Assessing the Safety of Stem Cell Therapeutics

Unprecedented developments in stem cell research herald a new era of hope and expectation for novel therapies. However, they also present a major challenge for regulators since safety assessment criteria, designed for conventional agents, are largely inappropriate for cell-based therapies. This article aims to set out the safety issues pertaining to novel stem cell-derived treatments, to identify knowledge gaps that require further research, and to suggest a roadmap for developing safety assessment criteria. It is essential that regulators, pharmaceutical providers, and safety scientists work together to frame new safety guidelines, based on “acceptable risk,” so that patients are adequately protected but the safety “bar” is not set so high that exciting new treatments are lost

Aligning, Bonding, and Testing Mirrors for Lightweight X-ray Telescopes

High-resolution, high throughput optics for x-ray astronomy entails fabrication of well-formed mirror segments and their integration with arc-second precision. In this paper, we address issues of aligning and bonding thin glass mirrors with negligible additional distortion. Stability of the bonded mirrors and the curing of epoxy used in bonding them were tested extensively. We present results from tests of bonding mirrors onto experimental modules, and on the stability of the bonded mirrors tested in x-ray. These results demonstrate the fundamental validity of the methods used in integrating mirrors into telescope module, and reveal the areas for further investigation. The alignment and integration methods are applicable to the astronomical mission concept such as STAR-X, the Survey and Time-domain Astronomical Research Explorer

Targeted reconstruction of T cell receptor sequence from single cell RNA-seq links CDR3 length to T cell differentiation state

Abstract The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed. Here we present TRAPeS, a publicly available tool that can efficiently extract TCR sequence information from short-read scRNA-seq libraries. We apply it to investigate heterogeneity in the CD8+ T cell response in humans and mice, and show that it is accurate and more sensitive than existing approaches. Coupling TRAPeS with transcriptome analysis of CD8+ T cells specific for a single epitope from Yellow Fever Virus (YFV), we show that the recently described ‘naive-like’ memory population have significantly longer CDR3 regions and greater divergence from germline sequence than do effector-memory phenotype cells. This suggests that TCR usage is associated with the differentiation state of the CD8+ T cell response to YFV

The JADES Origins Field: A New JWST Deep Field in the JADES Second NIRCam Data Release

We summarize the properties and initial data release of the JADES Origins Field (JOF), which will soon be the deepest imaging field yet observed with the James Webb Space Telescope (JWST). This field falls within the GOODS-S region about 8' south-west of the Hubble Ultra Deep Field (HUDF), where it was formed initially in Cycle 1 as a parallel field of HUDF spectroscopic observations within the JWST Advanced Deep Extragalactic Survey (JADES). This imaging will be greatly extended in Cycle 2 program 3215, which will observe the JOF for 5 days in six medium-band filters, seeking robust candidates for z>15 galaxies. This program will also include ultra-deep parallel NIRSpec spectroscopy (up to 104 hours on-source, summing over the dispersion modes) on the HUDF. Cycle 3 observations from program 4540 will add 20 hours of NIRCam slitless spectroscopy to the JOF. With these three campaigns, the JOF will be observed for 380 open-shutter hours with NIRCam using 15 imaging filters and 2 grism bandpasses. Further, parts of the JOF have deep 43 hr MIRI observations in F770W. Taken together, the JOF will soon be one of the most compelling deep fields available with JWST and a powerful window into the early Universe. This paper presents the second data release from JADES, featuring the imaging and catalogs from the year 1 JOF observations.Comment: Submitted to ApJ Supplement. Images and catalogs are available at https://archive.stsci.edu/hlsp/jades . A FITSmap portal to view the images is at https://jades.idies.jhu.ed

Cognitive Profile of Students Who Enter Higher Education with an Indication of Dyslexia

For languages other than English there is a lack of empirical evidence about the cognitive profile of students entering higher education with a diagnosis of dyslexia. To obtain such evidence, we compared a group of 100 Dutch-speaking students diagnosed with dyslexia with a control group of 100 students without learning disabilities. Our study showed selective deficits in reading and writing (effect sizes for accuracy between d = 1 and d = 2), arithmetic (d≈1), and phonological processing (d>0.7). Except for spelling, these deficits were larger for speed related measures than for accuracy related measures. Students with dyslexia also performed slightly inferior on the KAIT tests of crystallized intelligence, due to the retrieval of verbal information from long-term memory. No significant differences were observed in the KAIT tests of fluid intelligence. The profile we obtained agrees with a recent meta-analysis of English findings suggesting that it generalizes to all alphabetic languages. Implications for special arrangements for students with dyslexia in higher education are outlined

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead