cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 54: Probenecid Improves Myocardial Function in an Ischemic Heart Disease Murine Model

Introduction Probenecid, previously used for the treatment of gout, is a transient receptor potential vanilloid 2 (TRPV2) agonist. We have found TRPV2 in murine cardiomyocytes and when stimulated by probenecid, results in a positive inotropic response through Ca2+ influx independent of β-adrenergic signaling. Our hypothesis is that probenecid will increase contractility without affecting cell survival. Methods We studied the role of probenecid as a positive inotrope in a mouse model of ischemic heart disease. We administered probenecid via intraperitoneal injections (100mg/kg) before and after ischemia/reperfusion injury (I/R) and orally via treated water (100mg/kg daily for 4 weeks), using saline injections and untreated water as respective controls. Ischemia was induced by a 45 minute ligation of the LAD followed by reperfusion and all mice were followed serially via echocardiography. We also evaluated the effects of probenecid on HL-1 cell apoptosis by conducting cell viability assays. Results Treatment with probenecid before I/R had no effect on subsequent infarct size (51.6±3.71% vs. 53.4±1.54%;P=NS). However, post-I/R probenecid caused an increase in ejection fraction (EF) of 10.9±1.98% in mice with initial EF between 40-50% (n=6; P<0.01) and 7.28±1.63% in mice with higher initial EF (50-60%) (n=6; p<0.01). Echocardiographic analysis of mice with oral probenecid after I/R demonstrated higher EF and smaller diastolic volume (47.19±2.29%; 79.57mL±1.63; n=6) compared to untreated mice (43.67±2.91%; 89.05mL±5.67; n=6). Cell viability assays showed high concentrations of probenecid had minimal effect on cell viability (88.6±6.2% of control) whereas treatment with high concentrations of isoproterenol (10mM) greatly decreased cell viability (6.7±0.1% of control). Conclusions These experiments demonstrate 1) probenecid increases myocardial contractility at baseline and significantly more so after I/R injury; 2) probenecid therapy improves function when used chronically; 3) the increase in contractility is not associated with either increased infarct size in vivo or apoptosis in vitro. Thus, unlike other positive inotropes, such as isoproterenol, probenecid increases contractility without resulting in significant cell death.
“Do You Understand Why I Don’t Share That?”: Exploring Tellability Within Untellable Romantic Relationship Origin Tales

The purposes of this study were to gain a clearer conceptualization of what makes romantic relationship origin (RRO) stories untellable, and how an untellable RRO tale impacts a narrator. In-depth interviews and open-coding revealed RRO stories are untellable if the narrative might generate negative judgement of the characters or relationship, and/or negative sanctions. Untellable RRO stories caused narrators to feel narrative exhaustion, lack of validation, limit identity construction and joy, and perpetuate silence. Untellable RRO stories also created a secret story world for narrators. These findings provide a deeper understanding of narrative tellability and how narrators “story around” untellable tales.
Defining the role of NDRG1 in prostate cancer

4934 Progression of cancer from a localized disease to an advanced, invasive stage involves interplay of various molecules involved in cell adhesion, cell motility and cell cohesion. One such molecule that is involved with metastasis of prostate and breast cancer is the N-myc downregulated gene1 (NDRG1). The NDRG1 gene encodes a cytoplasmic 43-kDa protein. NDRG1 gene expression is silenced by native chromatin modulators and promoter methylation in prostate and breast cancer. Its expression is induced by various chemical agents like HDAC inhibitors, DNA methyl transferase inhibitors. Induction of NDRG1 leads to differentiation of cells and decreases metastasis. The exact function of how NDRG1 decreases metastasis is unknown. In an attempt to understand the function we carried out knockdown studies of NDRG1 in prostate cancer cell lines. Knockdown of NDRG1 in DU-145 prostate cancer cells led to knockdown of the cell adhesion molecule E-cadherin without changing the expression of other molecules in the E-cadherin complex. Reduced expression of E-cadherin correlates with metastasis of cancer including prostate cancer. Tissue array data of matched normal and tumor tissue from 42 patients using NDRG1 and E-cadherin antibodies indicated a highly significant correlation between NDRG1 and E-cadherin expression. A decrease in NDRG1 expression also correlated with the increase in grade of the tumor. We investigated the physical localization of NDRG1 after calcium chelation. Our immunofluorescent data revealed that NDRG1 strongly localizes with E-cadherin during the recovery/recycling phase. Ultracentrifugation experiments suggested that NDRG1 does strongly localize to an organelle after calcium chelation that cofractionates with markers of early/recycling and late endosome. Immunoprecipitation with flag tagged-NDRG1 showed NDRG1 physically interacts with Rab4GTpase. Pull-down assays using recombinant Rab4GTpase and NDRG1 revealed NDRG1 specifically interacts with Rab4 loaded with GTPγS indicating that the proteins interact on surface of endosomes. Live cell imaging using spinning disk confocal microscopy of HEK293 cells stably expressing NDRG1DsRed2 protein reveal NDRG1 localizes to discrete vesicles in the perinuclear region and interacts with both late and early endosomes and can recycle Alexa flour labeled- transferrin. In vitro reconstitution studies using purified endosome, in vitro translated NDRG1 and recombinant Rab4GTPase showed NDRG1 localizes to endosomes independent of Rab4GTPase. A lipid overlay analysis using recombinant NDRG1 revealed that the protein specifically binds to phosphatidylionositol 4- phosphate a lipid that defines microdomains in the trans-Golgi network and is involved with protein trafficking. Our data indicate that NDRG1 is involved in recycling of E-cadherin by endosomes and loss of NDRG1 may result in decrease in surface E-cadherin levels potentially resulting in an increase in metastasis.
Identification of a functional point defect in SrTi O 3

Unveiling both the presence and nature of point defects is one of the biggest challenges in condensed matter physics and materials science. Particularly in complex oxides, even a minute amount of unavoidable point defects could generate novel physical phenomena and functions, such as visible light emission and ferroelectricity, yet it remains elusive to clearly identify such point defects. Here, taking $\mathrm{SrTi}{\mathrm{O}}_{3}$ as a model system, we show that iterative feedback among atomic-layer- and stoichiometry-controlled thin-film epitaxy, hybrid density functional theory, and high-resolution cathodoluminescence spectroscopy allows for the identification of a functional cationic defect, the Ti antisite (${\mathrm{Ti}}_{\mathrm{Sr}}$) defect. Our cathodoluminescence measurements reveal sub-band-gap luminescence, whose spectral fine structures show excellent quantitative agreement, as well as a one-to-one correspondence, with the theoretically predicted optical transitions from intrinsic point defects such as ${\mathrm{Ti}}_{\mathrm{Sr}}$. Guided by the theory and spectroscopic results, we also control a cation stoichiometry, and it in turn results in good systematics in cathodoluminescence spectra. Not limited to the identification of ${\mathrm{Ti}}_{\mathrm{Sr}}$, this approach allows for more reliable, self-consistent defect study, and provides critical insight into a microscopic picture of point defects in complex oxides.
Penetración de las Tecnologías de la Información en las Realidades Hospitalarias de los Países Latinoamericanos y del Caribe

The ICT’s has been Technologies that in last years has been entering in the daily activities of people all throught the World. Medicine is not an exeption of these, because there has been an important impact of these Technologies in the last decades these area, telemedicine is an example of these. The Present Study shows the degee of penetration of the ICT in our continent, and the dificulties that exists to make that our countries can have all the virtues of these new elements, and the politics that may help solve them
[The use of ultra deep sequencing technique in the screening program on HIV-1 drug resistance mutation among ART-naїve patients in Hunan province].

Objective To determine the prevalence rates of nucleotide reverse-transcriptase inhibitor （NRTI） and nonnucleoside reverse transcriptase inhibitor （NNRTI） TDRs among HIV-1 ART-na？ve patients in Hunan province using the ultra deep sequencing（UDS） technique. Methods ART-na？ve subjects diagnosed in Hunan between 2010 and 2011 were evaluated by both UDS technique and Sanger sequencing techniques,to the 1%variant level. Mutations were scored using the Stanford HIVdb algorithm to infer the status on drug resistance. Results UDS method was performed on 90 ART-na？ve subjects that seeking service of care,in Hunan. In total,42.2%（38/90）of the subjects showed major NRTI or nonnucleoside reverse transcriptase inhibitor NNRTI TDRs by UDS technique,at a HIV variant frequency level of≥1%,15.6%（14/90）showed NRTI TDR,16.7%（15/90） showed a major NNRTI TDR and 10%（9/90）were both resistant to NRTI and NNRTI when variants were analyzed by Stanford HIVdb. Conclusion ART-na？ve subjects from Hunan province, which had been predominately infected by subtype AE,would frequently possess HIV variants with NRTI/NNRTI TDRs that would affect the use of first line ART in the region,identified by the UDS technique. Further studies were needed to describe the prevalence of TDRs and to gather related information. Key words: HIV- 1 ; Drug resistance; Ultra deep sequencing; Sanger sequencing; Nucleotidereverse-transcriptase inhibitor; Nonnucleoside reverse transcriptase inhibitor
Human Nature Genetically Re-Engineered: Moral Responsibilities to Future Generations

The prospect of human genetic germ-line engineering raises questions regarding the propriety of altering the human genome. It raises questions as well regarding the ways in which one might understand responsibilities to the future generations who will experience the result of such alterations. This essay explores the difficulty of disclosing content-full obligations regarding genetic germ-line engineering. Instead, as this essay shows, one is at best guided by general canons of prudence and caution. There are no absolute bars, indeed, no special proscriptions in general secular morality, against the use of germ-line genetic engineering or against the project of enhancing the human genome. In particular, this essay will argue that point 8 of the “World Declaration on Our Responsibilities Towards Future Generations,” namely, that one has a responsibility “to ensure the transmission of the unique human genetic inheritance, free from any engineered alterations” (Agius 1994, p. 310), is indefensible, at least in general secular terms. In deed, if one endorses the first principle, namely, that one ensure the existence of future generations, this first principle will plausibly entail altering the human genome (Agius 1994, p. 308). Not only can the proscription against altering the human genome not be defended as a general secular moral constraint, indeed, the very opposite appears plausible. There are many conceivable circumstances under which one would find oneself obliged to alter the human genome.
Pillows of Faith

I bring the window of Emily Dickinson’s It Dropped So Low in My Regard to the landscape of what might help us distinguish precious from ordinary in our vocational exercise, and suggest how we might tolerate and buffer the shattering of various vocational illusions. I illustrate this allegory with an experience from my supervision practice.
Shaping the Political Environment: An Ethnography of Public Affairs Professionals at Work:

Relying on an ethnographic study of in-house public affairs professionals, this article sheds light on the process by which boundary-spanning occupations can shape an organization’s environment. Pu...
Evaluating a university’s investment in arts programming on student arts participation

ABSTRACTAn individual’s level of education has the strongest relationship with his or her arts participation. What is unclear, however, is why high-educated individuals are more likely to participa...
Preoperative Vitamin D Repletion in Total Knee Arthroplasty: A Cost-Effectiveness Model.

Abstract Background Recent studies have identified vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] Methods A cost estimation predictive model was generated to determine the utility of both selective and nonselective 25(OH)D repletion in primary TKA to prevent PJI. Input data on the incidence of 25(OH)D deficiency, relative complication rates, and costs of serum 25(OH)D repletion and 2-stage revision for PJI were derived from previously published literature identified using systematic review and publicly available data from Medicare reimbursement schedules. Mean, lower, and upper bounds of 1-year cost savings were computed for nonselective and selective repletion relative to no repletion. Results Selective preoperative 25(OH)D screening and repletion were projected to result in $1,504,857 (range, $215,084-$4,256,388) in cost savings per 10,000 cases. Nonselective 25(OH)D repletion was projected to result in $1,906,077 (range, $616,304-$4,657,608) in cost savings per 10,000 cases. With univariate adjustment, nonselective repletion is projected to be cost-effective in scenarios where revision for PJI costs ≥$10,636, incidence of deficiency is ≥1.1%, and when repletion has a relative risk reduction ≥4.2%. Conclusion This predictive model supports the potential role of 25(OH)D repletion as a cost-effective mechanism of reducing PJI risk in TKA. Given the low cost of 25(OH)D repletion relative to serum laboratory testing, nonselective repletion appears to be more cost-effective than selective repletion. Further prospective investigation to assess this modifiable risk factor is warranted.
Indigenizing the Doctoral Experience to Build Indigenous Community Leaders in Educational Leadership

In this case, readers will learn how the University of New Mexico educational leadership program intentionally created a doctoral cohort that is Indigenous based and focused that included Indigenou...
Viral and Bacterial Fecal Indicators in Untreated Wastewater across the Contiguous United States Exhibit Geospatial Trends

Cultivated fecal indicator bacteria such as Escherichia coli and enterococci are typically used to assess the sanitary quality of recreational waters. However, these indicators suffer from several limitations, such as the length of time needed to obtain results and the fact that they are commensal inhabitants of the gastrointestinal tract of many animals and have fate and transport characteristics dissimilar to pathogenic viruses. Numerous emerging technologies that offer same-day water quality results or pollution source information or that more closely mimic persistence patterns of disease-causing pathogens that may improve water quality management are now available, but data detailing geospatial trends in wastewater across the United States are sparse. We report geospatial trends of cultivated bacteriophage (somatic, F+, and total coliphages and GB-124 phage), as well as genetic markers targeting polyomavirus, enterococci, E. coli, Bacteroidetes, and human-associated Bacteroides spp. (HF183/BacR287 and HumM2) in 49 primary influent sewage samples collected from facilities across the contiguous United States. Samples were selected from rural and urban facilities spanning broad latitude, longitude, elevation, and air temperature gradients by using a geographic information system stratified random site selection procedure. Most indicators in sewage demonstrated a remarkable similarity in concentration regardless of location. However, some exhibited predictable shifts in concentration based on either facility elevation or local air temperature. Geospatial patterns identified in this study, or the absence of such patterns, may have several impacts on the direction of future water quality management research, as well as the selection of alternative metrics to estimate sewage pollution on a national scale.IMPORTANCE This study provides multiple insights to consider for the application of bacterial and viral indicators in sewage to surface water quality monitoring across the contiguous United States, ranging from method selection considerations to future research directions. Systematic testing of a large collection of sewage samples confirmed that crAssphage genetic markers occur at a higher average concentration than key human-associated Bacteroides spp. on a national scale. Geospatial testing also suggested that some methods may be more suitable than others for widespread implementation. Nationwide characterization of indicator geospatial trends in untreated sewage represents an important step toward the validation of these newer methods for future water quality monitoring applications. In addition, the large paired-measurement data set reported here affords the opportunity to conduct a range of secondary analyses, such as the generation of new or updated quantitative microbial risk assessment models used to estimate public health risk.
An upper bound on the minimum PO2 for O2 consumption in red muscle.

At a certain PO2 the rate of O2 consumption (VO2) becomes limited by O2 availability rather than energy demand. This PO2 may be defined as the critical PO2 (PcritO2) for the corresponding rate of cytochrome turnover. PcritO2 sets the minimum PO2 which convective and diffusive transport must defend. To date there have been no estimates of PcritO2 for VO2 in vivo, though the influence of O2 on redox ratios has been studied extensively in heart, liver and brain. Some contend that cytochrome a,a3 is highly reduced in tissue over the entire physiologic range of O2 tensions.1,2 Such reduction implies that tissue respiration should be strongly O2 dependent and that there should be no PcritO2 for VO2 in vivo. Chance and associates studied O2 binding to cytochrome a, a3 in brain in the presence and absence of CO.3 They interpret their data to mean that cytochrome a, a3 is almost fully oxidized in vivo and in vitro. Lubbers and associates found cytochrome a, a3 more than 95% oxidized in rat heart (personal communication). Highly oxidized a, a3 suggests that VO2 depends solely on redox and phosphorylation potentials above a PO2 negligible for O2 transport.
Conformal, waterproof electronic decals for wireless monitoring of sweat and vaginal pH at the point-of-care.

Abstract While the monitoring of pH has demonstrated to be an effective technique to monitor an individual's health state, the design of wearable biosensors is subject to critical challenges, such as high fabrication costs, thermal drift, sensitivity to moisture, and the limited applicability for users with metal allergies. This work describes the low-cost fabrication of waterproof electronic decals (WPEDs): highly conformable disposable biosensors capable of monitoring sweat and vaginal pH. WPEDs contain a polyaniline/silver microflakes sensing layer optimized for accurate impedance-based pH quantification across the clinically relevant range of variation of most biofluids. WPEDs also contain a heating layer that serves to both stimulate sweating and prevent saturation of the sensing area, reducing the variability of the measurements. The conformability of WPEDs enables their simple and allergy-free attachment to skin, where they can monitor sweat pH, or to the surface of paper-based sample containers, for the pH-based diagnosis of bacterial vaginosis. WPEDs are mostly transparent, self-adhesive, breathable, flexible, moisture-insensitive, and able to maintain their accuracy under significant mechanical and thermal stresses. A cost-effective wearable and portable impedance analyzer wirelessly transmits pH data in real-time to the smartphone of the user, where a custom-developed App enables long term monitoring and telemedicine applications. Our results demonstrate the feasibility of using inexpensive single-use WPEDs and a reusable, wireless impedance analyzer to provide a wearable solution for the real-time monitoring of sweat pH and the accurate at-home diagnosis of bacterial vaginosis, improving the capabilities of current low-cost, point-of-care diagnostic tests.
Bilateral Ptosis and Limb Myokymia: Regional Variant of Guillain-Barré Syndrome? Biltateral ptosis and limb myokymia in Guillain-Barré Syndrome?

Isolated bilateral ptosis as an initial sign of Guillain-Barre Syndrome (GBS) with subsequent limb paralysis or paresis has been reported. However, to our knowledge, bilateral ptosis with subsequent limb myokymia but without ophthalmoplegia, facial or extremity weakness has not been observed. Our patient developed severe bilateral ptosis over several days. There was no facial or extremity weakness although limb myokymia was seen. Laboratory studies excluded common causes of ptosis and were suggestive of GBS. We believe our patient extends the clinical spectrum of GBS, and that binocular ptosis represents a mild regional variant of this neuropathy.
A novel method of donor‒recipient size matching in pediatric heart transplantation: A total cardiac volume‒predictive model

BACKGROUND The pediatric heart transplant community uses weight-based donor-to-recipient size matching almost exclusively, despite no evidence to validate weight as a reliable surrogate of cardiac size. Donor size mismatch is the second most common reason for the refusal of donor hearts in current practice (∼30% of all refusals). Whereas case-by-case segmentation of total cardiac volume (TCV) by computed tomography (CT) for direct virtual transplantation is an attractive option, it remains limited by the unavailability of donor chest CT. We sought to establish a predictive model for donor TCV on the basis of anthropomorphic and chest X-ray (CXR) cardiac measures. METHODS Banked imaging studies from 141 subjects with normal CT chest angiograms were obtained and segmented using 3-dimensional modeling to derive TCV. CXR data were available for 62 of those subjects. A total of 3 predictive models of TCV were fit through multiple linear regression using the following variables: Model A (weight only); Model B (weight, height, sex, and age); Model C (weight, height, sex, age, and 1-view anteroposterior CXR maximal horizontal cardiac width). RESULTS Model C provided the most accurate prediction of TCV (optimism corrected R2 = 0.99, testing set R2 = 0.98, mean absolute percentage error [MAPE] = 8.6%) and outperformed Model A (optimism corrected R2 = 0.94, testing set R2 = 0.94, MAPE = 16.1%) and Model B (optimism corrected R2 = 0.97, testing set R2 = 0.97, MAPE = 11.1%). CONCLUSIONS TCV can be predicted accurately using readily available anthropometrics and a 1-view CXR from donor candidates. This simple and scalable method of TCV estimation may provide a reliable and consistent method to improve donor size matching.
Affective Circuits: African migrations to Europe and the pursuit of social regeneration: edited by Jennifer Cole and Christian Groes, Chicago, University of Chicago Press, 2016, 354 pp., $38.00 (paperback), illustrations, bibliography, ISBN: 978-0-226-40515-5

Affective Circuits offers a remarkably stimulating reflection on mobility, social reproduction, and belonging at the intersection of affect theory and migration studies. Resolutely eschewing conven...
Transorbital penetrating injury: case series, review of the literature, and proposed management algorithm

Transorbital penetrating injury (TPI), an uncommon subset of head trauma, requires prompt multidisciplinary surgical intervention. While numerous case reports appear in the literature, there is a lack of discrete recommendations for initial evaluation, surgical intervention, and postoperative care of patients with TPI. A retrospective review of 4 cases of TPI at the University of Michigan Health System was undertaken to assess for diagnosis, treatment, and follow-up. In addition, a PubMed search using the terms “penetrating orbital trauma,” “penetrating orbital injury,” “transorbital penetration,” and “transorbital penetrating injury” were used to search for articles discussing the presentation and management of penetrating orbital trauma. All 4 of the patients at the University of Michigan underwent focused physical examination performed by a multidisciplinary trauma team followed by dedicated maxillofacial and head CT scanning. The patients' treatments varied, depending on the mechanism and extent of th...
Attempts to Detect Deoxyribonucleic Acid from Agrobacterium tumefaciens and Bacteriophage PS8 in Crown Gall Tumors by Complementary Ribonucleic Acid/Deoxyribonucleic Acid-Filter Hybridization

Labeled ribonucleic acid (RNA) complementary to Agrobacterium tumefaciens DNA and PS8 bacteriophage DNA (cRNA) were used in a systematic study of the sensitivity of cRNA/deoxyribonucleic acid (DNA)-filter hybridization for detection of small amounts of phage or bacterial DNA immobilized on filters. A. tumefaciens cRNA of specific activity 10(6) to 2 x 10(6) counts per min per mug reacted to a significant extent when the DNA-filter contained 1% A. tumefaciens DNA in a salmon DNA background, but 0.1% A. tumefaciens DNA was not detectable. PS8 phage cRNA of the same specific activity reacted to a significant extent when the DNA-filter contained as little as 0.01% PS8 DNA in a salmon DNA background. Both kinds of cRNA were found to bind to tobacco crown gall tumor DNA-filters. Similar reaction was found with control normal callus DNA-filters but not with tobacco seedling DNA-filters. The "hybrids" formed by cRNA with normal callus and tumor DNA-filters had low thermal stability. Attempts to purify the tumor and normal callus DNA prior to immobilization on the filter resulted in elimination of this spurious binding. No evidence was found for bacterial or phage DNA in crown gall tumor DNA.
The inexact and separate science of economics: Rationality and utility theory

Mainstream economics portrays agents as choosing rationally. Many generalizations in economics concerning how people do in fact choose are also claims about how they ought rationally to choose. If people are, to some reasonable degree of approximation, rational, then a theory of rational preference, belief, and choice will constitute an approximate theory of people's actual preferences, beliefs, and choices. The fact that economics is built around a theory of rationality distinguishes economics from the physical sciences, where quarks and polymers do not choose at all and whose theories have no comparable normative dimension. In common usage, someone is rational if and only if her motives, beliefs, and choices are appropriately sensitive to reasons. Spelling out this vague idea is a huge philosophical challenge. “Folk psychology” – the everyday theory of human rationality – takes actions to derive from constraints, beliefs, and a wide array of motivational factors such as urges, emotions, habits, and desires. So, for example, when one rainy Friday night a hungry student named Ellen takes a frozen pizza out of the refrigerator, unwraps it, puts it in her stove, and turns knobs on the stove, we folk psychologists explain Ellen's action by the constraints (pizzas do not get hot by themselves), Ellen's beliefs – including especially her beliefs that turning the knobs will cause the stove to heat the pizza – and her desire to eat hot pizza. This sort of explanation is familiar but not very satisfactory. Ellen might also like to eat her pizza frozen, or she might also have a desire to reheat some leftover meatloaf. Or she might rather skip dinner and keep studying decision theory. What explains her action is not merely wanting to eat hot pizza (plus possessing the requisite beliefs) but also wanting to do this as much as or more than she wants to carry out any of her feasible alternatives. The theory of rational choice that dominates economics is less ambitious than folk psychology: it aims only to specify formal conditions on preferences, beliefs, and choices. Economists tighten up the folk-psychological account of action by replacing the noncomparative notion of a “desire” with the comparative notion of a “preference.”
IMAGE RECONSTRUCTION FROM EXPERIMENTAL DATA IN DIFFUSION TOMOGRAPHY

The authors have recently introduced a novel imaging algorithm for optical/diffusion tomography, the “Elliptic Systems Method” (ESM). In this article the performance of the ESM is analyzed for experimental data. Images are obtained for the case of a single source and seven (7) detector locations, an unusually limited number of source/detector pairs. These images are verified by numerical simulation. A new approach to data fitting (at the detectors) is introduced.
A New Sensitive Method for Detecting Polyadenylate in Viral and Other Ribonucleic Acids Using Escherichia coli Deoxyribonucleic Acid Polymerase I

Abstract In the presence of messenger or viral RNA containing poly(A) stretches as a template and (dT)10 as a primer, DNA polymerase I from Escherichia coli synthesizes poly(dT) using dTTP as the sole precursor. No synthesis occurs when dATP is present as the sole precursor, although dATP is incorporated into acid-insoluble product in the presence of dTTP. Identical results were observed using the synthetic homopolymeric template poly(rA) with (dT)10 as added primer. Thus, poly(dT) synthesized on poly(A) stretches appears to serve as a template for the synthesis of poly(dA). Poly(dT) which has been synthesized using (dA)n·(dT)10 as template-primer does not allow the incorporation of dATP in the presence of dTTP. We have utilized these observations as a basis for the development of an extremely sensitive and precise technique for the detection of poly(A) stretches in any RNA sample. This technique can also be used in the presence of DNA but the sensitivity is decreased. Poly(A) can be detected in as little as 2 ng of mRNA.
Mycobacterium tuberculosis and Copper: A Newly Appreciated Defense Against an Old Foe?

Several independent studies have recently converged upon the conclusion that the human bacterial pathogen Mycobacterium tuberculosis encounters copper during infections. At least three independently regulated pathways respond to excess copper and are required for the full virulence of M. tuberculosis in animals. In this review, I will discuss the functions of the best-characterized copper-responsive proteins in M. tuberculosis, the potential sources of copper during an infection, and remaining questions about the interface between copper and tuberculosis.
Widespread Scaly Eruption in a Patient With Multiple Comorbidities

A 73-year-old African Americanwoman presented with a widespread scaly pruritic rash lasting 2 months. Her medical history included hypertension, diabetes, pulmonary sarcoidosis, and acid reflux, for which she takes amlodipine, carvedilol, repaglinide, hydroxychloroquine, and pantoprazole. Her history also included chronic renal insufficiency and chronic hepatitis C, for which she takes no medications. She reported no fevers, new skin exposures, oral ulcers, arthritis, alopecia, or photosensitivity and no worsening pulmonary symptoms of cough or shortness of breath. The rash did not improve after 2 weeks of applying topical triamcinolone ointment (0.1%). Physical examination revealed annular coalescing scaly patches with erythematous borders on her forehead, neck, back, and upper and lower extremities (Figure, panels A and B). Laboratory workup revealed an antinuclear antibodies titer of 1:80 with a speckled pattern, elevated Sjogren syndrome–related antigen A (SS-A) level (>8 AI), and no elevation of Sjogren syndrome–related antigen B (SS-B), ribonucleoprotein, double-stranded DNA, Smith, or anti-histone antibodies. Complete blood cell count, erythrocyte sedimentation rate, and C-reactive protein level were within normal limits. Creatinine level was elevated but stable at 1.8 mg/dL (159.1 μmol/L). Skin biopsy revealed an inflammatory pattern of vacuolar interface dermatitis (Figure, panel C). Quiz at jama.com A B
A sensitive enzymeless hydrogen-peroxide sensor based on epitaxially-grown Fe3O4 thin film.

Abstract A novel and facile approach has been developed to synthesize thin films of magnetite (Fe 3 O 4 ) with epitaxial needle-like columnar grains on titanium nitride (TiN) buffered substrate using DC magnetron reactive sputtering. TiN buffer layer was first sputtered onto a substrate at 550 °C as a preferable substrate for growth following sputtering of epitaxial crystalline Fe 3 O 4 at 300 °C. The as-synthesized epitaxial Fe 3 O 4 was extensively characterized. The electrocatalytic activity of the epitaxial Fe 3 O 4 thin-film sensor against hydrogen peroxide (H 2 O 2 ) reduction was rapid with a response time less than 5 s. The sensor also exhibited an acceptable stability, a satisfying sensitivity of 432.2 μA mM −1 cm −2 , good specificity to the substrate, a dynamic working range of up to 0.7 mM and a low detection limit of 1.0 μM. The sensor performance correlated well ( R 2 = 0.996) with results obtained using a commercial HPLC-UV device. The sensor performance was robust and accurate in measuring H 2 O 2 in some complex matrices. The advantages of relative simplicity and ease of mass production make the epitaxial Fe 3 O 4 thin film promising candidate for use in sensing applications.
Agonist-induced down-regulation of m1 muscarinic receptors and reduction of their mRNA level in a transfected cell line

Agonist-induced reduction in both the number of m1 muscarinic receptors and the mRNA coding for the receptor protein was investigated in Chinese hamster ovary (CHO) cells which were transfected with the m1 muscarinic receptor gene. Receptor concentration was measured by the specific binding of the muscarinic ligand, [3H]quinuclidinyl benzilate ([3H]QNB), and Northern blot hybridization analysis was used to evaluate the levels of receptor mRNA. Incubation of cells with 1 mM of the muscarinic agonist, carbamylcholine (CBC), for 24 h decreased receptor density and mRNA levels in cells by 65% and 73%, respectively. These results indicate that agonist-induced down-regulation of m1 muscarinic receptors might be due to, at least in part, a decrease in receptor synthesis resulting from a reduction in the steady-state level of their mRNA.
Central role of the Holliday junction helicase RuvAB in vlsE recombination and infectivity of Borrelia burgdorferi.

Antigenic variation plays a vital role in the pathogenesis of many infectious bacteria and protozoa including Borrelia burgdorferi, the causative agent of Lyme disease. VlsE, a 35 kDa surface-exposed lipoprotein, undergoes antigenic variation during B. burgdorferi infection of mammalian hosts, and is believed to be a critical mechanism by which the spirochetes evade immune clearance. Random, segmental recombination between the expressed vlsE gene and adjacent vls silent cassettes generates a large number of different VlsE variants within the infected host. Although the occurrence and importance of vlsE sequence variation is well established, little is known about the biological mechanism of vlsE recombination. To identify factors important in antigenic variation and vlsE recombination, we screened transposon mutants of genes known to be involved in DNA recombination and repair for their effects on infectivity and vlsE recombination. Several mutants, including those in BB0023 (ruvA), BB0022 (ruvB), BB0797 (mutS), and BB0098 (mutS-II), showed reduced infectivity in immunocompetent C3H/HeN mice. Mutants in ruvA and ruvB exhibited greatly reduced rates of vlsE recombination in C3H/HeN mice, as determined by restriction fragment polymorphism (RFLP) screening and DNA sequence analysis. In severe combined immunodeficiency (C3H/scid) mice, the ruvA mutant retained full infectivity; however, all recovered clones retained the ‘parental’ vlsE sequence, consistent with low rates of vlsE recombination. These results suggest that the reduced infectivity of ruvA and ruvB mutants is the result of ineffective vlsE recombination and underscores the important role that vlsE recombination plays in immune evasion. Based on functional studies in other organisms, the RuvAB complex of B. burgdorferi may promote branch migration of Holliday junctions during vlsE recombination. Our findings are consistent with those in the accompanying article by Dresser et al., and together these studies provide the first examples of trans-acting factors involved in vlsE recombination.
Linking Customer Management Effort to Customer Profitability in Business Markets

Abstract Chain-link frameworks such as the service–profit chain (SPC) are much discussed as a means to link customer profits to operational resources under the influence of vendor managers, though empirical testing to date has been limited primarily to consumer services settings. In this article, the authors adapt the SPC framework to accommodate characteristics of business markets, specifically the complex decisionmaking unit, strategic supplier selection, and resource allocation at the individual customer level. They also extend the SPC framework to allow for a richer description of the complex linkages between vendor effort and account profitability, namely, nonlinear linkages and differential responsiveness occasioned by customer-specific factors such as competitive context. Controlling for such factors illuminates, to some degree, why similar levels of customer management effort and/or performance can yield quite different customer profitability outcomes. The authors present an application that demon...
Molecular beam facility for studying mass spectrometer performance

An apparatus which produces neutral gas beams in the velocity range from thermal to 6 km/s makes possible studies simulating the motion of instruments through tenuous atmospheres. Use of the apparatus in studying the response of an open-source mass spectrometer is examined. Experiments performed include responses when the instrument is in a normal mode of operation, when the ion source potentials are adjusted to reject striking gas particles, when the beam is restricted so that portions of the ion source are struck, and when the beam strikes at angles other than normal incidence. Results indicate specular radiation of particles out of the source and stagnation ratios close to unity for normal operation. Retarding potential studies dropped the sensitivity by a factor of about 10, and as angles of attack are varied, the effect was found to depend upon beam velocity and the way the ions are initially accelerated.
Young Children's Production and Comprehension of Nonverbal Deictic Behaviors.

Summary The production of pointing, the understanding of pointing and the comprehension of another's line of regard was investigated in 36 male and female infants 9-, 12-, and 14-months-old. Production of pointing was present in eight out of twelve 12-month-olds and in eleven out of twelve 14-month-olds; only a few of the youngest Ss pointed. For the youngest infants comprehension of pointing was a function of the distance between the person pointing and the object pointed to. All 12- and 14-month-old children comprehended the pointing to a nearby object and most of them also understood the pointing to a distant object. Ten out of twelve 12-month-olds and eleven out of twelve 14-month-olds were able to tell where another person was looking if both the cues of movement and orientation of the head and the eyes were present; their performance was less perfect with only the cue of orientation present or with only the eyes moving. Never more than three out of the twelve youngest Ss succeeded on any of these pe...
Government Performance as a Basis for Machine Support

In this article we examine how well the classic model of the urban party organization, with its emphasis on patronage and other particularized incentives (Banfield and Wilson, 1963), explains the survival of Chicago's machine. Our analysis of survey data collected after Mayor Daley's last primary campaign suggests that the machine had expanded its base of support to include voters concerned with a more collective good: the efficient delivery of city services. "The city that works" was a public good that the machine had to deliver to continue its control of Chicago politics.
Magnetic field modulation of receptor binding

Although it is widely held that the magnetic fields encountered during magnetic resonance imaging (MRI) and other procedures have no discernible effect on biological systems, we find that at early times of incubation, the amount of binding of the neurotoxin, α-bungarotoxin, to nicotinic acetylcholine receptor is significantly reduced in a constant 2.0-T magnetic field. This finding suggests that steady magnetic fields can directly affect the functional activity of biologically important macromolecules, in this particular case a neurotransmitter receptor. © 1989 Academic press, Inc.
Enhancing West Nile Virus Surveillance, United States

We provide a method for constructing a county-level West Nile virus risk map to serve as an early warning system for human cases. We also demonstrate that mosquito surveillance is a more accurate predictor of human risk than monitoring dead and infected wild birds.
Ribonuclease-stable polysomes in the egg of Ascaris lumbricoides

Abstract Ribosomes from precleavage and cleaving eggs of Ascaris lumbricoides , pulse-labelled with 3 H-uridine, have been investigated by density-gradient centrifugation. It has been found that there is a large proportion of ribosomal aggregates (polysomes) compared to single ribosomes in the egg throughout early development. Much of the polysome fraction in the 0-day egg is unusually stable, both to preincubation and to low concentrations of RNase. This stability decreases during cleavage. Exposure to higher concentrations of RNase results in more extensive breakdown of the stable polysomes, while pretreatment with trypsin renders them susceptible to low concentrations of the enzyme. Some of the newly synthesized (radioactive) RNA is associated with the stable polysomes in the 0-day egg. During blastulation, however, much of the polysome fraction, and all of the newly synthesized RNA associated with it, is directly susceptible to decomposition by low concentrations of RNase. It has also been shown, by testing the protein synthesizing capacity of the ribosome preparations, that the stable polysomes are inactive in protein synthesis, but that they become activated following treatment with trypsin. The possible significance of these observations relative to the biology of Ascaris eggs is discussed.
The effect of sulfhydryl reagents on freezing resistance of hardened and unhardened cabbage cells.

Summary Pretreatment of cabbage sections with nontoxic concentrations of the sulfhydryl reagents PCMB or IA decreased their resistance to freezing injury. Thiols had no effect. As the plants hardened, the SH reagents produced less and less of a decrease in their resistance to freezing injury. This result is explained by a decrease in or protection of protein SH. The decrease in freezing resistance is the opposite of what would be predicted by the SH hypothesis of freezing injury, if the SH reagents simply prevent intermolecular SS formation, but other evidence indicates that they also induce some protein unfolding. It is proposed that this unfolding favors the aggregation of proteins on freezing.
A Semantic Congruity Effect in Children's Acquisition of High and Low

Abstract The Semantic Congruity Effect (SCE) is the finding that children and adults asked to compare pairs of objects drawn from a series perform better when the direction of comparison coincides with the location of the objects in the series. Experiment 1 confirmed that this effect is due to an understanding of the dimension words involved and not to general perceptual strategies by varying the words used to ask about the same stimuli (i.e.: higher / lower vs over / under ). Experiment 2 examined children's understanding of higher / lower and found that the SCE could be reduced or enhanced by altering the stimulus context. Theoretical explanations are discussed.
Novel type of murine B-cell lymphoma

ALTHOUGH several murine T-cell lymphomas have been well characterised (reviewed in ref. 1), only a single group of murine B-cell lymphomas, the Abelson lymphomas, has been described2. The Abelson lymphoma arose in a steroid-treated BALB/cCr mouse inoculated with Moloney leukaemia virus2, expresses surface immunoglobulin3–4 and can be transmitted by an infectious murine leukaemia virus2. We report here a new IgM-bearing B-cell lymphoma distinct from the Abelson lymphoma in its induction, pathogenesis and antigenic characteristics and which has many features in common with the widely studied guinea pig L2C lymphoma5–6.
The Federal Government and the Harassment of Black Leaders: A Case Study of Mayor Richard Arrington Jr. of Birmingham

Why do people break the rules? A tremendous amount of energy has been expended by citizens and academicians in trying to answer this question. But even a superficial survey of human behavior reveals that we all break rules. Therefore, a more relevant and interesting question is "Why, of all of the rule breakers, are some singled out for observation and investigation, being tried, and being officially pronounced as deviant?" At root, this question is based on the assumption that nothing is inherently deviant. That rules are the result of unique social environments is obvious by observing cross-cultural and historical variations in rule systems. That is, rules-whether they are values, role expectations, or a legal system-are not absolute; they are relative to culture and to historical period. It follows that there can be no rule breaking unless there are rules; and rules, including those defining crime, are socially developed. Crime, then, is behavior so defined. Furthermore, there can be no socially recognized rule breakers unless someone has recognized that rules have been broken and is
NMR study of sodium dispersed in zeolites

Abstract The electronic state of sodium metal dispersed in the cavities of zeolites was investigated by nuclear magnetic resonance. The dehydrated Na-zeolite samples were loaded with additional sodium by vapor transport. Using spin echo techniques at 77 K, a quadrupolar broadened 23 Na spectrum, assigned to Na introduced into zeolites NaX and NaY superimposed on the host framework 23 Na spectrum, was observed. Nuclear relaxation measurements reveal a rapid relaxation component of likely electronic origin. The temperature dependence and indications of magnetic order at low temperature suggest that the introduced Na is better described as interacting paramagnetic cluster ions than as metallic sodium clusters.
Intrinsic and extrinsic variables affecting sensitivity to radiation carcinogenesis

Mathematical models relating observed yield of cancers vs administered radiation dose have become popular in recent years, especially as means of predicting hazards associated with exposure conditions which are beyond the realm of practical experimentation. While the validity of these predictions remains a controversy, these models, especially the ..cap alpha..D + ..beta..D/sup 2/ model, have more recently been used to infer the mechanism(s) underlying the carcinogenic process. Through the analysis of simple experimental systems, we demonstrate in this report that aD + bD/sup 2/ kinetics can result from injury to the cells which eventually develop into the cancer (target cells) or from injury to those cells which affect target cell survival. Further, these kinetics can fail to predict the consequences of dose protraction, largely due to the fact that transformation increases with dose, while survival decreases. The role of these models in helping to develop an understanding of mechanisms should be restricted, therefore, to the formulation of basic hypotheses which are subject to direct testing in the laboratory.