Miracle-dz/UniFAR-FTUs huggingface dataset:
Local Translation in Primary Afferent Fibers Regulates Nociception

Recent studies have demonstrated the importance of local protein synthesis for neuronal plasticity. In particular, local mRNA translation through the mammalian target of rapamycin (mTOR) has been shown to play a key role in regulating dendrite excitability and modulating long-term synaptic plasticity associated with learning and memory. There is also increased evidence to suggest that intact adult mammalian axons have a functional requirement for local protein synthesis in vivo. Here we show that the translational machinery is present in some myelinated sensory fibers and that active mTOR-dependent pathways participate in maintaining the sensitivity of a subpopulation of fast-conducting nociceptors in vivo. Phosphorylated mTOR together with other downstream components of the translational machinery were localized to a subset of myelinated sensory fibers in rat cutaneous tissue. We then showed with electromyographic studies that the mTOR inhibitor rapamycin reduced the sensitivity of a population of myelinated nociceptors known to be important for the increased mechanical sensitivity that follows injury. Behavioural studies confirmed that local treatment with rapamycin significantly attenuated persistent pain that follows tissue injury, but not acute pain. Specifically, we found that rapamycin blunted the heightened response to mechanical stimulation that develops around a site of injury and reduced the long-term mechanical hypersensitivity that follows partial peripheral nerve damage - a widely used model of chronic pain. Our results show that the sensitivity of a subset of sensory fibers is maintained by ongoing mTOR-mediated local protein synthesis and uncover a novel target for the control of long-term pain states.
Pirfenidone treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a discrete clinicopathologic entity defined by the presence of usual interstitial pneumonia on high-resolution CT scan and/or open lung biopsy and the absence of an alternate diagnosis or exposure explaining these findings. There are currently no FDA-approved therapies available to treat this disease, and the 5-year mortality is ∼80%. The pyridone derivative pirfenidone has been studied extensively as a possible therapeutic agent for use in this deadly disease. This review will present the unique clinical features and management issues encountered by physicians caring for IPF patients, including the poor response to conventional therapy. The biochemistry and preclinical efficacy of pirfenidone will be discussed along with a comprehensive review of the clinical efficacy, safety, and side effects and patient-centered foci such as quality of life and tolerability. It is hoped that this information will lend insight into the complex issues surrounding the use of pirfenidone in IPF and lead to further investigation of this agent as a possible therapy in this devastating disease.
Evaluating the Potential for Recovery of Consciousness in the Intensive Care Unit

Purpose of Review: Evaluating patients in the intensive care unit (ICU) with disorders of consciousness has prognostic implications. When brainstem functions are intact, the neurologist must use ancillary testing to help determine prognosis. This article addresses the challenges of arriving at prognoses in patients with hypoxic-ischemic encephalopathy and traumatic brain injury (TBI) and discusses strategies for dealing with these challenges. This has some relevance to other conditions that are capable of causing irreversible brain damage. Recent Findings: Although practice parameters formulated by an American Academy of Neurology (AAN) subcommittee in 2006 were reliable for evaluating patients with hypoxic-ischemic encephalopathy who did not receive hypothermia, the advent of hypothermia has shown that some of these prognostic features were unreliable. Some patients with TBI thought to be vegetative have been found to have cognitive responses. These revelations require neurologists to reconsider prognostic strategies. Summary: To arrive at a more accurate prognosis, it is best to employ multiple pieces of evidence and incorporate the most updated information from the literature. In some cases, newer technologies can provide further insights into cortical function in behaviorally unresponsive patients.
Converting modified health assessment questionnaire (HAQ), multidimensional HAQ, and HAQII scores into original HAQ scores using models developed with a large cohort of rheumatoid arthritis patients

The Stanford Health Assessment Questionnaire Disability Index (HAQ) is the gold standard functional status questionnaire in rheumatology, but it is lengthy. Three shorter versions, the modified HAQ (MHAQ), the Multidimensional HAQ (MDHAQ), and the HAQII are often used in outcomes research as HAQ substitutes. We developed conversion formulas between these modified versions and the original HAQ.
Modified High‐Molecular‐Weight Hyaluronan Promotes Allergen‐Specific Immune Tolerance

&NA; The extracellular matrix in asthmatic lungs contains abundant low‐molecular‐weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high‐molecular‐weight hyaluronan (HMW‐HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW‐HA can be adapted to promote tolerance to airway allergens. HMW‐HA was thiolated to prevent its catabolism and was tethered to allergens via thiol linkages. This platform, which we call “XHA,” delivers antigenic payloads in the context of antiinflammatory costimulation. Allergen/XHA was administered intranasally to mice that had been sensitized previously to these allergens. XHA prevents allergic airway inflammation in mice sensitized previously to either ovalbumin or cockroach proteins. Allergen/XHA treatment reduced inflammatory cell counts, airway hyperresponsiveness, allergen‐specific IgE, and T helper type 2 cell cytokine production in comparison with allergen alone. These effects were allergen specific and IL‐10 dependent. They were durable for weeks after the last challenge, providing a substantial advantage over the current desensitization protocols. Mechanistically, XHA promoted CD44‐dependent inhibition of nuclear factor‐&kgr;B signaling, diminished dendritic cell maturation, and reduced the induction of allergen‐specific CD4 T‐helper responses. XHA and other potential strategies that target CD44 are promising alternatives for the treatment of asthma and allergic sinusitis.
Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants.

OBJECTIVE To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute-phase reactants. METHODS Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs. The CDAI does not contain an acute-phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used. RESULTS Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute-phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab-treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab-treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission. CONCLUSION Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.
Indirect rate distortion problems

The output of a source, the first of the two arguments of a distortion function, is seen by an encoder through a noisy channel. A decoder sees the encoder's signal through the usual communication channel. The second argument of the distortion function is obtained from the decoder's output via another noisy channel. The Dobrushin-Tsybakov reduction of this problem to a direct one is shown to follow at once from a "disconnection principle" for conditional expectations. The same principle applies to more general situations such as i) dependence between the noise variables acting in the input and output channels and ii) side information available only at the decoder.
Doppler Weather Radars and Wind Turbines

In many countries the number of wind turbines is growing rapidly as a response to the increasing demand for renewable energy. The cumulative capacity of wind turbines worldwide has shown a near 10-fold increase in the last decade (Global Wind Energy Council, 2011) and in the coming years many more wind turbines are expected to be built. Existing, older wind turbines are likely to be replaced by larger, next generation, turbines.
Enhanced metrology using preferential orientation of nitrogen-vacancy centers in diamond

We demonstrate preferential orientation of nitrogen-vacancy (NV) color centers along two of four possible crystallographic axes in diamonds grown by chemical vapor deposition on the ${100}$ face. We identify the relevant growth regime and present a possible explanation of this effect. We show that preferential orientation provides increased optical readout contrast for NV multispin measurements, including enhanced ac magnetic-field sensitivity, thus providing an important step towards high-fidelity multispin-qubit quantum information processing, sensing, and metrology.
Genetic and environmental influences on adolescent attachment

Background Twin studies consistently point to limited genetic influence on attachment security in the infancy period, but no study has examined whether this remains the case in later development. This study presents the findings from a twin study examining the relative importance of genetic and environmental influences on attachment in adolescence. Methods The sample included 551 twin pairs aged 15 years recruited from the larger Twins Early Development Study (TEDS). Attachment was assessed using a semistructured interview, the Child Attachment Interview. Results We found robust associations between MZ twins’ scores for Coherence and their overall security of attachment (r = .42, p < .001; kappa = .26, p < .001), but substantially lower associations for DZ twins (r = .20, p = .001; kappa = .09, p = .20), suggesting genetic influence on adolescent attachment (and substantial nonshared environment). Model-fitting analyses confirmed this impression, indicating approximately 40% heritability of attachment and negligible influence of the shared environment. Conclusions The results suggest that genes may play an important role in adolescent attachment and point to the potentially distinct aetiological mechanisms involved in individual differences in attachment beyond early childhood.
Types of Family Caregiving and Daily Experiences in Midlife and Late Adulthood: The Moderating Influences of Marital Status and Age

Guided by the life-course perspective, this study contributes to the family caregiving, aging, and disability literature by examining the daily experiences of three types of family caregivers in midlife and late adulthood. A sample of 162 caregivers from the National Survey of Midlife in the United States study completed interviews, questionnaires, and a Daily Diary Study. Multilevel models showed the patterns of daily time use did not differ by caregiver types. Caregivers of sons/daughters with developmental disabilities (DD) experienced more daily stressors than caregivers of parents with health conditions (HC) and caregivers of spouses with HC. Unmarried caregivers of sons/daughters with DD reported spending more time on daily leisure activities and exhibited greater daily stressor exposure than other family caregivers. Age did not moderate the associations between caregiver types and daily experiences. Findings highlight the important consideration of the caregivers’ characteristics to better determine the quality of their daily experiences in midlife and late adulthood.
Full-Field Electroretinography Obtained Using a Contact Lens Electrode with Built-In High-Intensity White-Light-Emitting Diodes Can Be Utilized in Toxicological Assessments in Rats

Full-field electroretinography (ERG) using contact lenses with built-in LED was performed on albino rats, and used to evaluate the visual toxicity of sodium iodate (NaIO3). Experiment 1 was carried out to determine the optimal conditions in rats relating to stimulus intensity, background illumination, and light adaptation period. As a result, we found that a full-field ERG was recorded under the following conditions: stimulus intensity: –3.5 log cd s/m2 in rod response; background intensity and light adaptation period: 10 cd/m2 and 10 min in cone and flicker responses. Experiment 2 was carried out to confirm the usefulness of full-field ERG using rats with retinal toxicities induced by NaIO3. Male rats were given NaIO3 intravenously at a dose of 50 mg/kg. ERG was recorded before administration and after 3, 8, 24 h, and 7 days of administration, and histopathological analysis was conducted after 8 h of administration. The rod response disappeared completely at 3 h, based on a reduced maximal response and oscillatory potentials. On the other hand, cone and flicker responses were still present at 8 h. All responses disappeared on the 7th day. These findings indicate that the retinal toxicity induced by NaIO3 was expressed first in rods, followed by cones. There were no microscopical changes after 8 h of administration, although the rod responses had completely disappeared by this time. These results suggest that full-field ERG in rats using an LED contact lens is useful for the separate evaluation of toxic effects on rods and cones.
Possibilities of photothermoplastic resolving power improvement under holographic recording procedure

The influence of the surface-active substances (SAS) on the evolution process of the charged surface instability has been investigated. It is indicated that the presence of the SAS grows the critical space frequency of deformation, which allows the SAS using for the resolving power growing of the information phototermoplastic carriers, destined for the recording of the optical imagines.
Galaxy Zoo:evidence for diverse star formation histories through the green valley

Does galaxy evolution proceed through the green valley via multiple pathways or as a single population? Motivated by recent results highlighting radically different evolutionary pathways between early- and late-type galaxies, we present results from a simple Bayesian approach to this problem wherein we model the star formation history (SFH) of a galaxy with two parameters, [t, τ] and compare the predicted and observed optical and near-ultraviolet colours. We use a novel method to investigate the morphological differences between the most probable SFHs for both disc-like and smooth-like populations of galaxies, by using a sample of 126 316 galaxies (0.01 < z < 0.25) with probabilistic estimates of morphology from Galaxy Zoo. We find a clear difference between the quenching time-scales preferred by smooth- and disc-like galaxies, with three possible routes through the green valley dominated by smooth- (rapid time-scales, attributed to major mergers), intermediate- (intermediate time-scales, attributed to minor mergers and galaxy interactions) and disc-like (slow time-scales, attributed to secular evolution) galaxies. We hypothesize that morphological changes occur in systems which have undergone quenching with an exponential time-scale τ < 1.5 Gyr, in order for the evolution of galaxies in the green valley to match the ratio of smooth to disc galaxies observed in the red sequence. These rapid time-scales are instrumental in the formation of the red sequence at earlier times; however, we find that galaxies currently passing through the green valley typically do so at intermediate time-scales.
High angular resolution Sunyaev-Zel’dovich observations of MACS J1423.8+2404 with NIKA: Multiwavelength analysis

NIKA, the prototype of the NIKA2 camera, is an instrument operating at the IRAM 30m telescope that can observe the sky simultaneously at 150 and 260GHz. One of the main goals of NIKA is to measure the pressure distribution in galaxy clusters at high angular resolution using the Sunyaev-Zel'dovich (SZ) effect. Such observations have already proved to be an excellent probe of cluster pressure distributions even at high redshifts. However, an important fraction of clusters host submm and/or radio point sources that can significantly affect the reconstructed signal. Here we report <20arcsec angular resolution observations at 150 and 260GHz of the cluster MACSJ1424, which hosts both radio and submm point sources. We examine the morphological distribution of the SZ signal and compare it to other datasets. The NIKA data are combined with Herschel satellite data to study the SED of the submm point source contaminants. We then perform a joint reconstruction of the ICM electronic pressure and density by combining NIKA, Planck, XMM-Newton and Chandra data, focussing on the impact of the radio and submm sources on the reconstructed pressure profile. We find that the large-scale pressure distribution is unaffected by the point sources due to the resolved nature of the NIKA observations. The reconstructed pressure in the inner region is slightly higher when the contribution of point sources are removed. We show that it is not possible to set strong constraints on the central pressure distribution without removing accurately these contaminants. The comparison with Xray only data shows good agreement for the pressure, temperature and entropy profiles, all indicating that MACSJ1424 is a dynamically relaxed cool core system. The present observations illustrate the possibility of measuring these quantities with a relatively small integration time, even at high redshift and without Xray spectroscopy.
Intelligent Audio Production Strategies Informed by Best Practices

The main focus of this article is to explore and investigate the fundamental constraints that should be at the basis of algorithm development in intelligent audio production systems. Through mix analysis and grounded theory strategies, a best-practices framework on the craft of mixing is sought out. Findings, while not to be taken as dogmatic, give a clear indication of preferred implementation strategies
Sequential Chemoradiotherapy with Accelerated Hypofractionated Radiotherapy Compared to Concurrent Chemoradiotherapy with Standard Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer

To compare the outcomes and treatment-related toxicities of two chemoradiotherapy schedules given to the patients with unresectable locally advanced non-small cell lung cancer (NSCLC): sequential chemotherapy with accelerated hypofractionated radiotherapy (SCRT), and concurrent chemotherapy with standard radiotherapy (CCRT), 68 patients from two prospective clinical trials were included. Thirty-four patients were treated with SCRT using an accelerated hypofractionated radiation schedule, 34 patients received CCRT with standard radiation. Between the two treatment groups there were no significant differences in terms of overall survival, progression-free survival (PFS), locoregional-PFS or distant metastasis-PFS. For the SCRT group, the median survival time and 2- and 4-year overall survival rates were 19 months, 38.2%, and 23.5%, respectively, and for the CCRT group these were 19 months, 44.1%, and 19.6%. Esophageal and constitutional toxicities were more pronounced in the CCRT group, while there was no significant difference in pulmonary toxicities. The results suggest that for unresectable stage III NSCLC, the outcomes of SCRT with accelerated hypofractionated radiotherapy and CCRT with standard radiotherapy are similar, but the toxicities associated with treatment are less in the SCRT group.
RAPID RISK ASSESSMENT New bornavirus strain detected in the EU 25 February 2015

Consulted experts Experts from ECDC: Hervé Zeller, Dragoslav Domanović, Celine Gossner, Denis Coulombier. External experts: Martin Beer, Paula M Kinnunen, Olli Vapalahti, Dennis Tappe, Jonas Schmidt-Chanasit, Bernd Hoffmann. Main conclusions and options for action A recently reported cluster of acute fatal encephalitis in three squirrel breeders possibly related to an infection with a newly identified bornavirus is an unusual event. The novel nature of this occurrence requires that additional investigations are undertaken into the role of a new bornavirus in the aetiology of these cases, the identification of natural hosts, reservoir and the transmission route. Nevertheless, pending the completion of the cluster investigation, it is advised that feeding or direct contact with living or dead variegated squirrels should be avoided, as a precautionary measure. Further investigations are ongoing to characterise these cases. In addition, testing of cases of human encephalitis for this newly identified bornavirus, especially in areas where the presence of bornavirus is documented in animals, can contribute to a better understanding of the risk of bornavirus infection in humans. RAPID RISK ASSESSMENT