From Earth to Orbit: An assessment of transportation options

The report assesses the requirements, benefits, technological feasibility, and roles of Earth-to-Orbit transportation systems and options that could be developed in support of future national space programs. Transportation requirements, including those for Mission-to-Planet Earth, Space Station Freedom assembly and operation, human exploration of space, space science missions, and other major civil space missions are examined. These requirements are compared with existing, planned, and potential launch capabilities, including expendable launch vehicles (ELV's), the Space Shuttle, the National Launch System (NLS), and new launch options. In addition, the report examines propulsion systems in the context of various launch vehicles. These include the Advanced Solid Rocket Motor (ASRM), the Redesigned Solid Rocket Motor (RSRM), the Solid Rocket Motor Upgrade (SRMU), the Space Shuttle Main Engine (SSME), the Space Transportation Main Engine (STME), existing expendable launch vehicle engines, and liquid-oxygen/hydrocarbon engines. Consideration is given to systems that have been proposed to accomplish the national interests in relatively cost effective ways, with the recognition that safety and reliability contribute to cost-effectiveness. Related resources, including technology, propulsion test facilities, and manufacturing capabilities are also discussed

Emission-Line Galaxies from the Hubble Space Telescope Probing Evolution and Reionization Spectroscopically (PEARS) Grism Survey. II: The Complete Sample

We present a full analysis of the Probing Evolution And Reionization Spectroscopically (PEARS) slitess grism spectroscopic data obtained with the Advanced Camera for Surveys on HST. PEARS covers fields within both the Great Observatories Origins Deep Survey (GOODS) North and South fields, making it ideal as a random survey of galaxies, as well as the availability of a wide variety of ancillary observations to support the spectroscopic results. Using the PEARS data we are able to identify star forming galaxies within the redshift volume 0< z<1.5. Star forming regions in the PEARS survey are pinpointed independently of the host galaxy. This method allows us to detect the presence of multiple emission line regions (ELRs) within a single galaxy. 1162 Ha, [OIII] and/or [OII] emission lines have been identified in the PEARS sample of ~906 galaxies down to a limiting flux of ~1e-18 erg/s/cm^2. The ELRs have also been compared to the properties of the host galaxy, including morphology, luminosity, and mass. From this analysis we find three key results: 1) The computed line luminosities show evidence of a flattening in the luminosity function with increasing redshift; 2) The star forming systems show evidence of disturbed morphologies, with star formation occurring predominantly within one effective (half-light) radius. However, the morphologies show no correlation with host stellar mass; and 3) The number density of star forming galaxies with M_* > 1e9} M_sun decreases by an order of magnitude at z<0.5 relative to the number at 0.5<z<0.9 in support of the argument for galaxy downsizing.Comment: Submitted. 48 pages. 19 figures. Accepted to Ap

Charge collection properties of TowerJazz 180 nm CMOS Pixel Sensors in dependence of pixel geometries and bias parameters, studied using a dedicated test-vehicle: the Investigator chip

This paper contains a compilation of parameters influencing the charge collection process extracted from a comprehensive study of partially depleted Monolithic Active Pixel Sensors with small (<25 um$^2$) collection electrodes fabricated in the TowerJazz 180 nm CMOS process. These results gave guidance for the optimisation of the diode implemented in ALPIDE, the chip used in the second generation Inner Tracking System of ALICE, and serve as reference for future simulation studies of similar devices. The studied parameters include: reverse substrate bias, epitaxial layer thickness, charge collection electrode size and the spacing of the electrode to surrounding in-pixel electronics. The results from pixels of 28 um pitch confirm that even in partially depleted circuits, charge collection can be fast (<10 ns), and quantify the influence of the parameters onto the signal sharing and amplitudes, highlighting the importance of a correct spacing between wells and of the impact of the reverse substrate bias

On cycles in the transcription network of Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>We investigate the cycles in the transcription network of <it>Saccharomyces cerevisiae</it>. Unlike a similar network of <it>Escherichia coli</it>, it contains many cycles. We characterize properties of these cycles and their place in the regulatory mechanism of the cell.</p> <p>Results</p> <p>Almost all cycles in the transcription network of <it>Saccharomyces cerevisiae </it>are contained in a single <it>strongly connected component</it>, which we call LSCC (L for "largest"), except for a single cycle of two transcription factors. The fact that LSCC includes almost all cycles is well explained by the properties of a random graph with the same in- and out-degrees of the nodes.</p> <p>Among different physiological conditions, cell cycle has the most significant relationship with LSCC, as the set of 64 transcription interactions that are active in all phases of the cell cycle has overlap of 27 with the interactions of LSCC (of which there are 49).</p> <p>Conversely, if we remove the interactions that are active in all phases of the cell cycle (25% of interactions to transcription factors), the LSCC would have only three nodes and 5 edges, many fewer than expected. This subgraph of the transcription network consists mostly of interactions that are active only in the stress response subnetwork.</p> <p>We also characterize the role of LSCC in the topology of the network. We show that LSCC can be used to define a natural hierarchy in the network and that in every physiological subnetwork LSCC plays a pivotal role.</p> <p>Conclusion</p> <p>Apart from those well-defined conditions, the transcription network of <it>Saccharomyces cerevisiae </it>is devoid of cycles. It was observed that two conditions that were studied and that have no cycles of their own are <it>exogenous</it>: diauxic shift and DNA repair, while cell cycle and sporulation are <it>endogenous</it>. We claim that in a certain sense (slow recovery) stress response is <it>endogenous </it>as well.</p

History of Galaxy Interactions and their Impact on Star Formation over the Last 7 Gyr from GEMS

We perform a comprehensive estimate of the frequency of galaxy mergers and their impact on star formation over z~0.24--0.80 (lookback time T_b~3--7 Gyr) using 3698 (M*>=1e9 Msun) galaxies with GEMS HST, COMBO-17, and Spitzer data. Our results are: (1) Among 790 high mass (M*>=2.5e10 Msun) galaxies, the visually-based merger fraction over z~0.24--0.80, ranges from 9%+-5% to 8%+-2%. Lower limits on the major and minor merger fractions over this interval range from 1.1% to 3.5%, and 3.6% to 7.5%, respectively. This is the first approximate empirical estimate of the frequency of minor mergers at z<1. For a visibility timescale of ~0.5 Gyr, it follows that over T_b~3--7 Gyr, ~68% of high mass systems have undergone a merger of mass ratio >1/10, with ~16%, 45%, and 7% of these corresponding respectively to major, minor, and ambiguous `major or minor' mergers. The mean merger rate is a few x 1e-4 Gyr-1 Mpc-3. (2) We compare the empirical merger fraction and rate for high mass galaxies to a suite of Lambda CDM-based models: halo occupation distribution models, semi-analytic models, and hydrodynamic SPH simulations. We find qualitative agreement between observations and models such that the (major+minor) merger fraction or rate from different models bracket the observations, and show a factor of five dispersion. Near-future improvements can now start to rule out certain merger scenarios. (3) Among ~3698 M*>=1e9 Msun galaxies, we find that the mean SFR of visibly merging systems is only modestly enhanced compared to non-interacting galaxies over z~0.24--0.80. Visibly merging systems only account for less than 30% of the cosmic SFR density over T_b~3--7 Gyr. This suggests that the behavior of the cosmic SFR density over the last 7 Gyr is predominantly shaped by non-interacting galaxies.Comment: Accepted for Publication in the Astrophysical Journal. 17 pages of text, 21 figures, 3 tables. Uses emulateapj5.st

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat

Introduction. A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods. Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg j1 of fluvoxamine. Analysis. With increasing dose a disproportional increase in brain concentrations was observed. Th

Targeted Drug Delivery by Gemtuzumab Ozogamicin: Mechanism-Based Mathematical Model for Treatment Strategy Improvement and Therapy Individualization

Gemtuzumab ozogamicin (GO) is a chemotherapy-conjugated anti-CD33 monoclonal antibody effective in some patients with acute myeloid leukemia (AML). The optimal treatment schedule and optimal timing of GO administration relative to other agents remains unknown. Conventional pharmacokinetic analysis has been of limited insight for the schedule optimization. We developed a mechanism-based mathematical model and employed it to analyze the time-course of free and GO-bound CD33 molecules on the lekemic blasts in individual AML patients treated with GO. We calculated expected intravascular drug exposure (I-AUC) as a surrogate marker for the response to the drug. A high CD33 production rate and low drug efflux were the most important determinants of high I-AUC, characterizing patients with favorable pharmacokinetic profile and, hence, improved response. I-AUC was insensitive to other studied parameters within biologically relevant ranges, including internalization rate and dissociation constant. Our computations suggested that even moderate blast burden reduction prior to drug administration enables lowering of GO doses without significantly compromising intracellular drug exposure. These findings indicate that GO may optimally be used after cyto-reductive chemotherapy, rather than before, or concomitantly with it, and that GO efficacy can be maintained by dose reduction to 6 mg/m2 and a dosing interval of 7 days. Model predictions are validated by comparison with the results of EORTC-GIMEMA AML19 clinical trial, where two different GO schedules were administered. We suggest that incorporation of our results in clinical practice can serve identification of the subpopulation of elderly patients who can benefit most of the GO treatment and enable return of the currently suspended drug to clinic