"The Stratified Record upon Which We Set Our Feet" : The Spatial Turn and the Multilayering of History, Geography, and Geology

In Thomas Mann’s tetralogy of the 1930s and 1940s, Joseph and His Brothers, the narrator declares history is not only “that which has happened and that which goes on happening in time,” but it is also “the stratified record upon which we set our feet, the ground beneath us.” By opening up history to its spatial, geographical, and geological dimensions Mann both predicts and encapsulates the twentieth-century’s “spatial turn,” a critical shift that divested geography of its largely passive role as history’s “stage” and brought to the fore intersections between the humanities and the earth sciences. In this paper, I draw out the relationships between history, narrative, geography, and geology revealed by this spatial turn and the questions these pose for thinking about the disciplinary relationship between geography and the humanities. As Mann’s statement exemplifies, the spatial turn itself has often been captured most strikingly in fiction, and I would argue nowhere more so than in Graham Swift’s Waterland (1983) and Anne Michaels’s Fugitive Pieces (1996), both of which present space, place, and landscape as having a palpable influence on history and memory. The geographical/geological line that runs through both Waterland and Fugitive Pieces continues through Tim Robinson’s non-fictional, two-volume “topographical” history Stones of Aran. Robinson’s Stones of Aran—which is not history, not geography, and not literature, and yet is all three—constructs an imaginative geography that renders inseparable geography, geology, history, memory, and the act of writing.

Cryptanalysis of the convex hull click human identification protocol

Recently, a convex hull-based human identification protocol was proposed by Sobrado and Birget, whose steps can be performed by humans without additional aid. The main part of the protocol involves the user mentally forming a convex hull of secret icons in a set of graphical icons and then clicking randomly within this convex hull. While some rudimentary security issues of this protocol have been discussed, a comprehensive security analysis has been lacking. In this paper, we analyze the security of this convex hull-based protocol. In particular, we show two probabilistic attacks that reveal the user’s secret after the observation of only a handful of authentication sessions. These attacks can be efficiently implemented as their time and space complexities are considerably less than brute force attack. We show that while the first attack can be mitigated through appropriately chosen values of system parameters, the second attack succeeds with a non-negligible probability even with large system parameter values that cross the threshold of usability.

TNF and TNF receptor expression and insulin sensitivity in human omental and subcutaneous adipose tissue--influence of BMI and adipose distribution

Tumour necrosis factor (TNF)alpha is implicated in the relationship between obesity and insulin resistance/ type 2 diabetes. In an effort to understand this association better we (i) profiled gene expression patterns of TNF, TNFR1 and TNFR2 and (ii) investigated the effects of TNF on glucose uptake in isolated adipocytes and adipose tissue explants from omental and subcutaneous depots from lean, overweight and obese individuals. TNF expression correlated with expression of TNFR2, but not TNFR1, and TNF and TNFR2 expression increased in obesity. TNFR1 expression was higher in omental than in subcutaneous adipocytes. Expression levels of TNF or either receptor did not differ between adipocytes from individuals with central and peripheral obesity. TNF only suppressed glucose uptake in insulin-stimulated subcutaneous tissue and this suppression was only observed in tissue from lean subjects. These data support a relationship between the TNF system and body mass index (BMI), but not fat distribution, and suggest depot specificity of the TNF effect on glucose uptake. Furthermore, adipose tissue from obese subjects already appears insulin 'resistant' and this may be a result of the increased TNF levels.

Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes

Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3-5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.

Loss of chromosomal integrity in human mammary epithelial cells subsequent to escape from senescence

The genomic changes that foster cancer can be either genetic or epigenetic in nature. Early studies focused on genetic changes and how mutational events contribute to changes in gene expression. These point mutations, deletions and amplifications are known to activate oncogenes and inactivate tumor suppressor genes. More recently, multiple epigenetic changes that can have a profound effect on carcinogenesis have been identified. These epigenetic events, such as the methylation of promoter sequences in genes, are under active investigation. In this review we will describe a methylation event that occurs during the propagation of human mammary epithelial cells (HMEC) in culture and detail the accompanying genetic alterations that have been observed.

A question of agency : applying Sen’s theory of human capability to the concept of secondary school student career ‘choice’

In this paper, we seek to operationalize Amartya Sen's concept of human capability to guide a scholarly investigation of student career choice capability. We begin by outlining factors affecting youth labour markets in Australia; a prosperous country that is affected by a ‘two-speed’ national economy. We then examine recent government initiatives that have been designed to combat youth unemployment and cyclical disadvantage by enhancing the aspirations and career knowledge of secondary school students. We argue that these policy measures are based on four assumptions: first, that career choice capability is a problem of individual agency; second, that the dissemination of career information can empower students to act as ‘consumers’ in an unequal job market; third, that agency is simply a question of will; and finally, that school education and career advice – as a means to freedom in the space of career development – is of equal quality, distribution and value to an increasingly diverse range of upper secondary school students. The paper concludes by outlining a conceptual framework capable of informing an empirical research project that aims to test these assumptions by measuring and comparing differences between groups in the range of freedom to achieve and, therefore, to choose.

Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells

Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.

Human exposure to brominated flame retardants

Human polybrominated diphenyl ether (PBDE) exposure occurs through a range of pathways including: ingestion of dust including hand-to-mouth contact; inhalation (air/particulate matter); and ingestion via food including the unique nutrition sources of human milk and placental transfer. While inhalation has been deemed a minor source of exposure, ingestion of food and dust make greater contributions to overall PBDE body burden with intake via dust reported to be much higher in infants than in adults. PBDEs have been detected in samples of human milk, blood serum, cord blood, and adipose tissue worldwide. Concentrations have been found to be highest in populations from North America, followed by Australia, Europe, and Asia. While factors such as gender and parity may not affect concentrations, occupational exposure and age (infants and children) are associated with higher PBDE concentrations. In contrast to “traditional” persistent organic pollutants, there is an inverse relationship between PBDE body burden and age. Predicted body burden calculated using available information on intake and elimination rates of BFRs appears to underestimate measured human body burden data obtained through analysis of BFRs in blood or human milk. This may be due to unknown exposure or inaccurate elimination data. Further exposure studies should focus on younger age groups and an investigation of human PBDE half-lives.

Identification of abundant alkyl ether glycerophospholipids in the human lens by tandem mass spectrometry techniques

Previous studies have shown that the human lens contains glycerophospholipids with ether linkages. These lipids differ from conventional glycerophospholipids in that the sn-1 substituent is attached to the glycerol backbone via an 1-O-alkyl or an 1-O-alk-1'-enyl ether rather than an ester bond. The present investigation employed a combination of collision-induced dissociation (CID) and ozone-induced dissociation (OzID) to unambiguously distinguish such 1-O-alkyl and 1-O-alk-1'-enyl ethers. Using these methodologies the human lens was found to contain several abundant 1-O-alkyl glycerophos-phoethanolamines, including GPEtn(16:0e/9Z-18:1), GPEtn(11Z-18:1e/9Z-18:1), and GPEtn(18:0e/9Z-18:1), as well as a related series of unusual 1-O-alkyl glycerophosphoserines, including GPSer(16:0e/9Z-18:1), GPSer(11Z-18:1e/9Z-18:1), GPSer(18:0e/9Z-18:1) that to our knowledge have not previously been observed in human tissue. Isomeric 1-O-alk-1'-enyl ethers were absent or in low abundance. Examination of the double bond position within the phospholipids using OzID revealed that several positional isomers were present, including sites of unsaturation at the n-9, n-7, and even n-5 positions. Tandem CID/OzID experiments revealed a preference for double bonds in the n-7 position of 1-O-ether linked chains, while n-9 double bonds predominated in the ester-linked fatty acids [e.g., GPEtn(11Z-18:1e/9Z-18:1) and GPSer(11Z-18:1e/9Z-18:1)]. Different combinations of these double bond positional isomers within chains at the sn-1 and sn-2 positions point to a remarkable molecular diversity of ether-lipids within the human lens.

Cryptanalysis of the convex hull click human identification protocol

Recently a convex hull based human identification protocol was proposed by Sobrado and Birget, whose steps can be performed by humans without additional aid. The main part of the protocol involves the user mentally forming a convex hull of secret icons in a set of graphical icons and then clicking randomly within this convex hull. In this paper we show two efficient probabilistic attacks on this protocol which reveal the user’s secret after the observation of only a handful of authentication sessions. We show that while the first attack can be mitigated through appropriately chosen values of system parameters, the second attack succeeds with a non-negligible probability even with large system parameter values which cross the threshold of usability.

A new human identification protocol and Coppersmith's baby-step giant-step algorithm

We propose a new protocol providing cryptographically secure authentication to unaided humans against passive adversaries. We also propose a new generic passive attack on human identification protocols. The attack is an application of Coppersmith’s baby-step giant-step algorithm on human identification protcols. Under this attack, the achievable security of some of the best candidates for human identification protocols in the literature is further reduced. We show that our protocol preserves similar usability while achieves better security than these protocols. A comprehensive security analysis is provided which suggests parameters guaranteeing desired levels of security.

Prospects for studying how high-intensity compression waves cause damage in human blast injuries

Since World War I, explosions have accounted for over 70% of all injuries in conflict. With the development of improved personnel protection of the torso, improved medical care and faster aeromedical evacuation, casualties are surviving with more severe injuries to the extremities. Understanding the processes involved in the transfer of blast-induced shock waves through biological tissues is essential for supporting efforts aimed at mitigating and treating blast injury. Given the inherent heterogeneities in the human body, we argue that studying these processes demands a highly integrated approach requiring expertise in shock physics, biomechanics and fundamental biological processes. This multidisciplinary systems approach enables one to develop the experimental framework for investigating the material properties of human tissues that are subjected to high compression waves in blast conditions and the fundamental cellular processes altered by this type of stimuli. Ultimately, we hope to use the information gained from these studies in translational research aimed at developing improved protection for those at risk and improved clinical outcomes for those who have been injured from a blast wave.

New criterion for the stability of a human body in floodwaters

The authors must be congratulated for their original and important study. The flooding of urbanised areas constitutes a hazard to the population and infrastructure. Floods through inundated urban environments have been studied only recently and few considered the potential impact of flowing waters on pedestrians...