RF model of the distribution system as a communication channel, phase 2. Volume 4: Sofware source program and illustrations ASCII database listings

Listings of source programs and some illustrative examples of various ASCII data base files are presented. The listings are grouped into the following categories: main programs, subroutine programs, illustrative ASCII data base files. Within each category files are listed alphabetically

RF model of the distribution system as a communication channel, phase 2. Volume 3: Appendices

Program documentation concerning the design, implementation, and verification of a computerized model for predicting the steady-state sinusoidal response of radial configured distribution feeders is presented in these appendices

RF model of the distribution system as a communication channel, phase 2. Volume 2: Task reports

Based on the established feasibility of predicting, via a model, the propagation of Power Line Frequency on radial type distribution feeders, verification studies comparing model predictions against measurements were undertaken using more complicated feeder circuits and situations. Detailed accounts of the major tasks are presented. These include: (1) verification of model; (2) extension, implementation, and verification of perturbation theory; (3) parameter sensitivity; (4) transformer modeling; and (5) compensation of power distribution systems for enhancement of power line carrier communication reliability

No Radio Bursts Detected from FIRST J141918.9+394036 in Green Bank Telescope Observations

Precise localization of the first-known repeating fast radio burst source, FRB 121102 (Spitler et al. 2016; Chatterjee et al. 2017), led to its association with a star-forming region inside a low-metallicity dwarf host galaxy (Tendulkar et al. 2017). This host environment is similar to that typically associated with long gamma-ray bursts (GRB) and superluminous supernovae, potentially linking these astrophysical phenomena (Metzger et al. 2017). In addition, the bursting source is found to be spatially coincident with a compact (< 0.7 pc; Marcote et al. 2017), persistent radio source (Chatterjee et al. 2017). Ofek (2017) identified similar radio sources in the Very Large Array FIRST survey (Becker et al. 1995). One of these sources, FIRST J141918.9+394036 (hereafter FIRST J1419+3940), was identified as a radio transient decaying in brightness by a factor of ~50 over several decades (Law et al. 2018). Very-long-baseline radio interferometric observations support the theory that FIRST J1419+3940 is the afterglow of a long GRB, based on the inferred physical size of the emission region (1.6 ± 0.3 pc; Marcote et al. 2019)

No Radio Bursts Detected from FIRST J141918.9+394036 in Green Bank Telescope Observations

Precise localization of the first-known repeating fast radio burst source, FRB 121102 (Spitler et al. 2016; Chatterjee et al. 2017), led to its association with a star-forming region inside a low-metallicity dwarf host galaxy (Tendulkar et al. 2017). This host environment is similar to that typically associated with long gamma-ray bursts (GRB) and superluminous supernovae, potentially linking these astrophysical phenomena (Metzger et al. 2017). In addition, the bursting source is found to be spatially coincident with a compact (< 0.7 pc; Marcote et al. 2017), persistent radio source (Chatterjee et al. 2017). Ofek (2017) identified similar radio sources in the Very Large Array FIRST survey (Becker et al. 1995). One of these sources, FIRST J141918.9+394036 (hereafter FIRST J1419+3940), was identified as a radio transient decaying in brightness by a factor of ~50 over several decades (Law et al. 2018). Very-long-baseline radio interferometric observations support the theory that FIRST J1419+3940 is the afterglow of a long GRB, based on the inferred physical size of the emission region (1.6 ± 0.3 pc; Marcote et al. 2019)

The miR-17 similar to 92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma

Medulloblastomas (MBs) are the most common brain tumors in children. Some are thought to originate from cerebellar granule neuron progenitors (GNPs) that fail to undergo normal cell cycle exit and differentiation. Because microRNAs regulate numerous aspects of cellular physiology and development, we reasoned that alterations in miRNA expression might contribute to MB. We tested this hypothesis using 2 spontaneous mouse MB models with specific initiating mutations, Ink4c(-/-); Ptch1(+/-) and Ink4c(-/-); p53(-/-). We found that 26 miRNAs showed increased expression and 24 miRNAs showed decreased expression in proliferating mouse GNPs and MBs relative to mature mouse cerebellum, regardless of genotype. Among the 26 overexpressed miRNAs, 9 were encoded by the miR-17 similar to 92 cluster family, a group of microRNAs implicated as oncogenes in several tumor types. Analysis of human MBs demonstrated that 3 miR-17 similar to 92 cluster miRNAs (miR-92, miR-19a, and miR-20) were also overexpressed in human MBs with a constitutively activated Sonic Hedgehog (SHH) signaling pathway, but not in other forms of the disease. To test whether the miR-17 similar to 92 cluster could promote MB formation, we enforced expression of these miRNAs in GNPs isolated from cerebella of postnatal (P) day P6 Ink4c(-/-); Ptch1(+/-) mice. These, but not similarly engineered cells from Ink4c(-/-); p53(-/-) mice, formed MBs in orthotopic transplants with complete penetrance. Interestingly, orthotopic mouse tumors ectopically expressing miR-17 similar to 92 lost expression of the wild-type Ptch1 allele. Our findings suggest a functional collaboration between the miR-17 similar to 92 cluster and the SHH signaling pathway in the development of MBs in mouse and man

Preclinical studies of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in pediatric brain tumors.

Chemotherapies active in preclinical studies frequently fail in the clinic due to lack of efficacy, which limits progress for rare cancers since only small numbers of patients are available for clinical trials. Thus, a preclinical drug development pipeline was developed to prioritize potentially active regimens for pediatric brain tumors spanning from in vitro drug screening, through intracranial and intra-tumoral pharmacokinetics to in vivo efficacy studies. Here, as an example of the pipeline, data are presented for the combination of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in three pediatric brain tumor models. The in vitro activity of nine novel therapies was tested against tumor spheres derived from faithful mouse models of Group 3 medulloblastoma, ependymoma, and choroid plexus carcinoma. Agents with the greatest in vitro potency were then subjected to a comprehensive series of in vivo pharmacokinetic (PK) and pharmacodynamic (PD) studies culminating in preclinical efficacy trials in mice harboring brain tumors. The nucleoside analog 5-fluoro-2'-deoxycytidine (FdCyd) markedly reduced the proliferation in vitro of all three brain tumor cell types at nanomolar concentrations. Detailed intracranial PK studies confirmed that systemically administered FdCyd exceeded concentrations in brain tumors necessary to inhibit tumor cell proliferation, but no tumor displayed a significant in vivo therapeutic response. Despite promising in vitro activity and in vivo PK properties, FdCyd is unlikely to be an effective treatment of pediatric brain tumors, and therefore was deprioritized for the clinic. Our comprehensive and integrated preclinical drug development pipeline should reduce the attrition of drugs in clinical trials