Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins

ABSTRACT Invasive bacterial pathogens can capture host plasminogen (Plg) and allow it to form plasmin. This process is of medical importance as surface-bound plasmin promotes bacterial spread by cleaving tissue components and favors immune evasion by degrading opsonins. In Staphylococcus aureus, Plg binding is in part mediated by cell surface fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here, we use single-cell and single-molecule techniques to demonstrate that FnBPs capture Plg by a sophisticated activation mechanism involving fibrinogen (Fg), another ligand found in the blood. We show that while FnBPs bind to Plg through weak (∼200-pN) molecular bonds, direct interaction of the adhesins with Fg through the high-affinity dock, lock, and latch mechanism dramatically increases the strength of the FnBP-Plg bond (up to ∼2,000 pN). Our results point to a new model in which the binding of Fg triggers major conformational changes in the FnBP protein, resulting in the buried Plg-binding domains being projected and exposed away from the cell surface, thereby promoting strong interactions with Plg. This study demonstrated a previously unidentified role for a ligand-binding interaction by a staphylococcal cell surface protein, i.e., changing the protein orientation to activate a cryptic biological function. IMPORTANCE Staphylococcus aureus captures human plasminogen (Plg) via cell wall fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here we show that the forces involved in the interaction between Plg and FnBPs on the S. aureus surface are weak. However, we discovered that binding of fibrinogen to FnBPs dramatically strengthens the FnBP-Plg bond, therefore revealing an unanticipated role for Fg in the capture of Plg by S. aureus. These experiments favor a model where Fg-induced conformational changes in FnBPs promote their interaction with Plg. This work uncovers a previously undescribed activation mechanism for a staphylococcal surface protein, whereby ligand-binding elicits a cryptic biological function. IMPORTANCE Staphylococcus aureus captures human plasminogen (Plg) via cell wall fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here we show that the forces involved in the interaction between Plg and FnBPs on the S. aureus surface are weak. However, we discovered that binding of fibrinogen to FnBPs dramatically strengthens the FnBP-Plg bond, therefore revealing an unanticipated role for Fg in the capture of Plg by S. aureus. These experiments favor a model where Fg-induced conformational changes in FnBPs promote their interaction with Plg. This work uncovers a previously undescribed activation mechanism for a staphylococcal surface protein, whereby ligand-binding elicits a cryptic biological function.
Goosecoid-like sequences and the smallest region of deletion overlap in DiGeorge and velocardiofacial syndromes.

We wish to thank Annalisa Botta for the isolation of the murine Gscl sequence. Research in the laboratory of Antonio Baldini is funded by National Institutes of Health grant HL51524 and by American Heart Association grant 94010250. The support of the cores of the Baylor Mental Retardation Research Center and Child Health Research Center is acknowledged.
Two algorithms for nearest-neighbor search in high dimensions

Representing data as points in a high-dimensional space, so as to use geometric methods for indexing, is an algorithmic technique with a wide array of uses. It is central to a number of areas such as information retrieval, pattern recognition, and statistical data analysis; many of the problems arising in these applications can involve several hundred or several thousand dimensions. We consider the nearest-neighbor problem for d-dimensional Euclidean space: we wish to pre-process a database of n points so that given a query point, one can efficiently determine its nearest neighbors in the database. There is a large literature on algorithms for this problem, in both the exact and approximate cases. The more sophisticated algorithms typically achieve a query time that is logarithmic in n at the expense of an exponential dependence on the dimension d; indeed, even the averagecase analysis of heuristics such as k-d trees reveals an exponential dependence on d in the query time. In this work, we develop a new approach to the nearest-neighbor problem, based on a method for combining randomly chosen one-dimensional projections of the underlying point set. From this, we obtain the following two results. (i) An algorithm for finding e-approximate nearest neighbors with a query time of O((d log d)(d + log n)). (ii) An e-approximate nearest-neighbor algorithm with near-linear storage and a query time that improves asymptotically on linear search in all dimensions. ∗Department of Computer Science, Cornell University, Ithaca NY 14853. Email: kleinber@cs.cornell. edu. This work was performed in large part while on leave at the IBM Almaden Research Center, San Jose CA 95120. The author is currently supported by an Alfred P. Sloan Research Fellowship and by NSF Faculty Early Career Development Award CCR-9701399.
Phylogeny, Seed Trait, and Ecological Correlates of Seed Germination at the Community Level in a Degraded Sandy Grassland

Seed germination strongly affects plant population growth and persistence, and it can be dramatically influenced by phylogeny, seed traits, and ecological factors. In this study, we examined the relationships among seed mass, seed shape, and germination percentage (GP), and assessed the extent to which phylogeny, seed traits (seed mass, shape, and color) and ecological factors (ecotype, life form, adult longevity, dispersal type, and onset of flowering) influence GP at the community level. All analyses were conducted on the log-transformed values of seed mass and arcsine square root-transformed values of GP. We found that seed mass and GP were significantly negatively correlated, whereas seed shape and GP were significantly positively correlated. The three major factors contributing to differences in GP were phylogeny, dispersal type, and seed shape (explained 5.8, 4.9, and 3.1% of the interspecific variations independently, respectively), but GP also influenced by seed mass and onset of flowering. Thus, GP was constrained not only by phylogeny but also by seed traits and ecological factors. These results indicated that GP is shaped by short-term selective pressures, and long-term phylogenetic constrains. We suggest that correlates of phylogeny, seed traits, and ecology should be taken into account in comparative studies on seed germination strategies.
On achievable rate regions for the Gaussian interference channel

The complete characterization of the capacity region of a two-user Gaussian interference channel (IC) is still an open problem unless the interference is strong. In this work, we derive an achievable rate region for this channel. It includes the rate region which is achieved by time/frequency division multiplexing (TDM/ FDM), and it also includes the rate region which is obtained by time sharing between the two rate pairs where one of the transmitters sends its data reliably at the maximal possible rate (i.e., the maximum rate it can achieve in the absence of interference), and the other transmitter decreases its data rate to the point where both receivers can reliably decode its message. The suggested rate region is easily calculable, though it is a particular case of the celebrated achievable rate region of Han and Kobayashi whose calculation is, in general, prohibitively complex. In the high-power regime, a lower bound on the sum-capacity (i.e., the maximal achievable total rate) is derived, and we show its superiority over the maximal total rate which is achieved by the TDM/FDM approach with moderate interference. For degraded and one-sided Gaussian ICs, we rely on some observations of Costa and Sato, and obtain directly their sum-capacities. We conclude our discussion by pointing out two interesting open problems.
Omega-3 Fatty Acids : Neuroprotective , Antioxidant and Anti-Inflammatory Effects in a Model of Parkinson ’ s Disease

Parkinson’s disease (PD) is a neurodegenerative pathology characterized by degeneration of dopaminergic neurons. The objectives were to evaluate the neuroprotective properties of Omega-3 (W3) in a model of PD. Wistar rats were distributed in groups: SO (unlesioned) and 6-OHDA-lesioned (untreated or treated with W3: 10, 20 and 100 mg/kg, p.o.). After 14 days, they were behaviorally evaluated and euthanized for monamines, nitrite and lipid peroxidation determinations. Striatal slices were immunohistochemicaly studied. The impaired locomotor activity and motor coordination observed in the untreated 6-OHDA-lesioned group, as related to the SO group, were partially reversed after W3 treatments. In apomorphine-induced rotations, while the SO group did not show any alteration, the untreated 6-OHDA-lesioned group increased this behavior, which was reduced by W3 treatments. Furthermore, DA and DOPAC levels were reduced in the untreated 6-OHDA-lesioned group, an effect partially reversed by W3. It also reversed the increased striatal concentrations of nitrite and lipid peroxidation and decreased neuron degeneration in the 6-OHDA-lesioned group. Similarly, decreases in striatal DAT and TH immunoreactivities found in the untreated 6-OHDA-lesioned group, relatively to the SO group, were also reversed. The results point out to the potential neuroprotective action of W3, for the treatment of neurodegenerative diseases, as PD. The W3 neuroprotection is probably related to its anti-inflammatory and antioxidant properties.
Modular Traffic Sign Recognition applied to on-vehicle real-time visual detection of American and European speed limit signs

We present a new modular traffic signs recognition system, successfully applied to both American and European speed limit signs. Our sign detection step is based only on shape-detection (rectangles or circles). This enables it to work on grayscale images, contrary to most European competitors, which eases robustness to illumination conditions (notably night operation). Speed sign candidates are classified (or rejected) by segmenting potential digits inside them (which is rather original and has several advantages), and then applying a neural digit recognition. The global detection rate is ~90% for both (standard) U.S. and E.U. speed signs, with a misclassification rate 150 minutes of video. The system processes in real-time ~20 frames/s on a standard high-end laptop.
Nature and Nurture in Psychiatry: A Predisposition-Stress Model of Mental Disorders

Introduction. Part I: Theory. Historical overview. Genetic predispositions to disease. The role of environmental stressors. The psychoanalytic model. Nature and nurture in the social sciences. Predisposition and stress in medical illness. Part II: Mental Disorders. Disorders, diagnoses, and traits. Schizophrenia. Mood disorders. Anxiety disorders and other neuroses. Posttraumatic stress disorder. Substance abuse. Eating disorders. Disorders arising in childhood. Personality disorders. Part III: Implications. Clinical implications. Preventive and research implications. Index.
Multiple Lineages of Ancient CR1 Retroposons Shaped the Early Genome Evolution of Amniotes

Chicken repeat 1 (CR1) retroposons are long interspersed elements (LINEs) that are ubiquitous within amniote genomes and constitute the most abundant family of transposed elements in birds, crocodilians, turtles, and snakes. They are also present in mammalian genomes, where they reside as numerous relics of ancient retroposition events. Yet, despite their relevance for understanding amniote genome evolution, the diversity and evolution of CR1 elements has never been studied on an amniote-wide level. We reconstruct the temporal and quantitative activity of CR1 subfamilies via presence/absence analyses across crocodilian phylogeny and comparative analyses of 12 crocodilian genomes, revealing relative genomic stasis of retroposition during genome evolution of extant Crocodylia. Our large-scale phylogenetic analysis of amniote CR1 subfamilies suggests the presence of at least seven ancient CR1 lineages in the amniote ancestor; and amniote-wide analyses of CR1 successions and quantities reveal differential retention (presence of ancient relics or recent activity) of these CR1 lineages across amniote genome evolution. Interestingly, birds and lepidosaurs retained the fewest ancient CR1 lineages among amniotes and also exhibit smaller genome sizes. Our study is the first to analyze CR1 evolution in a genome-wide and amniote-wide context and the data strongly suggest that the ancestral amniote genome contained myriad CR1 elements from multiple ancient lineages, and remnants of these are still detectable in the relatively stable genomes of crocodilians and turtles. Early mammalian genome evolution was thus characterized by a drastic shift from CR1 prevalence to dominance and hyperactivity of L2 LINEs in monotremes and L1 LINEs in therians.
Geographic rendezvous-based architectures for emergency data dissemination

Communication and information dissemination in times of disasters could have a critical role in aiding the emergency personnel and saving lives. Unfortunately, regular communication becomes more challenging at these times, as the infrastructure might be damaged or overloaded, and the requirements for communication (e.g., response time, capacity) becomes highly critical. Ad-hoc networks forming between wireless devices have always been considered as a promising technology at disaster recovery situations. In this paper, we examine the need for efficient and robust information dissemination mechanisms on top of infrastructure-less ad-hoc networks. We argue that distributed rendezvous-based approaches are more promising for emergency data dissemination than approaches based on network flooding or centralized storage. We present the design of a geographic rendezvous-based architecture and evaluate its performance in detail against other variants and traditional approaches. The study shows its efficiency, high success rate in delivering data, and its robustness to failures and mobility; characteristics highly valuable at emergency situations. Copyright © 2008 John Wiley & Sons, Ltd.
The Extraction of Reened Rules from Knowledge-based Neural Networks

Neural networks, despite their empirically-proven abilities, have been little used for the renement of existing knowledge because this task requires a three-step process. First, knowledge in some form must be inserted into a neural network. Second, the network must be re ned. Third, knowledge must be extracted from the network. We have previously described a method for the rst step of this process. Standard neural learning techniques can accomplish the second step. In this paper, we propose and empirically evaluate a method for the nal, and possibly most di cult, step. This method e ciently extracts symbolic rules from trained neural networks. The four major results of empirical tests of this method are that the extracted rules: (1) closely reproduce (and can even exceed) the accuracy of the network from which they are extracted; (2) are superior to the rules produced by methods that directly re ne symbolic rules; (3) are superior to those produced by previous techniques for extracting rules from trained neural networks; (4) are \human comprehensible. " Thus, the method demonstrates that neural networks can be an e ective tool for the re nement of symbolic knowledge. Moreover, the rule-extraction technique developed herein contributes to the understanding of how symbolic and connectionist approaches to arti cial intelligence can be pro tably integrated.
Modification of Left Ventricular Diastolic Behavior by Isometric Handgrip Exercise

To clarify the basis of increased left ventricular (LV) end-diastolic pressure associated with isometric exercise, LV diastolic and systolic function were examined in 25 patients during sustained handgrip. During handgrip, average systemic arterial mean pressure increased by 20 mm Hg, and LV systolic pressure rose by 31 mm Hg, though in five patients, no increase in mean arterial or LV systolic pressure occurred. LV end-diastolic pressure rose by 10 mm Hg, right ventricular systolic and end-diastolic pressures increased by 10 and 5 mm Hg, respectively (p < 0.01 for all pressures). LV end-systolic volume rose by 23%, but end-diastolic volume was unchanged. Reduction of ejection fraction by 13% and mean circumferential fiber shortening rate by 7% indicated further impairment of LV function, though ejection fraction was unchanged or augmented in 14 patients. In all patients, diastolic pressure-volume curves were displaced upward and to the right, without change in the rate constant of the exponentially fit pressure-volume or normalized pressure-volume elasticity relations, operational end-diastolic stiffness or the rate of isovolumic relaxation. Thus, upward transposition of diastolic pressure-volume relations during handgrip does not depend on changes in LV chamber elastic properties or relaxation, LV systolic function or coronary perfusion pressure, but appears, by inference, to be caused by the concomitantly increased right ventricular pressures, perhaps mediated in part by pericardial constraint in association with right ventricular distension.
Prognostic Factors for Reoperation After Plate Fixation of the Midshaft Clavicle

Objectives: To determine which prognostic factors were associated with an increased risk for all-cause reoperation in a heterogeneous population of patients treated with primary plate fixation of a midshaft clavicular fracture. Design: Retrospective observational study. Setting: Single university-affiliated tertiary care Level 1 trauma center. Patients: Of 235 consecutive patients with primary plate fixation for a midshaft clavicular fracture. A reviewer extracted data through a retrospective chart review regarding 20 possible prognostic variables and documented reoperations (defined as any surgical procedure after the initial surgery, including implant removal, bone grafts, implant exchanges, or debridement for infection). Intervention: Open reduction and internal fixation of the clavicle using straight and precontoured clavicle plates. Main Outcome Measurements: Complete 2-year follow-up information was available for 153 of 235 patients (65%). Of these 153 patients included in the analysis, 58 (38%) had reoperations. The preoperative risk factors for 3 specific “reoperation outcomes” were examined: (1) reoperation for implant removal alone; (2) reoperation for nonunion, infection, or fixation failure; and (3) multiple reoperations. Results: There was a significant reoperation rate in this patient series (58 of 153 patients, 38%). Although most were for isolated plate removal (42 of 153 patients, 27%), there were a minority of patients who required more complex (16 of 153 patients, 10%) or multiple (8 of 153 patients, 5%) procedures. For these 3 possible outcomes (reoperation for implant removal alone, reoperation for nonunion, infection, or fixation failure, and the need for multiple reoperations), significant risk factors were identified that can assist surgeons in patient selection and predicting reoperation after plate fixation of midshaft clavicle fractures. The significant risk factors for implant removal alone (42 of 153, 27%) were the use of a plate that was not precontoured and patient height <175 cm. The significant risk factors for reoperation for nonunion, infection, or fixation failure (16 of 153, 10%) were illicit drug use, diabetes, and previous surgery of the shoulder. The significant risk factors for multiple reoperations (8 of 153, 5%) were age >55 years and alcohol use >15 drinks per week. Conclusions: The use of precontoured plates can decrease the rate of hardware removal after primary fixation of displaced fractures of the midshaft clavicle. Also, specific preoperative prognostic factors may be used to counsel patients, maximize outcomes, minimize serious complications, and limit revision surgery. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Quantum Mass Correction of Solitons in (1+1)D via Numerical Methods

AbstractWe show how to calculate the quantum mass correction to (1+1)D solitonic ﬁeld theories usingnumerical methods. This is essential if we want to ﬁnd the correctionsto non-integrablemodels. Westart with a review of the standard derivation of the ﬁrst order quantum correction. Then, we re-derive a trace formula which allows us to compute the mass correction mode by mode. Speciﬁcally,we are interested in the extent to which the lowest modes from both, the soliton and the vacuum,sectors give the leading contribution. We apply the technique to both the Sine-Gordon and theφ 4 -kink model. Then, we compute all the modes numerically and hence the ﬁrst order quantumcontribution to the mass of the Sine-Gordon and φ 4 soliton. 1 Introduction We focus on the computation of the mass correction of (1+1)D solitonic theories theoretically andnumerically. We follow Rajaraman’s semi-classical quantisation procedure; another option is viapath integrals – see Dashen et al. [4]. Speciﬁcally, we are interested in the use of the normal modesto compute the mass correction and the extent to which the lowest modes from both, the solitonand the vacuum, sectors give the leading contribution. We start with a review of the derivationof the ﬁrst order quantum correction. Then, we derive the trace formula from ﬁrst principles.
Improved Stress Tolerance of GroESL-Overproducing Lactococcus lactis and Probiotic Lactobacillus paracasei NFBC 338

ABSTRACT The bacterial heat shock response is characterized by the elevated expression of a number of chaperone complexes. Two-dimensional polyacrylamide gel electrophoresis revealed that GroEL expression in probiotic Lactobacillus paracasei NFBC 338 was increased under heat adaptation conditions (52°C for 15 min). Subsequently, the groESL operon of L. paracasei NFBC 338 was PCR amplified, and by using the nisin-inducible expression system, two plasmids, pGRO1 and pGRO2, were constructed on the basis of vectors pNZ8048 and pMSP3535, respectively. These vectors were transferred into Lactococcus lactis(pGRO1) and L. paracasei(pGRO2), and after induction with nisin, overexpressed GroEL represented 15 and 20% of the total cellular protein in each strain, respectively. Following heat shock treatment of lactococci (at 54°C) and lactobacilli (at 60°C), the heat-adapted cultures maintained the highest level of viability (5-log-unit increase, approximately) in each case, while it was found that the GroESL-overproducing strains performed only moderately better (1-log-unit increase) than the controls. On the other hand, the salt tolerance of both GroESL-overproducing strains (in 5 M NaCl) was similar to that of the parent cultures. Interestingly, both strains overproducing GroESL exhibited increased solvent tolerance, most notably, the ability to grow in the presence of butanol (0.5% [vol/vol]) for 5 h, while the viability of the parent strain declined. These results confirm the integral role of GroESL in solvent tolerance, and to a lesser extent, thermotolerance of lactic acid bacteria. Furthermore, this study demonstrates that technologically sensitive cultures, including certain probiotic lactobacilli, can potentially be manipulated to become more robust for survival under harsh conditions, such as food product development and gastrointestinal transit.