bluuebunny/crossref_metadata_2025_split huggingface dataset:
The strength of genetic interactions scales weakly with mutational effects
Authors: Velenich Andrea , Gore Jeff 
Published: July 2013

Abstract
Background
Genetic interactions pervade every aspect of biology, from evolutionary theory, where they determine the accessibility of evolutionary paths, to medicine, where they can contribute to complex genetic diseases. Until very recently, studies on epistatic interactions have been based on a handful of mutations, providing at best anecdotal evidence about the frequency and the typical strength of genetic interactions. In this study, we analyze a publicly available dataset that contains the growth rates of over five million double knockout mutants of the yeast Saccharomyces cerevisiae.

Results
We discuss a geometric definition of epistasis that reveals a simple and surprisingly weak scaling law for the characteristic strength of genetic interactions as a function of the effects of the mutations being combined. We then utilized this scaling to quantify the roughness of naturally occurring fitness landscapes. Finally, we show how the observed roughness differs from what is predicted by Fisher's geometric model of epistasis, and discuss the consequences for evolutionary dynamics.

Conclusions
Although epistatic interactions between specific genes remain largely unpredictable, the statistical properties of an ensemble of interactions can display conspicuous regularities and be described by simple mathematical laws. By exploiting the amount of data produced by modern high-throughput techniques, it is now possible to thoroughly test the predictions of theoretical models of genetic interactions and to build informed computational models of evolution on realistic fitness landscapes.
Risk of dementia after anaesthesia and surgery
Authors: Chen Pin-Liang , Yang Chih-Wen , Tseng Yi-Kuan , Sun Wei-Zen , Wang Jane-Ling , Wang Shuu-Jiun , Oyang Yen-Jen , Fuh Jong-Ling 
Published: July 2013

BackgroundThe potential relationship between anaesthesia, surgery and onset of
dementia remains elusive.AimsTo determine whether the risk of dementia increases after surgery with
anaesthesia, and to evaluate possible associations among age, mode of
anaesthesia, type of surgery and risk of dementia.MethodThe study cohort comprised patients aged 50 years and older who were
anaesthetised for the first time since 1995 between 1 January 2004 and 31
December 2007, and a control group of randomly selected patients matched
for age and gender. Patients were followed until 31 December 2010 to
identify the emergence of dementia.ResultsRelative to the control group, patients who underwent anaesthesia and
surgery exhibited an increased risk of dementia (hazard ratio = 1.99) and
a reduced mean interval to dementia diagnosis. The risk of dementia
increased in patients who received intravenous or intramuscular
anaesthesia, regional anaesthesia and general anaesthesia.ConclusionsThe results of our nationwide, population-based study suggest that
patients who undergo anaesthesia and surgery may be at increased risk of
dementia.
Impact of clinical severity on outcomes of mentalisation-based treatment for borderline personality disorder
Authors: Bateman Anthony , Fonagy Peter 
Published: July 2013

BackgroundEvidence of remission from borderline personality disorder (BPD) without specialised treatment is accumulating.AimsTo establish whether specialised treatments are indicated for patients with clinically severe disorder.MethodThe impact of clinical severity on outcomes of a randomised controlled trial of mentalisation-based treatment (MBT) was contrasted with structured clinical management (SCM). Severity indicators were defined as severity of comorbid psychiatric syndromes, severity of BPD, severity of personality disturbance and severity of symptom distress. Logistic regressions were used to predict the likelihood of recovery at 18 months, and mixed-effects regression analysis was applied to examine the association of severity and rates of improvement across time in the two treatment groups.ResultsNone of the severity criteria predicted outcome at the end of treatment on logistic regression. However, testing the significance of distribution of cases of recovery v. non-recovery suggested that multiple Axis II diagnoses and symptom distress influenced outcomes.ConclusionsBorderline personality disorder with significant Axis II comorbidity is a possible but uncertain indicator for specialist treatment. Patients whose only personality disorder diagnosis is BPD do equally well with SCM. Prospective studies are needed.
Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus
Authors: Hadas Eran , Chao Wei , He Hongxia , Saini Manisha , Daley Eleen , Saifuddin Mohammed , Bentsman Galina , Ganz Eric , Volsky David J. , Potash Mary Jane 
Published: July 2013

SummaryHeterosexual transmission accounts for the majority of new human immunodeficiency virus (HIV) cases worldwide. The current approach to investigate HIV heterosexual transmission in animals involves application of virus stock to the vaginal surface, a method that does not reproduce the physiological conditions of vaginal intercourse that influence the rate of transmission. We have previously described efficient infection of conventional mice using EcoHIV/NL4-3 and EcoHIV/NDK, chimeric HIV molecular clones constructed to express all HIV structural and regulatory genes except envelope, which is replaced by a rodent-tropic envelope gene. Here we investigated whether EcoHIV/NDK-infected male mice transmit virus to females during coitus, and the sensitivity of this transmission to HIV pre-exposure prophylaxis and the estrus state. Our general approach was to allow mating between EcoHIV/NDK-infected male mice and uninfected females for 1-7 nights. At 1-6 weeks after mating, mice were euthanized and virus burdens were measured by quantitative PCR (qPCR) amplification of HIV RNA or DNA in peritoneal macrophages, inguinal lymph node cells, spleen cells or vas deferens, or by ELISA for antibodies to HIV Gag. We found that 70-100% of female mice mated to EcoHIV/NDK-infected males acquired infection. Pericoital treatment of females with either 2',3'-dideoxcytidine (ddC) or tenofovir largely prevented their EcoHIV/NDK infection by mating (P&lt;0.05 and P&lt;0.003, respectively). In males, T cells were dispensable for virus transmission. The rate of EcoHIV/NDK sexual transmission to females in estrus declined sharply (P=0.003) but their infection by injection was unaffected, indicating that the local environment in the female reproductive tract influences susceptibility to HIV. We conclude that this system of EcoHIV/NDK transmission during mouse mating reproduces key features of heterosexual transmission of HIV in humans and can be used to investigate its biology and control.
Nuclear PP2A-Cdc55 prevents APC-Cdc20 activation during the spindle assembly checkpoint
Authors: Rossio Valentina , Michimoto Takeshi , Sasaki Takeshi , Ohbayashi Iwai , Kikuchi Yoshiko , Yoshida Satoshi 
Published: July 2013

Summary
Cdc55, a regulatory B-subunit of protein phosphatase 2A (PP2A) complex, is essential for the spindle assembly checkpoint (SAC) in budding yeast, but the regulation and molecular targets of PP2A-Cdc55 have not been clearly defined or are controversial. Here, we show that an important target of Cdc55 in the SAC is the anaphase-promoting complex (APC) coupled with Cdc20 and that APC-Cdc20 is kept inactive by dephosphorylation by nuclear PP2A-Cdc55 when spindle is damaged. By isolating a new class of Cdc55 mutants specifically defective in the SAC and by artificially manipulating nucleocytoplasmic distribution of Cdc55, we further show that nuclear Cdc55 is essential for the SAC. Because the Cdc55-binding proteins Zds1 and Zds2 inhibit both nuclear accumulation of Cdc55 and SAC activity, we propose that spatial control of PP2A by Zds1 family proteins is important for tight control of SAC and mitotic progression.
Ligand signature in the membrane dynamics of single TrkA receptor molecules
Authors: Marchetti Laura , Callegari Andrea , Luin Stefano , Signore Giovanni , Viegi Alessandro , Beltram Fabio , Cattaneo Antonino 
Published: July 2013

Summary
The neurotrophin receptor TrkA (also known as NTRK1) is known to be crucially involved in several physio-pathological processes. However, a clear description of the early steps of ligand-induced TrkA responses at the cell plasma membrane is missing. We have exploited single particle tracking and TIRF microscopy to study TrkA membrane lateral mobility and changes of oligomerization state upon binding of diverse TrkA agonists (NGF, NGF R100E HSANV mutant, proNGF and NT-3). We show that, in the absence of ligands, most of the TrkA receptors are fast moving monomers characterized by an average diffusion coefficient of 0.47 µm2/second; about 20% of TrkA molecules move at least an order of magnitude slower and around 4% are almost immobile within regions of about 0.6 µm diameter. Ligand binding results in increased slow and/or immobile populations over the fast one, slowing down of non-immobile trajectories and reduction of confinement areas, observations that are consistent with the formation of receptor dimeric and oligomeric states. We demonstrate that the extent of TrkA lateral mobility modification is strictly ligand dependent and that each ligand promotes distinct trajectory patterns of TrkA receptors at the cell membrane (ligand ‘fingerprinting’ effect). This ligand signature of receptor dynamics results from a differential combination of receptor-binding affinity, intracellular effectors recruited in the signalling platforms and formation of signalling and/or recycling endosome precursors. Thus, our data uncover a close correlation between the initial receptor membrane dynamics triggered upon binding and the specific biological outcomes induced by different ligands for the same receptor.
Installation, Calibration, and Application of Dielectric Sensors in Laboratory Studies of Compacted Unsaturated Granular Materials
Authors: de Carteret Ryan , Buzzi Olivier , Fityus Stephen 
Published: July 2013

Abstract
The use of small-scale, instrumented laboratory columns for the study of moisture content and electrical conductivity response of soils has historically been restricted primarily to fine-grained materials because of the size of available instrumentation and probe installation difficulties. This study explores the suitability of capacitance-type dielectric sensors for studies of coarse-grained granular materials by assessing installation and calibration requirements. A number of different methods for installing a Hydra Probe dielectric sensor in a gravelly granular material were assessed and their repeatability compared with sensor installation in a fine-grained material. Typical installation methods were found to result in highly inconsistent installation in the compacted granular material, with poor repeatability. An alternative installation method is presented for gravelly granular materials, which resulted in an acceptable level of repeatability for both components of sensor measurement, consistent with that achieved by direct sensor insertion in fine-grained materials. It was also found necessary to develop a material-specific volumetric moisture content calibration relationship for the granular material as the manufacturer-supplied relationships were found to have very-low accuracy. This material-specific calibration was found to improve the accuracy of the dielectric sensor to ±0.03 m3/m3. To demonstrate the potential of dielectric sensors for use in the study of compacted granular materials, two laboratory experiments are described: one monitoring changes in moisture content with time and the other changes in electrical conductivity. General recommendations for use of dielectric sensors with granular materials are also presented.
Monitoring Field Lift Thickness Using Compaction Equipment Instrumented with Global Positioning System (GPS) Technology
Authors: Meehan Christopher L. , Khosravi Mohammad , Cacciola Daniel V. 
Published: July 2013

Abstract
When constructing earthen embankments, it is essential that the soil be placed and spread in uniform lifts prior to compaction. To ensure that the resulting soil lifts are evenly compacted, typical compaction specification approaches place restrictions on the thickness that is acceptable for each soil lift. In current practice, it can be extremely difficult for a field inspector to verify that lift thickness requirements are being met when soil is being placed and spread over a large area, without the use of frequent surveying (which adds both costs and delays to earthwork projects). Recent advances in compaction control include the development of continuous compaction control (CCC) and intelligent compaction (IC) systems, which provide real-time monitoring and feedback about the operation and performance of soil compaction. Typically, CCC and IC compaction equipment is outfitted with a real-time kinematic global positioning system (RTK-GPS) that monitors and records the position of the compacter as the soil lift is being compacted. This paper suggests that geotechnical engineers use field RTK-GPS measurements that are made by CCC or IC equipment to monitor and control the thickness of compacted soil lifts. Data collected from a full-scale field study is used to illustrate the practical issues with using GPS measurements for field monitoring of lift thickness during construction of a roadway embankment, such as varying roller position from lift-to-lift and the measurement uncertainty associated with RTK-GPS measurement data. The use of both simple and sophisticated spatial analysis techniques are explored for interpolating measured field elevation data onto a uniform grid for lift thickness assessment. The resulting methodology that is presented can be utilized to build spatial maps of compacted soil lift thickness, a process that can be used to great benefit by field engineers who are trying to ensure the quality of compacted soil lifts.
Determination of Soil Stabilizer Content Using X-Ray Fluorescence
Authors: Cerato A. B. , Miller G. A. 
Published: July 2013

Abstract
Currently, there are no simple methods routinely used to quantify the amount of chemical additive mixed into the soil during subgrade stabilization. Such a method was developed and validated for commonly used chemical additives including lime, cement kiln dust, and Class C fly ash mixed with different fine-grained soil types. The method employs the well-established x-ray fluorescence (XRF) technique. X-ray fluorescence was used to detect the amount of stabilizer, in the form of calcium oxide (CaO), in several stabilized subgrade soils. This technique was validated using four soils of different mineralogy and classification stabilized with three chemical stabilizers, and successfully implemented on several roadway stabilization projects. The results show that XRF accurately measures the amount of CaO in various soils, using different stabilizers, and can be a valuable tool for not only quality control, but forensic geotechnical investigations as well.
Calibration of Roller-Integrated Machine Drive Power Measurements Using Soil Compaction Forecasting Model
Authors: Thompson Mark J. , Schmitt Robert L. 
Published: July 2013

Abstract
Calibration of roller-integrated machine drive power (MDP) measurements is a necessary step for implementing the continuous compaction control technology into practice. State-of-the-practice calibration procedures use univariate or multivariate regression analysis of roller machine values with traditional compaction indices, such as modulus or soil unit weight. In this paper, a new calibration technique for estimating dry unit weight from MDP measurements was developed through investigation of the relationship between roller-integrated MDP and the inferred compactive effort associated with the corresponding moisture-density state of soil. Based on field data from eight test strips, linear trends were observed between compactive effort and cumulative MDP, and the proposed approach was able to detect how moisture content (a changing variable between test strips) substantially influences soil compactive effort and the soil–roller interaction affecting MDP measurements. Identifying slopes and intercepts of these moisture-dependent correlations allows for estimating roller-achieved compactive effort, and then converting estimated compactive effort to soil dry unit weight through a unified soil compaction model that is calibrated using traditional laboratory Proctor test data. The proposed forecasting calibration technique is based on accepted and defensible geotechnical principles on which earthworks practice is based, not relying solely on regression models. Observing the correlation of roller machine values and dry unit weight in the context of soil compaction behavior is expected to improve confidence in the continuous compaction control technology and ultimately result in more widespread acceptance and use.
Centrifuge Modeling of Deep Excavations and Their Interaction With Adjacent Buildings
Authors: Elshafie M. Z. E. B. , Choy C. K. C. , Mair R. J. 
Published: July 2013

Abstract
Major cities in the world are experiencing a rapid growth in population while becoming increasingly overcrowded and congested. In recent years, this has created a huge demand for underground infrastructure, which often involves the design of major mass transit tunnel systems; these tunnel systems (underground tunnels and metro stations) are becoming increasingly necessary to construct in very close proximity to existing buildings. The prediction of excavation-induced deformations, therefore, becomes a key issue in the planning and design process for these schemes. However, current design approaches are conservative and often lead to unnecessary concern and expenditure in the design and provision of protective measures. A better understanding of the mechanisms involved in the excavation soil–structure interaction could reduce costs and help avoid potential problems. A series of small-scale model tests was carried out in the geotechnical centrifuge at Cambridge University to investigate the interaction between excavations and model buildings. Excavations (simulated by adopting a novel two-fluid technique) in a “free field” were also undertaken to assess the difference between free-field ground movements and those affected by a stiff model building. A detailed description of the centrifuge models and test procedures is presented in this paper, followed by the presentation of test results that demonstrate the effect of the stiffness of the model building on the excavation-induced displacements.
A Large-Scale Soil-Structure Interface Testing Device
Authors: Vogelsang Jakob , Huber Gerhard , Triantafyllidis Theodoros 
Published: July 2013

Abstract
A large-scale testing device for the experimental investigation of soil-structure interactions was developed. It allows an observation of the evolution of deformations and the measurement of the stresses in the soil-structure contact zone under 1 g-conditions. The tests are designed as boundary value problems for benchmark tests of numerical simulations. They can be used to validate contact formulations and constitutive equations for the soil. The dimensions (soil height &gt;1.5 m) provide a sufficiently high stress level for simulations with constitutive models for soil. The major part of the device is an instrumented wall section with modifiable surface roughness representing, e.g., a part of a pile shaft or a steel sheet. This wall can be displaced quasi-statically relative to an adjacent soil body. The distribution of shear and normal stress and the wall displacements are measured. Digital image correlation (DIC) is used to evaluate the soil deformations. The paper focuses on the basic concept, the design, and the instrumentation details of the testing device. Additionally, some selected test results are shown.
Evaluation of Bouwer-Rice Large-Particle Correction Procedure for Soil Water Characteristic Curves
Authors: Bareither Christopher A. , Benson Craig H. 
Published: July 2013

Abstract
The Bouwer-Rice correction method to account for large particles excluded during laboratory testing to measure the soil water characteristic curve (SWCC) was evaluated on samples of well-graded alluvium. A large-scale hanging column apparatus was used so that tests could be conducted on specimens containing all particle sizes. The analyses show that SWCCs measured on the fraction of alluvium finer than the No. 4 U.S. sieve (4.8 mm) can be corrected reliably to represent the SWCC of bulk soil or fractions of bulk soil corresponding to different large-particle thresholds. The method can also be used reliably to correct SWCCs measured on soils prepared with different large-particle thresholds (e.g., finer than 25 mm, 12.5 mm, or 4.8 mm). Dry density of the finer fraction being tested must be carefully controlled to match the dry density of the finer fraction in the soils containing large particles. An equation is described for computing the dry density of the finer fraction in a bulk soil. A simplified version of the Bouwer-Rice method is also proposed and evaluated. In this method, a SWCC test is conducted on the finer soil fraction with dry density matching that anticipated in the field, the van Genuchten equation is fit to the measured SWCC to define the shape parameters α and n, and then the SWCC for the field application is computed using the fitted α and n from the test on the finer fraction, saturated volumetric water content of the bulk soil in the field, and a residual water content of zero. Analyses show that this modified Bouwer-Rice method is simpler and results in an accurate representation of the SWCC of soil containing large particles.
An Experimental Framework for BGP Security Evaluation
Authors: Perouli Debbie , Maennel Olaf , Phillips Iain , Fahmy Sonia , Bush Randy , Austein Rob 
Published: July 2013

Abstract
Internet routing is based on implicit trust assumptions. Given the critical importance of the Internet and the increasing security threats, such simple trust relationships are no longer sufficient. Over the past decade, significant research has been devoted to securing the Internet routing system. The Internet Engineering Task Force (IETF) is well along in the process of standardizing routing security enhancements (Secure Inter-Domain Routing — SIDR, Keying and Authentication for Routing Protocols — KARP, etc.). However, the research challenges are not over: not only do these new protocols need to be tested for protocol conformance and interoperability, they also need to be evaluated both for their security properties and scaling performance. The purpose of this paper is two-fold: we outline the main security challenges in inter-domain routing and argue that research in this area has barely begun; and we take a closer look at a production implementation of one component and evaluate it at a fairly large scale. We discuss the difficulties we experienced and lessons learned; we also present some initial results.