The Hepatitis C Virus (HCV) non-structural 5A protein (NS5A) has been studied for its ability to increase viral replication rates by repressing the host cell antiviral response and deregulating the host cell-cycle. Recent research conducted with NS5A mutants derived from the HCV replicon system demonstrated NS5A's capacity to repress activation of the IFN-beta promoter. Using luciferase assays, I compared the suppression capabilities of the NS5A mutants 10A and H27 with WT NS5A, revealing that WT NS5A suppresses the IFN-beta promoter more similar to the NS5A 10A mutant than the H27 mutant. I then used cell death assays to demonstrate NS5A's ability to block etoposide-induced cell death. To identify the mechanism by which NS5A is blocking cell death, I used cell death assays comparing cells expressing NS5A with cells lacking expression of the tumor-suppressor protein PKR, revealing that NS5A is must block cell death through interactions with a protein(s) other than PKR.

The focus of this study was to identify the phenotype and genotype of three mutants of the green alga Chlamydomonas reinhardtii. These three mutants, all of the mating type plus, were created by random insertional mutagenesis, and subsequently screened for their inability to form zygotes when mixed with mating type minus gametes. To characterize individual phenotypes, the mutants were observed at each individual stage of the fertilization process, from agglutination through mating structure fusion and zygote formation. All three mutants showed normal progression of fertilization but failed to form fertilization tubules. Following phenotypic characterization, each mutant was subject to TAIL-PCR and DNA sequencing to determine the location of the insert. The location of the insert was determined in two of the three mutants. One mutant was defective in the actin-encoding gene (ida5) while the second was a possible insertion into a portion of mitochondrial DNA.

Neurogenesis is well known to occur in the dentate gyrus of the hippocampus throughout adulthood, but the function of these new neurons is not fully understood. We performed a two-by-two experiment to test if these new neurons play a role in learning and memory. The mice were placed in either an enriched environment cage to increase neurogenesis, or a normal cage. We used a transgenic mouse with the ability to knock out neurogenesis using the antiviral drug ganciclovir, and half these mice were given ganciclovir while the other half were given saline. We tested the relationship between the number of new neurons in the dentate gyrus and with performance on behavioral and learning tasks. These behavioral tasks tested motor ability, anxiousness, spatial memory and hippocampus-dependent learning ability. We then compared the performance on these tests across all groups. Our findings show that there is a trend between number of new neurons and hippocampus learning ability.

Repeated observations of forest recovery using permanent plots allow scientists to map pathways of primary succession at the community level. This study continued the documentation of changes in forest composition on the Devastated Area in Lassen Volcanic National Park (LVNP) by re-sampling 34 randomly selected, permanent, 100-m2 plots first established and measured in 1988 (Kroh et al., 2000) in the Devastated Area. GPS coordinates and canopy closure of each plot were recorded. All living trees ≥ 0.10m tall were identified to species, and measured for height and diameter at breast height (DBH) in July of 2008. Pinus contorta, Abies magnifica and Pinus monticola were the dominant species on the Devastated Area. From 1988 to 2008, the mean height of trees per plot increased 73%, total mean basal area per plot increased 147%, and the mean density per plot increased by 19.9%. Despite large increases in basal area and height, full canopy closure has not occurred for most of the forest (median = 67%), indicating primary succession is still driven by abiotic factors. Comparison of the 2008 data to a similar age P. contorta stand on richer soils suggested that an additional 56 years may be required to reach a similar canopy closure of 91% and the onset of self-thinning due to biotic interactions.

The preparative and derivative chemistry of organoborane compounds that contain silicon-nitrogen functional groups is both diverse and synthetically useful. The wide variety of reactions that can occur at boron, in combination with facile cleavage of the Si-N bond, makes them potential precursors to polymeric B-N systems. We report here on the synthesis, characterization, and reactivity of three representative examples of the title systems of general types 1 and 2. Some of these systems are being studied as the precursors to new types of inorganic-organic hybrid polymers and/or novel ring systems.

Si nanowires (SiNWs) have been the focus of intense interest due to their potential applications in the field of nanophotonics, biological/chemical sensors, and molecular electronics. In more recent examples, impressive advances have been recognized in sensing events with single viral particles and communication with individual neurons. While much of these gains have explored the wires' semiconducting relevance to information storage or sensing events, it is perceived that semiconductor nanowires should also be considered for roles in active and selective therapeutic responses in diseased or injured tissue. Nanostructured silicon's utility as a biomaterial has been greatly amplified by reports of facile calcium phosphate growth on the surface of porous Si (PSi) in the presence or absence of electrical bias, suggesting that silicon itself could be an important bioactive material. More recently it has been demonstrated that SiNWs could not only affect cell adhesion and spreading of human hepatic cells, but also support the differentiation of osteoblasts. Previous work from our laboratories demonstrated the ability of SiNWs to facilitate the growth of uniform synthetic bone coatings along their surface. A preliminary cytocompatibility evaluation showed that SiNWs support the facile proliferation of fibroblast cells in their presence. One perceived advantage in the possible use of nanowires in drug delivery applications lies not only with the diverse surface functionalities that are possible with this vector but also with the density of such moieties. SiNWs possess a unique combination of biocompatibility and semiconducting properties that enable them to be easily functionalized with suitable surface species and therefore providing favorable environment for biological systems. When used as a drug delivery vehicle, their size may enable them to penetrate tumors due to the enhanced permeability and retention effect, and the high surface-to-volume ratio of SiNWs can contribute to a more specific drug loading with lower overall dose and reduced toxicity. In this work, a detailed study on the calcification behavior of SiNWs under various surface treatments is presented, as well as the fabrication of SiNW/polycaprolactone composites with a variety of surface topographies. Preliminary cytocompatibility assessments of these composites (with selected surface functionalization) in the presence of mouse stromal cells were performed. In addition, selected functionalization of SiNWs and PSi, making them suitable as delivery vehicles for Boron Neutron Capture Therapy, was investigated.

A highly reproducible method of producing SiC nanowires on a large scale is presented, and the average size of SiC nanowires was 30 nm. XRD revealed that the molar yield increased linearly with time. TEM showed a distribution of nanowire sizes that shifted towards larger diameters as sintering time increased. It is known that vapor-liquid-solid reactions involving a metal catalyst play a role in their formation, and there is further evidence that a vapor-solid mechanism contributes as well. The elastic properties of the following SiC morphologies were explored with pressure applied via a diamond anvil cell: 20 nm grains, 50 nm grains, 130 nm grains, and 30 nm nanowires The bulk modulus of nanowires increased by 8%, while that of 20 nm grains increased 30% in comparison to bulk material. The increased bulk modulus is explained by the core-shell model, where nanoparticles possess one or more distinct regions near the surface with identical crystal symmetry but different interatomic distances. Defects may also affect the bulk modulus, especially in the heavily faulted nanowires. As seen by TEM, planar faults were abundant, and their quantity decreased with decreasing diameter. The extended Convolutional Multiple Whole Profile (eCMWP) analysis was employed to quantitate the defects by XRD. This analysis concluded that twins are the most frequently occurring planar fault with a 2.20% probability of formation, which corresponds to a defect spacing of 38 nm. SiC nanowires are formed with an amorphous outer layer a few nanometers deep. It was concluded that the layer consisted mainly of amorphous SiC, but EDS confirmed that this structure was rich in oxygen. FTIR confirmed the presence of Si-O bands which increased in population with thermal treatment. The surface of SiC nanowires was modified by etching in HF and HNO3 acids. Silica bands were reduced and functional groups appeared after treatment. XRD found that grain size increased by 186% and dislocations decreased by 91% with treatment by nitric acid. It is proposed that modification of the surface leads to a reduction of surface stresses, thereby increasing the apparent grain size and reducing dislocations.

The present experiments were designed to determine whether bilateral electrolytic lesions on three prefrontal areas, anterior cingulate cortex (ACC), ventrolateral orbital cortex (VLO), and the medial prefrontal cortex (mPFC), modulate performance during reward downshift. ACC lesions retarded the recovery from a type of reward downshift, consummatory successive negative contrast (cSNC). VLO lesions had a small effect, in that they decreased cSNC during the late part of the downshift trial. There was no evidence that mPFC lesions played a role on cSNC, although they disrupted consummatory behavior and sucrose preference. Further testing showed that VLO lesions did not have effects on sucrose preference, but affected autoshaping acquisition under partial reinforcement. The present experiments, together with previous research, suggest that the ACC and the insular cortex are critical areas within the prefrontal cortex for the control of the response to and the recovery from cSNC.

This study explores effects of different types of institutionalization (cradle, maternity wards, orphanages) and foster parenting on Romanian foster children (ages 7 - 14; n = 68). Instruments used were Romanian language version of the Child Behavior Checklist (CBCL/6-18) and Teacher Report Form. Based on teacher reports, children from orphanages had significantly more problems than children in maternity and/or cradle group in the categories of Social Problems, Inattention, Rule-Breaking Behavior, and Externalizing subscales, as well as Total Problems scale. Behavioral problems increased as number of foster placements increased. Based on these findings, orphanages still provided the least beneficial environment for optimal development when compared with other types of institutions or foster care.

Individual outcomes in therapeutic community (TC) models of substance abuse treatment have been linked to a variety of psychosocial characteristics. However, questions surrounding the impact of asocial functioning on group process in a TC setting remain relatively unexplored. To investigate this relationship, a primary study goal was to develop and test an instrument for measuring cohesiveness, a key mechanism which facilities group process. The aim was to obtain participant ratings of cohesiveness for a therapeutic session. A second study goal was to examine how high asocial functioning impacts treatment for others by examining the primary treatment agent (i.e., group) and therapeutic factors (e.g., cohesiveness) which facilitate group process. For this aim, a group composite variable was created on the basis of the asocial characteristics of the group membership. The study design provided a framework for investigation of group-level effects that are specific to client-level treatment process within a therapeutic session. The results of analyses conducted with data from a sample of adult probationers demonstrated that the TCU Group Session Evaluation is a clinically useful, psychometrically sound instrument that captures dimensions of working and bonding which are associated with cohesiveness. However, the results of multilevel analysis did not support a relationship between client psychosocial functioning and group process.