Monster Talk

The child perspectives in "Monster Talk," "High Stakes on the Mississippi Racino," and "Where the Weird Comes From" are narrated through either the close third or first person point of view. These children encounter terribly real events that are beyond their full comprehension and thus narrated through a fantastical lens in an attempt to explain their experiences with adult mental illness, fundamentalism, and addiction. "A Sad Day at the Glitter Factory," "Worldsick in the Animal Garden," and "The Company We Keep" focus on how characters are affected by, and interact with, their settings. These pieces explore the narratives that result from direct encounters with their surrounding environment. Situations such as economic depression, homelessness, and large disasters caused by human error occur within these settings. The telling is the characters' innate response to their existence that is inevitably influenced by these worlds and it is how they compose personal identity and significance

A Magnetic Bead-Based Sensor for the Quantification of Multiple Prostate Cancer Biomarkers.

Novel biomarker assays and upgraded analytical tools are urgently needed to accurately discriminate benign prostatic hypertrophy (BPH) from prostate cancer (CaP). To address this unmet clinical need, we report a piezeoelectric/magnetic bead-based assay to quantitate prostate specific antigen (PSA; free and total), prostatic acid phosphatase, carbonic anhydrase 1 (CA1), osteonectin, IL-6 soluble receptor (IL-6sr), and spondin-2. We used the sensor to measure these seven proteins in serum samples from 120 benign prostate hypertrophy patients and 100 Gleason score 6 and 7 CaP using serum samples previously collected and banked. The results were analyzed with receiver operator characteristic curve analysis. There were significant differences between BPH and CaP patients in the PSA, CA1, and spondin-2 assays. The highest AUC discrimination was achieved with a spondin-2 OR free/total PSA operation--the area under the curve was 0.84 with a p value below 10(-6). Some of these data seem to contradict previous reports and highlight the importance of sample selection and proper assay building in the development of biomarker measurement schemes. This bead-based system offers important advantages in assay building including low cost, high throughput, and rapid identification of an optimal matched antibody pair

Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer.

The introduction of serum Prostate Specific Antigen (PSA) testing nearly 30 years ago has been associated with a significant shift towards localized disease and decreased deaths due to prostate cancer. Recognition that PSA testing has caused over diagnosis and over treatment of prostate cancer has generated considerable controversy over its value, and has spurred efforts to identify prognostic biomarkers to distinguish patients who need treatment from those that can be observed. Recent studies show that cancer is heterogeneous and forms a hierarchy of tumor cell populations. We developed a method of identifying prostate cancer differentiation states related to androgen signaling using Boolean logic. Using gene expression data, we identified two markers, CD38 and ARG2, that group prostate cancer into three differentiation states. Cancers with CD38-, ARG2- expression patterns, corresponding to an undifferentiated state, had significantly lower 10-year recurrence-free survival compared to the most differentiated group (CD38+ARG2+). We carried out immunohistochemical (IHC) staining for these two markers in a single institution (Stanford; n = 234) and multi-institution (Canary; n = 1326) cohorts. IHC staining for CD38 and ARG2 in the Stanford cohort demonstrated that combined expression of CD38 and ARG2 was prognostic. In the Canary cohort, low CD38 protein expression by IHC was significantly associated with recurrence-free survival (RFS), seminal vesicle invasion (SVI), extra-capsular extension (ECE) in univariable analysis. In multivariable analysis, ARG2 and CD38 IHC staining results were not independently associated with RFS, overall survival, or disease-specific survival after adjusting for other factors including SVI, ECE, Gleason score, pre-operative PSA, and surgical margins

On the flexibility of the design of Multiple Try Metropolis schemes

The Multiple Try Metropolis (MTM) method is a generalization of the classical Metropolis-Hastings algorithm in which the next state of the chain is chosen among a set of samples, according to normalized weights. In the literature, several extensions have been proposed. In this work, we show and remark upon the flexibility of the design of MTM-type methods, fulfilling the detailed balance condition. We discuss several possibilities and show different numerical results

Perspectives and Forecasts

As the twenty-first century approaches it is accompanied by dramatic changes for the South. Southerners have been inundated with demographic, technological, and social developments which have exercised and will continue to effect dramatic changes in the traditional southern life-style. Once sleeping villages have become busy cities complete with shopping malls and burgeoning industry. All white public schools, businesses, and even churches have yielded to pressures for social equality and racial integration. An equable climate and multitudinous recreational and retirement opportunities have magnetized millions of Americans from the Northeast and Midwest, luring them to the Southland. All of these developments will, or at least should have far-reaching implications for southern archives and professional archivists for years to come

Real-Time Measurements of Engine-Out Trace Elements: Application of a Novel Soot Particle Aerosol Mass Spectrometer for Emissions Characterization

Lubricant-derived trace element emissions are the largest contributors to the accumulation of incombustible ash in diesel particulate filters (DPF), eventually leading to filter plugging and an increase in engine fuel consumption. Particulate trace element emissions also pose adverse health effects and are the focus of increasingly stringent air quality regulations. To date, the rates and physical and chemical properties of lubricant-derived additive emissions are not well characterized, largely due to the difficulties associated with conducting the measurements. This work investigated the potential for conducting real-time measurements of lubricant-derived particle emissions. The experiment used the Soot Particle Aerosol Mass Spectrometer (SP-AMS) developed by Aerodyne Research to measure the size, mass and composition of submicron particles in the exhaust. Results confirm the ability of the SP-AMS to measure engine-out emissions of calcium, zinc, magnesium, phosphorous, and sulfur. Further, emissions of previously difficult to detect elements, such as boron, and low-level engine wear metals, such as lead, were also measured. This paper provides an overview of the results obtained with the SP-AMS, and demonstrates the utility of applying real-time techniques to engine-out and tailpipe-out trace element emissions. Application of the SP-AMS for engine exhaust characterization followed a two-part approach: (1) measurement validation, and (2) measurement of engine-out exhaust. Measurement validation utilized a diesel burner with precise control of lubricant consumption. Results showed a good correlation between CJ-4 oil consumption and measured levels of lubricant-derived trace elements in the particle phase. Following measurement validation, the SP-AMS measured engine-out emissions from a medium-duty diesel engine, operated over a standard speed/load matrix. This work demonstrates the utility of state-of-the-art online techniques (such as the SP-AMS) to measure engine-out emissions, including trace species derived from lubricant additives. Results help optimize the combined engine-lubricant-aftertreatment system and provide a real-time characterization of emissions. As regulations become more stringent and emission controls more complex, advanced measurement techniques with high sensitivity and fast time response will become an increasingly important part of engine characterization studies.United States. Environmental Protection Agency (Grant RD834560

A Sensitive Branched DNA HIV-1 Signal Amplification Viral Load Assay with Single Day Turnaround

Branched DNA (bDNA) is a signal amplification technology used in clinical and research laboratories to quantitatively detect nucleic acids. An overnight incubation is a significant drawback of highly sensitive bDNA assays. The VERSANT® HIV-1 RNA 3.0 Assay (bDNA) (“Versant Assay”) currently used in clinical laboratories was modified to allow shorter target incubation, enabling the viral load assay to be run in a single day. To dramatically reduce the target incubation from 16–18 h to 2.5 h, composition of only the “Lysis Diluent” solution was modified. Nucleic acid probes in the assay were unchanged. Performance of the modified assay (assay in development; not commercially available) was evaluated and compared to the Versant Assay. Dilution series replicates (>950 results) were used to demonstrate that analytical sensitivity, linearity, accuracy, and precision for the shorter modified assay are comparable to the Versant Assay. HIV RNA-positive clinical specimens (n = 135) showed no significant difference in quantification between the modified assay and the Versant Assay. Equivalent relative quantification of samples of eight genotypes was demonstrated for the two assays. Elevated levels of several potentially interfering endogenous substances had no effect on quantification or specificity of the modified assay. The modified assay with drastically improved turnaround time demonstrates the viability of signal-amplifying technology, such as bDNA, as an alternative to the PCR-based assays dominating viral load monitoring in clinical laboratories. Highly sensitive bDNA assays with a single day turnaround may be ideal for laboratories with especially stringent cost, contamination, or reliability requirements

The molecular basis for peptide repertoire selection in the human leukocyte antigen (HLA) C*06:02 molecule

Human leukocyte antigen (HLA)-C*06:02 is identified as the allele associated with the highest risk for the development of the autoimmune skin disease psoriasis. However, the diversity and mode of peptide presentation by the HLA-C*06:02 molecule remains unclear. Here, we describe the endogenous peptide repertoire of ∼3,000 sequences for HLA-C*06:02 that defines the peptide-binding motif for this HLA allomorph. We found that HLA-C*06:02 predominantly presents nonamer peptides with dominant arginine anchors at the P2 and P7 positions and a preference for small hydrophobic residues at the C terminus (PΩ). To determine the structural basis of this selectivity, we determined crystal structures of HLA-C*06:02 in complex with two self-peptides (ARTELYRSL and ARFNDLRFV) and an analogue of a melanocyte autoantigen (ADAMTSL5, VRSRR-abu-LRL) implicated in psoriasis. These structures revealed that HLA-C*06:02 possesses a deep peptide-binding groove comprising two electronegative B- and E-pockets that coincide with the preference for P2 and P7 arginine anchors. The ADAMTSL5 autoantigen possessed a P7-Leu instead of the P7-Arg residue, but nevertheless was accommodated within the HLA-C*06:02 antigen-binding cleft. Collectively, our results provide the structural basis for understanding peptide repertoire selection in HLA-C*06:02

Predicting functional responses in agro-ecosystems from animal movement data to improve management of invasive pests

Functional responses describe how changing resource availability affects con- sumer resource use, thus providing a mechanistic approach to prediction of the invasibility and potential damage of invasive alien species (IAS). However, functional responses can be context dependent, varying with resource characteristics and availability, consumer attributes, and environmental variables. Identifying context dependencies can allow invasion and damage risk to be predicted across different ecoregions. Understanding how ecological factors shape the functional response in agro-ecosystems can improve predictions of hotspots of highest impact and inform strategies to mitigate damage across locations with varying crop types and avail- ability. We linked heterogeneous movement data across different agro-ecosystems to predict ecologically driven variability in the functional responses. We applied our approach to wild pigs (Sus scrofa), one of the most successful and detrimental IAS worldwide where agricultural resource depredation is an important driver of spread and establishment. We used continental- scale movement data within agro-ecosystems to quantify the functional response of agricul- tural resources relative to availability of crops and natural forage. We hypothesized that wild pigs would selectively use crops more often when natural forage resources were low. We also examined how individual attributes such as sex, crop type, and resource stimulus such as dis- tance to crops altered the magnitude of the functional response. There was a strong agricul- tural functional response where crop use was an accelerating function of crop availability at low density (Type III) and was highly context dependent. As hypothesized, there was a reduced response of crop use with increasing crop availability when non-agricultural resources were more available, emphasizing that crop damage levels are likely to be highly heterogeneous depending on surrounding natural resources and temporal availability of crops. We found sig- nificant effects of crop type and sex, with males spending 20% more time and visiting crops 58% more often than females, and both sexes showing different functional responses depend- ing on crop type. Our application demonstrates how commonly collected animal movement data can be used to understand context dependencies in resource use to improve our under- standing of pest foraging behavior, with implications for prioritizing spatiotemporal hotspots of potential economic loss in agro-ecosystems

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology