Second-generation mobile satellite system. A conceptual design and trade-off study

In recent years, interest has grown in the mobile satellite (MSAT) system, a satellite-based communications system capable of providing integrated voice and data services to a large number of users. To explore the potential of a commercial mobile satellite system (MSS) beyond the horizon of the first generation, using technologies of the 1990's and to assist MSAT-X in directing its efforts, a conceptual design has been performed for a second-generation system to be launched around the mid-1990's. The design goal is to maximize the number of satellite channels and/or minimize the overall life-cycle cost, subject to the constraint of utilizing a commercial satellite bus with minimum modifications. To provide an optimal design, a series of trade-offs are performed, including antenna sizing, feed configurations, and interference analysis. Interference is a serious problem for MSAT and often an overlapping feed design is required to reduce interbeam interference. The trade-off studies will show that a simple non-overlapping feed is sufficient for the second-generation system, thus avoiding the need for the complicated beam-forming network that is associated with the overlapping feed designs. In addition, a system that operates at L-band, an alternative frequency band that is being considered by some for possible MSAT applications, is also presented

Decreased MCM2-6 in Drosophila S2 cells does not generate significant DNA damage or cause a marked increase in sensitivity to replication interference.

A reduction in the level of some MCM proteins in human cancer cells (MCM5 in U20S cells or MCM3 in Hela cells) causes a rapid increase in the level of DNA damage under normal conditions of cell proliferation and a loss of viability when the cells are subjected to replication interference. Here we show that Drosophila S2 cells do not appear to show the same degree of sensitivity to MCM2-6 reduction. Under normal cell growth conditions a reduction of >95% in the levels of MCM3, 5, and 6 causes no significant short term alteration in the parameters of DNA replication or increase in DNA damage. MCM depleted cells challenged with HU do show a decrease in the density of replication forks compared to cells with normal levels of MCM proteins, but this produces no consistent change in the levels of DNA damage observed. In contrast a comparable reduction of MCM7 levels has marked effects on viability, replication parameters and DNA damage in the absence of HU treatment

Scientific mindfulness: a foundation for future themes in international business

We conceptualize new ways to qualify what themes should dominate the future IB research agenda by examining three questions: Whom should we ask? What should we ask and which selection criteria should we apply? What are the contextual forces? We propose scientific mindfulness as the way forward for generating themes in IB research

On a class of invariant coframe operators with application to gravity

Let a differential 4D-manifold with a smooth coframe field be given. Consider the operators on it that are linear in the second order derivatives or quadratic in the first order derivatives of the coframe, both with coefficients that depend on the coframe variables. The paper exhibits the class of operators that are invariant under a general change of coordinates, and, also, invariant under the global SO(1,3)-transformation of the coframe. A general class of field equations is constructed. We display two subclasses in it. The subclass of field equations that are derivable from action principles by free variations and the subclass of field equations for which spherical-symmetric solutions, Minkowskian at infinity exist. Then, for the spherical-symmetric solutions, the resulting metric is computed. Invoking the Geodesic Postulate, we find all the equations that are experimentally (by the 3 classical tests) indistinguishable from Einstein field equations. This family includes, of course, also Einstein equations. Moreover, it is shown, explicitly, how to exhibit it. The basic tool employed in the paper is an invariant formulation reminiscent of Cartan's structural equations. The article sheds light on the possibilities and limitations of the coframe gravity. It may also serve as a general procedure to derive covariant field equations

Disease-specific, neurosphere-derived cells as models for brain disorders

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery

A New Approach to Measuring Estrogen Exposure and Metabolism in Epidemiologic Studies

Endogenous estrogen plays an integral role in the etiology of breast and endometrial cancer, and conceivably ovarian cancer. However, the underlying mechanisms and the importance of patterns of estrogen metabolism and specific estrogen metabolites have not been adequately explored. Long-standing hypotheses, derived from laboratory experiments, have not been tested in epidemiologic research because of the lack of robust, rapid, accurate measurement techniques appropriate for large-scale studies. We have developed a stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS(2)) method that can measure concurrently all 15 estrogens and estrogen metabolites (EM) in urine and serum with high sensitivity (level of detection=2.5-3.0fmol EM/mL serum), specificity, accuracy, and precision [laboratory coefficients of variation (CV\u27s) \u3c or =5% for nearly all EM]. The assay requires only extraction, a single chemical derivatization, and less than 0.5mL of serum or urine. By incorporating enzymatic hydrolysis, the assay measures total (glucuronidated+sulfated+unconjugated) EM. If the hydrolysis step is omitted, the assay measures unconjugated EM. Interindividual differences in urinary EM concentrations (pg/mL creatinine), which reflect total EM production, were consistently large, with a range of 10-100-fold for nearly all EM in premenopausal and postmenopausal women and men. Correlational analyses indicated that urinary estrone and estradiol, the most commonly measured EM, do not accurately represent levels of total urinary EM or of the other EM. In serum, all 15 EM were detected as conjugates, but only 5 were detected in unconjugated form. When we compared our assay methods with indirect radioimmunoassays for estrone, estradiol, and estriol and enzyme-linked immunosorbent assays for 2-hydroxyestrone and 16alpha-hydroxyestrone, ranking of individuals agreed well for premenopausal women [Spearman r (r(s))=0.8-0.9], but only moderately for postmenopausal women (r(s)=0.4-0.8). Our absolute readings were consistently lower, especially at the low concentrations characteristic of postmenopausal women, possibly because of improved specificity. We are currently applying our EM measurement techniques in several epidemiologic studies of premenopausal and postmenopausal breast cancer

Mortality in pulmonary arterial hypertension in the modern era: Early insights from the Pulmonary Hypertension Association Registry

Background Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry). Methods and Results We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935). We used Kaplan-Meier survival analysis and Cox proportional hazards models to assess mortality at 1, 2, and 3 years. Patients were stratified based on disease severity by 3 validated risk scores. In treatment-naïve patients, we compared survival based on initial treatment strategy. The median age was 56 years (44-68 years), and 76% were women. Of the 935 patients, 483 (52%) were ≤6 months from PAH diagnosis. There were 121 deaths (12.9%) during a median follow-up time of 489 days (281-812 days). The 1-, 2-, and 3-year mortality was 8% (95% CI, 6%-10%), 16% (95% CI, 13%-19%), and 21% (95% CI, 17%-25%), respectively. When stratified into low-, intermediate-, and high-risk PAH, the mortality at 1, 2, and 3 years was 1%, 4% to 6%, and 7% to 11% for low risk; 7% to 8%, 11% to 16%, and 18% to 20% for intermediate risk; and 12% to 19%, 22% to 38%, and 28% to 55% for high risk, respectively. In treatment-naïve patients, initial combination therapy was associated with better 1-year survival (adjusted hazard ratio, 0.43 [95% CI, 0.19-0.95]

First muon acceleration using a radio frequency accelerator

Muons have been accelerated by using a radio frequency accelerator for the first time. Negative muonium atoms (Mu$^-$), which are bound states of positive muons ($\mu^+$) and two electrons, are generated from $\mu^+$'s through the electron capture process in an aluminum degrader. The generated Mu$^-$'s are initially electrostatically accelerated and injected into a radio frequency quadrupole linac (RFQ). In the RFQ, the Mu$^-$'s are accelerated to 89 keV. The accelerated Mu$^-$'s are identified by momentum measurement and time of flight. This compact muon linac opens the door to various muon accelerator applications including particle physics measurements and the construction of a transmission muon microscope

Management of locally recurrent nasopharyngeal carcinoma

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.Peer reviewe