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.

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.

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.

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.

[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.

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.

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.

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.

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.

Cell cycle distribution in-vivo of mononuclear blood cells of renal allograft recipients.

In 47 healthy blood donors (controls) and 29 renal allograft recipients (patients) the relative contents of RNA and DNA of peripheral blood mononuclear (PBM) cell populations were estimated from the intensities of green and red fluorescences emitted by complexes that form with DNA and RNA, respectively, after staining the cells with the metachromatic dye, acridine orange. Based on the correlated DNA and RNA estimates for large numbers of cells, the percentages and the relative RNA contents of cells in particular compartments of the cell cycle were determined. PBM cell populations of controls contained less than 0.5% proliferating (SG2M) cells with highly variable relative RNA contents. Among controls, neither percentages nor relative RNA contents of SG2M-cells were correlated with percentages or relative RNA contents of G1-cells with an RNA content 2 (2SD) or 3 (3SD) standard deviations above the mean of the entire G0/1-cell population. Unlike controls, PBM cell populations of patients contained significantly higher percentages of SG2M-cells which were significantly correlated with the relative coefficients of variation (rCV) of the F530 histograms of G0/1-cells; the rCV represents the ratio of a patient's CV to a control's CV. Moreover, significant statistical correlations existed between percentages and relative RNA contents of 2SD-, 3SD-, SG2M- and G0/1-cells, suggesting a well-orchestrated progression of cells through the cell cycle. Different pairs of correlated parameters characterized clinically stable, acutely rejecting, and infected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered nucleic acid contents of mononuclear cells in blood of renal allograft recipients.

The DNA and RNA contents of blood mononuclear cell populations of 29 cadaver renal allograft recipients and 49 blood donors (controls) were estimated by acridine orange flow cytometry (AO FCM) to assess their cell cycle status. All patients received azathioprine and prednisone for immunosuppression. The patients represented three clinical categories: clinically stable patients, those with acute rejections (clinically overt or impending), and those with infections. Three cell cycle compartments were analyzed for percentage (%) and RNA content (R) of cells: G0/1, consisting of all cells with diploid DNA content; 2 S.D., consisting of cells with diploid DNA content and RNA content 2 standard deviations above the mean RNA content of controls; and SG2M, consisting of cells with a DNA content higher than that of G0/1 cells. The relative coefficient of variation (rCV) of the DNA distribution of G0/1 cells was also determined. In such cell cycle evaluations, the means of rCV and SG2M% of stable recipients were significantly different from those of blood donors. Multivariate analysis of the variables of the three categories of patients resulted in the tentative formulation of two simple logistic equations: one that differentiates stable patients from those with impending or overt rejections based on 2SD% and another one that distinguishes infected patients from those with impending or overt rejections based on SG2M% and RG0/1.

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.

Periodate and recombinant interleukin-2-activated autologous leukocytes can induce regression of metastases of renal cancer.

We present the results of a pilot study that determined the effects of both intermittent injections of periodate and recombinant interleukin-2 (rIL-2)-activated leukocytes and continuous infusions of low doses of rIL-2 on metastases of nine patients with stage IV renal cancer. Four patients experienced regressions, two patients stabilized, and only three patients did not respond. The responses of individual lesions in six patients were heterogeneous with regard to both the degree (ranging from cessation of growth to regression to undetectability) and the duration (ranging from less than 3 to up to 8 months). Survival times from the time of diagnosis and from the time of start of the protocol treatment ranged from 12 to 20 months and 6 to 12 months, respectively, for three patients who expired and from 10+ to 28+ months and 6+ to 12+ months, respectively, for six patients who are alive. Only one patient experienced a grade 4 toxicity (transient renal failure requiring hemodialysis). All other toxicities (grades 1-3) were easily controlled and resolved completely after 7 days. This pilot study deserves clinical testing on a larger scale, since it combines regression inductions in a hitherto treatment-resistant cancer with little complicating toxicity.

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.

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.

Erythropoietin-hematocrit feedback circuit in the anemia of end-stage renal disease.

Deficient erythropoietin (EP) production is thought to be a key factor in the pathogenesis of the anemia of end-stage renal disease. We describe the interrelationships between radioimmunoassayed plasma EP levels, reticulocyte counts corrected for anemia (CRC) and hematocrit (HCT) under challenge by hemorrhage, transfusions and hemodialysis in 32 chronically-hemodialyzed patients. Spontaneous hemorrhage resulted in a decrease in HCT (P = 0.001) and increases in both EP (P = 0.006) and CRC levels (P = 0.0065). Transfusions of two units of packed red cells into each of 16 patients suppressed EP (P = 0.0004) and CRC (P less than 0.0001) after about 28 and 42 hours, respectively. Repeat transfusions after one to 27 days resulted in similarly significant suppressions of both EP and CRC, except the CRC remained on higher levels for prolonged periods of times. Within a few hours after each transfusion of 2,3-diphosphoglycerate-poor red cells, both EP (P = 0.009) and CRC (P = 0.007) increased temporarily between one to 18 and three to 38 hours, respectively. Hemodialysis resulted in alkalinization (P = 0.008) of blood but not in changes of EP or CRC counts. The data show that, with the EP-HCT feedback loop persisting, increased endogenous hormone levels elicit erythropoietic responses, and that the regulation of EP levels may involve determinants such as oxy-deoxyhemoglobin interactions.

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.