Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pore-forming Toxin Interacts with a GPI-anchored Protein and Causes Vacuolation of the Endoplasmic Reticulum

In this paper, we have investigated the effects of the pore-forming toxin aerolysin, produced by Aeromonas hydrophila, on mammalian cells. Our data indicate that the protoxin binds to an 80-kD glycosyl-phosphatidylinositol (GPI)-anchored protein on BHK cells, and that the bound toxin is associated with specialized plasma membrane domains, described as detergent-insoluble microdomains, or cholesterol-glycolipid “rafts. ” We show that the protoxin is then processed to its mature form by host cell proteases. We propose that the preferential association of the toxin with rafts, through binding to GPI-anchored proteins, is likely to increase the local toxin concentration and thereby promote oligomerization, a step that it is a prerequisite for channel formation. We show that channel formation does not lead to disruption of the plasma membrane but to the selective permeabilization to small ions such as potassium, which causes plasma membrane depolarization. Next we studied the consequences of channel formation on the organization and dynamics of intracellular membranes. Strikingly, we found that the toxin causes dramatic vacuolation of the ER, but does not affect other intracellular compartments. Concomitantly we find that the COPI coat is released from biosynthetic membranes and that biosynthetic transport of newly synthesized transmembrane G protein of vesicular stomatitis virus is inhibited. Our data indicate that binding of proaerolysin to GPI-anchored proteins and processing of the toxin lead to oligomerization and channel formation in the plasma membrane, which in turn causes selective disorganization of early biosynthetic membrane dynamics.
A 3D Characteristics Database of Land Engraved Areas with Known Subclass

Subclass characteristics on bullets may mislead firearm examiners when they rely on traditional 2D images. In order to provide indelible examples for training and help avoid identification errors, 3D topography surface maps and statistical methods of pattern recognition are applied to toolmarks on bullets containing known subclass characteristics. This research was conducted by collecting 3D topography surface map data from land engraved areas of bullets fired through known barrels. This data was processed and used to train the statistical algorithms to predict their origin. The results from the algorithm are compared with the “right answers” (i.e. correct IDs) of the bullets in order to examine how well computational methods can work if subclass is present.
Analysis of data structures for admission control of advance reservation requests

Advance reservations are a useful method to allocate resources of various kinds in many different environments. Among others, a major advantage of this kind of reservation is the improved admission probability for requests that are made sufficiently early. In order to implement reliable admission control for these requests, it is important to store information in data structures about future allocations and to provide fast access to the available information. In this paper, two data structures are examined: a tree specially designed to support advance reservations is compared to arrays. Both structures are examined analytically and by measurements in a realistic network management system capable of advance reservations. It turns out that arrays are far better suited to support the required operations, in particular when large time intervals need to be scanned.
Generating Project Networks

Procedures for optimization and resource allocation in Operations Research first require a project network for the task to be specified. The specification of a project network is at present done in an intuitive way. AI work in plan formation has developed formalisms for specifying primitive activities, and recent work by Sacerdoti (1975a) has developed a planner able to generate a plan as a partially ordered network of actions. The "planning: a joint AI/OR approach" project at Edinburgh has extended such work and provided a hierarchic planner which can aid in the generation of project networks. This paper describes the planner (NONLIN) and the Task Formalism (TF) used to hierarchically specify a domain.
Is age at implant the only factor that counts? The influence of working memory on lexical and grammatical development in children with cochlear implants

In this study, we explored the influence of time factors (age at implant, time with cochlear implant and age), complex working memory and phonological short-term memory on lexical and grammatical development in congenitally deaf children with cochlear implants. Fifteen children (aged 5 years 4 months to 11 years 5 months) were examined with the use of several linguistic and cognitive measures after a minimum of 18 months of implant use. Phonological short-term memory was assessed with non-word repetition, where the percentage of correctly repeated consonants and vowels was counted. For the assessment of lexical acquisition, a novel word learning task was administered. Receptive and expressive grammar was tested. Our results corroborate earlier findings on the influence of phonological short-term memory on novel word learning. The percentage of vowels correctly produced in non-word repetition was more important in this group than age at implant, not only for novel word learning, but also for receptive and expressive grammar. Sumario En este estudio, exploramos la influencia sobre el desarrollo léxico y gramatical de los factores temporales (edad de implantación, edad y tiempo transcurrido con el implante), de la memoria activa compleja y de la memoria fonológica a corto plazo, en niños con sorderas congénitas y portadores de un implante coclear. Se examinaron quince niños (con edades de 5 años y 4 meses a 11 años y 5 meses) por medio de varias medidas cognitivas y lingüísticas, luego de un mínimo de 18 meses de uso del implante. La memoria fonológica a corto plazo fue evaluada por medio de la repetición de sonidos sin contenido semántico, donde se tabuló el porcentaje de vocales y consonantes correctamente repetidas. Para la evaluación de la adquisición del léxico, se administró una novedosa tarea de aprendizaje de palabras y se evaluó la gramática receptiva y expresiva. Nuestros resultados corroboraron hallazgos anteriores sobre la influencia de la memoria fonológica a corto plazo en el aprendizaje de nuevas palabras. El porcentaje de vocales correctamente producidas por medio de la repetición de sonidos sin contenido semántico fue más importante en este grupo que la edad de implantación, no sólo para el aprendizaje de palabras nuevas, sino también en cuanto a la gramática receptiva y expresiva.
The Small-Area Hypothesis: Effects of Progress Monitoring on Goal Adherence

This article examines a small-area hypothesis: individuals striving toward a goal end state exhibit greater motivation when their attention is directed to whichever is smaller in size—their accumulated or remaining progress. The result is that, at the beginning of goal pursuit, directing attention to accumulated progress increases goal adherence relative to directing attention to remaining progress (e.g., 20% completed is more impactful than 80% remaining). However, with closeness to the goal, directing attention to accumulated progress lessens goal adherence relative to directing attention to remaining progress (e.g., 20% remaining is more impactful than 80% completed; studies 1–2). The focus on small areas increases motivation by creating an illusion of fast progress (study 3). Therefore, when individuals wish to prolong goal pursuit and avoid reaching the goal’s end state, they slow down goal adherence when their attention is directed to small areas (study 4).
Characterization of lipids A of Ralstonia solanacearum lipopolysaccharides

The analysis of fatty acid profiles of lipopolysacharid.es has shown that R. solanacearum strains tested may be divided into two groups. The first group is represented by R. solanacearum strains (5712, 7945, 7955 and 8110) the lipids A of which contained hydroxylated fatty acids with long chains: 3-hydroxy­ tetradecanoic, 2-hydroxyhexadecanoic and 2-hydroxyoctadecanoic. The second group was represented by R. solanacearum strains the lipids A of which contained hydroxylated fatty acids with short chains: 3-hydroxydecanoic, 2-hydroxydodecanoic and 3-hydroxydodecanoic. 3-hydroxytetradecanoic acid was observed in a small amount. A comparative analysis of the fatty acid composition and biological activity gives a possibility to suppose that 3-hydroxytetradecanoic, 2-hydroxyhexadecanoic and 2-hydroxy­ octadecanoic acids may be responsible for the toxicity and pyrogenicity of the lipopolysaccharides tested.
Cell Wall-Bound Invertase Limits Sucrose Export and Is Involved in Symptom Development and Inhibition of Photosynthesis during Compatible Interaction between Tomato and Xanthomonas campestris pv vesicatoria[W][OA]

Cell wall-bound invertase (cw-Inv) plays an important role in carbohydrate partitioning and regulation of sink-source interaction. There is increasing evidence that pathogens interfere with sink-source interaction, and induction of cw-Inv activity has frequently been shown in response to pathogen infection. To investigate the role of cw-Inv, transgenic tomato (Solanum lycopersicum) plants silenced for the major leaf cw-Inv isoforms were generated and analyzed during normal growth and during the compatible interaction with Xanthomonas campestris pv vesicatoria. Under normal growth conditions, activities of sucrolytic enzymes as well as photosynthesis and respiration were unaltered in the transgenic plants compared with wild-type plants. However, starch levels of source leaves were strongly reduced, which was most likely caused by an enhanced sucrose exudation rate. Following X. campestris pv vesicatoria infection, cw-Inv-silenced plants showed an increased sucrose to hexose ratio in the apoplast of leaves. Symptom development, inhibition of photosynthesis, and expression of photosynthetic genes were clearly delayed in transgenic plants compared with wild-type plants. In addition, induction of senescence-associated and pathogenesis-related genes observed in infected wild-type plants was abolished in cw-Inv-silenced tomato lines. These changes were not associated with decreased bacterial growth. In conclusion, cw-Inv restricts carbon export from source leaves and regulates the sucrose to hexose ratio in the apoplast. Furthermore, an increased apoplastic hexose to sucrose ratio can be linked to inhibition of photosynthesis and induction of pathogenesis-related gene expression but does not significantly influence bacterial growth. Indirectly, bacteria may benefit from low invertase activity, since the longevity of host cells is raised and basal defense might be dampened.
Rapid Generation of Full Clinical-Grade Human Antiadenovirus Cytotoxic T Cells for Adoptive Immunotherapy

Adenovirus (ADV) infections are one of the major causes of morbidity and mortality after hematopoietic stem cell transplantation, despite new antiviral treatment strategies. We describe here a complete clinical-grade generation of human anti-ADV cytotoxic T cells to propose an adoptive immunotherapy. Peripheral blood mononuclear cells (PBMC) from 7 healthy donors, known for their good cellular immunity against ADV, were stimulated for 6 hours with a synthetic peptide pool covering the ADV5 Hexon protein interferon-γ (IFN-γ) secreting cells were isolated on a clinical device. After immunoselection, a mean number of 1.01±0.84×106 total nucleated cells was obtained. The isolated ADV-specific T cells were mainly CD4+ (mean=56%±20.8%, yield=51%±32.4%) but also CD8+ (mean=42%±27%, yield=56%±39.3%). Isolated T lymphocytes (CTL) were expanded to carry out functional tests. Ability of the expanded CTL to secrete IFN-γ and to proliferate after restimulation with the ADV peptide pool was confirmed. A high cytotoxicity against autologous target cells loaded with ADV antigens was observed but not against nonloaded target cells. We observed a decrease of 1.27 log of the allogeneic reaction against non HLA identical healthy donor PBMC with CTL compared with the PBMC before selection. Clinical-grade generation of ADV-specific T cells was achieved with a synthetic antigen. This technology has the advantage of being fast, and is sufficiently reactive to be proposed for immunotherapy if antiviral treatment fails.
Intestinal Bacteria Condition Dendritic Cells to Promote IgA Production

Immunoglobulin (Ig) A represents the predominant antibody isotype produced at the intestinal mucosa, where it plays an important role in limiting the penetration of commensal intestinal bacteria and opportunistic pathogens. We show in mice that Peyer's Patch-derived dendritic cells (PP-DC) exhibit a specialized phenotype allowing the promotion of IgA production by B2 cells. This phenotype included increased expression of the retinaldehyde dehydrogenase 1 (RALDH1), inducible nitric oxide synthase (iNOS), B cell activating factor of the tumor necrosis family (BAFF), a proliferation-inducing ligand (APRIL), and receptors for the neuropeptide vasoactive intestinal peptide (VIP). The ability of PP-DC to promote anti-CD40 dependent IgA was partially dependent on retinoic acid (RA) and transforming growth factor (TGF)-β, whilst BAFF and APRIL signaling were not required. Signals delivered by BAFF and APRIL were crucial for CD40 independent IgA production, although the contribution of B2 cells to this pathway was minimal. The unique ability of PP-DC to instruct naïve B cells to differentiate into IgA producing plasma cells was mainly imparted by the presence of intestinal commensal bacteria, and could be mimicked by the addition of LPS to the culture. These data indicate that exposure to pathogen-associated molecular patterns present on intestinal commensal bacteria condition DC to express a unique molecular footprint that in turn allows them to promote IgA production.
Factors associated with relapse in adult patients discharged from the emergency department following acute asthma: a systematic review

A significant proportion of patients discharged from the emergency department (ED) with asthma exacerbations will relapse within 4 weeks. This systematic review summarises the evidence regarding relapses and factors associated with relapse in adult patients discharged from EDs after being treated for acute asthma. Following a registered protocol, comprehensive literature searches were conducted. Studies tracking outcomes for adults after ED management and discharge were included if they involved adjusted analyses. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and the Risk of Bias (RoB) Tool. Results were summarised using medians and IQRs or mean and SD, as appropriate. 178 articles underwent full-text review and 10 studies, of various methodologies, involving 32 923 patients were included. The majority of the studies were of high quality according to NOS and RoB Tool. Relapse proportions were 8±3%, 12±4% and 14±6% at 1, 2 and 4 weeks, respectively. Female sex was the most commonly reported and statistically significant factor associated with an increased risk of relapse within 4 weeks of ED discharge for acute asthma. Other factors significantly associated with relapse were past healthcare usage and previous inhaled corticosteroids (ICS) usage. A median of 17% of patients who are discharged from the ED will relapse within the first 4 weeks. Factors such as female sex, past healthcare usage and ICS use at presentation were commonly and significantly associated with relapse occurrence. Identifying patients with these features could provide clinicians with guidance during their ED discharge decision-making.
A longitudinal study of World Wide Web users' information-searching behavior

A study of the "real world" Web information searching behavior of 206 college students over a 10-month period showed that, contrary to expectations, the users adopted a more passive or browsing approach to Web information searching and became more eclectic in their selection of Web hosts as they gained experience. The study used a longitudinal transaction log analysis of the URLs accessed during 5,431 user days of Web information searching to detect changes in information searching behavior associated with increased experience of using the Web. The findings have implications for the design of future Web information retrieval tools.
1 Validation of Intratumoral T-bet + Lymphoid Cells as Predictors of Disease-Free Survival in Breast Cancer

Dept. of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada Dept. of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada Dept. of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
Sample Size Determination for Kernel Regression Estimation Using Sequential Fixed-Width Confidence Bands

We consider a random design model based on independent and identically distributed pairs of observations (Xi,Yi), where the regression function m(x) is given by m(x) = E(Yi|Xi = x) with one independent variable. In a nonparametric setting the aim is to produce a reasonable approximation to the unknown function m(x) when we have no precise information about the form of the true density, f(x) of X. We describe an estimation procedure of non- parametric regression model at a given point by some appropriately constructed fixed-width (2d) confidence interval with the confidence coefficient of at least1 �. Here, d(> 0) and � 2 (0,1) are two preassigned values. Fixed-width confidence intervals are developed using both Nadaraya-Watson and local linear kernel esti- mators of nonparametric regression with data-driven bandwidths. The sample size was optimized using the purely and two-stage sequential procedures together with asymptotic properties of the Nadaraya-Watson and local linear estimators. A large scale simulation study was performed to compare their coverage accu- racy. The numerical results indicate that the confi- dence bands based on the local linear estimator have the better performance than those constructed by us- ing Nadaraya-Watson estimator. However both esti- mators are shown to have asymptotically correct cov- erage properties. Index Term —Nonparametric regression, random de- sign, Nadaraya-Watson estimator, Local linear esti- mator, fixed-width confidence interval, purely sequen- tial procedure, two-stage sequential procedure
Predictors of Spontaneous Closure of Isolated Secundum Atrial Septal Defect in Children: A Longitudinal Study

OBJECTIVES. The goals were to assess the frequency of spontaneous closure of isolated secundum atrial septal defect in children and to identify predictors of spontaneous atrial septal defect closure. METHODS. A retrospective cohort study was performed in a tertiary care pediatric cardiology center. Consecutive patients (n = 200) diagnosed as having isolated atrial septal defects (no multiple or fenestrated atrial septal defects, no additional congenital heart disease, and no syndromes) were monitored for >6 months with serial 2-dimensional echocardiography, according to a standardized protocol. RESULTS. The median age at diagnosis was 5 months (minimum: 0 months; maximum: 13.9 years). The atrial septal defect diameter at diagnosis was 4 to 5 mm in 40% of cases, 6 to 7 mm in 28% of cases, 8 to 10 mm in 21% of cases, and >10 mm in 11% of cases. The median age at the final follow-up evaluation was 4.5 years (range: 6.8 months to 16.2 years). Thirty-four percent of atrial septal defects showed spontaneous closure, and 28% decreased to a diameter of ≤3 mm. Logistic regression analysis revealed atrial septal defect diameter and age at diagnosis as independent predictors of spontaneous closure or regression to ≤3-mm defect size. Of atrial septal defects with a diameter of 4 to 5 mm at diagnosis, 56% showed spontaneous closure, 30% regressed to a diameter of ≤3 mm, and none required surgical closure. Of atrial septal defects with a diameter of >10 mm at diagnosis, none closed spontaneously, whereas 77% required surgical or device closure. Gender and observation time were not associated with spontaneous atrial septal defect closure or regression to ≤3 mm. CONCLUSIONS. In the present study population of children with atrial septal defects, 62% showed spontaneous closure (34%) or regression to ≤3 mm (28%). Initial atrial septal defect diameter was the main predictor of spontaneous closure.
The Role of Child Sexual Abuse in the Etiology of Substance-Related Disorders

ABSTRACT To elucidate the role of child sexual abuse in the etiology of substance-related disorders, a systematic review of the several articles on the childhood sexual abuse-related risk for developing substance problems in adolescence or adulthood is provided. Seven databases were searched, supplemented with hand-search of reference lists. Six reviews, including 200 studies, were included. Results indicate that child sexual abuse is a statistically significant, although general and nonspecific, risk factor for substance problems. Other biological and psychosocial variables contribute to substance-related disorders, with sexual abuse conferring additional risk, either as a distal, indirect cause or as a proximal, direct cause. Recommendations for future research are provided.
Complementary Learning Systems

This paper reviews the fate of the central ideas behind the complementary learning systems (CLS) framework as originally articulated in McClelland, McNaughton, and O'Reilly (1995). This framework explains why the brain requires two differentially specialized learning and memory systems, and it nicely specifies their central properties (i.e., the hippocampus as a sparse, pattern-separated system for rapidly learning episodic memories, and the neocortex as a distributed, overlapping system for gradually integrating across episodes to extract latent semantic structure). We review the application of the CLS framework to a range of important topics, including the following: the basic neural processes of hippocampal memory encoding and recall, conjunctive encoding, human recognition memory, consolidation of initial hippocampal learning in cortex, dynamic modulation of encoding versus recall, and the synergistic interactions between hippocampus and neocortex. Overall, the CLS framework remains a vital theoretical force in the field, with the empirical data over the past 15 years generally confirming its key principles.
NetReplay: a new network primitive

In this paper, we describe Net-Replay, a new network primitive to help application end points conduct in-band characterization of the glitches they encountered. In Net-Replay, each network infrastructure element remembers a small amount of information for every packet observed at the element over a certain time interval. Furthermore, network elements expose a simple "packet marking" interface, using which they can indicate to end-points whether or not they had seen a particular packet in the past. When application end-points observe glitches, they replay (i.e. retransmit) the packets which observed the glitch and leverage feedback from network elements to determine the type and location of the glitch encountered by the packets. We discuss how end-host network stacks should be modified to leverage Net-Replay in this fashion. We also consider how network infrastructure can support Net-Replay in a lowoverhead fashion. We argue that Net-Replay can enable applications to detect a variety of glitches and react to them in an accurate and informed manner, while ensuring that the infrastructure stays simple and fast. We believe that proactive support from the network in the form of Net-Replay-like functionality is crucial to ensure robust performance of future Internet applications, many of which are likely to be highly demanding and far less tolerant of network glitches than traditional applications.