A Relational Event Approach to Modeling Behavioral Dynamics

This chapter provides an introduction to the analysis of relational event data (i.e., actions, interactions, or other events involving multiple actors that occur over time) within the R/statnet platform. We begin by reviewing the basics of relational event modeling, with an emphasis on models with piecewise constant hazards. We then discuss estimation for dyadic and more general relational event models using the relevent package, with an emphasis on hands-on applications of the methods and interpretation of results. Statnet is a collection of packages for the R statistical computing system that supports the representation, manipulation, visualization, modeling, simulation, and analysis of relational data. Statnet packages are contributed by a team of volunteer developers, and are made freely available under the GNU Public License. These packages are written for the R statistical computing environment, and can be used with any computing platform that supports R (including Windows, Linux, and Mac).

Long Term Efficacy and Safety of Bronchoscopic Thermal Vapor Ablation in Patients with COPD: A Retrospective Study of 50 Patients

Barak Pertzov,1– 4 Merav Ben Avraham,1,2 Eldar Priel,3– 5 Lev Freidkin,1,2 Dror Rosengarten,1,2 Mordechai Reuven Kramer1,2 1Pulmonary Division, Rabin Medical Center, Petach Tikva, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Firestone Institute for Respiratory Health, St Joseph’s Healthcare, Hamilton, ON, Canada; 4Department of Medicine, McMaster University, Hamilton, ON, Canada; 5Division of Thoracic Surgery, St. Joseph’s Healthcare, Hamilton, ON, CanadaCorrespondence: Barak Pertzov, Pulmonary Division, Rabin Medical Center, Beilinson Campus, 39 Jabotinski St, Petach Tikva, 4941492, Israel, Tel +972-3-9377221/3, Fax +972-3-9242091, Email [email protected]: Bronchoscopic Thermal Vapor Ablation (BTVA) has demonstrated improvements in FEV1 and quality of life in clinical trials. However, the long-term benefits and overall efficacy of this procedure remain uncertain and are not yet fully established.Methods: We conducted a retrospective observational study of all patients who underwent BTVA at Rabin Medical Center, Israel. The primary outcome was the change in FEV₁ from baseline. Secondary outcomes included other pulmonary function parameters and procedural adverse events.Results: A total of 50 patients were included in the study. The mean FEV1 values at baseline, 6 months, and 12 months post-procedure (n=31) were 0.74± 0.21 L, 0.93± 0.32 L, and 0.85± 0.25 L, respectively (overall P< 0.001; pairwise comparisons: baseline to 6 months, P< 0.001; baseline to 12 months, P=0.016). The mean FVC values at baseline, 6 months, and 12 months post-procedure (n=31) were 1.97± 0.56 L, 2.27± 0.71 L, and 2.14± 0.68 L, respectively (overall P=0.003; pairwise comparisons: baseline to 6 months, P=0.002; baseline to 12 months, P=0.125). Post-procedural complications included pneumonia in 5 patients (11%), of whom 3 developed necrotizing pneumonia and subsequently died, resulting in a 6% post-procedural mortality rate in the entire cohort. Hemoptysis was reported in 1 patient (2%).Conclusion: Bronchoscopic thermal vapor ablation is a minimally invasive bronchoscopic intervention for lung volume reduction. The procedure was associated with significant improvements in FEV₁ at 6 to 12 months and in FVC at 6 months, followed by a gradual decline over 12 to 24 months. Further research is warranted to optimize patient selection, enhance procedural safety, and assess long-term efficacy.Plain Language Summary: COPD is a disease that damages lung tissue. The damaged areas become hyperinflated, compressing healthier parts of the lung and reducing their function. Bronchoscopic Thermal Vapor Ablation (BTVA) is a minimally invasive treatment that uses heated water vapor to target and shrink these damaged areas. During the procedure, a thin tube with a camera (bronchoscope) is inserted into the lungs to deliver vapor directly to diseased regions. The vapor causes controlled injury, leading to shrinkage of the targeted tissue and allowing healthier lung areas to expand and function more effectively. BTVA can be repeated by treating different regions over time, potentially maintaining its benefits.In this study, we evaluated the effectiveness and safety of BTVA in patients with advanced COPD. Lung function improved significantly at 6 and 12 months compared to baseline. Between 12 and 24 months, the benefits gradually declined but remained above baseline.Side effects were primarily pneumonia and temporary coughing up of blood, which resolved in most cases. However, three patients developed severe pneumonia and died, highlighting the need for further research.In conclusion, BTVA improved lung function, but careful selection of treatment areas and energy levels is important to reduce complications and enhance safety.Keywords: COPD, emphysema, BLVR, BTVA, vapor, FEV1, safet

Distinctive sequence patterns in metazoan and yeast nucleosomes: Implications for linker histone binding to AT-rich and methylated DNA

Linker histones (LHs) bind to the DNA entry/exit points of nucleosomes and demonstrate preference for AT-rich DNA, although the recognized sequence patterns remain unknown. These patterns are expected to be more pronounced in metazoan nucleosomes with abundant LHs, compared to yeast nucleosomes with few LHs. To test this hypothesis, we compared the nucleosome core particle (NCP) sequences from chicken, Drosophila and yeast, extending them by the flanking sequences extracted from the genomes. We found that the known ∼10-bp periodic oscillation of AT-rich elements goes beyond the ends of yeast nucleosomes, but is distorted in metazoan sequences where the ‘out-of-phase’ AT-peaks appear at the NCP ends. The observed difference is likely to be associated with sequence-specific LH binding. We therefore propose a new structural model for LH binding to metazoan nucleosomes, postulating that the highly conserved nonpolar ‘wing’ region of the LH globular domain (tetrapeptide GVGA) recognizes AT-rich fragments through hydrophobic interactions with the thymine methyl groups. These interactions lead to DNA bending at the NCP ends and formation of a ‘stem-like’ structure. The same mechanism accounts for the high affinity of LH to methylated DNA—a feature critical for stabilization of the higher-order structure of chromatin and for repression of transcription

Activation-induced disruption of nucleosome position clusters on the coding regions of Gcn4-dependent genes extends into neighbouring genes

We have used paired-end sequencing of yeast nucleosomal DNA to obtain accurate genomic maps of nucleosome positions and occupancies in control cells and cells treated with 3-aminotriazole (3AT), an inducer of the transcriptional activator Gcn4. In control cells, 3AT-inducible genes exhibit a series of distinct nucleosome occupancy peaks. However, the underlying position data reveal that each nucleosome peak actually consists of a cluster of mutually exclusive overlapping positions, usually including a dominant position. Thus, each nucleosome occupies one of several possible positions and consequently, different cells have distinct local chromatin structures. Induction results in a major disruption of nucleosome positioning, sometimes with altered spacing and a dramatic loss of occupancy over the entire gene, often extending into a neighbouring gene. Nucleosome-depleted regions are generally unaffected. Genes repressed by 3AT show the same changes, but in reverse. We propose that yeast genes exist in one of several alternative nucleosomal arrays, which are disrupted by activation. We conclude that activation results in gene-wide chromatin remodelling and that this remodelling can even extend into the chromatin of flanking genes

Principles of chromosomal organization: lessons from yeast

The spatial organization of genes and chromosomes plays an important role in the regulation of several DNA processes. However, the principles and forces underlying this nonrandom organization are mostly unknown. Despite its small dimension, and thanks to new imaging and biochemical techniques, studies of the budding yeast nucleus have led to significant insights into chromosome arrangement and dynamics. The dynamic organization of the yeast genome during interphase argues for both the physical properties of the chromatin fiber and specific molecular interactions as drivers of nuclear order

Effects of the Histone Deacetylase Inhibitor Valproic Acid on Human Pericytes In Vitro

Microvascular pericytes are of key importance in neoformation of blood vessels, in stabilization of newly formed vessels as well as maintenance of angiostasis in resting tissues. Furthermore, pericytes are capable of differentiating into pro-fibrotic collagen type I producing fibroblasts. The present study investigates the effects of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) on pericyte proliferation, cell viability, migration and differentiation. The results show that HDAC inhibition through exposure of pericytes to VPA in vitro causes the inhibition of pericyte proliferation and migration with no effect on cell viability. Pericyte exposure to the potent HDAC inhibitor Trichostatin A caused similar effects on pericyte proliferation, migration and cell viability. HDAC inhibition also inhibited pericyte differentiation into collagen type I producing fibroblasts. Given the importance of pericytes in blood vessel biology a qPCR array focusing on the expression of mRNAs coding for proteins that regulate angiogenesis was performed. The results showed that HDAC inhibition promoted transcription of genes involved in vessel stabilization/maturation in human microvascular pericytes. The present in vitro study demonstrates that VPA influences several aspects of microvascular pericyte biology and suggests an alternative mechanism by which HDAC inhibition affects blood vessels. The results raise the possibility that HDAC inhibition inhibits angiogenesis partly through promoting a pericyte phenotype associated with stabilization/maturation of blood vessels