Ribonucleoparticle-independent transport of proteins into mammalian microsomes

There are at least two different mechanisms for the transport of secretory proteins into the mammalian endoplasmic reticulum. Both mechanisms depend on the presence of a signal peptide on the respective precursor protein and involve a signal peptide receptor on the cis-side and signal peptidase on the trans-side of the membrane. Furthermore, both mechanisms involve a membrane component with a cytoplasmically exposed sulfhydryl. The decisive feature of the precursor protein with respect to which of the two mechanisms is used is the chain length of the polypeptide. The critical size seems to be around 70 amino acid residues (including the signal peptide). The one mechanism is used by precursor proteins larger than about 70 amino acid residues and involves two cytosolic ribonucleoparticles and their receptors on the microsomal surface. The other one is used by small precursor proteins and relies on the mature part within the precursor molecule and a cytosolic ATPase

Schedulability Analysis for Certification-friendly Multicore Systems

This paper presents a new schedulability test for safety-critical software undergoing a transition from single-core to multicore systems - a challenge faced by multiple industries today. Our migration model, consisting of a schedulability test and execution model, is distinguished by three aspects consistent with reducing transition cost. First, it assumes externally-driven scheduling parameters, such as periods and deadlines, remain fixed (and thus known), whereas exact computation times are not. Second, it adopts a globally synchronized conflict-free I/O model that leads to a decoupling between cores, simplifying the schedulability analysis. Third, it employs global priority assignment across all tasks on each core, irrespective of application, where budget constraints on each application ensure isolation. These properties enable us to obtain a utilization bound that places an allowable limit on total task execution times. Evaluation results demonstrate the advantages of our scheduling model over competing resource partitioning approaches, such as Periodic Server and TDMA.Ope

Past and future of a century old Citrus tristeza virus collection: a California citrus germplasm tale.

Citrus tristeza virus (CTV) isolates collected from citrus germplasm, dooryard and field trees in California from 1914 have been maintained in planta under quarantine in the Citrus Clonal Protection Program (CCPP), Riverside, California. This collection, therefore, represents populations of CTV isolates obtained over time and space in California. To determine CTV genetic diversity in this context, genotypes of CTV isolates from the CCPP collection were characterized using multiple molecular markers (MMM). Genotypes T30, VT, and T36 were found at high frequencies with T30 and T30+VT genotypes being the most abundant. The MMM analysis did not identify T3 and B165/T68 genotypes; however, biological and phylogenetic analysis suggested some relationships of CCPP CTV isolates with these two genotypes. Phylogenetic analysis of the CTV coat protein (CP) gene sequences classified the tested isolates into seven distinct clades. Five clades were in association with the standard CTV genotypes T30, T36, T3, VT, and B165/T68. The remaining two identified clades were not related to any standard CTV genotypes. Spatiotemporal analysis indicated a trend of reduced genotype and phylogenetic diversity as well as virulence from southern California (SC) at early (1907-1957) in comparison to that of central California (CC) isolates collected from later (1957-2009) time periods. CTV biological characterization also indicated a reduced number and less virulent stem pitting (SP) CTV isolates compared to seedling yellows isolates introduced to California. This data provides a historical insight of the introduction, movement, and genetic diversity of CTV in California and provides genetic and biological information useful for CTV quarantine, eradication, and disease management strategies such as CTV-SP cross protection

Expansion of specialized epidermis induced by hormonal state and mechanical strain

In mammals, some sites of specialized skin such as the palms, soles, and lips grow proportionally with the animal. However, other types of specialized skin such as the nipple and anal/genital region are dramatically altered with changes of reproductive status. The specific cell types that mediate the growth of these sites have not been identified. In the mouse, we observed a dramatic expansion of the specialized epidermis of the nipple, coupled to changes in connective tissue and hair shaft density, which we designate as areola formation. During this process thymidine analog uptake was elevated in the epidermis and hair follicles. Although there were no changes in connective tissue cell proliferation, we did observe an altered expression of extracellular matrix genes. In addition, the fibroblasts of the virgin nipple areola and region showed increased transcript and protein levels for estrogen, progesterone, relaxin, and oxytocin relative to those of ventral skin. To determine the role of pregnancy, lactation hormonal milieu, and localized mechanical strain on areola formation, we created models that separated these stimuli and evaluated changes in gross structure, proliferation and protein expression. While modest increases of epidermal proliferation and remodeling of connective tissue occurred as a result of individual stimuli, areola formation required exposure to pregnancy hormones, as well as mechanical strain

Creativity out of chaos

Creativity is said to be highly desired in post-modern and post-industrial organizations Creativity and anarchy on the one hand, and managerialism, on the other, can be seen as different forms of knowledge, two opposed ideals. In many organizational as well as societal reforms we currently observe it is the managerialist ideal that wins over the anarchic. In this paper, we wonder if people fear anarchy? We reflect on the possible reasons for the fear, and we also try to explain why we believe that anarchic organizing should not be avoided or feared

Continuum of vasodilator stress from rest to contrast medium to adenosine hyperemia for fractional flow reserve assessment

Objectives: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). Background: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. Methods: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. Results: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. Conclusions: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement

Polarization state of the optical near-field

The polarization state of the optical electromagnetic field lying several nanometers above complex dielectric structures reveals the intricate light-matter interaction that occurs in this near-field zone. This information can only be extracted from an analysis of the polarization state of the detected light in the near-field. These polarization states can be calculated by different numerical methods well-suited to near--field optics. In this paper, we apply two different techniques (Localized Green Function Method and Differential Theory of Gratings) to separate each polarisation component associated with both electric and magnetic optical near-fields produced by nanometer sized objects. The analysis is carried out in two stages: in the first stage, we use a simple dipolar model to achieve insight into the physical origin of the near-field polarization state. In the second stage, we calculate accurate numerical field maps, simulating experimental near-field light detection, to supplement the data produced by analytical models. We conclude this study by demonstrating the role played by the near-field polarization in the formation of the local density of states.Comment: 9 pages, 11 figures, accepted for publication in Phys. Rev.

Detectability of gravitational wave events by spherical resonant-mass antennas

We have calculated signal-to-noise ratios for eight spherical resonant-mass antennas interacting with gravitational radiation from inspiralling and coalescing binary neutron stars and from the dynamical and secular bar-mode instability of a rapidly rotating star. We find that by using technology that could be available in the next several years, spherical antennas can detect neutron star inspiral and coalescence at a distance of 15 Mpc and the dynamical bar-mode instability at a distance of 2 Mpc.Comment: 39 pages, 4 EPS Figures, some additional SNRs for secular instabilities, some changes to LIGO SNRs, Appendix added on the asymptotic expansion of energy sensitivity, corrected supernova rates. Results available at http://www.physics.umd.edu/rgroups/gen_rel_exp/snr.html Submitted to Phys. Rev.