Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Analytical Performance of TCP Variants in IP and MPLS Networks

Transmission control protocol (TCP) provides reliable end-to-end data communication under unpredictable and dynamic network conditions. Different variants of TCP have been proposed which show varying degree of resilience in best effort IP networks characteristics. Multi-protocol label switching (MPLS) has proven strength in providing quality of service based data services due to its traffic engineering procedures. This paper presents a comprehensive experimental analysis of TCP variants under MPLS with emphasis on Tahoe, Reno and Vegas. Under different traffic load, it has been found that Reno and Tahoe fail to take advantage of MPLS features where as Vegas has shown promising results with almost stable constant end-to-end delay after a transient phase of delay fluctuations in the early stages of data transmission session. The stable end-to-end delay under MPLS makes Vegas an attractive choice for medium to large size real-time traffic.
PrPSc Binding Antibodies Are Potent Inhibitors of Prion Replication in Cell Lines*

Conversion of the cellular α-helical prion protein (PrPC) into a disease-associated isoform (PrPSc) is central to the pathogenesis of prion diseases. Molecules targeting either normal or disease-associated isoforms may be of therapeutic interest, and the antibodies binding PrPC have been shown to inhibit prion accumulation in vitro. Here we investigate whether antibodies that additionally target disease-associated isoforms such as PrPSc inhibit prion replication in ovine PrP-inducible scrapie-infected Rov cells. We conclude from these experiments that antibodies exclusively binding PrPC were relatively inefficient inhibitors of ScRov cell PrPSc accumulation compared with antibodies that additionally targeted disease-associated PrP isoforms. Although the mechanism by which these monoclonal antibodies inhibit prion replication is unclear, some of the data suggest that antibodies might actively increase PrPSc turnover. Thus antibodies that bind to both normal and disease-associated isoforms represent very promising anti-prion agents.
Crystal structure of PurE (BA0288) from Bacillus anthracis at 1.8 Å resolution

Introduction. As part of a structural genomics program, Structural Proteomics in Europe (SPINE), we are determining protein structures from the causative agent of anthrax, Bacillus anthracis, a Gram-positive spore-forming bacterium. Among initial candidates for crystallographic analysis are enzymes involved in nucleotide biosynthesis. The BA0288 gene (www.tigr.org) of B. anthracis encodes a protein with 57% amino acid sequence identity to the Escherichia coli 5 -phosphoribosyl-5-aminoimidazole carboxylase (PurE). PurE proteins are highly conserved and are designated as Class I or Class II according to their enzymatic activity. Class I enzymes, found in yeast, plants, and prokaryotes, catalyze the second of a two-step conversion of 5-aminoimidazole ribonucleotide (AIR), via the intermediate N-carboxyaminoimidazole ribonucleotide (N-CAIR), to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR). The conversion of AIR to N-CAIR is catalyzed by N-CAIR synthetase (PurK) in the presence of ATP and bicarbonate. Class II enzymes from higher eukaryotes catalyze the conversion of AIR to CAIR directly, in the presence of bicarbonate or CO2. 4 Therefore, Class I PurE proteins function as phosphoribosylaminoimidazole mutases, while Class II enzymes are carboxylases. This difference in activity could be exploited to provide potential targets for antibacterial therapies.
Thinking about a nuclear matrix.

The possible existence in eukaryotic cells of an internal, non-chromatin nuclear structural framework that facilitates gene readout as a set of spatially concerted reactions has become a popular but controversial theater of investigation. This article endeavors to present a circumspect review of the nuclear matrix concept as we presently know it, framed around two contrasting hypotheses: (1) that an internal nuclear framework actively enhances gene expression (in much the same way the cytoskeleton mediates cell locomotion, mitosis and intracellular vesicular traffic) versus (2) that the interphase chromosomes have fixed, inherited positions and that the DNA replication, transcripton and RNA processing machinery diffusionally arrives at sites of gene readout, with some aspects of nuclear structure thus being more a result than a cause of gene expression. On balance, the available information suggests that interactions among various gene expression machines may contribute to isolated nuclear matrix preparations. Some components of isolated nuclear matrix preparations may also reflect induced or reconfigured protein-protein associations. The protein characterization and ultrastructural analysis of the isolated nuclear matrix has advanced significantly in recent years, although controversies remain. Important new clues are now coming in from promising contemporary lines of research that report on nuclear structure in living cells.
Mutations in the inter-SH2 domain of the regulatory subunit of phosphoinositide 3-kinase: effects on catalytic subunit binding and holoenzyme function

Abstract Class IA phosphoinositide 3-kinases (PI3Ks) represent a group of heterodimeric lipid kinases with important functions in cellular signal transduction. The regulatory p85 subunit constitutively binds to the catalytic p110 subunit and mediates the recruitment of the heterodimer to various membrane-localized proteins upon activation by a vast array of stimuli. The functional characterization of protein domains that mediate p85 function has been hampered by a lack of structural data. Therefore, we investigated a 35-aa region in the inter-SH2 domain of p85, reported to be necessary for binding of p110, by site-directed mutagenesis and evaluated the importance of individual amino acids for PI3K heterodimer formation. This approach led to the identification of an 11-aa region required for p110 binding in vitro and mesoderm induction during early Xenopus development in vivo. Further analyses revealed two pairs of hydrophobic amino acids within this region, which are particularly important for high-affinity intersubunit interaction. Thus, our data provide further insight into the molecular mechanisms of PI3K intersubunit interaction and led to the identification of new p85 mutant proteins with varying degrees of dominant-negative effects that will be helpful for future PI3K-related research.
La/Sm/Er Cation Doping Induced Thermal Properties of SrTiO3 Perovskite.

The La/Sm/Er cations with different radii doping SrTiO3 (STO) as model Sr0.9R0. 1TiO3 (R = La, Sm, Er) were designed to investigate structural characteristics and thermal properties by the molecular dynamics simulation with the Green-Kubo relation at 300-2000 K. The structural characteristics were composed of lattice constant, atoms excursion, and pair correlation function (PCF). The thermal properties consisted of heat capacity and thermal conductivity. The lattice constant of R-doped exhibited less than the STO at 300-1100 K and more than STO at 1500-2000 K, which was encouraged by atom excursion and PCF. The thermal properties was compared with literature data at 300-1100 K. In addition, the thermal properties at 1100-2000 K were predicted. It highlights that thermal conductivity tends to decrease at high temperature, due to perturbation of La, Sm, and Er, respectively.
Correction: Structural and Functional Similarities between Osmotin from Nicotiana Tabacum Seeds and Human Adiponectin

Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the b-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico. Copyright: ß 2011 Miele et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors have no support or funding to report.
The velocity of unloaded shortening and its relation to sarcomere length and isometric force in vertebrate muscle fibres.

1. The velocity of shortening at zero load was studied during fused tetanic contractions and single twitches in isolated skeletal muscle fibres of Rana temporaria. 2. The technique used for determination of the speed of unloaded shortening consisted of a series of quick releases of different amplitudes applied at a given instant during activity. The time, delta t, needed for the fibre to take up the slack was plotted against the amplitude of release, delta L. The slope of the straight line relating delta t‐delta L provided a measure of the velocity of shortening at zero load, V0. 3. V0 was compared with force‐velocity data obtained at finite loads (load‐clamp recordings). The predicted velocity of shortening at zero load, derived by hyperbolic extrapolation from velocities at low and intermediate loads, was not significantly different from V0. 4. The temperature dependence of isometric force and of shortening velocity was investigated between 2 and 12 degrees C in the same fibres. Q10 was 2.67 +/‐ 0.07 (S.E. of mean, n = 6) for V0 and 1.24 +/‐ 0.01 for tetanic force. 5. The velocity of unloaded shortening was determined at different sarcomere lengths in the range 1.4‐‐3.1 microns. V0 was constant between 1.65 microns and approximately 2.7 microns. It decreased below 1.65 microns and increased above 2.7 microns. 6. The decrease in velocity at short sarcomere lengths probably reflects an increase of the passive resistance to shortening. The increase in velocity at long sarcomere lengths can be accounted for by the passive compressive force that is produced by the parallel elastic elements of the prestretched fibre. 7. V0 was determined at the peak of the twitch and during the plateau of the fused tetanus in the same fibre. Whereas the peak twitch force varied between 38 and 85% of the tetanic tension in the different fibres (mean: 71 +/‐ 5%, n = 8), V0 during the twitch was 99 +/‐ 2% of the value recorded during the tetanus. Depression of the isometric twitch amplitude to 10% of the control value by dantrolene did not cause any significant reduction of V0.
Does isochromosome 7q mandate bone marrow transplant in children with Shwachman–Diamond syndrome?

Summary. We report on nine children with Shwachman–Diamond syndrome (SDS), eight of whom had clonal abnormalities of chromosome 7. Seven children had an isochromosome 7 [i(7)(q10)] and one a derivative chromosome 7, all with an apparently identical (centromeric) breakpoint. Children with SDS are predisposed to myelodysplasia (MDS) and acute myeloid leukaemia (AML) often with chromosome 7 abnormalities. Allogeneic transplants have been used to treat these children, however, they are a high‐risk transplant group and require careful evaluation. Three of the children were transplanted but only one survived, who to our knowledge remains the longest surviving SDS transplant patient (4·5 years +). The six non‐transplanted children are well. In classic MDS, chromosome 7 abnormalities are associated with rapid progression to acute leukaemia; however, we present evidence to suggest that isochromosome 7q may represent a separate disease entity in SDS children. This is a particularly interesting finding given that the SDS gene has recently been mapped to the centromeric region of chromosome 7. Our studies indicate that i(7)(q10) is a relatively benign rearrangement and that it is not advisable to offer allogeneic transplants to SDS children with i(7)(q10) alone in the absence of other clinical signs of disease progression.
15N and 1H NMR study of histidine containing protein (hpr) from staphylococcus carnosus at high pressure

The pressure‐induced changes in 15N enriched HPr from Staphylococcus carnosus were investigated by two‐dimensional (2D) heteronuclear NMR spectroscopy at pressures ranging from atmospheric pressure up to 200 MPa. The NMR experiments allowed the simultaneous observation of the backbone and side‐chain amide protons and nitrogens. Most of the resonances shift downfield with increasing pressure indicating generalized pressure‐induced conformational changes. The average pressure‐induced shifts for amide protons and nitrogens are 0.285 ppm GPa−1 at 278 K and 2.20 ppm GPa−1, respectively. At 298 K the corresponding values are 0.275 and 2.41 ppm GPa−1. Proton and nitrogen pressure coefficients show a significant but rather small correlation (0.31) if determined for all amide resonances. When restricting the analysis to amide groups in the β‐pleated sheet, the correlation between these coefficients is with 0.59 significantly higher. As already described for other proteins, the amide proton pressure coefficients are strongly correlated to the corresponding hydrogen bond distances, and thus are indicators for the pressure‐induced changes of the hydrogen bond lengths. The nitrogen shift changes appear to sense other physical phenomena such as changes of the local backbone conformation as well. Interpretation of the pressure‐induced shifts in terms of structural changes in the HPr protein suggests the following picture: the four‐stranded β‐pleated sheet of HPr protein is the least compressible part of the structure showing only small pressure effects. The two long helices a and c show intermediary effects that could be explained by a higher compressibility and a concomitant bending of the helices. The largest pressure coefficients are found in the active center region around His15 and in the regulatory helix b which includes the phosphorylation site Ser46 for the HPr kinase. This suggests that this part of the structure occurs in a number of different structural states whose equilibrium populations are shifted by pressure. In contrast to the surrounding residues of the active center loop that show large pressure effects, Ile14 has a very small proton and nitrogen pressure coefficient. It could represent some kind of anchoring point of the active center loop that holds it in the right place in space, whereas other parts of the loop adapt themselves to changing external conditions.
Performance evaluation of routing protocol on AODV and DSR under wormhole attack

Today’s Mobile Ad hoc Networks (MANETs) became a popular issue for scientists, and diverse studies have been made to increase the performance of ad hoc networks. In MANET nodes compromise to forward packets for each other communicate beyond their transmission range. The mobile nodes communicate with each other without any infrastructure. As wireless ad-hoc networks lack an infrastructure, they are exposed to a lot of attacks [1]. One of these attacks called Wormhole Attack that two adversary node collaborate together to transmit the packets in out of band channel. In this paper, performance of Ad hoc on-Demand Distance Vector (AODV) Protocol and Dynamic Source Routing (DSR) protocol are evaluated in presence of wormhole attack and without wormhole attack with Constant Bit Rate (CBR) traffic under dissimilar scalable network mobility. Also we evaluate effect and compare it with standard protocol in term of Packet Delivery Ratio, throughput and End to End Delay via simulation, using Network Simulation2 (NS2) for our research.
Wireless corner - Calibration-free RF-based localization algorithm for sensor actuator networks using particle filters

A calibration-free localization algorithm for sensor actuator networks is presented in this paper. The algorithm uses sequential importance sampling to estimate the location of a number of limited-capability sensors, using the strength of the signals transmitted from the sensor node to GPS-enabled mobile actuator nodes that work as anchor nodes. Simulation results show that the algorithm converges to an error range of 1 m in approximately 10 time steps, for very small Rice factors and four anchor nodes. The algorithm was verified using the network simulator NS-2.28
UbaLAI is a monomeric Type IIE restriction enzyme

Abstract Type II restriction endonucleases (REases) form a large and highly diverse group of enzymes. Even REases specific for a common recognition site often vary in their oligomeric structure, domain organization and DNA cleavage mechanisms. Here we report biochemical and structural characterization of the monomeric restriction endonuclease UbaLAI, specific for the pseudosymmetric DNA sequence 5′-CC/WGG-3′ (where W = A/T, and ‘/’ marks the cleavage position). We present a 1.6 Å co-crystal structure of UbaLAI N-terminal domain (UbaLAI-N) and show that it resembles the B3-family domain of EcoRII specific for the 5′-CCWGG-3′ sequence. We also find that UbaLAI C-terminal domain (UbaLAI-C) is closely related to the monomeric REase MvaI, another enzyme specific for the 5′-CCWGG-3′ sequence. Kinetic studies of UbaLAI revealed that it requires two recognition sites for optimal activity, and, like other type IIE enzymes, uses one copy of a recognition site to stimulate cleavage of a second copy. We propose that during the reaction UbaLAI-N acts as a handle that tethers the monomeric UbaLAI-C domain to the DNA, thereby helping UbaLAI-C to perform two sequential DNA nicking reactions on the second recognition site during a single DNA-binding event. A similar reaction mechanism may be characteristic to other monomeric two-domain REases.
Identification of a HLA-A*0201-restricted immunogenic epitope from the universal tumor antigen DEPDC1

ABSTRACT The identification of universal tumor-specific antigens shared between multiple patients and/or multiple tumors is of great importance to overcome the practical limitations of personalized cancer immunotherapy. Recent studies support the involvement of DEPDC1 in many aspects of cancer traits, such as cell proliferation, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most types of human tumors, and closely linked to a poorer prognosis; therefore, it might be regarded as a novel universal oncoantigen potentially suitable for targeting many different cancers. In this regard, we report the identification of a HLA-A*0201 allele-restricted immunogenic DEPDC1-derived epitope, which is able to induce cytotoxic T lymphocytes (CTL) exerting a strong and specific functional response in vitro toward not only peptide-loaded cells but also triple negative breast cancer (TNBC) cells endogenously expressing the DEPDC1 protein. Such CTL are also therapeutically active against human TNBC xenografts in vivo upon adoptive transfer in immunodeficient mice. Overall, these data provide evidence that this DEPDC1-derived antigenic epitope can be exploited as a new tool for developing immunotherapeutic strategies for HLA-A*0201 patients with TNBC, and potentially many other cancers.
Versatile silicon photodiode detector technology for scanning electron microscopy with high-efficiency sub-5 keV electron detection

A new silicon electron detector technology for Scanning Electron Microscopy, based on ultrashallow p+n boron-layer photodiodes, features nm-thin anodes enabling low-energy electron detection with record-high sensitivity down to 200 eV. Designs with segmented, closely-packed photodiodes and through-wafer apertures allow flexible configurations for optimal material and/or topographical contrasts. A high scanning speed is obtained by growing a well-controlled, lightly-doped, tens-of-microns-thick epi-layer for low capacitance, and by patterning a conductive grid directly on the photosensitive surface for low series resistance.
Nonstatin Low-Density Lipoprotein–Lowering Therapy and Cardiovascular Risk Reduction—Statement From ATVB Council

Pharmacological reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here, we consider the place of nonstatin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional nonstatins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin, and fibrates given as monotherapy each reduce CVD end points. From trials in which patients’ LDL cholesterol was already well controlled on a statin, adding ezetimibe incrementally reduced CVD end points, whereas adding a fibrate or niacin showed no incremental benefit. Among emerging nonstatins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 added to a statin and given for ⩽78 weeks showed preliminary evidence of reductions in CVD outcomes. Although these promising early findings contributed to the recent approval of these agents in Europe and in North America, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other nonstatin agents recently approved in the United States include lomitapide and mipomersen, which both act via distinctive LDL receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift toward more assertive LDL-lowering treatment, using both statins and nonstatins initiated earlier in appropriately selected patients.