Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential protein partitioning within the herpesvirus tegument and envelope underlies a complex and variable virion architecture

Significance Neuroinvasive herpesviruses cause diseases in humans ranging from cold sores to central nervous system infections. Unlike most icosahedral viruses, herpesvirus capsids are surrounded by protein layers that lack polyhedral architecture. The outer layers are critical for herpesvirus infectivity. Although the disorganized layers are visible by electron microscopy, the protein topography of these layers remains unclear. We fused fluorophores to virus proteins and pinpointed their positions within virions at nanometer resolution. The findings reveal a complex and variable asymmetric architecture, shed light on herpesvirus assembly, and provide a foundation for visualizing viral particle dynamics during herpesvirus infection. The herpesvirus virion is a multilayered structure consisting of a DNA-filled capsid, tegument, and envelope. Detailed reconstructions of the capsid are possible based on its icosahedral symmetry, but the surrounding tegument and envelope layers lack regular architecture. To circumvent limitations of symmetry-based ultrastructural reconstruction methods, a fluorescence approach was developed using single-particle imaging combined with displacement measurements at nanoscale resolution. An analysis of 11 tegument and envelope proteins defined the composition and plasticity of symmetric and asymmetric elements of the virion architecture. The resulting virion protein map ascribes molecular composition to density profiles previously acquired by traditional ultrastructural methods, and provides a way forward to examine the dynamics of the virion architecture during infection.
Challenging

My scholarly research over the past 25 years has focused on understanding autistic symptoms in children with neurogenetic disorders such as fragile X syndrome, Cornelia de Lange syndrome and Prader-Willi syndrome to determine how environmental and biological factors affect the development of these behaviors, toward the goal of creating patient-specific treatments. My investigations include extensive neuroimaging research (MRI, fMRI, DTI), state-of-the-art eye tracking, functional assessments of behavior under controlled experimental conditions, and novel behavioral and pharmacological interventions. I am extensively trained in behavioral assessment and interventions, and provide clinical evaluations and consultation as a doctoral-level Board Certified Behavior Analyst (BCBA-D). patient-specific methods for treating the symptoms of these disorders.
Characteristics of schizophrenia residents and staff rejection in community mental health hostels.

BACKGROUND In the era of deinstitutionalization, increasing numbers of schizophrenia patients reside and receive rehabilitational treatment within the framework of community hostels. The quality of staff-patient relationships is a crucial determinant of the rehabilitational process outcome. METHOD This study examined the characteristics of 56 schizophrenia hostel residents, measured the degree of staff criticism and rejection expressed towards these patients and assessed the contribution of residents and staff characteristics to the induction of staff rejection. Measures included assessments of patients' symptoms using the Positive and Negative Syndrome Scale (PANSS), staff attitudes using the Patient Rejection Scale (PRS), and patients' living skills using the Independent Living Skills Survey (ILSS). RESULTS Young, relatively inexperienced instructors represented 60% of the hostels staff. Residents' symptoms and staff rejection levels were overall low. However, significantly increased rejection was expressed towards patients who were more symptomatic, as measured by PANSS total and positive symptoms scores and had diminished job-related and health care living skills. Staff older age and longer professional experience were correlated with higher rejection scores. LIMITATIONS Relatively small sample size and catchment area. CONCLUSIONS These findings highlight the need for a better definition and understanding of schizophrenia residents selection criteria and treatment goals in community hostels. Moreover, they suggest that improvements in this area should be coupled with the provision of specialized staff training aiming at the achievement of more flexible staff attitudes. Within this framework, the PRS may serve as a practical, cost-effective tool for monitoring crucial aspects of staff-patients relationships.
Timing and Magnitude of Initial Change in Disease Activity Score 28 Predicts the Likelihood of Achieving Low Disease Activity at 1 Year in Rheumatoid Arthritis Patients Treated with Certolizumab Pegol: A Post-hoc Analysis of the RAPID 1 Trial

Objective. To determine the relationship between timing and magnitude of Disease Activity Score [DAS28(ESR)] nonresponse (DAS28 improvement thresholds not reached) during the first 12 weeks of treatment with certolizumab pegol (CZP) plus methotrexate, and the likelihood of achieving low disease activity (LDA) at 1 year in patients with rheumatoid arthritis. Methods. In a post-hoc analysis of the RAPID 1 study, patients achieving LDA [DAS28(ESR) ≤ 3.2] at Year 1 were assessed according to DAS28 nonresponse at various timepoints within the first 12 weeks. Results. Seven-hundred eighty-three patients were included (CZP 200 mg, n = 393; CZP 400 mg, n = 390). A total of 86.9% of patients in the CZP 200 mg group had a DAS28 improvement of ≥ 1.2 by Week 12. Of the 13.1% of patients with DAS28 improvement < 1.2 by Week 12, only 2.0% had LDA at Year 1. Failure to achieve LDA at Year 1 depended on timing of nonresponse — 22.3%, 8.4%, and 2.0% of patients with DAS28 improvement < 1.2 by Weeks 1, 6, and 12, respectively, had LDA at Year 1 — and magnitude of initial lack of DAS28 improvement; for example, compared with the patients with DAS28 < 1.2 improvement, fewer patients with DAS28 < 0.6 had LDA at Year 1 (17.4%, 2.4%, and 0.0% at Weeks 1, 6, and 12, respectively). Conclusion. Failure to achieve improvement in DAS28 within the first 12 weeks of therapy was predictive of a low probability of achieving LDA at Year 1. Moreover, the accuracy of the prediction was found to be strongly dependent on the magnitude and timing of the lack of the response. (Clinical Trial Registration Nos. NCT00152386 and NCT00175877).
Effects of silicon, nickel, and vanadium on impact toughness in spring steels

AbstractThe effects of alloying elements silicon, nickel, and vanadium, and the tempering temperatures on the mechanical properties, especially impact toughness, in 0.6C–(1.0–2.5)Si–(0.7–1.8)Ni–(0.1–0.2)V steels (wt-%), were investigated by performing hardness tests, impact tests, and TEM examination. The results obtained showed that the addition of silicon up to 2.5 wt-% shifted the embrittlement temperatures to higher temperatures, owing to the silicon retarding the formation and growth of cementite at boundaries. Additionally, it was found that the temperature of the peak in Charpy impact toughness v. tempering temperature curves coincided with the onset of the decomposition of retained austenite. The temperatures of the conversion of e carbide to cementite and of the onset of tempered martensite embrittlement were not changed by the addition of nickel up to 2.0 wt-% in the present steels. However, the decomposition of retained austenite was delayed and the toughness was increased over all the temperin.
Rape Victim and Perpetrator Blame: Effects of Victim Ethnicity, Perpetrator Ethnicity, Participant Gender, and Participant Ethnicity

The aim of the current study is to examine the influence of the victim's, perpetrator's, and participant's ethnicity on victim and perpetrator blame attributions. Additionally, comparisons between males and females and a community and student sample were made. Participants read a rape vignette in the form of a newspaper article and subsequently attributed victim and perpetrator blame. A 2 (victim's ethnicity) X 2 (perpetrator's ethnicity) X 2 (gender of participant) X 2 (ethnicity of participant) between subjects design were used. Measures of blame attributions toward the victim and perpetrator were used as dependent variables for both a community (n = 211) and student (n = 200) sample. Main results showed that participants with an immigrant background and participants from the community sample attributed significantly more victim and less perpetrator blame while gender of the participants failed to reach significance in most analyses. Several interactions involving victim and perpetrator ethnicity emerged and were subsequently discussed as well as suggestions for future research. (Less)
A p38 Mitogen-Activated Protein Kinase-Dependent Mechanism of Disinhibition in Spinal Synaptic Transmission Induced by Tumor Necrosis Factor-α

Tumor necrosis factor-α (TNFα) is a proinflammatory cytokine that contributes to inflammatory and neuropathic pain. The mechanism by which TNFα modulates synaptic transmission in mouse substantia gelatinosa was studied using whole-cell patch clamp and immunohistochemistry. TNFα was confirmed to significantly increase the frequency of spontaneous EPSCs (sEPSCs) in spinal neurons and to also produce a robust decrease in the frequency of spontaneous IPSCs (sIPSCs). The enhancement of excitatory synaptic transmission by TNFα is in fact observed to be dependent on the suppression of sIPSCs, or disinhibition, in that blockade of inhibitory synaptic transmission prevents the effect of TNFα on sEPSCs but not vice versa. TNFα-induced inhibition of sIPSCs was blocked by neutralizing antibodies to TNF receptor 1 (TNFR1) but not to TNFR2 and was abolished by the p38 mitogen-activated protein kinase inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole]. TNFα rapidly inhibited spontaneous action potentials in GABAergic neurons identified in transgenic mice expressing enhanced green fluorescent protein controlled by the GAD67 promoter. This inhibitory effect was also blocked by intracellular delivery of SB202190 to the targeted cells. The inhibition of spontaneous activity in GABAergic neurons by TNFα is shown as mediated by a reduction in the hyperpolarization-activated cation current (I h). These results suggest a novel TNFα–TNFR1–p38 pathway in spinal GABAergic neurons that may contribute to the development of neuropathic and inflammatory pain by TNFα.
NS-2 TCP-Linux: an NS-2 TCP implementation with congestion control algorithms from Linux

This paper introduces NS-2 TCP-Linux, a new NS-2 TCP implementation that embeds the source code of TCP congestion control modules from Linux kernels. Compared to existing NS-2 TCP implementations, NS-2 TCP-Linux has three improvements: 1) a standard interface for congestion control algorithms similar to that in Linux 2.6, ensuring better extensibility for emerging congestion control algorithms; 2) a redesigned loss detection module (i.e. Scoreboard) that is more accurate; and 3) a new event queue scheduler that increases the simulation speed. As a result, NS-2 TCP-Linux is more extensible, runs faster and produces simulation results that are much closer to the actual TCP behavior of Linux. In addition to helping the network research community, NS-2 TCP-Linux will also help the Linux kernel community to debug and test their new congestion control algorithms.In this paper, we explain the design of NS-2 TCP-Linux. We also present a preliminary evaluation of three aspects of NS-2 TCP-Linux: extensibility to new congestion control algorithms, accuracy of the simulation results and simulation performance in terms of simulation speed and memory usage.Based on these results, we strongly believe that NS-2 TCP-Linux is a promising alternative or even a replacement for existing TCP implementations in NS-2. We call for participation to test and improve this new TCP implementation.
Scanning Probe Microscopy of Clay Minerals

A set of surface-sensitive analytical techniques, collectively called scanning probe microscopy (SPM), has been developed and applied to a wide variety of materials. With SPM one can image nearly any surface in vacuum, in air, or in solution, and often can actually observe surfaces during reaction. Scanning tunneling microscopy (STM) and scanning force microscopy (SFM) have been used successfully in the geosciences to characterize mineral surface structure and topography, surface reactivity, and the rates and mechanisms of mineral-water reactions. SPM techniques are most easily applied to materials with nearly flat surfaces, and minerals with good cleavage, particularly clays, which are excellent prospects for investigation. However, there have been relatively few applications of SPM to geologic materials, particularly in comparison to applications in physics, chemistry, material science, or even biological sciences. The purpose of this volume is to introduce the theory and operation of SPM to clay mineralogists, summarize previous work using STM and SFM in mineralogy, and outline the advantages and limitations of SPM for future research applications.
Effects of the administration of cholera toxin as a mucosal adjuvant on the immune and protective response induced by Proteus mirabilis MrpA fimbrial protein in the urinary tract

Proteus mirabilis is commonly associated with complicated UTI and expresses several virulence factors, including MR/P fimbriae. In the present study mice were immunised nasally with MrpA, the structural subunit of MR/P, with or without CT as a mucosal adjuvant. The animals were then challenged with P. mirabilis and induction of specific serum and urine IgG and IgA, IFN‐γ production and bacterial kidney and bladder colonization were assessed. MrpA‐immunised mice exhibited significant induction of serum IgA and urine IgA and IgG. MrpA/CT‐immunised mice showed both significant serum and urine IgA and IgG production. Only this group showed significant IFN‐γ production. Both groups of animals had significant decrease in bacterial colonization of kidneys but not of bladders. No correlation between specific antibody induction in serum and CFU decrease was observed in any group of animals. Our results suggest that a mucosal adjuvant (CT) in the urinary tract enhanced humoral and cytokine response although it did not influence the degree of protection against UTI provided by MrpA. Further studies are necessary to understand immune modulation in the urinary tract.
Oral applications of ultra-short laser pulses: a new approach for gentle and painless treatment?

In dental hard tissue ablation, ultra-short laser pulses have proven sufficiently their potential for material ablation with negligible collateral damage providing many advantages. The absence of microcracks and the possibility to avoid overheating of the pulp during dental cavity preparation may be among the most important issues, the latter opening up an avenue for potential painless treatment. Beside the evident short interaction time of laser radiation with the irradiated tissue, scanning of the ultra-short pulse trains turned out to be crucial for ablating cavities of required quality and shape. Additionally, such a technique allows to treat larger areas like the ones dentists are used to work with, i.e. ~ 1 mm Ø. In this paper, an overview of different scanning methods together with the algorithms used and an assessment of their applicability is presented. A variety of pulse durations from ~100 fs up to several ps has been used by numerous authors over the last approximately ten years. Having employed 330 fs pulses, we present the corresponding ablation thresholds for dental hard tissue (enamel, dentine; human and bovine), for a number of dental restoration materials, as well as for different types of bovine bone. Dental implants frequently have to be cleaned from plaque being deposited around their necks in areas where the gums have already retreated. A preliminary investigation is presented on the applicability of ultra-short pulses with mentioned duration for the gentle cleaning of titanium implants focusing on the preservation of the special plasma-sprayed biocompatible implant surface.
Engagement of β-arrestin by transactivated insulin-like growth factor receptor is needed for V2 vasopressin receptor-stimulated ERK1/2 activation

G protein-coupled receptors (GPCRs) have been shown to activate the mitogen-activated protein kinases, ERK1/2, through both G protein-dependent and -independent mechanisms. Here, we describe a G protein-independent mechanism that unravels an unanticipated role for β-arrestins. Stimulation of the V2 vasopressin receptor (V2R) in cultured cells or in vivo in rat kidney medullar collecting ducts led to the activation of ERK1/2 through the metalloproteinase-mediated shedding of a factor activating the insulin-like growth factor receptor (IGFR). This process was found to be both Src- and β-arrestin–dependent. Whereas Src was found to act upstream of the metalloproteinase activation and be required for the release of the IGFR-activating factor, β-arrestins were found to act downstream of the IGFR transactivation. Unexpectedly, the engagement of β-arrestins by the IGFR but not by the V2R was needed to promote the vasopressin-stimulated ERK1/2 activation, indicating that a pool of β-arrestins distinct from those β-arrestins recruited to the V2R acts downstream of the receptor tyrosine kinase to activate ERK1/2. Such a dual site of action for β-arrestins helps explain the pleiotropic actions of this scaffolding protein. Given the role that V2R-stimulated ERK1/2 plays in kidney cell proliferation, this transactivation mechanism may have important implications for renal pathophysiology. Still, the role of β-arrestins downstream of a transactivation event is not limited to the V2R, because we observed a similar involvement for an unrelated GPCR (the platelet-activating factor receptor), indicating that it may be a general mechanism shared among GPCRs.
THE PRENATAL PARENTAL REFLECTIVE FUNCTIONING QUESTIONNAIRE: EXPLORING FACTOR STRUCTURE AND CONSTRUCT VALIDITY OF A NEW MEASURE IN THE FINN BRAIN BIRTH COHORT PILOT STUDY.

Parental reflective functioning (PRF) is the capacity to focus on experience and feelings in oneself and in the child. Individual differences in PRF reportedly affect child attachment and socioemotional development. In this study, we report work on developing a questionnaire to assess PRF during pregnancy (Prenatal Parental Reflective Functioning Questionnaire; P-PRFQ). The factor structure of the 33-item version of the P-PRFQ was explored using pilot study data from the Finn Brain Birth Cohort Study (n = 124 mothers, n = 82 fathers). Construct validity was assessed against the Pregnancy Interview (PI; A. Slade, L. Grunebaum, L. Huganir, & M. Reeves, 1987, 2002, 2011) in a subsample of 29 mothers from the same pilot sample. Exploratory and confirmatory factor analysis resulted in a 14-item P-PRFQ, with three factors which seem to capture relevant aspects of prenatal parental mentalization-F1: "Opacity of mental states," F2: "Reflecting on the fetus-child," and F3: "The dynamic nature of the mental states. " Functioning of the factor structure was further tested in the large cohort with 600 mothers and 600 fathers. Correlations with the PI result were high, both regarding total and factor scores of the P-PRFQ. Cost-effective tools to assess key areas of early parenting are needed for both research and clinical purposes. The 14-item P-PRFQ seems to be an applicable and promising new tool for assessing very early parental mentalizing capacity.
Lung and Systemic Inflammation in Preterm Lambs on Continuous Positive Airway Pressure or Conventional Ventilation

Intratracheal lipopolysaccharide (LPS) causes acute inflammation and injurious mechanical ventilation results in pulmonary and systemic inflammation. We aimed to determine in preterm lungs if continuous positive airway pressure (CPAP) protects against pulmonary and systemic inflammation, compared with conventional mechanical ventilation (CMV) after intratracheal LPS. Preterm fetuses were exposed to maternal betamethasone and Epostane 36 h before delivery at 133 d gestational age (term = 150 d). Lambs were intubated and randomized to receive gentle CMV (tidal volume 8 mL/kg) or CPAP with 8 cm H2O pressure. Surfactant (10 mg/kg) mixed with 1 mg LPS or saline was instilled into the trachea at 15 min. Blood gas status, ventilation variables, and arterial pressures were recorded for 3 h. Static pressure-volume curves and lung and systemic inflammation were assessed postmortem. CPAP lambs had elevated Paco2 and minute ventilation compared with the CMV lambs. Cytokine mRNA was increased in the lungs and liver of CPAP and CMV lambs relative to unventilated controls. Intratracheal LPS amplified the cytokine mRNA responses of IL-1β, IL-6, and IL-8 in the lung and liver. Blood neutrophils decreased similarly after LPS in CPAP and CMV groups. Cytokine markers of lung injury or the systemic response to intratracheal LPS were not decreased by CPAP relative to CMV, in preterm lambs.
Auralist: introducing serendipity into music recommendation

Recommendation systems exist to help users discover content in a large body of items. An ideal recommendation system should mimic the actions of a trusted friend or expert, producing a personalised collection of recommendations that balance between the desired goals of accuracy, diversity, novelty and serendipity. We introduce the Auralist recommendation framework, a system that - in contrast to previous work - attempts to balance and improve all four factors simultaneously. Using a collection of novel algorithms inspired by principles of "serendipitous discovery", we demonstrate a method of successfully injecting serendipity, novelty and diversity into recommendations whilst limiting the impact on accuracy. We evaluate Auralist quantitatively over a broad set of metrics and, with a user study on music recommendation, show that Auralist's emphasis on serendipity indeed improves user satisfaction.
A Semi-Automated Positioning System for Contact-Mode Atomic Force Microscopy (AFM)

Contact mode Atomic Force Microscopy (CM-AFM) is popularly used by the biophysics community to study mechanical properties of cells cultured in petri dishes, or tissue sections fixed on microscope slides. While cells are fairly easy to locate, sampling in spatially heterogeneous tissue specimens is laborious and time-consuming at higher magnifications. Furthermore, tissue registration across multiple magnifications for AFM-based experiments is a challenging problem, suggesting the need to automate the process of AFM indentation on tissue. In this work, we have developed an image-guided micropositioning system to align the AFM probe and human breast-tissue cores in an automated manner across multiple magnifications. Our setup improves efficiency of the AFM indentation experiments considerably.