Yebes 40m radio telescope is the main and largest observing instrument at Yebes Observatory and it is devoted to Very Long Baseline Interferometry (VLBI) and single dish observations since 2010. It ...has been covering frequency bands between 2 GHz and 90 GHz in discontinuous and narrow windows in most of the cases, to match the current needs of the European VLBI Network (EVN) and the Global Millimeter VLBI Array (GMVA).
Nanocosmos project, a European Union funded synergy grant, opened the possibility to increase the instantaneous frequency coverage to observe many molecular transitions with single tunnings in single dish mode. This reduces the observing time and maximises the output from the telescope.
We present the technical specifications of the recently installed 31.5 - 50GHz (Q band) and 72 - 90.5 GHz (W band) receivers along with the main characteristics of the telescope at these frequency ranges. We have observed IRC+10216, CRL 2688 and CRL 618, which harbour a rich molecular chemistry, to demonstrate the capabilities of the new instrumentation for spectral observations in single dish mode.
The results show the high sensitivity of the telescope in the Q band. The spectrum of IRC+10126 offers a signal to noise ratio never seen before for this source in this band. On the other hand, the spectrum normalised by the continuum flux towards CRL 618 in the W band demonstrates that the 40 m radio telescope produces comparable results to those from the IRAM 30 m radio telescope, although with a smaller sensitivity. The new receivers fulfil one of the main goals of Nanocosmos and open the possibility to study the spectrum of different astrophysical media with unprecedented sensitivity.
Summary
Background
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the most frequently involved groups of medicines in hypersensitivity drug reactions. Two mechanisms can induce the ...reaction: immunological (sensitization) due to a specific IgE or T cell response and pharmacological (cyclooxygenase inhibition). The contribution of each of these mechanisms to the reactions is not well known.
Objective
To analyse a large group of subjects with confirmed hypersensitivity reactions to NSAIDs.
Methods
The drugs involved, the clinical entities induced and the time interval between drug intake and appearance of the reaction were studied. In cases where the diagnosis was not confirmed, a drug provocation test was carried out. Atopy status was also assessed with prick test and total IgE in serum.
Results
A total of 659 patients were finally considered to have had hypersensitivity reactions to NSAIDs; 76% had cross‐intolerance (CI) and 24% were selective responders (SR). The most important drugs involved in CI were propionic acid derivatives, in most cases ibuprofen, and in SR pyrazolones. In CI, the most frequent clinical entity was urticaria and angio‐oedema and to a lesser extent airway involvement. The skin and airways were both involved in an important proportion of cases. The most frequent entities in SR were urticaria and/or angio‐oedema followed by anaphylaxis. Atopy was significantly associated in the CI group (P<0.005).
Conclusion and Clinical Relevance
Cutaneous hypersensitivity reactions by CI to NSAIDs are the most frequent entities induced by these compounds. In addition to aspirin, other NSAIDs are taking on a predominant role. Atopy can be a predisposing factor in patients with CI.
Cite this as: I. Doña, N. Blanca‐López, J. A. Cornejo‐García, M. J. Torres, J. J. Laguna, J. Fernández, A. Rosado, C. Rondón, P. Campo, J. A. Agúndez, M. Blanca and G. Canto, Clinical & Experimental Allergy, 2011 (41) 86–95.
The transformation of mechanical energy into electrical signals is the first step in mechanotransduction in the peripheral sensory nervous system and relies on the presence of mechanically gated ion ...channels within specialized sensory organs called mechanoreceptors. Piezo2 is a vertebrate stretch‐gated ion channel necessary for mechanosensitive channels in mammalian cells. Functionally, it is related to light touch, which has been detected in murine cutaneous Merkel cell–neurite complexes, Meissner‐like corpuscles and lanceolate nerve endings. To the best of our knowledge, the occurrence of Piezo2 in human cutaneous mechanoreceptors has never been investigated. Here, we used simple and double immunohistochemistry to investigate the occurrence of Piezo2 in human digital glabrous skin. Piezo2 immunoreactivity was detected in approximately 80% of morphologically and immunohistochemically characterized (cytokeratin 20+, chromogranin A+ and synaptophisin+) Merkel cells. Most of them were in close contact with Piezo2− nerve fibre profiles. Moreover, the axon, but not the lamellar cells, of Meissner's corpuscles was also Piezo2+, but other mechanoreceptors, i.e. Pacinian or Ruffini's corpuscles, were devoid of immunoreactivity. Piezo2 was also observed in non‐nervous tissue, especially the basal keratinocytes, endothelial cells and sweat glands. The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner's corpuscles) low‐threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch. These data offer additional insight into the molecular basis of mechanosensing in humans.
Background: Liver biopsy is an invasive technique with associated major complications. There is no information on the validity of five non-invasive indexes based on routinely available parameters, ...estimated and validated in hepatitis C virus (HCV) monoinfected patients, in human immunodeficiency virus (HIV)/HCV coinfected patients. Aim: To validate these predictive models of liver fibrosis in HIV/HCV coinfected patients. Patients: A total of 357 (90%) of 398 patients from five hospitals were investigated, who underwent liver biopsy and who had complete data to validate all of the models considered. Methods: The predictive accuracy of the indexes was tested by measuring areas under the receiver operating characteristic curves. Diagnostic accuracy was calculated by estimating sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results: The models performed better when liver biopsies ⩾15 mm were used as reference. In this setting, the Forns and Wai indexes, models aimed at discriminating significant fibrosis, showed PPV of 94% and 87%, respectively. Using these models, 27–34% of patients could benefit from exclusion of liver biopsy. If both models were applied sequentially, 41% of liver biopsies could be spared. The indexes aimed at predicting cirrhosis achieved NPV of up to 100%. However, they showed very low PPV. Conclusions: The diagnostic accuracy of these models was lower in HIV/HCV coinfected patients than in the validation studies performed in HCV monoinfected patients. However, simple fibrosis tests may render liver biopsy unnecessary in deciding anti-HCV treatment in over one third of patients with HIV infection and chronic hepatitis C.
Marine reserves are assumed to protect a wide range of species from deleterious effects stemming from exploitation. However, some species, due to their ecological characteristics, may not respond ...positively to protection. Very little is known about the effects of life history and ecological traits (e.g., mobility, growth, and habitat) on responses of fish species to marine reserves. Using 40 data sets from 12 European marine reserves, we show that there is significant variation in the response of different species of fish to protection and that this heterogeneity can be explained, in part, by differences in their traits. Densities of targeted size-classes of commercial species were greater in protected than unprotected areas. This effect of protection increased as the maximum body size of the targeted species increased, and it was greater for species that were not obligate schoolers. However, contrary to previous theoretical findings, even mobile species with wide home ranges benefited from protection: the effect of protection was at least as strong for mobile species as it was for sedentary ones. Noncommercial bycatch and unexploited species rarely responded to protection, and when they did (in the case of unexploited bentho-pelagic species), they exhibited the opposite response: their densities were lower inside reserves. The use of marine reserves for marine conservation and fisheries management implies that they should ensure protection for a wide range of species with different life-history and ecological traits. Our results suggest this is not the case, and instead that effects vary with economic value, body size, habitat, depth range, and schooling behavior.
Summary
Background
Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer‐prone genodermatoses whose causal ...genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders.
Objectives
To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC.
Methods
We conducted RNA‐Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies.
Results
Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA‐Seq data. In addition, enzyme‐linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB.
Conclusions
Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury‐sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS.
What's already known about this topic?
Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development.
Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders.
What does this study add?
We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix‐synthetic capacity.
This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor‐β signalling activation and oxidative state imbalance.
What is the translational message?
This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention.
It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB.
Linked Comment: Has. Br J Dermatol 2019; 181:440–441.
Plain language summary available online
Summary
Background
To date, genetic studies of hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs) have been carried out mainly in aspirin‐induced asthma and to a lesser ...extent in chronic urticaria, with no studies in patients with acute urticaria (AU), the most common entity induced by these drugs.
Objective
In this work, we analysed the association of common variants of 15 relevant genes encoding both enzymes and receptors from the arachidonic acid (AA) pathway with NSAID‐induced AU.
Methods
Patients were recruited in several Allergy Services that are integrated into the Spanish network RIRAAF, and diagnosed of AU induced by cross‐intolerance (CRI) to NSAIDs. Genotyping was carried out by TaqMan allelic discrimination assays.
Results
A total of 486 patients with AU induced by CRI to NSAIDs and 536 unrelated controls were included in this large Spanish case‐control study. Seven variants from 31 tested in six genes were associated in a discovery study population from Malaga (0.0003 ≤ p‐value ≤ 0.041). A follow‐up analysis in an independent sample from Madrid replicated three of the SNPs from the ALOX15 (rs7220870), PTGDR (rs8004654) and CYSLTR1 (rs320095) genes (1.055x10‐6≤meta‐analysis p‐value ≤ 0.003).
Conclusions and Clinical Relevance
Genetic variants of the AA pathway may play an important role in NSAID‐induced AU. These data may help understand the mechanism underlying this disease.
Abstract
We present a detailed prompt emission and early optical afterglow analysis of the two very-high-energy (VHE) detected bursts GRB 201015A and GRB 201216C, and their comparison with a subset ...of similar bursts. Time-resolved spectral analysis of multistructured GRB 201216C using the Bayesian binning algorithm revealed that during the entire duration of the burst, the low-energy spectral index (
α
pt
) remained below the limit of the synchrotron line of death. However, statistically some of the bins supported the additional thermal component. Additionally, the evolution of spectral parameters showed that both the peak energy (
E
p
) and
α
pt
tracked the flux. These results were further strengthened using the values of the physical parameters obtained by synchrotron modeling of the data. Our earliest optical observations of both bursts using the F/Photometric Robotic Atmospheric Monitor Observatorio del Roque de los Muchachos and Burst Observer and Optical Transient Exploring System robotic telescopes displayed a smooth bump in their early optical light curves, consistent with the onset of the afterglow due to synchrotron emission from an external forward shock. Using the observed optical peak, we constrained the initial bulk Lorentz factors of GRB 201015A and GRB 201216C to Γ
0
= 204 and Γ
0
= 310, respectively. The present early optical observations are the earliest known observations constraining outflow parameters and our analysis indicate that VHE detected bursts could have a diverse range of observed luminosity within the detectable redshift range of present VHE facilities.
In vehicular communications, the increase of the channel load caused by excessive periodical messages (beacons) is an important aspect which must be controlled to ensure the appropriate operation of ...safety applications and driver-assistance systems. To date, the majority of congestion control solutions involve including additional information in the payload of the messages transmitted, which may jeopardize the appropriate operation of these control solutions when channel conditions are unfavorable, provoking packet losses. This study exploits the advantages of non-cooperative, distributed beaconing allocation, in which vehicles operate independently without requiring any costly road infrastructure. In particular, we formulate the beaconing rate control problem as a Markov Decision Process and solve it using approximate reinforcement learning to carry out optimal actions. Results obtained were compared with other traditional solutions, revealing that our approach, called SSFA, is able to keep a certain fraction of the channel capacity available, which guarantees the delivery of emergency-related notifications with faster convergence than other proposals. Moreover, good performance was obtained in terms of packet delivery and collision ratios.
Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of ...response to these drugs. Experimental design: Four cycles of doxorubicin (75 mg/m
2
) or docetaxel (100 mg/m
2
) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate − PCR + class I of 56 vs. 0%;
P
= 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.
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