Visual acuity of pseudophakic patients predicted from in-vitro measurements of intraocular lenses with different design

The optical quality of a set of IOLs (modeling set: one monofocal and two bifocals) was assessed through focus by the area under the modulation transfer function (MTFa) metric and related to the visual acuity (VA) defocus curves of pseudophakic patients implanted with said IOLs. A non-linear relationship between the MTFa and clinical VA was obtained with an asymptotic limit found to be the best VA achievable by the patients. Two mathematical fitting functions between clinical VA and MTFa were derived with high correlation coefficients (R-2 >= 0.85). They were applied to the MTFa obtained from a different set of IOLs with advanced designs (trial set: one extended range of vision -ERV-, one trifocal ERV and one trifocal apodized) to predict VA versus defocus of patients implanted with these IOLs. Differences between the calculated VA and the clinical VA for both fitting models were within the standard deviation of the clinical measurements in the range of -3.00 D to 0.00 D defocus. thus proving the suitability of the MTFa metric to predict clinical VA performance of new IOL designs. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

PrePPI: a structure-informed database of protein–protein interactions

PrePPI (http://bhapp.c2b2.columbia.edu/PrePPI) is a database that combines predicted and experimentally determined protein–protein interactions (PPIs) using a Bayesian framework. Predicted interactions are assigned probabilities of being correct, which are derived from calculated likelihood ratios (LRs) by combining structural, functional, evolutionary and expression information, with the most important contribution coming from structure. Experimentally determined interactions are compiled from a set of public databases that manually collect PPIs from the literature and are also assigned LRs. A final probability is then assigned to every interaction by combining the LRs for both predicted and experimentally determined interactions. The current version of PrePPI contains ∼2 million PPIs that have a probability more than ∼0.1 of which ∼60 000 PPIs for yeast and ∼370 000 PPIs for human are considered high confidence (probability greater than 0.5). The PrePPI database constitutes an integrated resource that enables users to examine aggregate information on PPIs, including both known and potentially novel interactions, and that provides structural models for many of the PPIs

Studying the accretion geometry of EXO 2030+375 at luminosities close to the propeller regime

The Be X-ray binary EXO 2030+375 was in an extended low luminosity state during most of 2016. We observed this state with NuSTAR and Swift, supported by INTEGRAL observations as well as optical spectroscopy with the NOT. We present a comprehensive spectral and timing analysis of these data here to study the accretion geometry and investigate a possible onset of the propeller effect. The H-alpha data show that the circumstellar disk of the Be-star is still present. We measure equivalent widths similar to values found during more active phases in the past, indicating that the low-luminosity state is not simply triggered by a smaller Be disk. The NuSTAR data, taken at a 3-78 keV luminosity of ~6.8e35 erg/s (for a distance of 7.1 kpc), are well described by standard accreting pulsar models, such as an absorbed power-law with a high-energy cutoff. We find that pulsations are still clearly visible at these luminosities, indicating that accretion is continuing despite the very low mass transfer rate. In phase-resolved spectroscopy we find a peculiar variation of the photon index from ~1.5 to ~2.5 over only about 3% of the rotational period. This variation is similar to that observed with XMM-Newton at much higher luminosities. It may be connected to the accretion column passing through our line of sight. With Swift/XRT we observe luminosities as low as 1e34 erg/s during which the data quality did not allow us to search for pulsations, but the spectrum is much softer and well described by either a blackbody or soft power-law continuum. This softer spectrum might be due to the fact that accretion has been stopped by the propeller effect and we only observe the neutron star surface cooling.Comment: 11 pages, 6 figures, accepted for publication in A&A (v2 including language edits

A computational interactome and functional annotation for the human proteome

We present a database, PrePPI (Predicting Protein-Protein Interactions), of more than 1.35 million predicted protein-protein interactions (PPIs). Of these at least 127,000 are expected to constitute direct physical interactions although the actual number may be much larger (~500,000). The current PrePPI, which contains predicted interactions for about 85% of the human proteome, is related to an earlier version but is based on additional sources of interaction evidence and is far larger in scope. The use of structural relationships allows PrePPI to infer numerous previously unreported interactions. PrePPI has been subjected to a series of validation tests including reproducing known interactions, recapitulating multi-protein complexes, analysis of disease associated SNPs, and identifying functional relationships between interacting proteins. We show, using Gene Set Enrichment Analysis (GSEA), that predicted interaction partners can be used to annotate a protein’s function. We provide annotations for most human proteins, including many annotated as having unknown function

Visual acuity of pseudophakic patients predicted from in-vitro measurements of intraocular lenses with different design

Postprint (published version

NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics

Tissue Engineering of Lips and Muco-Cutaneous Junctions: In Vitro Development of Tissue Engineered Constructs of Oral Mucosa and Skin for Lip Reconstruction

We report for the first time the fabrication of a three-dimensional tissue structure containing, in a continuous layer, the morphological features of a lip: epidermal skin, vermillion, and oral mucosa. This tissue engineered muco-cutaneous (M/C) equivalent was manufactured using human oral and skin keratinocytes grown on an acellular, nonimmunogenic dermal equivalent (AlloDerm-) to produce a tissue equivalent with similar anatomic and handling properties as native human lips. Confirmation of the structural composition of the construct was performed using routine histology and immunohistochemistry by identification of epithelial markers that are differentially expressed in separate anatomic areas of the lips. These full-thickness human lip skin equivalents can be used in surgical lip reconstruction in individuals suffering from lip loss from cancer, congenital deformations, and injuries after accidents. We propose this technique can be used as a general basis for tissue engineering of M/C junctions in other parts of the body, such as anus and vagina.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90465/1/ten-2Etec-2E2011-2E0406.pd