OkCupid Data for Introductory Statistics and Data Science Courses

We present a data set consisting of user profile data for 59,946 San Francisco OkCupid users (a free online dating website) from June 2012. The data set includes typical user information, lifestyle variables, and text responses to 10 essay questions. We present four example analyses suitable for use in undergraduate introductory probability and statistics and data science courses that use R. The statistical and data science concepts covered include basic data visualization, exploratory data analysis, multivariate relationships, text analysis, and logistic regression for prediction

An Adhesive Peptide from the C-Terminal Domain of α-Synuclein for Single-Layer Adsorption of Nanoparticles onto Substrates

The two-dimensional (2D) homogeneous assembly of nanoparticle monolayer arrays onto a broad range of substrates constitutes an important challenge for chemistry, nanotechnology, and material science. α-Synuclein (αS) is an intrinsically disordered protein associated with neuronal protein complexes and has a high degree of structural plasticity and chaperone activity. The C-terminal domain of αS has been linked to the noncovalent interactions of this protein with biological targets and the activity of αS in presynaptic connections. Herein, we have systematically studied peptide fragments of the chaperone-active C-terminal sequence of αS and identified a 17-residue peptide that preserves the versatile binding nature of αS. Attachment of this short peptide to gold nanoparticles afforded colloidally stable nanoparticle suspensions that allowed the homogeneous 2D adhesion of the conjugates onto a wide variety of surfaces, including the formation of crystalline nanoparticle superlattices. The peptide sequence and the strategy reported here describe a new adhesive molecule for the controlled monolayer adhesion of metal nanoparticles and sets a stepping-stone toward the potential application of the adhesive properties of αSThis work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [BIO2015-70092-R, SAF2017-89890-R], the Xunta de Galicia (ED431C 2017/25, 2016-AD031, AGAUR (2017 SGR 324), and Centro Singular de Investigación de Galicia accreditation 2016–2019, ED431G/09), the ISCIII (COV20/00297), and the European Union (European Regional Development Fund – ERDF). X.S. acknowledges funding from the ERC (CONCERT-648201). IRB Barcelona is the recipient of a Severo Ochoa Award (Government of Spain). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Grant (DYNAP-677786), and a Young Investigator Grant from the HFSP (RGY0066/2017)S

EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor

ACKNOWLEDGEMENTS We thank J. M. Valverde (IRB) as well as the NMR facilities of the University of Barcelona (CCiT UB) and the Instituto de Química Física Rocasolano (IQFR, CSIC) for their assistance in, respectively, protein production and NMR. This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (Fellowship to E.D.M. and CancerTec grants to X.S.) MICINN (CTQ2009-08850 to X.S.), MINECO (BIO2012-31043 to X.S.; CTQ2014-56361-P to A.R), Marató de TV3 (102030 to X.S. and 102031 to E.E.P) the COFUND programme of the European Commission (C.T.W.P., A. R. and X.S.), the European Research Council (CONCERT, contract number 648201, to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.) the Serra Hunter Programme (E.E.P.) and AGAUR (SGR-2014-56RR14 to E.E.P). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)Peer reviewedPostprin

Gamma probe sentinel node localization and biopsy in breast cancer patients treated with a neoadjuvant chemotherapy scheme

The aim of this study was to analyse the accuracy of scintigraphic and gamma probe sentinel node (SN) localization in breast cancer patients who have been submitted to neoadjuvant chemotherapy (NC). Seventy-six patients with single breast cancer were included in the study, and were classified into two groups. Group 1 consisted of 40 women who had received NC, and Group 2 consisted of 36 women who did not receive NC. All patients received 111 MBq (3 mCi) of 99Tcm-nanocolloid in 3 ml, by peritumoural injection. Anterior and lateral thoracic scans were obtained 2 h post-injection. The following day (18-24 h post-injection) the patients underwent surgery and sentinel nodes were localized by using a gamma probe. Complete axillary lymph node dissection was performed in all patients. Histological analysis included haematoxylin-eosin in all cases and immunohistochemistry in 10 cases. In Group 1, SNs were localized in 36/40 patients, histological analysis was performed in 34 and there were four false negatives (22%). In Group 2, SNs were localized in 32/36 patients, histological analysis was performed in 29 and there were two false negatives (9%). Predictive negative values were 78% and 90% in Groups 1 and 2, respectively. In summary, sentinel node localization in breast cancer patients submitted to previous neoadjuvant chemotherapy is less accurate than in patients who do not receive this therapy. The procedure is not sufficiently accurate to localize the sentinel node, thus it cannot be recommended in these patients

A glutamine-based single ¿-helix scaffold to target globular proteins.

The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-helices. These interactions offer opportunities for therapeutic intervention but their modulation with small molecules is challenging because they bury large surfaces. Linear peptides that display the residues that are key for binding can be targeted to globular proteins when they form stable helices, which in most cases requires their chemical modification. Here we present rules to design peptides that fold into single α-helices by instead concatenating glutamine side chain to main chain hydrogen bonds recently discovered in polyglutamine helices. The resulting peptides are uncharged, contain only natural amino acids, and their sequences can be optimized to interact with specific targets. Our results provide design rules to obtain single α-helices for a wide range of applications in protein engineering and drug design.We thank Luis Serrano for help with the Agadir predictions and helpful discussions, Ben Lehner and Ernest Giralt for helpful discussions and the ICTS NMR facility, managed by the scientific and technological centers of the University of Barcelona (CCiT UB), for their help in NMR. B.M. acknowledges funding from the Asociación Española contra el Cáncer (FCAECC project #POSTD211371MATE). C.G. acknowledges a graduate fellowship from MINECO (PRE2018-084684). M.S.-N. acknowledges funding from MINECO (PID2020-119810RB-I00). M.S.-N. holds a Ramón y Cajal contract (RYC2018-024759-I) from the Spanish Ministry of Science, Innovation, and Universities. X.S. acknowledges funding from AGAUR (2017 SGR 324), MINECO (BIO2015-70092-R and PID2019-110198RB-I00), and the European Research Council (CONCERT, contract number 648201). B.B.K acknowledges funding from the Novo Nordisk Foundation (#NNF18OC0033926). M.O. acknowledges funding from the Instituto Nacional de Bioinformática, The EU BioExcel Centre of Excellence for HPC and the Spanish Ministry of Science (PID2021-122478NB-I00) and the Instituto de Salud Carlos III–Instituto Nacional de Bioinformatica (ISCIII PT 17/0009/0007 co-funded by the Fondo Europeo de Desarrollo Regional). M.O. is an ICREA Academy scholar and J.A. is a Juan de la Cierva fellow. M.C. was supported by institutional funds of the Max Planck Society. This project has been carried out using the resources of CSUC. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)

Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor

Polyglutamine (polyQ) tracts are low-complexity regions and their expansion is linked to certain neurodegenerative diseases. Here the authors combine experimental and computational approaches to find that the length of the androgen receptor polyQ tract correlates with its helicity and show that the polyQ helical structure is stabilized by hydrogen bonds between the Gln side chains and main chain carbonyl groups

EPI-001, a compound active against castration-resistant prostate cancer, targets transactivation unit 5 of the androgen receptor

Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by which this compound exerts its inhibitory activity is however not yet fully understood. Here we show, by using high resolution solution nuclear magnetic resonance spectroscopy, that EPI-001 selectively interacts with a partially folded region of the transactivation domain of the androgen receptor, known as transactivation unit 5, that is key for the ability of prostate cells to proliferate in the absence of androgens, a distinctive feature of castration-resistant prostate cancer. Our results can contribute to the development of more potent and less toxic novel androgen receptor antagonists for treating this disease

A glutamine-based single α-helix scaffold to target globular proteins

The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-helices. These interactions offer opportunities for therapeutic intervention but their modulation with small molecules is challenging because they bury large surfaces. Linear peptides that display the residues that are key for binding can be targeted to globular proteins when they form stable helices, which in most cases requires their chemical modification. Here we present rules to design peptides that fold into single α-helices by instead concatenating glutamine side chain to main chain hydrogen bonds recently discovered in polyglutamine helices. The resulting peptides are uncharged, contain only natural amino acids, and their sequences can be optimized to interact with specific targets. Our results provide design rules to obtain single α-helices for a wide range of applications in protein engineering and drug design.We thank Luis Serrano for help with the Agadir predictions and helpful discussions, Ben Lehner and Ernest Giralt for helpful discussions and the ICTS NMR facility, managed by the scientific and technological centers of the University of Barcelona (CCiT UB), for their help in NMR. B.M. acknowledges funding from the Asociación Española contra el Cáncer (FCAECC project #POSTD211371MATE). C.G. acknowledges a graduate fellowship from MINECO (PRE2018-084684). M.S.-N. acknowledges funding from MINECO (PID2020-119810RB-I00). M.S.-N. holds a Ramón y Cajal contract (RYC2018-024759-I) from the Spanish Ministry of Science, Innovation, and Universities. X.S. acknowledges funding from AGAUR (2017 SGR 324), MINECO (BIO2015-70092-R and PID2019-110198RB-I00), and the European Research Council (CONCERT, contract number 648201). B.B.K acknowledges funding from the Novo Nordisk Foundation (#NNF18OC0033926). M.O. acknowledges funding from the Instituto Nacional de Bioinformática, The EU BioExcel Centre of Excellence for HPC and the Spanish Ministry of Science (PID2021-122478NB-I00) and the Instituto de Salud Carlos III–Instituto Nacional de Bioinformatica (ISCIII PT 17/0009/0007 co-funded by the Fondo Europeo de Desarrollo Regional). M.O. is an ICREA Academy scholar and J.A. is a Juan de la Cierva fellow. M.C. was supported by institutional funds of the Max Planck Society. This project has been carried out using the resources of CSUC. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain).Peer reviewe

Entropy mapping of the outer electron radiation belt between the magnetotail and geosynchronous orbit

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94614/1/jgra21264.pd

Search for Decaying Dark Matter in the Virgo Cluster of Galaxies with HAWC

The decay or annihilation of dark matter particles may produce a steady flux of very-high-energy gamma rays detectable above the diffuse background. Nearby clusters of galaxies provide excellent targets to search for the signatures of particle dark matter interactions. In particular, the Virgo cluster spans several degrees across the sky and can be efficiently probed with a wide field-of-view instrument. The High Altitude Water Cherenkov (HAWC) observatory, due to its wide field of view and sensitivity to gamma rays at an energy scale of 300 GeV--100 TeV is well-suited for this search. Using 2141 days of data, we search for gamma-ray emission from the Virgo cluster, assuming well-motivated dark matter sub-structure models. Our results provide some of the strongest constraints on the decay lifetime of dark matter for masses above 10 TeV.Comment: 7 pages, 3 figures. Submitted to PR