1,689 research outputs found
Comets, historical records and vedic literature
A verse in book I of Rigveda mentions a cosmic tree with rope-like aerial
roots held up in the sky. Such an imagery might have ensued from the appearance
of a comet having `tree stem' like tail, with branched out portions resembling
aerial roots. Interestingly enough, a comet referred to as `heavenly tree' was
seen in 162 BC, as reported by old Chinese records. Because of weak surface
gravity, cometary appendages may possibly assume strange shapes depending on
factors like rotation, structure and composition of the comet as well as solar
wind pattern. Varahamihira and Ballala Sena listed several comets having
strange forms as reported originally by ancient seers such as Parashara,
Vriddha Garga, Narada and Garga.
Mahabharata speaks of a mortal king Nahusha who ruled the heavens when Indra,
king of gods, went into hiding. Nahusha became luminous and egoistic after
absorbing radiance from gods and seers. When he kicked Agastya (southern star
Canopus), the latter cursed him to become a serpent and fall from the sky. We
posit arguments to surmise that this Mahabharata lore is a mythical recounting
of a cometary event wherein a comet crossed Ursa Major, moved southwards with
an elongated tail in the direction of Canopus and eventually went out of sight.
In order to check whether such a conjecture is feasible, a preliminary list of
comets (that could have or did come close to Canopus) drawn from various
historical records is presented and discussed.Comment: This work was presented in the International Conference on Oriental
Astronomy held at IISER, Pune (India) during November, 201
Identification of candidate mediators of chemoresponse in breast cancer through therapy-driven selection of somatic variants
Purpose: More than a third of primary breast cancer patients are treated with cytotoxic chemotherapy, typically without guidance from predictive markers. Increased use of neoadjuvant chemotherapy provides opportunities for identification of molecules associated with treatment response, by comparing matched tumour samples before and after therapy. Our hypothesis was that somatic variants of increased prevalence after therapy promote resistance, while variants with reduced prevalence cause sensitivity.
Methods: We performed systematic analyses of matched pairs of cancer exomes from primary oestrogen receptor-positive/HER2-negative breast cancers (n = 6) treated with neoadjuvant epirubicin/cyclophosphamide. We identified candidate genes as mediators of chemotherapy response by consistent subclonal changes in somatic variant prevalence through therapy, predicted variant impact on gene function, and enrichment of specific functional pathways. Influence of candidate genes on breast cancer outcome was tested using publicly available breast cancer expression data (n = 1903).
Results: We identified 14 genes as the strongest candidate mediators of chemoresponse: TCHH, MUC17, ARAP2, FLG2, ABL1, CENPF, COL6A3, DMBT1, ITGA7, PLXNA1, S100PBP, SYNE1, ZFHX4, and CACNA1C. Genes contained somatic variants showing prevalence changes in up to 4 patients, with up to 3 being predicted as damaging. Genes coding for extra-cellular matrix components or related signalling pathways were significantly over-represented among variants showing prevalence changes. Expression of 5 genes (TCHH, ABL1, CENPF, S100PBP, and ZFHX4) was significantly associated with patient survival.
Conclusions: Genomic analysis of paired pre- and post-therapy samples resulting from neoadjuvant therapy provides a powerful method for identification of mediators of response. Genes we identified should be assessed as predictive markers or targets in chemo-sensitization
Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects
PublishedResearch Support, Non-U.S. Gov'tBACKGROUND: Environmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established. OBJECTIVES: We assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent). METHODS: Growth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17 alpha-ethinyl-estradiol (EE2)], and to EE2 alone. RESULTS: In addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE2 were modified when it was present in a complex mixture (i.e., spiked into effluent), suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes. CONCLUSION: These data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures.This work was funded by the Environment Agency to C.R.T. (project no. SC040078). T.N. was supported by a Fundação para a Ciência ea Tecnologia (FCT) fellowship (BPD/18192/04)
Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle
We reconsider the problem of the stability of the thermohaline circulation as
described by a two-dimensional Boussinesq model with mixed boundary conditions.
We determine how the stability properties of the system depend on the intensity
of the hydrological cycle. We define a two-dimensional parameters' space
descriptive of the hydrology of the system and determine, by considering
suitable quasi-static perturbations, a bounded region where multiple equilibria
of the system are realized. We then focus on how the response of the system to
finite-amplitude surface freshwater forcings depends on their rate of increase.
We show that it is possible to define a robust separation between slow and fast
regimes of forcing. Such separation is obtained by singling out an estimate of
the critical growth rate for the anomalous forcing, which can be related to the
characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy
Odorant Receptor from the Southern House Mosquito Narrowly Tuned to the Oviposition Attractant Skatole
Oviposition attractants are environmental cues that allow Culex gravid female mosquitoes to locate suitable sites for egg-laying and, therefore, may be exploited for environmentally friendly strategies for controlling mosquito populations. Naturally occurring skatole has been identified as an oviposition attractant for the Southern House mosquito, Culex quinquefasciatus. Previously, we identified in Cx. quinquefasciatus female antennae an olfactory receptor neuron (ORN) highly sensitive to skatole and an odorant-binding protein involved in the detection of this semiochemical. Here, we describe the characterization of an odorant receptor (OR), CquiOR10, which is narrowly tuned to skatole when expressed in the Xenopus oocyte system. Odorant-induced response profiles generated by heterologously expressed CquiOR10 suggest that this OR is expressed in the mosquito ORN sensitive to skatole. However, geranylacetone, which stimulates the antennal ORN, was not detected by CquiOR10-expressing oocytes, thus raising interesting questions about reception of oviposition attractants in mosquitoes
Detection of Exocometary CO within the 440 Myr Old Fomalhaut Belt: A Similar CO+CO 2 Ice Abundance in Exocomets and Solar System Comets
Recent Atacama Large Millimeter/submillimeter Array observations present mounting evidence for the presence of exocometary gas released within Kuiper Belt analogs around nearby main-sequence stars. This represents a unique opportunity to study their ice reservoir at the younger ages when volatile delivery to planets is most likely to occur. We here present the detection of CO J = 2-1 emission colocated with dust emission from the cometary belt in the 440 Myr old Fomalhaut system. Through spectrospatial filtering, we achieve a 5.4σ detection and determine that the ring's sky-projected rotation axis matches that of the star. The CO mass derived ((0.65\mbox{--}42)\times {10}^{-7}\,{M}_{\oplus }) is the lowest of any circumstellar disk detected to date and must be of exocometary origin. Using a steady-state model, we estimate the CO+CO2 mass fraction of exocomets around Fomalhaut to be between 4.6% and 76%, consistent with solar system comets and the two other belts known to host exocometary gas. This is the first indication of a similarity in cometary compositions across planetary systems that may be linked to their formation scenario and is consistent with direct interstellar medium inheritance. In addition, we find tentative evidence that % of the detected flux originates from a region near the eccentric belt's pericenter. If confirmed, the latter may be explained through a recent impact event or CO pericenter glow due to exocometary release within a steady-state collisional cascade. In the latter scenario, we show how the azimuthal dependence of the CO release rate leads to asymmetries in gas observations of eccentric exocometary belts
A Complete ALMA Map of the Fomalhaut Debris Disk
© 2017. The American Astronomical Society. All rights reserved. We present ALMA mosaic observations at 1.3 mm (223 GHz) of the Fomalhaut system with a sensitivity of 14 μJy/beam. These observations provide the first millimeter map of the continuum dust emission from the complete outer debris disk with uniform sensitivity, enabling the first conclusive detection of apocenter glow. We adopt an MCMC modeling approach that accounts for the eccentric orbital parameters of a collection of particles within the disk. The outer belt is radially confined with an inner edge of 136.3 ± 0.9 au and width of 13.5 ± 1.8 au. We determine a best-fit eccentricity of 0.12 ± 0.01. Assuming a size distribution power-law index of q = 3.46 ± 0.09, we constrain the dust absorptivity power-law index β to be 0.9 < β < 1.5. The geometry of the disk is robustly constrained with inclination 65.°6 ± 0.°3, position angle 337.°9 ± 0.°3, and argument of periastron 22.°5 ± 4.°3. Our observations do not confirm any of the azimuthal features found in previous imaging studies of the disk with Hubble Space Telescope, SCUBA, and ALMA. However, we cannot rule out structures ≤10 au in size or that only affect smaller grains. The central star is clearly detected with a flux density of 0.75 ± 0.02 mJy, significantly lower than predicted by current photospheric models. We discuss the implications of these observations for the directly imaged Fomalhaut b and the inner dust belt detected at infrared wavelengths
MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer
Background: poor prognosis primary breast cancers are typically treated with cytotoxic chemotherapy. However, recurrences remain relatively common even after this aggressive therapy. Comparison of matched tumours pre- and post-chemotherapy can allow identification of molecular characteristics of therapy resistance and thereby potentially aid discovery of novel predictive markers or targets for chemosensitisation. Through this comparison, we aimed to identify microRNAs associated with chemoresistance, define microRNA target genes, and assess targets as predictors of chemotherapy response. Methods: cancer cells were laser microdissected from matched breast cancer tissues pre- and post-chemotherapy from estrogen receptor positive/HER2 negative breast cancers showing partial responses to epirubicin/cyclophosphamide chemotherapy (n = 5). MicroRNA expression was profiled using qPCR arrays. MicroRNA/mRNA expression was manipulated in estrogen receptor positive/HER2 negative breast cancer cell lines (MCF7 and MDA-MB-175 cells) with mimics, inhibitors or siRNAs, and chemoresponse was assessed using MTT and colony forming survival assays. MicroRNA targets were identified by RNA-sequencing of microRNA mimic pull-downs, and comparison of these with mRNAs containing predicted microRNA binding sites. Survival correlations were tested using the METABRIC expression dataset (n = 1979). Results: miR-195 and miR-26b were consistently up-regulated after therapy, and changes in their expression in cell lines caused significant differences in chemotherapy sensitivity, in accordance with up-regulation driving resistance. SEMA6D was defined and confirmed as a target of the microRNAs. Reduced SEMA6D expression was significantly associated with chemoresistance, in accordance with SEMA6D being a down-stream effector of the microRNAs. Finally, low SEMA6D expression in breast cancers was significantly associated with poor survival after chemotherapy, but not after other therapies. Conclusions: microRNAs and their targets influence chemoresponse, allowing the identification of SEMA6D as a predictive marker for chemotherapy response that could be used to direct therapy or as a target in chemosensitisation strategies
Unsupervised reduction of random noise in complex data by a row-specific, sorted principal component-guided method
<p>Abstract</p> <p>Background</p> <p>Large biological data sets, such as expression profiles, benefit from reduction of random noise. Principal component (PC) analysis has been used for this purpose, but it tends to remove small features as well as random noise.</p> <p>Results</p> <p>We interpreted the PCs as a mere signal-rich coordinate system and sorted the squared PC-coordinates of each row in descending order. The sorted squared PC-coordinates were compared with the distribution of the ordered squared random noise, and PC-coordinates for insignificant contributions were treated as random noise and nullified. The processed data were transformed back to the initial coordinates as noise-reduced data. To increase the sensitivity of signal capture and reduce the effects of stochastic noise, this procedure was applied to multiple small subsets of rows randomly sampled from a large data set, and the results corresponding to each row of the data set from multiple subsets were averaged. We call this procedure Row-specific, Sorted PRincipal component-guided Noise Reduction (RSPR-NR). Robust performance of RSPR-NR, measured by noise reduction and retention of small features, was demonstrated using simulated data sets. Furthermore, when applied to an actual expression profile data set, RSPR-NR preferentially increased the correlations between genes that share the same Gene Ontology terms, strongly suggesting reduction of random noise in the data set.</p> <p>Conclusion</p> <p>RSPR-NR is a robust random noise reduction method that retains small features well. It should be useful in improving the quality of large biological data sets.</p
The clinical features of the piriformis syndrome: a systematic review
Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis
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