A simple local expression for the prefactor in transition state theory.

We present a simple and accurate computational technique to determine the frequency prefactor in harmonic transition state theory without necessitating full phonon density of states (DOS) calculations. The atoms in the system are partitioned into an "active region," where the kinetic process takes place, and an "environment" surrounding the active region. It is shown that the prefactor can be obtained by a partial phonon DOS calculation of the active region with a simple correction term accounting for the environment, under reasonable assumptions regarding atomic interactions. Convergence with respect to the size of the active region is investigated for different systems, as well as the reduction in computational costs when compared to full phonon DOS calculation. Additionally, we provide an open source implementation of the algorithm that can be added as an extension to Large-scale Atomic/Molecular Massively Parallel Simulator software.

Electronic Origins of Anomalous Twin Boundary Energies in Hexagonal Close Packed Transition Metals.

Density-functional-theory calculations of twin-boundary energies in hexagonal close packed metals reveal anomalously low values for elemental Tc and Re, which can be lowered further by alloying with solutes that reduce the electron per atom ratio. The anomalous behavior is linked to atomic geometries in the interface similar to those observed in bulk tetrahedrally close packed phases. The results establish a link between twin-boundary energetics and the theory of bulk structural stability in transition metals that may prove useful in controlling mechanical behavior in alloy design.

Ab initio calculations of the melting temperatures of refractory bcc metals.

We present ab initio calculations of the melting temperatures for bcc metals Nb, Ta and W. The calculations combine phase coexistence molecular dynamics (MD) simulations using classical embedded-atom method potentials and ab initio density functional theory free energy corrections. The calculated melting temperatures for Nb, Ta and W are, respectively, within 3%, 4%, and 7% of the experimental values. We compare the melting temperatures to those obtained from direct ab initio molecular dynamics simulations and see if they are in excellent agreement with each other. The small remaining discrepancies with experiment are thus likely due to inherent limitations associated with exchange-correlation energy approximations within density-functional theory.

A complete representation of structure-property relationships in crystals.

Whereas structure-property relationships have long guided the discovery and optimization of novel materials, formal quantitative methods to identify such relationships in crystalline systems are beginning to emerge. Among them is cluster expansion, which has been successfully used to parametrize the configurational dependence of important scalar physical properties such as bandgaps, Curie temperatures, equation-of-state parameters and densities of states. However, cluster expansion is currently unable to handle anisotropic properties, a key distinguishing feature of crystalline systems central to the design of modern epitaxial structures and devices. Here, I introduce a tensorial cluster expansion enabling the prediction of fundamental tensor-valued material properties such as elasticity, piezoelectricity, dielectric constants, optoelectric coupling, anisotropic diffusion coefficients, surface energy and stress. As an application, I develop predictive ab initio models of anisotropic properties relevant to the design and optimization of III-V semiconductor epitaxial optoelectronic devices.

Distribution and content of nuclear and cellular RNA among cell populations of acute lymphoblastic and nonlymphoblastic leukemia.

The RNA content of intact cells and isolated nuclei of normal human lymphocytes and mononuclear cell populations (containing at least 50% blasts) from patients with acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL) was measured by flow cytometry based on metachromatic red luminescence of acridine orange-stained cells. Relative nuclear RNA (n-RNA) and cellular RNA (c-RNA) content was estimated in relation to luminescence of RNase-treated nuclei, which served as a standard. The mean values (+/- SE) of n-RNA were 22.6 +/- 3.2, 25.8 +/- 3.2, and 51.5 +/- 6.1 arbitrary units for normal lymphocytes, ALL, and ANLL cell populations, respectively. The mean values for c-RNA were 51.3 +/- 5.2, 71.9 +/- 11.3, and 128 +/- 13.4 for the same cell populations, respectively. The differences between normal lymphocytes or ALL and ANLL cell populations were statistically significant (t-test, with respect to both n- and c-RNA), while differences between normal and ALL populations were not. The proportions of n-RNA versus c-RNA were similar within all three types of cell populations. The intercellular variabilities with respect to n- and c-RNA among the G0/1 cell populations of all three types of cells were characterized by the coefficient of variation (CV) of the mean RNA and the third moment about the mean (MOM3). CV and MOM3 of c-RNA were significantly different between all three types of cell populations, whereas CV and MOM3 of n-RNA showed significant differences between control and leukemic cells. Thus, mean RNA, CV, and MOM3 of RNA on the cellular and nuclear levels of G0/1 cells discriminate normal lymphocytes, ALL lymphoblasts, and ANLL blast cells from each other fully on statistically significant levels.

Binding of acridine orange to DNA in situ of cells from patients with acute leukemia.

Fluorescence flow cytometry was used to generate DNA histograms of acridine orange stained leukemic cell populations in G0-G1 phase of the cell cycle. Complexes of the intercalating agent, acridine orange, with double-stranded DNA in situ, emit green fluorescence upon excitation with blue laser light. The histograms were evaluated by first determining the standard deviation of the fluorescence intensity relative to the mean channel of fluorescence, i.e., the coefficient of variation, and then dividing the coefficient of variation of a patient's sample by that of a control sample (rCV). The mean rCV of cell populations of acute lymphoblastic leukemia (31 patients) differed significantly from that of nonlymphoblastic leukemia (21 patients). When cells were treated with a solution of citric acid and magnesium sulfate prior to their staining with acridine orange, the mean rCV of cell populations of acute lymphoblastic leukemia increased while that of acute nonlymphoblastic leukemia decreased compared to their respective pretreatment values. The mean difference of rCVs between untreated and treated cells (rCVD) within each disease category was statistically significant. A logistic regression model, based on rCVD, confirmed the conventional classification of acute lymphoblastic leukemia and acute nonlymphoblastic leukemia cells in 90% of the cases.

A phase II clinical trial of adoptive immunotherapy for advanced renal cell carcinoma using mitogen-activated autologous leukocytes and continuous infusion interleukin-2.

Forty patients with metastatic, recurrent, or unresectable renal cell carcinoma were entered into a study of the therapeutic efficacy of adoptive immunotherapy using periodate (IO4-) and interleukin-2 (IL2)-activated autologous leukocytes and continuous infusion low-dose IL2. Patient survival was also examined. The first 15 consecutive patients were enrolled in protocol A without an IL2 priming phase and the following 25 patients were entered in protocol B where a 5-day priming phase was initiated before leukapheresis. A maintenance regimen consisted of either 3 x 10(6) units of recombinant interferon-alpha (rIFN-alpha), three times per week only or together with leukapheresis and infusion of IO4-/IL2-activated cells and 2 days of continuous infusion IL2 per month. Thirty-four patients completed the protocol treatment. Four patients were removed from the study owing to rapid tumor progression and two patients died while receiving treatment. The clinical response rate was 22%: two patients had a complete response and five patients had a partial response. Among the 25 patients who had no clinical response, 11 patients had either a mixed response or stabilization. Neither response, response duration, nor site response correlated with the total dose of IL2 administered or the number of activated killer cells infused. Patients who received maintenance therapy had longer survival times than patients who did not receive such therapy. All toxicity and side effects associated with IL2 treatment were transient and resolved after discontinuation of the drug. Patients on maintenance therapy tolerated both rIFN-alpha and monthly infusions of activated killer cells and IL2 well. This study confirms the concept of adoptive immunotherapy as a new treatment approach for advanced renal cell carcinoma and suggests that maintenance therapy may prolong survival time.

The free energy of mechanically unstable phases.

Phase diagrams provide 'roadmaps' to the possible states of matter. Their determination traditionally rests on the assumption that all phases, even unstable ones, have well-defined free energies under all conditions. However, this assumption is commonly violated in condensed phases due to mechanical instabilities. This long-standing problem impedes thermodynamic database development, as pragmatic attempts at solving this problem involve delicate extrapolations that are highly nonunique and that lack an underlying theoretical justification. Here we propose an efficient computational solution to this problem that has a simple interpretation, both as a topological partitioning of atomic configuration space and as a minimally constrained physical system. Our natural scheme smoothly extends the free energy of stable phases, without relying on extrapolation, thus enabling a formal assessment of widely used extrapolation schemes.

Adoptive immunotherapy for stage IV renal cell carcinoma: a novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2.

In a pilot study involving 13 patients with advanced stage IV renal cell carcinoma, anti-tumor effects and toxicity of a novel form of adoptive immunotherapy were determined. The protocol utilizes infusions of autologous mononuclear leukocytes treated with the oxidizing mitogen sodium periodate (IO4-) and cultured in medium containing human recombinant interleukin-2 (IL-2), and continuous infusions of low-dose IL-2 (mean +/- SD dose = 39.5 +/- 8.6 X 10(3) U/kg/24 hours). Leukocytes (5 to 10 X 10(9] were removed by leukapheresis three times per week, mononuclear cells were separated, activated with IO4- and cultured in medium containing IL-2 (500 U/ml) for 48 to 72 hours. The cells were re-infused following the next leukapheresis procedure. IL-2 was administered five days per week. Treatment was continued for two three-week cycles. An increase in peripheral blood mononuclear cells bearing the natural killer cell (NK) surface marker, Leu 11, an increase in NK- and antibody-dependent cell-mediated cytotoxicity, and a slight increase in spontaneous cytotoxicity for non-NK targets were noted. Regressions (more than 50 percent decrease in tumor mass) of pulmonary, liver, bone, or soft tissue metastases were induced in six patients. Severe fluid retention did not develop in any patient and no patient required treatment in the intensive care unit. Five of the patients who showed a response have experienced a relapse at 5.2 +/- 1.0 (mean +/- SD) months. These observations indicate that IO4-/IL-2-activated killer cells plus continuous infusions of low-dose IL-2 can result in regression of metastatic renal cell carcinoma.

In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients.

High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo.

Identification of L3 leukemia and Burkitt's lymphoma cells by flow cytometric quantitation of nuclear and cellular RNA and DNA content.

Separate quantitations of nucleic acids of isolated nuclei and cells of L3 leukemia/Burkitt's lymphoma cell populations of peripheral blood (PB), bone marrow (BM) and lymph node (LN) cell suspensions of 17 patients were performed by acridine orange (AO) flow cytometry (FCM). The cell populations were analysed with respect to cell cycle characteristics and DNA/RNA distribution histograms of cells in various compartments of the cell cycle using mean value, coefficient of variation (CV), third moment about the mean as a measure of skewness (MOM3). The correlations between numbers of L3 blasts detected by microscopy and aneuploid cells quantified by FCM in 10 patients with aneuploid disease were r = 0.75 and r = 0.85 for BM and PB cell populations, respectively. Content of both nuclear and cellular RNA was 3-4 times higher in L3 cells than in normal donor lymphocytes. Percentages of cells in SG2M phase of L3 populations were significantly different from control populations in BM (p less than 0.01) and PB (p less than 0.0001). All samples with L3 blasts had abnormal CV of the DNA, and abnormal CV and MOM3 of the RNA peaks of G0/1 cell histograms. All samples with no blasts by morphology had normal DNA and RNA patterns. AO FCM correctly classified all specimens as involved or not involved with disease in accordance with the cytomorphological diagnoses. Combining AO FCM with prior cell separation increased the sensitivity of the method to detect abnormal cells to 0.02%, or 0.5 L3 cells per microliter of blood.

Multiparameter characterization of L3 leukemia cell populations.

Multiparameter analysis of 14 consecutive patients with L3 cell populations (FAB classification) in bone marrow showed consistently high mean cellular RNA content but heterogeneity with respect to percent cels in S- and G2M-phases of the cell cycle, cell surface phenotype, cytogenetic abnormalities, cellular DNA content, and nuclear activities of terminal deoxynucleotidyl transferase. Five of the 14 patients had the characteristic profile of L3 leukemia with high RNA content, a typical t(8;14) or t(8;22) translocation, low Tdt, B-cell surface phenotype, pseudodiploid modal number of chromosomes, high proliferation and normal DNA index. The remaining 9 patients had features thought to be unusual and they were very heterogeneous. Median survival time from time of diagnosis was 115 days with no patient alive after 474 days. The survival times exhibited excellent correlation with a parametric model assuming exponential distribution. Accordingly, the presence of abnormal DI predicted for decreased, and the presence of t(8;14) or pseudodiploidy was associated with increased survival rates. However, due to the small number of patients in this study, generally applicable conclusions should be drawn only from a collection of larger numbers of cases of this rare type of leukemia.

The effect of a low-dose infusion of ritodrine on cardiac output distribution and uteroplacental blood flow in unanaesthetized pregnant guinea pigs.

Cardiac output and its distribution were measured using the microsphere technique before and at 2 and 6 h during the infusion of ritodrine, 1.5 microgram X min-1 X kg-1 i.v., into near-term pregnant guinea pigs. Average cardiac output increased 16 and 25%, and total peripheral resistance decreased 16 and 19% after 2 and 6 h of ritodrine infusion. The carcass and gastrointestinal tract together received two-thirds of the extra cardiac output. Uteroplacental blood flow and uteroplacental vascular resistance were not significantly different from the preinfusion values after 2 h of ritodrine treatment, but were increased 35% and decreased 31%, respectively (p less than 0.05 and less than 0.01), after 6 h of infusion. The increase in uteroplacental blood flow between the 2- and 6-h measurements was positively, and the decrease in uteroplacental vascular resistance negatively correlated with the increase in cardiac output during the same period.

Effect of prolonged infusion of ritodrine on uteroplacental blood flow and cardiac output distribution in unanesthetized pregnant guinea pigs.

The effects of ritodrine, 15 micrograms X min-1 X kg-1 administered intravenously, on the maternal circulation and uteroplacental blood flow were investigated in eight chronically catheterized pregnant guinea pigs near term. Cardiac output and its distribution were measured by means of the radionuclide-labelled microsphere technique before, and after 2 and 6 h of infusion of ritodrine. Ritodrine produced a sustained elevation of cardiac output to 135 and 137% of the control value after 2 and 6 h, respectively. The carcass and gastrointestinal tract together accounted for the greatest portion of the extra blood flow, 77 and 84% at the times of the two flow measurements during treatment. After 2 h of ritodrine, mean placental blood flow was reduced to 85% of the control level (n.s.), uteroplacental vascular resistance was 127% of its initial value (n.s.), and the placental fraction of cardiac output had decreased from 18 to 12% (P less than 0.02). Continuation of the infusion to 6 h resulted in an increase in mean placental blood flow to 107% of the control value and return of uteroplacental vascular resistance to its initial level. The placental fraction of cardiac output increased to 14%, significantly (P less than 0.05) different from both the initial and the 2-h values. Blood flow to the skin, lungs, spleen and mammary glands decreased between the 2- and 6-h flow measurements. These observations are compatible with the hypothesis that the changes in uteroplacental blood flow during administration of ritodrine are passive, resulting from the balance between the increase in cardiac output and vasodilatation in extrauterine vascular beds.

William James' legacy to Alcoholics Anonymous: an analysis and a critique.

When evolving a philosophy and a "modus operandi" the pioneers of Alcoholics Anonymous made significant use of William James' Varieties of Religious Experience. Indeed, although AA carefully picked and chose various of James' ideas which seemed particularly relevant, James' imprint is clearly stamped upon AA philosophy and methodology. Here, I will review James' work and explore what specific ideas were particularly relevant to AA's evolution as a self-help movement. The implications of this heritage will be explored.

[An rare cause of vaginal discharge: sarcoma botryoides]. / Een zeldzame oorzaak van fluor vaginalis: sarcoma botryoides.

A general practitioner was consulted by a 15-year-old girl, virgo, suffering from foetid vaginal discharge. The girl was seen by a gynaecologist after antimicrobial treatment had failed. Further investigations revealed that a embryonal rhabdomyosarcoma was present, a sarcoma botryoides. The tumour originating from the cervix uteri was resected completely after which chemotherapy was started. One year later there were no sequelae or indications of metastases. Sarcoma botryoides has a better prognosis than other types of rhabdomyosarcoma. The prognosis is also influenced by the site of origin, which is favourable for the cervix.

First-principles thermodynamics of coherent interfaces in samarium-doped ceria nanoscale superlattices.

Nanoscale superlattices of samarium-doped ceria layers with varying doping levels have been recently proposed as a novel fuel cell electrolyte. We calculate the equilibrium composition profile across the coherent {100} interfaces present in this system using lattice-gas Monte Carlo simulations with long-range interactions determined from electrostatics and short-range interactions obtained from ab initio calculations. These simulations reveal the formation of a diffuse, nonmonotonic, and surprisingly wide (11 nm at 400 K) interface composition profile, despite the absence of space charge regions.

Overcoming the promotional bias in health care marketing: a human relations approach.

In recent years the health care industry in general and ambulatory care in specific has been in a state of intense competition. In an attempt to survive and prosper, many health related organizations have turned to marketing as a means of developing viable strategies. Unfortunately, all too often the marketing function is equated with advertising and promotion: a small subsection of what a total marketing effort should be. In this paper, means of overcoming this limitation will be discussed using a human relations approach.