418 research outputs found
Network Inference via the Time-Varying Graphical Lasso
Many important problems can be modeled as a system of interconnected
entities, where each entity is recording time-dependent observations or
measurements. In order to spot trends, detect anomalies, and interpret the
temporal dynamics of such data, it is essential to understand the relationships
between the different entities and how these relationships evolve over time. In
this paper, we introduce the time-varying graphical lasso (TVGL), a method of
inferring time-varying networks from raw time series data. We cast the problem
in terms of estimating a sparse time-varying inverse covariance matrix, which
reveals a dynamic network of interdependencies between the entities. Since
dynamic network inference is a computationally expensive task, we derive a
scalable message-passing algorithm based on the Alternating Direction Method of
Multipliers (ADMM) to solve this problem in an efficient way. We also discuss
several extensions, including a streaming algorithm to update the model and
incorporate new observations in real time. Finally, we evaluate our TVGL
algorithm on both real and synthetic datasets, obtaining interpretable results
and outperforming state-of-the-art baselines in terms of both accuracy and
scalability
ORB5: a global electromagnetic gyrokinetic code using the PIC approach in toroidal geometry
This paper presents the current state of the global gyrokinetic code ORB5 as
an update of the previous reference [Jolliet et al., Comp. Phys. Commun. 177
409 (2007)]. The ORB5 code solves the electromagnetic Vlasov-Maxwell system of
equations using a PIC scheme and also includes collisions and strong flows. The
code assumes multiple gyrokinetic ion species at all wavelengths for the
polarization density and drift-kinetic electrons. Variants of the physical
model can be selected for electrons such as assuming an adiabatic response or a
``hybrid'' model in which passing electrons are assumed adiabatic and trapped
electrons are drift-kinetic. A Fourier filter as well as various control
variates and noise reduction techniques enable simulations with good
signal-to-noise ratios at a limited numerical cost. They are completed with
different momentum and zonal flow-conserving heat sources allowing for
temperature-gradient and flux-driven simulations. The code, which runs on both
CPUs and GPUs, is well benchmarked against other similar codes and analytical
predictions, and shows good scalability up to thousands of nodes
Targeting of Natural Killer Cells by Rabbit Antithymocyte Globulin and Campath-1H: Similar Effects Independent of Specificity
T cell depleting strategies are an integral part of immunosuppressive regimens widely used in the hematological and solid organ transplant setting. Although it is known to induce lymphocytopenia, little is known about the effects of the polyclonal rabbit antithymocyte globulin (rATG) or the monoclonal anti-CD52 antibody alemtuzumab on Natural Killer (NK) cells in detail. Here, we demonstrate that induction therapy with rATG following kidney/pancreas transplantation results in a rapid depletion of NK cells. Treatment of NK cells with rATG and alemtuzumab in vitro leads to impairment of cytotoxicity and induction of apoptosis even at a 10-fold lower concentration (0.1 µg/ml) compared with T and B cells. By generating Fc-parts of rATG and alemtuzumab we illustrate that their ligation to FcγRIII (CD16) is sufficient for the significant induction of degranulation, apoptosis and inflammatory cytokine release (FasL, TNFα and IFNγ) exclusively in CD3−CD56dim NK cells whereas application of rATG and alemtuzumab F(ab) fragments abolishes these effects. These findings are of general importance as our data suggest that NK cells are also mediators of the clinically relevant cytokine release syndrome and that their targeting by therapeutic antibodies should be considered as they are functionally relevant for the effective clearance of opportunistic viral infections and anti-tumor activity posttransplantation
How university’s activities support the development of students’ entrepreneurial abilities: case of Slovenia and Croatia
The paper reports how the offered university activities support the development of students’ entrepreneurship abilities. Data were collected from 306 students from Slovenian and 609 students from Croatian universities. The study reduces the gap between theoretical researches about the academic entrepreneurship education and individual empirical studies about the student’s estimation of the offered academic activities for development of their entrepreneurial abilities. The empirical research revealed differences in Slovenian and Croatian students’ perception about (a) needed academic activities and (b) significance of the offered university activities, for the development of their entrepreneurial abilities. Additionally, the results reveal that the impact of students’ gender and study level on their perception about the importance of the offered academic activities is not significant for most of the considered activities. The main practical implication is focused on further improvement of universities’ entrepreneurship education programs through selection and utilization of activities which can fill in the recognized gaps between the students’ needed and the offered academic activities for the development of students’ entrepreneurial abilities
Selective Alpha-Particle Mediated Depletion of Tumor Vasculature with Vascular Normalization
BACKGROUND: Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. METHODOLOGY AND PRINCIPAL FINDINGS: Actinium-225 ((225)Ac)-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225)Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225)Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225)Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225)Ac-E4G10 therapy. CONCLUSIONS: The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy
The effects of prolonged wear of textured shoe insoles on gait, foot sensation and proprioception in people with Multiple Sclerosis: protocol for a randomised controlled trial
Background: Many people with multiple sclerosis experience problems with walking, which can make daily activities difficult and often leads to falls. Foot sensation plays an important role in keeping the body balanced whilst walking; however, people with multiple sclerosis often have poor sensation on the soles of their feet. Wearing a specially designed shoe insole, which enhances plantar sensory information, could help people with multiple sclerosis to walk better. This study will explore whether long-term wear of a textured insole can improve walking in people with multiple sclerosis
- …