Nova Geminorum 1912 and the Origin of the Idea of Gravitational Lensing

Einstein's early calculations of gravitational lensing, contained in a scratch notebook and dated to the spring of 1912, are reexamined. A hitherto unknown letter by Einstein suggests that he entertained the idea of explaining the phenomenon of new stars by gravitational lensing in the fall of 1915 much more seriously than was previously assumed. A reexamination of the relevant calculations by Einstein shows that, indeed, at least some of them most likely date from early October 1915. But in support of earlier historical interpretation of Einstein's notes, it is argued that the appearance of Nova Geminorum 1912 (DN Gem) in March 1912 may, in fact, provide a relevant context and motivation for Einstein's lensing calculations on the occasion of his first meeting with Erwin Freundlich during a visit in Berlin in April 1912. We also comment on the significance of Einstein's consideration of gravitational lensing in the fall of 1915 for the reconstruction of Einstein's final steps in his path towards general relativity.Comment: 31 p

A common NYX mutation in Flemish patients with X linked CSNB

Aims: The Schubert-Bornschein type of complete congenital stationary night blindness (CSNB) is a genetically heterogeneous retinal disorder. It is characterised by a non-progressive disease course, often associated with high myopia and nystagmus. So far, mutations in two genes, NYX (nyctalopin) and GRM6 (metabotropic glutamate receptor 6) have been associated with this form of CSNB. The purpose of this study was to identify the genetic defect in affected male patients from Flemish families with complete CSNB. Methods: Probands with CSNB from three large Flemish families underwent ophthalmological examination. DNA was extracted from peripheral blood, and the coding region of NYX along with parts of the 5'UTR and 3'UTR and intronic regions covering the splice sites were PCR amplified and sequenced. Results: In the affected individuals of three Flemish families with the complete form of CSNB a novel NYX mutation, c.855delG was identified. This deletion is predicted to lead to a frameshift mutation, p. Asp286ThrfsX62 causing a premature stop codon. Conclusion: Previously, both single families with different mutations in NYX as well as different families with an identical mutation, suggestive of a founder mutation, have been described. The c.855delG deletion in NYX seems to be a common mutation associated with CSNB in the Flemish population from Belgium. Thus, we suggest performing diagnostic testing for CSNB in the Flemish population initially directed towards the identification of this mutation. Subsequent screening for other mutations in NYX or GRM6 could be performed as a second step

Synthetic mammalian signaling circuits for robust cell population control

In multicellular organisms, cells actively sense, respond to, and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and improve cell therapies. However, a key challenge is avoiding their inherent sensitivity to “cheater” mutations that evade control. Here, we repurposed the plant hormone auxin to enable orthogonal mammalian cell-cell communication and quorum sensing. Further, we show that a “paradoxical” circuit design, in which auxin stimulates and inhibits net cell growth at different concentrations, achieves population control that is robust to cheater mutations, controlling growth for 43 days of continuous culture. By contrast, a non-paradoxical control circuit limited growth but was susceptible to mutations. These results establish a foundation for future cell therapies that can respond to and control their own population sizes

Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases

Background: This phase III study compared the efficacy of the new potent bisphosphonate, ibandronate, with placebo as intravenous (i.v.) therapy in metastatic bone disease due to breast cancer. Patients and methods: A total of 466 patients were randomised to receive placebo (n = 158), or 2 mg (n = 154) or 6 mg (n = 154) ibandronate every 3-4 weeks for up to 2 years. The primary efficacy parameter was the number of 12-week periods with new bone complications, expressed as the skeletal morbidity period rate (SMPR). Bone pain, analgesic use and safety were evaluated monthly. Results SMPR was lower in both ibandronate groups compared with the placebo group; the difference was statistically significant for the ibandronate 6 mg group (P = 0.004 versus placebo). Consistent with the SMPR, ibandronate 6 mg significantly reduced the number of new bone events (by 38%) and increased time to first new bone event. Patients on ibandronate 6 mg also experienced decreased bone pain scores and analgesic use. Treatment with ibandronate was well tolerated. Conclusions: These results indicate that 6 mg i.v. ibandronate is effective and safe in the treatment of bone metastases from breast cance

In situ readout of DNA barcodes and single base edits facilitated by in vitro transcription

Molecular barcoding technologies that uniquely identify single cells are hampered by limitations in barcode measurement. Readout by sequencing does not preserve the spatial organization of cells in tissues, whereas imaging methods preserve spatial structure but are less sensitive to barcode sequence. Here we introduce a system for image-based readout of short (20-base-pair) DNA barcodes. In this system, called Zombie, phage RNA polymerases transcribe engineered barcodes in fixed cells. The resulting RNA is subsequently detected by fluorescent in situ hybridization. Using competing match and mismatch probes, Zombie can accurately discriminate single-nucleotide differences in the barcodes. This method allows in situ readout of dense combinatorial barcode libraries and single-base mutations produced by CRISPR base editors without requiring barcode expression in live cells. Zombie functions across diverse contexts, including cell culture, chick embryos and adult mouse brain tissue. The ability to sensitively read out compact and diverse DNA barcodes by imaging will facilitate a broad range of barcoding and genomic recording strategies

F-18-FDG PET/CT in Infective Endocarditis:Indications and Approaches for Standardization

Purpose of Review: Additional imaging modalities, such as FDG-PET/CT, have been included into the workup for patients with suspected infective endocarditis, according to major international guidelines published in 2015. The purpose of this review is to give an overview of FDG-PET/CT indications and standardized approaches in the setting of suspected infective endocarditis. Recent Findings: There are two main indications for performing FDG-PET/CT in patients with suspected infective endocarditis: (i) detecting intracardiac infections and (ii) detection of (clinically silent) disseminated infectious disease. The diagnostic performance of FDG-PET/CT for intracardiac lesions depends on the presence of na

Qualitative grading of aortic regurgitation: a pilot study comparing CMR 4D flow and echocardiography.

Over the past 10 years there has been intense research in the development of volumetric visualization of intracardiac flow by cardiac magnetic resonance (CMR).This volumetric time resolved technique called CMR 4D flow imaging has several advantages over standard CMR. It offers anatomical, functional and flow information in a single free-breathing, ten-minute acquisition. However, the data obtained is large and its processing requires dedicated software. We evaluated a cloud-based application package that combines volumetric data correction and visualization of CMR 4D flow data, and assessed its accuracy for the detection and grading of aortic valve regurgitation using transthoracic echocardiography as reference. Between June 2014 and January 2015, patients planned for clinical CMR were consecutively approached to undergo the supplementary CMR 4D flow acquisition. Fifty four patients(median age 39 years, 32 males) were included. Detection and grading of the aortic valve regurgitation using CMR4D flow imaging were evaluated against transthoracic echocardiography. The agreement between 4D flow CMR and transthoracic echocardiography for grading of aortic valve regurgitation was good (j = 0.73). To identify relevant,more than mild aortic valve regurgitation, CMR 4D flow imaging had a sensitivity of 100 % and specificity of 98 %. Aortic regurgitation can be well visualized, in a similar manner as transthoracic echocardiography, when using CMR 4D flow imaging

A mathematical description of nerve fiber bundle trajectories and their variability in the human retina

AbstractWe developed a mathematical model wherein retinal nerve fiber trajectories can be described and the corresponding inter-subject variability analyzed. The model was based on traced nerve fiber bundle trajectories extracted from 55 fundus photographs of 55 human subjects. The model resembled the typical retinal nerve fiber layer course within 20° eccentricity. Depending on the location of the visual field test point, the standard deviation of the calculated corresponding angular location at the optic nerve head circumference ranged from less than 1° to 18°, with an average of 8.8°

Male-female differences in thoracic aortic diameters at presentation of acute type A aortic dissection

Background: Acute type A aortic dissection (ATAAD) is a highly lethal event, associated with aortic dilatation. It is not well known if patient height, weight or sex impact the thoracic aortic diameter (TAA) at ATAAD. The study aim was to identify male–female differences in TAA at ATAAD presentation. Methods: This retrospective cross-sectional study analysed all adult patients who presented with ATAAD between 2007 and 2017 in two tertiary care centres and underwent contrast enhanced computed tomography (CTA) before surgery. Absolute aortic diameters were measured at the sinus of Valsalva (SoV), ascending (AA) and descending thoracic aorta (DA) using double oblique reconstruction, and indexed for body surface area (ASI) and height (AHI). Z-scores were calculated using the Campens formula. Results: In total, 59 % (181/308) of ATAAD patients had CT-scans eligible for measurements, with 82 female and 99 male patients. Females were significantly older than males (65.5 ± 12.4 years versus 60.3 ± 2.3, p = 0.024). Female patients had larger absolute AA diameters than male patients (51.0 mm [47.0–57.0] versus 49.0 mm [45.0–53.0], p = 0.023), and larger ASI and AHI at all three levels. Z-scores for the SoV and AA were significantly higher for female patients (2.99 ± 1.66 versus 1.34 ± 1.77, p &lt; 0.001 and 5.27 [4.38–6.26] versus 4.06 [3.14–5.02], p &lt; 0.001). After adjustment for important clinical factors, female sex remained associated with greater maximal TAA (p = 0.019). Conclusion: Female ATAAD patients had larger absolute ascending aortic diameters than males, implying a distinct timing in disease presentation or selection bias. Translational studies on the aortic wall and studies on growth patterns should further elucidate these sex differences.</p