Perinatal mortality in the Cape Province, 1989 - 1991

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Resonant Diffraction Radiation from an Ultrarelativistic Particle Moving Close to a Tilted Grating

A simple model for calculating the diffraction radiation characteristics from an ultrarelativistic charged particle moving close to a tilted ideally conducting strip is developed. Resonant diffraction radiation (RDR) is treated as a superposition of the radiation fields for periodically spaced strips. The RDR characteristics have been calculated as a function of the number of grating elements, tilted angle, and initial particle energy. An analogy with both the resonant transition radiation in absorbing medium and the parametric X-ray radiation is noted.Comment: 17 pages, 12 figures, RevTe

Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype

Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported.Wehypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE).Apatient with anMSH6mutation was treated withimmunecheckpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level ofRNA expression, are the first report, to our knowledge, of MSH2andMSH6mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor

Down syndrome-recent progress and future prospects

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of deleterious phenotypes, including learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. Individuals with DS are affected by these phenotypes to a variable extent; understanding the cause of this variation is a key challenge. Here, we review recent research progress in DS, both in patients and relevant animal models. In particular, we highlight exciting advances in therapy to improve cognitive function in people with DS and the significant developments in understanding the gene content of Hsa21. Moreover, we discuss future research directions in light of new technologies. In particular, the use of chromosome engineering to generate new trisomic mouse models and large-scale studies of genotype-phenotype relationships in patients are likely to significantly contribute to the future understanding of DS

The COVID-19 Pandemic and Physical Activity

The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health, economy, and lifestyle. Although the virus usually first invades and infects the lung and respiratory track tissue, in extreme cases, almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people. Unfortunately, there is currently no effective treatment for this disease. Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality. The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained quarantine and social distancing can downregulate the ability of organs systems to resist to viral infection and increase the risk of damage to the immune, respiratory, cardiovascular, musculoskeletal systems and the brain. The cellular mechanisms and danger of this "second wave" effect of COVID-19 to the human body, along with the effects of aging, proper nutrition, and regular physical activity, are reviewed in this editorial article

Role of the 5-Lipoxygenase–activating Protein (FLAP) in Murine Acute Inflammatory Responses

Leukotrienes are potent inflammatory mediators synthesized from arachidonic acid (AA) predominately by cells of myeloid origin. The synthesis of these lipids is believed to be dependent not only on the expression of the enzyme 5-lipoxygenase (5-LO), which catalyzes the first steps in the synthesis of leukotrienes, but also on expression of a nuclear membrane protein termed the 5-LO–activating protein (FLAP). To study the relationship of these two proteins in mediating the production of leukotrienes in vivo and to determine whether the membrane protein FLAP has additional functions in various inflammatory processes, we have generated a mouse line deficient in this protein. FLAP-deficient mice develop normally and are healthy. However, an array of assays comparing inflammatory reactions in FLAP-deficient mice and in normal controls revealed that FLAP plays a role in a subset of these reactions. Although examination of DTH and IgE-mediated passive anaphylaxis showed no difference between wild-type and FLAP-deficient animals, mice without FLAP possessed a blunted inflammatory response to topical AA and had increased resistance to platelet-activating factor–induced shock compared to controls. Also, edema associated with Zymosan A–induced peritonitis was markedly reduced in animals lacking FLAP. To determine whether these differences relate solely to a deficit in leukotriene production, or whether they reflect an additional role for FLAP in inflammation, we compared the FLAP-deficient mice to 5-LO–deficient animals. Evaluation of mice lacking FLAP and 5-LO indicated that production of leukotrienes during inflammatory responses is dependent upon the availability of FLAP and did not support additional functions for FLAP beyond its role in leukotriene production

Electron Dynamics in Nd1.85_{1.85}Ce.15_{.15}CuO4+δ_{4+\delta}: Evidence for the Pseudogap State and Unconventional c-axis Response

Infrared reflectance measurements were made with light polarized along the a- and c-axis of both superconducting and antiferromagnetic phases of electron doped Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$. The results are compared to characteristic features of the electromagnetic response in hole doped cuprates. Within the CuO$_2$ planes the frequency dependent scattering rate, 1/$\tau(\omega)$, is depressed below $\sim$ 650 cm$^{-1}$; this behavior is a hallmark of the pseudogap state. While in several hole doped compounds the energy scales associated with the pseudogap and superconducting states are quite close, we are able to show that in Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$ the two scales differ by more than one order of magnitude. Another feature of the in-plane charge response is a peak in the real part of the conductivity, $\sigma_1(\omega)$, at 50-110 cm$^{-1}$ which is in sharp contrast with the Drude-like response where $\sigma_1(\omega)$ is centered at $\omega=0$. This latter effect is similar to what is found in disordered hole doped cuprates and is discussed in the context of carrier localization. Examination of the c-axis conductivity gives evidence for an anomalously broad frequency range from which the interlayer superfluid is accumulated. Compelling evidence for the pseudogap state as well as other characteristics of the charge dynamics in Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$ signal global similarities of the cuprate phase diagram with respect to electron and hole doping.Comment: Submitted to PR

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions