Logic gates using high Rydberg states

Connected logic gates can be operated on the levels of one molecule by making use of the special properties of high Rydberg states. Explicit experimental results for the NO molecule are provided as an example. A number of other options, including that of several gates concatenated so as to operate as a full adder, are discussed. Specific properties of high Rydberg states that are used are: their autoionization is delayed so that they can be distinguished from direct multiphoton ionization, during their long life such states also can decay by energy transfer to the molecular core in a way that can be controlled by the judicious application of very weak external electrical fields, and the Rydberg states can be detected by the application of an ionizing electrical field. The combination of two (or three) color photons with and without external weak fields allows the construction of quite elaborate logic circuit diagrams and shows that taking advantage of the different intramolecular dynamics of levels that differ by their excitation enables the compounding of logic operations on one molecular frame.

Identification of protein oligomerization states by analysis of interface conservation

The discrimination of true oligomeric protein–protein contacts from nonspecific crystal contacts remains problematic. Criteria that have been used previously base the assignment of oligomeric state on consideration of the area of the interface and/or the results of scoring functions based on statistical potentials. Both techniques have a high success rate but fail in more than 10% of cases. More importantly, the oligomeric states of several proteins are incorrectly assigned by both methods. Here we test the hypothesis that true oligomeric contacts should be identifiable on the basis of an increased degree of conservation of the residues involved in the interface. By quantifying the degree of conservation of the interface and comparing it with that of the remainder of the protein surface, we develop a new criterion that provides a highly effective complement to existing methods.

Chemically distinct transition states govern rapid dissociation of single L-selectin bonds under force

Carbohydrate–protein bonds interrupt the rapid flow of leukocytes in the circulation by initiation of rolling and tethering at vessel walls. The cell surface carbohydrate ligands are glycosylated proteins like the mucin P-selectin glycoprotein ligand-1 (PSGL-1), which bind ubiquitously to the family of E-, P-, and L-selectin proteins in membranes of leukocytes and endothelium. The current view is that carbohydrate–selectin bonds dissociate a few times per second, and the unbinding rate increases weakly with force. However, such studies have provided little insight into how numerous hydrogen bonds, a Ca2+ metal ion bond, and other interactions contribute to the mechanical strength of these attachments. Decorating a force probe with very dilute ligands and controlling touch to achieve rare single-bond events, we have varied the unbinding rates of carbohydrate–selectin bonds by detachment with ramps of force/time from 10 to 100,000 pN/sec. Testing PSGL-1, its outer 19 aa (19FT), and sialyl LewisX (sLeX) against L-selectin in vitro on glass microspheres and in situ on neutrophils, we found that the unbinding rates followed the same dependence on force and increased by nearly 1,000-fold as rupture forces rose from a few to ≈200 pN. Plotted on a logarithmic scale of loading rate, the rupture forces reveal two prominent energy barriers along the unbinding pathway. Strengths above 75 pN arise from rapid detachment (<0.01 sec) impeded by an inner barrier that requires a Ca2+ bond between a single sLeX and the lectin domain. Strengths below 75 pN occur under slow detachment (>0.01 sec) impeded by the outer barrier, which appears to involve an array of weak (putatively hydrogen) bonds.

New Members and Foreign Associates Elected to the National Academy of Sciences on May 1, 2001: 72 New Members Chosen by the Academy

The Academy has elected 72 new members and 15 foreign associates from 10 countries in recognition of their distinguished and continuing achievements in original research. The election was held during the business session of the 138th annual meeting of the Academy. Election to membership in the Academy is considered one of the highest honors that can be accorded a U.S. scientist or engineer. Foreign associates are non-voting members of the Academy, with citizenship outside of the United States.

Ecosystem impacts of three sequential hurricanes (Dennis, Floyd, and Irene) on the United States' largest lagoonal estuary, Pamlico Sound, NC

Three sequential hurricanes, Dennis, Floyd, and Irene, affected coastal North Carolina in September and October 1999. These hurricanes inundated the region with up to 1 m of rainfall, causing 50- to 500-year flooding in the watershed of the Pamlico Sound, the largest lagoonal estuary in the United States and a key West Atlantic fisheries nursery. We investigated the ecosystem-level impacts on and responses of the Sound to the floodwater discharge. Floodwaters displaced three-fourths of the volume of the Sound, depressed salinity by a similar amount, and delivered at least half of the typical annual nitrogen load to this nitrogen-sensitive ecosystem. Organic carbon concentrations in floodwaters entering Pamlico Sound via a major tributary (the Neuse River Estuary) were at least 2-fold higher than concentrations under prefloodwater conditions. A cascading set of physical, chemical, and ecological impacts followed, including strong vertical stratification, bottom water hypoxia, a sustained increase in algal biomass, displacement of many marine organisms, and a rise in fish disease. Because of the Sound's long residence time (≈1 year), we hypothesize that the effects of the short-term nutrient enrichment could prove to be multiannual. A predicted increase in the frequency of hurricane activity over the next few decades may cause longer-term biogeochemical and trophic changes in this and other estuarine and coastal habitats.

Changes in the prevalence of chronic disability in the United States black and nonblack population above age 65 from 1982 to 1999

Survey evidence through the early 1990s generally suggests a reduction in disability in the elderly population of the United States. Because the evidence is not fully consistent, several authors have speculated about whether disability declines will continue. This paper reports results from the 1999 National Long-Term Care Survey on disability trends from 1982 through 1999. It is found that disability continued to decline in the 1994 to 1999 period, and that the decline was greater in the 1990s than in the 1980s. The disability decline from 1982 to 1989 was 0.26% per year, from 1989 to 1994 it was 0.38% per year, and from 1994 to 1999 it was 0.56% per year. In addition, disability declined by a greater percentage for blacks than for nonblacks over the 1989 to 1999 period.

The spinal biology in humans and animals of pain states generated by persistent small afferent input

Behavioral models indicate that persistent small afferent input, as generated by tissue injury, results in a hyperalgesia at the site of injury and a tactile allodynia in areas adjacent to the injury site. Hyperalgesia reflects a sensitization of the peripheral terminal and a central facilitation evoked by the persistent small afferent input. The allodynia reflects a central sensitization. The spinal pharmacology of these pain states has been defined in the unanesthetized rat prepared with spinal catheters for injection and dialysis. After tissue injury, excitatory transmitters (e.g., glutamate and substance P) acting though N-methyl-d-aspartate (NMDA) and neurokinin 1 receptors initiate a cascade that evokes release of (i) NO, (ii) cyclooxygenase products, and (iii) activation of several kinases. Spinal dialysis show amino acid and prostanoid release after cutaneous injury. Spinal neurokinin 1, NMDA, and non-NMDA receptors enhance spinal prostaglandin E2 release. Spinal prostaglandins facilitate release of spinal amino acids and peptides. Activation by intrathecal injection of receptors on spinal C fiber terminals (μ,/∂ opiate, α2 adrenergic, neuropeptide Y) prevents release of primary afferent peptides and spinal amino acids and blocks acute and facilitated pain states. Conversely, consistent with their role in facilitated processing, NMDA, cyclooxygenase 2, and NO synthase inhibitors act to diminish only hyperalgesia. Importantly, spinal delivery of several of these agents diminishes human injury pain states. This efficacy emphasizes (i) the role of facilitated states in humans, (ii) shows the importance of spinal systems in human pain processing, and (iii) indicates that these preclinical mechanisms reflect processes that regulate the human pain experience.

New Members and Foreign Associates Elected to the National Academy of Sciences on May 2, 2000: 60 New Members Chosen by the Academy

The Academy has elected 60 new members and 15 foreign associates from 9 countries in recognition of their distinguished and continuing achievements in original research. The election was held during the business session of the 137th annual meeting of the Academy. Election to membership in the Academy is considered one of the highest honors that can be accorded a U.S. scientist or engineer. Foreign associates are non-voting members of the Academy, with citizenship outside of the United States.

Trends and patterns in research and development expenditures in the United States

This paper is a review of recent trends in United States expenditures on research and development (R&D). Real expenditures by both the government and the private sector increased rapidly between the mid-1970s and the mid-1980s, and have since leveled off. This is true of both overall expenditures and expenditures on basic research, as well as funding of academic research. Preliminary estimates indicate that about $170 billion was spent on R&D in the United States in 1995, with ≈60% of that funding coming from the private sector and about 35% from the federal government. In comparison to other countries, we have historically spent more on R&D relative to our economy than other advanced economies, but this advantage appears to be disappearing. If defense-related R&D is excluded, our expenditures relative to the size of the economy are considerably smaller than those of other similar economies.

The future of the national laboratories

The end of the Cold War has called into question the activities of the national laboratories and, more generally, the level of support now given to federal intramural research in the United States. This paper seeks to analyze the potential role of the laboratories, with particular attention to the possibility, on the one hand, of integrating private technology development into the laboratory’s menu of activities and, on the other hand, of outsourcing traditional mission activities. We review the economic efficiency arguments for intramural research and the political conditions that are likely to constrain the activities of the laboratories, and analyze the early history of programs intended to promote new technology via cooperative agreements between the laboratories and private industry. Our analysis suggests that the laboratories are likely to shrink considerably in size, and that the federal government faces a significant problem in deciding how to organize a downsizing of the federal research establishment.

Long-range transport of mineral dust in the global atmosphere: Impact of African dust on the environment of the southeastern United States

Soil dust is a major constituent of airborne particles in the global atmosphere. Dust plumes frequently cover huge areas of the earth; they are one of the most prominent and commonly visible features in satellite imagery. Dust is believed to play a role in many biogeochemical processes, but the importance of dust in these processes is not well understood because of the dearth of information about the global distribution of dust and its physical, chemical, and mineralogical properties. This paper describes some features of the large-scale distribution of dust and identifies some of the geological characteristics of important source areas. The transport of dust from North Africa is presented as an example of possible long-range dust effects, and the impact of African dust on environmental processes in the western North Atlantic and the southeastern United States is assessed. Dust transported over long distances usually has a mass median diameter <10 μm. Small wind-borne soil particles show signs of extensive weathering; consequently, the physical and chemical properties of the particles will greatly depend on the weathering history in the source region and on the subsequent modifications that occur during transit in the atmosphere (typically a period of a week or more). To fully understand the role of dust in the environment and in human health, mineralogists will have to work closely with scientists in other disciplines to characterize the properties of mineral particles as an ensemble and as individual particles especially with regard to surface characteristics.

Evidence for a circulating islet cell growth factor in insulin-resistant states

Insulin resistance is a feature of many common disorders including obesity and type 2 diabetes mellitus. In these disorders, the β-cells compensate for the insulin resistance for long periods of time with an increase in secretory capacity, an increase in β-cell mass, or both. To determine whether the β-cell response might relate to a circulating growth factor, we have transplanted normal islets under the kidney capsule of normoglycemic insulin-resistant mice with two different models of insulin resistance: lean mice that have a double heterozygous deletion of the insulin receptor and insulin receptor substrate-1 (DH) or the obese, hyperglycemic ob/ob mice. In the grafts transplanted into both hosts, there was a marked increase in β-cell mitotic activity and islet mass that was comparable with that observed in the endogenous pancreas. By contrast, islets of the DH mouse transplanted into normal mice showed reduced mitotic index. These data suggest the insulin resistance is associated with a circulating islet cell growth factor that is independent of glucose and obesity.

Public library consumer health information pilot project: results of a National Library of Medicine evaluation

In October 1998, the National Library of Medicine (NLM) launched a pilot project to learn about the role of public libraries in providing health information to the public and to generate information that would assist NLM and the National Network of Libraries of Medicine (NN/LM) in learning how best to work with public libraries in the future. Three regional medical libraries (RMLs), eight resource libraries, and forty-one public libraries or library systems from nine states and the District of Columbia were selected for participation. The pilot project included an evaluation component that was carried out in parallel with project implementation. The evaluation ran through September 1999. The results of the evaluation indicated that participating public librarians were enthusiastic about the training and information materials provided as part of the project and that many public libraries used the materials and conducted their own outreach to local communities and groups. Most libraries applied the modest funds to purchase additional Internet-accessible computers and/or upgrade their health-reference materials. However, few of the participating public libraries had health information centers (although health information was perceived as a top-ten or top-five topic of interest to patrons). Also, the project generated only minimal usage of NLM's consumer health database, known as MEDLINEplus, from the premises of the monitored libraries (patron usage from home or office locations was not tracked). The evaluation results suggested a balanced follow-up by NLM and the NN/LM, with a few carefully selected national activities, complemented by a package of targeted activities that, as of January 2000, are being planned, developed, or implemented. The results also highlighted the importance of building an evaluation component into projects like this one from the outset, to assure that objectives were met and that evaluative information was available on a timely basis, as was the case here.

Dynamical hierarchy in transition states: Why and how does a system climb over the mountain?

How a reacting system climbs through a transition state during the course of a reaction has been an intriguing subject for decades. Here we present and quantify a technique to identify and characterize local invariances about the transition state of an N-particle Hamiltonian system, using Lie canonical perturbation theory combined with microcanonical molecular dynamics simulation. We show that at least three distinct energy regimes of dynamical behavior occur in the region of the transition state, distinguished by the extent of their local dynamical invariance and regularity. Isomerization of a six-atom Lennard–Jones cluster illustrates this: up to energies high enough to make the system manifestly chaotic, approximate invariants of motion associated with a reaction coordinate in phase space imply a many-body dividing hypersurface in phase space that is free of recrossings even in a sea of chaos. The method makes it possible to visualize the stable and unstable invariant manifolds leading to and from the transition state, i.e., the reaction path in phase space, and how this regularity turns to chaos with increasing total energy of the system. This, in turn, illuminates a new type of phase space bottleneck in the region of a transition state that emerges as the total energy and mode coupling increase, which keeps a reacting system increasingly trapped in that region.

The relaxation dynamics of the excited electronic states of retinal in bacteriorhodopsin by two-pump-probe femtosecond studies

We present the results of two-pump and probe femtosecond experiments designed to follow the relaxation dynamics of the lowest excited state (S1) populated by different modes. In the first mode, a direct (S0 → S1) radiative excitation of the ground state is used. In the second mode, an indirect excitation is used where the S1 state is populated by the use of two femtosecond laser pulses with different colors and delay times between them. The first pulse excites the S0 → S1 transition whereas the second pulse excites the S1 → Sn transition. The nonradiative relaxation from the Sn state populates the lowest excited state. Our results suggest that the S1 state relaxes faster when populated nonradiatively from the Sn state than when pumped directly by the S0 → S1 excitation. Additionally, the Sn → S1 nonradiative relaxation time is found to change by varying the delay time between the two pump pulses. The observed dependence of the lowest excited state population as well as its dependence on the delay between the two pump pulses are found to fit a kinetic model in which the Sn state populates a different surface (called S′1) than the one being directly excited (S1). The possible involvement of the Ag type states, the J intermediate, and the conical intersection leading to the S0 or to the isomerization product (K intermediate) are discussed in the framework of the proposed model.