Miracle-dz/UniFAR-FTUs huggingface dataset:
Introduction of a mutation in the shutter region of antithrombin (Phe77 --> Leu) increases affinity for heparin and decreases thermal stability.

The shutter region of serpins consists of a number of highly conserved residues that are critical for both stability and function. Several variants of antithrombin with substitutions in this region are unstable and predispose the carrier to thrombosis. Although most mutations in the shutter region investigated to date are deleterious with respect to serpin stability and function, the substitution of Phe51 by Leu in alpha(1)-antitrypsin results in enhanced stability. Here, we have investigated the effects of introducing an analogous mutation into antithrombin (Phe 77 to Leu). The mutation did not affect the kinetics of interaction with proteases. Strikingly, however, the thermostability of the protein was markedly decreased, with the serpin displaying a 13 degrees C decrease in melting temperature as compared to wild-type recombinant antithrombin. Further studies revealed that in contrast to wild-type antithrombin, the mutant adopted the latent (inactive) conformation upon mild heating. Previous studies on shutter region mutations that destabilize antithrombin revealed that such variants possess enhanced affinity for both heparin pentasaccharide and full-length heparin. The N135A/F77L mutant had unchanged affinity for heparin pentasaccharide, but the affinity for full-length heparin was increased. We suggest that the Phe77Leu mutation causes conformational changes around the top of the D-helix in antithrombin, in particular, to the arginine 132 and 133 residues that may mediate additional antithrombin/heparin interactions. This paper also demonstrates that there are major differences between the shutter regions of antithrombin and alpha(1)-antitrypsin since a stabilizing mutation in antitrypsin has the converse effect in antithrombin.
Rac1 and Cdc42 but Not RhoA or Rho Kinase Activities Are Required for Neurite Outgrowth Induced by the Netrin-1 Receptor DCC (Deleted in Colorectal Cancer) in N1E-115 Neuroblastoma Cells*

Netrins are chemotropic guidance cues that attract or repel growing axons during development. DCC (deleted in colorectalcancer), a transmembrane protein that is a receptor for netrin-1, is implicated in mediating both responses. However, the mechanism by which this is achieved remains unclear. Here we report that Rho GTPases are required for embryonic spinal commissural axon outgrowth induced by netrin-1. Using N1E-115 neuroblastoma cells, we found that both Rac1 and Cdc42 activities are required for DCC-induced neurite outgrowth. In contrast, down-regulation of RhoA and its effector Rho kinase stimulates the ability of DCC to induce neurite outgrowth. In Swiss 3T3 fibroblasts, DCC was found to trigger actin reorganization through activation of Rac1 but not Cdc42 or RhoA. We detected that stimulation of DCC receptors with netrin-1 resulted in a 4-fold increase in Rac1 activation. These results implicate the small GTPases Rac1, Cdc42, and RhoA as essential components that participate in signaling the response of axons to netrin-1 during neural development.
&bgr;1-Adrenergic blockade during cardiopulmonary resuscitation improves survival

Objective:The short-acting &bgr;1-selective adrenergic blocking agent, esmolol, was administrated during cardiopulmonary resuscitation with the hypothesis that initial resuscitation and postresuscitation survival would be improved. Design:Prospective, randomized, controlled study Setting:Animal research laboratory. Subjects:Male Sprague-Dawley rats. Interventions:Ventricular fibrillation was induced in 18 male Sprague-Dawley rats, which were then left untreated for 6 mins before attempted resuscitation with precordial compression, mechanical ventilation, and electrical defibrillation. Animals were randomized to receive 300 &mgr;g/kg esmolol in a volume of 200 &mgr;L or an equivalent volume of saline placebo during cardiopulmonary resuscitation. Electrical defibrillation was attempted after 12 mins of ventricular fibrillation. Measurements and Main Results:Esmolol-treated animals required a significantly smaller number of electrical shocks before resuscitation. Each of the esmolol-treated but only five of nine placebo-treated animals were successfully resuscitated. Postresuscitation contractile and left ventricular diastolic functions of resuscitated animals were significantly better after esmolol administration and duration of survival was significantly increased. Conclusions:A short-acting &bgr;1-selective adrenergic blocking agent, when administered during cardiopulmonary resuscitation, significantly improved initial cardiac resuscitation, minimized postresuscitation myocardial dysfunction, and increased the duration of postresuscitation survival.
Endoproteolytic Processing of the Lymphocytic Choriomeningitis Virus Glycoprotein by the Subtilase SKI-1/S1P

ABSTRACT The envelope glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) is posttranslationally cleaved into two subunits. We show here that this endoproteolytic processing is not required for transport to the cell surface but is essential for LCMV GP to mediate infectivity of pseudotyped retroviral vectors. By systematic mutational analysis of the LCMV GP cleavage site, we determined that the consensus motif R-(R/K/H)-L-(A/L/S/T/F)265 is essential for the endoproteolytic processing. In agreement with the identified consensus motif, we show that the cellular subtilase SKI-1/S1P cleaves LCMV GP.
Parthenogenesis and asexual multiplication among parasitic platyhelminths

SUMMARY Among flatworms with parasitic and commensal modes of existence, parthenogenesis and asexual multiplication appear to be largely confined to the Digenea and Cestoda, the only parasitic platyhelminths that routinely utilize indirect life-cycles. Parthenogenesis is apparently restricted to a minority of adult digeneans and cestodes inhabiting their final hosts, and a survey is made of the particular modes of parthenogenesis (i.e. apomictic, automictic and generative) which are employed by such adults. Asexual (amictic) multiplication, in the form of fissioning, is demonstrated by young adults of the cyclophyllidean cestode, Mesoces-toides corti, but is otherwise not exhibited by adult cestodes or digeneans, other than in the perplexing phenomenon of proglottid formation in polyzoic tapeworms. Secondary multiplication is of ubiquitous occurrence in digenean life-cycles in the form of the proliferation which takes place within sporocysts and rediae (germinal sacs) located in the first intermediate host. The controversy concerning the nature of this multiplication is reconsidered in the context of recent findings which have centred on cellular aspects. On the basis of present evidence germinal sac multiplication should be regarded as an asexual rather than a parthen-ogenetic process. The cestode asexual multiplication which occurs in intermediate hosts is a function of the metacestode stage of development. Metacestode proliferation is only known from about 20 species and 6 families of polyzoic cestodes with approximately half the described instances occurring in the family Taeniidae. The organization of these proliferative metacestodes, findings concerning their totipotent stem cells and the ontogeny of buds and new scolices are all reviewed. Finally, the capacity for population expansion of multiplicative larval digeneans and metacestodes are compared, while the ecological roles and the genetical consequences of both parthenogenesis and amictic multiplication in the two taxa are also examined.
Introducing the Key Stages for Addressing Multi-perspective Summarization

Generating summaries from evaluative text (e.g., reviews) is a challenging task, in which available metadata is hardly exploited, thus leading to the creation of very generic and biased summaries. In this paper, the novel task of multi-perspective summarization is introduced. The key stages for generating this type of summaries are defined, and a preliminary analysis of their feasibility is conducted. The main novelties of this study include: i) the linguistic treatment of the text at the level of basic information units, instead of sentences; and ii) the analysis carried out over the distribution of opinions and topics.
A Regression Model for Correcting Intraocular Lens Power after Refractive Surgery Independent of Preoperative Data

Purpose To find a method of calculating intraocular lens (IOL) power that may be independent of preoperative data in eyes that have previously undergone myopic laser in situ keratomileusis (LASIK). Methods In 148 eyes of 75 patients, before and 6 months after LASIK, IOL power was calculated with SRK/T formula utilizing the spherical equivalent as the desired target refraction. Assuming that LASIK does not alter the crystalline lens refractive properties, IOL calculation error (CER) was estimated with this formula: CER = [pre-LASIK IOL power]/[post-LASIK IOL power]. Then the authors used postoperative biometry and Orbscan II corneal topography data in multiple regression models to find the best variables to predict the CER. Predicted amount of error which is calculated independent of preoperative data could be used to correct the post-LASIK calculated IOL: [corrected post-LASIK IOL power] = CER x [post-LASIK IOL power]. Results A regression model with these predictors was found: axial length in millimeters (L), radius of the anterior corneal surface best fitted sphere in millimeters divided by radius of the posterior corneal surface best fitted sphere in millimeters (AntBFS/PostBFS), corneal central 5 millimeters mean power in diopters divided by corneal central 3 millimeters mean power in diopters (mean 5 mm/mean 3 mm), the post-LASIK IOL power, and the post-LASIK simulated K reading. The model R square was 0.88. Conclusions There is correlation between post-LASIK biometry values and IOL power correction factor. This study presents a new model for further investigation.
Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Diabetes mellitus (DM) is characterised by alterations in the intrarenal renin-angiotensin system (RAS). Insulin treatment may reverse these changes by an unknown mechanism. We aimed to verify the association between somatic ACE with 136 kDa (sACE) and N-domain ACE with 69 kDa (nACE) from Wistar (W) rat tissue with DM.Three groups were studied: control (CT), insulin treated diabetic (DT) and untreated (D). ACE activity was determined using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates. In D group, urine ACE activity increased for both substrates when compared with CT and DT, despite the decreased activity of renal tissues. Immunostaining of renal tissue demonstrated that ACE is more strongly expressed in the proximaltubule of D than in the same nephron portion in the other groups. Angiotensin (Ang) 1-7 and Ang II are less expressed in DT group when compared with CT and D. Ang II levels decreased in the D and DT groups showed when compared to the control. Ang 1-7 was detected in all studied groups with low levels in DT.The modulation of angiotensin peptides suggests that sACE, nACE, ACE 2 and NEP could have important functions in renal RAS regulation through a counter-regulatory mechanism to protect the kidney in diabetes mellitus.
Comparison of Two Major Forms of the Shigella Virulence Plasmid pINV: Positive Selection Is a Major Force Driving the Divergence

ABSTRACT All Shigella and enteroinvasive Escherichia coli (EIEC) strains carry a 230-kb virulence plasmid (pINV) which is essential for their invasiveness. There are two sequence forms, pINV A and pINV B, of the plasmid (R. Lan, B. Lumb, D. Ryan, and P. R. Reeves, Infect. Immun. 69:6303-6309, 2001), and the recently sequenced pINV plasmid from Shigella flexneri serotype 5 is a pINV B form. In this study we sequenced the majority of the coding region of the pINV A form from S. flexneri serotype 6 other than insertion sequence or related sequences and compared it with the pINV B form. More than half of the genes sequenced appear to be under positive selection based on their low ratio of synonymous to nonsynonymous substitutions. This high proportion of selected differences indicates that the two pINV forms have functional differences, and comparative studies of pathogenicity in different Shigella-EIEC strains could be informative. There are also genes absent in the S. flexneri serotype 6 plasmid, including the sepA gene encoding serine protease, the major secreted protein of S. flexneri serotype 2a, and the stbAB genes, which encode one of the two partition systems found in S. flexneri serotype 5. The incompatibility of the two pINV forms appears to be due to either small differences in the mvpAT postsegregational killing system or the presence of an unknown system in pINVA.
Towards quantifying and defining privacy metrics for online users

With personal information being stored on information systems, there exists a need to determine the amount of information that is obtainable for an individual. In this paper, the authors work toward measuring the personal information of an individual as stored within different levels within multiple information systems. The proposal takes into account different identity elements and assigned a privacy score and weighting to it. This is done in order to quantify an individual's privacy. A total privacy score can then be assigned to an individual for them to ascertain what their level of “visibility” is on various information systems accessible on and off the Internet. A user can then make use of this score to further a potential risk assessment of their personal information.
Genetic Algorithms Applied to Multi-Objective Aerospace Shape Optimization

A genetic algorithm approach suitable for solving multi-objective optimization problems is described and evaluated using a series of aerodynamic shape optimization problems. Several new features including two variations of a binning selection algorithm and a gene-space transformation procedure are included. The genetic algorithm is suitable for finding pareto optimal solutions in search spaces that are defined by any number of genes and that contain any number of local extrema. A new masking array capability is included allowing any gene or gene subset to be eliminated as decision variables from the design space. This allows determination of the effect of a single gene or gene subset on the pareto optimal solution. Results indicate that the genetic algorithm optimization approach is flexible in application and reliable. The binning selection algorithms generally provide pareto front quality enhancements and moderate convergence efficiency improvements for most of the problems solved.
Dynamics of immersed clamped-clamped microresonators

Micro- and nanomechanical resonators are used in a variety of sensing applications. We investigate the dynamics of clamped-clamped micromechanical string resonators immersed in viscous fluids. The resonators are driven using a magneto-motive technique and an optical lever is used to detect their motion. The resonance frequencies and Q-factors of the odd flexural resonance modes are determined up to the 9th mode. Using liquids with varying density and viscosity, the inertial and viscous effects are discriminated by measuring the resonance frequencies and Q-factors.
Identification and characterisation of human endometrial stem/progenitor cells

The human endometrium is a dynamic, cyclically regenerating tissue. Because adult stem cells are present in other regenerative tissues, a clonal analysis of purified endometrial epithelial and stromal cells derived from hysterectomy tissue was undertaken, as a first attempt to identify and characterise endometrial stem/progenitor cells. Rare populations of epithelial and stromal cells were clonogenic. Only those cells initiating large clones, 0.09% of epithelial cells and 0.02% of stromal cells, are likely to be endometrial stem/progenitor cells.
Presentation of endogenous immunoglobulin determinant to immunoglobulin‐recognizing T cell clones by the thymic cells

Using immunoglobulin (Ig)‐recognizing T helper clones the expression of Ig peptide/major histocompatibility complex class II complexes derived by the processing of endogeneous Ig molecules in the thymus was demonstrated. It was found that thymic B cells but not “classic” thymic antigen‐presenting cells and macrophages represent the major antigen‐presenting cell type of determinants of endogenously synthesized surface Ig (Igx‐1b) and anti‐surface Ig antibodies (IdC3B9). The Igx‐1b‐presenting activity in the thymus appears relatively late, only after 3 weeks of postnatal life, while in the spleen an efficient presentation of endogenous Igx‐1b epitope is observed very early after birth. This difference between thymic and peripheral presentation of endogeneous Ig determinant could be important for understanding the mechanisms of T cell tolerance to self Ig and the role of self Ig in negative and positive selection of T cell repertoire.
Coupled Mooring Analyses for the WEC-Sim Wave Energy Converter Design Tool

A wave-energy-converter-specific time-domain modeling method (WEC-Sim) was coupled with a lumped-mass-based mooring model (MoorDyn) to improve its mooring dynamics modeling capability. This paper presents a verification and validation study on the coupled numerical method. First, a coupled model was built to simulate a 1/25 model scale floating power system connected to a traditional three-point catenary mooring with an angle of 120 between the lines. The body response and the tension force on the mooring lines at the fairlead in decay tests and under regular and irregular waves were examined. To validate and verify the coupled numerical method, the simulation results were compared to the measurements from a wave tank test and a commercial code (OrcaFlex). Second, a coupled model was built to simulate a two-body point absorber system with a chain-connected catenary system. The influence of the mooring connection on the point absorber was investigated. Overall, the study showed that the coupling of WEC-Sim and the MoorDyn model works reasonably well for simulating a floating system with practical mooring designs and predicting the corresponding dynamic loads on the mooring lines. Further analyses on improving coupling efficiency and the feasibility of applying the numerical method to simulate WEC systems with moremore » complex mooring configuration are still needed. « less
Optimized (2, 4) Stencil Runge–Kutta ADE-ADI FDTD With Application to Plasma

This paper discusses the improvement of the numerical dispersion characteristics of alternating direction implicit (ADI) finite-difference time-domain (FDTD) aimed at acquiring more accurate electromagnetic information of plasma. Through adding the optimization method, which is based on the optimization of spatial derivative to the (2, 4) stencil ADI FDTD, the optimized (2, 4) stencil ADI FDTD is proposed, and its unconditional stability is proved theoretically. The phase velocity error of the optimized (2, 4) stencil ADI FDTD versus propagation angle and grid density is investigated. In addition, the Runge–Kutta auxiliary differential equation (RKADE) scheme for tackling the constitutive relation equation of plasma is deduced, which is without additional storage occupation and computational burden compared with ADE scheme. Its numerical conductivity error is analyzed under different incident frequencies and electron collision frequencies. Through incorporating the RKADE scheme into the optimized (2, 4) stencil ADI FDTD, the optimized (2, 4) stencil RKADE-ADI FDTD is presented. The accuracy and relatively wideband capability of the proposed method is validated by two numerical experiments.
TIDAL SIGNATURES IN THE FAINTEST MILKY WAY SATELLITES: THE DETAILED PROPERTIES OF LEO V, PISCES II, AND CANES VENATICI II

We present deep wide-field photometry of three recently discovered faint Milky Way (MW) satellites: Leo V, Pisces II, and Canes Venatici II. Our main goals are to study the structure and star formation history of these dwarfs; we also search for signs of tidal disturbance. The three satellites have similar half-light radii (∼60–90 pc) but a wide range of ellipticities. Both Leo V and CVn II show hints of stream-like overdensities at large radii. An analysis of the satellite color–magnitude diagrams shows that all three objects are old (>10 Gyr) and metal-poor ([Fe/H] ∼ −2), though neither the models nor the data have sufficient precision to assess when the satellites formed with respect to cosmic reionization. The lack of an observed younger stellar population (≲ 10 Gyr) possibly sets them apart from the other satellites at Galactocentric distances ≳ 150 kpc. We present a new compilation of structural data for all MW satellite galaxies and use it to compare the properties of classical dwarfs to the ultra-faints. The ellipticity distribution of the two groups is consistent at the ∼2σ level. However, the faintest satellites tend to be more aligned toward the Galactic Center, and those satellites with the highest ellipticity (≳ 0.4) have orientations (ΔθGC) in the range 20° ≲ ΔθGC ≲ 40°. This latter observation is in rough agreement with predictions from simulations of dwarf galaxies that have lost a significant fraction of their dark matter halos and are being tidally stripped.
The Productivity of Information Technology Investments: New Evidence from IT Labor Data

This paper uses newly collected panel data that allow for significant improvements in the measurement and modeling of information technology (IT) productivity to address some longstanding empirical limitations in the IT business value literature. First, we show that using generalized method of moments--based estimators to account for the endogeneity of IT spending produces coefficient estimates that are only about 10% lower than unadjusted estimates, suggesting that the effects of endogeneity on IT productivity estimates may be relatively small. Second, analysis of the expanded panel suggests that (a) IT returns are substantially lower in midsize firms than in Fortune 500 firms; (b) they materialize more slowly in large firms---in midsize firms, unlike in larger firms, the short-run contribution of IT to output is similar to the long-run output contribution; and (c) the measured marginal product of IT spending is higher from 2000 to 2006 than in any previous period, suggesting that firms, and especially large firms, have been continuing to develop new, valuable IT-enabled business process innovations. Furthermore, we show that the productivity of IT investments is higher in manufacturing sectors and that our productivity results are robust to controls for IT labor quality and outsourcing levels.
Optimizing the Duration of Dual Antiplatelet Therapy After Implantation of Drug-eluting Coronary Stents

Percutaneous coronary intervention (PCI) with implantation of drug-eluting stents (DESs) has become the standard of care for coronary artery disease and gives a great impetus to device industry. [1,2] In 2013, approximately half million patients with coronary artery disease underwent PCI in China, with a penetration rate of DES reaching beyond 95%. [3] The use of DES including domestic ones is highly effective in preventing coronary restenosis, but there is a collateral cost to be borne in terms of delayed healing or re-endothelialization of the stented arterial segment and risk of stent thrombosis. [4] Therefore, dual antiplatelet therapy (DAPT) with aspirin and P2Y12 receptor antagonist for at least 12 months after DES implantation is strongly recommended by Chinese guidelines on PCI. [5] Since prolonged DAPT may increase major bleeding and subsequent mortality, balancing ischemia (or thrombotic events) and bleeding with DAPT is always important for improving overall clinical outcome after DES-based PCI. [6]