Investigation of electronic trap states in organic photovoltaic materials by current-based deep level transient spectroscopy

Current-based deep level transient spectroscopy was used to study trap states in poly(3- hexylthiophene-2,5-diyl) (P3HT), [6,6]-phenyl-C61 butyric acid methyl ester (PCBM) and P3HT:PCBM blend. The obtained spectra showed traps of 87 meV activation energy in pure P3HT and 21 meV for PCBM. The blend shows a complex emission rate spectrum consisting of several different emission rate bands in the range of (0.1-30) s^-1, yielding activation energies between about 30 meV and 160 meV.Comment: 4 pages, 3 figure

Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer: Updates and Challenges

Colorectal cancer (CRC) is a leading cause of death among cancer patients. This heterogeneous disease is characterized by alterations in multiple molecular pathways throughout its development. Mutations in RAS, along with the mismatch repair gene deficiency, are currently routinely tested in clinics. Such biomarkers provide information for patient risk stratification and for the choice of the best treatment options. Nevertheless, reliable and powerful prognostic markers that can identify “high-risk” CRC patients, who might benefit from adjuvant chemotherapy, in early stages, are currently missing. To bridge this gap, genomic information has increasingly gained interest as a potential method for determining the risk of recurrence. However, due to several limitations of gene-based signatures, these have not yet been clinically implemented. In this review, we describe the different molecular markers in clinical use for CRC, highlight new markers that might become indispensable over the next years, discuss recently developed gene expression-based tests and highlight the challenges in biomarker research

PrACTiC: A Predictive Algorithm for Chemoradiotherapy-Induced Cytopenia in Glioblastoma Patients

Background. Chemotherapy-induced cytopenia is the most frequent side effect of chemoradiotherapy in glioblastoma patients which may lead to reduced delivery of treatment. *is study aims to develop a predictive model that is able to forecast the cytopenia induced by temozolomide (TMZ) during concomitant chemoradiotherapy. Methods. Medical records of 128 patients with newly diagnosed glioblastoma were evaluated to extract the baseline complete blood test before and during the six weeks of chemoradiotherapy to create a dataset for the development of ML models. Using the constructed dataset, different ML algorithms were trained and tested. Results. Our proposed algorithm achieved accuracies of 85.6%, 88.7%, and 89.3% in predicting thrombocytopenia, lymphopenia, and neutropenia, respectively. Conclusions. *e algorithm designed and developed in this study, called PrACTiC, showed promising results in the accurate prediction of thrombocytopenia, neutropenia, and lymphopenia induced by TMZ in glioblastoma patients. PrACTiC can provide valuable insight for physicians and help them to make the necessary treatment modifications and prevent the toxicitie

Data format standards in analytical chemistry

Research data is an essential part of research and almost every publication in chemistry. The data itself can be valuable for reuse if sustainably deposited, annotated and archived. Thus, it is important to publish data following the FAIR principles, to make it findable, accessible, interoperable and reusable not only for humans but also in machine-readable form. This also improves transparency and reproducibility of research findings and fosters analytical work with scientific data to generate new insights, being only accessible with manifold and diverse datasets. Research data requires complete and informative metadata and use of open data formats to obtain interoperable data. Generic data formats like AnIML and JCAMP-DX have been used for many applications. Special formats for some analytical methods are already accepted, like mzML for mass spectrometry or nmrML and NMReDATA forNMRspectroscopy data. Other methods still lack common standards for data. Only a joint effort of chemists, instrument and software vendors, publishers and infrastructure maintainers can make sure that the analytical data will be of value in the future. In this review, we describe existing data formats in analytical chemistry and introduce guidelines for the development and use of standardized and open data formats

Asymmetric Interplay Between K+ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K+ Channel Blocker Release

Modulating the activity of ion channels by blockers yields information on both the mode of drug action and on the biophysics of ion transport. Here we investigate the interplay between ions in the selectivity filter (SF) of K+ channels and the release kinetics of the blocker tetrapropylammonium in the model channel KcvNTS. A quantitative expression calculates blocker release rate constants directly from voltage-dependent ion occupation probabilities in the SF. The latter are obtained by a kinetic model of single-channel currents recorded in the absence of the blocker. The resulting model contains only two adjustable parameters of ion-blocker interaction and holds for both symmetric and asymmetric ionic conditions. This data-derived model is corroborated by 3D reference interaction site model (3D RISM) calculations on several model systems, which show that the K+ occupation probability is unaffected by the blocker, a direct consequence of the strength of the ion-carbonyl attraction in the SF, independent of the specific protein background. Hence, KcvNTS channel blocker release kinetics can be reduced to a small number of system-specific parameters. The pore-independent asymmetric interplay between K+ and blocker ions potentially allows for generalizing these results to similar potassium channels

Identification of Intrahelical Bifurcated H‑Bonds as a New Type of Gate in K+ Channels

Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K+ channels, KcvS and KcvNTS. These small viral encoded K+ channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K+ channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular dynamics simulations show that the difference in open probability is caused by one long closed state in KcvS. This state is structurally created in the tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The resulting kink in the inner transmembrane domain swings the aromatic rings from downstream Phes in the cavity of the channel, which blocks ion flux. The frequent occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a similar mechanism could also occur in the gating of other ion channels. Includes Supporting Informatio

Identification of Intrahelical Bifurcated H‑Bonds as a New Type of Gate in K+ Channels

Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K+ channels, KcvS and KcvNTS. These small viral encoded K+ channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K+ channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular dynamics simulations show that the difference in open probability is caused by one long closed state in KcvS. This state is structurally created in the tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The resulting kink in the inner transmembrane domain swings the aromatic rings from downstream Phes in the cavity of the channel, which blocks ion flux. The frequent occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a similar mechanism could also occur in the gating of other ion channels. Includes Supporting Informatio

Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers.

Biosimilars present a necessary and timely opportunity for physicians, patients and healthcare systems. If suitably developed clinically, manufactured to the correct standards and used appropriately, they can positively impact on the financial sustainability of healthcare systems. A critical consideration regarding the introduction of biosimilars into the clinic centres on the required information concerning all the respective procedures. This position paper aims to describe the issues revolving around biosimilars that are relevant to the field of oncology, especially the prescribers. More specifically, we discuss aspects related to definition, forms of biosimilars, labelling, extrapolation, interchangeability, switching, automatic substitution, clinical standards on safety and efficacy, responsibilities among prescribers and pharmacists, potential impact on financial burden in healthcare and the current scenario and future prospects of biosimilars in Europe and the rest of the world

Os Momentos de transição nas rotinas de creche e de jardim de infância

Relatório do Projeto de Investigação Mestrado em Educação Pré-Escolar Versão Definitiva JaneiroO presente Relatório do Projeto de Investigação representa um estudo transversal alicerçado nas vivências ocorridas nos contextos de estágio, por outras palavras, no estágio em Creche e o no estágio em Jardim de Infância, no âmbito do Mestrado em Educação Pré-Escolar. No estudo participaram as duas Educadoras Cooperantes e os respetivos grupos de crianças. A temática em estudo consiste nos Momentos de Transição, isto é, os momentos em que as crianças transitam de uma atividade para a seguinte, e a metodologia que se considera mais apropriada ao estudo empírico posiciona-se na abordagem da investigação-ação. O método de recolha de informação baseia-se na observação participante, nas notas de campo e na análise documental, sendo complementada com inquéritos por questionário apresentados às Educadoras Cooperantes. Em jeito de complementaridade, articulam-se as experiências vivenciadas nos contextos. Este Projeto de Investigação tem como intencionalidade, refletir acerca da relação existente entre as conceções das Educadoras Cooperantes e as suas práticas pedagógicas, bem como, implementar melhorias, nas salas dos contextos de estágio, no que diz respeito à gestão dos momentos de transição. A partir desta investigação, é possível compreender que os momentos de transição são, de facto, valorizados nas conceções das Educadoras Cooperantes como momentos que requerem atenção e planeamento, porém efetivamente nem sempre a intervenção é congruente com o que defendem.This Report of the Investigation Project represents a cross-sectional study based on experiences that occured in the two internships - on nursery and on kindergarten. The two Cooperating Educators and their respective groups of children had participated in the study. The theme under study consist in the Moments of Transition, that is, the moments when the children move from one activity to the next one, and the methodology which is considered more appropriated to the empirical study is positioned in the action-research approach. The collecting information method is based on participant observation, field notes and document analysis, being complemented with questionnaire surveys presented to the Cooperating Educators. In a way of complementarity, the experiences lived in the contexts are articulated. This Investigation Project intends to reflect about the relationship between the Cooperating Educators concepts and their practices, it also intends to implement improvements in the rooms of the internship contexts, when it comes to the management of transition moments. From this investigation, it is possible to understand that transition moments are, in fact, valued in the Cooperative Educators conceptions as moments that require attention and planning, however, the intervention is not always consistent with what they defend