Explanation for twin tunnelling-induced surface settlements by changes in soil stiffness on account of stress history

In this article, a group of representative centrifuge tests were selected for numerical modelling to explain the surface settlements induced by sequential twin tunnelling. Both Modified Cam Clay model (MCC) and Three-Surface Kinematic Hardening model (3-SKH) were adopted in the simulation, which indicated the use of 3-SKH model conduced to mimicking more closely centrifuge model response. Via performing more contrastive numerical analyses with 3-SKH model, the influence of the first tunnel event on the stiffness of the soil around the second tunnel was quantitatively investigated, whereby the mechanism behind the observed surface settlements was finally made clear

An update on the Hirsch conjecture

The Hirsch conjecture was posed in 1957 in a letter from Warren M. Hirsch to George Dantzig. It states that the graph of a d-dimensional polytope with n facets cannot have diameter greater than n - d. Despite being one of the most fundamental, basic and old problems in polytope theory, what we know is quite scarce. Most notably, no polynomial upper bound is known for the diameters that are conjectured to be linear. In contrast, very few polytopes are known where the bound $n-d$ is attained. This paper collects known results and remarks both on the positive and on the negative side of the conjecture. Some proofs are included, but only those that we hope are accessible to a general mathematical audience without introducing too many technicalities.Comment: 28 pages, 6 figures. Many proofs have been taken out from version 2 and put into the appendix arXiv:0912.423

A different head? Parental agency and early intervention

This paper considers the agency and identity of parents of children with Down syndrome within early intervention. It draws upon semi-structured, conversational interviews with nine parents and the reflections of one of the authors upon their experiences within early intervention programmes. It considers how representations of the deficit model permeate the participation of the parent in this process. It explores the multiple identities of the parents and links these to notions of parental participation within the current policy context of early intervention in England. The notion of parental agency is an implicit driver within the current early intervention programmes, yet it appears to be compromised by the nature of those programmes. [ABSTRACT FROM AUTHOR

Intergroup struggles over victimhood in violent conflict: The victim-perpetrator paradigm

Most groups in violent, intergroup conflict perceive themselves to be the primary or sole victims of that conflict. This often results in contention over who may claim victim status and complicates a central aim of post-conflict processes, which is to acknowledge and address harms experienced by the victims. Drawing from victimology scholarship and intergroup relations theory, this article proposes the victim-perpetrator paradigm as a framework to analyse how, why and to what end groups in conflict construct and maintain their claims to the moral status of victim. This interdisciplinary paradigm builds on the knowledge that groups utilise the ‘ideal victim’ construction to exemplify their own innocence and blamelessness in contrast to the wickedness of the perpetrator, setting the two categories as separate and mutually exclusive even where experiences of violence have been complex. Additionally, this construction provides for a core intergroup need to achieve positive social identity, which groups may enhance by demonstrating a maximum differentiation between the in-group as victims and those out-groups identified as perpetrators. The paradigm contributes greater knowledge on the social roots of victim contention in conflict, as well as how groups legitimise their violence against out-groups during and after conflict

ASD: a comprehensive database of allosteric proteins and modulators

Allostery is the most direct, rapid and efficient way of regulating protein function, ranging from the control of metabolic mechanisms to signal-transduction pathways. However, an enormous amount of unsystematic allostery information has deterred scientists who could benefit from this field. Here, we present the AlloSteric Database (ASD), the first online database that provides a central resource for the display, search and analysis of structure, function and related annotation for allosteric molecules. Currently, ASD contains 336 allosteric proteins from 101 species and 8095 modulators in three categories (activators, inhibitors and regulators). Proteins are annotated with a detailed description of allostery, biological process and related diseases, and modulators with binding affinity, physicochemical properties and therapeutic area. Integrating the information of allosteric proteins in ASD should allow for the identification of specific allosteric sites of a given subtype among proteins of the same family that can potentially serve as ideal targets for experimental validation. In addition, modulators curated in ASD can be used to investigate potent allosteric targets for the query compound, and also help chemists to implement structure modifications for novel allosteric drug design. Therefore, ASD could be a platform and a starting point for biologists and medicinal chemists for furthering allosteric research. ASD is freely available at http://mdl.shsmu.edu.cn/ASD/

High levels of untreated distress and fatigue in cancer patients

The purpose of the study was to assess a large representative sample of cancer patients on distress levels, common psychosocial problems, and awareness and use of psychosocial support services. A total of 3095 patients were assessed over a 4-week period with the Brief Symptom Inventory-18 (BSI-18), a common problems checklist, and on awareness and use of psychosocial resources. Full data was available on 2776 patients. On average, patients were 60 years old, Caucasian (78.3%), and middle class. Approximately, half were attending for follow-up care. Types of cancer varied, with the largest groups being breast (23.5%), prostate (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of all patients met criteria for general distress in the clinical range. A higher proportion of men met case criteria for somatisation, and more women for depression. There were no gender differences in anxiety or overall distress severity. Minority patients were more likely to be distressed, as were those with lower income, cancers other than prostate, and those currently on active treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer patients were the most distressed. Almost half of all patients who met distress criteria had not sought professional psychosocial support nor did they intend to in the future. In conclusion, distress is very common in cancer patients across diagnoses and across the disease trajectory. Many patients who report high levels of distress are not taking advantage of available supportive resources. Barriers to such use, and factors predicting distress and use of psychosocial care, require further exploration

Order without design

Experimental reality in molecular and cell biology, as revealed by advanced research technologies and methods, is manifestly inconsistent with the design perspective on the cell, thus creating an apparent paradox: where do order and reproducibility in living systems come from if not from design

Crime among irregular immigrants and the influence of internal border control

Both the number of crime suspects without legal status and the number of irregular or undocumented immigrants held in detention facilities increased substantially in theNetherlands between 1997 and 2003. In this period, theDutch state increasingly attempted to exclude irregular immigrants from the formal labour market and public provisions. At the same time the registered crime among irregular migrants rose. The 'marginalisation thesis' asserts that a larger number of migrants have become involved in crime in response to a decrease in conventional life chances. Using police and administrative data, the present study takes four alternative interpretations into consideration based on: 1) reclassification of immigrant statuses by the state and redefinition of the law, 2) criminal migration and crossborder crime, 3) changes in policing, and 4) demographic changes. A combination of factors is found to have caused the rise in crime, but the marginalisation thesis still accounts for at least 28%. These findings accentuate the need for a more thorough discussion on the intended and unintended consequences of border control for immigrant crime

Voices of deficit: Mental health, criminal victimisation and epistemic injustice

People who endure mental and emotional distress experience a plethora of negative experiences beyond the effects of the symptoms themselves. For centuries, the designation of labels of difference; that is, those which transgress approved social norms, have affected the lived experiences of those individuals, and more widely in structuring responses, engagements with, and attitudes between society and the individual. Understanding the creation of tainted identities, particularly of those with experience of mental and emotional distress have been well rehearsed in the sociological literature of the second half of the twentieth century. Central to much of this analysis has been to understand the nature of the manufacture of deviant identities, how they are sustained and the impact of these identities on those who experience them. This paper explores the experience of those with mental and emotional distress as a victim of crime. The interconnectedness of matters of identity created though the application of a diagnosis of illness/disorder is addressed as is the crisis of criminal victimisation. This is achieved via an exploration of contemporary concerns surrounding victims of crime with experience of mental and emotional distress, including the (further) loss of voice and agency when interfacing with agencies of the State

The Mechanism of Ubiquitination in the Cullin-RING E3 Ligase Machinery: Conformational Control of Substrate Orientation

In cullin-RING E3 ubiquitin ligases, substrate binding proteins, such as VHL-box, SOCS-box or the F-box proteins, recruit substrates for ubiquitination, accurately positioning and orienting the substrates for ubiquitin transfer. Yet, how the E3 machinery precisely positions the substrate is unknown. Here, we simulated nine substrate binding proteins: Skp2, Fbw7, β-TrCP1, Cdc4, Fbs1, TIR1, pVHL, SOCS2, and SOCS4, in the unbound form and bound to Skp1, ASK1 or Elongin C. All nine proteins have two domains: one binds to the substrate; the other to E3 ligase modules Skp1/ASK1/Elongin C. We discovered that in all cases the flexible inter-domain linker serves as a hinge, rotating the substrate binding domain, optimally and accurately positioning it for ubiquitin transfer. We observed a conserved proline in the linker of all nine proteins. In all cases, the prolines pucker substantially and the pucker is associated with the backbone rotation toward the E2/ubiquitin. We further observed that the linker flexibility could be regulated allosterically by binding events associated with either domain. We conclude that the flexible linker in the substrate binding proteins orients the substrate for the ubiquitin transfer. Our findings provide a mechanism for ubiquitination and polyubiquitination, illustrating that these processes are under conformational control