Nucleation at the DNA supercoiling transition

Twisting DNA under a constant applied force reveals a thermally activated transition into a state with a supercoiled structure known as a plectoneme. Using transition state theory, we predict the rate of this plectoneme nucleation to be of order 10^4 Hz. We reconcile this with experiments that have measured hopping rates of order 10 Hz by noting that the viscosity of the bead used to manipulate the DNA limits the measured rate. We find that the intrinsic bending caused by disorder in the base-pair sequence is important for understanding the free energy barrier that governs the transition. Both analytic and numerical methods are used in the calculations. We provide extensive details on the numerical methods for simulating the elastic rod model with and without disorder.Comment: 18 pages, 15 figure

Cloning and characterization of a conjugated bile acid hydrolase gene from Clostridium perfringens.

The gene encoding a conjugated bile acid hydrolase (CBAH) from Clostridium perfringens 13 has been cloned and expressed in Escherichia coli, and its nucleotide sequence has been determined. Nucleotide and predicted amino acid sequence analyses indicated that the gene product is related to two previously characterized amidases, a CBAH from Lactobacillus plantarum (40% identity) and a penicillin V amidase from Bacillus sphaericus (34% identity). The product is apparently unrelated to a CBAH from C. perfringens for which N-terminal sequence information was determined. The gene product was purified from recombinant E. coli and used to raise antibody in rabbits. The presence of the protein in C. perfringens was then confirmed by immunoblot analysis. The protein was shown to have a native molecular weight of 147,000 and a subunit molecular weight of 36,100, indicating its probable existence as a tetramer. Disruption of the chromosomal C. perfringens CBAH gene with a chloramphenicol resistance cartridge resulted in a mutant strain which retained partial CBAH activity. Polyacrylamide gel electrophoresis followed by enzymatic activity staining and immunoblotting indicated that the mutant strain no longer expressed the cloned CBAH (CBAH-1) but did express at least one additional CBAH (CBAH-2). CBAH-2 was immunologically distinct from CBAH-1, and its mobility on native polyacrylamide gels was different from that of CBAH-1. Furthermore, comparisons of pH optima and substrate specificities of CBAH activities from recombinant E. coli and wild-type and mutant C. perfringens provided further evidence for the presence of multiple CBAH activities in C. perfringens. Originally published Applied and Environmental Microbiology, Vol. 61, No. 7, July 199

Personhood, consciousness, and god : how to be a proper pantheist

© Springer Nature B.V. 2018In this paper I develop a theory of personhood which leaves open the possibility of construing the universe as a person. If successful, it removes one bar to endorsing pantheism. I do this by examining a rising school of thought on personhood, on which persons, or selves, are understood as identical to episodes of consciousness. Through a critique of this experiential approach to personhood, I develop a theory of self as constituted of qualitative mental contents, but where these contents are also capable of unconscious existence. On this theory, though we can be conscious of our selves, consciousness turns out to be inessential to personhood. This move, I then argue, provides resources for responding to the pantheist’s problem of God’s person.Peer reviewedFinal Accepted Versio

Perioperative morbidity and mortality after transmyocardial laser revascularization: incidence and risk factors for adverse events

AbstractOBJECTIVESThe purpose of this study was to describe the incidence and spectrum of perioperative cardiac and noncardiac morbidity and mortality after transmyocardial laser revascularization (TMR) and to identify predictors of these adverse clinical events.BACKGROUNDClinical studies have demonstrated the efficacy of TMR for relieving angina pectoris, although no study to date has specifically addressed the associated perioperative morbidity and mortality.METHODSBetween October 1995 and August 1997, 34 consecutive patients with end-stage coronary artery disease (CAD) underwent isolated TMR. The majority of patients (94%) had class III or IV angina pectoris, and two patients (6%) had unstable symptoms preoperatively. Patient records were reviewed for fatal and nonfatal adverse cardiac and noncardiac events.RESULTSPerioperative death occurred in two patients (5.9%) due to cardiogenic shock complicating acute myocardial infarction. Perioperative cardiac morbidity occurred in 16 patients (47.1%); noncardiac morbidity was seen in 12 patients (35.3%). Preoperative unstable angina was the only variable predictive of perioperative death (p = 0.005). Cardiac (p = 0.005) and noncardiac (p < 0.001) morbidity rates were significantly higher for the initial 15 patients undergoing the procedure. Other predictors of perioperative complications included lack of postoperative treatment with a furosemide infusion (p ≤ 0.04) and preoperative unstable angina (p = 0.05).CONCLUSIONSPerioperative mortality in patients undergoing isolated TMR is low. Transmyocardial laser revascularization patients are at higher risk for adverse perioperative cardiac and noncardiac events, likely reflecting the lack of immediate benefit from the procedure in the setting of severe CAD. These patients merit vigilant surveillance for adverse events and aggressive medical management in the perioperative period

Dislocation Kinks in Copper: Widths, Barriers, Effective Masses, and Quantum Tunneling

We calculate the widths, migration barriers, effective masses, and quantum tunneling rates of kinks and jogs in extended screw dislocations in copper, using an effective medium theory interatomic potential. The energy barriers and effective masses for moving a unit jog one lattice constant are close to typical atomic energies and masses: tunneling will be rare. The energy barriers and effective masses for the motion of kinks are unexpectedly small due to the spreading of the kinks over a large number of atoms. The effective masses of the kinks are so small that quantum fluctuations will be important. We discuss implications for quantum creep, kink--based tunneling centers, and Kondo resonances

Theta-Vacuum of the Bosonized Massive Light-Front Schwinger Model

The massive Schwinger model in bosonic representation is quantized on the light front using the Dirac--Bergmann method. The non-perturbative theta- vacuum in terms of coherent states of the gauge-field zero mode is derived and found to coincide with the massless case. On the other hand, the mass term becomes highly non-linear due to the constrained zero mode of the scalar field. A non-trivial mixing between the normal-mode and zero-mode sectors of the model is crucial for the correct calculation of the theta-dependence of the leading order mass correction to the chiral condensate.Comment: 9 pages, LaTe

The Real Combination Problem : Panpsychism, Micro-Subjects, and Emergence

Panpsychism harbors an unresolved tension, the seriousness of which has yet to be fully appreciated. I capture this tension as a dilemma, and offer panpsychists advice on how to resolve it. The dilemma, briefly, is as follows. Panpsychists are committed to the perspicuous explanation of macro-mentality in terms of micro-mentality. But panpsychists take the micro-material realm to feature not just mental properties, but also micro-subjects to whom these properties belong. Yet it is impossible to explain the constitution of a macro-subject (like one of us) in terms of the assembly of micro-subjects, for, I show, subjects cannot combine. Therefore the panpsychist explanatory project is derailed by the insistence that the world’s ultimate material constituents (ultimates) are subjects of experience. The panpsychist faces a choice of abandoning her explanatory project, or recanting the claim that the ultimates are subjects. This is the dilemma. I argue that the latter option is to be preferred. This needn’t constitute a wholesale abandonment of panpsychism, however, since panpsychists can maintain that the ultimates possess phenomenal qualities, despite not being subjects of those qualities. This proposal requires us to make sense of phenomenal qualities existing independently of experiencing subjects, a challenge I tackle in the penultimate section. The position eventually reached is a form of neutral monism, so another way to express the overall argument is to say that, keeping true to their philosophical motivations, panpsychists should really be neutral monists.Peer reviewedFinal Accepted Versio

Opportunities to Target the Life Cycle of Epstein-Barr Virus (EBV) in EBV-Associated Lymphoproliferative Disorders

Many lymphoproliferative disorders (LPDs) are considered “EBV associated” based on detection of the virus in tumor tissue. EBV drives proliferation of LPDs via expression of the viral latent genes and many pre-clinical and clinical studies have shown EBV-associated LPDs can be treated by exploiting the viral life cycle. After a brief review of EBV virology and the natural life cycle within a host we will discuss the importance of the viral gene programs expressed during specific viral phases, as well as within immunocompetent vs. immunocompromised hosts and corresponding EBV-associated LPDs. We will then review established and emerging treatment approaches for EBV-associated LPDs based on EBV gene expression programs. Patients with EBV-associated LPDs can have a poor performance status, multiple comorbidities, and/or are immunocompromised from organ transplantation, autoimmune disease, or other congenital or acquired immunodeficiency making them poor candidates to receive intensive cytotoxic chemotherapy. With the emergence of EBV-directed therapy there is hope that we can devise more effective therapies that confer milder toxicity