Humans to Mars: The Greatest Adventure in Human History

The reasons for a human mission to Mars are many and include (1) World technological leadership, (2) Enhanced national security, (3) Enhanced economic vitality, (4) The human urge to explore new and distant frontiers, (5) Scientific discovery (how did Mars evolve from an early Earth-like, hospitable planet to its present inhospitable state? Is there life on Mars?) (6) Inspiring the American public and the next generation of scientists and engineers (following the launch of Sputnik I by the USSR on October 4, 1957, the U. S. and the rest of the world witnessed a significant increase in the number of students going into science and engineering), (7) Develop new technologies for potential non-space spin-off applications, and, (8) Enhanced national prestige, etc. Other reasons for colonizing the Red Planet are more catastrophic in nature, including Mars as a safe haven for the survival of the human species in the event of an impact with a large asteroid (remember the demise of the dinosaurs 65-million years as a result of an asteroid impact!). Some have also suggested that the colonization of Mars may be a solution to the global exponential population explosion on our planet! A human mission to and the colonization of the Red Planet requires multi-disciplined expertise in many areas including engineering, technology, science, human health and medicine and the human psychological and behavior. To capture the relevant areas of needed expertise, we have invited a group of more than 70 U. S. and foreign experts in these areas, including astronauts, scientists, engineers, technologists, medical doctors, psychologists and economists to share their views and thoughts on a human mission to Mars

Photometric and Spectroscopic Observations of SN 1990E in NGC 1035 Observational Constraints for Models of Type II Supernovae

We present 126 photometric and 30 spectral observations of SN 1990E spanning from 12 days before B maximum to 600 days past discovery. These observations show that SN 1990E was of type II-P, displaying hydrogen in its spectrum, and the characteristic plateau in its light curve. SN 1990E is one of the few SNe II which has been well observed before maximum light, and we present evidence that this SN was discovered very soon after its explosion. In the earliest spectra we identify, for the first time, several H II lines. We present a new technique for measuring extinction to SNe II based on the evolution of absorption lines, and use this method to estimate the extinction to SN 1990E, A_V_= 1.5+/-0.3 mag. From our photometric data we have constructed a bolometric light curve for SN 1990E and show that, even at the earliest times, the bolometric luminosity was falling rapidly. We use the late-time bolometric light curve to show that SN 1990E trapped a majority of the gamma rays produced by the radioactive decay of ^56^Co, and estimate that SN 1990E ejected 0.073_-0.051_^+0.018^ M_sun_ of ^56^Ni, an amount virtually identical to that of SN 1987A.Supernova research at the Harvard University is supported by NSF Grant No. AST 89-05529 and NASA Grant Nos. NAG 5-841 and NGT-51002. A.V.F acknowledges the support of NSF Grant Nos. AST-8957063 and AST-9115174, as well as NSF Cooperative Agreement AST-8809616 (Center for Particle Astrophysics, U. C. Berkeley). Construction of the SONIC was supported by the Scholarly Studies Fund of the Smithsonian Institution

Electrophysiological properties of sodium current subtypes in small cells from adult rat dorsal root ganglia

Whole-cell and single-channel Na+ currents were recorded from small (ca. 20 μm diameter) cells isolated from adult rat dorsal root ganglia (DRG). Currents were classified by their sensitivity to 0.3 μm tetrodotoxin (TTX), electrophysiological properties and single-channel amplitude. Cells were classified according to the types of current recorded from them.Type A cells expressed essentially pure TTX-sensitive (TTX-S) currents. Availability experiments with prepulse durations between 50 ms and 1 s gave a half-available voltage (Vh) of around -65 mV but the availability curves often had a complex shape, consistent with multiple inactivation processes. Measured inactivation time constants ranged from less than 1 ms to over 100 s, depending on the protocol used.Cell types B and C each had, in addition to TTX-S currents, substantial and different TTX-resistant (TTX-R) currents that we have designated TTX-R1 and TTX-R2, respectively. TTX-R1 currents had a 1 s Vh of -29 mV, showed little 1 Hz use dependence at -67 mV and recovered from the inactivation induced by a 60 ms depolarizing pulse with time constants of 1.6 ms (91 %) and 908 ms. They also exhibited slow inactivation processes with component time constants around 10 and 100 s. TTX-R2 currents activated and inactivated at more negative potentials (1 s Vh= -46 mV), showed substantial 1 Hz use dependence and had inactivation (60 ms pulse) recovery time constants at -67 mV of 3.3 ms (58 %) and 902 ms.Type D cells had little or no current in 0.3 μm TTX at a holding potential of -67 mV. Current amplitude increased on changing the holding potential to -107 mV. Type D cell currents had more hyperpolarized availability and I-V curves than even TTX-R2 currents and suggest the existence of TTX-R3 channels.In outside-out patches with 250 mM external NaCl, the single-channel conductance (γ) of TTX-S channels was 19.5 pS and the potential for half-maximal activation (Va) was -45 mV. One population of TTX-R channels had a γ of 9.2 pS and a Va of -27 mV. A second population had a γ of 16.5 pS and a more negative Va of -42 mV. The latter population may underlie the type D cell current.Small DRG cells express multiple Na+ currents with varied time constants and voltage dependences of activation and inactivation. Nociceptive cells still fire when chronically depolarized by an increased external K+ concentration. TTX-R1 and TTX-R2 Na+ channels may support that firing, while the range of inactivation time constants described here would increase the repertoire of DRG cell burst firing behaviour generally

Kinetic Structure of Large-Conductance Ca2+-activated K+ Channels Suggests that the Gating Includes Transitions through Intermediate or Secondary States

Mechanisms for the Ca(2+)-dependent gating of single large-conductance Ca(2+)-activated K(+) channels from cultured rat skeletal muscle were developed using two-dimensional analysis of single-channel currents recorded with the patch clamp technique. To extract and display the essential kinetic information, the kinetic structure, from the single channel currents, adjacent open and closed intervals were binned as pairs and plotted as two-dimensional dwell-time distributions, and the excesses and deficits of the interval pairs over that expected for independent pairing were plotted as dependency plots. The basic features of the kinetic structure were generally the same among single large-conductance Ca(2+)-activated K(+) channels, but channel-specific differences were readily apparent, suggesting heterogeneities in the gating. Simple gating schemes drawn from the Monod- Wyman-Changeux (MWC) model for allosteric proteins could approximate the basic features of the Ca(2+) dependence of the kinetic structure. However, consistent differences between the observed and predicted dependency plots suggested that additional brief lifetime closed states not included in MWC-type models were involved in the gating. Adding these additional brief closed states to the MWC-type models, either beyond the activation pathway (secondary closed states) or within the activation pathway (intermediate closed states), improved the description of the Ca(2+) dependence of the kinetic structure. Secondary closed states are consistent with the closing of secondary gates or channel block. Intermediate closed states are consistent with mechanisms in which the channel activates by passing through a series of intermediate conformations between the more stable open and closed states. It is the added secondary or intermediate closed states that give rise to the majority of the brief closings (flickers) in the gating

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making