Configuration development study of the X-24C hypersonic research airplane

Bottom line results were made of a three-phase study to determine the feasibility of designing, building, and operating, and maintaining an air-launched high performance aircraft capable of cruising at speeds up to Mach 8 for short durations. The results show that Lockalloy heat-sink structure affords the capability for a 'work-horse' vehicle which can serve as an excellent platform for this research. It was further concluded that the performance of a blended wing body configuration surpassed that of a lifting body design for typical X-24C missions. The cost of a two vehicle program, less engines, B-52 modification and contractor support after delivery, can be kept within $70M (in Jan. 1976 dollars)

Laser pump X ray probe experiments with electrons ejected from a Cu 111 target space charge acceleration

A comprehensive investigation of the emission characteristics for electrons induced by X rays of a few hundred eV at grazing incidence angles on an atomically clean Cu 111 sample during laser excitation is presented. Electron energy spectra due to intense infrared laser irradiation are investigated at the BESSY II slicing facility. Furthermore, the influence of the corresponding high degree of target excitation high peak current of photoemission on the properties of Auger and photoelectrons liberated by a probe X ray beam is investigated in time resolved pump and probe measurements. Strong electron energy shifts have been found and assigned to space charge acceleration. The variation of the shift with laser power and electron energy is investigated and discussed on the basis of experimental as well as new theoretical result

On-site correlation in valence and core states of ferromagnetic nickel

We present a method which allows to include narrow-band correlation effects into the description of both valence and core states and we apply it to the prototypical case of nickel. The results of an ab-initio band calculation are used as input mean-field eigenstates for the calculation of self-energy corrections and spectral functions according to a three-body scattering solution of a multi-orbital Hubbard hamiltonian. The calculated quasi-particle spectra show a remarkable agreement with photoemission data in terms of band width, exchange splitting, satellite energy position of valence states, spin polarization of both the main line and the satellite of the 3p core level.Comment: 14 pages, 10 PostScript figures, RevTeX, submitted to PR

Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma

Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA repair pathway and EYA3 expression in proteasome inhibitor sensitivity and major histocompatibility complex class II expression in the response to elotuzumab. Globally, ex vivo drug sensitivity associated with bone marrow microenvironmental signatures reflecting treatment stage, clonality and inflammation. Furthermore, ex vivo drug sensitivity significantly stratified clinical treatment responses, including to immunotherapy. Taken together, our study provides molecular and actionable insights into diverse treatment strategies for patients with MM

Two color synchrotron X ray spectroscopy based on transverse resonance island buckets

We report on a novel multi color method of X ray spectroscopy at a Synchrotron radiation source that uses two simultaneously filled electron orbits in an electron storage ring to generate multiple soft or tender X ray beams of different wavelength. To establish the second orbit, we use nonlinear beam dynamics in the so called TRIBs transverse resonance island buckets mode of the BESSY II storage ring, where a second electron orbit winds around the regular one leading to transversely separated source points. X ray beams of multiple colors are generated by imaging the individual source points via different pathways through a monochromator. The particular colors can be varied by changing the traversal electron beam positions through storage ring parameters and or via the monochromator dispersion. As a proof of principle, X ray absorption spectroscopy is performed on thin Fe films in transmission as well as a scanning transmission measurement on a Fe3GeTe2 sample of inhomogeneous thickness normalizing resonant signals with the pre edge intensity. Using the extraordinary pointing fidelity of successive X ray macro pulses arriving at MHz repetition rates, a detection of tiny contrasts in diluted systems, contrast enhancement in X ray microscopy as well as fast dynamics studies come into reac

Developing an e-learning course on the use of PRO measures in oncological practice: health care professionals' preferences for learning content and methods

PURPOSE: Implementation of patient-reported outcome measures (PROMs) in clinical routine requires knowledge and competences regarding their use. In order to facilitate implementation, an e-learning course for health care professionals (HCPs) on the utilisation of European Organisation for Research and Treatment of Cancer (EORTC) PROMs in oncological clinical practice is being developed. This study aimed to explore future users' educational needs regarding content and learning methods. METHODS: The sequential mixed methods approach was applied. A scoping literature review informed the guideline for qualitative interviews with HCPs with diverse professional backgrounds in oncology and cancer advocates recruited using a purposive sampling strategy. An international online survey was conducted to validate the qualitative findings. RESULTS: Between December 2019 and May 2020, 73 interviews were conducted in 9 countries resulting in 8 topic areas (Basic information on PROs in clinical routine, Benefits of PRO assessments in clinical practice, Implementation of PRO assessments in clinical routine, Setup of PRO assessments for clinical application, Interpretation of PRO data, Integration of PROs into the communication with patients, Use of PROs in clinical practice, Self-management recommendations for patients based on PROs) subsequently presented in the online survey. The online survey (open between 3 June and 19 July 2020) was completed by 233 HCPs from 33 countries. The highest preference was indicated for content on interpretation of PRO data (97%), clinical benefits of assessing PRO data (95.3%) and implementation of routine PRO data assessment (94.8%). Regarding learning methods, participants indicated a high preference for practical examples that use a mixed approach of presentation (written, audio, video and interactive). CONCLUSION: Educational needs for an integration of PROs in communication in clinical care and coherent implementation strategies became evident. These results inform the development of an e-learning course to support HCPs in the clinical use of EORTC PRO measures

Matrilineal behavioral and physiological changes following the death of a non-alpha matriarch in rhesus macaque

In many species, the loss of alpha matriarchs is associated with a number of negative outcomes such as troop fission, eviction, wounding, and reduced vitality. However, whether the dramatic consequences of their loss are due to their role as an old experienced figure or to their alpha status remains unclear. In a retrospective study, we tested that in a semi-free ranging colony of rhesus macaques (Macaca mulatta), the removal of a non-alpha matriarch, who had a large set of kin, led to changes in behavior and physiological stress within her matriline. Following her removal, her matriline increased in aggression, vigilance, and social grooming. Additionally, hierarchical stability, measured by levels of rank changes, decreased within her matriline, and levels of intense aggression by high-ranking animals were more frequent, as well as matrilineal wounding. Although ordinal rank was positively associated with higher chronic hair cortisol concentrations (HCCs) in the months before the matriarch’s removal, following her removal, only those who experienced large increases in rank within her matriline displayed higher HCCs. Changes in matrilineal stability, aggression, behavior, and HCCs within the other two matrilines in the troop were not evident, although caution is needed due to the small sample sizes. We conclude that the removal of the non-alpha matriarch led to matrilineal instability, characterized by higher levels of aggression and subsequent vigilance, rank changes, physiological stress, and grooming. We suggest that non-alpha matriarchs with a large number of kin and social support can be integral to the stability of matrilines.Division of Intramural Research, National Institute of Child Health and Human Development, 1ZIAHD001107- 3

Determining Signalling Nodes for Apoptosis by a Genetic High-Throughput Screen

With the ever-increasing information emerging from the various sequencing and gene annotation projects, there is an urgent need to elucidate the cellular functions of the newly discovered genes. The genetically regulated cell suicide of apoptosis is especially suitable for such endeavours as it is governed by a vast number of factors.We have set up a high-throughput screen in 96-well microtiter plates for genes that induce apoptosis upon their individual transfection into human cells. Upon screening approximately 100,000 cDNA clones we determined 74 genes that initiate this cellular suicide programme. A thorough bioinformatics analysis of these genes revealed that 91% are novel apoptosis regulators. Careful sequence analysis and functional annotation showed that the apoptosis factors exhibit a distinct functional distribution that distinguishes the cell death process from other signalling pathways. While only a minority of classic signal transducers were determined, a substantial number of the genes fall into the transporter- and enzyme-category. The apoptosis factors are distributed throughout all cellular organelles and many signalling circuits, but one distinct signalling pathway connects at least some of the isolated genes. Comparisons with microarray data suggest that several genes are dysregulated in specific types of cancers and degenerative diseases.Many unknown genes for cell death were revealed through our screen, supporting the enormous complexity of cell death regulation. Our results will serve as a repository for other researchers working with genomics data related to apoptosis or for those seeking to reveal novel signalling pathways for cell suicide