cssi/SciSciGPT-SciSciNet huggingface dataset:
DATA LAKES: A PRIMER

A data lake is a centralized storage that allows you to store all your structured and unstructured data at any scale. It is a place to put all the data an organization wants to collect, store, and analyze and turn into insights ad actions. Once data is placed in the data lake, it is available for analysis by everyone in the organization. The purpose of this paper is to provide a brief introduction on data lakes.
Negotiating: How, When and Why

The subject of negotiating in the work place often conjures images of power struggles and leveraging to obtain more resources and/or support. In reality, negotiating is not an event, but rather a process. From the moment that each day begins, we must consider tradeoffs and negotiate where to invest our time. While contracts are important, contracts are only a small part of negotiating in the workplace. As individuals seek resources, higher pay, and greater job opportunities, it is important to realize that negotiating with supervisors begins when you are first hired, occurs each day, and continues until the employment ends. Negotiations occur constantly and planning is essential to maximize the outcome for both parties. Preparation with adjusted style and body language are essential for success. Using intuition alone is not as effective as a planned approach and negotiation is learned skill. Listening, building trust and compromise are the keys to success in most negotiations.
Copy Number Variation Detection Using Total Variation

Next-generation sequencing (NGS) technologies offer new opportunities for precise and accurate identification of genomic aberrations, including copy number variations (CNVs). For high-throughput NGS data, using depth of coverage has become a major approach to identify CNVs, especially for whole exome sequencing (WES) data. Due to the high level of noise and biases of read-count data and complexity of the WES data, existing CNV detection tools identify many false CNV segments. Besides, NGS generates a huge amount of data, requiring to use effective and efficient methods. In this work, we propose a novel segmentation algorithm based on the total variation approach to detect CNVs more precisely and efficiently using WES data. The proposed method also filters out outlier read-counts and identifies significant change points to reduce false positives. We used real and simulated data to evaluate the performance of the proposed method and compare its performance with those of other commonly used CNV detection methods. Using simulated and real data, we show that the proposed method outperforms the existing CNV detection methods in terms of accuracy and false discovery rate and has a faster runtime compared to the circular binary segmentation method.
Germaine Tillion: Observations of Algeria and Ravensbrück

This chapter features Germaine Tillion, a French ethnologist who studied rural Algeria and also participated in a French Resistance network under the aegis of the Musee de l’Homme. This study evokes Tillion’s autobiographical writings and scientific observations in relation to her experiences as a prisoner in the Ravensbruck concentration camp to show how she both “lived” and “wrote” resistance. Of particular interest here is her one literary masterpiece, Le Verfugbar aux enfers: Une operette a Ravensbruck (The Campworker Goes to Hell: An Operetta at Ravensbruck), a musical drama that she secretly composed during her imprisonment at Ravensbruck. Tillion draws from her extensive professional background in social anthropology and ethnography throughout this stark drama. Although her experiences as an ethnologist conducting field studies in rural Algeria and the toxic carceral environment of Ravensbruck were quite different, she deftly brings them into focus alongside each other in her scholarly and political writings.
Mapping the Autochthonous Indigenous Church: Toward a Decolonial History of Christianity in las Américas

Toward a decolonial history of Christianity in Latin America, this chapter identifies indigenous counterclaims to the Spanish narrative of spiritual conquest. In the course of the sixteenth century, indigenous communities across New Spain grafted the Christian church onto their own histories, cosmologies, and landscapes, creating the mythologies, structures, and institutions that ensured the church’s projection into the future. Through the emplacement of churches, these maps summon an idealized landscape that projects the church into an indigenous future. Accepting Christianity but refusing Spanish authority over Christian practice the version of indigenous Christianity depicted in the mapas is geographically bounded and defined in relation to indigenous structures of authority.
Flip This House!: Updating and Designing An Online First Year Seminar Module Series

Appalachian State University’s First Year Seminar Online Library Component is a set of information literacy modules designed to introduce students to university-level research. Originally deployed ...
Spin-lock relaxation rate dispersion reveals spatiotemporal changes associated with tubulointerstitial fibrosis in murine kidney.

Purpose To develop and evaluate a reliable non-invasive means for assessing the severity and progression of fibrosis in kidneys. We used spin-lock MR imaging with different locking fields to detect and characterize progressive renal fibrosis in an hHB-EGFTg/Tg mouse model. Methods Male hHB-EGFTg/Tg mice, a well-established model of progressive fibrosis, and age-matched normal wild type (WT) mice, were imaged at 7T at ages 5-7, 11-13, and 30-40 weeks. Spin-lock relaxation rates R1 ρ were measured at different locking fields (frequencies) and the resultant dispersion curves were fit to a model of exchanging water pools. The obtained MRI parameters were evaluated as potential indicators of tubulointerstitial fibrosis in kidney. Histological examinations of renal fibrosis were also carried out post-mortem after MRI. Results Histology detected extensive fibrosis in the hHB-EGFTg/Tg mice, in which collagen deposition and reductions in capillary density were observed in the fibrotic regions of kidneys. R2 and R1 ρ values at different spin-lock powers clearly dropped in the fibrotic region as fibrosis progressed. There was less variation in the asymptotic locking field relaxation rate R 1 ρ ∞ between the groups. The exchange parameter Sρ and the inflection frequency ωinfl changed by larger factors. Conclusion Both Sρ and ωinfl depend primarily on the average exchange rate between water and other chemically shifted resonances such as hydroxyls and amides. Spin-lock relaxation rate dispersion, rather than single measurements of relaxation rates, provides more comprehensive and specific information on spatiotemporal changes associated with tubulointerstitial fibrosis in murine kidney.
The role and function of IκKα/β in monocyte impairment

Following major trauma, sepsis or surgery, some patients exhibit an impaired monocyte inflammatory response that is characterized by a decreased response to a subsequent bacterial challenge. To investigate this poorly understood phenomenon, we adopted an in-vitro model of endotoxin tolerance utilising primary human CD14 + monocytes to focus on the effect of impairment on IκKα/β, a critical part of the NFκB pathway. Impaired monocytes had decreased IκKα mRNA and protein expression and decreased phosphorylation of the IκKα/β complex. The impaired monocyte secretome demonstrated a distinct cytokine/chemokine footprint from the naive monocyte, and that TNF-α was the most sensitive cytokine or chemokine in this setting of impairment. Inhibition of IκKα/β with a novel selective inhibitor reproduced the impaired monocyte phenotype with decreased production of TNF-α, IL-6, IL-12p70, IL-10, GM-CSF, VEGF, MIP-1β, TNF-β, IFN-α2 and IL-7 in response to an LPS challenge. Surgical patients with infection also exhibited an impaired monocyte phenotype and had decreased SITPEC, TAK1 and MEKK gene expression, which are important for IκKα/β activation. Our results emphasize that impaired monocyte function is, at least in part, related to dysregulated IκKα/β activation, and that IκKα/β is likely involved in mounting a sufficient monocyte inflammatory response. Future studies may wish to focus on adjuvant therapies that augment IκKα/β function to restore monocyte function in this clinically important problem.
Teaching Geriatrics and Transitions of Care to Internal Medicine Resident Physicians.

(1) Background: Internal medicine (IM) resident physicians need to be trained to care for older adults and transition them safely across care settings. Objective: The study purpose was to evaluate the efficacy of a curriculum in geriatrics assessment and communication skills for transitions of care (TOCs) to IM resident physicians. (2) Methods: IM residents rotated for 4 weeks on the geriatrics consult service at a large public teaching hospital, where they received didactic lectures and clinical experience in consultation and transitional care. The curriculum was designed to meet consensus guidelines for minimum geriatrics competencies expected of IM residents. Previously validated and published assessment tools were used for geriatrics knowledge and attitudes. Locally developed tools were used to directly observe and rate communication skills, and self-assess geriatrics assessment and health literacy skills. The curriculum was evaluated using a quasi-experimental, nonrandomized, single-group pre- and post-test observational design. Data on 31 subjects were collected over 18 months and analyzed using mixed-effects models. (3) Results: Average knowledge scores improved from 65% to 74% (Δ9%, 95% CI 4–13%, p < 0.001). Communication skills improved by an average of 1.15 points (95% CI 0.66–1.64, p < 0.001) on a 9-point scale. Attitudes did not change significantly. Self-rated confidence in geriatrics assessment and health literacy skills improved modestly. (4) Conclusions: The curriculum is effective in teaching basic geriatrics knowledge and communication skills, and increasing self-confidence in geriatrics assessment skills. In settings where an inpatient geriatrics consult service is feasible, the curriculum may be a model for combining geriatrics and TOC training.
A physical upper limit on the HI column density of gas clouds

An intriguing fact about cosmic gas clouds is that they all appear to have neutral (atomic) hydrogen column densities smaller than 10^{22} cm^{-2}. Observations of damped Ly-alpha (DLA) absorption systems further indicate that the maximum N(HI) decreases with increasing metallicity. It is generally assumed that this trend is due to a dust-induced selection bias: DLA systems with high N(HI) and high metallicity contain so much dust that the background QSO becomes too dim to be included in optically selected surveys. Here, it is argued that this explanation may not be viable. Instead, it is proposed that conversion to molecular hydrogen determines the maximum HI column density. Molecular hydrogen forms on the surface of dust grains and is destroyed by photodissociation. Therefore, the molecular fraction correlates with both the dust content and, because of self-shielding, the total hydrogen column density, and anticorrelates with the intensity of the incident UV radiation. It is shown that the first relation can account for the observed anticorrelation between the maximum N(HI) and metallicity.
Knowledge broker teachers and professional development

Like their counterparts in business, teachers who act as knowledge brokers play a key role in transferring and translating knowledge from those who have it to those who need it. This article report...
Clonal evolution in serially passaged Cryptococcus neoformans x deneoformans hybrids reveals a heterogenous landscape of mitotic recombination

Abstract Cryptococcus neoformans x deneoformans hybrids (also known as serotype AD hybrids) are basidiomycete yeasts that are common in a clinical setting. Like many hybrids, the AD hybrids are largely locked at the F1 stage and are mostly unable to undergo normal meiotic reproduction. However, these F1 hybrids, which display a high (∼10%) sequence divergence are known to genetically diversify through mitotic recombination and aneuploidy, and this diversification may be adaptive. In this study, we evolved a single AD hybrid genotype to six diverse environments by serial passaging and then used genome resequencing of evolved clones to determine evolutionary mechanisms of adaptation. The evolved clones generally increased fitness after passaging, accompanied by an average of 3.3 point mutations and 2.9 loss of heterozygosity (LOH) events per clone. LOH occurred through nondisjunction of chromosomes, crossing over consistent with break-induced replication, and gene conversion, in that order of prevalence. The breakpoints of these recombination events were significantly associated with regions of the genome with lower sequence divergence between the parents and clustered in subtelomeric regions, notably in regions that had undergone introgression between the two parental species. Parallel evolution was observed, particularly through repeated homozygosity via nondisjunction, yet there was little evidence of environment-specific parallel change for either LOH, aneuploidy, or mutations. These data show that AD hybrids have both a remarkable genomic plasticity and yet are challenged in the ability to recombine through sequence divergence and chromosomal rearrangements, a scenario likely limiting the precision of adaptive evolution to novel environments.
On the sparsity of fitness functions and implications for learning

Fitness functions map biological sequences to a scalar property of interest. Accurate estimation of these functions yields biological insight and sets the foundation for model-based sequence design. However, the amount of fitness data available to learn these functions is typically small relative to the large combinatorial space of sequences; characterizing how much data is needed for accurate estimation remains an open problem. There is a growing body of evidence demonstrating that empirical fitness functions display substantial sparsity when represented in terms of epistatic interactions. Moreover, the theory of Compressed Sensing provides scaling laws for the number of samples required to exactly recover a sparse function. Motivated by these results, we develop a framework to study the sparsity of fitness functions sampled from a generalization of the NK model, a widely-used random field model of fitness functions. In particular, we present results that allow us to test the effect of the Generalized NK (GNK) model9s interpretable parameters---sequence length, alphabet size, and assumed interactions between sequence positions---on the sparsity of fitness functions sampled from the model and, consequently, the number of measurements required to exactly recover these functions. We validate our framework by demonstrating that GNK models with parameters set according to structural considerations can be used to accurately approximate the number of samples required to recover two empirical protein fitness functions and an RNA fitness function. In addition, we show that these GNK models identify important higher-order epistatic interactions in the empirical fitness functions using only structural information.
Robust Receptive Vocabulary Instruction for Students With Significant Cognitive Disabilities Who Use AAC

Robust vocabulary instruction is an important part of comprehensive English language arts (ELA) instruction. Vocabulary instruction supports students in learning the meaning of words to build a rec...
Financial Literacy, Naive Diversification, and Security Selection

Low levels of financial literacy have been linked to costly errors in investing behavior. This paper examines the relationship between financial literacy and the two financial tasks of asset allocation and security selection in an online survey of college students. Results suggest that financial literacy can slightly attenuate the naive diversification bias and improve security selection decisions. The results support educational efforts to increase financial literacy to improve retirement savings and financial decisions.
The impacts of vehicle automation on transport-disadvantaged people

Abstract As an emerging technology, vehicle automation will have profound impacts on various aspects of society. Although recent studies have examined the impacts of the proliferation of vehicles with high/full-level automation, few have emphasized the implications for social equity. To better understand how autonomous vehicles (AVs) may influence equity, this study explores the potential influence of AVs on eight groups of transportation-disadvantaged people. Specifically, we synthesize prominent travel behaviors of the identified groups and explore possible impacts of AVs on these groups. We found that AVs tend to bring more benefits than harm to some people but may have mixed effects on others. Based on the findings, we provide policy recommendations for future policy decision-making, which will likely to play an essential role in maximizing AVs’ benefits and mitigating their challenges.
Fixed-window constant modulus algorithms: adaptive implementations

Adaptive implementations of two previously proposed block-iterative algorithms; referred to as fixed-window constant modulus algorithms (FWCMA), are developed. Their transient behavior, in relation to the delay at which the user sequence is recovered, is discussed and compared with other existing variations of CMA. The adaptive FWCMA-2 appears to be particularly promising, attaining convergence with little data. It retains the merits of its batch counterpart, namely, fast convergence, robustness to ill-conditioning, no required step-size tuning, and relatively low complexity. The built-in control over the converged delay translates into more reliable and predictable transient behavior. Equalizer calculation can be initiated from any initialization, and at any time instant, to attain convergence instantaneously without storing any received data. Thus, different initializations can be used to easily obtain multiple equalizers recovering the signal at different delays or recovering distinct users under a near-far simulation.
Electrostatic contribution of phosphorylation to the stability of the CREB-CBP activator-coactivator complex.

Electrostatic contribution of phosphorylation to the stability of the CREB–CBP activator–coactivator complex
Improving High-Resolution Weather Forecasts Using the Weather Research and Forecasting (WRF) Model with an Updated Kain–Fritsch Scheme

AbstractEfforts to improve the prediction accuracy of high-resolution (1–10 km) surface precipitation distribution and variability are of vital importance to local aspects of air pollution, wet deposition, and regional climate. However, precipitation biases and errors can occur at these spatial scales due to uncertainties in initial meteorological conditions and/or grid-scale cloud microphysics schemes. In particular, it is still unclear to what extent a subgrid-scale convection scheme could be modified to bring in scale awareness for improving high-resolution short-term precipitation forecasts in the WRF Model. To address these issues, the authors introduced scale-aware parameterized cloud dynamics for high-resolution forecasts by making several changes to the Kain–Fritsch (KF) convective parameterization scheme in the WRF Model. These changes include subgrid-scale cloud–radiation interactions, a dynamic adjustment time scale, impacts of cloud updraft mass fluxes on grid-scale vertical velocity, and lift...
The Übermensch meets the “One Best Way”

Purpose – The purpose of this paper is to shed light on the eugenic beliefs of behavioral geneticist Barbara S. Burks and scientific‐management pioneers B. Frank and Lillian M. Moeller Gilbreth.Design/methodology/approach – Drawing on personal communications with the Gilbreths' daughter, Ernestine Gilbreth Carey, and archival records, this paper clarifies the relationship between Barbara S. Burks and the Gilbreth family.Findings – This research establishes that the unnamed psychologist described in an unflattering manner in the best‐selling book on the Gilbreth family, Cheaper by the Dozen, was not Barbara S. Burks.Originality/value – Based on information that only Ernestine Gilbreth Carey could have provided, this paper sets the record straight regarding the Gilbreths' involvement with eugenicist Barbara S. Burks.
Affinity purifications of aldose reductase and xylitol dehydrogenase from the xylose-fermenting yeast Pachysolen tannophilus.

Although xylose is a major product of hydrolysis of lignocellulosic materials, few yeasts are able to convert it to ethanol. In Pachysolen tannophilus, one of the few xylose-fermenting yeasts found, aldose reductase and xylitol dehydrogenase were found to be key enzymes in the metabolic pathway for xylose fermentation. This paper presents a method for the rapid and simultaneous purification of both aldose reductase and xylitol dehydrogenase from P. tannophilus. Preliminary studies indicate that this method may be easily adapted to purify similar enzymes from other xylose-fermenting yeasts.
Bidirectionalization of polar promoters in plants

A typical eukaryotic promoter consists of a minimal promoter and other upstream cis elements. The minimal promoter is essentially a TATA box region where RNA polymerase II, TATA-binding protein (TBP), and TBP-associated factors (TAFs) bind to initiate transcription, but minimal promoters alone have no transcriptional activity. The cis elements, to which tissue-specific or development-specific transcription factors bind, individually or in combination, determine the spatio-temporal expression pattern of a promoter at the transcriptional level. The arrangement of upstream cis elements followed by a minimal promoter sets the polarity of the promoter. Promoters in plants that have been cloned and widely used for both basic research and biotechnological application are generally unidirectional, directing only one gene that has been fused at its 3' end (downstream). It is often necessary to introduce multiple genes into plants for metabolic engineering and trait stacking. It is also desirable to minimize or avoid repeated use of a single promoter that may cause transcriptional gene silencing. Here we describe a strategy to make polar promoters bidirectional so that one promoter can direct the expression of two genes, one on each end of the promoter.
On Time: An Empirical Analysis of U.S. Law School Admissions Deadlines

Setting an application deadline is an important decision for a law school admissions committee because the deadline partly determines the quantity and quality of applications that a law school receives. As such, information that would help an admissions committee set its deadline appropriately and strategically is valuable. The intention of this essay is to provide such information. To do so, we treat law school admissions as a market and set up an econometric model, which provides information on how various types of schools set their deadlines. From this, we interpret a number of strategies in which law schools seem to engage. We find that better law schools tend to set earlier deadlines, generally. However, we also find that the most elite schools tend to set later deadlines than the general model would predict while medium-quality law schools tend to set deadlines earlier than the general model would predict. We use economic theory to interpret these deviations from the general model as strategic signaling of quality to potential applicants. Furthermore, we find that some in-state tuition reciprocity agreements may significantly affect deadlines.
The atomic nucleus observed with electromagnetic probes

The basic formalism used when investigating nuclear structure via electron scattering is summarized. Two of the major themes that run through contemporary studies are emphasized: exploration of the extended sets of response functions that become accessible when one or more particles are detected in coincidence with the scattered electron and/or when polarization degrees of freedom are active. In contrast to previous decades when the focus was largely restricted to studies of unpolarized inclusive electron scattering, these have come into the mainstream of the field since modern experimental facilities are now able to address both themes.
THE AZTEC ATLATL IN THE BRITISH MUSEUM

The British Museum's Aztec atlatl is one of their most famous Mesoamerican objects, yet it has not been studied as a weapon in light of current knowledge of spear-throwers, and the details necessary to do so have not been published. Close examination and experimental replication shows that although it is ornately decorated, it is a serviceable spear-thrower. While evidence of actual use of this specimen is ambiguous, we can at least accept the form as an example of working weapons of Contact period Mesoamerica. The actual effects and circumstances of atlatl use against the Spanish and others are difficult to judge from surviving accounts. The iconography of the decoration, as in other instances, associated this atlatl with elite warfare and deities of war and sacrifice.
Metabolic Interconversions of Enzymes: Relation to the Hysteretic Response

I would like to thank the Organizers of this Symposium for inviting me to present some ideas on the concept of hysteresis. At first, it seemed to me that such a concept might be somewhat removed from the regulation of metabolic control by the enzymatically catalyzed interconversion of enzyme forms. However, I later realized that under some conditions one can apply the predictions of the hysteresis concept to the kind of interconvertible enzyme systems which are the topic of this Symposium. I appreciate the efforts of the Organizers for their round- about way of bringing this fact to my attention.
The Impact of the 5α-Reductase Inhibitors (5α-RIs) on Male Sexual Function and Psychological Well-Being

5α-Reductase inhibitors (5α-RIs) such as finasteride and dutasteride have proven useful in clinical management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and also in treatment of androgenetic alopecia (AGA). However, these drugs have serious and, in some patients, persistent or irreversible sexual side effects. These agents interfere with the biosynthesis and metabolism of neurosteroids and may adversely affect mood, stress, and anxiety and potentiate the onset of depression. Data from preclinical and clinical studies have provided substantial evidence that these agents cause loss or reduction of libido, increase the risk of erectile dysfunction and ejaculatory dysfunction, and may contribute to the onset of depression. It is imperative that clinicians give serious considerations to these adverse effects and their impact on patients’ health and engage their patients in an open and honest discussion regarding the potential harm of these agents prior to prescribing them.
Terabit/s data communication in distributed computer cluster networks

High performance computer network architectures with interactive multi-task programs require concurrent and real-time program execution, which is achieved via inter-processor ultra-high data links requiring massive data transfers over long links that only fiber can support. We present a new method for inter-computer communication, which is characterized by elastic ultrahigh bandwidth, long fiber links, and low cost. We examine network topologies and we study a cost-effective point-to-point link capable to transport Terabits per second by utilizing wavelength division multiplexing (WDM) technology. We model and simulate exemplary cases at different fiber lengths and data rates. Simulation results suggest exceptional performance over 100 km links without amplification and with data transfers at Tbit/s.
Performance analysis of MIMO systems with cochannel interference over Rayleigh fading channels

Relying on the Khatri distribution of the largest eigenvalue of certain quadratic forms in complex Gaussian vectors, we develop an analytical framework for the performance analysis of multiple-input-multiple output (MIMO) systems subject to cochannel interference and operating over Rayleigh fading channels. We consider interference limited systems in which the number of interferers exceeds or is equal to the number of receiving antenna elements and we present new closed-form expressions for the probability density function of the output signal-to-interference ratio and for the MIMO system outage probability. When applicable, these expressions are compared to the special case which dealt with the performance of single-input-multiple-output (SIMO) systems (see Shah, A. and Haimovich, A.M., IEEE Trans. Commun., vol.46, p.473-9, 1998). These analytical results are validated by Monte-Carlo simulations and as an illustration of the mathematical formalism some numerical examples for particular cases of interest are plotted and discussed. The results show that, given a fixed number of total antenna elements and cochannel interferers, (i) SIMO systems always outperform multiple-input-single-output systems and (ii) it is preferable to distribute the number of antenna elements evenly between the transmitter and the receiver for optimum performance.
Bacillus thuringiensis serovar. israelensis (ABG-6108) against chironomids and some nontarget aquatic invertebrates

Abstract A wettable powder formulation (ABG-6108) of Bacillus thuringiensis serovar. israelensis was tested against chironomid larvae in experimental ponds at 1, 2, 3, 4 and 10 kg/ha (0.25–2.5 ppm), and in a golf pond at 3 kg/ha (0.5 ppm). Significant reductions (18–88%) in populations of Chrinomini and Tanytarsini experimental ponds, and 27–65% reduction of midges in the golf pond occurred during the 4-week evaluation period. The highest dose in experimental ponds had no adverse effects on rotifers, Cyclops spp., Daphnia sp., ostracods, Baetis sp., corixids and notonectids, and Coleoptera. The nontarget invertebrates in the golf pond also remained unaffected.
Characterizing Heat Release Rates Using an Inverse Fire Modeling Technique

A ubiquitous source of uncertainty in fire modeling is specifying the proper heat release rate (HRR) for the fuel packages of interest. An inverse HRR calculation method is presented to determine an inverse HRR solution that satisfies measured temperature data. The methodology uses a predictor-corrected method and the Consolidated Model of Fire and Smoke Transport (CFAST) zone model to calculate hot gas layer (HGL) temperatures in single compartment configurations. The inverse method runs at super-real-time speeds while calculating an inverse HRR solution that reasonably matches the original HRR curve. Examples of the inverse method are demonstrated by using a multiple step HRR case, complex HRR curves, experimental temperature data with a constant HRR, and a case with an experimentally measured HRR. In principle, the methodology can be applied using any reasonably accurate fire model to invert for the HRR.
Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc.

In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD+-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Collectively, this study identifies a role for NAD+-dependent SIRT deacetylase activity in regulating the expression of mitochondrial steroidogenic P450.
Catabolism of epoxy fatty esters by the purified epoxide hydrolase from mouse and human liver

Epoxymethylsterate, 9,10- and 12,13-epoxymethyloleates, and a mixture of isomers of epoxymethylarachidonate and diepoxymethylstearate were synthesized, and their metabolic rates were measured using crude and purified cytosolic epoxide hydrolase. Hepatic epoxide hydrolase was purified from human samples and clofibrate-fed mice by affinity chromatography. The major metabolites under these conditions of all the epoxy fatty esters were their vicinal diols whose structures were confirmed by GC-MS. 12,13-Epoxymethyloleate was metabolized faster than 9,10-epoxymethyloleate and other epoxy fatty esters, but all substrates were turned over rapidly. This rapid turnover suggests that epoxy fatty acids may be endogenous substrates for the cytosolic epoxide hydrolase.
Determining the percentages of semi-conducting and metallic single-walled carbon nanotubes in bulk soot

Abstract A procedure is presented to determine the percentages of metallic and semi-conducting single-walled carbon nanotubes (SWCNTs) in as-produced soot synthesized by a cobalt/molybdenum-catalyzed chemical vapor deposition (CVD) process. The procedure involves the acquisition of UV–Vis–NIR absorption spectra of solvent-suspended soot samples, and the key aspect is the use of a physically-based subtraction of the π-plasmon absorbance from the overall absorbance to ensure that the percentage of semi-conducting SWCNTs is not overstated. The improvement in accuracy using the procedure is demonstrated using two lots of soot with different amounts of non-tubular carbon (NTC) contaminants. The semi-conducting SWCNT percentage of the soot containing low NTC levels was 82 ± 3%, and this mean was overestimated by 4% when the π-plasmon absorbance was not subtracted. The semi-conducting SWCNT percentage of the soot containing higher NTC levels was 76 ± 9%, and this mean was overestimated by 6% without subtraction of the π-plasmon absorbance.
Detection of m2 muscarinic acetylcholine receptor mRNA in human corpus cavernosum by in-situ hybridization

Relaxation and contraction of the smooth muscle of human corpus cavernosum (HCC) of the penis is essential for penile erection and detumescence. Relaxation of the smooth muscle is controlled, locally, by cholinergic, adrenergic and nonadrenergic, noncholinergic neurotransmitters as well as by the vascular endothelium, which lines the lacunar spaces and releases endothelium-derived relaxing factor. Cholinergic neurotransmitters are postulated to act on other neuroeffectors and on the endothelium rather than act directly on the trabecular smooth muscle. We use in-situ hybridization to determine the presence and distribution of muscarinic acetylcholine receptor (mAChR) subtype mRNA in HCC. First, we verified that the riboprobe used for in-situ hybridization is specific for m2 mAChR subtype using Chinese Hamster Ovary cells transfected with m2 mAChR subtype. Then, we validated that the tissue obtained from surgical specimens is adequate for in-situ hybridization. The data demonstrate that m2 mAChR subtype mRNA is expressed in HCC smooth muscle cells. m2 mAChR subtype mRNA expression is not detected in endothelium or nerves. It is possible that this receptor subtype plays a role in smooth muscle contraction.
The feasibility of on-chip interconnection using antennas

The feasibility of integrating antennas and required circuits to form wireless interconnects in foundry digital CMOS technologies has been demonstrated. The key challenges including the effects of metal structures associated with integrated circuits, heat removal, packaging, and interaction of transmitted and received signals with nearby circuits appear to be manageable. Besides, on-chip interconnection, this technology can potentially be applied for implementation of true single chip radio and radar, interchip communication systems, RFID tags and others.
Effects of prococene II on the nutritional physiology of last instar Heliothis zea larvae

When precocene II was fed to last instar larvae of Heliothis zea, it caused significant reductions in the calculated rate of growth, rate of nutrient assimilation, and conversion of ingested and digested food to body mass. No change in the rate of food consumption occurred but respiration was significantly higher. Transport of the nutrient [1-14C] linoleic acid across midgut tissue was hindered when larvae were fed precocence II. There was also a precocene-induced change in the apical (luminal) morphology of midgut cells, including absence of the glycocalyx and loss of the microvillar absorptive surface. The influence of precocene II on the midgut physiology and metabolic processes in last instar larvae of H. zea may account for the observed reduced growth and delayed development. © 1992 wiley-Liss, Inc.
A simple and accurate high-pass filter and spectrometer using Huygen's principle

We have developed a new type of high pass filter and a new type of spectrometer. These devices are currently under testing and have yielded good agreement with theory. These devices seem to be easier to use and appear to be more accurate than devices now used.
Variability in in situ shear strength of gassy muds

Torque measurements are made by divers with a vane apparatus to a sediment depth of 136 cm in the high-porosity, gassy sediments of Eckernforde Bay. Corrected shear strength values calculated from torque measurements are quite variable in the Eckernforde Bay sediments, varying from less than 0.5 kPa in the top 10 cm of sediment to 4–5 kPa at 136 cm sediment depth. Variability increases markedly below 60 cm sediment depth, probably because of the presence of methane gas bubbles within the sediment fabric.
Poster Abstract #4: Development of Long-Duration Accelerometry for Use in Clinical Trials of Essential Tremor

Background Essential tremor (ET) is a common movement disorder affecting 0.4% of the general population and 14% of people 65 years and older. Current therapies provide modest tremor suppression and are often accompanied by intolerable side effects. Key to the success of future studies is the development of objective biomarkers to assess tremor in a sensitive and unbiased manner. Numerous subjective and objective tremor measures are available, including laboratory-based accelerometry, electromyography, spirography, and surveys assessing quality of life or impact on activities of daily living. The utility of objective measures are limited by time and expense, and subjective measures lack sensitivity and rely heavily on standardization of ratings or patient responses. Furthermore, all these methods are temporally biased, in that they reflect only brief time intervals. We hypothesized that portable uniaxial monitoring devices could be used to reliably measure tremor over long durations in patients with ET. Methods The study population consisted of adults with ET who underwent an ethanol challenge to assess tremor response, prior to enrollment in a clinical trial at NIH. Wrist-based accelerometers were used (Cambridge Neurotechnology, Cambridge, UK) to record the intensity and duration of tremor and nontremor movements. We developed an algorithm to calculate a Tremor Severity Score (TSS) characterizing tremor patterns over extended time periods. To assess individual subject changes, we normalized the TSS at each timepoint by each subject's own baseline TSS. The primary outcome measures were TSS at baseline, 0–30, 30–60, and 60–90 minutes after ethanol challenge. Results Thirteen patients were included in the analysis. Mean percent reduction in tremors from baseline TSS was 165%, 408%, and 423% at 0–30, 30–60, and 60–90 minutes after ethanol challenge, respectively. A post hoc linear regression of the TSS total score and baseline TSS revealed high correlation ( R 2 = 0.77). Conclusions Our results show that the TSS, based on long-duration accelerometry data, provides a sensitive and reliable method for objectively measuring ET outcomes. This method could serve as a model for the development of low-cost, high-throughput clinical trials. Further work is needed to validate this method with tremor measures in current use.
Nonerosive reflux disease— current concepts and dilemmas

Nonerosive reflux disease is defined as the presence of typical symptoms of gastroesophageal reflux disease caused by intraesophageal acid in the absence of visible esophageal mucosal injury at endoscopy. Recent studies demonstrate that it is a chronic disease with a significant impact on quality of life, and it is very common in primary care settings. Treatment with acid inhibitory agents is effective, and proton pump inhibitors are the most effective form of therapy.
SNoW: Understanding the causes of strong, neutral, and weak face impostor pairs

The Strong, Neutral, or Weak Face Impostor Pairs problem was generated to explore the causes and impact of impostor face pairs that span varying strengths of scores. We develop three partitions within the impostor distribution for a given algorithm. The Strong partition contains image pairs that are easy to categorize as impostors. The Neutral partition contains image pairs that are less easily categorized as impostors. The Weak partition contains image pairs that are likely to cause false positives. Three algorithms, and the fusion of their scores, were used to analyze the performance of these three partitions using the same set of authentic scores employed in the Face Recognition Vendor Test (FRVT) 2006 Challenge Dataset. The results of these experiments provide evidence that varying degrees of impostor scores impact the overall performance and thus the underlying causes of weak impostor pairs are worthy of further exploration.
Development of a novel neuroprotective strategy: Combined treatment with hypothermia and valproic acid improves survival in hypoxic hippocampal cells

Background Therapeutic hypothermia and histone deacetylase inhibitors, such as valproic acid (VPA), independently have been shown to have neuroprotective properties in models of cerebral ischemic and traumatic brain injury. However, the depth of hypothermia and the dose of VPA needed to achieve the desired result are logistically challenging. It remains unknown whether these two promising strategies can be combined to yield synergistic results. We designed an experiment to answer this question by subjecting hippocampal-derived HT22 cells to severe hypoxia in vitro. Methods Mouse hippocampal HT22 cells were exposed to 200 μM cobalt chloride (CoCl 2 ), which created hypoxic conditions in vitro. Cells were incubated for 6 or 30 hours under the following conditions: (1) Dulbecco's Modified Eagle Medium; (2) 200 μM CoCl 2 ; (3) 200 μM CoCl 2 plus 1 mmol/L VPA; (4) 200 μM CoCl 2 plus 32°C hypothermia; and (5) 200 μM CoCl 2 plus both 1 mmol/L VPA and 32°C hypothermia. Cellular viability was evaluated by (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and lactate dehydrogenase release assays at 30 hours after treatment. Levels of acetylated histone H3, hypoxia-inducible factor-1α, phospho-GSK-3β, β-catenin, and high-mobility group box-1 were measured by Western blotting. Results High levels of acetylated histone H3 were detected in the VPA-treated cells. The release of lactate dehydrogenase was greatly suppressed after the combined hypothermia + VPA treatment (0.269 ± 0.003) versus VPA (0.836 ± 0.026) or hypothermia (0.451 ± 0.005) treatments alone ( n = 3, P = .0001). (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay showed that the number of viable cells was increased by 17.6 % when VPA and hypothermia were used in combination ( n = 5, P = .0001). Hypoxia-inducible factor-1α and phospho-GSK-3β expression were synergistically affected by the combination treatment, whereas high-mobility group box-1 was increased by VPA treatment, and inhibited by the hypothermia. Conclusion This is the first study to demonstrate that the neuroprotective effects of VPA and hypothermia are synergistic. This novel approach can be used to develop more effective therapies for the prevention of neuronal death.
Connections between 3′-end processing and DNA damage response

The cellular DNA damage response (DDR) involves changes in the functional and structural properties of a number of nuclear proteins, resulting in a coordinated control of gene expression and DNA repair. This response includes functional interactions of the DNA repair, transcription, and RNA processing machineries. Following DNA damage, cellular levels of polyadenylated transcripts are transiently decreased and normal recovery depends on transcription-coupled repair (TCR). In addition, DNA damage has gene-specific effects regulating the mRNA levels of factors involved in the DDR itself at different times after the damage. The 3'-end processing machinery, which is important in the regulation of mRNA stability, is involved in these general and gene-specific responses to DNA damage. The role of 3'-end processing in DDR supports the idea that the steady-state levels of different mRNAs change upon DNA-damaging conditions as a result of regulation of not only their biosynthesis but also their turnover. Here, we review the mechanistic connections between 3'-end processing and DDR, and discuss the implications of deregulation of this important step of mRNA maturation in the cellular recovery after DNA-damaging treatment. The relevance of these functional connections is illustrated by the increasing number of reports on this relatively unexplored field.
Nuclear suppressors define three factors that participate in both 5' and 3' end processing of mRNAs in Chlamydomonas chloroplasts.

Summary Chloroplast RNA processing and degradation are orchestrated by nucleus-encoded factors. Although several transcript-specific factors have been identified, those involved in global RNA metabolism have mostly remained elusive. Using Chlamydomonas reinhardtii, we have identified three pleiotropic nuclear mutations, mcd3, mcd4 and mcd5, which cause quantitative variation between polycistronic transcripts and accumulation of transcripts with novel 3′ ends. The mcd3, mcd4 and mcd5 mutants were initially isolated as photoautotrophic suppressors of the petD 5′ mutants LS2 and LS6, which harbour four nucleotide linker-scanning mutations near the 5′ end of the mature transcript. The LS mutants accumulate 1–3% of the wild-type (WT) petD mRNA level and no cytochrome b6/f complex subunit IV, which is the petD gene product and required for photosynthesis. Each suppressor restores approximately 15% of the WT petD mRNA and subunit IV levels. Genetic analysis showed mcd4 to be recessive, and suggested that MCD4 interacts with the petD mRNA stability factor MCD1. To assess the specificity of mcd3, mcd4 and mcd5, transcripts from 32 chloroplast genes were analysed by RNA filter hybridizations. mcd3 and mcd4 displayed aberrant transcript patterns for 17 genes, whereas only three were altered in mcd5. Since the mutations affect multiple RNAs in a variety of ways, our data suggest that MCD3, MCD4 and MCD5 may participate in a series of multiprotein complexes responsible for RNA maturation and degradation in Chlamydomonas chloroplasts.