Antibiotic Resistance and Substrate Utilization by Bacteria Affi liated with Cave Streams at Diff erent Levels of Mammoth Cave

Located in south-central Kentucky, Mammoth Cave is one of the most unique National Parks in the United States. The surface landscape includes complex relationships between the flora and fauna along with human influences. However, the primary ecological focus is concealed below ground. Over four-hundred miles of cave passages, created by fl owing groundwater over millions of years, host a variety of macro and micro organisms. The Green River has cut into the limestone formation over geologic time, creating a complex network of passages that are stacked, one below the other, with the newer levels of cave lying near the bottom. Palmer (2007, 1987) describes 4 main levels of cave passages in the Mammoth Cave system. A detailed discussion of the geology and conditions that formed the cave levels can be found in several reports (Palmer, 1987; Palmer 1989; White and White, 1989; Granger, et al, 2001). Precipitation continues to provide water that traverses from the surface, through the unsaturated vadose levels of the cave, and down to the water table in the lower level. Water enters the cave system through direct recharge at sinkholes and through diff use percolation. The rapid infiltration of stormwater often exceeds the carrying capacity of the upper cave passages and excess water is pushed into void pore-spaces near the top of bedrock. This stored water is slowly released and provides base-fl ow to cave streams that replenish the pools and streams in the lowest level of the cave (Ryan and Meimen, 1996). These perennial cave streams carry many of the organic compounds that provide energy to the cave ecosystem (Barr, 1976)

The Longest Words Using the Fewest Letters

An essay about metric entropy within the English language and examples of the longest words using the fewest letters

Voreloxin Is an Anticancer Quinolone Derivative that Intercalates DNA and Poisons Topoisomerase II

Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research.Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more potent.As a first-in-class anticancer quinolone derivative, voreloxin is a toposiomerase II-targeting agent with a unique mechanistic signature. A detailed understanding of voreloxin's molecular mechanism, in combination with its evolving clinical profile, may advance our understanding of structure-activity relationships to develop safer and more effective topoisomerase II-targeted therapies for the treatment of cancer

ADAPTATIONS OF INDIGENOUS BACTERIA TO FUEL CONTAMINATION IN KARST AQUIFERS IN SOUTH-CENTRAL KENTUCKY

Abstract: The karst aquifer systems in southern Kentucky can be dynamic and quick to change. Microorganisms that live in these unpredictable aquifers are constantly faced with environmental changes. Their survival depends upon adaptations to changes in water chemistry, taking advantage of positive stimuli and avoiding negative environmental conditions. The U.S. Geological Survey conducted a study in 2001 to determine the capability of bacteria to adapt in two distinct regions of water quality in a karst aquifer, an area of clean, oxygenated groundwater and an area where the groundwater was oxygen depleted and contaminated by jet fuel. Water samples containing bacteria were collected from one clean well and two jet fuel contaminated wells in a conduit-dominated karst aquifer. Bacterial concentrations, enumerated through direct count, ranged from 500,000 to 2.7 million bacteria per mL in the clean portion of the aquifer, and 200,000 to 3.2 million bacteria per mL in the contaminated portion of the aquifer over a twelve month period. Bacteria from the clean well ranged in size from 0.2 to 2.5 mm, whereas bacteria from one fuel-contaminated well were generally larger, ranging in size from 0.2 to 3.9 mm. Also, bacteria collected from the clean well had a higher density and, consequently, were more inclined to sink than bacteria collected from contaminated wells. Bacteria collected from the clean portion of the karst aquifer were predominantly (,95%) Gram-negative and more likely to have flagella present than bacteria collected from the contaminated wells, which included a substantial fraction (,30%) of Gram-positive varieties. The ability of the bacteria from the clean portion of the karst aquifer to biodegrade benzene and toluene was studied under aerobic and anaerobic conditions in laboratory microcosms. The rate of fuel biodegradation in laboratory studies was approximately 50 times faster under aerobic conditions as compared to anaerobic, sulfur-reducing conditions. The optimum pH for fuel biodegradation ranged from 6 to 7. These findings suggest that bacteria have adapted to water-saturated karst systems with a variety of active and passive transport mechanisms

Neuromagnetic Index of Hemispheric Asymmetry Prognosticating the Outcome of Sudden Hearing Loss

The longitudinal relationship between central plastic changes and clinical presentations of peripheral hearing impairment remains unknown. Previously, we reported a unique plastic pattern of “healthy-side dominance” in acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). This study aimed to explore whether such hemispheric asymmetry bears any prognostic relevance to ISSNHL along the disease course. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole amplitude and latency of N100m to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at two stages: initial and fixed stage (1 month later). Dynamics/Prognostication of hemispheric asymmetry were assessed by the interplay between hearing level/hearing gain and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m amplitude was observed in ISSNHL initially. The pattern changed with disease process. There is a strong correlation between the hearing level at the fixed stage and initial I/Camplitude on affected-ear stimulation in ISSNHL. The optimal cut-off value with the best prognostication effect for the hearing improvement at the fixed stage was an initial I/Clatency on affected-ear stimulation of 1.34 (between subgroups of complete and partial recovery) and an initial I/Clatency on healthy-ear stimulation of 0.76 (between subgroups of partial and no recovery), respectively. This study suggested that a dynamic process of central auditory plasticity can be induced by peripheral lesions. The hemispheric asymmetry at the initial stage bears an excellent prognostic potential for the treatment outcomes and hearing level at the fixed stage in ISSNHL. Our study demonstrated that such brain signature of central auditory plasticity in terms of both N100m latency and amplitude at defined time can serve as a prognostication predictor for ISSNHL. Further studies are needed to explore the long-term temporal scenario of auditory hemispheric asymmetry and to get better psychoacoustic correlates of pathological hemispheric asymmetry in ISSNHL

Landscape Impacts of Hydraulic Fracturing Development and Operations on Surface Water and Watersheds

Landscapes and watersheds are complex cultural biogeoclimatic systems that are not easily bounded, measured or understood by a single body of expertise. This makes it very challenging to locate and synthesize the best available science to identify what decision‐makers need to know about landscape and watershed impacts of hydraulic fracturing. ‘Landscape’ is not a physical object as much as it is a spatial context for multiple natural processes and human activities. As such, what decision‐makers need to know depends upon the specific locations and situational conditions in which hydraulic fracturing is operating. Fracking exists in landscape and watershed contexts that are highly variable at different scales and across different regions. There is a relatively high degree of certainty, within predictable engineered limits, about specific well‐based fracking operations. In contrast, there is a lot of uncertainty about how complex social ecological landscape and watershed systems function. Potential landscape and watershed impacts exist in the context of a complex and integrated system of spatial and functional inter‐connections and inter‐relationships and needs to be understood in this system context (Figure A‐1). We approached landscape and watershed impacts of hydraulic fracturing from a multi‐disciplinary social and natural science framework in order to try and capture this complexity. We emerged with common agreement around the difficulties presented by ‘silos’ of expertise when trying to deal with complex systems. The primary learning from our multidisciplinary approach is the need for greater institutional opportunities to integrate and coordinate a spectrum of approaches to address knowledge gaps in multiple system interactions across scales and involving system threshold effects that may be social in nature as well as biogeochemical

Drilling their own graves:How the European oil and gas supermajors avoid sustainability tensions through mythmaking

This study explores how paradoxical tensions between economic growth and environmental protection are avoided through organizational mythmaking. By examining the European oil and gas supermajors’ ‘‘CEOspeak’’ about climate change, we show how mythmaking facilitates the disregarding, diverting, and/or displacing of sustainability tensions. In doing so, our findings further illustrate how certain defensive responses are employed: (1) regression, or retreating to the comforts of past familiarities, (2) fantasy, or escaping the harsh reality that fossil fuels and climate change are indeed irreconcilable, and (3) projecting, or shifting blame to external actors for failing to address climate change. By highlighting the discursive effects of enacting these responses, we illustrate how the European oil and gas supermajors self-determine their inability to substantively address the complexities of climate change. We thus argue that defensive responses are not merely a form of mismanagement as the paradox and corporate sustainability literature commonly suggests, but a strategic resource that poses serious ethical concerns given the imminent danger of issues such as climate change

Influence of cloud and solar zenith angle on the diffuse solar erythemal UV short wavelength cut-offs and maximum spectral irradiance wavelengths

Cloud and the solar zenith angle (SZA) influence the magnitude of the diffuse erythemal UV. The aim of this research was to investigate the variation of the short wavelength cut-off and the maximum spectral irradiance wavelength for the diffuse spectral erythemal UV. The diffuse spectral solar UV was measured on a horizontal plane at ten minute intervals over a four month period with a UV spectroradiometer for the SZA range of 4.1 to 80 degrees. The short wavelength cut-offs and the maximum spectral irradiance wavelengths of the diffuse erythemal UV did not change significantly with cloud cover. The short wavelength cut-off was influenced by SZA and ranged from 290.5 ± 0.3 nm for the small SZA to 295.1 ± 0.7 nm for the larger SZA. The maximum spectral irradiance wavelength of the diffuse erythemal UV was not influenced significantly for SZA of 40 degrees or less. For higher SZA, the maximum spectral irradiance wavelength of the diffuse erythemal UV increased from 305 nm to 313.9 nm