76 research outputs found
An Analysis of Air Mobility Express Requirements Operating Within a Lean Logistics Wartime Environment
Lean Logistics was developed in response to budget cuts, force reductions, and a new political world order. The primary objective of Lean Logistics is to minimize the total system wide costs of the Air Force organization. Currently, the Air Force is seeking to cut costs by reducing inventories, improving repair processes, and employing faster transportation where possible. The purpose of this thesis is to determine if the Air Mobility Express (AMX) current sizing plan is capable of supporting the retrograde assets generated during the sustainment portion of a war. The Dyna-METRIC version 6.4 simulation program is employed to analyze the effect of varying such parameters as flying hours and retrograde shipment time on the weight and space required to move retrograde assets. Analysis of the results was accomplished using a Small Sample Test of Hypothesis. The results indicated that the current sizing plan is capable of handling the retrograde cargo generated by four F-16C squadrons for the six scenarios evaluated. This research also hints that while the current plan is capable of supporting four F-16C squadrons, it should be increased to support the transportation of reparables for all weapon systems involved in the war effort
Short-range forces due to Lorentz-symmetry violation
Complementing previous theoretical and experimental work, we explore new
types of short-range modifications to Newtonian gravity arising from
spacetime-symmetry breaking. The first non-perturbative, i.e., to all orders in
coefficients for Lorentz-symmetry breaking, are constructed in the Newtonian
limit. We make use of the generic symmetry-breaking terms modifying the gravity
sector and examine the isotropic coefficient limit. The results show new kinds
of force law corrections, going beyond the standard Yukawa parameterization.
Further, there are ranges of the values of the coefficients that could make the
resulting forces large compared to the Newtonian prediction at short distances.
Experimental signals are discussed for typical test mass arrangements.Comment: 33 pages, 8 color figure
DNA-protein pi-interactions in nature: abundance, structure, composition and strength of contacts between aromatic amino acids and DNA neucleobases or deoxyribose sugar
Sherpa Romeo green journal, open accessFour hundred twenty-eight high-resolution DNA–
protein complexes were chosen for a bioinformatics
study. Although 164 crystal structures (38% of those
searched) contained no interactions, 574 discrete pi-
contacts between the aromatic amino acids and the
DNA nucleobases or deoxyribose were identified using
strict criteria, including visual inspection. The
abundance and structure of the interactions were determined
by unequivocally classifying the contacts
as either pi–pi stacking, Pi–pi T-shaped or sugar–
pi contacts. Three hundred forty-four nucleobase–
amino acid pi–pi contacts (60% of all interactions
identified) were identified in 175 of the crystal structures
searched. Unprecedented in the literature, 230
DNA–protein sugar–pi contacts (40% of all interactions
identified) were identified in 137 crystal structures,
which involve C–H···pi and/or lone–pair···pi interactions,
contain any amino acid and can be classified
according to sugar atoms involved. Both pi–pi
and sugar–pi interactions display a range of relative
monomer orientations and therefore interaction energies
(up to –50 (–70) kJ mol−1 for neutral (charged)
interactions as determined using quantum chemical
calculations). In general, DNA–protein pi-interactions
are more prevalent than perhaps currently accepted
and the role of such interactions in many biological
processes may yet to be uncovered.Ye
Computational investigation of the mechanism of action of DNA glycosylases
xix, 390 leaves : ill. (chiefly col.) ; 29 cm + 1 CD-ROMThe integrity of the base pair sequence that makes up the information storage system of cells is
under continual assault. Two of the most prevalent forms of nucleobase damage are conversion of
cytosine to uracil, and guanine to 8-oxoguanine. Repair of these lesions is initiated by a specific
glycosylase that hydrolyzes the N-glycosidic (sugar–nucleobase) bond of the damaged
nucleotide. The present thesis uses advanced computational chemistry techniques to study the
mechanism of action of three glycosylases, namely human uracil–DNA glycosylase (hUNG2),
adenine–DNA glycosylase (MutY) and human 8-oxoguanine–DNA glycosylase (hOgg1).
Truncated active-site models treated entirely with quantum mechanics, and reaction potential
energy surfaces, provide detailed structural and energetic information regarding how these
enzymes catalyze deglycosylation of their substrates. From these results, a novel and informative
method for predicting the mechanism (e.g., degree of asychronicity) and relative rate is proposed
The structure of the caspase recruitment domain of BinCARD reveals that all three cysteines can be oxidized
The caspase recruitment domain (CARD) is present in death-domain superfamily proteins involved in inflammation and apoptosis. BinCARD is named for its ability to interact with Bcl10 and inhibit downstream signalling. Human BinCARD is expressed as two isoforms that encode the same N-terminal CARD region but which differ considerably in their C-termini. Both isoforms are expressed in immune cells, although BinCARD-2 is much more highly expressed. Crystals of the CARD fold common to both had low symmetry (space group P1). Molecular replacement was unsuccessful in this low-symmetry space group and, as the construct contains no methionines, first one and then two residues were engineered to methionine for MAD phasing. The double-methionine variant was produced as a selenomethionine derivative, which was crystallized and the structure was solved using data measured at two wavelengths. The crystal structures of the native and selenomethionine double mutant were refined to high resolution (1.58 and 1.40 Å resolution, respectively), revealing the presence of a cis-peptide bond between Tyr39 and Pro40. Unexpectedly, the native crystal structure revealed that all three cysteines were oxidized. The mitochondrial localization of BinCARD-2 and the susceptibility of its CARD region to redox modification points to the intriguing possibility of a redox-regulatory role
Genomic Analysis of Individual Differences in Ethanol Drinking: Evidence for Non-Genetic Factors in C57BL/6 Mice
Genetic analysis of factors affecting risk to develop excessive ethanol drinking has been extensively studied in humans and animal models for over 20 years. However, little progress has been made in determining molecular mechanisms underlying environmental or non-genetic events contributing to variation in ethanol drinking. Here, we identify persistent and substantial variation in ethanol drinking behavior within an inbred mouse strain and utilize this model to identify gene networks influencing such “non-genetic” variation in ethanol intake. C57BL/6NCrl mice showed persistent inter-individual variation of ethanol intake in a two-bottle choice paradigm over a three-week period, ranging from less than 1 g/kg to over 14 g/kg ethanol in an 18 h interval. Differences in sweet or bitter taste susceptibility or litter effects did not appreciably correlate with ethanol intake variation. Whole genome microarray expression analysis in nucleus accumbens, prefrontal cortex and ventral midbrain region of individual animals identified gene expression patterns correlated with ethanol intake. Results included several gene networks previously implicated in ethanol behaviors, such as glutamate signaling, BDNF and genes involved in synaptic vesicle function. Additionally, genes functioning in epigenetic chromatin or DNA modifications such as acetylation and/or methylation also had expression patterns correlated with ethanol intake. In verification for the significance of the expression findings, we found that a histone deacetylase inhibitor, trichostatin A, caused an increase in 2-bottle ethanol intake. Our results thus implicate specific brain regional gene networks, including chromatin modification factors, as potentially important mechanisms underlying individual variation in ethanol intake
SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States
This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe
Genomic comparisons reveal biogeographic and anthropogenic impacts in the koala (Phascolarctos cinereus): a dietary-specialist species distributed across heterogeneous environments
The Australian koala is an iconic marsupial with highly specific dietary requirements distributed across heterogeneous environments, over a large geographic range. The distribution and genetic structure of koala populations has been heavily influenced by human actions, specifically habitat modification, hunting and translocation of koalas. There is currently limited information on population diversity and gene flow at a species-wide scale, or with consideration to the potential impacts of local adaptation. Using species-wide sampling across heterogeneous environments, and high-density genome-wide markers (SNPs and PAVs), we show that most koala populations display levels of diversity comparable to other outbred species, except for those populations impacted by population reductions. Genetic clustering analysis and phylogenetic reconstruction reveals a lack of support for current taxonomic classification of three koala subspecies, with only a single evolutionary significant unit supported. Furthermore, similar to 70% of genetic variance is accounted for at the individual level. The Sydney Basin region is highlighted as a unique reservoir of genetic diversity, having higher diversity levels (i.e., Blue Mountains region; AvHe(corr)-0.20, PL% = 68.6). Broad-scale population differentiation is primarily driven by an isolation by distance genetic structure model (49% of genetic variance), with clinal local adaptation corresponding to habitat bioregions. Signatures of selection were detected between bioregions, with no single region returning evidence of strong selection. The results of this study show that although the koala is widely considered to be a dietary-specialist species, this apparent specialisation has not limited the koala's ability to maintain gene flow and adapt across divergent environments as long as the required food source is available
Mammal responses to global changes in human activity vary by trophic group and landscape
Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe
Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility
Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes
- …