Finite sections of the Fibonacci Hamiltonian

We study finite but growing principal square submatrices $A_n$ of the one- or two-sided infinite Fibonacci Hamiltonian $A$. Our results show that such a sequence $(A_n)$, no matter how the points of truncation are chosen, is always stable -- implying that $A_n$ is invertible for sufficiently large $n$ and $A_n^{-1}\to A^{-1}$ pointwise

Jesus Tradition and the Gospel of John. The Inspiration of Memory and the Truth of Writing

L’Evangeli de Joan és una font important per a reconstruir les circumstàncies de la vida i la mort de Jesús. Aquest Evangeli és un document de la tradició de Jesús que combina la fe en Crist amb un interès teològic en la seva vida i la seva mort, en la seva predicació i en la seva pregària, el seu poder i la seva passió. L’Evangeli de Joan és també un llibre amb una història i un discurs que necessita lectors inspirats per a entendre la veritat de Jesús i el missatge d’amor de Déu. El camí per a reconstruir l’anomenat «Jesús històric» va des dels sinòptics, que donen la informació i orientació bàsiques, fins a Joan, que il·lustra amb els colors de Jesús el fons sobre el qual l’evangeli de Jesús s’ha d’explicar i llegir com a evangeli de Déu

The LED Paradox: How Light Pollution Challenges Experts to Reconsider Sustainable Lighting

In the 21st century, the notion of “sustainable lighting” is closely associated with LED technology. In the past ten years, municipalities and private light users worldwide have installed light-emitting diodes in urban spaces and public streets to save energy. Yet an increasing body of interdisciplinary research suggests that supposedly sustainable LED installations are in fact unsustainable, because they increase light pollution. Paradoxically, blue-rich cool-white LED lighting, which is the most energy-efficient, also appears to be the most ecologically unfriendly. Biologists, physicians and ecologists warn that blue-rich LED light disturbs the circadian day-and-night rhythm of living organisms, including humans, with potential negative health effects on individual species and whole ecosystems. Can the paradox be solved? This paper explores this question based on our transdisciplinary research project Light Pollution—A Global Discussion. It reveals how light pollution experts and lighting professionals see the challenges and potential of LED lighting from their different viewpoints. This expert feedback shows that “sustainable LED lighting” goes far beyond energy efficiency as it raises complex design issues that imply stakeholder negotiation. It also suggests that the LED paradox may be solved in context, but hardly in principle

Of bits and bugs

Pur-α is a nucleic acid-binding protein involved in cell cycle control, transcription, and neuronal function. Initially no prediction of the three-dimensional structure of Pur-α was possible. However, recently we solved the X-ray structure of Pur-α from the fruitfly Drosophila melanogaster and showed that it contains a so-called PUR domain. Here we explain how we exploited bioinformatics tools in combination with X-ray structure determination of a bacterial homolog to obtain diffracting crystals and the high-resolution structure of Drosophila Pur-α. First, we used sensitive methods for remote-homology detection to find three repetitive regions in Pur-α. We realized that our lack of understanding how these repeats interact to form a globular domain was a major problem for crystallization and structure determination. With our information on the repeat motifs we then identified a distant bacterial homolog that contains only one repeat. We determined the bacterial crystal structure and found that two of the repeats interact to form a globular domain. Based on this bacterial structure, we calculated a computational model of the eukaryotic protein. The model allowed us to design a crystallizable fragment and to determine the structure of Drosophila Pur-α. Key for success was the fact that single repeats of the bacterial protein self-assembled into a globular domain, instructing us on the number and boundaries of repeats to be included for crystallization trials with the eukaryotic protein. This study demonstrates that the simpler structural domain arrangement of a distant prokaryotic protein can guide the design of eukaryotic crystallization constructs. Since many eukaryotic proteins contain multiple repeats or repeating domains, this approach might be instructive for structural studies of a range of proteins

"Padre, perdónalos"... El perdón "difícil" y la novedad de Jesús

El presente ensayo propone un diálogo sobre el perdón con el pensamiento filosófico de H. Arendt y P. Ricoeur y la reflexión bíblico-teológica de C. di Sante y L. Basset. En él se articulan la necesidad del perdón en la vida cotidiana y la seriedad de un perdón “difícil” que respete la verdad y la dignidad del ofendido y del ofensor y se arriesgue a restaurar la relación personal. La novedad de Jesús, ofrecida a partir de su oración y entrega en la cruz (cf. Lc 23,34) y de su resurrección, abre la posibilidad de ir más allá de la cuenta de los males cometidos; más aún, más allá de la culpa, para acceder por amor a una vida digna de ser celebrada con los otros.This essay proposes a dialogue on forgiveness with the philosophical thought of H. Arendt and P. Ricoeur and biblical-theological reflection of C. di Sante and L. Basset. It articulates the need for forgiveness in daily life and the seriousness of a “difficult” pardon that respects the truth and dignity of the victim and the offender and takes the risk to restore personal relationships. The novelty of Jesus, offered in his prayer and sacrifice in the cross (cf. Lk 23:34) and his resurrection, opens the possibility to go beyond the account of the wrongs committed; even more, beyond guilt, in order to access a life of love worthy of being celebrated with others

Transcriptome- and genome-targeted cancer immunotherapy

Precision oncology targets cancer cells using antibodies or small-molecule inhibitors directed against a mutated or overexpressed oncogenic protein. Targeted drugs are developed individually for each protein at huge costs, and only a small fraction of proteins can be targeted at all. We propose to target cancer cells through their mutated transcripts and genomes instead, leveraging their mutations to alert the immune system. Nanoparticles delivered systemically could be loaded with RNA- or DNA-directed Cas mRNA and guide RNAs targeting multiple patient-specific cancer mutations. In transcriptome-targeted immunotherapy, patient-specific guide RNAs would target CRISPR/Cas to cleave the transcripts mutated in the patient's cancer cells. The cleaved transcripts would hybridize with patient-specific 5'-triphosphate RNAs to form blunt-ended dsRNAs, triggering RIG-I and type-I interferon signaling that induces a strong systemic, long-lasting immune response against all cancer cells. This approach could potentially work for all cancers and prevent resistance by targeting many mutations jointly

Do inhibitors targeted against mutant oncogenic kinases act via kinase degradation-induced immune activation?

Targeted cancer therapies by small-molecule inhibitors of receptor tyrosine and other kinases have achieved great success in recent years. Most targeted medications specifically inhibit a protein kinase mutated in the patient's tumor. Although many possible mechanisms have been investigated, the drugs' astounding efficacies are not well understood. We propose a unifying mechanism of action. Strong binding by the inhibitor could lead to increased ubiquitination and degradation by the proteasome, boosting the presentation of kinase-associated neoantigen peptides. This would facilitate tumor cell recognition by T cells, leading to a sustained immune attack. The model suggests that the as yet inevitable failure to shrink tumors further after a few months might be caused by a transition to chronic inflammation. If true, the model has a multitude of implications for cancer and clinical research

Gottes Wort im Munde Jesu uns sein Echo im Neuen Testament

El text, ple de connotacions, que recorda tan el Sinaí com la promesa profètica d’una nova aliança, es refereix a la comunitat, a la comunitat de fe dels cristians vius, com al lloc on l’anunci es fa concret. L’autor apostòlic també és lector: mirant-se els corintis llegeix la carta que ell mateix ha escrit: L’autor inspirat suposa lectors inspirats. El que crea el lligam és «l’Esperit del Déu vivent». Se serveix d’homes febles que no solament anuncien, sinó que també l’escolten. La carta, que parla de tot això, no és pas ella mateixa Paraula de Déu, sinó que en dóna testimoni, fa sentir el seu ressó perquè arribi a tots els temps i espais, perquè Jesús ha ressuscitat d’entre els morts i està tant proper als missatgers, com als receptors, als que ensenyen, com als que aprenen, als que parlen, com als que escolten. La Paraula de Déu en boca de Jesús troba el seu ressò en la carta de l’Apòstol i en tot el NT.The text, full of connotations, that harks to both the Sinai and to the prophetic promise of a new alliance, refers to the community, to the community of the faith of living Christians, as a place where the annunciation comes into its own. The apostolic author is also a reader; he reads the letter from the Corinthians that he himself has written: An inspired author presupposes inspired readers. What creates the link is «the Spirit of the living God». He profits from weak men who not only herald, but who also listen. The letter that refers to all of this is not of itself the Word of God, but it gives testimony and makes its voice heard because it reaches out to all epochs and places, because Jesus has resurrected from among the dead and is as proximate to the messengers as he is to the recipients, to those who instruct as to those who learn, to those who speak as to those who listen. The word of God as spoken by Jesus is echoed in the Apostle’s letter and throughout the whole New Testament

The immune activation model for targeted inhibitors of mutated oncogenic kinases

Targeted cancer therapies by small-molecule inhibitors of receptor tyrosine and other kinases have achieved great success in recent years. Most targeted medications specifically inhibit a protein kinase mutated in the patient's tumor. Although many possible mechanisms have been investigated, the drugs' astounding efficacies are not well understood. Here we propose a unifying mechanism of action. Strong binding by the inhibitor could lead to increased ubiquitination and degradation by the proteasome, boosting the presentation of kinase-associated neoantigen peptides. This could facilitate tumor cell recognition by T cells, leading to a sustained immune attack. We discuss implications for experimental and clinical cancer research