Nuclear reactor power as applied to a space-based radar mission

The SP-100 Project was established to develop and demonstrate feasibility of a space reactor power system (SRPS) at power levels of 10's of kilowatts to a megawatt. To help determine systems requirements for the SRPS, a mission and spacecraft were examined which utilize this power system for a space-based radar to observe moving objects. Aspects of the mission and spacecraft bearing on the power system were the primary objectives of this study; performance of the radar itself was not within the scope. The study was carried out by the Systems Design Audit Team of the SP-100 Project

The Ursinus Weekly, December 21, 1914

Schaff anniversary play well rendered • Freshmen banquet held in Norristown • Football banquet a grand success • Christmas in Germany • East wing banquet • To the reader • From the fieldhttps://digitalcommons.ursinus.edu/weekly/2647/thumbnail.jp

Women’s Access to Land and Economic Empowerment in Selected Nigerian Communities

Despite various land policies that prescribe rights to land in many societies, women remain marginalized in access to and economic utilization of land. This is widespread in rural communities where informal institutions such as customs and traditions subsist. In most of these communities, the patriarchal structure of families is championed by the informal institutions that support male dominance. This study focuses on economic empowerment of women as it encapsulates sustainable wealth of women. It provides answers to two main research questions: a) what kind of relationship exists between land access and empowerment of women? And b) how important are individual and household attributes in informing women’s empowerment through land rights? The empirical results of this study provide some new insights as they demonstrate how land rights influence women’s economic empowerment. The study also finds that women’s earning capacity reduces when they take up the responsibility of becoming the heads of households and that their income increases as they become more educate

BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein

Patients with chronic myeloid leukemia in whom tyrosine kinase inhibitors (TKIs) fail often present mutations in the BCR-ABL catalytic domain. We noticed a lack of substitutions involving 4 amino acids (E286, M318, I360, and D381) that form hydrogen bonds with ponatinib. We therefore introduced mutations in each of these residues, either preserving or altering their physicochemical properties. We found that E286, M318, I360, and D381 are dispensable for ABL and BCR-ABL protein stability but are critical for preserving catalytic activity. Indeed, only a "conservative" I360T substitution retained kinase proficiency and transforming potential. Molecular dynamics simulations of BCR-ABLI360T revealed differences in both helix αC dynamics and protein-correlated motions, consistent with a modified ATP-binding pocket. Nevertheless, this mutant remained sensitive to ponatinib, imatinib, and dasatinib. These results suggest that changes in the 4 BCR-ABL residues described here would be selected against by a lack of kinase activity or by maintained responsiveness to TKIs. Notably, amino acids equivalent to those identified in BCR-ABL are conserved in 51% of human tyrosine kinases. Hence, these residues may represent an appealing target for the design of pharmacological compounds that would inhibit additional oncogenic tyrosine kinases while avoiding the emergence of resistance due to point mutations.This work was supported by an investigator grant to P.V. from Associazione Italiana per la Ricerca sul Cancro (AIRC) and by funding from the Biotechnology and Biological Sciences Research Council (BB/I023291/1 and BB/H018409/1 to AP and FF). P.B. is the recipient of an AIRC - Marie Curie fellowship

Attempts to detect retrotransposition and de novo deletion of Alus and other dispersed repeats at specific loci in the human genome

Dispersed repeat elements contribute to genome instability by de novo insertion and unequal recombination between repeats. To study the dynamics of these processes, we have developed single DNA molecule approaches to detect de novo insertions at a single locus and Alu-mediated deletions at two different loci in human genomic DNA. Validation experiments showed these approaches could detect insertions and deletions at frequencies below 10(-6) per cell. However, bulk analysis of germline (sperm) and somatic DNA showed no evidence for genuine mutant molecules, placing an upper limit of insertion and deletion rates of 2 x 10(-7) and 3 x 10(-7), respectively, in the individuals tested. Such re-arrangements at these loci therefore occur at a rate lower than that detectable by the most sensitive methods currently available

A droplet digital PCR detection method for rare L1 insertions in tumors

Background: The active human mobile element, long interspersed element 1 (L1) currently populates human genomes in excess of 500,000 copies per haploid genome. Through its mobility via a process called target primed reverse transcription (TPRT), L1 mobilization has resulted in over 100 de novo cases of human disease and has recently been associated with various cancer types. Large advances in high-throughput sequencing (HTS) technology have allowed for an increased understanding of the role of L1 in human cancer; however, researchers are still limited by the ability to validate potentially rare L1 insertion events detected by HTS that may occur in only a small fraction of tumor cells. Additionally, HTS detection of rare events varies greatly as a function of read depth, and new tools for de novo element discovery are needed to fill in gaps created by HTS. Results: We have employed droplet digital PCR (ddPCR) to detect rare L1 loci in mosaic human genomes. Our assay allows for the detection of L1 insertions as rare as one cell in every 10,000. Conclusions: ddPCR represents a robust method to be used alongside HTS techniques for detecting, validating and quantitating rare L1 insertion events in tumors and other tissues. Electronic supplementary material The online version of this article (doi:10.1186/s13100-014-0030-4) contains supplementary material, which is available to authorized users

Current desires of conspecific observers affect cache-protection strategies in California scrub-jays and Eurasian jays

Many corvid species accurately remember the locations where they have seen others cache food, allowing them to pilfer these caches efficiently once the cachers have left the scene [1] . To protect their caches, corvids employ a suite of different cache-protection strategies that limit the observers’ visual or acoustic access to the cache site [2,3] . In cases where an observer’s sensory access cannot be reduced it has been suggested that cachers might be able to minimise the risk of pilfering if they avoid caching food the observer is most motivated to pilfer [4] . In the wild, corvids have been reported to pilfer others’ caches as soon as possible after the caching event [5] , such that the cacher might benefit from adjusting its caching behaviour according to the observer’s current desire. In the current study, observers pilfered according to their current desire: they preferentially pilfered food that they were not sated on. Cachers adjusted their caching behaviour accordingly: they protected their caches by selectively caching food that observers were not motivated to pilfer. The same cache-protection behaviour was found when cachers could not see on which food the observers were sated. Thus, the cachers’ ability to respond to the observer’s desire might have been driven by the observer’s behaviour at the time of caching.We thank the BBSRC, the ERC and the Leverhulme Trust for funding the research. K.F.B., F.L. and C.D. were funded by ERASMUS scholarships

Application of deep learning-based image reconstruction in MR imaging of the shoulder joint to improve image quality and reduce scan time

OBJECTIVES To compare the image quality and diagnostic performance of conventional motion-corrected periodically rotated overlapping parallel line with enhanced reconstruction (PROPELLER) MRI sequences with post-processed PROPELLER MRI sequences using deep learning-based (DL) reconstructions. METHODS In this prospective study of 30 patients, conventional (19 min 18 s) and accelerated MRI sequences (7 min 16 s) using the PROPELLER technique were acquired. Accelerated sequences were post-processed using DL. The image quality and diagnostic confidence were qualitatively assessed by 2 readers using a 5-point Likert scale. Analysis of the pathological findings of cartilage, rotator cuff tendons and muscles, glenoid labrum and subacromial bursa was performed. Inter-reader agreement was calculated using Cohen's kappa statistic. Quantitative evaluation of image quality was measured using the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). RESULTS Mean image quality and diagnostic confidence in evaluation of all shoulder structures were higher in DL sequences (p value = 0.01). Inter-reader agreement ranged between kappa values of 0.155 (assessment of the bursa) and 0.947 (assessment of the rotator cuff muscles). In 17 cases, thickening of the subacromial bursa of more than 2 mm was only visible in DL sequences. The pathologies of the other structures could be properly evaluated by conventional and DL sequences. Mean SNR (p value = 0.01) and CNR (p value = 0.02) were significantly higher for DL sequences. CONCLUSIONS The accelerated PROPELLER sequences with DL post-processing showed superior image quality and higher diagnostic confidence compared to the conventional PROPELLER sequences. Subacromial bursa can be thoroughly assessed in DL sequences, while the other structures of the shoulder joint can be assessed in conventional and DL sequences with a good agreement between sequences. KEY POINTS • MRI of the shoulder requires long scan times and can be hampered by motion artifacts. • Deep learning-based convolutional neural networks are used to reduce image noise and scan time while maintaining optimal image quality. The radial k-space acquisition technique (PROPELLER) can reduce the scan time and has potential to reduce motion artifacts. • DL sequences show a higher diagnostic confidence than conventional sequences and therefore are preferred for assessment of the subacromial bursa, while conventional and DL sequences show comparable performance in the evaluation of the shoulder joint

Advances in the treatment of chronic myeloid leukemia

Although imatinib is firmly established as an effective therapy for newly diagnosed patients with chronic myeloid leukemia (CML), the field continues to advance on several fronts. In this minireview we cover recent results of second generation tyrosine kinase inhibitors in newly diagnosed patients, investigate the state of strategies to discontinue therapy and report on new small molecule inhibitors to tackle resistant disease, focusing on agents that target the T315I mutant of BCR-ABL. As a result of these advances, standard of care in frontline therapy has started to gravitate toward dasatinib and nilotinib, although more observation is needed to fully support this. Stopping therapy altogether remains a matter of clinical trials, and more must be learned about the mechanisms underlying the persistence of leukemic cells with treatment. However, there is good news for patients with the T315I mutation, as effective drugs such as ponatinib are on their way to regulatory approval. Despite these promising data, accelerated or blastic phase disease remains a challenge, possibly due to BCR-ABL-independent resistance