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PubMed2005

Transformation of expression intensities across generations of Affymetrix microarrays using sequence matching and regression modeling.

The utility of previously generated microarray data is severely limited owing to small study size, leading to under-powered analysis, and failure of replication. Multiplicity of platforms and various sources of systematic noise limit the ability to compile existing data from similar studies. We present a model for transformation of data across different generations of Affymetrix arrays, developed using previously published datasets describing technical replicates performed with two generations of arrays. The transformation is based upon a probe set-specific regression model, generated from replicate measurements across platforms, performed using correlation coefficients. The model, when applied to the expression intensities of 5069 shared, sequence-matched probe sets in three different generations of Affymetrix Human oligonucleotide arrays, showed significant improvement in inter generation correlations between sample-wide means and individual probe set pairs. The approach was further validated by an observed reduction in Euclidean distance between signal intensities across generations for the predicted values. Finally, application of the model to independent, but related datasets resulted in improved clustering of samples based upon their biological, as opposed to technical, attributes. Our results suggest that this transformation method is a valuable tool for integrating microarray datasets from different generations of arrays.

Algorithms↗
PubMed1980

Host immune status in uraemia. II. Serum factors and lymphocyte transformation.

A model of experimentally induced uraemia has been used to study the effect of serum from uraemic rats on the immune responsiveness of thymus-derived (T) lymphocytes. Splenic lymphocytes from normal or uraemic animals responded to mitogenic stimulation with concanavalin A to a similar degree when cultured in a tissue culture medium containing the maximum non-toxic concentration of normal or uraemic serum in the culture system (3%). Serum from uraemic animals, however, had an immunosuppressive effect if the serum was first dialysed for 24 hr before being added to the tissue culture medium. When an alternative vessel was used which allowed the concentration of serum in the medium to be increased to 10%, serum from severely uraemic animals markedly suppressed the capacity of lymphocytes from normal animals to respond to Con A. Thus while serum from uraemic animals can be shown to be immunosuppressive, the results of the experiments are influenced by the conditions in vitro. The type of culture vessel and the concentration of serum in the culture medium are particularly critical determinants. It is likely that variations in laboratory procedures have contributed to the differences of opinion on the effect of serum from uraemic individuals on lymphocyte function.

Animals↗
PubMed1988

Image analysis and three-dimensional model of chymotrypsin-transformed human alpha 2-macroglobulin complexed with a monoclonal antibody specific for this conformation.

Alpha 2-macroglobulin (alpha 2M) is a plasma inhibitor of proteinases, the steric mechanism of which is based on a considerable conformational change. The typical and distinct H-like shape of alpha 2M-chymotrypsin (alpha 2M-chy) complexes seen by electron microscopy led us to an ultrastructural study of the binding of a monoclonal antibody (Mab) specific for this conformation of alpha 2M. The epitope of this Mab is located near the extremities of the 4 arms of the H-like alpha 2M-chy, at a site that is not accessible on the native molecule. The identical binding of the Mab on the 4 arms of the tetrameric molecule demonstrates that these arms are equivalent portions of the 4 monomers. Various types of immune complexes between alpha 2M and IgG are described, and images of individual immune complexes were processed by correspondence analysis. This extracts new information concerning the organization of chymotrypsin-transformed alpha 2M. The molecule appears asymmetrical, presents 2 conformational states (which we describe as relaxed and twisted), and has flexible arms. These intramolecular motions are supposed to be related to IgG binding. The results are discussed in comparison with previously published models of proteinase-transformed alpha 2M.

Antibodies, Monoclonal↗
PubMed1976

Increased sarcoma virus RNA in cells transformed by leukemia viruses: model for leukemogenesis.

A morphologically flat revertant of mink cells nonproductively infected with Moloney sarcoma virus exhibited contact inhibition and lacked detectable sarcoma virus RNA. Superinfection by usually nontransforming type C mammalian leukemia-causing viruses induced transformation and increased sarcoma virus RNA. The results suggest a model for leukemogenesis in animals by increasing, during replication of usually nontransforming leukemia viruses, the levels of RNA from potentially oncogenic cell or integrated virus transforming genes.

Cell Transformation, Neoplastic↗
PubMedDate not supplied

Improving healthcare delivery with the transformational whole person care model.

A Whole Person Care model was developed by The New England School of Whole Health Education following a 2-year pilot study that demonstrated the transformational effects of whole health education. This holistic model of health education and behavioral interaction provides a tool for nurses, physicians, and staff to redirect the momentum of care toward in-the-moment, relationship-centered whole person care, improving healthcare worker and patient satisfaction and outcomes.

Attitude of Health Personnel↗
PubMed1988

A model system for leukemic transformation of immortalized hemopoietic cells in irradiated recipient mice.

Proliferation in vitro of the murine hemopoietic cell line FDC-P1 is dependent on stimulation by granulocyte-macrophage colony stimulating factor or multipotential colony stimulating factor. Although immortalized, the cells are not tumorigenic on subcutaneous inoculation. Intravenous injection of FDC-P1 cells into syngeneic DBA/2 mice was followed by the development of transplantable leukemias in 15% of nonirradiated animals and in virtually all animals that had received 100-350 rad whole-body irradiation prior to injection. Karyotypic analysis showed that the leukemias originated from FDC-P1 cells, and primary tumor cells from different animals displayed a wide spectrum of altered growth patterns when cultured in agar. In most cases, colony formation by leukemic cells in vitro exhibited autonomy with respect to stimulation by exogenous colony stimulating factors. These observations indicate that leukemic transformation of FDC-P1 cells is enhanced by irradiation of recipient mice and document a useful model for analyzing the mechanisms by which irradiation induces leukemia.

Animals↗
PubMedDate not supplied

[Physical model of initial stages of energy transformation during oxidative phosphorylation].

A model of non-dissipative energy transmission of activated electron into proton subsystem energy was considered. The model is based on the effect of resonance tunneling of the electrons, which provides for non-dissipative energy transmission. Within the scope of the model the energized proton formed in the protein membrane structure has enough energy to perform phosphorylation.

Energy Transfer↗
PubMed2002

Development and test of a model linking safety-specific transformational leadership and occupational safety.

The authors developed, tested, and replicated a model in which safety-specific transformational leadership predicted occupational injuries in 2 separate studies. Data from 174 restaurant workers (M age = 26.75 years, range = 15-64) were analyzed using structural equation modeling (LISREL 8; K. G. Jöreskog & D. Sörbom, 1993) and provided strong support for a model whereby safety-specific transformational leadership predicted occupational injuries through the effects of perceived safety climate, safety consciousness, and safety-related events. Study 2 replicated and extended this model with data from 164 young workers from diverse jobs (M age = 19.54 years, range = 14-24). Safety-specific transformational leadership and role overload were related to occupational injuries through the effects of perceived safety climate, safety consciousness, and safety-related events.

Adult↗
PubMed1995

Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure.

An improved lithium acetate (LiAc)/single-stranded DNA (SS-DNA)/polyethylene glycol (PEG) protocol which yields > 1 x 10(6) transformants/micrograms plasmid DNA and the original protocol described by Schiestl and Gietz (1989) were used to investigate aspects of the mechanism of LiAc/SS-DNA/PEG transformation. The highest transformation efficiency was observed when 1 x 10(8) cells were transformed with 100 ng plasmid DNA in the presence of 50 micrograms SS carrier DNA. The yield of transformants increased linearly up to 5 micrograms plasmid per transformation. A 20-min heat shock at 42 degrees C was necessary for maximal yields. PEG was found to deposit both carrier DNA and plasmid DNA onto cells. SS carrier DNA bound more effectively to the cells and caused tighter binding of 32P-labelled plasmid DNA than did double-stranded (DS) carrier. The LiAc/SS-DNA/PEG transformation method did not result in cell fusion. DS carrier DNA competed with DS vector DNA in the transformation reaction. SS plasmid DNA transformed cells poorly in combination with both SS and DS carrier DNA. The LiAc/SS-DNA/PEG method was shown to be more effective than other treatments known to make cells transformable. A model for the mechanism of transformation by the LiAc/SS-DNA/PEG method is discussed.

Acetates↗
PubMed2004

Simplified crossover droplet model for adsorption of pure fluids in slit pores.

We present a generalized crossover (GC) model for the excess adsorption of pure fluids at a flat solid-liquid interface, which reproduces scaling behavior of the excess adsorption in the critical region and is reduced to the classical, van der Waals-type analytical model far away from the bulk critical point. In developing this model, we used the density-functional theory (DFT) approach for the order parameter profile calculations with a generalized corresponding states model for the local free-energy density. The GC DFT model well represents the available experimental adsorption data for Kr/graphite, C2H4/graphite, C3H8/graphite, CO2/silica, and SF6/graphite systems in the entire density range 0 < rho < or = 3rhoc and temperatures up to 1.7Tc. In the critical region 0.5 rhoc < r < or = 1.5rhoc and T < or = 1.15Tc, the GC DFT model is consistent with the predictions of the asymptotic renormalization-group crossover model for the critical adsorption in a semi-infinite system developed earlier. For the excess adsorption on the critical isochore, both theories predict a scaling-law behavior Gamma proportional tau(-nu+beta), but fail to reproduce a "critical depletion" of the excess adsorption along the critical isochore of the SF6/graphite system near Tc. We show that an anomalous decrease of adsorption observed in this system at tau = T/Tc - 1 < 10(-2) can be explained by finite-size effect and develop a simplified crossover droplet (SCD) model for the excess adsorption in a slit pore. With the effective size of the pore of L = 50 nm, the SCD model reproduces all available experimental data for SF6/graphite, including the critical isochore data where tau-->0, within experimental accuracy. At L >> xib (where xib is a bulk correlation length) the SCD model is transformed into the GC DFT model for semi-infinite systems. Application of the SCD model to the excess adsorption of carbon dioxide on the silica gel is also discussed.

Journal Article↗
PubMed2006

Direct costs of warfarin treatment among patients with atrial fibrillation in a Finnish health care setting.

OBJECTIVE: The main objective was to estimate the mean direct costs of warfarin treatment for atrial fibrillation (AF) patients. Secondly, the costs of initiating warfarin treatment during a 60-day period and the impact of International Normalized Ratio (INR) and co-morbidities on costs were estimated. DESIGN AND DATA: The study was performed as a retrospective cohort study over a 12-month period in a Finnish communal health care setting. All AF patients aged 65 years or older (n = 250) with warfarin treatment were identified from the database of the health service district of an urban area. Patient specific information related to comorbidities, INR-control, complications and health care resource use were collected. Cost information was obtained from the Finnish national health care unit cost list. METHODS: The effect of treatment balance and other background variables on treatment costs were evaluated using ordinary least squares regression (OLS), log-transformed OLS and generalized linear model (GLM). The mean costs were calculated on the basis of the different models and bias corrected and accelerated (BCa) bootstrap confidence intervals (CIs) were calculated for the mean costs. RESULTS: The best fitting cost model was log-transformed OLS. The costs of warfarin treatment on the basis of the log-transformed model were 589.82 Euros (BCa 95% CI: 586.68-591.99) per patient compared to 616.00 Euros (BCa 95% CI: 579.98-652.96) obtained with the OLS-model. For the treatment initiation period, the mean costs were 263 Euros (BCa 95% CI: 218.90-314.71). Depending on the way that INR-control was defined, the mean costs were 95.27 Euros or 166.92 Euros higher for patients who were not in the defined INR-balance. CONCLUSIONS: The INR-control has a significant impact on the warfarin treatment costs. The choice of model influences the estimated mean costs. In addition, different models identify statistically significant effects between different background variables and costs.

Aged↗
PubMed2006

Prediction of Lyme meningitis in children from a Lyme disease-endemic region: a logistic-regression model using history, physical, and laboratory findings.

BACKGROUND: Differentiating Lyme meningitis (LM) from other forms of aseptic meningitis (AM) in children is a common diagnostic dilemma in Lyme disease-endemic regions. Prior studies have compared clinical characteristics of patients with LM versus patients with documented enteroviral infections. No large studies have compared patients with LM to all patients presenting with AM and attempted to define a clinical prediction model. OBJECTIVE: To create a statistical model to predict LM versus AM in children based on history, physical, and laboratory findings during the initial presentation of meningitis. METHODS: Children older than 2 years presenting to the Alfred I. duPont Hospital for Children between October 1999 and September 2004 were identified if both Lyme serology and cerebrospinal fluid (CSF) were collected during the same hospital encounter. Patients were considered to have Lyme disease only if they met Centers for Disease Control and Prevention criteria (documented erythema migrans and/or positive Lyme serology). Patients were eligible for study inclusion if they had documented meningitis (CSF white blood cell count: >8 per mm3). Retrospective chart review abstracted duration of headache and cranial neuritis (papilledema or cranial nerve palsy) on physical examination and percent CSF mononuclear cells. Using logistic-regression analysis, the type of meningitis (LM versus AM) was simultaneously regressed on these 3 variables. The Hosmer-Lemeshow test was performed and the area under the receiver operating characteristic curve was calculated. RESULTS: A total of 175 children with meningitis were included in the final statistical model. Logistic-regression analysis included 27 patients with LM and 148 patients classified as having AM. Duration of headache, cranial neuritis, and percent CSF mononuclear cells independently predicted LM. The Hosmer-Lemeshow test revealed a good fit for the model, and the Nagelkerke R2 effect size demonstrated good predictive efficacy. Odds ratios based on the logistic-regression results were calculated for these variables. The final model was transformed into a clinical prediction model that allows practitioners to calculate the probability of a child having LM. CONCLUSIONS: Longer duration of headache, presence of cranial neuritis, and predominance of CSF mononuclear cells are predictive of LM in children presenting with meningitis in a Lyme disease-endemic region. The clinical prediction model can help guide the clinician about the need for parenteral antibiotics while awaiting serology results.

Child↗
PubMed2025

Integration of Gene Expression and Digital Histology to Predict Treatment-Specific Responses in Breast Cancer.

Deep learning models applied to digital histology can predict gene expression signatures (GES) and offer a low-cost, rapidly available alternative to molecular testing at the time of diagnosis. We optimized transformer-based models to infer GES results and applied this approach to pre-treatment H&E-stained biopsies from 1,940 breast cancer patients treated with neoadjuvant chemotherapy in clinical trial and real-world cohorts. The most predictive histology-derived GES for pathologic complete response (pCR) in the I-SPY2 trial was validated in four external cohorts: CALGB 40601, CALGB 40603, a trial of durvalumab plus CT, and standard-of-care CT-treated patients from the University of Chicago. Among HER2-negative patients, a transformer-based model trained using a signature composed of estrogen-regulated genes, proliferation, apoptosis, and interferon response genes predicted pCR with an AUC of 0.794, outperforming models based on clinical features alone (AUC 0.704, p = 0.001), pathologist TIL assessment, and a model trained directly to predict response from I-SPY2 cases. Tertiles of this signature stratify patients into clinically relevant groups with increasing likelihood of complete response, with pCR rates &#x2265;50% in the top tertile regardless of treatment or hormone receptor status. Additional transformer-based signature models predicted response to specific therapies (but not chemotherapy alone), including a HER2 signaling signature in IO-treated patients, and a claudin-low signature in bevacizumab treated patients. In HER2- cohorts with available gene expression data and histology, models trained on expression data performed similarly to digital histology predictions, but the combination of gene expression and histology outperformed histology alone. These findings suggest that histology-based GES provides additive information to RNA sequencing data and can inform precision treatment selection across breast cancer subtypes.

Journal Article↗
PubMed1997

Recent developments in formulating model descriptors for subsurface transformation and sorption of trinitrotoluene.

Recent published data show that transformation and sorption are key processes involved in the subsurface transport of TNT. The state-of-the-art understanding of TNT soil transformation and sorption phenomena is summarized below: There is unequivocal evidence of reductive transformation of TNT in soils. However, soil properties affecting TNT transformation are only partially understood. Edaphic factors such as redox are probably important since highest reductive transformation rates occur under anaerobic conditions. TNT transformation products include 2A-DNT, 4A-DNT, 2,4-DANT, and 2,6-DANT. Azoxytoluenes have also been reported. Triaminotoluene may be an important TNT transformation product, but this product has not been routinely measured. TNT soil sorption is rapid and can be modeled as equilibrium controlled. Poor mass balances are difficult to interpret owing to lack of information on transformation products. Various irreversible disappearance mechanisms other than transformation to elutable transformation products are possible.

Adsorption↗
PubMed2004

An ordinary differential equation model for the multistep transformation to cancer.

Cancer is viewed as a multistep process whereby a normal cell is transformed into a cancer cell through the acquisition of mutations. We reduce the complexities of cancer progression to a simple set of underlying rules that govern the transformation of normal cells to malignant cells. In doing so, we derive an ordinary differential equation model that explores how the balance of angiogenesis, cell death rates, genetic instability, and replication rates give rise to different kinetics in the development of cancer. The key predictions of the model are that cancer develops fastest through a particular ordering of mutations and that mutations in genes that maintain genomic integrity would be the most deleterious type of mutations to inherit. In addition, we perform a sensitivity analysis on the parameters included in the model to determine the probable contribution of each. This paper presents a novel approach to viewing the genetic basis of cancer from a systems biology perspective and provides the groundwork for other models that can be directly tied to clinical and molecular data.

Cell Division↗
PubMed2006

[Comparative evaluation of health hazards associated with industrial chemicals and their derivates forming during water chlorination].

Many industrial chemicals found in waste waters are able to form organochlorine by-products during water disinfection. The transformation of seven model compounds, cyclohexene, n-butanol, diphenylmethane, acetophenone, aniline, 1-methylnaphthalene, and phenylxylylethane during a reaction with active chlorine was studied. Aqueous chlorine and sodium hypochlorite were used as chlorinating agents. The products of the reaction were analyzed by means of chromatomass-spectrometry. A schematic model of diphenylmethane transformation was proposed. Comparative evaluation of hazards associated with the model chemicals and their derivates confirmed that chlorination products can be more toxic and dangerous than the initial compounds, and may possess mutagenic and cancerigenic properties.

Aminophenols↗