Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Doses of Parenterally Administered Split Influenza Virus Vaccine Elicited High Serum IgG Concentrations which Effectively Limited Viral Shedding upon Challenge in Mice

We have previously found that whole influenza virus vaccine induced a more rapid and stronger humoral response, particularly after the first dose of vaccine, than split virus vaccine in mice. In this study, we have evaluated the protective efficacy of whole and split influenza virus vaccines in mice using a nonlethal upper respiratory tract challenge model. We have also investigated the immunological correlates associated with no or very little viral shedding after viral challenge. Vaccination resulted in reduced viral shedding and shortened the duration of infection by at least 2 days. After one dose of vaccine, whole virus vaccine generally resulted in less viral shedding than split virus vaccine. In contrast, two doses of split virus vaccine, particularly the highest vaccine strengths of 15 and 30 µg HA, most effectively limited viral replication and these mice had high concentrations of prechallenge influenza‐specific serum IgG. The vaccine formulation influenced the IgG2a/IgG1 ratio, and this IgG subclass profile was maintained upon challenge to some extent, although it did not influence the level of viral shedding. The concentration of postvaccination serum IgG showed an inverse relationship with the level of viral shedding after viral challenge. Therefore, serum IgG is an important factor in limiting viral replication in the upper respiratory tract upon challenge of an antigenically similar virus.
Uptake and recycling of pro-BDNF for transmitter-induced secretion by cortical astrocytes

Activity-dependent secretion of brain-derived neurotrophic factor (BDNF) is thought to enhance synaptic plasticity, but the mechanisms controlling extracellular availability and clearance of secreted BDNF are poorly understood. We show that BDNF is secreted in its precursor form (pro-BDNF) and is then cleared from the extracellular space through rapid uptake by nearby astrocytes after θ-burst stimulation in layer II/III of cortical slices, a paradigm resulting in long-term potentiation of synaptic transmission. Internalization of pro-BDNF occurs via the formation of a complex with the pan-neurotrophin receptor p75 and subsequent clathrin-dependent endocytosis. Fluorescence-tagged pro-BDNF and real-time total internal reflection fluorescence microscopy in cultured astrocytes is used to monitor single endocytic vesicles in response to the neurotransmitter glutamate. We find that endocytosed pro-BDNF is routed into a fast recycling pathway for subsequent soluble NSF attachment protein receptor–dependent secretion. Thus, astrocytes contain an endocytic compartment competent for pro-BDNF recycling, suggesting a specialized form of bidirectional communication between neurons and glia.
Scalable and Efficient Bayes-Adaptive Reinforcement Learning Based on Monte-Carlo Tree Search

Bayesian planning is a formally elegant approach to learning optimal behaviour under model uncertainty, trading off exploration and exploitation in an ideal way. Unfortunately, planning optimally in the face of uncertainty is notoriously taxing, since the search space is enormous. In this paper we introduce a tractable, sample-based method for approximate Bayes-optimal planning which exploits Monte-Carlo tree search. Our approach avoids expensive applications of Bayes rule within the search tree by sampling models from current beliefs, and furthermore performs this sampling in a lazy manner. This enables it to outperform previous Bayesian model-based reinforcement learning algorithms by a significant margin on several well-known benchmark problems. As we show, our approach can even work in problems with an in finite state space that lie qualitatively out of reach of almost all previous work in Bayesian exploration.
Semi-global stabilization and output regulation of constrained linear plants via measurement feedback

We developed the design of observer-based measurement feedback controllers for constrained semi-global stabilization and constrained semi-global output regulation for linear systems with right invertible constraints. The observers use high-gain feedback. To avoid the possible constraint violation caused by peaking phenomenon associated with an high-gain observer, appropriate saturation mechanisms are employed in the control laws.
Small coronary calcium deposits and elevated plasma levels of oxidized low density lipoprotein are characteristic of acute myocardial infarction.

AIM Predictions of the onset of acute myocardial infarction (AMI) in high risk individuals are of great clinical importance. Among various risk factors, elevated levels of oxidized low density lipoprotein (ox-LDL) in plasma have been shown to reflect unstable coronary plaques. Coronary calcification is a common finding in the elderly, however, its clinical implications as a risk factor for plaque rupture are controversial. This study was designed to investigate the clinical implications of plasma ox-LDL levels and coronary calcification detected by electron-beam computed tomography (EBCT), by comparing patients with AMI with those with stable angina pectoris (SAP). METHODS We measured plasma ox-LDL levels in AMI (n=34) and SAP (n=49) patients. In addition, a coronary calcium score was quantified with the Agatston system. The total coronary calcium score (TCS) was defined as the sum of the scores for each lesion. RESULTS TCS and total calcium area were significantly smaller in patients with AMI than in those with SAP. On the other hand, plasma ox-LDL levels were significantly higher in AMI patients than in SAP patients (p<0.0005). CONCLUSION These results suggest that a combined assessment of coronary calcium and plasma ox-LDL levels may be useful for screening patients with unstable coronary plaques.
Stabilization of Bernoulli--Euler Beams by Means of a Pointwise Feedback Force

We study the energy decay of a Bernoulli--Euler beam which is subject to a pointwise feedback force. We show that both uniform and nonuniform energy decay may occur. The uniform or nonuniform decay depends on the boundary conditions. In the case of nonuniform decay in the energy space we give explicit polynomial decay estimates valid for regular initial data. Our method consists of deducing the decay estimates from observability inequalities for the associated undamped problem via sharp trace regularity results.
Drought Tip: Use of Shallow Groundwater for Crop Production

Author(s): Grismer, Mark E | Abstract: In drought times, it can't be “irrigation as usual. ” Depending on your crop and soil structure, shallow groundwater (any water within the first 6 feet or so of soil depth) can make a significant contribution to crop production and farm survival.
Pseudomonas aeruginosa Alginate Promotes Burkholderia cenocepacia Persistence in Cystic Fibrosis Transmembrane Conductance Regulator Knockout Mice

ABSTRACT Pseudomonas aeruginosa, a major respiratory pathogen in cystic fibrosis (CF) patients, facilitates infection by other opportunistic pathogens. Burkholderia cenocepacia, which normally infects adolescent patients, encounters alginate elaborated by mucoid P. aeruginosa. To determine whether P. aeruginosa alginate facilitates B. cenocepacia infection in mice, cystic fibrosis transmembrane conductance regulator knockout mice were infected with B. cenocepacia strain BC7 suspended in either phosphate-buffered saline (BC7/PBS) or P. aeruginosa alginate (BC7/alginate), and the pulmonary bacterial load and inflammation were monitored. Mice infected with BC7/PBS cleared all of the bacteria within 3 days, and inflammation was resolved by day 5. In contrast, mice infected with BC7/alginate showed persistence of bacteria and increased cytokine levels for up to 7 days. Histological examination of the lungs indicated that there was moderate to severe inflammation and pneumonic consolidation in isolated areas at 5 and 7 days postinfection in the BC7/alginate group. Further, alginate decreased phagocytosis of B. cenocepacia by professional phagocytes both in vivo and in vitro. P. aeruginosa alginate also reduced the proinflammatory responses of CF airway epithelial cells and alveolar macrophages to B. cenocepacia infection. The observed effects are specific to P. aeruginosa alginate, because enzymatically degraded alginate or other polyuronic acids did not facilitate bacterial persistence. These observations suggest that P. aeruginosa alginate may facilitate B. cenocepacia infection by interfering with host innate defense mechanisms.
Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen

Retinoic acid (RA) is essential for both embryonic and adult growth, activating gene transcription via specific nuclear receptors. It is generated, via a retinaldehyde intermediate, from retinol (vitamin A). RA levels require precise regulation by controlled synthesis and catabolism, and when RA concentrations deviate from normal, in either direction, abnormal growth and development occurs. This review describes: (i) how the pattern of RA metabolic enzymes controls the actions of RA; and (ii) the type of abnormalities that result when this pattern breaks down. Examples are given of RA control of the anterior/posterior axis of the hindbrain, the dorsal/ventral axis of the spinal cord, as well as certain sex‐specific segments of the spinal cord, using varied animal models including mouse, quail and mosquitofish. These functions are highly sensitive to abnormal changes in RA concentration. In rodents, the control of neural patterning and differentiation are disrupted when RA concentrations are lowered, whereas inappropriately high concentrations of RA result in abnormal development of cerebellum and hindbrain nuclei. The latter parallels the malformations seen in the human embryo exposed to RA due to treatment of the mother with the acne drug Accutane (13‐cis RA) and, in cases where the child survives beyond birth, a particular set of behavioural anomalies can be described. Even the adult brain may be susceptible to an imbalance of RA, particularly the hippocampus. This report shows how the properties of RA as a neural induction agent and organizer of segmentation can explain the consequences of RA depletion and overexpression.
Guardians' Perceptions of Dogs' Welfare and Behaviors Related to Visiting the Veterinary Clinic

A large survey of Italian dog guardians (n = 906) was conducted to assess dog behavior and welfare at the veterinary clinic and to investigate how guardians and veterinarians affect them. This study confirmed that the veterinary clinic is a source of stress for most dogs, who showed impaired welfare in all phases: in the waiting room, entering the examination room, on the examination table, and when approached by the vet. This study also characterizes some factors related to the guardians' and veterinarians' behavior that affect the dogs' behavior and welfare during the veterinary examination. If dogs had not been examined by a vet since puppyhood, if they did not accept treatments by their guardians, and if they were scolded when refusing a treatment, the risk for having problems with dog welfare and behavior at the veterinary clinic increased. The attention paid by the vet to the dog was found to be positively related with a good response of the dog to the vet. Prevention seems to be the key for the protection of dog welfare related to veterinary care.
Supported self-management for asthma

Key points Self-management education in asthma is not an optional extra. Healthcare professionals have a responsibility to ensure that everyone with asthma has personalised advice to enable them to optimise how they self-manage their condition. Overviews of the extensive evidence-base conclude that asthma self-management supported by regular professional review, improves asthma control, reduces exacerbations and admissions, and improves quality of life. Self-management education should be reinforced by a written personalised asthma action plan which provides a summary of the regular management strategy, how to recognise deterioration and the action to take. Successful implementation combines education for patients, skills training for professionals in the context of an organisation committed to both the concept and the practice of supported self-management. Educational aims To summarise the evidence base underpinning supported self-management for asthma To provide clinicians with a practical approach to providing supported self-management for asthma To suggest an appropriate strategy for implementing supported self-management Summary The evidence in favour of supported self-management for asthma is overwhelming. Self-management including provision of a written asthma action plan and supported by regular medical review, almost halves the risk of hospitalisation, significantly reduces emergency department attendances and unscheduled consultations, and improves markers of asthma control and quality of life. Demographic and cultural tailoring enables effective programmes to be implemented in deprived and/or ethnic communities or within schools. A crucial component of effective asthma self-management interventions is the provision of an agreed, written personalised action plan which advises on using regular medication, recognising deterioration and appropriate action to take. Monitoring can be based on symptoms or on peak flows and should specify thresholds for action including increasing inhaled steroids, commencing oral steroids, and when (and how) to seek professional help. Plans should be personalised to reflect asthma severity and treatment regimes, avoidance of triggers, co-morbid rhinitis and the individual’s preferences. Implementation is a challenge. Systematic review evidence suggests that it is possible to implement asthma self-management in routine care, but that to be effective this requires a whole systems approach which considers implementation from the perspective of patient education and resources, professional skills and motivation and organisation priorities and routines.
Tunstall Code, Khodak Variations, and Random Walks

A variable-to-fixed length encoder partitions the source string into variable-length phrases that belong to a given and fixed dictionary. Tunstall, and independently Khodak, designed variable-to-fixed length codes for memoryless sources that are optimal under certain constraints. In this paper, we study the Tunstall and Khodak codes using variety of techniques ranging from stopping times for sums of independent random variables to Tauberian theorems and Mellin transform. After proposing an algebraic characterization of the Tunstall and Khodak codes, we present new results on the variance and a central limit theorem for dictionary phrase lengths. This analysis also provides a new argument for obtaining asymptotic results about the mean dictionary phrase length and average redundancy rates.
Development and Validation of a Prediction Model to Estimate Individual Risk of Pancreatic Cancer

Introduction There is no reliable screening tool to identify people with high risk of developing pancreatic cancer even though pancreatic cancer represents the fifth-leading cause of cancer-related death in Korea. The goal of this study was to develop an individualized risk prediction model that can be used to screen for asymptomatic pancreatic cancer in Korean men and women. Materials and Methods Gender-specific risk prediction models for pancreatic cancer were developed using the Cox proportional hazards model based on an 8-year follow-up of a cohort study of 1,289,933 men and 557,701 women in Korea who had biennial examinations in 1996–1997. The performance of the models was evaluated with respect to their discrimination and calibration ability based on the C-statistic and Hosmer-Lemeshow type χ2 statistic. Results A total of 1,634 (0.13%) men and 561 (0.10%) women were newly diagnosed with pancreatic cancer. Age, height, BMI, fasting glucose, urine glucose, smoking, and age at smoking initiation were included in the risk prediction model for men. Height, BMI, fasting glucose, urine glucose, smoking, and drinking habit were included in the risk prediction model for women. Smoking was the most significant risk factor for developing pancreatic cancer in both men and women. The risk prediction model exhibited good discrimination and calibration ability, and in external validation it had excellent prediction ability. Conclusion Gender-specific risk prediction models for pancreatic cancer were developed and validated for the first time. The prediction models will be a useful tool for detecting high-risk individuals who may benefit from increased surveillance for pancreatic cancer.
Effects of estrogen against LPS-induced inflammation and toxicity in primary rat glial and neuronal cultures

Several lines of evidence link inflammation with neurodegenerative diseases, which are aggravated by the age-related decline in estrogen levels in postmenopausal women. Lipopolysaccharide (LPS) is used widely to stimulate glial cells to produce pro-inflammatory mediators such as NO, PGE2, and TNF-α, and was found to be toxic in high doses. We examined the effects of a physiological dose of 17β-estradiol (E2) against LPS-induced inflammation and toxicity (cell death) in rat primary glial and neuronal cultures. Cultures were treated with 0.1 nM E2 for 24 h and then exposed to LPS 0.5—200 µg/ml for another 24 h. Levels of NO, PGE2, and TNF-α in the culture medium were determined by the Griess reaction assay, radio-immunoassay, and enzyme-linked immunoassay, respectively. Cell death was quantified by measuring the leakage of lactate dehydrogenase (LDH) into the medium from dead or dying cells using the non-radioactive cytotoxicity assay. E2 significantly reduced the LPS-induced increase in NO and TNF-α (but not PGE2) production in glial cells. PGE 2 and TNF-α were undetectable in neuronal cultures, while only basal levels of NO were detected, even after stimulation with LPS. Moreover, pretreatment with E2 significantly reduced LPS-induced cell death, as measured by the release of LDH, in both glial and neuronal cultures. These results suggest that the neuroprotective effects attributed to E2 are derived, at least in part, from its anti-inflammatory and cytoprotective effects in both glial and neuronal cells.
A comprehensive review and update on the biologic treatment of adult noninfectious uveitis: part II

Introduction: Treatment of adult, noninfectious uveitis remains a major challenge for ophthalmologists around the world, especially in regard to recalcitrant cases. It is reported to comprise approximately 10% of preventable blindness in the USA. The cause of uveitis can be idiopathic or associated with infectious and systemic disorders. The era of biologic medical therapies provides new options for patients with otherwise treatment-resistant inflammatory eye disease. Areas covered: This two-part review gives a comprehensive overview of the existing medical treatment options for patients with adult, noninfectious uveitis, as well as important advances for the treatment ocular inflammation. Part I covers classic immunomodulation and latest information on corticosteroid therapy. In part II, emerging therapies are discussed, including biologic response modifiers, experimental treatments and ongoing clinical studies for uveitis. Expert opinion: The hazard of chronic corticosteroid use in the treatment of adult, noninfectious uveitis is well documented. Corticosteroid-sparing therapies, which offer a very favorable risk–benefit profile when administered properly, should be substituted. Although nothing is currently approved for on-label use in this indication, many therapies, through either translation or novel basic science research, have the potential to fill the currently exposed gaps.
The Innate Mononuclear Phagocyte Network Depletes B Lymphocytes through Fc Receptor–dependent Mechanisms during Anti-CD20 Antibody Immunotherapy

Anti-CD20 antibody immunotherapy effectively treats non-Hodgkin's lymphoma and autoimmune disease. However, the cellular and molecular pathways for B cell depletion remain undefined because human mechanistic studies are limited. Proposed mechanisms include antibody-, effector cell–, and complement-dependent cytotoxicity, the disruption of CD20 signaling pathways, and the induction of apoptosis. To identify the mechanisms for B cell depletion in vivo, a new mouse model for anti-CD20 immunotherapy was developed using a panel of twelve mouse anti–mouse CD20 monoclonal antibodies representing all four immunoglobulin G isotypes. Anti-CD20 antibodies rapidly depleted the vast majority of circulating and tissue B cells in an isotype-restricted manner that was completely dependent on effector cell Fc receptor expression. B cell depletion used both FcγRI- and FcγRIII-dependent pathways, whereas B cells were not eliminated in FcR common γ chain–deficient mice. Monocytes were the dominant effector cells for B cell depletion, with no demonstrable role for T or natural killer cells. Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3, C4, or C1q complement components. That the innate monocyte network depletes B cells through FcγR-dependent pathways during anti-CD20 immunotherapy has important clinical implications for anti-CD20 and other antibody-based therapies.
Toward an Estimation of User Tagging Credibility for Social Image Retrieval

Existing image retrieval systems exploit textual or/and visual information to return results. The retrieval process is mostly focused on data themselves and disregards the data sources. In Web 2.0 platforms, the quality of annotations provided by different users can vary strongly. To account for this variability, we complement existing methods by introducing user tagging credibility in the retrieval process. Tagging credibility is automatically estimated by leveraging a large set of visual concept classifiers learned with Overfeat, a convolutional neural network (CNN) based feature. A good image retrieval system should return results that are both relevant and diversified and tackle both challenges. We diversify results by using a k-Means algorithm with user based cluster ranking. We increase relevance by favoring images uploaded from users with good credibility estimates. Evaluation is performed on DIV400, a publicly available social image retrieval dataset. Experiments show that our method provides interesting performances compared to existing approaches.
HIV‐1 IN alternative molecular recognition of DNA induced by raltegravir resistance mutations

Virologic failure during treatment with raltegravir, the first effective drug targeting HIV integrase, is associated with two exclusive pathways involving either Q148H/R/K, G140S/A or N155H mutations. We carried out a detailed analysis of the molecular and structural effects of these mutations. We observed no topological change in the integrase core domain, with conservation of a newly identified Ω‐shaped hairpin containing the Q148 residue, in particular. In contrast, the mutations greatly altered the specificity of DNA recognition by integrase. The native residues displayed a clear preference for adenine, whereas the mutant residues strongly favored pyrimidines. Raltegravir may bind to N155 and/or Q148 residues as an adenine bioisoster. This may account for the selected mutations impairing raltegravir binding while allowing alternative DNA recognition by integrase. This study opens up new opportunities for the design of integrase inhibitors active against raltegravir‐resistant viruses. Copyright © 2009 John Wiley & Sons, Ltd.