Lunar base launch and landing facilities conceptual design

The purpose of this study was to perform a first look at the requirements for launch and landing facilities for early lunar bases and to prepared conceptual designs for some of these facilities. The emphasis of the study is on the facilities needed from the first manned landing until permanent occupancy, the Phase 2 lunar base. Factors including surface characteristics, navigation system, engine blast effects, and expected surface operations are used to develop landing pad designs, and definitions fo various other elements of the launch and landing facilities. Finally, the dependence of the use of these elements and the evolution of the facilities are established

Space transportation nodes assumptions and requirements: Lunar base systems study task 2.1

The Space Transportation Nodes Assumptions and Requirements task was performed as part of the Advanced Space Transportation Support Contract, a NASA Johnson Space Center (JSC) study intended to provide planning for a Lunar Base near the year 2000. The original task statement has been revised to satisfy the following queries: (1) What vehicles are to be processed at the transportation node; (2) What is the flow of activities involved in a vehicle passing through the node; and (3) What node support resources are necessary to support a lunar scenario traffic model composed of a mix of vehicles in an active flight schedule. The Lunar Base Systems Study is concentrating on the initial years of the Phase 2 Lunar Base Scenario. The study will develop the first five years of that phase in order to define the transportation and surface systems (including mass, volumes, power requirements, and designs)

Expressions of Cushing’s syndrome in multiple endocrine neoplasia type 1

Cushing’s syndrome (CS) resulting from endogenous hypercortisolism can be sporadic or can occur in the context of familial disease because of pituitary or extra-pituitary neuroendocrine tumors. Multiple endocrine neoplasia type 1 (MEN1) is unique among familial endocrine tumor syndromes because hypercortisolism in this context can result from pituitary, adrenal, or thymic neuroendocrine tumors and can therefore reflect either ACTH-dependent or ACTH-independent pathophysiologies. The prominent expressions of MEN1 include primary hyperparathyroidism, tumors of the anterior pituitary, gastroenteropancreatic neuroendocrine tumors, and bronchial carcinoid tumors along with several common non-endocrine manifestations such as cutaneous angiofibromas and leiomyomas. Pituitary tumors are present in about 40% of MEN1 patients, and up to 10% of such tumors secrete ACTH that can result in Cushing’s disease. Adrenocortical neoplasms occur frequently in MEN1. Although such adrenal tumors are mostly clinically silent, this category can include benign or malignant tumors causing hypercortisolism and CS. Ectopic tumoral ACTH secretion has also been observed in MEN1, almost exclusively originating from thymic neuroendocrine tumors. The range of clinical presentations, etiologies, and diagnostic challenges of CS in MEN1 are reviewed herein with an emphasis on the medical literature since 1997, when the MEN1 gene was identified

On The Interpretation Of Unusual Events In Geologic Records Illustrated By Recent Examples

Geological Science

Familial Syndromes of Primary Hyperparathyroidism

Regulation of serum calcium in vertebrates is maintained by the actions of the parathyroid glands working in concert with vitamin D and critical target tissues that include the renal tubules, the small intestine, and bone cells. The parathyroid glands release parathyroid hormone (PTH) into the systemic circulation as is required in order to maintain the serum calcium concentration within a narrow physiologic range. Excessive secretion of PTH from one or more abnormal parathyroid glands however results in primary hyperparathyroidism (HPT), a metabolic disease typically associated with abnormally elevated serum calcium. Although HPT is typically a sporadic disease, it can represent a manifestation of an inherited syndrome. Many sporadic parathyroid tumors result from inactivating mutations in tumor suppressor genes that were first discovered by the analysis of genomic DNA from patients with HPT as part of an inherited syndrome. Somatic and inherited alterations in DNA encoding proto-oncogenes can also cause parathyroid neoplasia. Two promising future approaches for the discovery of novel genes pertinent to parathyroid tumor development are the analysis of acquired genetic alterations in DNA isolated from parathyroid tumors and the investigation of familial HPT in kindreds lacking germline mutation in the known genes predisposing to HPT

The parafibromin tumor suppressor protein interacts with actin-binding proteins actinin-2 and actinin-3

<p>Abstract</p> <p>Background</p> <p>Germline and somatic inactivating mutations in the <it>HRPT2 </it>gene occur in the inherited hyperparathyroidism-jaw tumor syndrome, in some cases of parathyroid cancer and in some cases of familial hyperparathyroidism. <it>HRPT2 </it>encodes parafibromin. To identify parafibromin interacting proteins we used the yeast two-hybrid system for screening a heart cDNA library with parafibromin as the bait.</p> <p>Results</p> <p>Fourteen parafibromin interaction positive preys representing 10 independent clones encoding actinin-2 were isolated. Parafibromin interacted with muscle alpha-actinins (actinin-2 and actinin-3), but not with non-muscle alpha-actinins (actinin-1 and actinin-4). The parafibromin-actinin interaction was verified by yeast two-hybrid, GST pull-down, and co-immunoprecipitation. Yeast two-hybrid analysis revealed that the N-terminal region of parafibromin interacted with actinins. In actin sedimentation assays parafibromin did not dissociate skeletal muscle actinins from actin filaments, but interestingly, parafibromin could also bundle/cross-link actin filaments. Parafibromin was predominantly nuclear in undifferentiated proliferating myoblasts (C2C12 cells), but in differentiated C2C12 myotubes parafibromin co-localized with actinins in the cytoplasmic compartment.</p> <p>Conclusion</p> <p>These data support a possible contribution of parafibromin outside the nucleus through its interaction with actinins and actin bundling/cross-linking. These data also suggest that actinins (and actin) participate in sequestering parafibromin in the cytoplasmic compartment.</p

R7-binding protein targets the G protein β5/R7-regulator of G protein signaling complex to lipid rafts in neuronal cells and brain

<p>Abstract</p> <p>Background</p> <p>Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins), composed of Gα, Gβ, and Gγ subunits, are positioned at the inner face of the plasma membrane and relay signals from activated G protein-coupled cell surface receptors to various signaling pathways. Gβ5 is the most structurally divergent Gβ isoform and forms tight heterodimers with regulator of G protein signalling (RGS) proteins of the R7 subfamily (R7-RGS). The subcellular localization of Gβ 5/R7-RGS protein complexes is regulated by the palmitoylation status of the associated R7-binding protein (R7BP), a recently discovered SNARE-like protein. We investigate here whether R7BP controls the targeting of Gβ5/R7-RGS complexes to lipid rafts, cholesterol-rich membrane microdomains where conventional heterotrimeric G proteins and some effector proteins are concentrated in neurons and brain.</p> <p>Results</p> <p>We show that endogenous Gβ5/R7-RGS/R7BP protein complexes are present in native neuron-like PC12 cells and that a fraction is targeted to low-density, detergent-resistant membrane lipid rafts. The buoyant density of endogenous raft-associated Gβ5/R7-RGS protein complexes in PC12 cells was similar to that of lipid rafts containing the palmitoylated marker proteins PSD-95 and LAT, but distinct from that of the membrane microdomain where flotillin was localized. Overexpression of wild-type R7BP, but not its palmitoylation-deficient mutant, greatly enriched the fraction of endogenous Gβ5/R7-RGS protein complexes in the lipid rafts. In HEK-293 cells the palmitoylation status of R7BP also regulated the lipid raft targeting of co-expressed Gβ5/R7-RGS/R7BP proteins. A fraction of endogenous Gβ5/R7-RGS/R7BP complexes was also present in lipid rafts in mouse brain.</p> <p>Conclusion</p> <p>A fraction of Gβ5/R7-RGS/R7BP protein complexes is targeted to low-density, detergent-resistant membrane lipid rafts in PC12 cells and brain. In cultured cells, the palmitoylation status of R7BP regulated the lipid raft targeting of endogenous or co-expressed Gβ5/R7-RGS proteins. Taken together with recent evidence that the kinetic effects of the Gβ5 complex on GPCR signaling are greatly enhanced by R7BP palmitoylation through a membrane-anchoring mechanism, our data suggest the targeting of the Gβ5/R7-RGS/R7BP complex to lipid rafts in neurons and brain, where G proteins and their effectors are concentrated, may be central to the G protein regulatory function of the complex.</p

Lunar highland rock types : their implications for impact-induced fractionation

Lunar rocks may be classified into three major groups: (1) coarse-grained igneous rocks, (2) fine-grained igneous rocks, and (3) breccias. Group 1 is interpreted as primitive lunar crustal rocks that display various degrees of crushing and/or annealing. Group 2 is interpreted as volcanic rocks. Group 3 is interpreted as resulting from impacts on the lunar surface and is subdivided on the basis of matrix textures into fragmental breccias, crystalline breccias that have been annealed, and crystalline breccias with igneous matrices. A synthesis of the data concerning lunar highlands polymict breccias compels the prediction that the breccias should have homogeneous matrices from rock to rock within regions of the highlands of limited size where impact mixing has been efficient and extensive. But the returned breccias, even from one landing site, display a wide range in composition. This incompatibility between prediction and observation is a paradox that may be resolved by a process that acts after impact mixing to cause a differentiation of the breccia compositions. Partial melting of the local average crustal composition (as modeled by the average soil composition for each site) and separation of melt and residue in ejecta and/or fall-back blankets are compatible with the reviewed data and may resolve the paradox.W. C. Phinney and J. L. Warner, NASA/ Johnson Space Center, Houston, Texas, C. H. Simonds, Lunar Science Institute, Houston, Texa

Patients with MEN1 are at an increased risk for venous thromboembolism VTE risk in MEN1

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing to the development of multiple functional and non-functional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (&lt;1%) and ACTH-producing tumors (&lt;5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have increased risk of VTE. Methods: We queried a prospective natural history study of germline mutation positive MEN1 patients (n=286) between 1991-2019 for all lifetime events of VTE. Search terms were: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban and apixaban. Incidence rates were calculated accounting for age and sex. Comparison was made to published incidence rates in healthy populations, different types of cancer, and Cushing's syndrome. Results: Thirty-six subjects (median age 45 years, range 16-75) experienced a VTE event, yielding a prevalence rate of 12.9%. The age-sex adjusted incidence rate of VTE is 9.11 per 1,000 patient-years, with a sex-adjusted lifetime incidence rate of 2.81 per 1,000 patient-years. MEN1-associated lifetime incidence rates are ~two-fold higher than the estimated annual incidence rate in the general population and are comparable to known risk in the setting of various types of cancer. Approximately 80% were diagnosed with pancreatic NETs, of which 24% were insulinomas. Fourteen patients (42%) experienced peri-operative VTE events. Conclusions: MEN1 patients have an increased risk of VTE. Further mechanistic investigation and validation from other MEN1 cohorts are needed to confirm the increased prevalence of VTE in MEN1

GateFinder: projection-based gating strategy optimization for flow and mass cytometry

Motivation: High-parameter single-cell technologies can reveal novel cell populations of interest, but studying or validating these populations using lower-parameter methods remains challenging.Results: Here, we present GateFinder, an algorithm that enriches high-dimensional cell types with simple, stepwise polygon gates requiring only two markers at a time. A series of case studies of complex cell types illustrates how simplified enrichment strategies can enable more efficient assays, reveal novel biomarkers and clarify underlying biology