Increasing breast and cervical cancer screening in low-income women

Active cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) was treated with an intraocular sustained-release ganciclovir implant. A total number of 19 implants were performed in 15 eyes of 9 AIDS patients. The intraocular sustained-release ganciclovir was effective in preventing reactivation of CMV retinitis in 15 of the 19 implants, ineffective in 3, and undetermined in 1. All ineffective cases had been resistant to ganciclovir therapy before the implants. Vision after the therapy was maintained at better than 0.5 except for one eye. There were no serious ocular complications caused by the therapy. Among 5 patients with unilateral CMV retinitis, 2 unaffected eyes developed CMV retinitis during this therapy. In addition, another patient developed presumed CMV infection in other systemic organs. Based on these data, the intraocular sustained-release ganciclovir implant was considered to be useful for the treatment of CMV retinitis in AIDS.     

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.     

Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.     

Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.     

Energetics of Defect Fluorite and Pyrochlore Phases in Lanthanum and Gadolinium Hafnates

Aerodynamic levitation combined with laser heating was used to prepare melts in the HfO₂–La₂O₃ (–Gd₂O₃) systems. All melts crystallized upon quenching in oxygen. Hf₂La₂O₇ pyrochlore and Gd_0.5Hf_0.5O_1.75 fluorite phases were identified. Gd_0.5Hf_0.5O_1.75 fluorite was transformed into the pyrochlore structure by annealing at 1450°C. Pyrochlore that crystallized from HfO₂- La₂O₃ melts contained 31.6–34.2 mol% La₂O₃. The unit cell parameter increased linearly with La content from 10.736 to 10.789 Å. Drop solution calorimetric experiments were performed in 3Na₂O·4MoO₃ melt at 702°C. The enthalpies of formation from the oxides for pyrochlore phases are −107.0±5.0 kJ/mol for Hf₂La₂O₇ and −48.8±4.7 kJ/mol for Hf₂Gd₂O₇. The enthalpy of the pyrochlore–fluorite phase transition in Hf₂Gd₂O₇ is 23.6±3.1 kJ/mol.     

Microwave Dielectric Properties of CaTiO3-Ca(Al1/2Ta1/2)O3 Ceramics

The microwave dielectric properties of CaTi_1-χ(Al_1/2Ta_1/2)_cHO₃ solid solutions (0.3 ≤χ≤ 0.5) have been investigated. The ceramic samples had perovskite structures similar to CaTiO₃. The partial substitution of Ti₄₊ by a coupled Al₃₊/Ta_s+ permitted improvement of the quality factor Q . The dielectric constant (τ_r) and temperature coefficient of resonant frequency (τ_r) decrease rapidly with an increase of χ. A new high-quality microwave dielectric material was found at χ= 0.46 with σ_r= 46.5, Q f = 27300 GHz, and π_f= 0 ppm/°C. The relationship between microstructures and dielectric properties is presented.     

Finite-time coordination in multiagent systems using sliding mode control approach

Finite-time stability in dynamical systems theory involves systems whose trajectories converge to an equilibrium state in finite time. In this paper, we use the notion of finite-time stability to apply it to the problem of coordinated motion in multiagent systems. Specifically, we consider a group of agents described by fully actuated Euler–Lagrange dynamics along with a leader agent with an objective to reach and maintain a desired formation characterized by steady-state distances between the neighboring agents in finite time. We use graph theoretic notions to characterize communication topology in the network determined by the information flow directions and captured by the graph Laplacian matrix. Furthermore, using sliding mode control approach, we design decentralized control inputs for individual agents that use only data from the neighboring agents which directly communicate their state information to the current agent in order to drive the current agent to the desired steady state. Sliding mode control is known to drive the system states to the sliding surface in finite time. The key feature of our approach is in the design of non-smooth sliding surfaces such that, while on the sliding surface, the error states converge to the origin in finite time, thus ensuring finite-time coordination among the agents in the network. In addition, we discuss the case of switching communication topologies in multiagent systems. Finally, we show the efficacy of our theoretical results using an example of a multiagent system involving planar double integrator agents.     

Exploiting Batch Processing on Streaming Architectures to Solve 2D Elliptic Finite Element Problems: A Hybridized Discontinuous Galerkin (HDG) Case Study

Numerical methods for elliptic partial differential equations (PDEs) within both continuous and hybridized discontinuous Galerkin (HDG) frameworks share the same general structure: local (elemental) matrix generation followed by a global linear system assembly and solve. The lack of inter-element communication and easily parallelizable nature of the local matrix generation stage coupled with the parallelization techniques developed for the linear system solvers make a numerical scheme for elliptic PDEs a good candidate for implementation on streaming architectures such as modern graphical processing units (GPUs). We propose an algorithmic pipeline for mapping an elliptic finite element method to the GPU and perform a case study for a particular method within the HDG framework. This study provides comparison between CPU and GPU implementations of the method as well as highlights certain performance-crucial implementation details. The choice of the HDG method for the case study was dictated by the computationally-heavy local matrix generation stage as well as the reduced trace-based communication pattern, which together make the method amenable to the fine-grained parallelism of GPUs. We demonstrate that the HDG method is well-suited for GPU implementation, obtaining total speedups on the order of 30–35 times over a serial CPU implementation for moderately sized problems.     

DSGE Model Estimation on the Basis of Second-Order Approximation

This article compares the properties of different non-linear Kalman filters: the well-known Unscented Kalman filter (UKF), the central difference Kalman filter (CDKF) and the new Quadratic Kalman filter (QKF). A small financial DSGE model is repeatedly estimated by several quasi-likelihood methods with different filters for data generated by the model. Errors in parameters estimation are a measure of the filters’ quality. The result shows that the QKF has a reasonable advantage in terms of quality over the CDKF and the UKF, albeit with some loss in speed.