independent primary cancers. We suggest the new term “perforinopathy” to signify the common functional endpoints of all the known consequences of perforin deficiency and failure to deliver fully functional perforin.
TRYPSIN AND PROTEIN DENATURATION INHIBITORY ACTIVITY OF LEAF AND ROOT OF JUSTICIA GENDARUSSA Patel SS * and Zaveri MN

Rheumatoid arthritis is a major ailment among autoimmune disorders. A large number of herbal extracts were used for the treatment of various types of rheumatoid disorder. The leaf and root of Justicia gendarussa belonging to Acanthaceae family, commonly known as Nilinirgundi is traditionally used for chronic rheumatism. The present study deals with in-vitro anti-arthritic activity in pharmacological models were studied such as inhibition of protein denaturation and trypsin (proteinase) inhibitory activity. Different fractions and isolated compound from alcoholic extract of leaf and root of J. gendarussa with different concentrations (10, 100, 1000μg/ml ) were studied and results were compared with standard drug Indomethacin. The alcoholic extract of leaf and root of J. gendarussa showed dose dependent activity which was found comparable to that of standard drug Indomethacin. Isolated compound-La of leaf of J. gendarussa inhibited the activity of trypsin with IC50 values 13.43 μg/ml and protein denaturation inhibition at the IC50 value of 24.74 μg/ml as compared to the standard drug Indomethacin.
Notes on Neglected and Underutilized Crops Genetic Diversity Assessment in Pandanus Amaryllifolius Roxb. Populations of India

Pandanus amaryllifolius is cultivated in home gardens in coastal regions of India. Leaves of P. amaryllifolius are scented and exploited commercially by flavour industry. In the present attempt, 40 clonal populations were used for genetic diversity assessment using ISSR and AFLP molecular marker. In ISSR based diversity analysis, out of 38 scorable primers, only one primer showed polymorphism and most of the polymorphic fragments were found in clonal populations from Thailand locality only. In AFLP based diversity analysis all clonal populations from India showed very low genetic distance except Kolkata and Amtala but these populations showed more similarity with Sri Lanka clones and these two localities showed more similarity with Thailand population. Present study confirms that the species has very low level of genetic variation even though it is exposed to a wide range of environmental conditions across peninsular India. Thus, the genome of P. amaryllifolius is said to be highly conserved and remained unaffected through its spread. As per previous report P. amaryllifolius has been introduced in Kolkata, India in 1798 from Indonesia, the similarity is shown by the populations of West Bengal with Thailand population which is close to Indonesia. The populations from Sri Lanka showed similarity with the populations from east and west coast of India suggests that Sri Lanka may be the another source of introduction of P. amaryllifolius in India.
Assembly of ER-associated protein degradation in vitro: dependence on cytosol, calnexin, and ATP

To investigate the mechanisms of ER-associated protein degradation (ERAD), this process was reconstituted in vitro. Established procedures for post-translational translocation of radiolabeled prepro-alpha factor into isolated yeast microsomes were modified to inhibit glycosylation and to include a posttranslocation "chase" incubation period to monitor degradation. Glycosylation was inhibited with a glyco- acceptor peptide to compete for core carbohydrates, or by using a radio- labeled alpha factor precursor that had been genetically engineered to eliminate all three glycosylation sites. Inhibition of glycosylation led to the production of unglycosylated pro-alpha factor (p alpha F), a processed form of the alpha factor precursor shown to be a substrate of ERAD in vivo. With this system, both glycosylated and unglycosylated forms of pro-alpha factor were stable throughout a 90-min chase incubation. However, the addition of cytosol to the chase incubation reaction induced a selective and rapid degradation of p alpha F. These results directly reflect the behavior of alpha factor precursor in vivo; i.e., p alpha F is a substrate for ERAD, while glycosylated pro- alpha factor is not. Heat inactivation and trypsin treatment of cytosol, as well as addition of ATP gamma S to the chase incubations, led to a stabilization of p alpha F. ERAD was observed in sec12 microsomes, indicating that export of p alpha F via transport vesicles was not required. Furthermore, p alpha F but not glycosylated pro-alpha factor was found in the supernatant of the chase incubation reactions, suggesting a specific transport system for this ERAD substrate. Finally, the degradation of p alpha F was inhibited when microsomes from a yeast strain containing a disrupted calnexin gene were examined. Together, these results indicate that cytosolic protein factor(s), ATP hydrolysis, and calnexin are required for ER-associated protein degradation in yeast, and suggest the cytosol as the site for degradation.
Unconscious processing of information in dynamic decision-making – an experimental approach

The purpose of the paper is to investigate the effects of unconscious versus conscious ways of making decisions in a dynamic decision-making task. An experimental setting is used to study this question; three experimental groups are distinguished: immediate decision-making (only limited time for cognitive processing), considered decisionmaking (time for conscious processing), and distracted decision-making (time for unconscious processing). As experimental stimulus, a simulator based on the Kaibab Plateau model is employed. Although more than 100 subjects have been tested so far, group differences are not significant for most data examined. Implications comprise the improvement of the experiment in order to derive at more substantial results. The value of the paper lies in the fact that it connects to a recent discussion in psychology and transfers it into a domain in the core interest of the system dynamics community: decision-making in situations with dynamic complexity.
Generation of Megawatt Optical Solitons in Hollow-Core Photonic Band-Gap Fibers

The measured dispersion of a low-loss, hollow-core photonic band-gap fiber is anomalous throughout most of the transmission band, and its variation with wavelength is large compared with that of a conventional step-index fiber. For an air-filled fiber, femtosecond self-frequency–shifted fundamental solitons with peak powers greater than 2megawatts can be supported. For Xe-filled fibers, nonfrequency-shifted temporal solitons with peak powers greater than 5.5 megawatts can be generated, representing an increase in the power that can be propagated in an optical fiber of two orders of magnitude. The results demonstrate a unique capability to deliver high-power pulses in a single spatial mode over distances exceeding 200 meters.
Realizing packet-optical integration with SDN and OpenFlow 1.1 extensions

This paper discusses the benefits of applying software defined networking (SDN) to circuit based transport networks. It first establishes the need for SDN in the context of transport networks. This paper argues that the use of SDN in the transport layers could be the enabler for both packet-optical integration and improved transport network applications. Then, this paper proposes extensions to OpenFlow 1.1 to achieve control of switches in multi-technology transport layers. The approach presented in this paper is simple, yet it distinguishes itself from similar work by its friendliness with respect to the current transport layer control plane based on generalized multiprotocol label switching (GMPLS). This is important as it will enable an easier and gradual injection of SDN into existing transport networks. This paper is completed with a few use case applications of SDN in transport networks.
Computing near-optimal solutions to combinatorial optimization problems

In the pastfew years, therehas beensigni(cid:12)cantprogressin our understanding of the extent to which near-optimal solutions can be e(cid:14)-ciently computed for NP-hard combinatorial optimization problems. This paper surveys these recent developments, while concentrating on the advances made in the design and analysis of approximation algorithms