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Let G $G$be an additive abelian group of size v $v$ . A k $k$ ‐subset D $D$of G $G$is called a (v,k,λ) $(v, k, \\lambda )$ ‐difference set if every non‐identity element in G $G$can be written in λ $\\lambda$ways as the difference of two elements in D $D$ . This letter proves the non‐existence of (pm,k,1) $(p^m, k, 1)$ ‐difference sets, for all prime p $p$and m>1 $m>1$ .

Methods for site-selective chemistry on proteins are in high demand for the synthesis of chemically modified biopharmaceuticals, as well as for applications in chemical biology, biosensors and more. Inadvertent N-terminal gluconoylation has been reported during expression of proteins with an N-terminal His tag. Here we report the development of this side-reaction into a general method for highly selective N-terminal acylation of proteins to introduce functional groups. We identify an optimized N-terminal sequence, GHHH n − for the reaction with gluconolactone and 4-methoxyphenyl esters as acylating agents, facilitating the introduction of functionalities in a highly selective and efficient manner. Azides, biotin or a fluorophore are introduced at the N-termini of four unrelated proteins by effective and selective acylation with the 4-methoxyphenyl esters. This Gly-His n tag adds the unique capability for highly selective N-terminal chemical acylation of expressed proteins. We anticipate that it can find wide application in chemical biology and for biopharmaceuticals. His-tagged proteins can undergo N-terminal acylation as an undesired side-reaction. Here, the authors utilize this to develop a method for highly selective acylation and further modification of peptides and proteins using an optimized His sequence and 4-methoxyphenyl esters as acyl donors.

Developing methodology for computing accurate forecasts of electricity prices in liberalised markets is necessary to improve the bids submitted to the market operator by both consumers and producers to maximise their benefits and utilities, respectively. Here, the authors propose the extraction of common factors from the 24-dimensional vector of prices, and using them for one-day-ahead forecasting. This methodology is based on the Pena-Box and Lee-Carter models and is able to take into account the multivariate structure of the data. The data selected to illustrate the proposed methodology are those from the Iberian Market in the period January 2007 to January 2009, and numerical results in terms of prediction accuracy have also been compared with those by Garcia-Martos et al, obtaining a statistically significant improvement. A very important feature of the proposed methodology, the Dynamic Factor Model (DFM) is that is a powerful tool for mid- and long-term forecasting. This is an important difference between DFM and other methodologies for which the accuracy dramatically degrades when increasing the forecasting horizon.

Peptide-based structures can be designed to yield artificial proteins with specific folding patterns and functions. Template-based assembly of peptide units is one design option, but the use of two orthogonal self-assembly principles, oligonucleotide triple helix and a coiled coil protein domain formation have never been realized for de novo protein design. Here, we show the applicability of peptide–oligonucleotide conjugates for self-assembly of higher-ordered protein-like structures. The resulting nano-assemblies were characterized by ultraviolet-melting, gel electrophoresis, circular dichroism (CD) spectroscopy, small-angle X-ray scattering and transmission electron microscopy. These studies revealed the formation of the desired triple helix and coiled coil domains at low concentrations, while a dimer of trimers was dominating at high concentration. CD spectroscopy showed an extraordinarily high degree of α-helicity for the peptide moieties in the assemblies. The results validate the use of orthogonal self-assembly principles as a paradigm for de novo protein design. Peptide and oligonucleotide systems are known to self-assemble both in nature and artificial systems. Here, the authors combine both forms of self-assembly through the synthesis of peptideoligonucleotide conjugates and show formation of a three-helix structure that dimerises at higher concentrations.

Background Up-to-date cancer burden indicators are essential to support political decision making, to enable epidemiological research and as an information source for citizens. Nevertheless, observed cancer incidence and mortality suffer from an endemic registration delay in the data production workflow. To overcome this, the European Commission's Joint Research Centre in collaboration with the WHO's International Agency for Research on Cancer have computed estimates of cancer incidence and mortality, for the year 2020 and for European countries, in the framework of the European Cancer Information System (ECIS). Methods Predicted values for the year 2020 are based on the incidence data of more than 150 European population-based cancer registries included in the ECIS, and on the WHO mortality database. According to previously developed and applied methodology, the estimates of 2020 cancer incidence and mortality rates were produced for 40 European countries, on the basis of the most recent time trends of observed data, where possible. Estimated rates were then applied to the projected 2020 population from EUROSTAT, to calculate the predicted number of new cases and deaths for 2020 in each European country. Results The number of new cancer cases and deaths in 2020 has been estimated per country by sex and age group, for 25 major cancer sites. The results are included and disseminated through the ECIS web application (https://ecis.jrc.ec.europa.eu/). Conclusions The release of up-to-date cancer incidence and mortality estimates is of crucial importance in supporting evidence-based EU cancer policies. The homogeneity of the estimation methods applied throughout Europe guarantees the comparability of the estimated values between countries. Reliable and comparable estimates enable highlighting differences between countries in cancer incidence and mortality, thus facilitating the identification of possible intervention areas. Key messages The EC’s JRC, in collaboration with WHO’s IARC, have computed estimates of cancer incidence and mortality for the year 2020 for European countries, in the framework of the ECIS. The number of new cancer cases and deaths in 2020 has been estimated in 40 European countries for 25 major cancer sites and included in the ECIS web application (https://ecis.jrc.ec.europa.eu/).

Galectin-3 is considered a cancer biomarker and bioindicator of fibrosis and cardiac remodeling and, therefore, it is desirable to develop convenient methods for its detection. Herein, an approach based on the development of multivalent electrochemical probes with high galectin-3 sensing abilities is reported. The probes consist of multivalent presentations of lactose–ferrocene conjugates scaffolded on poly (amido amine) (PAMAM) dendrimers and gold nanoparticles. Such multivalent lactose–ferrocene conjugates are synthesized by coupling of azidomethyl ferrocene–lactose building blocks on alkyne-functionalized PAMAM, for the case of the glycodendrimers, and to disulfide-functionalized linkers that are then used for the surface modification of citrate-stabilized gold nanoparticles. The binding and sensing abilities toward galectin-3 of both ferrocene-containing lactose dendrimers and gold nanoparticles have been evaluated by means of isothermal titration calorimetry, UV–vis spectroscopy, and differential pulse voltammetry. The highest sensitivity by electrochemical methods to galectin-3 was shown by lactosylferrocenylated gold nanoparticles, which are able to detect the lectin in nanomolar concentrations.

Interferon (IFN)-γ release assays (IGRAs) are used to diagnose latent tuberculosis (TB) infection (LTBI). To improve the accuracy of these tests, different approaches, such as alternative cytokine detection and using different antigens, are considered. Following this purpose, this study aims to evaluate the addition of EspC, EspF and Rv2348-B to those present in the QuantiFERON-TB Gold In-Tube (QFN-G-IT). We included 115 subjects: 74 active TB patients, 17 LTBI individuals and 24 healthy controls. Whole blood samples were collected in QFN-G-IT and in-house tubes containing different combinations of EspC, EspF and Rv2348-B, together with ESAT-6, CFP-10, and TB7.7. After overnight incubation at 37 ºC, plasma was harvested and IFN-γ quantified. IFN-γ levels in the QFN-G-IT and in-house tubes correlated very good (Spearman Rho(r) > 0.86). In-house antigen combinations distinguished healthy individuals from those with active TB and LTBI (specificities and sensitivities higher than 87.5% and 96.3%, respectively [AUC > 0.938]). Adding EspC, EspF and Rv2348-B, increased the sensitivity of the test, being the addition of EspC and Rv2348-B the combination that yielded a higher sensitivity with no specificity loss. Addition of these antigens could improve diagnosis in patients with impaired or immature immune response who are at high risk of developing TB.

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43–51%) overall increase in the risk of a primary cancer after NHL. A strongly significant ( P <0.001) increase was observed for cancers of the lip, tongue, oropharynx * , stomach, small intestine, colon * , liver, nasal cavity * , lung, soft tissues * , skin melanoma * , nonmelanoma skin * , bladder * , kidney * , thyroid * , Hodgkin's lymphoma * , lymphoid leukaemia * and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.

Rapid antigen detection tests (RADTs) are immunoassays that produce results in 15 min or less, have low sensitivity (50 %), but high specificity (95 %). We studied the clinical impact and laboratory savings of a diagnostic algorithm for influenza infection using RADTs as a first-step technique during the influenza season. From January 15th to March 31st 2014, we performed a diagnostic algorithm for influenza infection consisting of an RADT for all respiratory samples received in the laboratory. We studied all the patients with positive results for influenza infection, dividing them into two groups: Group A with a negative RADT but positive reference tests [reverse transcription polymerase chain reaction (RT-PCR) and/or culture] and Group B with an initial positive RADT. During the study period, we had a total of 1,156 patients with suspicion of influenza infection. Of them, 217 (19 %) had a positive result for influenza: 132 (11 %) had an initial negative RADT (Group A) and 85 (7 %) had a positive RADT (Group B). When comparing patients in Group A and Group B, we found significant differences, as follows: prescribed oseltamivir (67 % vs. 82 %; p  = 0.02), initiation of oseltamivir before 24 h (89 % vs. 97 %; p  = 0.03), antibiotics prescribed (89 % vs. 67 %; p  = <0.01), intensive care unit (ICU) admissions after diagnosis (23 % vs. 14 %; p  = 0.05), and need for supplementary oxygen (61 % vs. 47 %; p  = 0.01). An influenza algorithm including RADTs as the first step improves the time of administration of proper antiviral therapy, reduces the use of antibiotics and ICU admissions, and decreases hospital costs.

We report on a strategy to model both the size ( d ) and the polydispersity ( PdI ) of magnetic oxygen-sensitive nanoparticles with a typical size of 200 nm in order to increase the surface area. The strategy is based on experimental design and Response Surface Methodology. Nanoparticles were prepared by miniemulsion solvent evaporation of solutions of poly(styrene-co-maleic anhydride). Features of this strategy include (1) a quick selection of the most important variables that govern d and PdI ; (2) a better understanding of the parameters that affect the performance of the polymer; and (3) optimized conditions for the synthesis of nanoparticles of targeted d and PdI . The results were used to produce nanoparticles in sizes that range from 100 to 300 nm and with small polydispersity. The addition of a platinum porphyrin complex that acts as a luminescent probe for oxygen and of magnetite (Fe 3 O 4 ) to the polymeric particles, did not affect d and PdI , thus demonstrating that this strategy simplifies their synthesis. The resulting luminescent and magnetic sensor nanoparticles respond to dissolved oxygen with sensitivity (Stern-Volmer constant) of around 35 bar −1 . Figure ᇵ