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Metastasis is responsible for most breast cancer-related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature

Recent advances in high‐throughput molecular profiling technologies and multiplexed imaging platforms have revolutionized our ability to characterize the tumor immune microenvironment. As a result, studies of tumor‐associated immune cells increasingly involve complex data sets that require sophisticated methods of computational analysis. In this review, we present an overview of key assays and related bioinformatics tools for analyzing the tumor‐associated immune system in bulk tissues and at the single‐cell level. In parallel, we describe how data science strategies and novel technologies have advanced tumor immunology and opened the door for new opportunities to exploit host immunity to improve cancer clinical outcomes.

Single-cell RNA-sequencing has emerged as a powerful technique for characterizing cellular heterogeneity, but it is currently impractical on large sample cohorts and cannot be applied to fixed specimens collected as part of routine clinical care. We previously developed an approach for digital cytometry, called CIBERSORT, that enables estimation of cell type abundances from bulk tissue transcriptomes. We now introduce CIBERSORTx, a machine learning method that extends this framework to infer cell-type-specific gene expression profiles without physical cell isolation. By minimizing platform-specific variation, CIBERSORTx also allows the use of single-cell RNA-sequencing data for large-scale tissue dissection. We evaluated the utility of CIBERSORTx in multiple tumor types, including melanoma, where single-cell reference profiles were used to dissect bulk clinical specimens, revealing cell-type-specific phenotypic states linked to distinct driver mutations and response to immune checkpoint blockade. We anticipate that digital cytometry will augment single-cell profiling efforts, enabling cost-effective, high-throughput tissue characterization without the need for antibodies, disaggregation or viable cells. CIBERSORTx, a suite of computational tools, enables inference of cell type abundance and cell-type-specific gene expression profiles from bulk RNA profiles.

Background Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate has previously been identified as a growth suppressor in some cancer types and was tested as a new treatment option in B-cell lymphoma. Methods We included artesunate in a cancer sensitivity drug screen in B lymphoma cell lines. The preclinical properties of artesunate was tested as single agent in vitro in 18 B-cell lymphoma cell lines representing different histologies and in vivo in an aggressive B-cell lymphoma xenograft model, using NSG mice. Artesunate-treated B lymphoma cell lines were analyzed by functional assays, gene expression profiling, and protein expression to identify the mechanism of action. Results Drug screening identified artesunate as a highly potent anti-lymphoma drug. Artesunate induced potent growth suppression in most B lymphoma cells with an IC50 comparable to concentrations measured in serum from artesunate-treated malaria patients, while leaving normal B-cells unaffected. Artesunate markedly inhibited highly aggressive tumor growth in a xenograft model. Gene expression analysis identified endoplasmic reticulum (ER) stress and the unfolded protein response as the most affected pathways and artesunate-induced expression of the ER stress markers ATF-4 and DDIT3 was specifically upregulated in malignant B-cells, but not in normal B-cells. In addition, artesunate significantly suppressed the overall cell metabolism, affecting both respiration and glycolysis. Conclusions Artesunate demonstrated potent apoptosis-inducing effects across a broad range of B-cell lymphoma cell lines in vitro, and a prominent anti-lymphoma activity in vivo, suggesting it to be a relevant drug for treatment of B-cell lymphoma.

Biological heterogeneity in diffuse large B cell lymphoma (DLBCL) is partly driven by cell-of-origin subtypes and associated genomic lesions, but also by diverse cell types and cell states in the tumor microenvironment (TME). However, dissecting these cell states and their clinical relevance at scale remains challenging. Here, we implemented EcoTyper, a machine learning framework integrating transcriptome deconvolution and single-cell RNA sequencing, to characterize clinically relevant DLBCL cell states and ecosystems. Using this approach, we identified five cell states of malignant B cells that vary in prognostic associations and differentiation status. We also identified striking variation in cell states for 12 other lineages comprising the TME and forming cell-state interactions in stereotyped ecosystems. While cell-of-origin subtypes have distinct TME composition, DLBCL ecosystems capture clinical heterogeneity within existing subtypes and extend beyond cell-of-origin and genotypic classes. These results resolve the DLBCL microenvironment at systems-level resolution and identify opportunities for therapeutic targeting (https://ecotyper.stanford.edu/lymphoma).

Determining how cells vary with their local signaling environment and organize into distinct cellular communities is critical for understanding processes as diverse as development, aging, and cancer. Here we introduce EcoTyper, a machine learning framework for large-scale identification and validation of cell states and multicellular communities from bulk, single-cell, and spatially resolved gene expression data. When applied to 12 major cell lineages across 16 types of human carcinoma, EcoTyper identified 69 transcriptionally defined cell states. Most states were specific to neoplastic tissue, ubiquitous across tumor types, and significantly prognostic. By analyzing cell-state co-occurrence patterns, we discovered ten clinically distinct multicellular communities with unexpectedly strong conservation, including three with myeloid and stromal elements linked to adverse survival, one enriched in normal tissue, and two associated with early cancer development. This study elucidates fundamental units of cellular organization in human carcinoma and provides a framework for large-scale profiling of cellular ecosystems in any tissue.

Summary Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

Postpartum depression is a serious health issue affecting as many as 10-15 % of postpartum women. This longitudinal study aimed to explore how psychological variables such as cognitive emotion regulation strategies, breastfeeding self-efficacy (BSE), and dimensions of social support predicted postpartum depressive symptoms (Edinburgh Postnatal Depression Scale). The data were collected with web-based survey questionnaires between May 2008 and December 2009, in a sample of 737 new mothers. The same questionnaire was surveyed at three points in time: 6 weeks, 3 months, and 6 months postpartum. Data were analyzed using multilevel modeling (level 1, time points; level 2, person). Results showed that BSE, certain cognitive emotion regulation strategies, perceived available support, and need for support predicted the rate of postpartum depressive symptoms. Only breastfeeding self-efficacy predicted change in postpartum depressive symptoms. This study illustrates the importance of psychological variables with regard to postpartum depressive symptoms. Implications for preventative efforts are discussed.

Food fraud is receiving considerable attention with the growing body of literature that recognises its importance. No system exists that collects media reports on food fraud. In this study, we used the infrastructure provided by the European Media Monitor (EMM), in particular it's MedISys portal for this purpose. We developed a food fraud tool (MedISys-FF) that collects, processes and presents food fraud reports published world-wide in the media. MedISys-FF is updated every 10 min 24/7. Food fraud reports were collected with MedISys-FF for 16 months (September 2014 to December 2015) and benchmarked against food fraud reports published in Rapid Alert for Food and feed (RASFF), Economically Motivated Adulteration Database (EMA) and HorizonScan. The results showed that MedISys-FF collects food fraud publications with high relevance >75% and the top 4 most reported fraudulent commodities in the media were i) meat, ii) seafood, iii) milk and iv) alcohol. These top stories align with those found in RASFF and EMA but differences in frequency are apparent. Analysis of the collected articles can help understanding food fraud issues in the origin countries and can facilitate the development of control measures and to detect food fraud in the food supply chain.

To study short- and long-term improvement in obstetric anal incontinence after secondary overlapping sphincteroplasty and repeat repairs.A prospective analysis based on incontinence scores and patient satisfaction.Department of Gastroenterological Surgery, Oslo University Hospital, a tertiary unit also dealing with sphincter repair.Of 40 obstetric patients operated consecutively from February 1996 to April 2004, 33 (83%) patients with median age of 36 years were eligible for evaluation.Wexner's and St. Mark's incontinence score, clinical examination, anal ultrasonography and manometry, and neurophysiological examination when indicated. Patient satisfaction to treatment was recorded. The patients had anterior overlapping sphincteroplasty. Five had repeat operations, four sphincteroplasty and two post-anal repair.Anal incontinence, patient satisfaction.The 33 patients were examined after median 7 (range 2-62) months and 103 (62-162) months. Median incontinence scores preoperatively and after short- and long-term follow-up were 12 (5-20), 7 (5-20) (p0.01) and 9 (0-18) (p0.05), respectively. Three patients (9%) had normalized anal incontinence (score ≤1) after short- and long-term follow-up. Corresponding numbers for improved anal incontinence were 22 (67%) and 16 (49%), respectively. Improvement in incontinence scores and patients' satisfaction were concordant. Symptom duration (n = 7), pudendal neuropathy (n = 6), repeat repair (n = 5) and instrument delivery (n = 3) were associated with adverse outcome.Improvement in anal incontinence at short-term follow-up is attenuated at long-term follow-up. Stoma formation, sacral nerve stimulation and neo-sphincter formation must be considered in compliant patients.

The Core Content for Clinical Informatics defines the boundaries of the discipline and informs the Program Requirements for Fellowship Education in Clinical Informatics. The Core Content includes four major categories: fundamentals, clinical decision making and care process improvement, health information systems, and leadership and management of change. The AMIA Board of Directors approved the Core Content for Clinical Informatics in November 2008.

This document comprises an AMIA Board of Directors approved White Paper that presents a roadmap for national action on clinical decision support. It is published in JAMIA for archival and dissemination purposes. The full text of this material has been previously published on the AMIA Web site (www.amia.org/inside/initiatives/cds). AMIA is the copyright holder.

To develop a method for quantifying risks of death and dementia in relation to vascular risk factors the Gothenburg H-70 1901-02 birth cohort was studied (n=380, was followed over 20 years, with 103 incident dementia cases). Separate vascular risk factor indices were calculated using 23 vascular risk factors to predict: (i) dementia-free-survival, and (ii) incident dementia derived from post hoc optimal separation of affected and unaffected cases. Classification of adverse outcomes (dementia/non-dementia; alive/dead) was assessed using receiver-operator characteristic (ROC) curves, and the area under the curve (AUC). Each index showed high separation between affected and unaffected cases. For dementia/non-dementia, the AUC was 0.74+/-0.02 for 10 year and 0.67+/-0.02 for 20 year; for death/survival, the AUC was 0.75+/-0.02 for 10 years and 0.79+/-0.03 for 20 years. Of note, few items were important in both indexes, and most showed reciprocal effects (e.g. decreased the risk of death but increased the risk of dementia). Our results suggest that vascular risk factor indexes can give robust estimates of dementia and life span prognoses in elderly people, but death and dementia have different risk profiles. This may be because of death being a competing risk for incident late-onset dementia.

Cancer is generally believed to arise from a single cell which has become 'initiated' by mutation of a few crucial genes, caused by random 'hits' in its DNA, a 'hit' being an error in DNA replication or a reaction of the DNA with free radicals or other chemical species of exogenous or endogenous origin. It is not obvious how the epidemiological data on cancer incidence can be interpreted within the framework of this paradigm. For example, it cannot account quantitatively for the age dependence of cancer incidence, or for the fact that the incidence of cancer in people with hereditary mutations in tumour suppressor genes is much lower than expected, or for the observation that while in some types of cancer, like colon and pancreas, certain highly oncogenic mutations, such as that of TP53, are prevalent, there is no significant increase in the incidence of these cancers in people who carry the mutations by heredity. It is argued here that although mutations in such genes appear to be of crucial importance in carcinogenesis they may not be the rate limiting events in common cancer. The epidemiological data are consistent with the hypothesis that the rate limiting processes involve large numbers of cells. Conceivably, the mutations directly underlying neoplastic transformation may be the result of a local collapse in the system of intercellular processes on which the stability of the normal genotype and phenotype depends, and thereby trigger a cascade of mutations, among them the highly oncogenic ones. This local collapse may be due to mutations of many different genes in many cells as well as to other factors affecting the integrity of tissue.

Within the framework of the gerontological and geriatric population studies in Goteborg, Sweden, H70, 617 85-year-old people were studied in a cross-sectional study. The purpose was to describe disability in activities of daily living (ADL) and how it is related to visual impairment, focusing on age-related macular degeneration (AMD). People with visual impairment, especially those with AMD, were found to be more dependent on help in both personal activities of daily living and instrumental activities of daily living compared with elderly persons with normal vision. The proportion of participants with disability in ADL and the relative risk of developing ADL dependence increased with the decrease in visual acuity (VA). However, the relationship between ADL and VA was weak, implying that people adapt to the consequences of the disease, although to different degrees. The results indicate that early detection and intervention might be essential to improve the odds for successful rehabilitation.

Endothelial cells assume divergent physiologic postures, from a 'quiescent' to an 'activated' state, and this ability is thought to critically regulate homeostasis of the vascular milieu. While establishing endothelial cell lines, we observed that most of the endothelial cells exhibited 'spontaneous' activation with morphological changes once the cells surpassed confluence. In the present study, we investigated whether accumulation and subsequent availability of certain factors in the cells might induce morphologic changes indicating activated phenotype in confluent endothelial cells. Cell lysate from nonactivated confluent endothelial cells activated autologous target cells, whereas culture supernatants did not. Stimulatory activity of the cell lysate was dependent on the concentration of cell lysate, i.e., nonactivated endothelial cell lysate at 25% concentration induced a substantial level of morphologic change. The 'spontaneous' as well as the cell lysate-induced change in morphology of endothelial cells was inhibited by neutralization of interleukin (IL)-1alpha with anti-IL-1alpha antibody. Correspondingly, cell lysate from confluent non-IL-1-expressing endothelial cells did not alter the morphology of autologous confluent cells even at a higher concentration. Cells that spontaneously changed their morphology correspondingly upregulated IL-1alpha and IL-8 transcripts. The results indicate that the accumulation and availability of endogenous IL-1alpha is responsible for the 'spontaneous' activation of endothelial cells in culture. Ultimately, through this property, endothelial cells may facilitate normal in vivo host responses, including the regulation of leukocyte trafficking.

The implications of aberrations in the p53 pathway for induction of apoptosis and regulation of S phase entry, and for patient survival, were investigated in 83 B-cell Non-Hodgkin's lymphomas. Eight cases had missense mutations in exons 5, 7, 8 and 9 as revealed by constant denaturant gel electrophoresis and sequencing. Fifteen cases had lost 1 TP53 allele as revealed by fluorescent in situ hybridization and comparative genomic hybridization. Ten cases expressed high levels of p53 as assessed by immunoblotting and immunohistochemistry. S phase fractions were higher, apoptotic fractions were the same and survival times were shorter in all aberration groups compared with the cases with no TP53/p53 aberrations. Since many tumors had more than one TP53/p53 aberration, the tumors were divided into groups with the following characteristics: no TP53/p53 aberrations; loss of one TP53 allele only (9 cases), TP53 point mutation (8 cases), high-level p53 expression and no TP53 mutation (3 cases). Tumors from the 3 latter groups had higher median S phase fractions (5%, 7.6%, and 5%, respectively, p0.02) than the cases without any aberrations (1.1%), and survival time for these patients was much shorter (relative risks of 5.9, 8.9, and 6.6, respectively, p0.003). Apoptotic fractions were similar in all these groups (p=0.09). Multivariate analysis showed that the presence of TP53/p53 aberrations is a strong and independent prognostic parameter in B-cell Non-Hodgkin's lymphoma.

To study the ability of colour naming, colour discrimination and colour preference in Alzheimer's disease (AD).Descriptive, consecutive sample.Fifty subjects65 years with AD.Testing colour discrimination, colour naming and colour preferences.Ability to detect colour differences in the yellow, red, blue and green areas, ability to assign a name to 22 colour samples, ability to rank seven colours in order of preference.Discrimination ability was significantly better in the yellow and red area and for lightness variations. Cognitive decline had a significant impact on naming mixed colours and using elaborate colour names. Severity of dementia did not affect the preference rank order of colours.Ability to discriminate is affected in AD, with most errors in the blue and green area. Naming colours shows a cognitive decline. Preferences for colour are stable despite the disease.

Human colon adenocarcinoma cells (WiDr) and Chinese hamster lung fibroblasts cells (V79) were incubated with different concentrations of 5-aminolevulinic acid (ALA), and the production of protoporphyrin IX (PpIX) was studied using several techniques. The amount of PpIX produced per cell increased with increasing ALA concentration according to different kinetics for the 2 cell lines. For both cell lines a cell density dependency of the PpIX synthesis was observed. For saturating ALA concentrations, 2-3 times more PpIX was produced per cell at a density of 5 x 10(4) than at a density of 5 x 10(3) cells/cm2. The photosensitivity of cells appeared to increase even more than the PpIX content, indicating a cooperative effect in inactivation. The PpIX production rate increased with cell size and was about 1.9 times higher for cells in the G2 + M phase than for cells in the G1 phase of the cell cycle. Neither cell size nor cell cycle distribution were significantly dependent on cell density.

Erythrocytes from patients with erythropoietic protoporphyria contain large amounts of protoporphyrin. The photosensitivity experienced by these patients is assumed to be due to a leakage of protoporphyrin from the erythrocytes and transfer to the skin, where protoporphyrin acts as a photosensitizer. The leakage of protoporphyrin from the erythrocytes has been offered as an explanation for the great variety in protoporphyrin content observed among erythrocytes in this disease. Based on density gradient separation of red cells, it has been concluded that all reticulocytes and young erythrocytes contain large amounts of protoporphyrin. From our results, density gradient centrifugation is not suitable for age separation of red cells from patients with erythropoietic protoporphyria. By developing a new method for isolation of reticulocytes and applying flow cytometry to determine protoporphyrin content in individual cells, it was observed that two populations of reticulocytes were present in patients with erythropoietic protoporphyria, one with and the other without protoporphyrin. The half-life of protoporphyrin in red cells was found to be 12-14 days, in contrast to 1-2 days described previously, suggesting a slower release of protoporphyrin from the red cells than previously anticipated.

We have investigated how the population dynamics of two types of vertebrates is influenced by food shortage. One type consists of animals which show indeterminate growth rate (cut the coat to the cloth) e.g. fish. The other type includes animals which show a determinate type of growth rate (require a minimum daily food supply to survive), e.g. mammals and birds. To this end we have developed a model which assumes that animals biomass is regulated by food biomass alone (i.e. no predation), while food biomass follows self-regulating dynamics. The model predicts stable biomass for the first type of animals and unstable, cyclic biomass for the other. The results help to explain why fish in a pond often develop a stable population of numerous, small individuals, while e.g. hares or moose on an island, shielded from predation, develop a fluctuating population

An isokinetic sampler for the determination of particle flux in flue gases, ventilators and ambient air was developed. Basically the sampler consists of a small cylinder which is open at both ends. During sampling its axis is oriented parallel to the flow lines. The fluid is allowed to pass isokinetically through a nozzle at the front end of the cylinder by means of its own inertia. The particles are charged and deposited on the cylinder wall. The cylinder acts as a collecting electrode in an electrostatic precipitator and its weight is determined before and after the sampling. The collection efficiency is above 90% for most particles. The sampler is battery-operated and its total weight is 2.3 kg.

A fraction of the erythrocytes from patients with erythropoietic protoporphyria contains large amounts of protoporphyrin. By extraction methods, only a mean value of the protoporphyrin content in erythrocytes is obtained. In this study, flow cytometry was used to determine the protoporphyrin content in each individual erythrocyte. The mean erythrocyte protoporphyrin fluorescence, calculated from flow cytometric data, correlated linearly to the mean cellular protoporphyrin concentration measured by ethyl acetate/acetic acid extraction. This indicates that flow cytometry gives a reliable quantitative determination of protoporphyrin in individual cells. Erythrocytes from patients with erythropoietic protoporphyria had a markedly skewed distribution of protoporphyrin. In the most fluorescent erythrocytes (protoporphyrin concentration 3.3 mM), there was about one protoporphyrin molecule for every sixth haeme molecule. This might explain the slight anaemia in some of these patients.

Nest humidity (\(P_{{\text{H}}_2 {\text{O}}} \)) under an incubating bantam hen was measured at ambient\(P_{{\text{H}}_2 {\text{O}}} \) ranging from 1.3 to 25.0 mmHg. Weight loss of eggs was recorded in clutches of varying size. Nest\(P_{{\text{H}}_2 {\text{O}}} \) and ambient\(P_{{\text{H}}_2 {\text{O}}} \) were also measured in wild incubating willow ptarmigan nests in dry and wet habitats.

One purpose of teacher education is to help future teachers develop the necessary knowledge, abilities, and skill for good teaching. A second purpose is to develop the commitment to use this knowledge, ability, and skill when trainees graduate from the training program and begin their teaching careers. There is evidence to suggest that teacher education programs can successfully achieve the first purpose, but success in the development of commitment to good teaching has not yet been demonstrated. By applying Becker's conception of commitment, a two-step plan for developing commitment in teacher education is proposed. The first step is to identify and assess commitment, the second step is to record behavioral indicators of commitment and to use these records to help future teachers develop commitment. In physical education, the improvement of teaching is vital to the future of the field; thus it is critical that teacher education programs help their students develop commitment to good teaching as well as d...

O2 consumption, electromyographic activity (EMG), heart rate (HR), cloacal temperature (Tb) and broodpatch temperature (Tsb) were measured in bantam hens incubating eggs of different temperatures (Te). For comparison, the metabolic response to low ambient temperature (Ta) was measured in non-incubating hens.

The luminescence emitted during x‐ray irradiation of H2O and D2O ice at 77 K exhibits an identical emission band peaked at 373 nm. D2O also exhibits a band peaked at 534 nm which is not seen for H2O. The 373 nm band appears to have a decay time in the range 10−4–10−3 sec, whereas the 534 nm band decays completely in less than 10−4 sec. The emission yield is G∼2×10−2 and G∼2×10−3 for D2O and H2O, respectively. The yield of the peak at 373 nm is significantly increased by NaCl, NaBr, NaI, and HCl in concentrations above 10−3M, whereas the 534 nm band in D2O is not affected by any of these additives. AgNO3, H2O2, and NaNO3 reduce the emission yield whereas other efficient electron and OH scavengers like CCl3COONa and acrylamide do not affect the luminescence even in concentrations of 1M. The identity of the luminescent species is obscure. The scavenger effects indicate that it has a mobile precursor which is not electrons or OH and probably not H atoms. The emission yields, as well as the decay time of the 3...

1. The poikilothermic state of house martin nestlings has been studied by measuring body temperature (Tb), oxygen uptake (VO2), heart rate (HR), breathing rate (BR), and shivering at different ambient temperatures (Ta). 2. TheTb of nestlings less than 4 days old followedTa within 0.5°C, and the nestlings survived at least 6 h atTb about 10°C. 3. There was no difference in either cooling or warming rate between living and dead 3-day-old nestlings. 4. The Q10 of VO2 and HR was 2.1–2.5 atTb above 35°C but increased progressively as theTb was lowered. 5. When the nestlings were cooled, breathing stopped atTb=10°C; upon rewarming it was resumed at 15°–25°C. 6. We conclude that the cold tolerance of nestlings less than 1 week old is an important part of their survival strategy. Metabolically, they behave like true poikilotherms with the exception that their metabolic function decreases more sharply at low temperatures and that they stop breathing and die at prolonged exposure atTb below 10°C.

Emission samples were obtained from two medium-sized power plants, one fired with oil and the other with pulverized coal. Particles obtained by a miniscale plume stack gas sampler (MIPSGAS), simulating the dilution process in the plume, were subjected to detailed physical, chemical and biological characterization. Studies by scanning electron microscopy and by Coulter counter demonstrated that the particles from the oil-fired boiler were considerably larger than the particles from the coal-fired boiler. Chemical analyses revealed more organic substances and more S, Ni, V, in the oil than in the coal particles. The latter contained a larger proportion of Al, Si, Cl, K, Ca, Ti, Mn, Fe, Se, Rb, Y, Zr, Ba and Pb. Biological testing revealed a greater acute and subacute toxicity by the intratracheal route in the hamster, a greater toxicity to alveolar macrophages and a greater lung retention of BaP coated on the particles from oil combustion than on those from coal combustion. In another sampling line, employed simultaneously with the MIPSGAS-particulate sampler, the total emissions were collected, i.e., both particle and gas phase. These samples were used for chemical analyses and Ames mutagenicity test. Analyses of specific PAHs in emissions from both plants demonstrated that concentrations were below the detection limit (less than 4 ng/m3 of benzo(a)pyrene), which is in accord with an efficient combustion of the fuel. The mutagenicity of the samples were below the detection limit of the mutagenicity assay. Images FIGURE 4. FIGURE 5.

The luminescence of indole and tryptophan in EG/H2O glass at 77 K during irradiation with x rays and uv light has been studied with various concentrations of two electron scavengers (acrylamide and trichloroacetate). The two types of radiation gave identical emission spectra except for a considerable enhancement of the phosphorescence to fluorescence ratio with x irradiation. The effect of the scavengers on the yields of x‐ray‐induced singlet (S) and triplet (T) levels were calculated from the results. It was found that the yield versus scavenger concentration curves could be decomposed into two components, one being independent of the scavenger, the other one decreasing exponentially with increasing scavenger concentration. Associating the former component with excitation directly from the ground state and the latter with excitation resulting from recombination between solute cations and electrons, it was found that about 80% of the solute excitation is due to recombination. In the case of indole the ratio of triplets to singlets T/S formed by direct excitation was T/S=0.2, whereas for the recombination T/S=1.2. The latter value was attributed primarily to spin relaxation of the recombining ion pairs, whereas intersystem crossing between highly excited levels and recombination in spurs appeared to be of minor importance in this respect. The spin relaxation of the recombining ions, the large scavenger concentrations needed to quench recombination, and the observation that T/S was independent of the LET of the radiation indicated that the recombining ions are closely associated so that the ion pair may be comparable to the CTTS states involved in photoionization of solutes rather than to pairs of free separate ions.

There have been several reports on the distribution of DNA in premalignant and malignant liver cells after carcinogen treatment in rodents. The most striking result so far is that ploidy distributions seems to depend more on experimental protocols and less on carcinogenesis per se. The present study demonstrates that an evaluation by means of flow cytometry and stereological image analysis yields results showing similar ploidy distributions throughout the known sequence of tissue changes seen during liver cancer development. Furthermore, our results demonstrate inter-individual differences between the lesions in each of the steps in these tissue changes, (foci, nodules and hepatocarcinomas). The present study gives no reason to conclude that changes in ploidy distribution are essential in liver carcinogenesis.

Eels (Anguilla anguilla) which were exposed to copper-contaminated fresh water (30–60 ρg Cu/I) died with signs of vibriosis (Vibrio anguillarum). Eels kept in non-contaminated fresh water (

The effect of colchicine and colcemid (1 × 10−6 M) on the blastogenic response of human lymphocytes to concanavalin A was studied in vitro by three different methods. (a) Measurement of [3H]thymidine ([3H]dThd) incorporation which was strongly suppressed by the drugs. (b) Volume spectroscopy showing that the growth of cellular and nuclear volume was only moderately affected by the drugs during the first two days of culture: in drug-treated cultures, 25% of the cells responded by measureable growth of their nuclear volume as compared to 30% in untreated cultures. After two days, however, growth stagnated in drug-treated cultures, and cell division never occurred. (c) Flow cytofluorometry, showing that in drug-treated cultures the number of cells measurably increasing their DNA content, i.e. entering S-phase, was about 60% of that in untreated cultures. However, the drugs caused a majority of the responding cells to stop DNA synthesis before completing S-phase. This effect could not fully account for the strong suppression of the [3H]dThd incorporation indicating that colchicine and colcemid caused a malfunction of the [3H]dThd assay. It is concluded that colchicine and colcemid do not significantly inhibit initiation of a blastogenic response indicating that microtubuli, which are known to be affected by these drugs, are not essential for the triggering of blastogenesis.

The blastogenic response of human lymphocytes in vitro to hyperoptimal concentrations of concanavalin A (Con A) has been studied by means of volume spectroscopy (measuring cellular and nuclear volume), flow cytofluorometry (measuring cellular DNA content) and incorporation of [3H]thymidine ([3H]dThd). The optimal Con A dose with respect to [3H]dThd incorporation was about 30 micrograms/ml. In cultures given hyperoptimal doses, e.g. 100 micrograms/ml, [3H]dThd incorporation was strongly inhibited, whereas the number of cells entering S-phase and significantly increasing their cellular and nuclear volume was considerably larger than with 30 micrograms/ml. With 200 micrograms/ml Con A, which induced negligible [3H]dThd incorporation, the percentage of responding cells was even larger. Hence, doses of Con A, which were hyperoptimal with regard to [3H]dThd incorporation, induced blastogenic response, including DNA synthesis, in a larger percentage of the cells than did the optimal dose. However, in cultures with hyperoptimal Con A doses, the progression of the cell cycle stagnated mainly during S- and G2-phase and few cells completed mitosis. Thus, the blocking effect of hyperoptimal doses was not confined to any particular point of the cell cycle. The reduced [3H]dTd incorporation, seen with hyperoptimal doses, is attributed partly to a failure of this assay under such conditions.

— The lumincscence arising from L-tryptophane and L-tyrosine in aqueous solutions at 77dK during irradiation with u.v.-light and with X-rays has been studied. The spectra obtained with the two types of radiation were largely similar, differing only in that the yields of phosphorescence relative to fluorescence were considerably enhanced in the case of X-irradiation. The decay times observed for the exponentially decaying phosphorescence, being 6.6 sec and 2.7 sec for tryptophane and tyrosine respectively, were the same for both kinds of irradiation. The G-value of the X-ray induced luminescence was about 10 for both tryptophane and tyrosine. Thus, about 30 per cent of the total energy absorbed from X-rays in these compounds was re-emitted as light. It was concluded that the X-ray induced fluorescence and phosphorescence originate from the same levels as does the luminescence caused by u.v.-light, i.e. the lowest excited singlet and the lowest triplet level of the aromatic structure of these compounds. In the case of X-irradiation the enhanced ratios between the yields of phosphorescence and fluorescence indicated that some process other than excitation directly from the ground state contributed considerably to the luminescence yields. Assuming this process to be a recombination between the ionized molecule and its electron, it was calculated that the contribution to the luminescence yield from excitations directly from the ground state relative to that from ionizations, was negligible for both compounds.

This article reviews a study of the radiation-induced luminescence of tryptophan, tyrosine, and trypsin, with the intention of elucidating the possible importance of molecular excitations for the radiation damage of proteins. In all these substances, the spectrum of the X-ray induced emission, as obtained at 77°K, was similar to that excited by uv light, except that a considerable enhancement of the phosphorescence to fluorescence ratio occurred with X-irradiation. This could be accounted for by assuming that about 90 per cent of the emission resulted from electron-ion recombination, subsequently giving rise to excitation of the radiative levels. The G-value for the emission of light was 5 for both tryptophan and tyrosine, leading to the conclusion that at least 40 per cent of the total number of ionizations resulted in recombination and subsequent emission of light. The emission from trypsin appeared to originate almost exclusively from the tryptophan residues. The emission yield (G = 0.17) indicated tha...

— The light emitted by adenine and thymine and the related nucleosides and nucleotides in ethylene glycol/water glass during irradiation at 77°K with X-rays and 270 nm U.V. light has been studied. It was found that the same radiative levels were excited by both types of radiation. However, the phosphorescence to fluorescence ratios observed with X-rays were considerably enhanced relative to those obtained with U.V. light. This observation was taken to mean that a major fraction of the excitation results from ion recombination, although direct excitation of the triplet manifold as well as intersystem crossing between upper excited levels may have contributed to the enhancement as well. The yields of the X-ray-induced excitation of radiative levels. which were calculated by combining the yields of X-ray-induced emission and the quantum yields observed with u.v.-excitation, corresponded to: G≥ 4.0 excitations per 100 eV of dose absorbed in the solute for adenine and G≥ 1.8 for thymine. The excitation yields obtained for the nucleosides and nucleotides were somewhat smaller than those observed for the corresponding bases. It was inferred from the yields that a substantial fraction of the dose absorbed in the ribose of the nucleosides was transferred to the radiative levels of the constituent bases.

— The luminescence from tryptophan in the dry state and in aqueous glass. induced by u.v.-light and X-rays at 77°K, has been studied. The spectra of the luminescence from the dry material, which were identical for the two types of irradiation, were attributed to the same excited singlet level as that giving rise to the fluorescence from the aqueous sample. The strong phosphorescence exhibited by the latter. could not be detected for the dry material with either type of irradiation. This was attributed to a strong quenching of the radiative triplet level occurring upon crystallization of the substance. The yield of X-ray induced fluorescence of tryptophan in aqueous glass was found to be similar to that observed in the dry state. It was concluded that there is no extensive transfer of energy between the solvent and the solute molecules contributing to the fluorescence yield of tryptophan in aqueous glass.

The decay of x‐ray‐induced et− in glycol‐water glass and the reduction of G(et−) by various scavengers have been studied as functions of the temperature. The decay of et− was independent of temperature from 77 to 113 K as expected if the reaction occurs primarily by electron tunneling. The reduction of G(et−), however, decreased significantly with increasing temperature in the same region, the temperature dependence being larger for less efficient scavengers. The results are qualitatively accounted for by the assumption that a significant fraction of the electrons react prior to formation of stable traps, viz. from shallow, transient traps.

Summary A representative sample of 368 70-year-old males and females in Goteborg, Sweden, participated in an odontological examination and a dietary interview. The aim of the study was to relate dental state to dietary habits and, furthermore, to study the possible influence of some social factors on these relations. The degree of dental invalidity was measured with Eichner's index. There was a highly significant correlation between this index and the number of teeth and tooth contacts. Dietary interviews were performed by a dietitian according to the dietary history method. Intake of several food items was significantly inversely related to the degree of dental invalidity in males but less so in females. The proportion of probands with insufficient intake of nutrients was in one or more respects higher among the edentulous than in the dentate and highest in the female edentulous probands with only one or no denture. Insufficient intakes of some nutrients were significantly related to the degree of dental invalidity. These relations remained unchanged in males but not in females when some socio-economic factors were introduced as confounding factors in a multivariate relation analysis; which might be due to the fact that these social factors play a more important role in females than in males.