An Organic Borate Salt with Superior p‐Doping Capability for Organic Semiconductors

Molecular doping allows enhancement and precise control of electrical properties of organic semiconductors, and is thus of central technological relevance for organic (opto‐) electronics. Beyond single‐component molecular electron acceptors and donors, organic salts have recently emerged as a promising class of dopants. However, the pertinent fundamental understanding of doping mechanisms and doping capabilities is limited. Here, the unique capabilities of the salt consisting of a borinium cation (Mes2B+; Mes: mesitylene) and the tetrakis(penta‐fluorophenyl)borate anion [B(C6F5)4]− is demonstrated as p‐type dopant for polymer semiconductors. With a range of experimental methods, the doping mechanism is identified to comprise electron transfer from the polymer to Mes2B+, and the positive charge on the polymer is stabilized by [B(C6F5)4]−. Notably, the former salt cation leaves during processing and is not present in films. The anion [B(C6F5)4]− even enables the stabilization of polarons and bipolarons in poly(3‐hexylthiophene), not yet achieved with other molecular dopants. From doping studies with high ionization energy polymer semiconductors, the effective electron affinity of Mes2B+[B(C6F5)4]− is estimated to be an impressive 5.9 eV. This significantly extends the parameter space for doping of polymer semiconductors.Peer Reviewe

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p 10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features

Serodiagnosis of Echinococcus spp. Infection: Explorative Selection of Diagnostic Antigens by Peptide Microarray

Crude or purified, somatic or metabolic extracts of native antigens are routinely used for the serodiagnosis of human helminthic infections. These antigens are often cross-reactive, i.e., recognized by sera from patients infected with heterologous helminth species. To overcome limitations in antigen production, test sensitivity and specificity, chemically synthesized peptides offer a pure and standardized alternative, provided they yield acceptable operative characteristics. Ongoing genome and proteome work create new resources for the identification of antigens. Making use of the growing amount of genomic and proteomic data available in public databases, we tested a bioinformatic procedure for the selection of potentially antigenic peptides from a collection of protein sequences including conceptually translated nucleotide sequence data of Echinococcus multilocularis and E. granulosus (Plathyhelminthes, Cestoda). The in silico selection was combined with high-throughput screening of peptides on microarray and systematic validation of reactive candidates in enzyme-linked immunosorbent assay. Our study proved the applicability of this approach for selection of peptide antigens with good diagnostic characteristics. Our results suggested the pooling of several peptides to reach a high level of sensitivity required for reliable immunodiagnosis

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Synthetic peptides in the diagnosis of human echinococcosis

Echinococcus granulosus and Echinococcus multilocularis are the two tapeworm species responsible for the majority of human echinococcosis cases. Infection of this zoonosis can be acquired all over the world by accidental ingestion of eggs. The prevalence of echinococcosis is highest in areas with extensive animal husbandry. Most diagnostic tests for the detection of antibodies against echinococcosis in humans are based on crude or partly purified native antigen extracts. The production of standardized diagnostic-grade native antigen is not possible. Native antigen suffers from batch-to-batch variation depending on purity, origin and developmental stage of the parasite material. In addition, native antigen is limited in availability. Substantial progress in the development of standardized reagents has been achieved by the production of recombinant antigens. Consequent further development of antigens might lead to the production of synthetic antigen. This PhD thesis investigated the applicability of synthetic peptides ranging from 24 to 47 amino acids in length for the use as synthetic antigens in serological diagnosis of cystic and alveolar echinococcosis. A bioinformatic selection procedure was established for identification of potentially antigenic protein sequences. From each of these parent proteins one or several peptides were selected for chemical synthesis. Peptides were designed from predicted domains of alpha-helical coiled-coils and intrinsically unstructured regions. These two motifs are capable of adopting their natural conformation even if synthesized as isolated fragments. The diagnostic performance of a synthetic antigen depends on its ability to fold into its native structure and thus be recognized by antibodies that had been naturally induced in the course of an infection. Peptide candidates were designed from different sets of parent proteins which had been selected by three different approaches: i) a genomics approach, ii) a proteomics approach, and iii) a transcriptomics approach. These three approaches identified 6 promising peptide candidates. The synthetic peptide performing best obtained a sensitivity of 74% for the detection of CE infection and 43% for the detection of AE infection in adult patients. Specificity was 94%. All identified peptides, apart from one candidate, were not able to discriminate between CE and AE infection. The major drawback of using peptides for serodiagnosis was their reduced sensitivity compared to EgHF, the native antigen used in routine diagnostics. Our results indicated that test sensitivity could be increased by combination of several peptides into a pool of synthetic antigen. This strategy can solve the problem of decreased sensitivity in future assay development. The most promising candidate, peptide longD8-9, was investigated as potential marker for serological follow-up of treatment success in young patients. This represents a novelty, as synthetic peptides have not yet been tested as marker for serological follow-up of CE patients. The performance of longD8-9-ELISA compared well to that of EgHF-ELISA, but it was superior in that within three years after treatment, more cured CE patients reached seronegativity in peptide ELISA compared to EgHF ELISA. Non-cured CE patients produced highly positive test results until the end of the follow-up period. This thesis provides proof-of-principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. It also showed the value of synthetic peptides as potential markers not only in primary diagnosis, but also in monitoring of treatment outcome in follow-up patients