In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted ...treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food allergy. Subcutaneous, epicutaneous, intralymphatic, oral and sublingual protocols of AIT exist. In animals, most data are available in dogs where subcutaneous AIT is an accepted treatment for atopic dermatitis. Initiating a regulatory response and a production of “blocking” IgG antibodies with AIT are similar mechanisms in human beings and dogs with allergic diseases. Although subcutaneous immunotherapy is used for atopic dermatitis in cats, data for its efficacy are sparse. There is some evidence for successful treatment of feline asthma with AIT. In horses, most studies evaluate the effect of AIT on insect hypersensitivity with conflicting results although promising pilot studies have demonstrated the prophylaxis of insect hypersensitivity with recombinant antigens of biting midges (Culicoides spp.). Optimizing AIT using allergoids, peptide immunotherapy, recombinant allergens and new adjuvants with the different administration types of allergen extracts will further improve compliance and efficacy of this proven treatment modality.
The SLC4 family of bicarbonate (HCO3-) transporters Romero, Michael F.; Chen, An-Ping; Parker, Mark D. ...
Molecular aspects of medicine,
April-June 2013, 2013 Apr-Jun, 2013-4-00, 20130401, Volume:
34, Issue:
2-3
Journal Article
Peer reviewed
Open access
The SLC4 family consists of 10 genes (SLC4A1–5; SLC4A7–11). All encode integral membrane proteins with very similar hydropathy plots—consistent with 10–14 transmembrane segments. Nine SLC4 members ...encode proteins that transport HCO3- (or a related species, such as CO32-) across the plasma membrane. Functionally, eight of these proteins fall into two major groups: three Cl–HCO3 exchangers (AE1–3) and five Na+-coupled HCO3- transporters (NBCe1, NBCe2, NBCn1, NBCn2, NDCBE). Two of the Na+-coupled transporters (NBCe1, NBCe2) are electrogenic; the other three Na+-coupled HCO3- transporters and all three AEs are electroneutral. In addition, two other SLC4 members (AE4, SLC4A9 and BTR1, SLC4A11) do not yet have a firmly established function. Most, though not all, SLC4 members are functionally inhibited by 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS). SLC4 proteins play important roles many modes of acid–base homeostasis: the carriage of CO2 by erythrocytes, the transport of H+ or HCO3- by several epithelia, as well as the regulation of cell volume and intracellular pH.
Clustering, the process of grouping together similar items into distinct partitions, is a common type of unsupervised machine learning that can be useful for summarizing and aggregating complex ...multi-dimensional data. However, data can be clustered in many ways, and there exist a large body of algorithms designed to reveal different patterns. While having access to a wide variety of algorithms is helpful, in practice, it is quite difficult for data scientists to choose and parameterize algorithms to get the clustering results relevant for their dataset and analytical tasks. To alleviate this problem, we built Clustervision, a visual analytics tool that helps ensure data scientists find the right clustering among the large amount of techniques and parameters available. Our system clusters data using a variety of clustering techniques and parameters and then ranks clustering results utilizing five quality metrics. In addition, users can guide the system to produce more relevant results by providing task-relevant constraints on the data. Our visual user interface allows users to find high quality clustering results, explore the clusters using several coordinated visualization techniques, and select the cluster result that best suits their task. We demonstrate this novel approach using a case study with a team of researchers in the medical domain and showcase that our system empowers users to choose an effective representation of their complex data.
Evidence of strong quasar feedback in the early Universe Maiolino, R.; Gallerani, S.; Neri, R. ...
Monthly notices of the Royal Astronomical Society. Letters,
September 2012, 2012-09-01, 20120901, Volume:
425, Issue:
1
Journal Article
Peer reviewed
Open access
ABSTRACT
Most theoretical models invoke quasar‐driven outflows to quench star formation in massive galaxies, and this feedback mechanism is required to account for the population of old and passive ...galaxies observed in the local Universe. The discovery of massive, old and passive galaxies at z∼ 2 implies that such quasar feedback on to the host galaxy must have been at work very early on, close to the reionization epoch. We have observed the C ii 158 m transition in SDSS J114816.64+525150.3, which, at z= 6.4189, is one of the most distant quasars known. We detect broad wings of the line tracing a quasar‐driven massive outflow. This is the most distant massive outflow ever detected and is likely tracing the long‐sought quasar feedback, already at work in the early Universe. The outflow is marginally resolved on scales of ∼16 kpc, implying that the outflow can really affect the whole galaxy, as required by quasar feedback models. The inferred outflow rate, , is the highest ever found. At this rate, the outflow can clean the gas in the host galaxy, and therefore quench star formation, in a few million years.
Protein dynamics are essential for protein function, and yet it has been challenging to access the underlying atomic motions in solution on nanosecond-to-microsecond time scales. We present a ...structural ensemble of ubiquitin, refined against residual dipolar couplings (RDCs), comprising solution dynamics up to microseconds. The ensemble covers the complete structural heterogeneity observed in 46 ubiquitin crystal structures, most of which are complexes with other proteins. Conformational selection, rather than induced-fit motion, thus suffices to explain the molecular recognition dynamics of ubiquitin. Marked correlations are seen between the flexibility of the ensemble and contacts formed in ubiquitin complexes. A large part of the solution dynamics is concentrated in one concerted mode, which accounts for most of ubiquitin's molecular recognition heterogeneity and ensures a low entropic complex formation cost.
Purpose To provide guidance to oncology clinicians on how to use effective communication to optimize the patient-clinician relationship, patient and clinician well-being, and family well-being. ...Methods ASCO convened a multidisciplinary panel of medical oncology, psychiatry, nursing, hospice and palliative medicine, communication skills, health disparities, and advocacy experts to produce recommendations. Guideline development involved a systematic review of the literature and a formal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, and randomized controlled trials published from 2006 through October 1, 2016. Results The systematic review included 47 publications. With the exception of clinician training in communication skills, evidence for many of the clinical questions was limited. Draft recommendations underwent two rounds of consensus voting before being finalized. Recommendations In addition to providing guidance regarding core communication skills and tasks that apply across the continuum of cancer care, recommendations address specific topics, such as discussion of goals of care and prognosis, treatment selection, end-of-life care, facilitating family involvement in care, and clinician training in communication skills. Recommendations are accompanied by suggested strategies for implementation. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .
Abstract
The adaptation of CRISPR/Cas9 systems for pooled library genetic knockout screens in mammalian cells has substantially advanced the state of the art in human functional genomics. Screening ...panels of cell lines for genes whose knockout imposes a significant fitness defect has dramatically expanded our catalog of high-confidence essential genes, and has already proven useful in identifying tumor-specific essential genes for the development of targeted therapies. However, nonexperts currently lack an easy to use way to access this data and to identify whether their genes of interest are essential across different genetic backgrounds. The volume of screening data is expected to grow massively, making the problem more intractable. Here we describe PICKLES, the database of Pooled In vitro CRISPR Knockout Library Essentiality Screens, where end users can display and download raw or normalized essentiality profiles for more that 18 000 protein-coding genes across more than 50 cell lines. An additional data set with 15,000 genes targeted by pooled library shRNA in over 100 cell lines is also included. Researchers can see at a glance the relative fitness defect and tissue specificity of their genes of interest, generate and save figures locally, and download all raw data. The database is available at http://pickles.hart-lab.org.
Understanding how super-massive black holes form and grow in the early Universe has become a major challenge
since it was discovered that luminous quasars existed only 700 million years after the Big ...Bang
. Simulations indicate an evolutionary sequence of dust-reddened quasars emerging from heavily dust-obscured starbursts that then transition to unobscured luminous quasars by expelling gas and dust
. Although the last phase has been identified out to a redshift of 7.6 (ref.
), a transitioning quasar has not been found at similar redshifts owing to their faintness at optical and near-infrared wavelengths. Here we report observations of an ultraviolet compact object, GNz7q, associated with a dust-enshrouded starburst at a redshift of 7.1899 ± 0.0005. The host galaxy is more luminous in dust emission than any other known object at this epoch, forming 1,600 solar masses of stars per year within a central radius of 480 parsec. A red point source in the far-ultraviolet is identified in deep, high-resolution imaging and slitless spectroscopy. GNz7q is extremely faint in X-rays, which indicates the emergence of a uniquely ultraviolet compact star-forming region or a Compton-thick super-Eddington black-hole accretion disk at the dusty starburst core. In the latter case, the observed properties are consistent with predictions from cosmological simulations
and suggest that GNz7q is an antecedent to unobscured luminous quasars at later epochs.
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