Monoclonal antibodies to a membrane glycoprotein induce the phosphorylation of histone H1 in sea urchin spermatozoa.

Two groups of mAbs reacting with external domains of a major sea urchin sperm membrane glycoprotein of 210 kD were isolated. Previous studies have shown that group I mAbs inhibit the acrosome reaction induced by egg jelly and also cause large increases in intracellular Ca2+ [( Ca2+]i). Group II mAbs, at comparable levels of cell surface binding, neither inhibit the egg jelly-induced acrosome reaction nor cause increases in [Ca2+]i. In this paper, we investigate the ability of these mAbs to induce the cAMP-dependent phosphorylation of sperm histone H1. Group I mAbs induce H1 phosphorylation to the same level and on the same peptide, as occurs upon treatment of sperm with egg jelly. These mAbs also activate adenylate cyclase to the same extent as egg jelly. Group II mAbs do not induce H1 phosphorylation and are only poor activators of adenylate cyclase. Group I mAbs compete with each other, but not with group II mAbs, for binding to the cell surface. These data indicate that the activation of adenylate cyclase is an initial event in the pathway leading from the binding of mAbs to a specific domain of the 210-kD protein at the cell surface, to the discrete phosphorylation of histone H1 in highly condensed sperm chromatin. The domain on the 210-kD protein recognized by group I mAbs plays a critical role in signal transduction during the early events of fertilization

Electrostatics of ions inside the nanopores and trans-membrane channels

A model of a finite cylindrical ion channel through a phospholipid membrane of width $L$ separating two electrolyte reservoirs is studied. Analytical solution of the Poisson equation is obtained for an arbitrary distribution of ions inside the trans-membrane pore. The solution is asymptotically exact in the limit of large ionic strength of electrolyte on the two sides of membrane. However, even for physiological concentrations of electrolyte, the electrostatic barrier sizes found using the theory are in excellent agreement with the numerical solution of the Poisson equation. The analytical solution is used to calculate the electrostatic potential energy profiles for pores containing charged protein residues. Availability of a semi-exact interionic potential should greatly facilitate the study of ionic transport through nanopores and ion channels

Confinement Effects on the Kinetics and Thermodynamics of Protein Dimerization

In the cell, protein complexes form relying on specific interactions between their monomers. Excluded volume effects due to molecular crowding would lead to correlations between molecules even without specific interactions. What is the interplay of these effects in the crowded cellular environment? We study dimerization of a model homodimer both when the mondimers are free or tethered to each other. We consider a structured environment: Two monomers first diffuse into a cavity of size $L$ and then fold and bind within the cavity. The folding and binding are simulated using molecular dynamics based on a simplified topology based model. The {\it confinement} in the cell is described by an effective molecular concentration $C \sim L^{-3}$. A two-state coupled folding and binding behavior is found. We show the maximal rate of dimerization occurred at an effective molecular concentration $C^{op}\simeq 1m$M which is a relevant cellular concentration. In contrast, for tethered chains the rate keeps at a plateau when $CC^{op}$. For both the free and tethered cases, the simulated variation of the rate of dimerization and thermodynamic stability with effective molecular concentration agrees well with experimental observations. In addition, a theoretical argument for the effects of confinement on dimerization is also made

Measuring decision quality: psychometric evaluation of a new instrument for breast cancer chemotherapy

Background: Women diagnosed with early stage (I or II) breast cancer face a highly challenging decision – whether or not to undergo adjuvant chemotherapy. We developed a decision quality instrument for chemotherapy for early stage breast cancer and sought to evaluate its performance. Methods: Cross-sectional, mailed survey of recent breast cancer survivors, providers, and healthy controls and a retest survey of survivors. The decision quality instrument includes questions on knowledge and personal goals. It results in a knowledge score and concordance score, which reflects the percentage of patients who received treatments that match their goals. Hypotheses related to acceptability, feasibility, validity, and reliability of the survey instrument were examined. Results: Responses were received from 352 patients, 89 providers and 35 healthy controls. The decision quality instrument was feasible to implement with few missing data. The knowledge scores had good retest reliability (intraclass correlation coefficient (ICC) =0.75). Knowledge scores discriminated between providers and patients (mean difference 31.1%, 95% CI 26.9, 35.3) and between patients and healthy controls (mean difference 11.2, 95% CI 5.4, 17.1). Most providers reported that the knowledge items covered essential content. Two of the five goal items had a ceiling effect, and one goal had low content validity. The goal items had moderate retest reliability (ICC’s 0.57 to 0.78). In the multivariable model of treatment, none of the patient goals was associated with receipt of chemotherapy. Age and hormone receptor status were the only variables independently associated with chemotherapy. Most patients (77.6%) had treatment concordant with that predicted by the model. Patients who had concordant treatment had similar levels of confidence and regret as those who did not. Conclusions: The Decision Quality Instrument is a reliable and valid measure of patient knowledge about chemotherapy, but its ability to measure concordance with patient goals is limited. In this sample, patient goals were not associated with treatment, and most patients reported they were not asked their preference, suggesting that goals were not adequately considered in decision making

Tai chi mind-body exercise in patients with COPD: study protocol for a randomized controlled trial

Background: Chronic obstructive pulmonary disease (COPD) is a chronic, progressively debilitating condition that is prevalent in the US and worldwide. Patients suffer from progressive dyspnea and exercise intolerance. Physical exercise is beneficial, but conventional pulmonary rehabilitation programs are underutilized. There remains a need for novel interventions that improve symptoms, quality-of-life, and functional capacity. Tai chi is an increasingly popular mind-body exercise that includes physical exercise, breathing training, mindful awareness, and stress management--components that are essential to the self-management of COPD. There are, however, limited data on the effectiveness of tai chi as a therapeutic intervention in this population. Methods/Design The Primary Aims are to evaluate the efficacy, safety, and feasibility of a 12-week tai chi program for patients with COPD. We utilize a randomized controlled trial design, with participants assigned in a 2:1 ratio to either a group tai chi program (N = 63) or a time/attention-matched education control (N = 31). Our primary outcomes are COPD-specific quality-of-life and exercise capacity. Secondary outcomes include dyspnea, mood, functional status, self-efficacy, and lung function. Cardiopulmonary exercise testing is done in a subset of patients (N = 50). To explore optimal training duration, a subgroup of patients in tai chi are randomly assigned to complete an additional 12 weeks training (total 24 weeks) (Exploratory Aim 1). To explore the impact of a simplified seated intervention including only a subset of tai chi’s training components, a third randomly assigned group (N = 31) receives a 12- week mind-body breathing program (N = 31) (Exploratory Aim 2). Discussion Results of the BEAM study (Breathing, Education, Awareness, Movement) will provide preliminary evidence regarding the value of tai chi for improving quality of life and exercise capacity in patients with COPD, including information regarding optimal duration. They will also inform the feasibility and potential benefit of an alternative mind-body breathing intervention, and provide insight regarding how isolated mind-body exercise components contribute to the overall effects of tai chi. Should the results be positive, tai chi and related mind-body practices may offer a novel exercise option that is potentially accessible to a large proportion of patients with COPD. Trial registration This trial is registered in Clinical Trials.gov, ID number NCT01551953. Date of Registration March 1 2012. Electronic supplementary material The online version of this article (doi:10.1186/1745-6215-15-337) contains supplementary material, which is available to authorized users

Effects of interatomic collisions on atom laser outcoupling

We present a computational approach to the outcoupling in a simple one-dimensional atom laser model, the objective being to circumvent mathematical difficulties arising from the breakdown of the Born and Markov approximations. The approach relies on the discretization of the continuum representing the reservoir of output modes, which allows the treatment of arbitrary forms of outcoupling as well as the incorporation of non-linear terms in the Hamiltonian, associated with interatomic collisions. By considering a single-mode trapped condensate, we study the influence of elastic collisions between trapped and free atoms on the quasi steady-state population of the trap, as well as the energy distribution and the coherence of the outcoupled atoms.Comment: 25 pages, 11 figures, to appear in J. Phys.

Coherent Tunneling of Atoms from Bose-condensed Gases at Finite Temperatures

Tunneling of atoms between two trapped Bose-condensed gases at finite temperatures is explored using a many-body linear response tunneling formalism similar to that used in superconductors. To lowest order, the tunneling currents can be expressed quite generally in terms of the single-particle Green's functions of the isolated Bose gases. A coherent first-order tunneling Josephson current between two atomic Bose-condensates is found, in addition to coherent and dissipative contributions from second-order condensate-noncondensate and noncondensate-noncondensate tunneling. Our work is a generalization of Meier and Zwerger, who recently treated tunneling between uniform atomic Bose gases. We apply our formalism to the analysis of an out-coupling experiment induced by light wave fields, using a simple Bogoliubov-Popov quasiparticle approximation for the trapped Bose gas. For tunneling into the vacuum, we recover the results of Japha, Choi, Burnett and Band, who recently pointed out the usefulness of studying the spectrum of out-coupled atoms. In particular, we show that the small tunneling current of noncondensate atoms from a trapped Bose gas has a broad spectrum of energies, with a characteristic structure associated with the Bogoliubov quasiparticle u^2 and v^2 amplitudes.Comment: 26 pages, 5 figures, minor changes, to appear in PR

Adiabatic Output Coupling of a Bose Gas at Finite Temperatures

We develop a general theory of adiabatic output coupling from trapped atomic Bose-Einstein Condensates at finite temperatures. For weak coupling, the output rate from the condensate, and the excited levels in the trap, settles in a time proportional to the inverse of the spectral width of the coupling to the output modes. We discuss the properties of the output atoms in the quasi-steady-state where the population in the trap is not appreciably depleted. We show how the composition of the output beam, containing condensate and thermal component, may be controlled by changing the frequency of the output coupler. This composition determines the first and second order coherence of the output beam. We discuss the changes in the composition of the bose gas left in the trap and show how nonresonant output coupling can stimulate either the evaporation of thermal excitations in the trap or the growth of non-thermal excitations, when pairs of correlated atoms leave the condensate.Comment: 22 pages, 6 Figs. To appear in Physical Review A All the typos from the previous submission have been fixe

Program analysis is harder than verification: A computability perspective

We study from a computability perspective static program analysis, namely detecting sound program assertions, and verification, namely sound checking of program assertions. We first design a general computability model for domains of program assertions and correspond- ing program analysers and verifiers. Next, we formalize and prove an instantiation of Rice\u2019s theorem for static program analysis and verifica- tion. Then, within this general model, we provide and show a precise statement of the popular belief that program analysis is a harder prob- lem than program verification: we prove that for finite domains of pro- gram assertions, program analysis and verification are equivalent prob- lems, while for infinite domains, program analysis is strictly harder than verification

Boojums and the Shapes of Domains in Monolayer Films

Domains in Langmuir monolayers support a texture that is the two-dimensional version of the feature known as a boojum. Such a texture has a quantifiable effect on the shape of the domain with which it is associated. The most noticeable consequence is a cusp-like feature on the domain boundary. We report the results of an experimental and theoretical investigation of the shape of a domain in a Langmuir monolayer. A further aspect of the investigation is the study of the shape of a ``bubble'' of gas-like phase in such a monolayer. This structure supports a texture having the form of an inverse boojum. The distortion of a bubble resulting from this texture is also studied. The correspondence between theory and experiment, while not perfect, indicates that a qualitative understanding of the relationship between textures and domain shapes has been achieved.Comment: replaced with published version, 10 pages, 13 figures include