Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

Designer Anti-HIV Developing a protective HIV vaccine remains a top global health priority. One strategy to identify potential vaccine candidates is to isolate broadly neutralizing antibodies from infected individuals and then attempt to elicit the same antibody response through vaccination (see the Perspective by Burton and Weiss). Wu et al. (p. 856, published online 8 July) now report the identification of three broadly neutralizing antibodies, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike. Zhou et al. (p. 811, published online 8 July) analyzed the crystal structure for one of these antibodies, VRC01, in complex with an HIV-1 gp120. VRC01 focuses its binding onto a conformationally invariant domain that is the site of initial CD4 attachment, which allows the antibody to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. The epitopes recognized by these antibodies suggest potential immunogens that can inform vaccine design. A human antibody achieves broad neutralization by binding the viral site of recognition for the primary host receptor, CD4. During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.
Intrinsic content, active memory and the extended mind

Clark and Chalmers (1998) defend the view that the human mind need not be in the human head. To speak more carefully, they defend the view that the material vehicles 1 of cognition can be spread out across brain, body and certain aspects of the physical environment itself. Critics of this view (which has become known as the ‘extended mind hypothesis’, henceforth EM) have pointed to the supposedly intrinsic nature of the contents carried by inner biological vehicles. External, non-biological vehicles, such critics claim, are not (at least in any typical human case) similarly endowed, and thus fail to exhibit one of the key ‘marks of the cognitive’ (Adams and Aizawa 2001: 48). I shall argue that this response is mistaken. First, though I shall not dwell upon this, it is unclear that there is any such thing as intrinsic content anyway. Second, in so far as the notion is intelligible at all, there is no reason to believe that external, non-biological structures are incapable of supporting such content. And third, even if they were incapable of so doing, this would not actually compromise the case for the extended mind. The worry about intrinsic content, I conclude, is multiply fatally flawed. Despite all this, there are some related and legitimate worries that may well be informing the unease expressed by Adams, Aizawa and others. 2 The paper ends by briefly discussing these worries, pointing to a possible solution, and then gesturing at the larger picture of the extended mind and its place in nature. The original argument for EM took the form of some thought experiments, a principle meant to command rational assent, and a battery of
Decision-Theoretic Planning: Structural Assumptions and Computational Leverage

Planning under uncertainty is a central problem in the study of automated sequential decision making, and has been addressed by researchers in many different fields, including AI planning, decision analysis, operations research, control theory and economics. While the assumptions and perspectives adopted in these areas often differ in substantial ways, many planning problems of interest to researchers in these fields can be modeled as Markov decision processes (MDPs) and analyzed using the techniques of decision theory. This paper presents an overview and synthesis of MDP-related methods, showing how they provide a unifying framework for modeling many classes of planning problems studied in AI. It also describes structural properties of MDPs that, when exhibited by particular classes of problems, can be exploited in the construction of optimal or approximately optimal policies or plans. Planning problems commonly possess structure in the reward and value functions used to describe performance criteria, in the functions used to describe state transitions and observations, and in the relationships among features used to describe states, actions, rewards, and observations. Specialized representations, and algorithms employing these representations, can achieve computational leverage by exploiting these various forms of structure. Certain AI techniques -- in particular those based on the use of structured, intensional representations -- can be viewed in this way. This paper surveys several types of representations for both classical and decision-theoretic planning problems, and planning algorithms that exploit these representations in a number of different ways to ease the computational burden of constructing policies or plans. It focuses primarily on abstraction, aggregation and decomposition techniques based on AI-style representations.
MEPP - 3D Mesh Processing Platform

This paper presents MEPP, an open source platform for 3D mesh processing. This platform already contains a large set of processing tools from classical ones (simplification, subdivision, segmentation) to more technical algorithms (compression, watermarking, Boolean operation, perceptual metrics, etc.). Its main objective is to allow a quick start for both users and developers by providing highly detailed tutorials and simple integration mechanisms, through a modular architecture where components are implemented as dynamic plugins.
Fluticasone furoate nasal spray: Profile of an enhanced-affinity corticosteroid in treatment of seasonal allergic rhinitis

Of the classes of pharmacotherapy for seasonal allergic rhinitis, intranasal corticosteroids are the preferred treatment and are recommended in practice guidelines as first-line pharmacotherapy for rhinitis with prominent nasal congestion. The enhanced-affinity intranasal corticosteroid fluticasone furoate nasal spray (GW685698X), is one of the newest additions to the armamentarium for allergic rhinitis. This review summarizes the preclinical and clinical data on fluticasone furoate nasal spray and discusses its place in pharmacotherapy for seasonal allergic rhinitis. Important attributes of fluticasone furoate in seasonal allergic rhinitis include low systemic bioavailability (<0.5%), onset of symptom relief as early as eight hours after initiation of treatment, 24-hour symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these attributes, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance and reduce the need for polypharmacy in the management of seasonal allergic rhinitis.
A vector set for systematic metabolic engineering in Saccharomyces cerevisiae

A set of shuttle vectors was constructed to facilitate expression of genes for metabolic engineering in Saccharomyces cerevisiae. Selectable markers include the URA3, TRP1, MET15, LEU2‐d8, HIS3 and CAN1 genes. Differential expression of genes can be achieved as each marker is available on both CEN/ARS‐ and 2 µ‐containing plasmids. Unique restriction sites downstream of TEF1, PGK1 or HXT7‐391 promoters and upstream of the CYC1 terminator allow insertion of open‐reading frame cassettes for expression. Furthermore, a fragment appropriate for integration into the genome via homologous recombination can be readily generated in a polymerase chain reaction. Vector marker genes are flanked by loxP recognition sites for the CreA recombinase to allow efficient site‐specific marker deletion and recycling. Expression and copy number were characterized for representative high‐ and low‐copy vectors carrying the different marker and promoter sequences. Metabolic engineering typically requires the stable introduction of multiple genes and genomic integration is often preferred. This requires an expanded number of stable expression sites relative to standard gene expression studies. This study demonstrated the practicality of polymerase chain reaction amplification of an expression cassette and genetic marker, and subsequent replacement of endogenous retrotransposons by homologous recombination with flanking sequences. Such reporters were expressed comparably to those inserted at standard integration loci. This expands the number of available characterized integration sites and demonstrates that such sites provide a virtually inexhaustible pool of integration targets for stable expression of multiple genes. Together these vectors and expression loci will facilitate combinatorial gene expression for metabolic engineering. Copyright © 2010 John Wiley & Sons, Ltd.
Amplify-and-Forward Cooperative Systems with Fixed Gain Relays

Multi-hop and multi-branch wireless transmission systems with nonregenerative fixed gain relays employing amplify-and-forward relaying are studied. Simple closed-form expressions for the outage and bit error probabilities of these systems are derived. The analysis is valid for an arbitrary number of hops, arbitrary number of branches and any fading channel model whose signal power probability density function has nonzero value at the origin. It is shown that while a multi-hop transmission system does not offer diversity gain, it can perform better than a single hop system if its average individual link SNRs satisfy a certain condition. In addition, the analysis clearly shows the diversity gains achieved by multi-branch systems for any fading channel model.
Distance Determination from Pairs of Images from Low Cost Cameras August 2005 The University of Edinburgh School of Engineering and Electronics MSc in Signal Processing and Communication The King ’ s Buildings

This thesis presents an implementation of a stereo vision system, using image processing techniques to determine depth information from pairs of stereo images. This system, which aims to aid vehicle reversal, involves working with stereo images of different vehicles, and the distance between the stereo cameras and the target vehicle is determined. For a pair of stereo images, the system algorithm extracts feature points from each image, and then a block matching technique is used to find the corresponding points between the two images and calculate the displacement. The experimental results are presented in this thesis as well. An introduction to stereo vision and some widely used image processing techniques is given. Additionally a discussion on the improvement and modification of the system is made. Conclusions are presented regarding the success of the proposed system algorithms and the possible future research work.
Exploring continental-scale stand health - N : P ratio relationships for European forests.

Understanding the relationship between nitrogen (N) availability and stand health in forest ecosystems is crucial, because a large proportion of European forests is subjected to N-deposition levels beyond their retention capacity. We used data from a long-term forest monitoring programme (ICP Forests) to test the relationship between an index of N availability, foliar nitrogen : phosphorus (N : P) ratios, tree defoliation and discoloration. We hypothesized a segmented response of stand health to N : P ratios and an improved model-fit after correcting for climatic covariates. In accordance with the hypothesis, we found a segmented response with a breakpoint for conifer defoliation at N : P ratios as low as 7.3. Inclusion of climatic variables improved the fit of the models, but there was significant collinearity with N : P. Increases in N availability appear, at least for conifers, to have a negative effect on tree health even under N-limiting conditions. Regulation of N-deposition levels is consequently as timely as ever. We propose that increases in tree defoliation, other than resulting in serious plant fitness issues, may represent early diagnostic symptoms of N-addition related imbalances.
First-order queries on finite structures over the reals

We investigate properties of finite relational structures over the reals expressed by first-order sentences whose predicates are the relations of the structure plus arbitrary polynomial inequalities, and whose quantifiers can range over the whole set of reals. In constraint programming terminology, this corresponds to Boolean real polynomial constraint queries on finite structures. The fact that quantifiers range over all reals seems crucial; however, we observe that each sentence in the first-order theory of the reals can be evaluated by letting each quantifier range over only a finite set of real numbers without changing its truth value. Inspired by this observation, we then show that when all polynomials used are linear, each query can be expressed uniformly on all finite structures by a sentence of which the quantifiers range only over the finite domain of the structure. In other words, linear constraint programming on finite structures can be reduced to ordinary query evaluation as usual in finite model theory and databases. Moreover, if only "generic" queries are taken into consideration, we show that this can be reduced even further by proving that such queries can be expressed by sentences using as polynomial inequalities only those of the simple form z
Assessment of endothelial dysfunction by flow‐mediated dilatation in men on long‐term androgen deprivation therapy for prostate cancer

• What is the central question of this study? Androgen deprivation therapy (ADT) for prostate cancer has been linked with increased cardiovascular risk, but the mechanisms are unclear. Is there evidence that endothelial dysfunction, as evidenced by reduced flow‐mediated dilatation (FMD), is associated with ADT? • What is the main finding and its importance? Reduction in FMD with preservation of glyceryl trinitrate‐mediated dilatation indicates endothelial dysfunction in men with prostate cancer on long‐term ADT compared with well‐matched control subjects. Vascular endothelial dysfunction associated with long‐term ADT for prostate cancer might explain the observed epidemiological increases in adverse cardiovascular events. Assessment of FMD may be useful in the monitoring of cardiovascular risk in men with prostate cancer on ADT.
Hierarchical Location and Topic Based Query Expansion

In this paper, we propose a novel approach to expand queries by exploring both location information and topic information of the queries. Users at different locations tend to have different vocabularies, while the different expressions coming from different vocabularies may relate to the same topics. Thus these expressions are identified as location sensitive and can be used for query expansion. We propose a hierarchical query expansion model, which employs a two-level SVM classification model to classify queries as location sensitive or location non-sensitive, where the former are further classified into same location sensitive and different location sensitive. For the location sensitive queries, we propose an LDA based topic-level query similarity measure to rank the list of similar queries. Experiments with 2G raw log data from CiteSeer and Excite show that our hierarchical classification model predicts the query location sensitivity with more than 80% precision and that the final search result is significantly better than existing query expansion methods.
Antimullerian Hormone and Its Receptor Gene Expression in Prenatally Androgenized Female Rats

Background: Anti-mullerian hormone (AMH) levels reflect the number of small antral follicles in ovaries and expression changes of AMH and its receptor are suspected to be involved in the pathogenesis of polycystic ovary syndrome (PCOS). Objectives: The aim of this study was to evaluate gene expression of AMH and its receptor in immature and adult rats prenatally exposed to androgen excess. Materials and Methods: Six pregnant Wistar rats in the experimental group were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 6) received only 500 mL of solvent. Female pups of each mother were randomly divided into three groups as day 0 (newborn), 10-day old and days 75-85 (adult). RNAs were extracted from ovarian tissues and relative expression levels for AMH and its receptor genes were measured using TaqMan Real-Time PCR. Serum AMH and testosterone levels were measured using ELISA method. Results: Relative AMH expression decreased in newborns, 10-day olds and adults (0.806, 0.443 and 0.809 fold, respectively). AMHR expression was higher in newborns and adults (1.432 and 1.057 fold, respectively), while it decreased by 0.263 fold in 10-day olds, although none of them were significant (P > 0.05). In addition, AMH levels were consistent with the results of gene expression. Testosterone hormone levels from 10 day-olds to adults were significantly increased in both study groups (P = 0.016). Conclusions: While AMH receptor expression was higher in experimental rats, their serum concentrations of AMH were decreased. Further researches with greater sample sizes and measurement of bioactive forms of hormones are recommended to confirm the findings of this study.
Force Modulation and Adaptability of 3D‐Bioprinted Biological Actuators Based on Skeletal Muscle Tissue

The integration of biological systems into robotic devices might provide them with capabilities acquired from natural systems and significantly boost their performance. These abilities include real‐time bio‐sensing, self‐organization, adaptability, or self‐healing. As many muscle‐based bio‐hybrid robots and bio‐actuators arise in the literature, the question of whether these features can live up to their expectations becomes increasingly substantial. Herein, the force generation and adaptability of skeletal‐muscle‐based bio‐actuators undergoing long‐term training protocols are analyzed. The 3D‐bioprinting technique is used to fabricate bio‐actuators that are functional, responsive, and have highly aligned myotubes. The bio‐actuators are 3D‐bioprinted together with two artificial posts, allowing to use it as a force measuring platform. In addition, the force output evolution and dynamic gene expression of the bio‐actuators are studied to evaluate their degree of adaptability according to training protocols of different frequencies and mechanical stiffness, finding that their force generation could be modulated to different requirements. These results shed some light into the fundamental mechanisms behind the adaptability of muscle‐based bio‐actuators and highlight the potential of using 3D bioprinting as a rapid and cost‐effective tool for the fabrication of custom‐designed soft bio‐robots.
Photometric validation of a model independent procedure to extract galaxy clusters

By means of CCD photometry in three bands (Gunn g, r, i ) we investigate the existence of 12 candidate clusters extracted via a model independent peak finding algorithm ([CITE]) from DPOSS data. The derived color-magnitude diagrams allow us to confirm the physical nature of 9 of the cluster candidates, and to estimate their photometric redshifts. Of the other candidates, one is a fortuitous detection of a true cluster at $z \sim 0.4$, one is a false detection and the last is undecidable on the basis of the available data. The accuracy of the photometric redshifts is tested on an additional sample of 8 clusters with known spectroscopic redshifts. Photometric redshifts turn out to be accurate within $z \sim 0.01$ (interquartile range).
Resting State Functional Connectivity in Patients with Chronic Hallucinations

Auditory verbal hallucinations (AVH) are not only among the most common but also one of the most distressing symptoms of schizophrenia. Despite elaborate research, the underlying brain mechanisms are as yet elusive. Functional MRI studies have associated the experience of AVH with activation of bilateral language-related areas, in particular the right inferior frontal gyrus (rIFG) and the left superior temporal gyrus (lSTG). While these findings helped to understand the neural underpinnings of hearing voices, they provide little information about possible brain mechanisms that predispose a person to experience AVH, i.e. the traits to hallucinate. In this study, we compared resting state connectivity between 49 psychotic patients with chronic AVH and 49 matched controls using the rIFG and the lSTG as seed regions, to identify functional brain systems underlying the predisposition to hallucinate. The right parahippocampal gyrus showed increased connectivity with the rIFG in patients as compared to controls. Reduced connectivity with the rIFG in patients was found for the right dorsolateral prefrontal cortex. Reduced connectivity with the lSTG in patients was identified in the left frontal operculum as well as the parietal opercular area. Connectivity between the lSTG and the left hippocampus was also reduced in patients and showed a negative correlation with the severity of hallucinations. Concluding, we found aberrant connectivity between the seed regions and medial temporal lobe structures which have a prominent role in memory retrieval. Moreover, we found decreased connectivity between language-related areas, indicating aberrant integration in this system potentially including corollary discharge mechanisms.
Transient oxidative stress evokes early changes in the functional properties of neonatal rat hypoglossal motoneurons in vitro

Oxidative stress of motoneurons is believed to be an important contributor to neurodegeneration underlying the familial (and perhaps even the sporadic) form of amyotrophic lateral sclerosis (ALS). This concept has generated numerous rodent genetic models with inborn oxidative stress to mimic the clinical condition. ALS is, however, a predominantly sporadic disorder probably triggered by environmental causes. Thus, it is interesting to understand how wild‐type motoneurons react to strong oxidative stress as this response might cast light on the presymptomatic disease stage. The present study used, as a model, hypoglossal motoneurons from the rat brainstem slice to investigate how hydrogen peroxide could affect synaptic transmission and intrinsic motoneuron excitability in relation to their survival. Hydrogen peroxide (1 mm; 30 min) induced inward current or membrane depolarization accompanied by an increase in input resistance, enhanced firing and depressed spontaneous synaptic events. Despite enhanced intracellular oxidative processes, there was no death of motoneurons, although most cells were immunopositive for activating transcription factor 3, a stress‐related transcription factor. Voltage‐clamp experiments indicated increased frequency of excitatory or inhibitory miniature events, and reduced voltage‐gated persistent currents of motoneurons. The global effect of this transient oxidative challenge was to depress the input flow from the premotor interneurons to motoneurons that became more excitable due to a combination of enhanced input resistance and impaired spike afterhyperpolarization. Our data show previously unreported changes in motoneuron activity associated with cell distress caused by a transient oxidative insult.