Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel human anti-interleukin-1β neutralizing monoclonal antibody showing in vivo efficacy

The pro-inflammatory cytokine interleukin (IL)-1β is a clinical target in many conditions involving dysregulation of the immune system; therapeutics that block IL-1β have been approved to treat diseases such as rheumatoid arthritis (RA), neonatal onset multisystem inflammatory diseases, cryopyrin-associated periodic syndromes, active systemic juvenile idiopathic arthritis. Here, we report the generation and engineering of a new fully human antibody that binds tightly to IL-1β with a neutralization potency more than 10 times higher than that of the marketed antibody canakinumab. After affinity maturation, the derived antibody shows a >30-fold increased affinity to human IL-1β compared with its parent antibody. This anti-human IL-1β IgG also cross-reacts with mouse and monkey IL-1β, hence facilitating preclinical development. In a number of mouse models, this antibody efficiently reduced or abolished signs of disease associated with IL-1β pathology. Due to its high affinity for the cytokine and its potency both in vitro and in vivo, we propose that this novel fully human anti-IL-1β monoclonal antibody is a promising therapeutic candidate and a potential alternative to the current therapeutic arsenal.
Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses

The emergence of a highly pathogenic H5N1 influenza virus in Hong Kong in 1997, and the subsequent appearance of other H5N1 strains and their spread to several countries in south-east Asia, Africa, the Middle East, and Europe has evoked fear of a global influenza pandemic. Vaccines offer the best hope to combat the threat of an influenza pandemic. However, the global demand for a pandemic vaccine cannot be fulfilled by the current egg-based vaccine manufacturing strategies, thus creating a need to explore alternative technologies for vaccine production and delivery. Several egg-independent vaccine approaches such as cell culture-derived whole virus or subvirion vaccines, recombinant protein-based vaccines, virus like particle (VLP) vaccines, DNA vaccines and viral vector-based vaccines are currently being investigated and appear promising both in preclinical and clinical studies. The present review will highlight the various egg-independent alternative vaccine approaches for pandemic influenza.
Toxicity of cobalt–chromium nanoparticles released from a resurfacing hip implant and cobalt ions on primary human lymphocytes in vitro

Adverse tissue responses to prostheses wear particles and released ions are important contributors to hip implant failure. In implant‐related adverse reactions T‐lymphocytes play a prominent role in sustaining the chronic inflammatory response. To further understand the involvement of lymphocytes in metal‐on‐metal (MoM) implant failure, primary human lymphocytes were isolated and treated with cobalt–chromium (Co‐Cr) wear debris and Co ions, individually, and in combination, for 24, 48 and 120 h. There was a significant increase in cell number where debris was present, as measured by the Neutral Red assay. Interleukin‐6 (IL‐6), interferon‐γ (IFN‐γ) and tumour necrosis factor‐α (TNF‐α) secretion levels significantly decreased in the presence of metal particles, as measured by ELISA. Interleukin‐2 (IL‐2) secretion levels were significantly decreased by both debris and Co ions. Flow cytometry analysis showed that the metal nanoparticles induced a significant increase in apoptosis after 48‐h exposure. This investigation showed that prolonged exposure (120 h) to metal debris induces lymphocyte proliferation, suggesting that activation of resting lymphocytes may have occurred. Although cytokine production was affected mainly by metal debris, cobalt toxicity may also modulate IL‐2 secretion, and even Co ion concentrations below the MHRA guideline levels (7 ppb) may contribute to the impairment of immune regulation in vivo in patients with MoM implants. Copyright © 2015 John Wiley & Sons, Ltd.
Quantitative Estimates of Time-Averaging in Brachiopod Shell Accumulations from a Holocene Tropical Shelf (SW Brazil)

Time-averaging, the mixing of fossils of different ages within a single bed, defines the limit of temporal resolution of the fossil record. Quantitative estimates of this resolution threshold have not been acquired for any group other than mollusks. This study provides the first quantitative estimates of time-averaging for brachiopods, extending our understanding of intrinsic, or group specific controls on this process. Estimates were obtained by direct dating of individual terebratulid brachiopod shells Bouchardia rosea (Mawe) collected from modern surficial shelly accumulations in the Southeast Brazilian Bight (SW Atlantic). Using amino acid racemization dating calibrated with radiocarbon, 82 individual brachiopod shells, collected from four nearshore localities, were dated. The shells vary in age from modern to 3000 years, standard deviation = 680 years. The age distribution is significantly right-skewed (K3=2.48). At 50-year resolution, the temporal completeness is 75% for the last 1000 years and declines to 20% completeness for 1000-2000 yr. BP. Preservational quality (taphonomy) of modern (<50 yr.) shells is statistically indistinguishable from that of older shells, demonstrating that shell taphonomy is not a good predictor of within-assemblage relative age. These results conform to previously published results for mollusks. Therefore, brachiopods can show considerable time-averaging and this timeaveraging can be on a scale similar to aragonitic mollusks despite the apparent lack of robustness of calcitic brachiopod shells. This suggests that the brachiopod fossil record can be notably time-averaged, but estimates of this mixing cannot be reliably deciphered from the taphonomic condition of shells.
A Template-Based Design Methodology for Graph-Parallel Hardware Accelerators

Graph applications have been gaining importance in the last decade due to emerging big data analytics problems such as Web graphs, social networks, and biological networks. For these applications, traditional CPU and GPU architectures suffer in terms of performance and power consumption due to irregular communications, random memory accesses, and load balancing problems. It has been shown that specialized hardware accelerators can achieve much better power and energy efficiency compared to the general purpose CPUs and GPUs. In this paper, we present a template-based methodology specifically targeted for hardware accelerator design of big-data graph applications. Important architectural features that are key for energy efficient execution are implemented in a common template. The proposed template-based methodology is used to design hardware accelerators for different graph applications with little effort. Compared to an application-specific high-level synthesis methodology, we show that the proposed methodology can generate hardware accelerators with up to $18\boldsymbol \times$ better energy efficiency and requires less design effort.
Software agent application to support the patient-at-home

This work is motivated by the Patient-at-Home (PAH). He or she is an ambulatory patient who requires a greater level of attention, such as individuals with chronic conditions, elderly patients, those with trauma injuries, etc. Latest developments in US national-level health care standards and specifications have focused on needs of in-hospital scenarios and interoperability among diverse institutionally-situated software systems. This work provides a focus of bringing the Patient-at-Home into collaborative partnership with the emerging standards-based electronic health care support. To accomplish this, an approach involving collaborative elements was developed. These include interactions between the PAH and an agent-based software application named Patient-at-Home Supporting Software Agents (PAHSSA) and between the PAH and the Family Physician. The point of connection between the Patient-at-Home and the emerging electronic health care system involves the Family Physician's Electronic Health Record (EHR). In this work, we develop a set of scenario elements that pertain to the PAH. We then derive requirements that can be utilized as use case snippets in order to design meaningful collaboration between the PAH and the health care system. Finally, we present an initial agent system design for PAHSSA to support the collaboration.
Design of a continuous multifaceted guideline-implementation strategy based on computerized decision support

Implementation of clinical practice guidelines into daily care is hindered by a variety of barriers related to professional knowledge, collaboration in teams and organizations, and practicability of the guidelines. Clinical computerized decision support (CCDS) has been shown to be one of the most effective instruments to improve compliance to practice guidelines by tackling barriers related to professional knowledge. To address other barriers, however, additional interventions are needed. In this study, a continuous multifaceted guideline implementation strategy was developed which is based on CCDS but extends beyond the professional knowledge barrier. Two additional interventions were designed and embedded with CCDS in a continuous quality improvement framework. First, to address barriers within teams and organizations guideline compliance data are periodically aggregated into feedback reports for care providers. Second, barriers related to practicability of the underlying guidelines are addressed in a guideline-maintenance cycle. A case study in the field of cardiac rehabilitation is presented to demonstrate the feasibility of the developed strategy.
Social Capital and Adoption of Agronomic Practices: Theory and Findings

Social capital is a concept that captures ways that human relations support productive activities. The concept had a meteoric rise in academia during the 1990s and has been picked up more by multinational corporations who are using the concept to improve their production and brand. This study explores: (1) what are the common assumptions behind social capital research; (2) can social capital increase the adoption of agronomic technology and practice; and (3) can social capital be purposefully built? Tying practical questions to a deeper understandings of social capital is instructive for future social capital research, as it identifies productive ways of dealing with theoretical tensions in the literature.
A short survey of methods for voltage instability detection

This paper shortly surveys existing and proposed methods for voltage instability detection. The emphasis is on methods relying on real-time measurements as well as on long-term voltage instability. Methods are classified according to the required measurement configuration: local vs. wide-area, standard SCADA-type vs. synchronized phasor measurements, etc. In the various categories, some of the features are summarized, and what appears to the authors as advantages or limitations is shortly discussed. An important feature is the ability to anticipate instability. Some tracks for further work on the subject are also outlined.
Dual-Band Monopole Antenna Using Substrate-Integrated Suspended Line Technology for WLAN Application

In this letter, a substrate-integrated suspended line high-efficiency monopole antenna designed for 2.4/5.2 GHz wireless local area network (WLAN) application is proposed. The proposed antenna is composed of five stacked substrate layers with two embedded air cavities. Compared with the conventional monopole antennas, more metal surfaces of the proposed antenna can be used for radiation and impedance matching, which provides more flexibility for multiband antenna design. By utilizing the embedded air cavities, the loss of the whole structure is significantly decreased, thus efficiency of higher than 95% is achieved. Moreover, the stable omnidirectional radiation patterns are obtained in the two operating frequency bands of 2.25–2.90 and 4.95–5.94 GHz, which cover corresponding WLAN operation frequency bands.
Small and large artery elasticity indices in peripheral arterial occlusive disease (PAOD)

In peripheral arterial occlusive disease (PAOD), arterial compliance of the central arteries has been reported to be reduced. It is, however, not clear whether, in PAOD, decreased arterial compliance is also accompanied by similar changes in the peripheral arteries. Therefore the aim of the study was to determine the large (C1) and small (C2) artery elasticity indices in PAOD and their relations to its well-accepted characteristics (ankle-brachial index, ABI; pulse pressure, PP; absolute claudication distance, ACD). A total of 43 patients with PAOD (mean age 68 ± 9 years; ABI of the limiting leg 0.65 ± 0.14; SBP (systolic blood pressure) 149 ± 20 mmHg, and ACD 488 ± 187 m) were enrolled as well as 16 control subjects of comparable age (69 ± 4 years) and blood pressure (SBP 147 ± 27 mmHg). All subjects underwent non-invasive pulse wave analysis in order to determine arterial compliance of the aorta and major side branches (C1) and of the distal circulation (C2), using a modified Windkessel model. In PAOD, both C1 (1.41 ± 0.56 ml/mmHg) and C2 (0.023 ± 0.012 ml/mmHg) were comparable to values in an age and blood pressure-matched control group (C1, 1.25 ± 0.66 ml/mmHg; C2, 0.027 ± 0.008 ml/mmHg). C1 was significantly correlated with ACD (r = 0.36, p = 0.02), PP (r =-0.33, p < 0.02) and only borderline with ABI (r = 0.28, p = 0.07). C2 was correlated with PP (r =-0.38, p < 0.01), ABI (r = 0.36, p < 0.02) but not with ACD. Large (C1) and small (C2) artery elasticity indices in PAOD were decreased but comparable to values in an elderly group with isolated systolic hypertension. Moreover, C1 and C2 correlated with markers (ABI and PP) of severity of vascular disease.
Food-initiated outbreak of methicillin-resistant Staphylococcus aureus analyzed by pheno- and genotyping

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) involving 27 patients and 14 health-care workers (HCW) was studied. The outbreak started in the hematology unit of the University Hospital Rotterdam, Dijkzigt, The Netherlands, and spread to the surgical unit. Twenty-one patients (77.8%) developed clinical disease, and five died. Subsequently, MRSA was detected in food and in the throat of one of the HCW who prepared food for hematology patients. Food contaminated by an HCW most likely caused the first case of MRSA septicemia. This route of transmission has not been described before. The outbreak strain was probably transmitted to the surgical unit by a colonized nurse, where it caused an explosive outbreak. Airborne probably transmitted to the surgical unit by a colonized nurse, where it caused an explosive outbreak. Airborne MRSA transmission played an important role in disseminating the organism. The outbreak was controlled within 6 months by intensifying surveillance, temporarily closing the affected wards, treating carriers, and instituting an MRSA ward outside the hospital. Phage typing, insertion sequence probing, protein A gene typing, and DNA fingerprinting by PCR revealed that all outbreak-related isolates were identical. By pulsed-field gel electrophoresis, all but one of the outbreak-related isolates were determined to be identical. Protein A gene typing identified numerous (11) repeat units in all outbreak-related isolates, which supports the suggestion that the outbreak strain may have been more virulent and more transmissible than other MRSA strains. Pheno- and genotyping studies underlined the value of DNA fingerprinting methods for investigation of MRSA epidemiology. Optimal discriminatory power was achieved by combining the results of four genotyping methods.
Automated parallel detection based analyzer for integrated bioassays in digital microfluidic biochip

In this paper we have proposed a design of an intelligent detection and analysis system that has been interfaced with a digital microfluidic biochip. The system is capable of performing automated detection and analysis of multiple bioassay protocols executed simultaneously within the same microfluidic device. The proposed design has been tested for both heterogeneous as well as homogeneous detection simultaneously within a scalable and integrated DMFB system for human physiological samples.
Depressive symptomatology as a predictor of exposure to intimate partner violence among US female adolescents and young adults.

OBJECTIVE To examine whether depressive symptomatology is predictive of subsequent intimate partner violence victimization among a national prospective sample of female adolescents and young adults. DESIGN Home interview data from 2 waves of the school-based National Longitudinal Study of Adolescent Health were used to examine whether baseline depressive symptomatology was associated with increased risk of past-year exposure to physical abuse by a current partner at 5-year follow-up, controlling for age, race/ethnicity, parental education, retrospective childhood physical and sexual abuse, and baseline dating violence and forced sex. SETTING A stratified random sample of 80 US high schools and 52 middle schools. PARTICIPANTS All young women (n = 1659) were in a current opposite-sex relationship at follow-up. MAIN EXPOSURE Baseline past-week depressive symptomatology, measured as both a dichotomous and continuous variable. MAIN OUTCOME MEASURES Past-year exposure to mild and moderate to severe physical abuse by a current intimate partner. RESULTS In adjusted models with dichotomous depressive symptoms, high baseline symptom levels were associated with 1.86 times the odds of subsequent exposure to moderate to severe partner violence (95% confidence interval, 1.05-3.29). In adjusted models with continuous depressive symptoms, an increase of 1 SD in baseline symptom levels was associated with a 24% increase in odds of exposure to mild partner violence and a 24% increase in the odds of exposure to moderate to severe partner violence. CONCLUSIONS The findings of this study suggest that depressive symptomatology among girls during adolescence is associated with increased risk of subsequent exposure to physical partner violence. Prevention, identification, and treatment of depressive symptomatology among adolescent girls may help to reduce the likelihood of subsequent victimization.
Intermediate-energy Coulomb excitation of 104 Sn: Moderate E2 strength decrease approaching 100 Sn

The reduced transition probability B(E2)↑ of the first excited 2 + state in the nucleus 104 Sn was measured via Coulomb excitation in inverse kinematics at intermediate energies. A value of 0.173(28) e 2 b 2 was extracted from the absolute cross section on a Pb target. Feeding contributions in 104 Sn from higher lying states were estimated by a reference measurement of the stable 112 Sn. Corresponding only to a moderate decrease of excitation strength relative to the almost constant values observed in the proton-rich, even-A 106−114 Sn isotopes, present state-of-the-art shell-model predictions, which include proton and neutron excitations across the N = Z = 50 shell closures as well as standard polarization charges, underestimate the experimental findings.
C. elegans avoids toxin-producing Streptomyces using a seven transmembrane domain chemosensory receptor

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic acid, which is sensed by SRB-6. This behavioral adaptation represents an important strategy for the nematode, which utilizes specialized sensory organs and a chemoreceptor that is tuned to recognize the bacteria. These findings provide a window into the molecules and organs used in the coevolutionary arms race between predator and potential prey.
Rapid Detection of Chlamydia pneumoniae by PCR-Enzyme Immunoassay

ABSTRACT Chlamydia pneumoniae is an important human respiratory pathogen. Laboratory diagnosis of infection with this organism is difficult. To facilitate the detection of C. pneumoniae by PCR, an enzyme immunoassay (EIA) for analysis of PCR products was developed. Biotin-labeled PCR products generated from the 16S rRNA gene of C. pneumoniae were hybridized to a digoxigenin-labeled probe and then immobilized to streptavidin-coated microtiter plates. Bound PCR product-probe hybrids were detected with antidigoxigenin peroxidase conjugate and a colorimetric substrate. This EIA was as sensitive as Southern blot hybridization for the detection of PCR products and 100 times more sensitive than visualization of PCR products on agarose gels. The diagnostic value of the PCR-EIA in comparison to cell culture was assessed in throat swab specimens from children with respiratory tract infections. C. pneumoniaewas isolated from only 1 of 368 specimens tested. In contrast, 15 patient specimens were repeatedly positive for C. pneumoniae by PCR and Southern analysis. All of these 15 specimens were also identified by PCR-EIA. Of the 15 specimens positive by 16S rRNA-based PCR, 13 specimens could be confirmed byomp1-based PCR or direct fluorescent-antibody assay. Results of this study demonstrate that PCR is more sensitive than cell culture for the detection of C. pneumoniae. The EIA described here is a rapid, sensitive, and simple method for detection of amplified C. pneumoniae DNA.
Stochastic simulation of ligand-receptor interaction.

We have developed an algorithm for the stochastic simulation of ligand-receptor interactions based on 10(4)-10(5) fictitious binding sites. Reversible receptor binding was simulated by alternate random selection of sites, the first selection resulting in "occupation" if the selected site was "free," the second selection resulting in "dissociation" if the selected site was "occupied. " We show that the mathematical formalism of mass action kinetics is predicted on purely statistical grounds. The model was extended by the introduction of two further selections, simulating a conformational change in the ligand-receptor complex ("receptor isomerization model"). All random selections were gauged separately by "probability barriers," taking the place of macroscopic kinetic rate constants. Simulation of gradual increases and gradual decreases of the fraction of occupied fictitious binding sites in the receptor isomerization model, using various combinations of "rate constants," resulted in biexponential time dependencies, in agreement with predictions from the integrated rate equations. Stochastic simulation of molecular processes is a powerful and versatile technique, providing the researcher with a means of studying mechanisms of increasing complexity.