Orbital Cargo Transfer Simulation

Future space operations will require transfers of a large variety of cargo under both intravehicular and extravehicular conditions. In order to determine the techniques, human factor considerations, assistive devices, package limitations, training procedures, and so forth related to the cargo transfer problem, extensive ground-based simulation is required. To date, several zero- and reduced-gravity simulation techniques have been developed and utilized. All of these techniques have both limitations and definite areas of application. Two of these techniques, water-immersion and zero-g aircraft, are considered usable for cargo transfer simulation. However, the results being obtained using the techniques differ substantially. The reasons for disagreement are to be found in the limitations of the techniques and how they are considered. The purpose of this paper is to provide a comparison of zero-g aircraft .and water-immersion simulation, and to discuss various techniques which can be used to minimize the limitations associated with water immersion

PROTEIN STRUCTURE REPORT Solution structure of the E3 ligase HOIL-1 Ubl domain

Abstract: The E3 ligases HOIL-1 and parkin are each comprised of an N-terminal ubiquitin-like (Ubl) domain followed by a zinc-binding region and C-terminal RING-In-between-RING-RING domains. These two proteins, involved in the ubiquitin-mediated degradation pathway, are the only two known E3 ligases to share this type of multidomain architecture. Further, the Ubl domain of both HOIL-1 and parkin has been shown to interact with the S5a subunit of the 26S proteasome. The solution structure of the HOIL-1 Ubl domain was solved using NMR spectroscopy to compare it with that of parkin to determine the structural elements responsible for S5a intermolecular interactions. The final ensemble of 20 structures had a b-grasp Ubl-fold with an overall backbone RMSD of 0.59 6 0.10 Å in the structured regions between I55 and L131. HOIL-1 had a unique extension of both b1 and b2 sheets compared to parkin and other Ubl domains, a result of a four-residue insertion in this region. A similar 15-residue hydrophobic core in the HOIL-1 Ubl domain resulted in a comparable stability to the parkin Ubl, but significantly lower than that observed for ubiquitin. A comparison with parkin and other Ubl domains indicates that HOIL-1 likely uses a conserved hydrophobic patch (W58, V102, Y127, Y129) found on the b1 face, the b3-b4 loop and b5, as well as a C-terminal basic residue (R134) to recruit the S5a subunit as part of the ubiquitin-mediated proteolysis pathway

Effects of donor cause of death, ischemia time, inotrope exposure, troponin values, cardiopulmonary resuscitation, electrocardiographic and echocardiographic data on recipient outcomes: A review of the literature

BackgroundHeart transplantation has become standard of care for pediatric patients with either end‐stage heart failure or inoperable congenital heart defects. Despite increasing surgical complexity and overall volume, however, annual transplant rates remain largely unchanged. Data demonstrating pediatric donor heart refusal rates of 50% suggest optimizing donor utilization is critical. This review evaluated the impact of donor characteristics surrounding the time of death on pediatric heart transplant recipient outcomes.MethodsAn extensive literature review was performed to identify articles focused on donor characteristics surrounding the time of death and their impact on pediatric heart transplant recipient outcomes.ResultsPotential pediatric heart transplant recipient institutions commonly receive data from seven different donor death‐related categories with which to determine organ acceptance: cause of death, need for CPR, serum troponin, inotrope exposure, projected donor ischemia time, electrocardiographic, and echocardiographic results. Although DITs up to 8 hours have been reported with comparable recipient outcomes, most data support minimizing this period to <4 hours. CVA as a cause of death may be associated with decreased recipient survival but is rare in the pediatric population. Otherwise, however, in the setting of an acceptable donor heart with a normal echocardiogram, none of the other data categories surrounding donor death negatively impact pediatric heart transplant recipient survival.ConclusionsEchocardiographic evaluation is the most important donor clinical information following declaration of brain death provided to potential recipient institutions. Considering its relative importance, every effort should be made to allow direct image visualization.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154939/1/petr13676.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154939/2/petr13676_am.pd

Open String Wavefunctions in Warped Compactifications

We analyze the wavefunctions for open strings in warped compactifications, and compute the warped Kahler potential for the light modes of a probe D-brane. This analysis not only applies to the dynamics of D-branes in warped backgrounds, but also allows to deduce warping corrections to the closed string Kahler metrics via their couplings to open strings. We consider in particular the spectrum of D7-branes in warped Calabi-Yau orientifolds, which provide a string theory realizations of the Randall-Sundrum scenario. We find that certain background fluxes, necessary in the presence of warping, couple to the fermionic wavefunctions and qualitatively change their behavior. This modified dependence of the wavefunctions are needed for consistency with supersymmetry, though it is present in non-supersymmetric vacua as well. We discuss the deviations of our setup from the RS scenario and, as an application of our results, compute the warping corrections to Yukawa couplings in a simple model. Our analysis is performed both with and without the presence of D-brane world-volume flux, as well as for the case of backgrounds with varying dilaton.Comment: 52 pages, refs. added, minor correction

Prospective observational study in patients with obstructive lung disease : NOVELTY design

Peer reviewedPublisher PD

The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery

&lt;p&gt;Background: The small ruminant parasite Haemonchus contortus is the most widely used parasitic nematode in drug discovery, vaccine development and anthelmintic resistance research. Its remarkable propensity to develop resistance threatens the viability of the sheep industry in many regions of the world and provides a cautionary example of the effect of mass drug administration to control parasitic nematodes. Its phylogenetic position makes it particularly well placed for comparison with the free-living nematode Caenorhabditis elegans and the most economically important parasites of livestock and humans.&lt;/p&gt; &lt;p&gt;Results: Here we report the detailed analysis of a draft genome assembly and extensive transcriptomic dataset for H. contortus. This represents the first genome to be published for a strongylid nematode and the most extensive transcriptomic dataset for any parasitic nematode reported to date. We show a general pattern of conservation of genome structure and gene content between H. contortus and C. elegans, but also a dramatic expansion of important parasite gene families. We identify genes involved in parasite-specific pathways such as blood feeding, neurological function, and drug metabolism. In particular, we describe complete gene repertoires for known drug target families, providing the most comprehensive understanding yet of the action of several important anthelmintics. Also, we identify a set of genes enriched in the parasitic stages of the lifecycle and the parasite gut that provide a rich source of vaccine and drug target candidates.&lt;/p&gt; &lt;p&gt;Conclusions: The H. contortus genome and transcriptome provides an essential platform for postgenomic research in this and other important strongylid parasites. &lt;/p&gt

The Maintaining Musculoskeletal Health (MAmMOTH) Study: Protocol for a randomised trial of cognitive behavioural therapy versus usual care for the prevention of chronic widespread pain

Background Cognitive behavioural therapy (CBT) has been shown to improve outcomes for patients with fibromyalgia, and its cardinal feature chronic widespread pain (CWP). Prediction models have now been developed which identify groups who are at high-risk of developing CWP. It would be beneficial to be able to prevent the development of CWP in these people because of the high cost of symptoms and because once established they are difficult to manage. We will test the hypothesis that among patients who are identified as at high-risk, a short course of telephone-delivered CBT (tCBT) reduces the onset of CWP. We will further determine the cost-effectiveness of such a preventative intervention. Methods The study will be a two-arm randomised trial testing a course of tCBT against usual care for prevention of CWP. Eligible participants will be identified from a screening questionnaire sent to patients registered at general practices within three Scottish health boards. Those returning questionnaires indicating they have visited their doctor for regional pain in the last 6 months, and who have two of, sleep problems, maladaptive behaviour response to illness, or high number of somatic symptoms, will be invited to participate. After giving consent, participants will be randomly allocated to either tCBT or usual care. We aim to recruit 473 participants to each treatment arm. Participants in the tCBT group will have an initial assessment with a CBT therapist by telephone, then 6 weekly sessions, and booster sessions 3 and 6 months after treatment start. Those in the usual care group will receive no additional intervention. Follow-up questionnaires measuring the same items as the screening survey questionnaire will be sent 3, 12 and 24 months after start of treatment. The main outcome will be CWP at the 12 month questionnaire. Discussion This will be the first trial of an intervention aimed at preventing fibromyalgia or CWP. The results of the study will help to inform future treatments for the prevention of chronic pain, and aetiological models of its development

Purification and Structural Characterization of Siderophore (Corynebactin) from Corynebacterium diphtheriae

During infection, Corynebacterium diphtheriae must compete with host iron-sequestering mechanisms for iron. C. diphtheriae can acquire iron by a siderophore-dependent iron-uptake pathway, by uptake and degradation of heme, or both. Previous studies showed that production of siderophore (corynebactin) by C. diphtheriae is repressed under high-iron growth conditions by the iron-activated diphtheria toxin repressor (DtxR) and that partially purified corynebactin fails to react in chemical assays for catecholate or hydroxamate compounds. In this study, we purified corynebactin from supernatants of low-iron cultures of the siderophore-overproducing, DtxR-negative mutant strain C. diphtheriae C7(β) ΔdtxR by sequential anion-exchange chromatography on AG1-X2 and Source 15Q resins, followed by reverse-phase high-performance liquid chromatography (RP-HPLC) on Zorbax C8 resin. The Chrome Azurol S (CAS) chemical assay for siderophores was used to detect and measure corynebactin during purification, and the biological activity of purified corynebactin was shown by its ability to promote growth and iron uptake in siderophore-deficient mutant strains of C. diphtheriae under iron-limiting conditions. Mass spectrometry and NMR analysis demonstrated that corynebactin has a novel structure, consisting of a central lysine residue linked through its α- and ε- amino groups by amide bonds to the terminal carboxyl groups of two different citrate residues. Corynebactin from C. diphtheriae is structurally related to staphyloferrin A from Staphylococcus aureus and rhizoferrin from Rhizopus microsporus in which d-ornithine or 1,4-diaminobutane, respectively, replaces the central lysine residue that is present in corynebactin

Chiral matter wavefunctions in warped compactifications

We analyze the wavefunctions for open strings stretching between intersecting 7-branes in type IIB/F-theory warped compactifications, as a first step in understanding the warped effective field theory of 4d chiral fermions. While in general the equations of motion do not seem to admit a simple analytic solution, we provide a method for solving the wavefunctions in the case of weak warping. The method describes warped zero modes as a perturbative expansion in the unwarped spectrum, the coefficients of the expansion depending on the warping. We perform our analysis with and without the presence of worldvolume fluxes, illustrating the procedure with some examples. Finally, we comment on the warped effective field theory for the modes at the intersection.Comment: 64 pages, 1 figure. References updated, typos fixed, discussion on varying dilaton case slightly modified. Version to appear in JHE