DOMESTIC RELATIONS Adoption: Limit Recourse When Adoption Petition is Predicated on Exception to Requiring Surrender or Termination of Parental Rights

The Act provides a six-month time limitation on challenging adoptions. The Act also provides a six-month time limitation from the effective date of the Act for a judicial challenge of any adoption prior to the Act’s effective date

PUBLIC UTILITIES AND PUBLIC TRANSPORTATION Telephone and Telegraph Service: Create Telecommunications and Competition Development Act of 1995

The Act establishes a regulatory framework under which competition will be phased into Georgia’s local telephone services market. In addition, the Act provides for a modification in Georgia’s area code designations and provides penalties for obtaining and disseminating a caller’s unlisted number through a telephone caller identification service

PUBLIC UTILITIES AND PUBLIC TRANSPORTATION Telephone and Telegraph Service: Create Telecommunications and Competition Development Act of 1995

The Act establishes a regulatory framework under which competition will be phased into Georgia’s local telephone services market. In addition, the Act provides for a modification in Georgia’s area code designations and provides penalties for obtaining and disseminating a caller’s unlisted number through a telephone caller identification service

Ion Implantation of Porous Silicon

Investigates the ion implantation of porous silicon (Si). Properties of light-emitting Si; Application of continuous-wave and time dependent photoluminescence spectroscopies; Comparison of dopant implantation effect in varying doses

Direct measurements of intramolecular electron transfer rates between cytochrome c and cytochrome c peroxidase: effects of exothermicity and primary sequence on rate.

Rapid mixing of ferrocytochrome c peroxidase [cyt c peroxidase(II)] and ferricytochrome c [cyt c(III)] results in the reduction of cyt c(III) by cyt c peroxidase(II). In 10 mM phosphate, pH 7.0, the rate of decay of cyt c peroxidase(II) and the rate of accumulation of cyt c(II) give equal first-order rate constants: k = 0.23 +/- 0.02 s-1. Equivalent results are obtained by pulse radiolysis using isopropanol radical as the reducing agent. This rate is independent of the initial cyt c(III):cyt c peroxidase(II) ratios. These results are consistent with unimolecular electron transfer occurring within a cyt c(III)-cyt c peroxidase(II) complex. When cyt c is replaced by porphyrin cyt c (iron-free cyt c), a complex still forms with cyt c peroxidase. On radiolysis, using e-aq as the reducing agent, intracomplex electron transfer occurs from the porphyrin cyt c anion radical to cyt c peroxidase(III) with k = 150 s-1. This large rate increase with increasing delta G degrees suggests that the barrier for intracomplex electron transfer is large. Finally, we have briefly investigated how the cyt c peroxidase(II)----cyt c(III) rate depends on the primary structure of cyt c(III). We find the reactivity order to be as follows: yeast (k = 3.4 s-1) greater than horse (k = 0.3 s-1) greater than tuna (k = 0.2 s-1). These results mirror a report [Ho, P. S., Sutoris, C., Liang, N., Margoliash, E. & Hoffman, B. M. (1985) J. Am. Chem. Soc. 107, 1070-1071] on excited state reactions of the cyt c/cyt c peroxidase couple

Millisecond-Timescale Optical Control of Neural Dynamics in the Nonhuman Primate Brain

To understand how brain states and behaviors are generated by neural circuits, it would be useful to be able to perturb precisely the activity of specific cell types and pathways in the nonhuman primate nervous system. We used lentivirus to target the light-activated cation channel channelrhodopsin-2 (ChR2) specifically to excitatory neurons of the macaque frontal cortex. Using a laser-coupled optical fiber in conjunction with a recording microelectrode, we showed that activation of excitatory neurons resulted in well-timed excitatory and suppressive influences on neocortical neural networks. ChR2 was safely expressed, and could mediate optical neuromodulation, in primate neocortex over many months. These findings highlight a methodology for investigating the causal role of specific cell types in nonhuman primate neural computation, cognition, and behavior, and open up the possibility of a new generation of ultraprecise neurological and psychiatric therapeutics via cell-type-specific optical neural control prosthetics.Helen Hay Whitney Foundation (Fellowship)National Institutes of Health (U.S.) (NIH-EY002621-31)McGovern Institute for Brain Research at MIT (Neurotechnology Award)National Institutes of Health (U.S.) (Grant NIH-EY12848)National Institutes of Health (U.S.) (Grant NIH-EY017292)National Institutes of Health (U.S.) (NIH Director's New Innovator Award (DP2 OD002002-01))Brain & Behavior Research FoundationUnited States. Dept. of DefenseNational Science Foundation (U.S.)Alfred P. Sloan FoundationDr. Gerald Burnett and Marjorie BurnettSFN Research Award for Innovation in NeuroscienceMassachusetts Institute of Technology. Media LaboratoryBenesse FoundationWallace H. Coulter Foundatio

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3–4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Isolation and Mutagenesis of a Capsule-Like Complex (CLC) from Francisella tularensis, and Contribution of the CLC to F. tularensis Virulence in Mice

BACKGROUND: Francisella tularensis is a category-A select agent and is responsible for tularemia in humans and animals. The surface components of F. tularensis that contribute to virulence are not well characterized. An electron-dense capsule has been postulated to be present around F. tularensis based primarily on electron microscopy, but this specific antigen has not been isolated or characterized. METHODS AND FINDINGS: A capsule-like complex (CLC) was effectively extracted from the cell surface of an F. tularensis live vaccine strain (LVS) lacking O-antigen with 0.5% phenol after 10 passages in defined medium broth and growth on defined medium agar for 5 days at 32°C in 7% CO₂. The large molecular size CLC was extracted by enzyme digestion, ethanol precipitation, and ultracentrifugation, and consisted of glucose, galactose, mannose, and Proteinase K-resistant protein. Quantitative reverse transcriptase PCR showed that expression of genes in a putative polysaccharide locus in the LVS genome (FTL_1432 through FTL_1421) was upregulated when CLC expression was enhanced. Open reading frames FTL_1423 and FLT_1422, which have homology to genes encoding for glycosyl transferases, were deleted by allelic exchange, and the resulting mutant after passage in broth (LVSΔ1423/1422_P10) lacked most or all of the CLC, as determined by electron microscopy, and CLC isolation and analysis. Complementation of LVSΔ1423/1422 and subsequent passage in broth restored CLC expression. LVSΔ1423/1422_P10 was attenuated in BALB/c mice inoculated intranasally (IN) and intraperitoneally with greater than 80 times and 270 times the LVS LD₅₀, respectively. Following immunization, mice challenged IN with over 700 times the LD₅₀ of LVS remained healthy and asymptomatic. CONCLUSIONS: Our results indicated that the CLC may be a glycoprotein, FTL_1422 and -FTL_1423 were involved in CLC biosynthesis, the CLC contributed to the virulence of F. tularensis LVS, and a CLC-deficient mutant of LVS can protect mice against challenge with the parent strain