Multicritical behavior in coupled directed percolation processes

We study a hierarchy of directed percolation (DP) processes for particle species A, B, ..., unidirectionally coupled via the reactions A -> B, ... When the DP critical points at all levels coincide, multicritical behavior emerges, with density exponents \beta^{(k)} which are markedly reduced at each hierarchy level k >= 2. We compute the fluctuation corrections to \beta^{(2)} to O(\epsilon = 4-d) using field-theoretic renormalization group techniques. Monte Carlo simulations are employed to determine the new exponents in dimensions d <= 3.Comment: 5 pages, RevTex, no figures; final version, to appear in Phys. Rev. Lett. (1998

Force generation in small ensembles of Brownian motors

The motility of certain gram-negative bacteria is mediated by retraction of type IV pili surface filaments, which are essential for infectivity. The retraction is powered by a strong molecular motor protein, PilT, producing very high forces that can exceed 150 pN. The molecular details of the motor mechanism are still largely unknown, while other features have been identified, such as the ring-shaped protein structure of the PilT motor. The surprisingly high forces generated by the PilT system motivate a model investigation of the generation of large forces in molecular motors. We propose a simple model, involving a small ensemble of motor subunits interacting through the deformations on a circular backbone with finite stiffness. The model describes the motor subunits in terms of diffusing particles in an asymmetric, time-dependent binding potential (flashing ratchet potential), roughly corresponding to the ATP hydrolysis cycle. We compute force-velocity relations in a subset of the parameter space and explore how the maximum force (stall force) is determined by stiffness, binding strength, ensemble size, and degree of asymmetry. We identify two qualitatively different regimes of operation depending on the relation between ensemble size and asymmetry. In the transition between these two regimes, the stall force depends nonlinearly on the number of motor subunits. Compared to its constituents without interactions, we find higher efficiency and qualitatively different force-velocity relations. The model captures several of the qualitative features obtained in experiments on pilus retraction forces, such as roughly constant velocity at low applied forces and insensitivity in the stall force to changes in the ATP concentration.Comment: RevTex 9 pages, 4 figures. Revised version, new subsections in Sec. III, removed typo

Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12)

It has been known for the past 20 years that two pathways exist in nature for the de novo biosynthesis of the coenzyme form of vitamin B12, adenosylcobalamin, representing aerobic and anaerobic routes. In contrast to the aerobic pathway, the anaerobic route has remained enigmatic because many of its intermediates have proven technically challenging to isolate, because of their inherent instability. However, by studying the anaerobic cobalamin biosynthetic pathway in Bacillus megaterium and using homologously overproduced enzymes, it has been possible to isolate all of the intermediates between uroporphyrinogen III and cobyrinic acid. Consequently, it has been possible to detail the activities of purified cobinamide biosynthesis (Cbi) proteins CbiF, CbiG, CbiD, CbiJ, CbiET, and CbiC, as well as show the direct in vitro conversion of 5-aminolevulinic acid into cobyrinic acid using a mixture of 14 purified enzymes. This approach has resulted in the isolation of the long sought intermediates, cobalt-precorrin-6A and -6B and cobalt-precorrin-8. EPR, in particular, has proven an effective technique in following these transformations with the cobalt(II) paramagnetic electron in the dyz orbital, rather than the typical dz2. This result has allowed us to speculate that the metal ion plays an unexpected role in assisting the interconversion of pathway intermediates. By determining a function for all of the pathway enzymes, we complete the tool set for cobalamin biosynthesis and pave the way for not only enhancing cobalamin production, but also design of cobalamin derivatives through their combinatorial use and modification

Ion Charge States in Halo CMEs: What can we Learn about the Explosion?

We describe a new modeling approach to develop a more quantitative understanding of the charge state distributions of the ions of various elements detected in situ during halo Coronal Mass Ejection (CME) events by the Advanced Composition Explorer (ACE) satellite. Using a model CME hydrodynamic evolution based on observations of CMEs propagating in the plane of the sky and on theoretical models, we integrate time dependent equations for the ionization balance of various elements to compare with ACE data. We find that plasma in the CME ``core'' typically requires further heating following filament eruption, with thermal energy input similar to the kinetic energy input. This extra heating is presumably the result of post eruptive reconnection. Plasma corresponding to the CME ``cavity'' is usually not further ionized, since whether heated or not, the low density gives freeze-in close the the Sun. The current analysis is limited by ambiguities in the underlying model CME evolution. Such methods are likely to reach their full potential when applied to data to be acquired by STEREO when at optimum separation. CME evolution observed with one spacecraft may be used to interpret CME charge states detected by the other.Comment: 20 pages, accepted by Ap

Exercise for the Treatment of Knee Osteoarthritis

Regular exercise reduces osteoarthritic knee pain and improves functioning. (Strength of Recommendation: A, based on systematic reviews.) Aerobic and strength-training exercises, including land- and water-based exercises, are effective for treating knee osteoarthritis. (Strength of Recommendation: A, based on a randomized controlled trial [RCT].

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV