Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a Novel HIV-1 Inhibitor Targeting Vif-dependent Degradation of Human APOBEC3G Protein*

Background: The interaction between HIV Vif protein and innate antiviral factor APOBEC3G represents a potential therapeutic target. Results: Screening for inhibitors of Vif-APOBEC3G interaction identified a small molecule, N.41, that protects APOBEC3G from Vif-mediated degradation and exhibits antiviral activity. Conclusion: N.41 is a lead for further development as an antiviral. Significance: These findings suggest new strategies for developing anti-HIV therapeutics. APOBEC3G (A3G) is a cellular cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA and by deamination-independent mechanisms. HIV-1 Vif binds to A3G, resulting in its degradation via the 26 S proteasome. Therefore, this interaction represents a potential therapeutic target. To identify compounds that inhibit interaction between A3G and HIV-1 Vif in a high throughput format, we developed a homogeneous time-resolved fluorescence resonance energy transfer assay. A 307,520 compound library from the NIH Molecular Libraries Small Molecule Repository was screened. Secondary screens to evaluate dose-response performance and off-target effects, cell-based assays to identify compounds that attenuate Vif-dependent degradation of A3G, and assays testing antiviral activity in peripheral blood mononuclear cells and T cells were employed. One compound, N.41, showed potent antiviral activity in A3G(+) but not in A3G(−) T cells and had an IC50 as low as 8.4 μm and a TC50 of >100 μm when tested against HIV-1Ba-L replication in peripheral blood mononuclear cells. N.41 inhibited the Vif-A3G interaction and increased cellular A3G levels and incorporation of A3G into virions, thereby attenuating virus infectivity in a Vif-dependent manner. N.41 activity was also species- and Vif-dependent. Preliminary structure-activity relationship studies suggest that a hydroxyl moiety located at a phenylamino group is critical for N.41 anti-HIV activity and identified N.41 analogs with better potency (IC50 as low as 4.2 μm). These findings identify a new lead compound that attenuates HIV replication by liberating A3G from Vif regulation and increasing its innate antiviral activity.
An Incentive Early Retirement Model for College and University Faculty

This paper outlines simulated results of an incentive, early-retirement model for college and university faculty. An alternative employment propensity, reflecting off-campus or professional employment prospects, is used to determine the incentive portion of an early-retirement offer. Benefit determination involves present-value calculations of future compensation, adjusted for survival rates, continued employment prospects, and enrollment changes. The cost determination involves similar present-value calculations of projected future salary. The consequence is that if the institution uses this method, it will realize declining net benefits as an individual faculty member's alternative employment prospects decline. On the other hand, the institution is also more likely to experience an acceptance of an early-retirement offer by a faculty member.
Shift of Power and Transformation of IIAs: A Power Structure Analysis of International Investment Agreements Regime

Doctrinal analysis of IIAs explains little about the convergence in contents yet divergence in forms of IIAs. The evolutionary paradox of IIAs regime demands the political analysis of international legal process. This research is devoted to critically appraise the desirability and feasibility of IIAs from the perspective of power shift under international investment law regime. Supply of IIAs as public good implies the dominating role of major states in the collective governance of transnational investment activities. The power underlying IIAs negotiating states functions as a tool to drive the initiation and compromise of IIAs negotiations and to commensurate and aggregate the divergent or even conflicting IIAs preferences. This research identifies three functioning mechanisms of power in legal process of IIAs, namely coercion with unilateral concessions of weak states to strong states, contract with bilateral concessions between negotiating states, and preference output.From a static perspective, coercion functions as a reveal mechanism of the centricity of conflicted preferences and would be adopted first in the negotiation while contract function only when coercion fails. IIAs would be supplied through coordination approach if the preference difference between contracting states are inessential and powerful state is willing to bear the cost to initiate the negotiation, and by coercion (contract) approach if the centricity of conflicting preference is low (high) and asymmetry of power disparity between states is high(low). From a dynamic perspective, this research proposes the power structure in terms of diffusion and aggregation underlying IIAs regime at systematic level shifts from a Centre-Fringe Structure to a Multi-hub Network Structure. During the transition, the importance of coercion as preference reveal mechanism decreases in contrast to the increasing function of contract and therefore, the number of new initiated and successful concluded IIAs decreases but the proportion of IIAs with bilateral concessions increases. As a complex system, the long term evolution of IIAs regime is oriented by shift of underlying power structure, diluted by institutional inertia and perturbed by incidental events.
PALSAR Wide-Area Mapping of Borneo: Methodology and Map Validation

This paper describes the operational radar mapping processing chain developed and steps taken to produce a provisional wide-area PALSAR forest and land cover map covering Borneo for the year 2007, compliant with emerging international standards (CEOS guidelines, FAO LCCS). A Bayesian approach based on (unsupervised) mixture modeling followed by Markov Random Field (MRF) classification has been selected for its suitability and flexibility to deal with a situation where ground truth is sparse and sometimes ambiguous. The methodology is based on the classification of Fine Beam Single (FBS) and Fine Beam Dual (FBD) polarization (path) image pairs. To cover Borneo the equivalent of 554 standard images is required. Qualitative and quantitative validation results and findings are reported. The final overall accuracy assessment result shows the demonstration map product is in 85.5% full agreement with the independent reference dataset and in 7.8% 'partial agreement'. The accuracy achieved is widely considered adequate, a very promising result for a sub-continental high resolution map based on just single-year radar data. Approaches for further improvement of the accuracy of less accurately classified thematic classes such as grassland, cropland and shrubland are suggested. This work has been undertaken in part within the framework of the ALOS Kyoto & Carbon Initiative.
Automated monitoring and detection of resource-limited NFV-based services

The growing demand for flexibility and cost reduction in the telecommunication landscape directs the focus of service development heavily to programmability and softwarization. In the domain of Network Function Virtualization (NFV), one of the goals is to replace dedicated hardware devices (such as switches, routers, firewalls) with software-based network functionalities, showing comparable performance when deployed on common servers. In this paper, we discuss how current VNF implementation and deployment strategies impact the efficient monitoring of their resources. In a multi-tenant, NFV-based ecosystem, different Service Providers deploy VNFs on a shared infrastructure, where the Infrastructure Provider exposes only VNF specific metrics and little information about the physical hosts where the VNFs are eventually orchestrated. Especially in the situation where datacenters are overcommitted, detecting the risk of e.g. CPU starvation is not straight-forward, when no information from the physical host is available. A new monitoring technique is introduced, based on the skewness of the measured probability distribution of the VNF resource consumption. Our measurements show that this metric is a good indicator for the (un)availability of the required CPU resources in the datacenter.
Relationship between craniofacial abnormalities and sleep-disordered breathing in Marfan's syndrome.

OBJECTIVES To examine the prevalence and nature of craniofacial abnormalities in patients with Marfan's syndrome and to investigate the relationship between craniofacial abnormalities and obstructive sleep apnea (OSA) severity in these patients. DESIGN Cross-sectional. SETTING Marfan's syndrome clinic in a tertiary teaching hospital. PATIENTS Fifteen consecutive adult patients (7 men and 8 women; mean [+/- SD] age, 34.8 +/- 13.2 years) who had Marfan's syndrome. MEASUREMENTS AND RESULTS Apneic status was determined from standard overnight polysomnography testing. Measurements from standardized lateral cephalometric radiographs were compared to normative data. Thirteen patients had OSA, which was defined as an apnea/hypopnea index (AHI) of > 5 episodes per hour (mean AHI, 22 +/- 15 episodes per hour). A high prevalence of craniofacial abnormalities was found with significant gender differences for some of the variables. Significant abnormalities for the entire group were bimaxillary retrusion, a reduced maxillary length, an increased total anterior face height, a long lower anterior face height, an obtuse gonial angle, a steep mandibular plane, a reduced posterior nasal airway height, a reduced posterior airway space, and an increased distance from the mandibular plane to the hyoid bone. Univariate analysis revealed significant correlations among the total anterior face height, the upper anterior and posterior face heights, the mandibular length, and AHI. There was a significant correlation between the rank of the number of cephalometric abnormalities per patient and AHI in those patients with OSA. CONCLUSIONS Craniofacial abnormalities are common in patients with Marfan's syndrome. The relationship between some cephalometric parameters and apnea severity suggests a potential role of craniofacial structure in the pathogenesis of OSA in these patients.
Effects of extrusion of flaxseed on ruminal and postruminal nutrient digestibilities

A study was conducted to determine the effects of extrusion on ruminal, post-ruminal and whole tract digestibility of flaxseed. Extrusion was performed at 155°C with a residence time of 43 s. Two non-lactating Holstein cows fitted with ruminal and duodenal cannulas were used in a randomized complete block design. Results showed that extruded flaxseed had higher (P < 0.05) in situ soluble and lower (P < 0.05) slowly degradable DM and CP fractions than unheated flaxseed. Extrusion increased (P < 0.05) ruminal DM and CP degradability of flaxseed by 7 and 13%, respectively. Ruminal undegraded DM, CP and NDF were all lower (P < 0.05) for extruded flaxseed than for unheated flaxseed. Extrusion increased (P < 0.05) ruminal degradability and reduced (P < 0.05) post-ruminal availability of most amino acids of flaxseed. Whole tract digestibility of DM, CP, NDF and amino acids were higher (P < 0.05) for extruded than for unheated flaxseed. It was concluded that extrusion under the conditions used in the present experiment increases ruminal and whole tract nutrient degradabilities of flaxseed and therefore was ineffective in increasing the post-ruminal supply of amino acids from flaxseed.
Cost allocation rules for elastic single‐attribute situations

Many cooperative games, especially ones stemming from resource pooling in queueing or inventory systems, are based on situations in which each player is associated with a single attribute (a real number representing, say, a demand) and in which the cost to optimally serve any sum of attributes is described by an elastic function (which means that the per‐demand cost is non‐increasing in the total demand served). For this class of situations, we introduce and analyze several cost allocation rules: the proportional rule, the serial cost sharing rule, the benefit‐proportional rule, and various Shapley‐esque rules. We study their appeal with regard to fairness criteria such as coalitional rationality, benefit ordering, and relaxations thereof. After showing the impossibility of combining coalitional rationality and benefit ordering, we show for each of the cost allocation rules which fairness criteria it satisfies. © 2017 Wiley Periodicals, Inc. Naval Research Logistics 64: 271–286, 2017
Bayesian statistics as applied to hypertension diagnosis

The Bayesian approach was applied to a specific case of medical diagnosis, i.e. essential hypertension and five types of secondary hypertension (fibrodysplasic renal artery stenosis, atheromatous renal artery stenosis, Conn's syndrome, renal cystic disease, and pheochromocytoma). Only blood pressures, general information and general biochemical data are taken into account. Nineteen items were finally selected through statistical investigation of the experimental data as being both discriminative and independent. The marginal density distributions of every item, and then joint density distribution functions were determined within six types of hypertension. The frequency of a given hypertension type within the hypertensive patients was used as prior probability of this state. The loss matrix was established by medical arguments. The expected loss corresponding to six possible decisions was calculated for all cases. Both the ratio of secondary hypertensions that could be inferred from this set of data (not including the results of complementary tests) and that of correct essential hypertension diagnosis provided to be satisfactory. <<ETX>>
Fibroblasts within concentrated collagen hydrogels favour chronic skin wound healing

Apligraf®, a skin substitute currently used in skin chronic wound treatment, acts as a source of macromolecules and cytokines to promote wound healing. Normal collagen hydrogel (NCH), obtained from collagen at low concentration (0.66 mg/ml), is the base of the dermal layer. Apligraf has several drawbacks, such as poor persistence of fibroblasts within the normal collagen hydrogel. In the present study we have evaluated concentrated collagen hydrogels at 5 mg/ml (CCH5s) as dermal substitutes for the treatment of skin chronic wounds. The effect of raised collagen concentration on hydrogel stability, cell growth, apoptosis and fibroblast phenotype was evaluated over 21 days in culture. In contrast to NCHs, CCH5s were more stable because no contraction was observed during the first week. CCH5 favoured cell proliferation and protected fibroblasts against apoptosis. At day 21, cell number assessed in CCH5 was around one million, i.e about 10 times higher than in NCH. Matrix metalloproteinases detection appeared lower in CCH5 than in NCH. In CCH5, fibroblasts exhibited a sustained collagen I gene expression for 14 days, while it was inhibited from day 4 in NCH. Moreover, gene expression of KGF was constant in CCH5 and that of VEGFA increased from day 7. Taken together, our results demonstrate that concentrated collagen hydrogels at 5 mg/ml can be considered as new candidates for cell therapy in chronic skin wounds. They are stable, enhance cell viability and allow gene expression of matrix macromolecules and cytokines involved in re‐epithelialization or neovascularization. Copyright © 2011 John Wiley & Sons, Ltd.
Avian-Pathogenic Escherichia coli Strains Are Similar to Neonatal Meningitis E. coli Strains and Are Able To Cause Meningitis in the Rat Model of Human Disease

ABSTRACT Escherichia coli strains causing avian colibacillosis and human neonatal meningitis, urinary tract infections, and septicemia are collectively known as extraintestinal pathogenic E. coli (ExPEC). Characterization of ExPEC strains using various typing techniques has shown that they harbor many similarities, despite their isolation from different host species, leading to the hypothesis that ExPEC may have zoonotic potential. The present study examined a subset of ExPEC strains: neonatal meningitis E. coli (NMEC) strains and avian-pathogenic E. coli (APEC) strains belonging to the O18 serogroup. The study found that they were not easily differentiated on the basis of multilocus sequence typing, phylogenetic typing, or carriage of large virulence plasmids. Among the APEC strains examined, one strain was found to be an outlier, based on the results of these typing methods, and demonstrated reduced virulence in murine and avian pathogenicity models. Some of the APEC strains tested in a rat model of human neonatal meningitis were able to cause meningitis, demonstrating APEC's ability to cause disease in mammals, lending support to the hypothesis that APEC strains have zoonotic potential. In addition, some NMEC strains were able to cause avian colisepticemia, providing further support for this hypothesis. However, not all of the NMEC and APEC strains tested were able to cause disease in avian and murine hosts, despite the apparent similarities in their known virulence attributes. Thus, it appears that a subset of NMEC and APEC strains harbors zoonotic potential, while other strains do not, suggesting that unknown mechanisms underlie host specificity in some ExPEC strains.
Endfire antennas based on spoof surface plasmon polaritons

A linear polarized (LP) endfire antenna based on spoof surface plasmon polaritons (SSPP) is proposed, which is composed of a feed monopole and ultrathin corrugated metallic strips. The metallic strips are utilized to couple guided wave into SSPP, propagate SSPP, and radiate the SSPP into free space. As an example, an X-band prototype is designed, fabricated, and measured. Both the simulated and measured results show good agreement, and verify that the proposed antenna behaves good performances. Similar to travelling wave antennas, gain of the proposed antenna is in proportional to the length of the strips structure. Furthermore, a circular polarized (CP) endfire antenna is also designed by arranging two LP antennas with different strip height in orthogonal. The simulated results verify our prediction.
Coaching Leadership: Building Educational Leadership Capacity through Coaching Partnerships

Coaching Leadership is about building leadership capacity in individuals, and in institutions, through enhancing professional relationships. It is based on the importance of maximising potential, and harnessing the ongoing commitment and energy needed to meet personal and professional goals. Based on over a decade of research and development, nationally and internationally, Coaching Leadership brings you the empirical evidence, the principles, and the skills, to be able to develop your own leadership and that of others you work with. This book: Challenges you to critically reflect on your leadership and professional relationships Offers practical activities and exercises Describes leadership coaching based on reciprocal processes Seeks to connect theory and practice Provides a basis for workshop activities in coaching, appraisal, and mentoring. Coaching Leadership will assist educators who believe in the development of leadership at all levels, to dialogue effectively with professional colleagues for the improvement of leadership practice. This book comes highly recommended to those professionals committed to lifelong, experiential learning and reflective practice.
Crystal structures of the complexes of a group IIA phospholipase A2 with two natural anti‐inflammatory agents, anisic acid, and atropine reveal a similar mode of binding

Secretory low molecular weight phospholipase A2s (PLA2s) are believed to be involved in the release of arachidonic acid, a precursor for the biosynthesis of pro‐inflammatory eicosanoids. Therefore, the specific inhibitors of these enzymes may act as potent anti‐inflammatory agents. Similarly, the compounds with known anti‐inflammatory properties should act as specific inhibitors. Two plant compounds, (a) anisic acid (4‐methoxy benzoic acid) and (b) atropine (8‐methyl‐8‐azabicyclo oct‐3‐hydroxy‐2‐phenylpropanoate), have been used in various inflammatory disorders. Both compounds (a) and (b) have been found to inhibit PLA2 activity having binding constants of 4.5 × 10−5 M and 2.1 × 10−8 M, respectively. A group IIA PLA2 was isolated and purified from the venom of Daboia russelli pulchella (DRP) and its complexes were made with anisic acid and atropine. The crystal structures of the two complexes (i) and (ii) of PLA2 with compounds (a) and (b) have been determined at 1.3 and 1.2 Å resolutions, respectively. The high‐quality observed electron densities for the two compounds allowed the accurate determinations of their atomic positions. The structures revealed that these compounds bound to the enzyme at the substrate ‐ binding cleft and their positions were stabilized by networks of hydrogen bonds and hydrophobic interactions. The most characteristic interactions involving Asp 49 and His 48 were clearly observed in both complexes, although the residues that formed hydrophobic interactions with these compounds were not identical because their positions did not exactly superimpose in the large substrate‐binding hydrophobic channel. Owing to a relatively small size, the structure of anisic acid did not alter upon binding to PLA2, while that of atropine changed significantly when compared with its native crystal structure. The conformation of the protein also did not show notable changes upon the bindings of these ligands. The mode of binding of anisic acid to the present group II PLA2 is almost identical to its binding with bovine pancreatic PLA2 of group I. On the other hand, the binding of atropine to PLA2 is similar to that of another plant alkaloid aristolochic acid. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Inhibition of Na+/Ca2+ exchange by KB-R7943: transport mode selectivity and antiarrhythmic consequences.

The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+ levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit the reverse mode (i.e., Ca2+ entry) of Na+/Ca2+ exchange transport, although many aspects of its inhibitory properties remain controversial. We evaluated the inhibitory effects of KB-R7943 on Na+/Ca2+ exchange currents using the giant excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis oocytes expressing the cloned cardiac Na+/Ca2+ exchanger NCX1.1, and outward, inward, and combined inward-outward currents were studied. KB-R7943 preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The inhibitory mechanism consists of direct effects on the transport machinery of the exchanger, with additional influences on ionic regulatory properties. Competitive interactions between KB-R7943 and the transported ions were not observed. The antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion model of cardiac injury in Langendorff-perfused whole rabbit hearts using electrocardiography and measurements of left ventricular pressure. When 3 microM KB-R7943 was applied for 10 min before a 30-min global ischemic period, ventricular arrhythmias (tachycardia and fibrillation) associated with both ischemia and reperfusion were almost completely suppressed. The observed electrophysiological profile of KB-R7943 and its protective effects on ischemia-reperfusion-induced ventricular arrhythmias support the notion of a prominent role of Ca2+ entry via reverse Na+/Ca2+ exchange in this process.