Altered JS-2 expression in colorectal cancers and its clinical pathological relevance

JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.

Signet-ring cell carcinoma of colorectum : current perspectives and molecular biology

PURPOSE Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available. METHODS The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed. RESULTS Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma. CONCLUSIONS Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.

Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8+CD4+ T cells : evidence from myeloma-bearing mouse model

The graft-versus-myeloma (GVM) effect represents a powerful form of immune attack exerted by alloreactive T cells against multiple myeloma cells, which leads to clinical responses in multiple myeloma transplant recipients. Whether myeloma cells are themselves able to induce alloreactive T cells capable of the GVM effect is not defined. Using adoptive transfer of T naive cells into myeloma-bearing mice (established by transplantation of human RPMI8226-TGL myeloma cells into CD122(+) cell-depleted NOD/SCID hosts), we found that myeloma cells induced alloreactive T cells that suppressed myeloma growth and prolonged survival of T cell recipients. Myeloma-induced alloreactive T cells arising in the myeloma-infiltrated bones exerted cytotoxic activity against resident myeloma cells, but limited activity against control myeloma cells obtained from myeloma-bearing mice that did not receive T naive cells. These myeloma-induced alloreactive T cells were derived through multiple CD8(+) T cell divisions and enriched in double-positive (DP) T cells coexpressing the CD8alphaalpha and CD4 coreceptors. MHC class I expression on myeloma cells and contact with T cells were required for CD8(+) T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-gamma and/or perforin compared with single-positive CD8(+) T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones. These observations suggest that myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones are enriched with DP-T cells equipped with cytotoxic effector functions that are likely to be involved in the GVM effect.

GAEC1 and colorectal cancer : a study of the relationships between a novel oncogene and clinicopathologic features

GAEC1 is a novel gene located at 7q22.1 that was detected in our previous work in esophageal cancer. The aims of the present study are to identify the copy number of GAEC1 in different colorectal tissues including carcinomas, adenomas, and nonneoplastic tissues and characterize any links to pathologic factors. The copy number of GAEC1 was studied by evaluating the quantitative amplification of GAEC1 DNA in 259 colorectal tissues (144 adenocarcinomas, 31 adenomas, and 84 nonneoplastic tissues) using real-time polymerase chain reaction. Copy number of GAEC1 DNA in colorectal adenocarcinomas was higher in comparison with nonneoplastic colorectum. Seventy-nine percent of the colorectal adenocarcinomas showed amplification and 15% showed deletion of GAEC1 (P < .0001). Of the adenomas, 90% showed deletion of GAEC1, with the remaining 10% showing normal copy number. The differences in GAEC1 copy number between colorectal adenocarcinoma, colorectal adenoma, and nonneoplastic colorectal tissue are significant (P < .0001). GAEC1 copy number was significantly higher in adenocarcinomas located in distal colorectum compared with proximal colon (P = .03). In conclusion, GAEC1 copy number was significantly different between colorectal adenocarcinomas, adenomas, and nonneoplastic colorectal tissues. The copy number was also related to the site of the cancer. These findings along with previous work in esophageal cancer imply that GAEC1 is commonly involved in the pathogenesis of colorectal adenocarcinoma.

Telomerase activity : detection and clinical implications in human cancer

Telomerase is an extremely important enzyme required for the immortalisation of tumour cells. Because the gene is activated in the vast majority of tumour tissues and remains unused in most somatic cells, it represents a marker with huge diagnostic, prognostic and treatment implications in cancer. This article summarises the basic structure and functions of telomerase and considers its clinical implications in colorectal and other cancers.

Quantitative analysis of survivin in colorectal adenocarcinoma : increased expression and correlation with telomerase activity

The aims of the present study are to quantitatively analyze survivin expression, its clinicopathologic roles, and correlation with telomerase activity in a large cohort of patients with colorectal adenocarcinoma. Real-time polymerase chain reaction was used to quantitate expression level of survivin messenger RNA and human telomerase reverse transcriptase messenger RNA (telomerase activity) in 51 patients with colorectal adenocarcinomas. The findings were correlated with the clinicopathologic features of patients, which were prospectively collected into a computerized database. Survivin messenger RNA was expressed in all tumor samples. The level of expression in tumor tissues was increased in comparison with matched nontumor mucosa in the same patient (P = .01). The level of expression of survivin was significantly correlated with the level of human telomerase reverse transcriptase expression (P = .008) and size of the colorectal adenocarcinomas (P = .004). Survival of the patients with colorectal adenocarcinoma was associated with the TNM stages (P = .001) and not with the level of expression of survivin. Thus, survivin activity was altered in colorectal adenocarcinoma. The high prevalence of survivin expression and correlation with telomerase activity are important factors for consideration in gene targeting therapy for colorectal adenocarcinoma.

Coping strategies used by ballet dancers: effects of individual differences in competitive trait anxiety

The world of classical ballet exerts considerable physical and psychological stress upon those who participate, and yet the process of coping with such stressors is not well understood. Relationships between coping strategies and competitive trait anxiety were investigated among 104 classical dancers (81 females and 23 males) from three professional ballet companies, two private dance schools, and two full-time, university dance courses in Australia. Coping strategies were assessed using the Modified COPE scale (MCOPE: Crocker & Graham, 1995), a 48-item measure of 12 dimensions of coping. Competitive trait anxiety was assessed using the Sport Anxiety Scale (SAS: Smith, Smoll, & Schutz, 1990), a 21-item measure of three anxiety dimensions. Trait anxiety scores, in particular for Somatic Anxiety and Worry, predicted seven of the 12 coping strategies (Suppression of Competing Activities: R2 = 27.1%; Venting of Emotions: R2 = 23.2%; Active Coping: R2 = 14.3%; Denial: R2 = 17.7%; Self-Blame: R2 = 35.7%; Effort: R2 = 16.6%; Wishful Thinking: R2 = 42.3%). High trait anxious dancers reported more frequent use of all categories of coping strategies, some of which are considered to be maladaptive. No effects of gender or status (professional versus students) were identified. Results emphasize the need for the effectiveness of specific coping strategies to be considered during the process of preparing young classical dancers for a career in professional ballet.

Coping strategies used by ballet dancers : effects of individual differences in competitive trait anxiety

The world of classical ballet exerts considerable physical and psychological stress upon those who participate, and yet the process of coping with such stressors is not well understood. The purpose of the present investigation was to examine relationships between coping strategies and competitive trait anxiety among ballet dancers. Participants were 104 classical dancers (81 females and 23 males) ranging in age from 15 to 35 years (M = 19.4 yr., SD = 3.8 yr.) from three professional ballet companies, two private dance schools, and two full-time, university dance courses in Australia. Participants had a mean of 11.5 years of classical dance training (SD = 5.2 yr.), having started dance training at 6.6 years of age (SD = 3.4 yr.). Coping strategies were assessed using the Modified COPE scale (MCOPE: Crocker & Graham, 1995), a 48-item measure comprising 12 coping subscales (Seeking Social Support for Instrumental Reasons, Seeking Social Support for Emotional Reasons, Behavioral Disengagement, Planning, Suppression of Competing Activities, Venting of Emotions, Humor, Active Coping, Denial, Self-Blame, Effort, and Wishful Thinking). Competitive trait anxiety was assessed using the Sport Anxiety Scale (SAS: Smith, Smoll, & Schutz, 1990), a 21-item measure comprising three anxiety subscales (Somatic Anxiety, Worry, Concentration Disruption). Standard multiple regression analyses showed that trait anxiety scores, in particular for Somatic Anxiety and Worry, were significant predictors of seven of the 12 coping strategies (Suppression of Competing Activities: R2 = 27.1%; Venting of Emotions: R2 = 23.2%; Active Coping: R2 = 14.3%; Denial: R2 = 17.7%; Self-Blame: R2 = 35.7%; Effort: R2 = 16.6%; Wishful Thinking: R2 = 42.3%). High trait anxious dancers reported more frequent use of all categories of coping strategies. A separate two-way MANOVA showed no significant main effect for gender nor status (professional versus students) and no significant interaction effect. The present findings are generally consistent with previous research in the sport psychology domain (Crocker & Graham, 1995; Giacobbi & Weinberg, 2000) which has shown that high trait anxious athletes tend, in particular, to use more maladaptive, emotion-focused coping strategies when compared to low trait anxious athletes; a tendency which has been proposed to lead to negative performance effects. The present results emphasize the need for the effectiveness of specific coping strategies to be considered during the process of preparing young classical dancers for a career in professional ballet. In particular, the results suggest that dancers who are, by nature, anxious about performance may need special attention to help them to learn to cope with performance-related stress. Given the absence of differences in coping strategies between student and professional dancers and between males and females, it appears that such educational efforts should begin at an early career stage for all dancers.

Histogram matching and global initialization for laser-only SLAM in large unstructured environments

This paper presents an enhanced algorithm for matching laser scan maps using histogram correlations. The histogram representation effectively summarizes a map's salient features such that pairs of maps can be matched efficiently without any prior guess as to their alignment. The histogram matching algorithm has been enhanced in order to work well in outdoor unstructured environments by using entropy metrics, weighted histograms and proper thresholding of quality metrics. Thus our large-scale scan-matching SLAM implementation has a vastly improved ability to close large loops in real-time even when odometry is not available. Our experimental results have demonstrated a successful mapping of the largest area ever mapped to date using only a single laser scanner. We also demonstrate our ability to solve the lost robot problem by localizing a robot to a previously built map without any prior initialization.

Grassland productivity limited by multiple nutrients

Terrestrial ecosystem productivity is widely accepted to be nutrient limited1. Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP)2,3, the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized4,​5,​6,​7,​8. However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+μ), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+μ co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment.

Consistent responses of soil microbial communities to elevated nutrient inputs in grasslands across the globe

Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.

Infection and cellular defense dynamics in a novel 17beta-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation

Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (106–107 CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.

Energy gap in the aetiology of body weight gain and obesity: A challenging concept with a complex evaluation and pitfalls

The concept of energy gap(s) is useful for understanding the consequence of a small daily, weekly, or monthly positive energy balance and the inconspicuous shift in weight gain ultimately leading to overweight and obesity. Energy gap is a dynamic concept: an initial positive energy gap incurred via an increase in energy intake (or a decrease in physical activity) is not constant, may fade out with time if the initial conditions are maintained, and depends on the 'efficiency' with which the readjustment of the energy imbalance gap occurs with time. The metabolic response to an energy imbalance gap and the magnitude of the energy gap(s) can be estimated by at least two methods, i.e. i) assessment by longitudinal overfeeding studies, imposing (by design) an initial positive energy imbalance gap; ii) retrospective assessment based on epidemiological surveys, whereby the accumulated endogenous energy storage per unit of time is calculated from the change in body weight and body composition. In order to illustrate the difficulty of accurately assessing an energy gap we have used, as an illustrative example, a recent epidemiological study which tracked changes in total energy intake (estimated by gross food availability) and body weight over 3 decades in the US, combined with total energy expenditure prediction from body weight using doubly labelled water data. At the population level, the study attempted to assess the cause of the energy gap purported to be entirely due to increased food intake. Based on an estimate of change in energy intake judged to be more reliable (i.e. in the same study population) and together with calculations of simple energetic indices, our analysis suggests that conclusions about the fundamental causes of obesity development in a population (excess intake vs. low physical activity or both) is clouded by a high level of uncertainty.

The North in the Old English Orosius : A Geographical Narrative in Context

This doctoral dissertation examines the description of the North as it appears in the Old English Orosius (OE Or.) in the form of the travel accounts by Ohthere and Wulfstan and a catalogue of peoples of Germania. The description is discussed in the context of ancient and early medieval textual and cartographic descriptions of the North, with a special emphasis on Anglo-Saxon sources and the intellectual context of the reign of King Alfred (871-899). This is the first time that these sources, a multidisciplinary approach and secondary literature, also from Scandinavia and Finland, have been brought together. The discussion is source-based, and archaeological theories and geographical ideas are used to support the primary evidence. This study belongs to the disciplines of early medieval literature and (cultural) history, Anglo-Saxon studies, English philology, and historical geography. The OE Or. was probably part of Alfred s educational campaign, which conveyed royal ideology to the contemporary elite. The accounts and catalogue are original interpolations which represent a unique historical source for the Viking Age. They contain unparalleled information about peoples and places in Fennoscandia and the southern Baltic and sailing voyages to the White Sea, the Danish lands, and the Lower Vistula. The historical-philological analysis reveals an emphasis on wealth and property, rank, luxury goods, settlement patterns, and territorial divisions. Trade is strongly implied by the mentions of central places and northern products, such as walrus ivory. The references to such peoples as the Finnas, the Cwenas, and the Beormas appear in connection with information about geography and subsistence in the far North. Many of the topics in the accounts relate to Anglo-Saxon aristocratic culture and interests. The accounts focus on the areas associated with the Northmen, the Danes and the Este. These areas resonated in the Anglo-Saxon geographical imagination: they were curious about the northern margin of the world, their own continental ancestry and the geography of their homeland of Angeln, and they had an interest in the Goths and their connection with the southern Baltic in mythogeography. The non-judgemental representation of the North as generally peaceful and relatively normal place is related to Alfredian and Orosian ideas about the unity and spreading of Christendom, and to desires for unity among the Germani and for peace with the Vikings, who were settling in England. These intellectual contexts reflect the innovative and organizational forces of Alfred s reign. The description of the North in the OE Or. can be located in the context of the Anglo-Saxon worldview and geographical mindset. It mirrors the geographical curiosity expressed in other Anglo-Saxon sources, such as the poem Widsith and the Anglo-Saxon mappa mundi. The northern section of this early eleventh-century world map is analyzed in detail here for the first time. It is suggested that the section depicts the North Atlantic and the Scandinavian Peninsula. The survey of ancient and early medieval sources provides a comparative context for the OE Or. In this material, produced by such authors as Strabo, Pliny, Tacitus, Jordanes, and Rimbert, the significance of the North was related to the search for and definition of the northern edge of the world, universal accounts of the world, the northern homeland in the origin stories of the gentes, and Carolingian expansion and missionary activity. These frameworks were transmitted to Anglo-Saxon literary culture, where the North occurs in the context of the definition of Britain s place in the world.

Die Großstadt als Gegner? : Zur Wahrnehmung Berlins in Literatur, Film und Hörspiel der späten Weimarer Republik

Tässä tutkielmassa tarkastellaan, miten Berliinin suurkaupunki vaikutti Weimarin tasavallan loppuaikoina yksilöön. Tutkimusaineistona on Alfred Döblinin romaani Berlin Alexanderplatz sekä Walter Ruttmannin elokuva Berlin. Die Sinfonie der Großstadt ja kuunnelma Weekend. Teoreettisena taustana hyödynnetään kulttuuri- ja mediahistorian mentaliteetti- ja sosiaalihistoriaa. Aihetta käsitellään myös historiallis-temaattisesta lähtökohdasta, eli työssä tutkitaan todellisen Berliinin asemaa kyseisenä aikana, modernin metropolin olemusta, modernin ajan murrosvaihetta sekä uusasiallisen taidesuuntauksen vaikutusta teoksiin. Weimarin tasavallan aikana Saksassa elettiin murroksen keskellä. Toisaalta yhteiskunta oli poliittisesti pirstoutunut ja taloudellisesti epävakaa, mutta toisaalta kulttuurielämä oli lyhyen aikaa rikasta. Suurkaupungin asukkailla oli enemmän vapaa-aikaa ja mahdollisuuksia toteuttaa itseään omassa ympäristössään. Toisaalta ajan ristiriitaisuus kuitenkin vaikeutti yksilöllisen elämäntavan toteutumista; ihmiset odottivat murroskauden päättymiseltä materiaalista tyydytystä, jolloin henkiselle kehitykselle jäi vähän tilaa. Tärkein kysymyksenasettelu koskee suurkaupungin roolia oman aikansa tuotteena: missä määrin kaupunki oli ihmisen todellinen vastustaja ja missä määrin sen asema oli kuviteltua? Todellisen Berliinin suhdetta reflektoidaan fiktiiviseen suurkaupunkiympäristöön. Ensin tarkastellaan Berliiniä toimijana murroskaudella ja sitten käsitellään ajan ja tilan havainnointia. Koska teokset ovat fiktiivisiä, erityisen tarkastelun kohteena on todellisuuden, fiktion ja simulaation suhde. Tässä yhteydessä tarkastellaan myös kaupungin ja maaseudun välistä problematiikkaa. Kolmannessa osassa esille nousee yksilön ja massan välinen suhde, joka sekin vaikuttaa ihmisen ja suurkaupungin väliseen vastakkainasetteluun. Ilmensikö koneiden ja liikenteen dominoiva asema futuristista asetelmaa? Lisäksi käsitellään alamaailman ja kultaisen 20-luvun välistä kuilua. Kaikkia kolmea teosta yhdistää 24 tunnin aikakäsite; ajalla on selkeästi rajattu alku ja loppu, ja myös tilan käsite on tarkastelussa tärkeä. Kaikissa teoksissa on hyödynnetty montaasitekniikkaa. Kohtaukset vaihtuvat hyvinkin nopeasti, jolloin lukija, katsoja tai kuulija vieraantuu varsinaisesta kohteestaan. Montaasi vaikuttaa ratkaisevasti myös kaupungin ja yksilön suhteen kuvaukseen. Suurkaupungista muotoutuu lähes hirviömäinen, personifioitu subjekti, joka konemaisella olemuksellaan pyrkii nujertamaan pienen ihmisen. Döblinin romaanissa kertoja toimii ikään kuin yksilöä vastaan liittämällä kerronnan väliin uutisaiheita, säätiedotuksia ja kohtalokertomuksia. Elokuvassa ja kuunnelmassa teknologisen kehityksen ihannointi on noussut etualalle: ihmiset muistuttavat sekä yksilöinä että massana koneita, jotka liikkuvat hektisen mekaanisesti eteenpäin kuin liikennevälineet. He eivät kyseenalaista ympäristöään eivätkä koe olevansa oravanpyörässä. Romaanin päähenkilö on heijastanut omat pelkonsa konkreettisesti suurkaupungin infrastruktuuriin, kerrostaloihin, jotka tuntuvat kaatuvan hänen päälleen. Yksilöllinen kehitys on vaarassa pysähtyä, sillä koneistuminen tekee yksilöistä massaa. Elokuvassa ja kuunnelmassa kamppailu suurkaupunkiorganismin ja ihmisten välillä jatkuu, mutta romaanissa kamppailu päättyy päähenkilön parantumiseen. Hänestä tulee mallikansalainen - vaiennettu ja kuuliainen. Kaikkien kolmen teoksen hahmoja kuvataan modernin ajan uhreina. Heiltä puuttuu mekanismi, jolla he voisivat käsitellä kokonaisuuksia. Modernin ajan hahmojen elämä on lopulta kuin tanssia tulivuoren päällä - epävarmaa ja riskialtista.