Identification of a lineage of multipotent hematopoietic progenitors

All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1^(lo) Sca-1^+ Lin^(-/lo) c-kit^+ cells: long-term reconstituting Mac-1^-CD4^-c-kit^+ cells and transiently reconstituting Mac-1^(lo)CD4^-or Mac-1^(lo) CD4^(lo) cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1- CD4^-c-kit^+ cells gave rise to Mac-1^(lo)CD4^- cells, which gave rise to Mac-1^(lo)CD4^(lo) cells. Mac-1^- CD4^-c-kit^+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 10^4 functionally similar Mac-1^-CD4^-c-kit^+ cells. At least half of Mac-1^(lo)CD4^- cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1^(lo)CD4^(lo) cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment

An interstellar precursor mission

A mission out of the planetary system, with launch about the year 2000, could provide valuable scientific data as well as test some of the technology for a later mission to another star. Primary scientific objectives for the precursor mission concern characteristics of the heliopause, the interstellar medium, stellar distances (by parallax measurements), low energy cosmic rays, interplanetary gas distribution, and mass of the solar system. Secondary objectives include investigation of Pluto. Candidate science instruments are suggested. Individual spacecraft systems for the mission were considered, technology requirements and problem areas noted, and a number of recommendations made for technology study and advanced development. The most critical technology needs include attainment of 50-yr spacecraft lifetime and development of a long-life NEP system

Barkhausen Noise in a Relaxor Ferroelectric

Barkhausen noise, including both periodic and aperiodic components, is found in and near the relaxor regime of a familiar relaxor ferroelectric, PbMg$_{1/3}$Nb$_{2/3}$O$_3$, driven by a periodic electric field. The temperature dependences of both the amplitude and spectral form show that the size of the coherent dipole moment changes shrink as the relaxor regime is entered, contrary to expectations based on some simple models.Comment: 4 pages RevTeX4, 5 figures; submitted to Phys Rev Let

Dual frequency scatterometer measurement of ocean wave height

A technique for remotely measuring wave height averaged over an area of the sea surface was developed and verified with a series of aircraft flight experiments. The measurement concept involves the cross correlation of the amplitude fluctuations of two monochromatic reflected signals with variable frequency separation. The signal reflected by the randomly distributed specular points on the surface is observed in the backscatter direction at nadir incidence angle. The measured correlation coefficient is equal to the square of the magnitude of the characteristic function of the specular point height from which RMS wave height can be determined. The flight scatterometer operates at 13.9 GHz and 13.9 - delta f GHz with a maximum delta f of 40 MHz. Measurements were conducted for low and moderate sea states at altitudes of 2, 5, and 10 thousand feet. The experimental results agree with the predicted decorrelation with frequency separation and with off-nadir incidence angle

Stellar 36,38^{36,38}Ar(n,γ)37,39(n,\gamma)^{37,39}Ar reactions and their effect on light neutron-rich nuclide synthesis

The $^{36}$Ar$(n,\gamma)^{37}$Ar ($t_{1/2}$ = 35 d) and $^{38}$Ar$(n,\gamma)^{39}$Ar (269 y) reactions were studied for the first time with a quasi-Maxwellian ($kT \sim 47$ keV) neutron flux for Maxwellian Average Cross Section (MACS) measurements at stellar energies. Gas samples were irradiated at the high-intensity Soreq applied research accelerator facility-liquid-lithium target neutron source and the $^{37}$Ar/$^{36}$Ar and $^{39}$Ar/$^{38}$Ar ratios in the activated samples were determined by accelerator mass spectrometry at the ATLAS facility (Argonne National Laboratory). The $^{37}$Ar activity was also measured by low-level counting at the University of Bern. Experimental MACS of $^{36}$Ar and $^{38}$Ar, corrected to the standard 30 keV thermal energy, are 1.9(3) mb and 1.3(2) mb, respectively, differing from the theoretical and evaluated values published to date by up to an order of magnitude. The neutron capture cross sections of $^{36,38}$Ar are relevant to the stellar nucleosynthesis of light neutron-rich nuclides; the two experimental values are shown to affect the calculated mass fraction of nuclides in the region A=36-48 during the weak $s$-process. The new production cross sections have implications also for the use of $^{37}$Ar and $^{39}$Ar as environmental tracers in the atmosphere and hydrosphere.Comment: 18 pages + Supp. Mat. (13 pages) Accepted for publication in Phys. Rev. Let

The helicase Ded1p controls use of near-cognate translation initiation codons in 5' UTRs.

The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian orthologue DDX3 are critical for the initiation of translation1. Mutations in DDX3 are linked to tumorigenesis2-4 and intellectual disability5, and the enzyme is targeted by a range of viruses6. How Ded1p and its orthologues engage RNAs during the initiation of translation is unknown. Here we show, by integrating transcriptome-wide analyses of translation, RNA structure and Ded1p-RNA binding, that the effects of Ded1p on the initiation of translation are connected to near-cognate initiation codons in 5' untranslated regions. Ded1p associates with the translation pre-initiation complex at the mRNA entry channel and repressing the activity of Ded1p leads to the accumulation of RNA structure in 5' untranslated regions, the initiation of translation from near-cognate start codons immediately upstream of these structures and decreased protein synthesis from the corresponding main open reading frames. The data reveal a program for the regulation of translation that links Ded1p, the activation of near-cognate start codons and mRNA structure. This program has a role in meiosis, in which a marked decrease in the levels of Ded1p is accompanied by the activation of the alternative translation initiation sites that are seen when the activity of Ded1p is repressed. Our observations indicate that Ded1p affects translation initiation by controlling the use of near-cognate initiation codons that are proximal to mRNA structure in 5' untranslated regions

Challenges to Satellite Sensors of Ocean Winds: Addressing Precipitation Effects

Measurements of global ocean surface winds made by orbiting satellite radars have provided valuable information to the oceanographic and meteorological communities since the launch of the Seasat in 1978, by the National Aeronautics and Space Administration (NASA). When Quick Scatterometer (QuikSCAT) was launched in 1999, it ushered in a new era of dual-polarized, pencil-beam, higher-resolution scatterometers for measuring the global ocean surface winds from space. A constant limitation on the full utilization of scatterometer-derived winds is the presence of isolated rain events, which affect about 7% of the observations. The vector wind sensors, the Ku-band scatterometers [NASA\u27s SeaWinds on the QuikSCAT and Midori-II platforms and Indian Space Research Organisation\u27s (ISRO\u27s) Ocean Satellite (Oceansat)-2], and the current C-band scatterometer [Advanced Wind Scatterometer (ASCAT), on the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT)\u27s Meteorological Operation (MetOp) platform] all experience rain interference, but with different characteristics. Over this past decade, broad-based research studies have sought to better understand the physics of the rain interference problem, to search for methods to bypass the problem (using rain detection, flagging, and avoidance of affected areas), and to develop techniques to improve the quality of the derived wind vectors that are adversely affected by rain. This paper reviews the state of the art in rain flagging and rain correction and describes many of these approaches, methodologies, and summarizes the results

Antibiotic prophylaxis is associated with subsequent resistant infections in children with an initial extended-spectrum-cephalosporin-resistant Enterobacteriaceae infection

ABSTRACT The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae . We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged &lt;22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH ( E. coli ) or tonB ( Klebsiella pneumoniae ) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections. </jats:p

The aggregation of cytochrome C may be linked to its flexibility during refolding

Large-scale expression of biopharmaceutical proteins in cellular hosts results in production of large insoluble mass aggregates. In order to generate functional product, these aggregates require further processing through refolding with denaturant, a process in itself that can result in aggregation. Using a model folding protein, cytochrome C, we show how an increase in final denaturant concentration decreases the propensity of the protein to aggregate during refolding. Using polarised fluorescence anisotropy, we show how reduced levels of aggregation can be achieved by increasing the period of time the protein remains flexible during refolding, mediated through dilution ratios. This highlights the relationship between the flexibility of a protein and its propensity to aggregate. We attribute this behaviour to the preferential urea-residue interaction, over self-association between molecules

How a spin-glass remembers. Memory and rejuvenation from intermittency data: an analysis of temperature shifts

The memory and rejuvenation aspects of intermittent heat transport are explored theoretically and by numerical simulation for Ising spin glasses with short-ranged interactions. The theoretical part develops a picture of non-equilibrium glassy dynamics recently introduced by the authors. Invoking the concept of marginal stability, this theory links irreversible `intermittent' events, or `quakes' to thermal fluctuations of record magnitude. The pivotal idea is that the largest energy barrier $b(t_w,T)$ surmounted prior to $t_w$ by thermal fluctuations at temperature $T$ determines the rate $r_q \propto 1/t_w$ of the intermittent events occurring near $t_w$. The idea leads to a rate of intermittent events after a negative temperature shift given by $r_q \propto 1/t_w^{eff}$, where the `effective age' $t_w^{eff} \geq t_w$ has an algebraic dependence on $t_w$, whose exponent contains the temperatures before and after the shift. The analytical expression is verified by numerical simulations. Marginal stability suggests that a positive temperature shift $T \to T'$ could erase the memory of the barrier $b(t_w,T)$. The simulations show that the barrier $b(t_w,T') \geq b(t_w,T)$ controls the intermittent dynamics, whose rate is hence $r_q \propto 1/t_w$. Additional `rejuvenation' effects are also identified in the intermittency data for shifts of both signs.Comment: Revised introduction and discussion. Final version to appear in Journal of Statistical Mechanics: Theory and Experimen