Miracle-dz/UniFAR-FTUs huggingface dataset:
Monoclonal IgM rheumatoid factors derived from arthritic MRL/Mp-lpr/lpr mice

MRL/lpr/lpr (MRL/l) mice develop a lupus-like syndrome and a disease histologically and serologically similar to human rheumatoid arthritis. Their sera contain polyclonal IgM rheumatoid factors (RF) reactive with all murine IgG subclasses (frequently strongest with IgG2a) and several heterologous IgG. To examine the repertoire and epitopic specificities of these RF, we fused splenocytes from 3.5-mo-old seropositive MRL/l mice with appropriate myeloma partners and derived 1,723 hybridomas of which 23 secreted IgMRF. These monoclonal IgMRF bound to murine IgG only, not to other murine isotypes. Eight murine IgG subclass-specific clonotypes were identified. Most clones reacted with either multiple IgG subclasses or with IgG2a alone. A few clones reacted solely with IgG2b but none reacted exclusively with IgG1 or IgG3. Monoclonal IgMRF with exclusively anti-IgG2a activity exhibited allotypic specificity, reacting, with few exceptions, with a, c, and e, but not b, d, or j IgG2a allotypes. Four clonotypes could be distinguished by cross- reactivity with IgG from species other than mice. Monoclonals possessing activity against several murine subclasses cross-reacted extensively with heterologous IgG, including all human IgG subclasses without allotypic restrictions. Monoclonal IgMRF specific for murine IgG2a or 2b did not cross-react with heterologous IgG. Based on the absence of cross-reactions by IgG2a-specific monoclonal autoantibodies, certain peptides of the IgG CH2 and CH3 domains appear to generate the antigenic determinants of the anti-IgG2a RF in MRL/l mice. All of the monoclonal RF bound to Fc and, with one exception, not to Fab fragments of murine IgG. Binding of the monoclonal RF to substrate IgG was not inhibited by Clq, thus excluding the Clq-binding site at the CH2 domain as one of the responsible epitopes in the induction of MRL/l RF. mIgMRF could be categorized as strongly, weakly, or noninhibitable by protein A, which interacts with IgG molecules at or near the CH2-CH3 junction. Inhibition appears to be caused by conformational changes and/or steric shielding of certain IgG areas distant from this junction and not by identical binding sites between protein A and RF. Certain of the mIgMRF that were weakly or not at all inhibitable by protein A were found to cross-react equally well with human Fc (CH2-CH3 domains) and pFc' (CH3 domain) fragments, indicating that the binding site for these monoclonals is at the CH3 domain. Monoclonal RF were devoid of anti- double-strand DNA, anticollagen, or antipeptidoglycan pentapeptide cross-reactivity, but one of the monoclonals cross-reacted with histones, four with single-strand DNA, and one with both histones and single-strand DNA.
Amylocyclicin, a Novel Circular Bacteriocin Produced by Bacillus amyloliquefaciens FZB42

ABSTRACT Bacillus amyloliquefaciens FZB42 is a Gram-positive plant growth-promoting bacterium with an impressive capacity to synthesize nonribosomal secondary metabolites with antimicrobial activity. Here we report on a novel circular bacteriocin which is ribosomally synthesized by FZB42. The compound displayed high antibacterial activity against closely related Gram-positive bacteria. Transposon mutagenesis and subsequent site-specific mutagenesis combined with matrix-assisted laser desorption ionization–time of flight mass spectroscopy revealed that a cluster of six genes covering 4,490 bp was responsible for the production, modification, and export of and immunity to an antibacterial compound, here designated amylocyclicin, with a molecular mass of 6,381 Da. Peptide sequencing of the fragments obtained after tryptic digestion of the purified peptide revealed posttranslational cleavage of an N-terminal extension and head-to-tail circularization of the novel bacteriocin. Homology to other putative circular bacteriocins in related bacteria let us assume that this type of peptide is widespread among the Bacillus/Paenibacillus taxon.
Chapter 2 Comparison of HRRT and HR + Scanners

Purpose: To directly compare HRRT (high resolution brain) and HR+ (standard wholebody) PET only scanners for quantitative brain studies using three tracers with vastly different tracer distributions. Procedures: Healthy volunteers underwent successive scans on HR+ and HRRT scanners (in random order) using either (R)-[C]verapamil (n=6), [C]raclopride (n=7) or [C]flumazenil (n=7). For all tracers metabolite-corrected plasma input functions were generated. Results: After resolution matching, HRRT derived kinetic parameter values correlated well with those of HR+ for all tracers (intra-class correlation coefficients ≥0.78), having a good absolute interscanner test-retest variability (≤15%). However, systematic differences can be seen for HRRT derived kinetic parameter values (range: -13 to +15%). Conclusion: Quantification of kinetic parameters based on plasma input models leads to comparable results when spatial resolution between HRRT and HR+ data is matched. When using reference tissue models differences remain that are likely caused by differences in attenuation and scatter corrections and/or image reconstruction.
Role of nitric oxide and oxidative stress in a sheep model of persistent atrial fibrillation.

AIMS Oxidative stress can modulate nitric oxide (NO) signalling pathways. Both pathways have been shown to be involved in the pathophysiology of atrial fibrillation (AF), but data are conflicting. We aimed to characterize the NO-pathway and its relation to oxidative stress in persistent AF in a sheep model. METHODS AND RESULTS Persistent AF was induced by rapid atrial pacing for a mean of 136.5 ± 21.7 days. Non-stimulated sheep served as controls. Nicotine adenine dinucleotide phosphate (NADPH) oxidase-stimulated superoxide production was significantly increased in the AF group (+51.3 ± 23.2%, P < 0.01). Although there were no changes in mRNA expression of the different NADPH oxidase subunits, the increased activity was associated with markedly increased protein expression of the NADPH oxidase activator, Rac1 (+26 ± 4.6%, P < 0.05). No differences were seen in superoxide dismutase activity, but glutathione peroxidase activity was lower in the AF group. There was a marked accumulation of 3-nitrotyrosine, a biomarker for peroxynitrite, in atrial tissue of AF animals, as demonstrated by immunohistochemical staining and dot blot analysis (+15.6 ± 1.8%, P < 0.05). Expression of atrial NOS3 mRNA was 24.9 ± 4.4% lower in the AF group vs. control (P < 0.05), while NOS1 and 2 were unchanged. Immunoblot analysis revealed no changes in protein expression. Nitrite/nitrate levels were significantly lower during AF (-24.8 ± 5.8%, P < 0.05). CONCLUSION In a sheep model of persistent AF, NOS3 transcript levels are attenuated and circulating NOx levels decreased. Persistent AF is associated with increased oxidative stress, probably resulting from increased NADPH oxidase activity, without major changes in anti-oxidant capacity of the atrial tissue.
Dose-response relationships for foot and mouth disease in cattle and sheep

The relationships between the inhaled dose of foot and mouth disease virus and the outcomes of infection and disease were examined by fitting dose-response models to experimental data. The parameters for both the exponential and beta-poisson models were estimated using maximum likelihood and Bayesian methods. The median probability of infection given a single inhaled TCID50 was estimated to be 0·031 with 95% Bayesian credibility intervals (CI) of 0·018–0·052 for cattle, and 0·045 (CI = 0·024–0·080) for sheep. These estimates were used to construct dose-response curves and uncertainty distributions for use in quantitative risk assessments.
Commentary: Use of the body mass index to assess the risk of health outcomes: time to say goodbye?

In this issue of the journal, Yun et al. 1 report on the association of changes in body mass index (BMI; the weight in kilograms divided by the square of the height in metres) with risk of cause-specific mortality in a cohort of 473 358 Korean men aged 30–64 years at baseline. When controlled for BMI at baseline, those persons whose BMI increased moderately (between 5.0 and 9.9%) over the subsequent 6 years compared with persons with stable BMI (BMI changes between 5.0 and 4.9%) had a slightly (albeit non-significantly) reduced risk of subsequent death from cardiovascular diseases (CVD), non-CVD and overall mortality; whereas those persons whose BMI increased severely (by 510%) had a significantly higher risk of all three outcomes. In analyses stratified by BMI at baseline, the risk reductions for non-CVD and overall mortality associated with a moderate BMI increase were strongest in persons who started with a low BMI; whereas the enlarged risk associated with severe BMI increase was strongest among persons who started with higher BMI levels. These results suggest that a severe gain in BMI during adulthood is associated with increased mortality, whereas modest gain in BMI may not increase the risk of premature death, and it may even be beneficial, particularly among persons who start with a low BMI. However, the interpretation of these results is limited because BMI reflects different body compartments, and it is not clear whether the changes observed by Yun et al. reflect changes in fat mass or fat-free mass. Further, it is not clear to what extent these changes were associated with changes in body fat distribution. Current guidelines classify states of obesity primarily based on the BMI; 2,3 however, we now have good evidence that measurement of BMI alone does not accurately reflect the risk of disease and mortality that is associated with adiposity, 4 and
Differential effects of insulin on sympathetic nerve activity in agouti obese mice

Objective Hyperinsulinemia, which often coexists with obesity and type 2 diabetes, is a major risk factor for cardiovascular disease and thought to promote hypertension through the sympathetic effects of insulin. Here, we examined the effect of insulin on regional sympathetic nerve activity (SNA) in obesity. Methods Glucose and insulin tolerance tests were performed to examine insulin sensitivity in agouti obese mice. We used also multifiber recording to compare the regional SNA response to intracerebroventricular (ICV) insulin between lean and agouti obese mice. Results Agouti obese mice have significantly elevated levels of blood glucose and plasma insulin associated with glucose intolerance and insulin resistance. In lean mice, ICV administration of insulin (20 and 100 μU) caused a dose-dependent increase in SNA subserving hindlimb, kidney and brown adipose tissue (BAT). Of note, the regional SNA responses to insulin were differentially altered in agouti obese mice. Whereas lumbar SNA response to insulin was intact in the obese mice, renal and BAT sympathetic activation to insulin were significantly attenuated in these agouti obese mice. Finally, we assessed the role of phosphoinositol-3 kinase (PI3K) signaling pathway in mediating sympathetic activation to insulin in obesity. Notably, ICV pretreatment with a PI3K inhibitor (LY294002) blocked the increase in lumbar SNA induced by ICV insulin in lean and agouti obese mice. Conclusions Our data suggest a differential regulation by insulin of sympathetic outflow to peripheral tissues in obesity. Our findings also demonstrate the importance of PI3K in lumbar sympathetic activation to insulin in obesity.
Uncertainty, epistemics and active inference

Biological systems—like ourselves—are constantly faced with uncertainty. Despite noisy sensory data, and volatile environments, creatures appear to actively maintain their integrity. To account for this remarkable ability to make optimal decisions in the face of a capricious world, we propose a generative model that represents the beliefs an agent might possess about their own uncertainty. By simulating a noisy and volatile environment, we demonstrate how uncertainty influences optimal epistemic (visual) foraging. In our simulations, saccades were deployed less frequently to regions with a lower sensory precision, while a greater volatility led to a shorter inhibition of return. These simulations illustrate a principled explanation for some cardinal aspects of visual foraging—and allow us to propose a correspondence between the representation of uncertainty and ascending neuromodulatory systems, complementing that suggested by Yu & Dayan (Yu & Dayan 2005 Neuron 46, 681–692. (doi:10.1016/j.neuron.2005.04.026)).
Aquarius Third Stokes Parameter Measurements: Initial Results

This letter reports a first look at the polarimetric (third Stokes parameter) channel on the Aquarius L-band radiometer that was launched in June of 2011 on the Aquarius/Satélite de Aplicaciones Cientificas (SAC)-D observatory. The primary purpose of the polarimetric channel is to provide an in situ measure of Faraday rotation which can be important for remote sensing at L-band, particularly in the case of sea surface salinity. However, it also provides an additional mode of observation and a chance to look for new features of the surface. Initial results show good agreement with expectations. In particular, the values of retrieved Faraday rotation agree with predicted values, and a nonzero signal is seen to occur over mixed scenes as predicted by theory.
An MDP model for optimal handover decisions in mmWave cellular networks

The new frontier in cellular networks is harnessing the enormous spectrum available at millimeter wave (mmWave) frequencies above 28 GHz. The challenging radio propagation characteristics at these frequencies, and the use of highly directional beamforming, lead to intermittent links between the base station (BS) and the user equipment (UE). In this paper, we revisit the problem of cell selection to maintain an acceptable level of service, despite the underlying intermittent link connectivity typical of mmWave links. We propose a Markov Decision Process (MDP) framework to study the properties and performance of our proposed cell selection strategy, which jointly considers several factors such as dynamic channel load and link quality. We use the Value Iteration Algorithm (VIA) to solve the MDP, and obtain the optimal set of associations. We address the multi user problem through a distributed iterative approach, in which each UE characterizes the evolution of the system based on stationary channel distribution and cell selection statistics of other UEs. Through simulation results, we show that our proposed technique makes judicious handoff choices, thereby providing a significant improvement in the overall network capacity. Further, our technique reduces the total number of handoffs, thus lowering the signaling overhead, while providing a higher quality of service to the UEs.
Transfer function estimation using elemental sets

Nonlinear least-squares (NLS) fitting of rational transfer functions to frequency response data yields the maximum likelihood estimator (MLE) of the transfer function coefficient vector under mild conditions on the observation noise. Furthermore, the NLS approach is robust to errors in the modeling of data. However the NLS criterion is in general difficult to minimize. Here we show that an asymptotic realization of the NLS estimator can be obtained from the elemental set parameter estimates by simple linear operations. The latter estimates are derived by matching the frequency response data on many "elemental sets" comprising a number of frequencies equal to half the number of unknown parameters.
Caching considerations for generational garbage collection

Garbage-collected systems allocate and reuse memory cyclically; this imposes a cyclic pattern on memory accesses that has its own distinctive locality characteristics. The cyclic reuse of memory tends to defeat caching strategies if the reuse cycle is too large to fit in fast memory. Generational garbage collectors allow a smaller amount of memory to be reused more often. This improves virtual memory performance, because the frequently-reused area stays in main memory. The same principle can be applied at the level of highspeed cache memories, if the cache is larger than the youngest generation. Because of the repeated cycling through a fixed amount of memory, however, generational garbage collection interacts with cache design in unusual ways, and modestly set-associative caches can significantly outperform direct-mapped caches. While our measurements show do not show very high miss rates for garbage collected systems, they indicate that performance problems are likely in faster nextgeneration systems, where second-level cache misses may cost scores of cycles. Software techniques can improve cache performance of garbage-collected systems, by decreasing the cache “footprint” of the youngest generation; compiler techniques that reduce the amount of heap allocation also improve locality. Still, garbagecollected systems with a high rate of heap allocation require somewhat more cache capacity and/or main memory bandwidth than conventional systems.
The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.
Evaluation of a statistical approach to voiced-unvoiced-silence analysis for telephone-quality speech

Recently, a statistical-decision approach to the problem of voiced-unvoiced-silence detection of speech was proposed by Atal and Rabiner. This method was found to perform well on high-quality speech. However, the five speech parameters used in the analysis were not found to be as good for telephone-quality speech. Thus, an investigation was undertaken to determine a suitable set of parameters that would provide a reliable voiced-unvoiced-silence decision across a variety of standard telephone connections. A large number of parameters (70) were included in the investigation, including 12 lpc coefficients, 12 correlation coefficients, 12 parcor coefficients, 12 lpc partial error terms, etc. Many of the parameters were immediately eliminated because they provided almost no separability between the three decision classes. The remaining parameters were used in a knockout optimization to determine the five best parameters to use for a voiced-unvoiced-silence analysis. Various error weights were investigated to see what types of errors occurred and how they could be minimized. Finally, the use of the Itakura two-pole spectral normalization was investigated to see its effect on the error scores.
Temporal variation in phenotypic gender and expected functional gender within and among individuals in an annual plant.

BACKGROUND AND AIMS Adaptive explanations for variation in sex allocation centre on variation in resource status and variation in the mating environment. The latter can occur when dichogamy causes siring opportunity to vary across the flowering season. In this study, it is hypothesized that the widespread tendency towards declining fruit-set from first to last flowers on plants can similarly lead to a varying mating environment by causing a temporal shift in the quality (not quantity) of siring opportunities. METHODS A numerical model was developed to examine the effects of declining fruit-set on the expected male versus female reproductive success (functional gender) of first and last flowers on plants, and of early- and late-flowering plants. Within- and among-plant temporal variation in pollen production, ovule production and fruit-set in 70 Brassica rapa plants was then characterized to determine if trends in male and female investment mirror expected trends in functional gender. KEY RESULTS Under a wide range of model conditions, functional femaleness decreased sharply in the last flowers on plants, and increased from early- to late-flowering plants in the population. In B. rapa, pollen production decreased more rapidly than ovule production from first to last flowers, leading to a within-plant increase in phenotypic femaleness. Among plants, ovule production decreased from early- to late-flowering plants, causing a temporal decrease in phenotypic femaleness. CONCLUSIONS The numerical model confirmed that declining fruit-set can drive temporal variation in functional gender, especially among plants. The discrepancy between observed trends in phenotypic gender in B. rapa and expected functional gender predicted by the numerical model does not rule out the possibility that male reproductive success decreases with later flowering onset. If so, plants may experience selection for early flowering through male fitness.
Co-occurring substance abuse and mental health problems among homeless persons: Suggestions for research and practice

Abstract Communities throughout the U.S. are struggling to find solutions for serious and persistent homelessness. Alcohol and drug problems can be causes and consequences of homelessness, as well as co-occurring problems that complicate efforts to succeed in finding stable housing. Two prominent service models exist, one known as “Housing First” takes a harm reduction approach and the other known as the “linear” model typically supports a goal of abstinence from alcohol and drugs. Despite their popularity, the research supporting these models suffers from methodological problems and inconsistent findings. One purpose of this paper is to describe systematic reviews of the homelessness services literature, which illustrate weaknesses in research designs and inconsistent conclusions about the effectiveness of current models. Problems among some of the seminal studies on homelessness include poorly defined inclusion and exclusion criteria, inadequate measures of alcohol and drug use, unspecified or poorly implemented comparison conditions, and lack of procedures documenting adherence to service models. Several recent papers have suggested broader based approaches for homeless services that integrate alternatives and respond better to consumer needs. Practical considerations for implementing a broader system of services are described and peer-managed recovery homes are presented as examples of services that address some of the gaps in current approaches. Three issues are identified that need more attention from researchers: (1) improving upon the methodological limitations in current studies, (2) assessing the impact of broader based, integrated services on outcome, and (3) assessing approaches to the service needs of homeless persons involved in the criminal justice system.