Complete determination of the reflection coefficient in neutron specular reflection by absorptive non-magnetic media

An experimental method is proposed which allows the complete determination of the complex reflection coefficient for absorptive media for positive and negative values of the momenta. It makes use of magnetic reference layers and is a modification of a recently proposed technique for phase determination based on polarization measurements. The complex reflection coefficient resulting from a simulated application of the method is used for a reconstruction of the scattering density profiles of absorptive non-magnetic media by inversion.Comment: 14 pages, 4 figures, reformulation of abstract, ref.12 added, typographical correction

Classes of fast and specific search mechanisms for proteins on DNA

Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms which allow for a fast and selective target location. Initially we argue that DNA-binding proteins can be classified, broadly, into three distinct classes which we illustrate using experimental data. Each class calls for a different search process and we discuss the possible application of different search mechanisms proposed over the years to each class. The main thrust of this review is a new mechanism which is based on barrier discrimination. We introduce the model and analyze in detail its consequences. It is shown that this mechanism applies to all classes of transcription factors and can lead to a fast and specific search. Moreover, it is shown that the mechanism has interesting transient features which allow for stability at the target despite rapid binding and unbinding of the transcription factor from the target.Comment: 65 pages, 23 figure

Peanut yellow spot virus: A distinct tospovirus species based on serology and nucleic acid hybridisation

Nucleocapsids of peanut yellow spot virus (PYSV), purified from peanut (= groundnut) plant tissue, contained a protein with a molecular mass of 29 kDa. In ELISA and immuno-blot analysis the virus did not react with tomato spotted wilt virus (TSWV), Impatiens necrotic spot virus (INSV) and peanut bud necrosis virus (PBNV) antisera. PYSV contained three RNA species, a large (L) RNA (c.8900 nucleotides), a medium (M) RNA (c.4800 nucleotides) and a small (S) RNA (c.3000 nucleotides), similar to other tospoviruses. In addition, a fourth RNA species of approximately 1800 nucleotides was also present in purified preparations. Hybridisation analysis under high stringency conditions revealed no hybridisation between PYSV RNAs and cDNA probes representing the nucleocapsid (N) gene, the glycoprotein (GP) gene and the 3' half of the RNA polymerase gene of PBNV. PYSV genomic RNAs also failed to hybridise with cDNA probes from the GP genes of TSWV and INSV. In reciprocal tests, the cDNA clones of PYSV S and M RNAs did not hybridise with any of the PBNV RNAs. Based on the absence of serological relationships between PYSV and PBNV, TSWV and INSV and lack of nucleotide homology based on hybridisation studies between the PYSV RNAs and cDNA clones from PBNV, TSWV and INSV, PYSV should be considered as a distinct species of the genus Tospovirus under a new serogroup, putatively designated ‘V

Genetical genomics: spotlight on QTL hotspots

No abstract available

Vortex dynamics and states of artificially layered superconducting films with correlated defects

Linear resistances and $IV$-characteristics have been measured over a wide range in the parameter space of the mixed phase of multilayered a-TaGe/Ge films. Three films with varying interlayer coupling and correlated defects oriented at an angle $\approx 25$ from the film normal were investigated. Experimental data were analyzed within vortex glass models and a second order phase transition from a resistive vortex liquid to a pinned glass phase. Various vortex phases including changes from three to two dimensional behavior depending on anisotropy have been identified. Careful analysis of $IV$-characteristics in the glass phases revealed a distinctive $T$ and $H$-dependence of the glass exponent $\mu$. The vortex dynamics in the Bose-glass phase does not follow the predicted behavior for excitations of vortex kinks or loops.Comment: 16 pages, 10 figures, 3 table

Combining transcriptional profiling and genetic linkage analysis to uncover gene networks operating in hematopoietic stem cells and their progeny

Stem cells are unique in that they possess both the capacity to self-renew and thereby maintain their original pool as well as the capacity to differentiate into mature cells. In the past number of years, transcriptional profiling of enriched stem cell populations has been extensively performed in an attempt to identify a universal stem cell gene expression signature. While stem-cell-specific transcripts were identified in each case, this approach has thus far been insufficient to identify a universal group of core “stemness” genes ultimately responsible for self-renewal and multipotency. Similarly, in the hematopoietic system, comparisons of transcriptional profiles between different hematopoietic cell stages have had limited success in revealing core genes ultimately responsible for the initiation of differentiation and lineage specification. Here, we propose that the combined use of transcriptional profiling and genetic linkage analysis, an approach called “genetical genomics”, can be a valuable tool to assist in the identification of genes and gene networks that specify “stemness” and cell fate decisions. We review past studies of hematopoietic cells that utilized transcriptional profiling and/or genetic linkage analysis, and discuss several potential future applications of genetical genomics

Priorities and preferences of advanced soft tissue sarcoma patients starting palliative chemotherapy:baseline results from the HOLISTIC study

INTRODUCTION: Palliative chemotherapy is the principal treatment of patients with advanced soft tissue sarcomas (STS); however prognosis is limited (median overall survival 12-19 months). In this setting, patient values and priorities are central to personalised treatment decisions. PATIENTS AND METHODS: The prospective HOLISTIC study was conducted in the UK and the Netherlands assessing health-related quality of life in STS patients receiving palliative chemotherapy. Participants completed a questionnaire before starting chemotherapy, including attitudes towards quality of life (QoL) versus length of life (LoL), decisional control preferences, and decisional conflict. Chi-square and Fisher’s exact tests were used to evaluate associations between patient characteristics and preferences. RESULTS: One hundred and thirty-seven patients with advanced STS participated (UK: n = 72, the Netherlands: n = 65). Median age was 62 (27-79) years. Preference for extended LoL (n = 66, 48%) was slightly more common than preference for QoL (n = 56, 41%); 12 patients (9%) valued LoL and QoL equally (missing: n = 3). Younger patients (age <40 years) prioritised LoL, whereas two-thirds of older patients (aged ≥65 years) felt that QoL was equally or more important than LoL (P = 0.020). Decisional conflict was most common in patients who prioritised QoL (P = 0.024). Most patients preferred an active (n = 45, 33%) or collaborative (n = 59, 44%) role in treatment decisions. Gender, performance status, and country were significantly associated with preferred role. Concordance between preferred and actual role in chemotherapy decision was high (n = 104, 76%). CONCLUSIONS: Heterogeneous priorities and preferences among advanced STS patients support personalised decisions about palliative treatment. Considering individual differences during treatment discussions may enhance communication and optimise patient-centred care

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project

\ua9 2023, The Author(s).Introduction and Objective: The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. Methods: Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. Results: The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73–94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0–24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0–2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0–4% between DAPs). Conclusions: Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible