The rockefeller university

Conventional nonequilibrium thermodynamics is mainly concerned with systems in local equilibrium and their entropy production, due to the irreversible processes which take place in these systems. In this paper, fluids will be considered in a state of local equilibrium. We argue that the main feature of such systems is not the entropy production, but the organization of the flowing currents in such systems. These currents do not only have entropy production, but must also have an organization needed to flow in a certain direction. It is the latter, which is the source of the equilibrium entropy, when the fluid goes from a local equilibrium state to an equilibrium state. This implies a transmutation of the local equilibrium currents' organization into the equilibrium entropy. Alternatively, when a fluid goes from an equilibrium state to a local equilibrium state, its entropy transmutes into the organization of the currents of that state.

Disulfide-rich peptide toxins found in the secretions of venomous organisms such as snakes, spiders, scorpions, leeches, and marine snails are highly efficient and effective tools for novel therapeutic drug development. Venom peptide toxins have been used extensively to characterize ion channels in the nervous system and platelet aggregation in haemostatic systems. A significant hurdle in characterizing disulfide-rich peptide toxins from venomous animals is obtaining significant quantities needed for sequence and structural analyses. Presented here is a strategy for the structural characterization of venom peptide toxins from sample limited (4 ng) specimens via direct mass spectrometry sequencing, chemical synthesis and NMR structure elucidation. Using this integrated approach, venom peptide Tv1 from Terebra variegata was discovered. Tv1 displays a unique fold not witnessed in prior snail neuropeptides. The novel structural features found for Tv1 suggest that the terebrid pool of peptide toxins may target different neuronal agents with varying specificities compared to previously characterized snail neuropeptides.

Housekeeping sigma factors are initiation factors for the bacterial RNA polymerase at most promoters, whereas alternative sigma s direct focused responses to specific environmental conditions. Structural and functional analysis of an alternative sigma complexed with its cognate -10 motif elucidates the mechanism for initiation of strand opening, highlighting two critical properties: why alternative sigma s, compared to housekeeping sigma s, recognize so few promoters and how their promoter-recognition strategy was diversified during evolution.

Bisindolylmaleimides represent a naturally occurring class of metabolites that are of interest because of their protein kinase inhibition activity. From a metagenomic library constructed with soil DNA, we identified the four gene mar cluster, a bisindolylmaleimide gene cluster that encodes for methylarcyriarubin (1) production. Heterologous expression of the mar gene cluster in E. coli revealed that the Rieske dioxygenase MarC facilitates the oxidative decarboxylation of a chromopyrrolic acid (CPA) intermediate to yield the bisindolylmaleimide core. The characterization of the mar cluster defines a new role for CPA in the biosynthesis of structurally diverse bacterial tryptophan dimers.

We use ideas from kinetic proofreading, an error-correcting mechanism in biology, to identify new kinetic regimes in nonequilibrium systems. These regimes are defined by the sensitivity of the occupancy of a state of the system to a change in its energy. In biological contexts, higher sensitivity corresponds to stronger discrimination between molecular substrates with different energetics competing in the same reaction. We study this discriminatory ability in systems with discrete states that are connected by a general network of transitions. We find multiple regimes of different discriminatory ability when the energy of a given state of the network is varied. Interestingly, the occupancy of the state can even increase with its energy, corresponding to an "antiproofreading" regime. The number and properties of such discriminatory regimes are limited by the topology of the network. Finally, we find that discriminatory regimes can be changed without modifying any "hard-wired" structural aspects of the system but rather by simply changing external chemical potentials.

Quadratic ordering of rectangular real matrices implies Chebyshev's inequality: If Ai, Ar are m x n real matrices and B-1, ... , B-r are n x q real matrices such that, for all i, j with 1 <= i, j <= r, elementwise (A(i) - A(j))(B-i - B-j) >= 0(mxq), then for any real pj >= 0, j = 1, ... , r, Sigma(j)p(j) = 1, elementwise (Sigma(j)p(j)A(j))(Sigma(j)p(j)B(j)) <= Sigma(j)p(j)A(j)B(j). Further, linear ordering of rectangular real matrices implies Gruss's inequality: If, elementwise, A(j) <= A(j+1), j = 1,..., r - 1 and elementwise B-j <= Bj+1 = 1,..., r - 1 then elementwise Sigma(j)p(j)A(j)B(j) - (Sigma(j)p(j)A(j))(Sigma(j)p(j)B(j)) <= 1/4(A(r) - A(1))(B-r - B-1). The bounds are sharp. These inequalities lead to inequalities for the spectral radius of nonnegative matrices. Linear ordering and quadratic ordering are equivalent for real scalars but not for real matrices, (C) 2013 Elsevier Inc. All rights reserved.

Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC)-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.

We present a measurement of the W-boson mass, M-W, using data corresponding to 2.2 fb(-1) of integrated luminosity collected in p (p) over bar collisions at root s = 1.96 TeV with the CDF II detector at the Fermilab Tevatron. The selected sample of 470 126 W -> ev candidates and 624 708 W -> mu nu candidates yields the measurement M-W = 80387 +/- 12 (stat) +/- 15(syst) = 80387 +/- 19 MeV/c(2). This is the most precise single measurement of the W-boson mass to date.

Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control.