Localized-density-matrix, segment-molecular-orbitals and poly(p-phenylenevinylene) aggregates

The segment-molecular-orbital representation is developed and incorporated into the recently developed linear-scaling localized-density-matrix method. The entire system is divided into many segments, and the molecular orbitals of all segments form the basis functions of the segment-molecular-orbital representation. Introduction of different cutoff lengths for different segment-molecular-orbitals leads to a drastic reduction of the computational cost. As a result, the modified localized-density-matrix method is employed to investigate the optical responses of large Poly(p-phenylenevinylene) aggregates. In particular, the interchain excitations are studied. The complete neglect of differential overlap in spectroscopy hamiltonian is employed in the calculation. © 1999 American Institute of Physics.published_or_final_versio

X-ray absorption by the low-redshift intergalactic medium: A numerical study of the Lambda cold dark matter model

Using a hydrodynamic simulation of a cold dark matter universe with a cosmological constant, we investigate the X-ray forest absorption imprinted on the spectra of background quasars by the intervening intergalactic medium (IGM), at redshift z 0. In agreement with previous studies, we find that O VII and O VIII produce the strongest absorption features. The strong oxygen absorbers that might be detectable with Chandra or XMM-Newton arise in gas with T ~ 105.5-106.5 K and overdensities δ 100 that are characteristic of galaxy groups. Future X-ray missions could detect weaker oxygen absorption produced by gas with a wider range of temperatures and the lower densities of unvirialized structures; they could also detect X-ray forest absorption by carbon, nitrogen, neon, iron, and possibly silicon. If the IGM metallicity is Z = 0.1 Z, as we assume in most of our calculations, then the predicted number of systems strong enough for a ~5 σ detection with Chandra or XMM-Newton is extremely low. However, scatter in metallicity increases the number of strong absorbers even if the mean metallicity remains the same, making the predictions somewhat more optimistic. Our simulation reproduces the high observed incidence of O VI (λλ1032, 1038) absorbers, and the most promising strategy for finding the X-ray forest is to search at the redshifts of known O VI systems, thus reducing the signal-to-noise ratio threshold required for a significant detection. However, while many O VI absorbers have associated O VII or O VIII absorption, the O VI systems trace only the low-temperature phases of the X-ray forest, and a full accounting of the strong O VII and O VIII systems will require a mission with the anticipated capabilities of Constellation-X. The large effective area of the XEUS satellite would make it an extremely powerful instrument for studying the IGM, measuring X-ray forest absorption by a variety of elements, and revealing the shock-heated filaments that may be an important reservoir of cosmic baryons

Entrectinib-related myocarditis in a young female patient with metastatic non-small cell lung cancer

A 51-year-old woman presented with a 2-week history of off balance, left lower limb weakness and neglect and neck pain radiating down the right arm. Investigations revealed a metastatic, ROS1 fusion-positive, non-small cell lung cancer, and treatment with entrectinib, a recently approved multikinase inhibitor, was started. Two weeks after, she was admitted to the emergency department with new-onset pressure-like chest pain and dyspnoea. Laboratory evaluation showed elevated troponin and mild left ventricular systolic dysfunction with reduced global longitudinal strain on transthoracic echocardiogram. Cardiac magnetic resonance revealed mild oedema and non-ischaemic fibrosis. A diagnosis of drug-induced myocarditis was made. Cardioprotective medication with an angiotensin-converting enzyme inhibitor and a beta-blocker was started. Entrectinib was temporarily discontinued and restarted at a reduced dose after a multidisciplinary team meeting involving both the oncology and cardio-oncology teams. This is the second described case of entrectinib-induced myocarditis and the first one without eosinophilia

DeltaPhish: Detecting Phishing Webpages in Compromised Websites

The large-scale deployment of modern phishing attacks relies on the automatic exploitation of vulnerable websites in the wild, to maximize profit while hindering attack traceability, detection and blacklisting. To the best of our knowledge, this is the first work that specifically leverages this adversarial behavior for detection purposes. We show that phishing webpages can be accurately detected by highlighting HTML code and visual differences with respect to other (legitimate) pages hosted within a compromised website. Our system, named DeltaPhish, can be installed as part of a web application firewall, to detect the presence of anomalous content on a website after compromise, and eventually prevent access to it. DeltaPhish is also robust against adversarial attempts in which the HTML code of the phishing page is carefully manipulated to evade detection. We empirically evaluate it on more than 5,500 webpages collected in the wild from compromised websites, showing that it is capable of detecting more than 99% of phishing webpages, while only misclassifying less than 1% of legitimate pages. We further show that the detection rate remains higher than 70% even under very sophisticated attacks carefully designed to evade our system.Comment: Preprint version of the work accepted at ESORICS 201

Modeling the functional genomics of autism using human neurons.

Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD

The relationship between web enjoyment and student perceptions and learning using a web-based tutorial

Web enjoyment has been regarded as a component of system experience. However, there has been little targeted research considering the role of web enjoyment alone in student learning using web-based systems. To address this gap, this study aims to examine the influence of web enjoyment on learning performance and perceptions by controlling system experience as a variable in the study. 74 students participated in the study, using a web-based tutorial covering subject matter in the area of 'Computation and algorithms'. Their learning performance was assessed with a pre-test and a post-test and their learning perceptions were evaluated with a questionnaire. The results indicated that there are positive relationships between the levels of web enjoyment and perceived usefulness and non-linear navigation for users with similar, significant levels of system experience. The implications of these findings in relation to web-based learning are explored and ways in which the needs of students who report different levels of web enjoyment might be met are discussed

Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor-Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching.

We have assessed whether HLA immunogenicity as defined by differences in donor-recipient HLA amino-acid sequence (amino-acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor-recipient HLA mismatch to induce donor-specific antibody (DSA). HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02-2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02-1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA-DR and HLA-DQ DSA, but only EMS correlated with the risk of HLA-A and -B DSA development. Differences in donor-recipient HLA amino-acid sequence and physicochemical properties enable better assessment of the risk of HLA-specific sensitization than conventional HLA matching.This study was supported by the Cambridge NIHR Biomedical Research Centre and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or NHSBT . VK was supported by an Academy of Medical Sciences Grant and an Evelyn Trust Grant. DHM was supported by an RCSEng Research Fellowship.This is the author accepted manuscript. The final version is available from Wiley via https://doi.org/10.1111/ajt.13707