Biomimetic Promotion and Inhibition of Crystal Growth in Calcium Carbonate

Living organisms have evolved effective mechanisms to control the growth of inorganic crystalline materials as structural elements. Previous research has shown that proteins rich in aspartic acid play a pivotal role in driving crystalline orientation, structure, and morphology of calcium carbonate biominerals in the formation of shells in marine bivalves (mussels, clams, abalone). In our research, we examine the effect of aspartic acid on the growth of calcium carbonate by a novel vapor diffusion-based growth technique. The vapor diffusion approach uses a gas-permeable membrane as a barrier to control the physical location of crystal growth. In this way, we are able to directly observe the crystal nucleation and growth using optical microscopy and record changes in growth rates and crystal orientation as we add peptide or polyelectrolyte-based modifiers to the growing crystals. Raman spectroscopy was employed to characterize the resulting crystals and provide insight into the actions of the growth modifiers. Our work is directed towards understanding how molecular modifiers interact with inorganic materials. Developing controls for the growth of calcium carbonate materials could have impacts in many industries which rely on the materials (including pharmaceutical development, household products, and paper, rubber, and paint manufacturing)

Characterization of Elevated Temperature Properties of Heat Exchanger and Steam Generator Alloys

The Next Generation Nuclear Plant project is considering Alloy 800H and Alloy 617 for steam generator and intermediate heat exchangers. It is envisioned that a steam generator would operate with reactor outlet temperatures from 750 to 800°C, while an intermediate heat exchanger for primary to secondary helium would operate up to an outlet temperature of 950°C. Although both alloys are of interest due in part to their technical maturity, a number of specific properties require further characterization for design of nuclear components. Strain rate sensitivity of both alloys has been characterized and is found to be significant above 600°C. Both alloys also exhibit dynamic strain aging, characterized by serrated flow, over a wide range of temperatures and strain rates. In general dynamic strain aging is observed to begin at higher temperatures and serrated flow persists to higher temperatures in Alloy 617 compared to Alloy 800H. Dynamic strain aging is a concern for these materials since it is observed to result in reduced ductility for many solid solution alloys. The role of dynamic strain aging in the creep-fatigue behavior of Alloy 617 at temperatures of 800°C and above has also been examined in detail. Serrated flow is found to persist in cyclic stress-strain curves up to nearly the cycle to failure in some temperature and strain regimes. Results of those experiments and implications for creep-fatigue testing protocols will be described

Computational and Biological Analogies for Understanding Fine-Tuned Parameters in Physics

In this philosophical paper, we explore computational and biological analogies to address the fine-tuning problem in cosmology. We first clarify what it means for physical constants or initial conditions to be fine-tuned. We review important distinctions such as the dimensionless and dimensional physical constants, and the classification of constants proposed by Levy-Leblond. Then we explore how two great analogies, computational and biological, can give new insights into our problem. This paper includes a preliminary study to examine the two analogies. Importantly, analogies are both useful and fundamental cognitive tools, but can also be misused or misinterpreted. The idea that our universe might be modelled as a computational entity is analysed, and we discuss the distinction between physical laws and initial conditions using algorithmic information theory. Smolin introduced the theory of "Cosmological Natural Selection" with a biological analogy in mind. We examine an extension of this analogy involving intelligent life. We discuss if and how this extension could be legitimated. Keywords: origin of the universe, fine-tuning, physical constants, initial conditions, computational universe, biological universe, role of intelligent life, cosmological natural selection, cosmological artificial selection, artificial cosmogenesis.Comment: 25 pages, Foundations of Science, in pres

The Mathematical Universe

I explore physics implications of the External Reality Hypothesis (ERH) that there exists an external physical reality completely independent of us humans. I argue that with a sufficiently broad definition of mathematics, it implies the Mathematical Universe Hypothesis (MUH) that our physical world is an abstract mathematical structure. I discuss various implications of the ERH and MUH, ranging from standard physics topics like symmetries, irreducible representations, units, free parameters, randomness and initial conditions to broader issues like consciousness, parallel universes and Godel incompleteness. I hypothesize that only computable and decidable (in Godel's sense) structures exist, which alleviates the cosmological measure problem and help explain why our physical laws appear so simple. I also comment on the intimate relation between mathematical structures, computations, simulations and physical systems.Comment: Replaced to match accepted Found. Phys. version, 31 pages, 5 figs; more details at http://space.mit.edu/home/tegmark/toe.htm

Determination of Inflationary Observables by Cosmic Microwave Background Anisotropy Experiments

Inflation produces nearly Harrison-Zel'dovich scalar and tensor perturbation spectra which lead to anisotropy in the cosmic microwave background (CMB). The amplitudes and shapes of these spectra can be parametrized by $Q_S^2$, $r\equiv Q_T^2/Q_S^2$, $n_S$ and $n_T$ where $Q_S^2$ and $Q_T^2$ are the scalar and tensor contributions to the square of the CMB quadrupole and $n_S$ and $n_T$ are the power-lawspectral indices. Even if we restrict ourselves to information from angles greater than one third of a degree, three of these observables can be measured with some precision. The combination $130^{1-n_S}Q_S^2$ can be known to better than $\pm 0.3\%$. The scalar index $n_S$ can be determined to better than $\pm 0.02$. The ratio $r$ can be known to about $\pm 0.1$ for $n_S \simeq 1$ and slightly better for smaller $n_S$. The precision with which $n_T$ can be measured depends weakly on $n_S$ and strongly on $r$. For $n_S \simeq 1$ $n_T$ can be determined with a precision of about $\pm 0.056(1.5+r)/r$. A full-sky experiment with a $20'$beam using technology available today, similar to those being planned by several groups, can achieve the above precision. Good angular resolution is more important than high signal-to-noise ratio; for a given detector sensitivity and observing time a smaller beam provides significantly more information than a larger beam. The uncertainties in $n_S$ and $r$ are roughly proportional to the beam size. We briefly discuss the effects of uncertainty in the Hubble constant, baryon density, cosmological constant and ionization history.Comment: 28 pages of uuencoded postscript with 8 included figures. A postscript version is also available by anonymous ftp at ftp://astro.uchicago.edu/pub/astro/knox/fullsim.p

A Qualitative Study of an Integrated Maternity, Drugs and Social Care Service for Drug-using Women

Background: The care of drug-using pregnant women is a growing health and social care concern in many countries. A specialist clinic was established offering multidisciplinary care and advice to pregnant drug users in and around Aberdeen (UK) in 1997. The majority of women stabilise and reduce their drug use. By determining the needs and views of the women more appropriate services and prevention strategies may be developed. There has been little research conducted in this area and none in Scotland. Methods: This is a qualitative study that aimed to gain an understanding of the experiences of women drug users, seeking and receiving prenatal care and drug services from a specialist clinic. Twelve women participated in semi-structured one-to-one interviews. Results: The women preferred the multidisciplinary clinic (one-stop shop) to traditional prenatal care centred within General Practice. The relationships of the clients to the range of Clinic professionals and in hospital were explored as well as attitudes to Clinic care. The study participants attributed success in reducing their drug use to the combination of different aspects of care of the multi-agency clinic, especially the high level prenatal support. It is this arrangement of all aspects of care together that seem to produce better outcomes for mother and child than single care elements delivered separately. Some women reported that their pregnancy encouraged them to rapidly detoxify due to the guilt experienced. The most important aspects of the Clinic care were found to be non-judgemental attitude of staff, consistent staff, high level of support, reliable information and multi-agency integrated care. Conclusion: There is an impetus for women drug users to change lifestyle during pregnancy. The study highlighted a need for women to have access to reliable information on the effects of drugs on the baby. Further research is required to determine whether positive outcomes related to clinic attendance in the prenatal period are sustained in the postnatal period. Early referral to a specialist clinic is of benefit to the women, as they reported to receive more appropriate care, especially in relation to their drug use. A greater awareness of needs of the pregnant drug user could help the design of more effective prevention strategies

Repeatability and measurement error in the assessment of choline and betaine dietary intake: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Background The repeatability of a risk factor measurement affects the ability to accurately ascertain its association with a specific outcome. Choline is involved in methylation of homocysteine, a putative risk factor for cardiovascular disease, to methionine through a betaine-dependent pathway (one-carbon metabolism). It is unknown whether dietary intake of choline meets the recommended Adequate Intake (AI) proposed for choline (550 mg/day for men and 425 mg/day for women). The Estimated Average Requirement (EAR) remains to be established in population settings. Our objectives were to ascertain the reliability of choline and related nutrients (folate and methionine) intakes assessed with a brief food frequency questionnaire (FFQ) and to estimate dietary intake of choline and betaine in a bi-ethnic population. Methods We estimated the FFQ dietary instrument reliability for the Atherosclerosis Risk in Communities (ARIC) study and the measurement error for choline and related nutrients from a stratified random sample of the ARIC study participants at the second visit, 1990–92 (N = 1,004). In ARIC, a population-based cohort of 15,792 men and women aged 45–64 years (1987–89) recruited at four locales in the U.S., diet was assessed in 15,706 baseline study participants using a version of the Willett 61-item FFQ, expanded to include some ethnic foods. Intraindividual variability for choline, folate and methionine were estimated using mixed models regression. Results Measurement error was substantial for the nutrients considered. The reliability coefficients were 0.50 for choline (0.50 for choline plus betaine), 0.53 for folate, 0.48 for methionine and 0.43 for total energy intake. In the ARIC population, the median and the 75th percentile of dietary choline intake were 284 mg/day and 367 mg/day, respectively. 94% of men and 89% of women had an intake of choline below that proposed as AI. African Americans had a lower dietary intake of choline in both genders. Conclusion The three-year reliability of reported dietary intake was similar for choline and related nutrients, in the range as that published in the literature for other micronutrients. Using a brief FFQ to estimate intake, the majority of individuals in the ARIC cohort had an intake of choline below the values proposed as AI

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

A model of quiescent tumour microregions for evaluating multicellular resistance to chemotherapeutic drugs

The quiescent cell population of tumours poses a barrier to the success of many cancer therapies. Most chemotherapeutic drugs target proliferating cells, but the growth fraction of many tumours is low. Based on the multicellular tumour spheroid model, a system was developed using human colon adenocarcinoma (DLD-1) cells to mimic the microenvironment of quiescent microregions of solid tumours. The quiescent tumour spheroids (TSQ) showed decreased expression of the proliferation marker Ki-67 and increased expression of the quiescence marker p27kip1 compared to proliferating spheroids (TSP). The quiescent status of the TSQ was confirmed by long-term growth assessment. The quiescence was completely reversible demonstrating that the TSQ retained the ability to proliferate and morphological assessment by light microscopy confirmed the absence of significant apoptosis. When the efficacy of widely used chemotherapeutic drugs was determined, vinblastine, doxorubicin, cisplatin and 5-fluorouracil (5-FU) all produced significant cell death in the TSP. However, while still effective, the potencies of doxorubicin and cisplatin were significantly reduced in TSQ. In contrast, 5-FU and vinblastine did not produce cell death in the TSQ. In summary, TSQ show considerable resistance to a panel of established chemotherapeutic agents and represent a useful model for evaluating the efficacy of drugs and other cancer therapies in quiescent tumours