Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of a Conjugate Vaccine Containing Polymannuronic Acid and Flagellin against Experimental Pseudomonas aeruginosa Lung Infection in Mice

ABSTRACT Vaccines that could effectively prevent Pseudomonas aeruginosa pulmonary infections in the settings of cystic fibrosis (CF) and nosocomial pneumonia could be exceedingly useful, but to date no effective immunotherapy targeting this pathogen has been successfully developed for routine use in humans. Evaluations using animals and limited human trials of vaccines and their associated immune effectors against different P. aeruginosa antigens have suggested that antibody to the conserved surface polysaccharide alginate, as well as the flagellar proteins, often give high levels of protection. However, alginate itself does not elicit protective antibody in humans, and flagellar vaccines containing the two predominant serotypes of this antigen may not provide sufficient coverage against variant flagellar types. To evaluate if combining these antigens in a conjugate vaccine would be potentially efficacious, we conjugated polymannuronic acid (PMA), containing the blocks of mannuronic acid conserved in all P. aeruginosa alginates, to type a flagellin (FLA) and evaluated immunogenicity, opsonic killing activity, and passive protective efficacy in mice. The PMA-FLA conjugate was highly immunogenic in mice and rabbits and elicited opsonic antibodies against mucoid but not nonmucoid P. aeruginosa, but nonetheless rabbit antibody to PMA-FLA showed evidence of protective efficacy against both types of this organism in a mouse lung infection model. Importantly, the PMA-FLA conjugate vaccine did not elicit antibodies that neutralized the Toll-like receptor 5 (TLR5)-activating activity of flagellin, an important part of innate immunity to flagellated microbial pathogens. Conjugation of PMA to FLA appears to be a promising path for developing a broadly protective vaccine against P. aeruginosa.
Too many shots? Parent, nurse, and physician attitudes toward multiple simultaneous childhood vaccinations.

OBJECTIVE To learn about parent, nurse, and family physician attitudes toward multiple simultaneous childhood vaccinations. DESIGN Survey. SETTING Thirty-two family practice clinics in Minnesota. PATIENTS/PARTICIPANTS Forty-six volunteer Minnesota Academy of Family Physicians Research Network members, 42 of their nurses, and 342 parents of their patients aged less than 6 years who have had at least one injection. MAIN OUTCOME MEASURES Number of injections believed to be too many for a child to receive simultaneously and comfort level associated with children's receiving three simultaneous injectable vaccinations. RESULTS Most parents, nurses, and physicians (71%, 76%, and 59%, respectively) think that three injections are too many for a child to receive at one visit. Similar percentages of parents, nurses, and physicians are uncomfortable with a child's receiving three injections at one visit. Sixty-seven percent of the physicians who do not offer universal newborn hepatitis B vaccinations cite the number of required simultaneous injections as a factor in that decision. Only 15% of physicians order all three recommended injections for most of their 15-month-old patients. CONCLUSIONS Most parents, nurses, and physicians are uncomfortable with three simultaneous injections for children. This discomfort may be a significant barrier to the adoption of the new immunization recommendations. The development of effective combination vaccines should be a research priority.
In vivo effects of antibodies to immune response gene products. I. Haplotype-specific suppression of humoral immune responses with a monoclonal anti-I-A

Immune response (Ir) gene products control immunologic function at several critical sites. We administered in vivo a monoclonal antibody reactive with I-Ak to F1 mice with the genotype H-2k/b. These treated mnice made a markedly reduced antibody response to antigen (H,G)-A--L, under the control of I-Ak, but not to antigen (T,G)-A--L, under the control of I-Ab. This relative specificity was lost if the antigen was given in complete Freund's adjuvant rather than aqueous solution. The monoclonal antibody reduced the antibody titer in an ongoing, secondary response as well. Several potential mechanisms can be postulated for this effect. This haplotypic specificity might ultimately be relevant to human disease.
Parsing Learner Text: to Shoehorn or not to Shoehorn

The texts written by language learners can be considered a type of non-canonical text. Language learners tend to make errors when writing in a second language and in this regard, can be seen to violate the canonical rules of a language. The kinds of errors that learners may make include: spelling, grammatical, vocabulary, collocation. The extent and degree to which learners make errors will depend on their proficiency level and this is a factor that should be taken into account when thinking about non-native writing. Highly proficient speakers will make very few errors, and given just a small sample of text it may not even be possible to identify that they are language learners. However, at the same time, the kinds of errors that even highlyproficient language learners make are often very different from the kinds of errors that a native speaker will make. A non-native speaker is likely to have the most trouble with collocations and lexical choice, whereas a native speaker will be less likely to have difficulty here (Leacock et al., 2014).
The Utility of Safety Counseling in a Pediatric Emergency Department

Objective. Pediatric injuries have a significant impact on the medical system, costing lives and disabling many survivors. Although injury-prevention measures do exist, they are underutilized. A majority of families do not consistently receive counseling by a primary care provider (PCP). We attempted to demonstrate the efficacy of counseling families who presented to a pediatric emergency department with unrelated medical complaints. Methods. A self-report questionnaire was administered to assess the home safety of patients 2 weeks to 12 years old presenting to the emergency department. Targeted counseling on areas noted to be unsafe was provided, and a 2-week follow-up telephone call was made to assess the effectiveness of the counseling. Information on previous counseling by a PCP was also collected and analyzed. Logistic regression was performed to determine significance and calculate odds ratios. Results. Thirty-seven percent of caregivers recalled receiving any counseling at a PCP visit. Caregivers who had received prior counseling by a PCP were significantly more likely to have a safe home environment. Patients who were English speaking were significantly more likely to have received safety counseling than their Spanish-speaking counterparts. One hundred fifty families received counseling in the emergency department, and 117 were eligible for follow-up. Of these families, 39% made a positive change in the safety of their child's environment at the 2-week telephone follow-up. Conclusions. Caregivers receiving counseling by a PCP are more likely to provide a safe home environment for their children. Spanish-speaking patients are at particularly high risk of not receiving counseling. Of caregivers reporting unsafe practices during an unrelated emergency-department encounter, targeted counseling made a positive impact on behavior after discharge.
Inflation Targets as Focal Points

In a world characterised by noisy information and conflicting signals, no Central Bank is always able to affect private sector expectations. Based on Morris and Shin's model, monetary policy then becomes an information game, in which individuals form their expectations based on all the information that is available to them (public and private). However individual agents also know that ultimately inflation is affected by both the objectives of the Central Bank (and hence the policies it pursues) as well as the average expectation formed by the all agents. They thus need to evaluate both actions. Central to our argument is the way that individuals interpret these actions to form their expectations. We apply Bacharach's methodology to provide a framework for assessing everyone's interpretations. Our contribution is to merge these two models to show that a monetary policy regime that has explicit quantitative objectives may provide individuals with better anchors for expectations to coordinate at. However, that is only true first, if no great shocks are anticipated to hit the economy and second, when all other public information is very unclear thus rendering the inflation target the only clear piece of information. We derive in detail the conditions under which this is true.
Image Segmentation Using an Efficient Rotationally Invariant 3 D Region-Based Hidden Markov Model

We present a novel three dimensional (3D) region-based hidden Markov model (rbHMM) for unsupervised image segmentation. Our contributions are twofold. First, our rbHMM employs a more efficient representation of the image than approaches based on a rectangular lattice or grid; thus, resulting in a faster optimization process. Second, our proposed novel tree-structured parameter estimation algorithm for the rbHMM provides a locally optimal data labeling that is invariant to object rotation. We demonstrate the advantages of our segmentation technique by validating on synthetic images of geometric shapes as well as both simulated and clinical magnetic resonance imaging (MRI) data of the brain. For the geometric shape data, we show that our method produces more accurate results in less time than a grid-based HMM framework using a similar optimization strategy. For the brain MRI data, our white and gray matter segmentation results in substantially greater accuracy than both block-based 3D HMM estimation and expectation-maximization hidden Markov random field (HMRF-EM) approaches.
Security considerations for IEEE 802.15.4 networks

The IEEE 802.15. 4 specification outlines a new class of wireless radios and protocols targeted at low power devices, personal area networks, and sensor nodes. The specification includes a number of security provisions and options. In this paper, we highlight places where application designers and radio designers should exercise care when implementing and using 802.15. 4 devices. Specifically, some of the 802.15. 4 optional features actually reduce security, so we urge implementors to ignore those extensions. We highlight difficulties in safely using the security API and provide recommendations on how to change the specification to make it less likely that people will deploy devices with poor security configurations.
Molecular composition of dissolved organic matter in the Mediterranean Sea

The molecular composition of marine dissolved organic matter (DOM) is still poorly understood, particularly in the Mediterranean Sea. In this work, DOM from the open Mediterranean Sea and the adjacent Northeast Atlantic Ocean was isolated by solid‐phase extraction (SPE‐DOM) and molecularly characterized using Fourier‐transform ion cyclotron resonance mass spectrometry. We assessed the gradual reworking of the SPE‐DOM transported by the shallow overturning circulation of the Mediterranean Sea by following the increase in molecular weight (+20 Da), oxygenation (+5%), degradation index (Ideg +22%), and the proportional decrease of unsaturated aliphatic compounds (+34%) along the Levantine Intermediate Water. This reworked SPE‐DOM that leaves the Mediterranean Sea through the Strait of Gibraltar strongly contrasts with the fresh material transported by the inflow of Atlantic water (Ideg −25%). In the deep eastern and western overturning cells, the molecular composition of the deep waters varied according to their area and/or time of formation. SPE‐DOM of the waters formed in the Aegean Sea during the Eastern Mediterranean Transient (EMT) was more processed than the DOM in pre‐EMT waters formed in the Adriatic Sea (molecular weight and the proportion of unsaturated aliphatic compounds were increased by 5 Da and 9%, respectively). Furthermore, pre‐EMT waters contain more reworked SPE‐DOM (Ideg +7%) than post‐EMT waters formed also in the Adriatic Sea. In summary, our study shows that the Mediterranean Sea constitutes a laboratory basin where degradation processes and diagenetic transformations of DOM can be observed on close spatial and temporal scales.
I feel good, therefore I am real: Testing the causal influence of mood on state authenticity

Although the literature has focused on individual differences in authenticity, recent findings suggest that authenticity is sensitive to context; that is, it is also a state. We extended this perspective by examining whether incidental affect influences authenticity. In three experiments, participants felt more authentic when in a relatively positive than negative mood. The causal role of affect in authenticity was consistent across a diverse set of mood inductions, including explicit (Experiments 1 and 3) and implicit (Experiment 2) methods. The link between incidental affect and state authenticity was not moderated by ability to down-regulate negative affect (Experiments 1 and 3) nor was it explained by negative mood increasing private self-consciousness or decreasing access to the self system (Experiment 3). The results indicate that mood is used as information to assess one's sense of authenticity.
Rev3, the catalytic subunit of Polζ, is required for maintaining fragile site stability in human cells

It has been long speculated that mammalian Rev3 plays an important, yet unknown role(s) during mammalian development, as deletion of Rev3 causes embryonic lethality in mice, whereas no other translesion DNA synthesis polymerases studied to date are required for mouse embryo development. Here, we report that both subunits of Polζ (Rev3 and Rev7) show an unexpected increase in expression during G2/M phase, but they localize independently in mitotic cells. Experimental depletion of Rev3 results in a significant increase in anaphase bridges, chromosomal breaks/gaps and common fragile site (CFS) expression, whereas Rev7 depletion primarily causes lagging chromosome defect with no sign of CFS expression. The genomic instability induced by Rev3 depletion seems to be related to replication stress, as it is further enhanced on aphidicolin treatment and results in increased metaphase-specific Fanconi anemia complementation group D type 2 (FANCD2) foci formation, as well as FANCD2-positive anaphase bridges. Indeed, a long-term depletion of Rev3 in cultured human cells results in massive genomic instability and severe cell cycle arrest. The aforementioned observations collectively support a notion that Rev3 is required for the efficient replication of CFSs during G2/M phase, and that the resulting fragile site instability in Rev3 knockout mice may trigger cell death during embryonic development.
A mixture representation of π with applications in Markov chain Monte Carlo and perfect sampling

Let X={Xn:n=0,1,2,…} be an irreducible, positive recurrent Markov chain with invariant probability measure π. We show that if X satisfies a one-step minorization condition, then π can be represented as an infinite mixture. The distributions in the mixture are associated with the hitting times on an accessible atom introduced via the splitting construction of Athreya and Ney [Trans. Amer. Math. Soc. 245 (1978) 493–501] and Nummelin [Z. Wahrsch. Verw. Gebiete 43 (1978) 309–318]. When the small set in the minorization condition is the entire state space, our mixture representation of π reduces to a simple formula, first derived by Breyer and Roberts [Methodol. Comput. Appl. Probab. 3 (2001) 161–177] from which samples can be easily drawn. Despite the fact that the derivation of this formula involves no coupling or backward simulation arguments, the formula can be used to reconstruct perfect sampling algorithms based on coupling from the past (CFTP) such as Murdoch and Green’s [Scand. J. Statist. 25 (1998) 483–502] Multigamma Coupler and Wilson’s [Random Structures Algorithms 16 (2000) 85–113] Read-Once CFTP algorithm. In the general case where the state space is not necessarily 1-small, under the assumption that X satisfies a geometric drift condition, our mixture representation can be used to construct an arbitrarily accurate approximation to π from which it is straightforward to sample. One potential application of this approximation is as a starting distribution for a Markov chain Monte Carlo algorithm based on X.
Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally but not centrally.

Peripheral and central injections of recombinant rat interleukin-1 beta (IL-1 beta) have been shown to decrease social exploration in rats. To test the involvement of vagal afferents in the communication between the immune system and the brain, sham-operated and vagotomized rats were injected peripherally or centrally with physiological saline or IL-1 beta 4 weeks after surgery. Vagotomy attenuated the depression in social exploration induced by i.p. administration of IL-1 beta (15 micrograms) but did not alter the behaviour-depressing effects of an intracerebroventricular (i.c.v.) injection of IL-1 beta (45 ng). These results confirm the role of vagal afferent nerves in the transmission of an immune message from the periphery to the brain, and show that vagotomy does not impair the direct sensitivity of the brain itself to immune signals.
Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti’s neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a “directly observed treatment” strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained– 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH—and the significant reduction in burden of infection– 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti’s very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of “best practices” for NTD control but also are poised to help solve two of the most important future NTD challenges—how to maintain control of STH infections after the community-based LF “treatment platform” ceases and how to ensure appropriate morbidity management for patients currently suffering from lymphatic filarial disease.
A Fine-Grained Analysis on the Evolutionary Coupling of Cloned Code

Code clones are identical or similar code fragments in a code base. A group of code fragments that are similar to one another forms a clone class. Clone fragments from the same clone class often need to be changed together consistently and thus, they exhibit evolutionary coupling. Evolutionary coupling among clone fragments within a clone class has already been investigated and reported. However, a change to a clone fragment of a clone class may also trigger changes to non-cloned code as well as to clone fragments of other clone classes. Such coupling information is equally important for the proper management of clones during software maintenance. Unfortunately, there are no such studies reported in the literature. In this paper, we describe a large scale empirical study that we conduct to examine whether a clone fragment from a particular clone class exhibits evolutionary coupling with non-clone fragments and/or with clone fragments of other clone classes. Our experimental results on thousands of revisions of six diverse subject systems written in two programming languages indicate the presence of such couplings. We consider both exact and near-miss clones in our study. By analyzing the evolutionary couplings of a particular clone fragment from a particular clone class, we are able to predict its three types of co-change candidates with considerable accuracy in terms of precision and recall. These co-change candidates are: (1) non-clone fragments, (2) clone fragments from clone classes other than its own class, and (3) other clone fragments from its own clone class. Thus, we can improve existing clone tracking techniques so that they can also infer and suggest which non-clone fragments as well as which clone fragments from other clone classes might need to be co-changed correspondingly when modifying a clone fragment from a particular clone class.
Genetic risk factors of thrombosis in the antiphospholipid syndrome

The possibility of a genetic predisposition to develop antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies and lupus anticoagulant has been addressed by family studies and population studies. Various studies suggest a familial occurrence of anticardiolipin antibodies and lupus anticoagulant, with or without clinical evidence of APS. This familial tendency could be genetically determined. Multiple human leucocyte antigen‐DR or ‐DQ associations with antiphospholipid antibodies have been described. Genetic studies of a representative antigen, beta2‐glycoprotein‐I (β2GPI), have been carried‐out and a particular valine247/leucine polymorphism could be a genetic risk for presenting anti‐β2GPI antibodies and APS. Many other thrombosis‐related genetic factors have been investigated in APS, but no additional risk for thrombosis has been indicated in affected patients. Although the mechanisms and pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial, different genes and acquired factors seem to be involved. In this review, we will focus on those genetic variants that could contribute to the development of thrombosis in APS.