Miracle-dz/UniFAR-FTUs huggingface dataset:
A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene

ABSTRACT Recombinant trimeric mimics of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike should expose as many epitopes as possible for broadly neutralizing antibodies (bNAbs) but few, if any, for nonneutralizing antibodies (non-NAbs). Soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A strain BG505 approach this ideal and are therefore plausible vaccine candidates. Here, we report on the production and in vitro properties of a new SOSIP.664 trimer derived from a subtype B env gene, B41, including how to make this protein in low-serum media without proteolytic damage (clipping) to the V3 region. We also show that nonclipped trimers can be purified successfully via a positive-selection affinity column using the bNAb PGT145, which recognizes a quaternary structure-dependent epitope at the trimer apex. Negative-stain electron microscopy imaging shows that the purified, nonclipped, native-like B41 SOSIP.664 trimers contain two subpopulations, which we propose represent an equilibrium between the fully closed and a more open conformation. The latter is different from the fully open, CD4 receptor-bound conformation and may represent an intermediate state of the trimer. This new subtype B trimer adds to the repertoire of native-like Env proteins that are suitable for immunogenicity and structural studies. IMPORTANCE The cleaved, trimeric envelope protein complex is the only neutralizing antibody target on the HIV-1 surface. Many vaccine strategies are based on inducing neutralizing antibodies. For HIV-1, one approach involves using recombinant, soluble protein mimics of the native trimer. At present, the only reliable way to make native-like, soluble trimers in practical amounts is via the introduction of specific sequence changes that confer stability on the cleaved form of Env. The resulting proteins are known as SOSIP.664 gp140 trimers, and the current paradigm is based on the BG505 subtype A env gene. Here, we describe the production and characterization of a SOSIP.664 protein derived from a subtype B gene (B41), together with a simple, one-step method to purify native-like trimers by affinity chromatography with a trimer-specific bNAb, PGT145. The resulting trimers will be useful for structural and immunogenicity experiments aimed at devising ways to make an effective HIV-1 vaccine.
Rendering and Visualization in Parallel Environments

The continuing commoditization of the computer market has precipitated a qualitative change. Increasingly powerful processors, large memories, big harddisk, high-speed networks, and fast 3D rendering hardware are now affordable without a large capital outlay. Clusters of workstations and SMPservers are utilizing these technologies to drive interactive applications like large graphical display walls (i.e., Powerwall or CAVE systems). I nt his tutorial, attendees will learn how to understand and leverage (technical and personal) workstation- and server-based systems as components for par allel rendering. The goal of the tutorial is twofold: Attendees will thoroughly understand the important characteristics workstations architectures. We will present an overview of different workstation (Intel-based and others) and server architectures (including graphics hardware), addressing both single-processors as well as SMP architectures. We will also introduce important methods of programming in parallel environment with special attention how such techniques apply to developing cluster-based parallel renderers. Attendees will learn about different approaches to implement parallel renderers. The tutorial will cover parallel polygon and volume rendering. We will explain the underlying concepts of workload characterization, workload partitioning, and static, dynamic, and adaptive load balancing. We will then apply these concepts to characterize various parallelization strateg ies reported in the literature for polygon and volume rendering. We abstract from the actual implementation of these strategies and instead focus on a comparison of their benefits and drawbacks. Case studies will provide additional material to explain the use of these techniques. The tutorial will be structured into three main sections: We will first discuss the fundamentals of parallel programming and parallel machine architectures. Topics include message passing vs. shared memory, thread programming, a review of different SMP architectures, clustering techniques, PC architectures for personal workstations, and graphics hardware architectures. The second section builds on this foundation to describe key concep ts and particular algorithms for parallel polygon and volume rendering. These concepts are supplemented with concrete parallel rendering implementations.
Human Head Modeling Based on an Improved Generic Model

With the development of computer graphics, virtual reality technology is becoming the focus of the research gradually. 3D face modeling technology, which is an important component of the virtual reality technology, has been used in many fields more and more widely. Comparing with the face modeling, the researches in the entire head modeling are less now. This paper proposed an approach to the construction of 3D human head models using an improved generic face model (Candide3) and some 2D human head images. Some simple human expressional controls are realized by adding the animation units (AUs) to the model.
Improving the Accuracy of Latent-space-based Recommender Systems by Introducing a Cut-off Criterion

Copyright is held by the author/owner(s). EICS’16, June 21-24, 2016, Bruxelles, Belgium. Abstract Recommender systems filter the items a user did not evaluate, in order to acquire knowledge on the those that might be suggested to her. To accomplish this objective, they employ the preferences the user expressed in forms of explicit ratings or of implicitly values collected through the browsing of the items. However, users have different rating behaviors (e.g., users might use just the ends of the rating scale, to expressed whether they loved or hated an item), while the system assumes that the users employ the whole scale. Over the last few years, Singular Value Decomposition (SV D) became the most popular and accurate form of recommendation, because of its capability of working with sparse data, exploiting latent features. This paper presents an approach that pre-filters the items a user evaluated and removes those she did not like. In other words, by analyzing a user’s rating behavior and the rating scale she used, we capture and employ in the recommendation process only the items she really liked. Experimental results show that our form of filtering leads to more accurate recommendations.
Testing subgraphs in directed graphs

Let H be a fixed directed graph on h vertices, let G be a directed graph on n vertices and suppose that at least ε n2 edges have to be deleted from it to make it H-free. We show that in this case G contains at least f(ε,H) nh copies of H. This is proved by establishing a directed version of Szemeredi's regularity lemma, and implies that for every H there is a one-sided error property tester whose query complexity is bounded by a function of ε only for testing the property PH of being H-free.
A comparison of peak expiratory flow measured from forced vital capacity and peak flow meter manoeuvres in healthy volunteers

BACKGROUND: Spirometry measures the mechanical function of lungs, chest wall and respiratory muscles by assessing the total volume of air exhaled from total lung capacity to residual volume. Spirometry and peak flow measurements have usually been carried out on separate equipments using different expiratory maneuvers. AIMS: The present study was carried out to determine whether there is a significant difference between peak expiratory flow (PEF) derived from a short sharp exhalation (PEF maneuver) and that derived from a full forced vital capacity (FVC) maneuver in healthy volunteers. SETTINGS: A medical college and tertiary level hospital. MATERIALS AND METHODS: The present study was carried out during the period from January 2006 to July 2006. The study included 80 healthy volunteers with no coexisting illnesses, who were in the 15-45 years age group and belonging to either sex. They were asked to perform two sets of PEF and FVC maneuvers using the same turbine spirometer; the order was randomly assigned. STATISTICAL ANALYSIS: The difference between PEF obtained from a peak flow maneuver (PEFPF) and that obtained from a forced vital capacity maneuver (PEFVC) in healthy volunteers was analyzed separately for males and females, as well as for both groups combined, and statistical significance of its correlations with study data parameters was analyzed. RESULTS: The difference between PEF obtained from a peak flow maneuver (PEFPF) and that obtained from a forced vital capacity maneuver (PEFVC) was statistically significant (P < 0.001) in males and in females separately and also for both groups combined. PEFPF (517.25 ± 83.22 liters/min) was significantly greater than PEFVC (511.09 ± 83.54 liters/min), as found on combined group mean analysis. However, the difference was small (6.16 + 7.09 liters/min). CONCLUSIONS: FVC maneuver can be used over spirometers to detect the PEF; and on follow-up subsequently, the same maneuver should be used to derive PEF. If we are using a peak flow maneuver subsequently, corrections are required to compensate for the difference due to the different maneuver.
Component Retrieval Based on Ontology and Graph Patterns Matching

Recently, the Component Based Software Development has become the main direction of software development, and with the expansion of the component library, efficient retrieval is crucial for us to improve the software development, in which the trend is semantic retrieval. The component concept ontology model and component domain ontology model this paper proposes, provide common knowledge foundation for component semantic retrieval. The users retrieval content is regularized to normal retrieval pattern, and then matched with component domain ontology model in accordance with matching algorithm, and the matching results are components which meet users need. The ontology models and component retrieval algorithm based on graph patterns matching, not only make up for the lack of semantic expression, but also enhance the retrieval efficiency.
Role of ELA region in auto-activation of mutant KIT receptor: a molecular dynamics simulation insight

KIT receptor is the prime target in gastrointestinal stromal tumor (GISTs) therapy. Second generation inhibitor, Sunitinib, binds to an inactivated conformation of KIT receptor and stabilizes it in order to prevent tumor formation. Here, we investigated the dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805–850) by conducting molecular dynamics simulation (∼100 ns). We analyzed different properties such as root mean square cutoff or deviation, root mean square fluctuation, radius of gyration, solvent-accessible surface area, hydrogen bonding network analysis, and essential dynamics. Apart from this, clustering and cross-correlation matrix approach was used to explore the conformational space of the wild type and mutant EAL region of KIT receptor. Molecular dynamics analysis indicated that mutation (D816H) was able to alter intramolecular hydrogen bonding pattern and affected the structural flexibility of EAL region. Moreover, flexible secondary elements, specially, coil and turns were dominated in EAL region of mutant KIT receptor during simulation. This phenomenon increased the movement of EAL region which in turn helped in shifting the equilibrium towards the active kinase conformation. Our atomic investigation of mutant KIT receptor which emphasized on EAL region provided a better insight into the understanding of Sunitinib resistance mechanism of KIT receptor and would help to discover new therapeutics for KIT-based resistant tumor cells in GIST therapy.
Functional stoichiometric analysis of metabolic networks

MOTIVATION An important tool in Systems Biology is the stoichiometric modeling of metabolic networks, where the stationary states of the network are described by a high-dimensional polyhedral cone, the so-called flux cone. Exhaustive descriptions of the metabolism can be obtained by computing the elementary vectors of this cone but, owing to a combinatorial explosion of the number of elementary vectors, this approach becomes computationally intractable for genome scale networks. RESULT Hence, we propose to instead focus on the conversion cone, a projection of the flux cone, which describes the interaction of the metabolism with its external chemical environment. We present a direct method for calculating the elementary vectors of this cone and, by studying the metabolism of Saccharomyces cerevisiae, we demonstrate that such an analysis is computationally feasible even for genome scale networks.
Serotonergic dysfunction in the A53T alpha‐synuclein mouse model of Parkinson's disease

Parkinson's disease, neuropathologically defined by the aggregation of α‐synuclein, is characterized by neuropsychiatric symptoms such as depression and anxiety preceding the onset of motor symptoms. A loss of serotonergic neurons or their projections into the hippocampus and alterations in serotonin release may be linked to these symptoms. Here, we investigate the effect of human A53T α‐synuclein on serotonergic neurons using 12‐months‐old transgenic mice. We detected human α‐synuclein in the perikarya of brainstem median and dorsal raphe neurons as well as in serotonergic fibers in the hippocampus. Despite intracellular α‐synuclein accumulation there was no loss of serotonergic neurons in dorsal and median raphe nuclei of A53T α‐synuclein mice. However, serotonin levels were significantly reduced in the brainstem. In addition, serotonergic fiber density in the dorsal dentate gyrus was significantly less dense in transgenic mice. Interestingly, we detected a significantly compromised increase in doublecortin+ neuroblasts after chronic treatment with fluoxetine at the site of reduced serotonergic innervation, the infrapyramidal blade of the dorsal dentate gyrus in A53T α‐synuclein mice. This suggests that α‐synuclein affects serotonergic projections in a spatially distinct pattern within the hippocampus thereby influencing the response to antidepressant treatment.
A New 5α,8α-Epidioxysterol from the Soft Coral Sinularia gaweli

A new sterol, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methyl-cholest-6,9(11)-dien-3β-ol (1), and two known sterols, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methylcholest-6-en-3β-ol (2) and 24-methylenecholestane-1α,3β,5α, 6β,11α-pentol (3), were isolated from the soft coral Sinularia gaweli. The structure of sterol 1 was established by spectroscopic methods and by comparison of the spectral data with those of known analogues. The cytotoxicity of sterols 1–3 towards various tumor cells is reported.
Building simulated queries for known-item topics: an analysis using six european languages

There has been increased interest in the use of simulated queries for evaluation and estimation purposes in Information Retrieval. However, there are still many unaddressed issues regarding their usage and impact on evaluation because their quality, in terms of retrieval performance, is unlike real queries. In this paper, wefocus on methods for building simulated known-item topics and explore their quality against real known-item topics. Using existing generation models as our starting point, we explore factors which may influence the generation of the known-item topic. Informed by this detailed analysis (on six European languages) we propose a model with improved document and term selection properties, showing that simulated known-item topics can be generated that are comparable to real known-item topics. This is a significant step towards validating the potential usefulness of simulated queries: for evaluation purposes, and becausebuilding models of querying behavior provides a deeper insight into the querying process so that better retrieval mechanisms can be developed to support the user.
Analysis and Significance of Anti-Latent Membrane Protein-1 Antibodies in the Sera of Patients with EBV-Associated Diseases

Anti-latent membrane protein-1 (LMP-1) is an EBV-encoded type III integral membrane protein with oncogenic potential that is expressed most consistently in various EBV-associated malignancies. Unlike many other EBV proteins, LMP-1 Abs have rarely been demonstrated in EBV-associated disease conditions. We established a high level LMP-1-expressing cell clone and used it for the detection, quantitation, and characterization of these Abs in various human sera in immunoblots and ELISA. Our results demonstrate that, in contrast to the commonly held notion, LMP-1 induces significant humoral immune responses in EBV-associated malignant conditions especially in nasopharyngeal carcinoma (NPC) patients in whom >70% sera are positive for these Abs, and their titers correlate with the clinical condition of the tumors. Interestingly, anti-LMP-1 Abs of IgA isotype were found only in NPC patients. These Abs were absent from the sera of infectious mononucleosis and chronic EBV infection patients, whereas a small fraction (∼5%) of the healthy, EBV-seropositive individuals were positive for them; however, their OD values were much lower than those of NPC patients. These studies demonstrate, for the first time, the potential significance of LMP-1-specific Abs for the diagnosis and prognosis of EBV-associated malignancies, especially of NPC.
A Linear Baseline Classifier for Cross-Lingual Pronoun Prediction

This paper presents baseline models us-ing linear classiﬁers for the pronoun translation task at WMT 2016. We explore various local context features and include history features of potential antecedents extracted by means of a simple PoS-matching strategy. The results show the difﬁculties of the task in general but also represent valuable baselines to compare other more-informed systems with. Our experiments reveal that the predictions of English correspondences for given ambiguous pronouns in French and German is easier than the other way around. This seems to verify that predictions, which need to follow more complex agreement constraints, require more reliable information about the referential links of the to-kens to be inserted.
Exploring Autophagy in Drosophila

Autophagy is a catabolic process in eukaryotic cells promoting bulk or selective degradation of cellular components within lysosomes. In recent decades, several model systems were utilized to dissect the molecular machinery of autophagy and to identify the impact of this cellular “self-eating” process on various physiological and pathological processes. Here we briefly discuss the advantages and limitations of using the fruit fly Drosophila melanogaster, a popular model in cell and developmental biology, to apprehend the main pathway of autophagy in a complete animal.
CD34+/CD38− stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin

Background CD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias. Design and Methods We analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targeting drug, gemtuzumab/ozogamicin, were examined. Results As assessed by flow cytometry, stem cell-enriched CD34+/CD38−/CD123+ leukemic cells expressed significantly higher levels of CD33 compared to normal CD34+/CD38− stem cells. Moreover, highly enriched leukemic CD34+/CD38− cells (>98% purity) displayed higher levels of CD33 mRNA. In chronic phase patients, CD33 was found to be expressed invariably on most or all stem cells, whereas in accelerated or blast phase of the disease, the levels of CD33 on stem cells varied from donor to donor. The MDR1 antigen, supposedly involved in resistance against ozogamicin, was not detectable on leukemic CD34+/CD38− cells. Correspondingly, gemtuzumab/ozogamicin produced growth inhibition in leukemic progenitor cells in all patients tested. The effects of gemtuzumab/ozogamicin were dose-dependent, occurred at low concentrations, and were accompanied by apoptosis in suspension culture. Moreover, the drug was found to inhibit growth of leukemic cells in a colony assay and long-term culture-initiating cell assay. Finally, gemtuzumab/ozogamicin was found to synergize with nilotinib and bosutinib in inducing growth inhibition in leukemic cells. Conclusions CD33 is expressed abundantly on immature CD34+/CD38− stem cells and may serve as a stem cell target in chronic myeloid leukemia.
MuJava: a mutation system for java

Mutation testing is a valuable experimental research technique that has been used in many studies. It has been experimentally compared with other test criteria, and also used to support experimental comparisons of other test criteria, by using mutants as a method to create faults. In effect, mutation is often used as a ``gold standard'' for experimental evaluations of test methods. Although mutation testing is powerful, it is a complicated and computationally expensive testing method. Therefore, automated tool support is indispensable for conducting mutation testing. This demo presents a publicly available mutation system for Java that supports both method-level mutants and class-level mutants. MuJava can be freely downloaded and installed with relative ease under both Unix and Windows. MuJava is offered as a free service to the community and we hope that it will promote the use of mutation analysis for experimental research in software testing.
Tetracycline-Inducible Gene Expression in Conditionally Immortalized Mouse Podocytes

Background: Conditionally immortalized podocytes are valuable research tools but are difficult to efficiently transfect and do not provide graded transgene expression. Methods: Conditionally immortalized mouse podocyte cell lines were established employing a tetracycline-inducible system. Glomerular cells, isolated from transgenic mice bear- ing two transgenes, NPHS2-reverse tetracycline-controlled transactivator, rtTA (A transgene) and H2-Kb-thermosensitive SV40 T, ts58A (I transgene), were cloned. One clone (AI podocytes) expressing WT1 and synaptopodin was transfected with pBI-EGFP (enhanced green fluorescent protein, G transgene) and separately with ptTS-Neo (transcriptional suppressor, T transgene) to produce stable transformants, AIG podocytes and AIT podocytes. Results: AIG podocytes expressed EGFP at 33 and 37°C after doxycycline treatment, and retained podocin and rtTA mRNA expression and temperature-sensitive growth regulation. AIT podocytes, transiently transfected with luciferase-BI-EGFP (LG transgene), showed reduced background expression of EGFP and luciferase in the absence of doxycycline. In AITLG podocytes, generated by stable transfection of AIT podocytes with the LG transgene, luciferase expression was tightly regulated by doxycycline in a time- and concentration-dependent manner both at 33 and 37°C, although background expression was not entirely eliminated. These podocytes retained temperature-sensitive growth regulation and expression of podocyte differentiation markers. Conclusion: Mouse podocytes expressed tetracycline-induced transgenes efficiently while retaining differentiation markers.