cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of newly evolved enzymes. IV. Directed evolution of the Ebg repressor.

In Escherichia coli, the wild-type repressor of ebg (evolved β-galactosidase) enzyme synthesis, specified by the ebgR+ gene, responds very weakly to lactulose (fructose-β-D-galactopyranoside). Selection for a functional repressor that responds strongly to lactulose as an inducer reveals the existence of ebgR+L mutants, which occur spontaneously at a frequency of about 2 x 10-10. ebgR+L mutants are pleiotropic in that they specify ebg repressor with a greatly increased response to lactulose, lactose, galactose-arabinoside and methyl-galactoside as inducers. Selection of ebgR+L mutants is discussed within the framework of directed evolution of a regulatory function.
Monitoring ecosystems vulnerable to climate change

Using seventeen years of annual maximum value Normalized Difference Vegetation Index (NDVI) data, interannual variations in global vegetation dynamics are assessed. Comparisons are made between NDVI variability, rainfall, land cover classes and climate classes. Semi-arid regions covered by open shrublands exhibit the highest inter-annual variability among different land cover classes. These areas received a mean monthly rainfall of 10-30mm with a coefficient of variation in rainfall greater than 20% between years.
Numerical study of inviscid shock interactions on double-wedge geometries

Computational fluid dynamics has been used to study inviscid shock interactions on double-wedge geometries with the purpose of understanding the fundamental gas dynamics of these interactions. The parameter space of the interactions has been explored and the different types of interactions that occur have been identified. Although the interactions are produced by a different geometry, all but one of them may be identified as an Edney Type I, IV, V, or VI interaction. The previously unidentified interaction occurs because of the geometrical constraints imposed by the double wedge. The physical mechanisms for transition have been studied, and the transition criteria have been identified. An important result is that there are two different regimes of the parameter space in which the state of the flow downstream of the interaction point is fundamentally different. At high Mach numbers this flow is characterized by an underexpanded jet which impinges on the wedge and produces large-amplitude surface pressure variations. At low Mach numbers, the jet becomes a shear layer which no longer impinges on the wedge surface.
Rethinking the Restoration: Dissenting cases for conscience, 1667–1672*

On what religious and political grounds did restoration nonconformists argue for ‘ease to tender consciences’, and what did they mean by conscience? These questions are central to any evaluation of nonconformist political thought in the early restoration. Such dissenting thinkers as Slingsby Bethel, John Humfrey, Philip Nye, John Owen, William Penn, and Sir Charles Wolseley authored arguments for conscience during the intense debate about the restoration church settlement that occurred between 1667 and 1672. This essay outlines four different cases for conscience to which these arguments contributed. Two of these cases reconciled claims for conscience with the ecclesiastical authority of the monarch. Two other cases for conscience challenged the traditional religious authority of the crown.Should any or all of these arguments for conscience be considered radical arguments? The answer to this question requires a definition of the term ‘radical’ – one that is appropriate for the late Stuart period. The grounds upon which early restoration advocates of conscience accepted an indulgence under the royal prerogative in 1672 are also explained.The essay addresses the historiography of the restoration by considering Christopher Hill's and Richard Ashcraft's views about dissenting thought. It also proposes that the 1667–72 debate about the state and religion raised so many critical issues as to constitute an early restoration crisis about conscience.
14th Conference on Retroviruses and Opportunistic Infections (CROI 2007)

In the category ‘Best new drug’: raltegravir This integrase inhibitor was previously called MK-0518 and will have the trade name Isentress® (Merck). In Los Angeles, results from two Phase III trials, called Benchmrk 1 and 2, were presented. In both trials, patients with advanced HIV infection and multi-resistant viruses were recruited in the USA (Benchmrk 2) and in the rest of the world (Benchmrk 1) [1,2]. An optimal background treatment (OBT) was constructed with conventional drugs and resistance tests. To OBT, either placebo or raltegravir, 400 mg/twice daily, were added. Results from Benchmrck 1 are shown in Table 1. These are excellent results in such an advanced patient population; additional good news was the absence of any identifiable side effect that could plausibly be attributed to raltegravir, and a pharmacokinetic profile suggesting that drug interactions will be few. It is a safe bet that such a powerful drug will select resistance mutations; indeed, in patients from a Phase II study already presented at the Toronto Conference, two typical resistance mutations emerged, namely N155H and Q148H/K/S. With these results, submission to the US FDA will probably occur soon and approval, at least for advanced patients with multiresistance, might be granted as early as the second quarter of 2007. There are plans to use raltegravir earlier, in patients who have less-resistant virus or are even treatment naive. Studies in these patient populations are in progress. One handicap is the twicedaily administration, but pharmacokinetic data suggest that raltegravir will also be active once daily. Combination pills have proven to be very successful; we can anticipate that raltegravir will be paired with other new substances. In contrast to other new drugs such as darunavir or TMC-125 that, although effective, are more cubersome to use, raltegravir has a real chance to become part of the basic treatment regimen in most types of HIV-infected patients. A second integrase inhibitor formally called GS-9137 (Gilead) [2] has now morphed into elvitegravir. In contrast to raltegravir, it needs boosting by ritonavir, and is administrated once daily. In a Phase study, 20 mg/day was ineffective, whereas higher doses, particularly 125 mg/day combined with 100 mg of ritonavir, reduce viral load more than the background regimen (Table 2), without noticeable side effects. However, in cases where elvitegravir was the only active substance, resistance development was quite rapid.
Universal extra dimensions and the Higgs boson mass

We study the combined constraints on the compactification scale $1/R$ and the Higgs boson mass ${m}_{H}$ in the standard model with one or two universal extra dimensions. Focusing on precision measurements and employing the Peskin-Takeuchi S and T parameters, we analyze the allowed region in the ${(m}_{H},1/R)$ parameter space consistent with current experiments. For this purpose, we calculate complete one-loop KK mode contributions to S, T, and U, and also estimate the contributions from physics above the cutoff of the higher-dimensional standard model. A compactification scale $1/R$ as low as 250 GeV and significantly extended regions of ${m}_{H}$ are found to be consistent with current precision data.
Ultrasound Examination of the Achilles Tendon

imaging can benefit patients with Achilles tendon pathology. Although ultrasonography has been stigmatized as too operator dependent and necessitating a steep learning curve, it has been our experience that the modality is relatively straightforward. Surgeons are in a unique position to utilize this technology, as they have the firm grasp of anatomy that is essential to the interpretation of sonograms. Ultrasound provides real-time dynamic imaging in the office and in the operative setting that directly benefits our patients. Ultrasound images can assist the clinician in determining the exact pathologic process, including location of symptoms, assessment of concurrent pathology, response to treatment, and the planning and intraoperative assessment of tendinous pathology. The Achilles tendon is the largest superficially located tendon of the body and is ideally suited to ultrasound examination. Achilles tendon morphology is best visualized with a high-frequency linear transducer (5 to 10 MHz). After an appropriate history and physical is obtained, the patient is positioned prone with both lower extremities disrobed ( Fig. 2.1 ). As with all tendons, images of the Achilles tendon should be obtained in two orthogonal planes. Longitudinal and transverse images should be obtained from the musculotendinous junction to the distal tendon insertion on the calcaneus. To obtain an orderly and reproducible examination, imaging begins directly over the area of pain or tenderness with the foot in the gravity neutral position. In general, transverse imaging is followed by longitudinal imaging. Because ultrasound is a dynamic imaging modality, movie clips of the examination can be saved in the patient’s electronic record. After the static examination of the area of interest, the surgeon grasps the patient’s foot, introducing passive dorsiflexion and plantarflexion. This is followed by visualization of the symptomatic area with active range of motion. Finally, a full examination of the tendon from its most distal insertion proximally to the myotendinous junction is performed. Obviously, examination may be extended to the gastrocnemius and soleus muscles, depending on the clinical situation. The normal Achilles tendon, as shown in Figure 2.2 , appears echogenic (bright) with an organized fibrillar ultrastructure. The paratenon envelops the tendon as a thin, echogenic tissue layer clearly distinct from the tendon under 2
A Microprocessor Controlled Respiratory Monitor

Development of a respiratory care data collection and monitoring system is based upon the philosophy that it is imperative to have accurate quantitative patient data at the bedside in order to insv e quality patient care. Presently, computer systems can adequately provide the means to collection and dissemination of information. The basic consideration becomes one of the quality of the sensor information to be utilized. Primary to respiratory care are the measurements of gas composition, flows, pressures and temperature. New technology is rapidly putting these measurements within reach of the clinicians in the critical care facilities and it is now their responsibility to provide adequate input into the processing of the basic measurements.
Immigrants from Mongolia – their health and experience with healthcare in the Czech Republic

Abstract At present, foreigners form over four percent of the Czech population. According to the Czech Statistical Office, nearly six thousand of them are immigrants from Mongolia. The reason for this migration is usually the possibility of getting a job and therefore improving their economic situation. The aim of the research, which is part of the project entitled “Social Determinants of Health in Selected Target Groups”, was to analyze the relationship between a set of selected social characteristics and characteristics of health. The paper refers to immigrants from Mongolia who are living in South Bohemia. The qualitative survey was performed by interviewing nineteen respondents. After the interviews and analysis of the data, major semantic categories and subcategories were identified. This paper focuses on the current health status of immigrants, the type of health insurance, experience with doctors, and their level of satisfaction with receiving healthcare. The results helped to reveal numerous problems concerning the health of immigrants, and the use of healthcare in our country. Respondents reported health problems such as chronic backache, headaches, fatigue and hearing impairments. These problems were all associated with an unsuitable work environment. While receiving healthcare, the respondents met with a negative attitude from medical staff. According to the respondents, the most common causes of this were language barriers, and doctors and nurses prejudice towards foreigners.
Fructose levels are markedly elevated in cerebrospinal fluid compared to plasma in pregnant women.

Background Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose→sorbitol→fructose) contributes to brain exposure to fructose.
BI-33, a novel and potent pan-Bcl-2 inhibitor, induces apoptosis in cancer cells and shows combinational effect with chemo drugs

C229 Introduction: BI-33 is a novel flavonoid compound which mimics the Bim BH3 peptide. Our study is to determine the biological effect of BI-33 and its therapeutic potential used as a single agent or in combinational treatment with chemo drugs. Experimental Procesures: BI-33 binds to Bcl-2, Bcl-xL and Mcl-1 with Ki value at 17nM, 1.2uM and 18nM, respectively, as shown in fluorescence-polarization-based binding assay. BI-33 inhibits cell growth in 2LMP breast cancer cell line and PC3 prostate cancer cell line as shown by 4 days WST assay, with IC50 at 50nM and 40nM, respectively. BI-33 used at 1uM for 4 days induces ~50% of cell death in these two cell lines as demonstrated by trypan blue assay and confirmed by AnnexinV-PI apoptotic assay. BI-112, served as compound control which has low binding affinity to Bcl-2, Bcl-xL and Mcl-1, does not induce cell death even at 10uM. To determine if mitochondrial apoptotic pathway is activated by BI-33, cytochrome C release and caspase3 activation is investigated. BI-33 at 10uM for 2 days induces cytochrome C release in cytosolic fraction and PARP cleavage in nuclear fraction from 2LMP cells. Caspase3 activity was increased 6 fold by BI-33 in 2LMP cells. To further determine if BI-33 targets Bcl-2 or Bcl-xL for cell killing, stable clones of Bcl-2 or Bcl-xL in MDA-MB-435 cells were established and confirmed the increased resistance to VP16. BI-33 counters overexpression of Bcl-2 or Bcl-xL as shown by efficient killing of these stable clones. To investigate if BI-33 synergizes with chemo drugs to induce cell death, Paclitaxel is tested in 2LMP cells and IC50 of Paclitaxel is decreased 10 fold by co-treatment with BI-33. We further tested Jurkat cells with overexpression of Bcl-2 or Bcl-xL, which show increased resistance to VP-16. BI-33 can also sensitize these stable clones to VP-16 treatment. Conclusion: Taken together, our study shows that BI-33, as a pan-Bcl-2 inhibitor, induces cancer cell death through activation of mitochondrial apoptotic pathway, and has potential to be used as single agent or in combinational treatment with chemotherapy, to kill cancer cells which have high level of Bcl-2, Bcl-xL and Mcl-1.
Discrete-event simulation using R

R is a free software package with extensive statistical capability, customizable graphics, and both imperative and vectorized programming capabilities. For use in an introductory simulation course, the capabilities of R for analyzing simulation statistics, and for generating corresponding graphics, aid in developing student intuition. R also provides flexibility in determining whether simulation and analysis should be done using simulation code that students implement from scratch, using skeleton code which students modify, or using completed code given as a black box. These aspects of R make it a unique platform for programming and analyzing discrete-event simulations. In this paper, we present an R function named ssq which we wrote to simulate a single-server queue, and we provide several illustrations showing its use as an exemplar for using R in an introductory simulation course. All of the code to analyze the output from ssq uses functions from the base distribution of R.
Guest Editorial Special Issue on Systematic Approaches to Human–Machine Interface: Improving Resilience, Robustness, and Stability

The papers in this special section focus on systematic approaches to human-machine interface applications. The motivation for this special issue is the growing increase of remote mission management, unmanned aircraft systems, NextGen operations in the U.S. and its Single European Sky Air Traffic Management Research counterparts in Europe, and other similarly integrated systems of systems that include complex human–machine systems with high levels of autonomy and team dynamics that are difficult to understand and analyze. The issue explores key research areas that impact the properties of these systems, which rely on varied degrees of human and machine interactions. The special issue is a result of the continued interest in the formal verification of complex human–machine systems.
Corticotrophic activity of human plasma constituents.

SummaryFractions of human plasma prepared by methods 6 and 9 of Cohn and his associates have been assayed for ACTH activity by the procedure of Nelson and Hume. ACTH activity was found in Fraction II + III and occasionally in Fraction IV-1 and Fraction IV-4. Fractionation of human plasma to which ACTH had been added in vivo and in vitro gave similar results.
Quantification of Model-Form Uncertainty in Drift-Diffusion Simulation Using Fractional Derivatives

In modeling and simulation, model-form uncertainty arises from the lack of knowledge and simplification during modeling process and numerical treatment for ease of computation. Traditional uncertainty quantification approaches are based on assumptions of stochasticity in real, reciprocal, or functional spaces to make them computationally tractable. This makes the prediction of important quantities of interest such as rare events difficult. In this paper, a new approach to capture model-form uncertainty is proposed. It is based on fractional calculus, and its flexibility allows us to model a family of non-Gaussian processes, which provides a more generic description of the physical world. A generalized fractional Fokker-Planck equation (fFPE) is proposed to describe the drift-diffusion processes under long-range correlations and memory effects. A new model calibration approach based on the maximum accumulative mutual information is also proposed to reduce model-form uncertainty, where an optimization procedure is taken.Copyright © 2015 by ASME
GEOGRAPHIC POPULATION STRUCTURE AND SPECIES DIFFERENCES IN MITOCHONDRIAL DNA OF MOUTHBROODING MARINE CATFISHES (ARIIDAE) AND DEMERSAL SPAWNING TOADFISHES (BATRACHOIDIDAE).

Restriction-fragment length polymorphisms in mitochondrial DNA (mtDNA) were used to evaluate population-genetic structure and matriarchal phylogeny in four species of marine fishes that lack a pelagic larval stage: the catfishes Arius felis and Bagre marinus, and the toadfishes Opsanus tau and O. beta. Thirteen informative restriction enzymes were used to assay mtDNAs from 134 specimens collected from Massachusetts to Louisiana. Considerable genotypic diversity was observed in each species. However, major mtDNA phylogenetic assemblages in catfish and toadfish (as identified in Wagner networks and UPGMA phenograms) exhibited contrasting patterns of geographic distribution: in catfish, distinct mtDNA clades were widespread, while such clades in toadfish tended to be geographically localized. By both the criteria of species' ranges and the geographic pattern of intraspecific mtDNA phylogeny, populations of marine catfish in the western Atlantic have had greater historical interconnectedness than have toadfish. Results are also compared to previously published mtDNA data in freshwater and other marine fishes. Although mtDNA differentiation among conspecific populations of continuously distributed marine fishes is usually lower than that among discontinuously distributed freshwater species inhabiting separate drainages, it is apparent that historical biogeographic factors can importantly influence genetic structure in marine as well as freshwater species.
Abstract 249: Inhibition of protein phosphatase 2A supports androgen-independent growth of prostate cancer cells

Clinical progression of prostate cancer (PCa) is characterized by a transition from androgen-dependent (AD) to androgen-independent (AI) stage. Once the PCa has recurred in AI form, it progresses to a highly aggressive disease and poses an increased risk of morbidity and death. Therefore, understanding the mechanisms involved in AI progression of PCa is a significant area of research. Earlier, we identified PPP2CA, which encodes for alpha-isoform of the protein phosphatase 2A catalytic subunit (PP2Acα), as one of the downregulated genes in AI PCa cells. PP2A is a ser/thr phosphatase and a potent tumor suppressor involved in broad cellular functions; however, its role in PCa has not yet been determined. Here, we have investigated the effect of PP2A downregulation on the growth of AD PCa (LNCaP) cells under steroid-deprived condition. Furthermore, we have examined the effect of PP2A inhibition on the signaling pathways and delineated their role in AI growth of LNCaP cells. Our data show that the downregulation of PP2A activity by pharmacological inhibition or siRNA-mediated PPP2CA silencing sustains the growth of AD PCa cells under androgen-deprived condition by relieving the androgen-deprivation-induced cell cycle arrest and preventing apoptosis. Immunoblot analysis revealed enhanced phosphorylation of Akt, ERK, BAD, increased expression of cyclins (cyclin A1 and cyclin D1) and decreased expression of cyclin inhibitor (p27) upon PP2A downregulation. Furthermore, our data show that PP2A inhibition partially maintains AR signaling through its increased expression and ligand-independent phosphorylation, which is also supported by AR transcriptional activity assay and its target gene, KLK3, expression. Pharmacological inhibition of Akt, ERK and AR confirmed a role of these signaling pathways in facilitating the AI growth of LNCaP cells. Altogether, our findings suggest that modulation of PP2A activity may represent an alternative therapeutic approach for the treatment of advanced androgen-independent prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 249. doi:10.1158/1538-7445.AM2011-249
Spatial and Temporal Genetic Variability of the Eastern Cottontail on West Texas Playa Basins

Spatial and temporal changes in allelic frequency, genotypic proportions, and total and single locus heterozygosity of the eastern cottontail ( Sylvilagus floridanus ) were studied on two playa lake basins in the Texas Panhandle. Playa basins in this region are separated by extensive areas of agricultural and pasture lands, and therefore constitute the only significant cottontail habitat. Blood plasma samples were obtained from 543 individuals captured on both playa basins, during seven live-trapping periods from February through November, 1981. Adult and seven juvenile age classes were identified. Prereproductive adult cottontail populations had observed genotypic proportions that deviated significantly from expected Hardy-Weinberg equilibrium, seemingly the result of heterozygote deficiencies related to differential overwinter selection and/or nonrandom genotypic dispersal. These findings are inconsistent with previous studies in which increases in heterozygosity were shown to correlate with superior fitness. Significant ( P > 0.05) changes in allelic frequencies, genotypic proportions, and heterozygosity were related to population demographic characteristics. Apparent random matings by individuals of parental genotypes and subsequent juvenile recruitment dampened or eliminated the disequilibrium in Hardy-Weinberg proportions. Changes in population number due to reproductive recruitment and dispersal were accompanied by changes in gene frequency and heterozygosity. Spatial differences in genetic attributes were maintained between the two playa basins throughout the study because of the large distances between breeding groups. However, parallel trends were observed in population genetic and demographic characteristics on both playa basins.
Assessment of cardiovascular disease risk factors in the coastal region of South Carolina.

Objective : To assess risk factors for cardiovascular disease, barriers to health care, and desired health care education topics for Hispanics in the coastal region of South Carolina known as the Low country. Methods : 174 Hispanic adults were surveyed at visits at the Mexican consulate using a novel interview instrument. The prevalence of cardiovascular risk factors was compared to the Behavioral Risk Factor Surveillance System (BRFSS), an annual telephone survey, to evaluate the validity of the survey instrument. Results : Results are comparable to the BRFSS telephone study of the Hispanics in the same area. However, participants in our study were older (Age >35 =41.4% vs. 34.9%) and reported fewer years of formal education (higher level education >12.9% vs. 44.2%). Cost of care (72.8%) and language barriers (46.8%) were the main difficulties reported in obtaining health care access. The main educational topics of interest were diabetes (61.5%), hypertension (43.7%), stress (42.5%), and cardiac disease (40.2%). Conclusion : Our study supports the evidence that there is a demand and need for cardiovascular disease and diabetes education among Hispanics. Our study also shows that a large proportion of Hispanics experience barriers to health care and that large telephone studies may underrepresent higher risk Hispanic populations. ( Ethn Dis . 2014;24[2]: 155–161)
Atomic Excitation by a Jump-Noisy Laser

Recent experimental interest[1,2] in the effects of laser bandwidth on atomic absorption and emission suggests the need for a wider range of theoretical models capable of describing noisy quasi-monochromatic lasers. Of the results already known[3], almost all are derived from theories based on lasers whose bandwidth arises from a white-noise process. We shall describe a number of results obtained from studies of laser-induced atomic excitation when the laser noise arises from jump noise or generalized random telegraph noise[4]. We shall report on the response of a simple two-level transition to laser excitation in the case that the laser has phase, frequency, and amplitude noise, and several combinations of such noise processes. As one example, we show in the figure below the atom’s emission spectrum as a function of the size of the phase jump and the mean interval between jumps, when the random phase is a pure telegraph, i.e., has only two possible states.
International implications of the United States ‘global settlement’ of tobacco litigation

Litigation against the tobacco industry has exploded in the United States and is spreading worldwide. On 20 June 1997, a ‘global settlement’ of this litigation was announounced that had been negotiated by some state attorneys general and the tobacco industry. This settlement is neither ‘global’ in the sense that it applies only to the United States nor a ‘settlement’ in that it is not a binding agreement that resolves legal disputes among the parties in the litigation. The agreement raises a complex array of issues for public health and public policy and legal and economic issues. It was intended to be a blueprint for national tobacco control legislation that would end the most important current and potential litigation against the tobacco industry. As with most complex legislation, the deal, after it was announced, underwent a great deal of scrutiny and criticism. Many public health and policy groups analysed it in whole or in part in order to provide guidance for those who wished to distil the essential elements and implications. (A complete report on the proposed resolution of United States tobacco litigation by the same authors is available on the World Wide Web at http://galen.library.ucsf.edu/tobacco/ustl/.) While many have pronounced the original deal to be ‘dead’ as a result of this criticism, it remains the fundamental framework around which most proposals for Federal legislation on tobacco has been based. As a result, a careful analysis of the terms and implications of the original deal remains worthwhile.
Ursolic acid, a potential anticancer compound for breast cancer therapy.

AbstractThere are growing interests in the health benefits associated with consumption of fruits and vegetables, especially for the prevention of cancer, cardiovascular or other chronic diseases. Epidemiological studies and clinical trials suggest that these health benefits are strongly associated with phytochemicals found in fruits and vegetables. Ursolic acid is a naturally synthesized pentacyclic triterpenoid, widely distributed in different fruits and vegetables. Current research suggested that ursolic acid and its derivatives exhibited anticancer activity, anti-inflammatory effects, and induction of apoptosis in several human cancer cells. In particular, ursolic acid inhibited breast cancer proliferation by inducing cell G1/G2 arrest and regulating the expression of key proteins in signal transduction pathways. In addition, ursolic acid induced apoptosis in human breast cancer cells through intrinsic and extrinsic apoptotic pathways. Ursolic acid was also determined to scavenge free radicals and have...
EARTHTIME: Teaching Geochronology to High School Students in the USA

As part of the EARTHTIME outreach initiative, we have developed an educational module that teaches students about the basics of geochronology and how geologic time is measured. The exercises focus on the uranium-lead (U-Pb) dating method using the mineral zircon with applications to solving geological problems. During several Lab Day tutorials, students from local high schools attended a day of workshops, participating in hands-on exercises and a discussion of geochronology in earth science research. Student performance and learning impact were assessed using pre-tests (1 week before the event) and two post-tests (1 week after the event and 4 months after the event). These revealed that students greatly appreciated the hands-on exercises and that the exercises resulted in a significant increase in knowledge. We also developed and tested a “Lab Day on the road,” where scientists traveled to a local high school to introduce hands-on exercises and lead discussions related to geochronology. To further develop the module, a teacher workshop was conducted to identify educators’ needs and perspectives. The teaching methods, developed iteratively during 2 years of Lab Days, were incorporated in a Geochronology Lesson Plan and Material Kit. The finalized lesson plan is a 90- to 120-min educational module, downloadable at http://www.earth-time.org/Lesson_Plan.pdf, along with supporting spreadsheets and a video demonstration of the material. An EARTHTIME geochronology kit, linked to the lesson plan activities, is available by request to K-12 teachers in the USA.
Speed Versus Accuracy in Visual Search: Optimal Performance and Neural Implementations

What is psychophysics? In its traditional definition, psychophysics studies how mental states (psycho) are affected by physical stimuli (physics). For instance, a cute dog (physical stimulus) may elicit a feeling of warmth and affection (psycho state), and psychophysics studies how specific attributes (breed, size, smell, etc.) of the dog relate to our feelings.
Promoting Patient and Caregiver Engagement during Discharge from a Healthcare Facility

Greater patient involvement in the healthcare process is a key pillar of the patient centered health-care model. However, observations of a healthcare facility identified limited communication as a...
Modification of 3’ Terminal Ends of DNA and RNA Using DNA Polymerase θ Terminal Transferase Activity

DNA polymerase θ (Polθ) is a promiscuous enzyme that is essential for the error-prone DNA double-strand break (DSB) repair pathway called alternative end-joining (alt-EJ). During this form of DSB repair, Polθ performs terminal transferase activity at the 3' termini of resected DSBs via templated and non-templated nucleotide addition cycles. Since human Polθ is able to modify the 3' terminal ends of both DNA and RNA with a wide array of large and diverse ribonucleotide and deoxyribonucleotide analogs, its terminal transferase activity is more useful for biotechnology applications than terminal deoxynucleotidyl transferase (TdT). Here, we present in detail simple methods by which purified human Polθ is utilized to modify the 3' terminal ends of RNA and DNA for various applications in biotechnology and biomedical research.
Sex and Trait Anxiety Differences in Psychological Stress are Modified by Environment.

Evidence-based research has revealed how physiological and emotional responses to acute stress are adaptive. However, under conditions of unpredictable or protracted stress, health and drug vulnerability can be compromised. In this study, we examined anxiety-like behavioral responses of 4th generation adolescent male and female Long Evans rats selectively bred for high (HAn) and low (LAn) anxiety-like behavior when housed in an isolated environment (IE) versus a social environment (SE). After 35 days in IE or SE, animals were tested in the elevated plus maze (EPM), injected with amphetamine (AMPH: 0.5 mg/kg, IP) in the locomotor activity (LMA) chamber, measured for basal and post air puff-stressor core body temperature and blood pressure. Following select rearing, SE reduced the anxiogenic response in HAn rats with females displaying the lowest anxiety-like behavior in the EPM. During habituation in the LMA, IE rats remained active, while post-AMPH injection HAn females were hyperactive, followed closely by LAn females. Our findings from the post-stressor physiological measurements indicate that temperature differences due to environment are observed only in the SE females. We also observed group differences for diastolic (DBP) and systolic (SBP) blood pressure. HAn IE males experienced higher DBP and SBP but LAn IE females only experienced higher SBP. Not only do our findings corroborate earlier work on HAn/LAn lines but the findings obtained from this research offer new insights about the role of environment and the role of sex in (1) modulation of anxiety-like behavior, (2) AMPH sensitivity, and (3) basal and stress-induced physiological changes.
Evaluation of Cycloferin Supplement on Health Parameters in Experimentally Induced Diabetic Rats with and Without Exogenous Insulin.

ABSTRACTCycloferin is an extract of the chemicals from the Cyclopia species, which grows only in small areas in the southwest and southeast of South Africa and has been consumed traditionally as a ...
Studies on intracellular processing of the capsid protein of human astrovirus serotype 1 in infected cells.

Astroviruses are non-enveloped, positive-strand RNA viruses. Their structural (capsid) protein is processed extracellularly into several smaller fragments which are found on the mature viral particle. In addition, intracellular cleavage of the capsid protein has been proposed. However, analysis of capsid protein processing has been hampered by the lack of antibodies to regions near the N and C termini of the protein. Here we describe the construction of two infectious mutants of human astrovirus serotype 1 (HAstV-1), in which amino acids (aa) 11–30 or aa 783–787, respectively, of the 787 aa capsid protein were replaced by tag sequences. Processing of the tagged capsid proteins in infected Caco-2 cells was analysed by immunoprecipitation with specific reagents directed against the tags or against native internal regions of the capsid protein. No intracellular processing of the capsid protein in infected cells could be detected, while assembled viral particles were readily observed within cells.
Stochastic Arima Models for Monthly Streamflows

Abstract The non-stationary and seasonal nature of the monthly flows are modeled using ARIMA class of models. A step-by-step procedure is designed to obtain valid models through proper model identification, parameter estimation, performance evaluation, model parsimony and validation of residuals. Several statistical indices of performance, and statistical tests are used to properly screen the candidate models for obtaining the best models. The importance of obtaining parsimonious models and validation of residuals for whiteness is emphasized. The procedure is demonstrated for the monthly flows of the Chattahoochee River in Georgia in obtaining a valid model capable of acceptable prediction results.
Quantifying of the Effect of Rain-Induced Sub-Footprint Scale Wind Variability on the Rapidscat Ku-Band Nrcs

The recent advances in Ku-band wind speed retrievals [Fore, 2014] in the presence of rain [Stiles and Dunbar, 2010] indicate that there is an opportunity to learn more about the physical relationship between the spatial variation of surface winds within a scatterometer resolution cell (wind vector cell; WVC) and the observed backscatter. There is a need for improvement in the ability of this type of scatterometer to estimate wind speed and direction, in the presence of rain. The wind vector products that are currently available, derived using these approaches and without a separate bias adjustment such as Stiles et al. [2014], often have relatively large errors in speed and direction [Bourassa, 2017]. In effect, the presence of rain frequently leads to erroneous solutions by these methods. This effort descried herein is engaged with data from the RapidScat scatterometer mission on the International Space Station. We are assessing the sub-footprint variability in wind and how rain contributes to the area averaged backscatter. The sub-footprint winds are from a new high-resolution wind vector product (hourly, 2.5 km spacing), for which data assimilation of NEXRAD observations should enhance the consistency with sub-footprint variability in rain contributions to the radar cross section. This product is the Real Time Mesoscale Analysis, from NOAA-NCEP. We are comparing the PO.DAAC NRCS products (after adjustment for rain) to the values estimated from the higher resolution wind product, transferred to backscatter, through the RapidScat geophysical model function (GMF). The rain data is available through a special RScat “RadRain” product created by Remote Sensing Systems using a variety of collocated, coincident satellite sensors.
Living outside the Financial Mainstream: Alternative Financial Service Use among People with Disabilities

This study explored factors related to the use of alternative financial services (i.e., payday loans, prepaid debit cards, pawn shops, auto title lenders, and rent-to-own stores) among a nationally...
Using Multisensory Integration to Understand the Human Auditory Cortex

Accurate and meaningful parcellation of the human cortex is an essential endeavor to facilitate the collective understanding of brain functions across sensory and cognitive domains. Unlike in the visual cortex, the details of anatomical and functional mapping associated with the earliest stages of auditory processing in the cortex are still a topic of active debate. Interestingly, aspects of multisensory processing may provide a unique window to meaningfully subdivide the auditory sensory areas by exploring different functional properties other than the traditional tonotopic approach. In this chapter, a tour of the auditory cortical areas is first provided, starting from its core area, Heschl’s gyrus, then moving onto surrounding areas. Evidence from different sources, including postmortem studies of the human auditory cortex, resting-state functional connectivity derived from the Human Connectome Project, and electrocorticographic studies, is presented to better understand how different subdivisions of the human auditory cortex and its surrounding areas are involved in auditory and multisensory processing. The chapter concludes with the remaining challenges to account for individual variability in functional anatomy, particularly pertaining to multisensory processing.
The unit sphere and CR geometry

CR geometry considers the interplay between real and complex spaces. The name itself has an interesting history, which we do not discuss here, other than to say that CR stands both for Cauchy-Riemann and for Complex-Real. See [DT] for a survey of CR Geometry and its connections with other branches of mathematics. See [J] for a good exposition of the theory of CR structures, and see [BER] for a definitive treatment of CR mappings.
Neurosurgery Elective for Preclinical Medical Students with and without a Home Neurosurgery Program.

Background Preclinical neurosurgery electives have been shown to increase student familiarity with neurosurgery, yet the impact on students without a home neurosurgery program is unknown. We conducted a preclinical neurosurgery elective in a mixed cohort of students with and without home neurosurgery programs to 1) evaluate changes in neurosurgery perceptions, 2) discern differences between cohorts, and 3) identify important factors in those considering neurosurgery. Methods A yearly elective was offered to students at Vanderbilt University School of Medicine (VUSM; home program) or Meharry Medical College (MMC; no home program) from 2017 to 2018. Each class included a student-led presentation, faculty academic lecture, and faculty round-table discussion. Precourse and postcourse surveys were completed. Results Thirty-two students completed the course. VUSM students (n = 15) showed no changes in initial perceptions, whereas MMC students (n = 17) had multiple improved perceptions, including collegiality (P = 0.001) and family achievability (P = 0.010), and believed residency to be less rigorous than their initial perceptions (P = 0.046). Fourteen students (44%) showed an increase in the likelihood of considering a neurosurgical career; eight (57%) were MMC students. These 14 students had improved perceptions of neurosurgery as less emotionally draining (P = 0.042), with favorable collegiality (P = 0.003) and work/life balance (P = 0.001) but did not believe residency to be less difficult (P = 0.102) or have added financial security (P = 0.380). Conclusions Early exposure to neurosurgery at medical schools without home programs through preclinical electives may improve students' perceptions of neurosurgery, provide valuable information about the benefits and rigors of neurosurgery, and allow students to make informed decisions about further pursuit of neurosurgery.
The Molecular Basis of Susceptibility to Rheumatoid Arthritis

Publisher Summary This chapter discusses the development, current understanding, and some of the implications of the molecular basis of susceptibility to rheumatoid arthritis as it relates to the inheritance of particular polymorphic conformations of the major histocompatibility complex (MHC) class II molecules. The way the interpretation of these susceptibility structures as peptide-binding pockets alters the paradigm underlying the study of histocompatibility leukocyte antigens (HLA)-disease associations to one based on rational structural hypotheses is discussed. Disease susceptibility genes, rather than being “disease genes,” are MHC class II alleles that are positively selected and physiologic. The penetrance of rheumatoid arthritis is accordingly low, but in the heterozygous state, the gene encoding the shared epitope confers susceptibility indicating it has a dominant mode of action. However, when two susceptibility alleles are inherited together this greatly increase the penetrance and severity of the ensuing disease and raises questions about the way these structures act cooperatively to provide the molecular basis of susceptibility. From the perspective of the person with rheumatoid arthritis, the illness usually appears to be a sporadic event that often makes its appearance only well into adulthood.
Mathematical Modeling of Blood Flow in the Eye

Mathematical models linking ocular mechanics, circulation, and oxygenation are needed to improve the interpretation and prediction of key components of ocular health and disease. This chapter presents the most recent achievements in modeling the retinal, retrobulbar, and choroidal vascular beds in the eye. These models incorporate elements of flow regulation, oxygen transport, angiogenesis, and venous collapsibility and are used to answer important questions related to ocular diseases such as glaucoma and age-related macular degeneration.
How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia.

Abstract Administering asparaginase has always been problematic in adults because most general oncologists who treat adults are not familiar with its usage and toxicity. The toxicity profile of the drug is unique and is not observed with any other chemotherapy agent. Furthermore, asparaginase is almost exclusively used in acute lymphoblastic leukemia (ALL), which is a very rare cancer in adults. Currently, the long-acting pegylated form (pegasparaginase) is the only Escherichia coli–derived asparaginase available in the United States. The use of pediatric regimens is likely to lead to more adult patients receiving multiple doses of pegasparaginase. However, oncologists who treat adults may be reluctant to use pegasparaginase or may unnecessarily discontinue administering it because of certain adverse effects. As a result, the clinical benefit of multiple doses of pegasparaginase will be missed. Despite the fact that pegasparaginase is associated with unique toxicities, the majority are nonfatal, manageable, and reversible. Here, we describe real-life cases of adults with ALL who were treated with pediatric-inspired regimens that incorporated pegasparaginase to illustrate the management of several pegasparaginase-associated adverse effects and guide whether and how to continue the drug.
Sensors and Instrumentation for Downhole Environments - Challenges and Opportunities

This paper focuses on sensors and instrumentation utilized in the oil/gas industry for logging and well navigation and methods of downhole communication. To address the tradeoff between cost/reliability vs opportunity, currently available logging tools, such as wireline and logging-while-/measurement-while drilling (LWD/MWD) tools, and emerging technologies, such as mobile Micro-electro-mechanical systems (MEMS) devices, are reviewed from different aspects such as principles of operation, electronics, power generation, size, packaging and cost.
Power Optimization Using Embedded Automatic Gain Control Algorithm with Photoplethysmography Signal Quality Classification

This paper presents the design and implementation of an Automatic Gain Control (AGC) embedded algorithm for photoplethysmographic (PPG) sensors. We use a number of statistical and spectral characteristics of the raw and filtered PPG signals, referred to as multi-dimensional Signal Quality Metric (SQM) from the measured PPG signals on subjects’ wrists. Using the Analog Devices (ADI) Vital Signs Monitoring (VSM) platform, and running the AGC in real time in an embedded ARM Cortex-M3 processor, we are able to save more than 50% LED power on average without compromising PPG signal quality needed for the VSM algorithms.
Chapter 9 – Glutamate Metabolism

The majority of energy consumed by the brain is used to maintain membrane potentials of neurons after action potentials are fired. Glutamate, the main neurotransmitter in the central nervous system (CNS), is responsible for a large percentage of this energy expenditure. Accumulation of glutamate, however, can be toxic to neurons and, therefore, must be tightly regulated. The brain uses a combination of the blood–brain barrier, powerful glial transporters, metabolic enzymes, and glutamate cycling to maintain low extracellular levels of glutamate. These protective mechanisms, however, can become dysregulated in epilepsy. Both human and animal studies have shown that glutamate uptake into astrocytes is hindered, the metabolic processing of glutamate is slowed, and the cycling of glutamate to glutamine is downregulated in epileptic tissue. Future studies should be aimed at furthering our understanding of the functional consequences of these changes.