Massively parallel computing on an organic molecular layer

Current computers operate at enormous speeds of ~10^13 bits/s, but their principle of sequential logic operation has remained unchanged since the 1950s. Though our brain is much slower on a per-neuron base (~10^3 firings/s), it is capable of remarkable decision-making based on the collective operations of millions of neurons at a time in ever-evolving neural circuitry. Here we use molecular switches to build an assembly where each molecule communicates-like neurons-with many neighbors simultaneously. The assembly's ability to reconfigure itself spontaneously for a new problem allows us to realize conventional computing constructs like logic gates and Voronoi decompositions, as well as to reproduce two natural phenomena: heat diffusion and the mutation of normal cells to cancer cells. This is a shift from the current static computing paradigm of serial bit-processing to a regime in which a large number of bits are processed in parallel in dynamically changing hardware.Comment: 25 pages, 6 figure

Delik Pornografi Dikaitkan Dengan Kebebasan Pers

Kebebasan pers dalam era reformasi tidak dapat diwujudkan dengan sebebas-bebasnya tanpa melihat adanya batasan-batasan, baik oleh peraturan tertulis ya itu peraturan perundang-undangan atau peraturan tidak tertulis yang berlaku di dalam masyarakat. Delik pornografi dapat diartikan sebagai perbuatan pidana yang dilakukan oleh seseorang yang menyatakan pikirannya dalam sebuah media cetak , pernyataan pikiran tersebut secara sengaja dibuat untuk membangkitkan nafsu pembaca, dan diedarkan untuk umum tanpa mengenal batasan usia dan tempat , isi media cetak tersebut tidak dapat diambil manfaatnya bahkan cenderung melar1ggar norma-norma yang berlaku dalam masyarakat serta peraturan perundang-undangan yang ada, sehingga perbuatan tersebut dapat diancam pidana penjara atau denda . Seharusnya kebebasan pers ditujukan untuk melaksanakan tugas dan fungsi pers dengan tepat dan seimbang antara penyampainan informasi, pendidikan, hiburan dan kontrol sosial, sehingga pers dapat memenuhi kebutuhan masyarakat yang sebenarnya yaitu untuk memperoleh berita yang memang diperlukan

Surfactants, nanomedicines and nanocarriers: a critical evaluation on clinical trials

Advances, perspectives and innovation in drug delivery have increased in recent years; however, there is limited information available regarding the actual presence of surfactants, nanomed-icines and nanocarriers in investigational medicinal products submitted as part of a request for authorization of clinical trials, particularly for those authorized in the European Economic Area. We retrieve, analyze and report data available at the Clinical Trial Office of the Italian Medicines Agency (AIFA), increasing the transparency and availability of relevant information. An analysis of quality documentation submitted along with clinical trials authorized by the AIFA in 2018 was carried out, focusing on the key terms “surfactant”, “nanomedicine” and “nanocarrier”. Results suggest potential indications and inputs for further reflection and actions for regulators to actively and safely drive innovation from a regulatory perspective and to transpose upcoming evolution of clinical trials within a strong regulatory framework

Modeling of negative Poisson’s ratio (auxetic) crystalline cellulose Iβ

Energy minimizations for unstretched and stretched cellulose models using an all-atom empirical force field (Molecular Mechanics) have been performed to investigate the mechanism for auxetic (negative Poisson’s ratio) response in crystalline cellulose Iβ from kraft cooked Norway spruce. An initial investigation to identify an appropriate force field led to a study of the structure and elastic constants from models employing the CVFF force field. Negative values of on-axis Poisson’s ratios nu31 and nu13 in the x1-x3 plane containing the chain direction (x3) were realized in energy minimizations employing a stress perpendicular to the hydrogen-bonded cellobiose sheets to simulate swelling in this direction due to the kraft cooking process. Energy minimizations of structural evolution due to stretching along the x3 chain direction of the ‘swollen’ (kraft cooked) model identified chain rotation about the chain axis combined with inextensible secondary bonds as the most likely mechanism for auxetic response

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

Background: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs). Summary: Since immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions. Key messages: Many clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, costeffective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts

Using Clinical Evidence in a national continuing medical education program in Italy.

No abstrac

Breaking barriers in triple negative breast cancer (TNBC) – Unleashing the power of antibody-drug conjugates (ADCs)

Antibody-drug conjugates (ADCs) represent a novel class of molecules composed of a recombinant monoclonal antibody targeted to a specific cell surface antigen, conjugated to a cytotoxic agent through a cleavable or non-cleavable synthetic linker. The rationale behind the development of ADCs is to overcome the limitations of conventional chemotherapy, such as the narrow therapeutic window and the emergence of resistance mechanisms. ADCs had already revolutionized the treatment algorithm of HER2-positive breast cancer. Currently, emergent non-HER2 targeted ADCs are gaining momentum, with special focus on triple-negative disease therapeutic landscape. Sacituzumab govitecan (SG) is an ADC consisting of a humanized monoclonal antibody hRS7 targeting trophoblast cell surface antigen 2 (Trop2), linked to the topoisomerase I inhibitor SN-38 by a hydrolysable linker. It currently stands as the only non-HER2 targeted ADC that already received approval for the treatment of unresectable locally advanced or metastatic triple negative breast cancer (TNBC) in patients who had received two or more prior systemic therapies, with at least one for advanced disease. The purpose of these review is to analyze the available evidence regarding ADCs in TNBC, alongside with providing an overview on the ongoing and future research horizons in this field

Photoionization Dynamics of the Tetraoxo Complexes OsO4 and RuO4

The photoionization dynamics of OsO4 and RuO4, chosen as model systems of small-size mononuclear heavy-metal complexes, has been theoretically studied by the time-dependent density functional theory (TDDFT). Accurate experimental measurements of photoionization dynamics as a benchmarking test for the theory are reported for the photoelectron asymmetry parameters of outer valence ionizations of OsO4, measured in the 17-90 eV photon energy range. The theoretical results are in good agreement with the available experimental data. The observed dynamical behavior of partial cross sections and asymmetry parameters has been related to both the coupling to the continuum of discrete excited states, giving strong modulations in the photon energy dependency, and the atomic composition of the initial ionized states, which determines the rate of decay of ionization probability for increasing excitation energies. Overall, an extensive analysis of the photoionization dynamics for valence and core orbitals is presented, showing good agreement with all the available experimental data. This provides confidence for the validity of the TDDFT approach in describing photoionization of heavy transition element compounds, with the perspective of being used for larger systems. Further experimental work is suggested for RuO4 to gather evidence of the sensitivity of the theoretical method to the nature of the metal atom

PyfastSPM: A Python package to convert 1D FastSPM data streams into publication quality movies

peer reviewedSince the invention of scanning probe microscopy, researchers have desired to use this technique to monitor sub-second surface dynamics with atomic spatial resolution. A recently presented add-on electronics module enables the speed-up of existing, conventional scanning probe microscopes without any modification of the actual instrument. The resulting one-dimensional (1D) data stream, recorded while the tip oscillates in a sinusoidal motion, has to be reconstructed into a layered rectangular matrix in order to visualize the movie. The Python-based pyfastspm package performs this conversion, while also correcting for sample tilt, noise frequencies, piezo creep, and thermal drift. Quick automatic conversion even of considerable batches of data is achieved by efficient algorithms that bundle time-expensive steps, such as interpolation based on Delaunay triangulation

Valutazione della bontà educativa dei casi clinici di ECCE, il programma di formazione a distanza (FAD) basato sulle evidenze destinato ai medici italiani

OBIETTIVO. Valutare la qualit\ue0 dei percorsi clinici di un programma FAD destinato a tutti i medici italiani verificando le loro propriet\ue0 psicometriche. METODI. AIFA ha lanciato un programma nazionale di sostegno dell\u2019informazione indipendente tramite la distribuzione gratuita ai medici di Clinical Evidence (CE). Sulla base dei contenuti di CE \ue8 stato sviluppato un programma FAD all\u2019interno del sistema di Educazione Continua in Medicina (ECM) dal nome ECCE, anch\u2019esso gratuito. I medici hanno accesso a CE online e ai relativi percorsi clinici. Superandoli il medico ottiene i crediti ECM. Nel corso del 2006 \ue8 stata valutata la qualit\ue0 di un campione di venti percorsi, su un totale di 120. La valutazione formale della qualit\ue0 dei 20 casi selezionati \ue8 avvenuta attraverso le seguenti dimensioni psicometriche: Giudizio generale sui percorsi da parte degli utilizzatori (face validity); Valutazione dei contenuti da parte di clinici esperti (content validity); Valutazione della attendibilit\ue0 del test attraverso un criterio di consistenza interna (internal reliability); Difficolt\ue0 degli items; Capacit\ue0 del test di rilevare una modificazione della conoscenza (responsiveness). RISULTATI: Alcune migliaia di utenti hanno partecipato alla valutazione fornendo esiti contrastanti: mentre la face e content validity sono state valutate positivamente dagli utilizzatori e dai clinici esperti, altri parametri come l\u2019internal reliability e la difficolt\ue0 degli items hanno mostrato grande variabilit\ue0 tra i percorsi. Sette casi mostrano un valore di alpha complessivo inferiore a 0.50 (soglia minima di affidabilit\ue0). I casi si sono dimostrati nel complesso medio-facili. Facendo riferimento solo alle proprie conoscenze i partecipanti rispondevano correttamente a circa a met\ue0 delle domande. La lettura delle fonti era associata a un miglioramento della performance (miglioramento prima-dopo statisticamente significativo, p<0.05 per 19/20 percorsi). CONCLUSIONI: L\u2019importante eterogeneit\ue0 tra percorsi dimostrerebbe come differenti casi possono analizzare in maniera molto disomogenea il domino conoscenza evidence-based derivata dai contenuti di CE