cssi/SciSciGPT-SciSciNet huggingface dataset:
An apparent pause site in the transcription unit of the rabbit α-globin gene

Abstract Transcription of the rabbit α-globin gene begins primarily at the cap site, although some upstream start sites are also observed. Analysis by RNA polymerase run-on assays in nuclei shows that transcription continues at a high level past the polyadenylation site, after which the polymerase density actually increases in a region of about 400 nucleotides, followed by a gradual decline over the 700 nucleotides. These features are also observed in the transcription unit of the rabbit β-globin gene. The region with the unexpectedly high nascent RNA hybridization signal in the 3' flank contains a conserved sequence, KGCAGCWGGR (K = G or T, W = A or T, R = A or G), followed by an inverted repeat. The inverted repeat (perhaps with the conserved sequence) may be a pause site for RNA polymerase II, thus accounting for the increase in polymerase density. This sequence and inverted repeat are found in the 3′ flank of several globin genes and the simian virus 40 (SV40) early genes, as well as in the regions implicated in pausing or termination of transcription of eight different genes. Deletion of the conserved sequence and inverted repeat from the 3′ flank of the SV40 early region causes a small increase in the levels of transcription downstream from this site. Replacement with the conserved sequence and inverted repeat from the rabbit α-globin gene causes an accumulation of polymerases, supporting the hypothesis that polymerases pause at this site. This proposed pause site may affect the efficiency of termination at some sites further downstream, perhaps by loss of a processivity factor.
The ordered assembly of the phiX174-type primosome. I. Isolation and identification of intermediate protein-DNA complexes.

The φX-type primosome was discovered during the resolution and reconstitution in vitro of the complementary strand DNA replication step of the φX174 viral life cycle. This multienzyme bidirectional helicase-primase complex can provide the DNA unwinding and Okazaki fragment-priming functions at the replication fork and has been implicated in cellular DNA replication, repair, and recombination. We have used gel mobility shift assays and enhanced chemiluminescence Western analysis to isolate and identify the pathway of primosome assembly at a primosome assembly site (PAS) on a 300-nucleotide-long single-stranded DNA fragment. The first three steps do not require ATP and are as follows: (i) PriA recognition and binding to the PAS, (ii) stabilization of the PriA-PAS complex by the addition of PriB, and (iii) formation of a PriA-PriB-DnaT-PAS complex. Subsequent formation of the preprimosome involves the ATP-dependent transfer of DnaB from a DnaB-DnaC complex to the PriA-PriB-DnaT-PAS complex. The final preprimosomal complex contains PriA, PriB, DnaT, and DnaB but not DnaC. A transient interaction between the preprimosome and DnaG generates the five-protein primosome. As described in an accompanying article (Ng, J. Y., and Marians, K. J. (1996) J. Biol. Chem. 271, 15649-15655), when assembled on intact φX174 phage DNA, the primosome also contains PriC.
Accommodating institutional audit requirements within a liberal arts college integrated library system

Abstract By using an electronic spreadsheet in tandem with accounts payable activities in the fund-level-specific acquisitions module of an integrated library system (ILS), a library can assure itself of meeting institutional audit requirements. This additional step of T-ledger “journal” monitoring at the payee level does not involve a great deal of time when compared with the frustration of audit trail reconstruction relying solely on the limited sorting and proprietary data output capabilities of the ILS. In addition, true reconciliation with the institution's Business Office reports through use of this dual methodology provides the library with an accurate as well as timely cash-balance figure at the close of progressive report periods. It also enables budget-expenditure progress to be measured against previous calendar or fiscal year periods for either a random or cumulative average history.
Organizing for effective environmental design

The ability to incorporate environmental concerns into the product development process is becoming increasingly important as diverse constituents make greater demands upon firms for improved environmental performance. Based on a review of the capabilities literature, we propose that environmental design capability derives from expertise on environmental impacts and technologies both internal and external to the firm (knowledge resources) coordinated with product development teams through dense information networks (communication linkages) embedded in a context where environmental information is understood and valued (interpretive structures). Through a series of case studies, we find support for our proposition that environmental design capabilities are related to the integration of diverse knowledge resources. © 1997 John Wiley & Sons, Ltd and ERP Environment.
The Evaluation of Wood-Fired Cogeneration Investments Using Monte-Carlo Simulation

Monte-Carlo simulation was used in a capital budgeting decision involving the purchase of a wood-fired cogeneration plant. Two alternative capacities, 6-MW and 9-MVV plants, were considered in the analysis using net present value as the evaluation criterion. Risk profiles were generated for both investments as well as for the mean and variance of returns. When cash flows were approximated using annual cash flows, the resulting risk profiles did not produce a clear choice. However, using more realistic monthly cash flows, the 6-MW plant showed both a higher return and less risk than the 9-MW facility. The difference in the results arises from the fact that the annual-period model masks the effects of the inherent monthly variability of some cash flows and timing of cash savings. Consequently, the use of probabilistic, monthly-period models is recommended over the annual-period model in this as well as in other investments that incorporate a large degree of seasonal variability.
Su1481 Large Sessile Colorectal Polyps: Reduction in Delayed Bleeding With Prophylactic Clipping

Large Sessile Colorectal Polyps: Reduction in Delayed Bleeding With Prophylactic Clipping Hammad Liaquat*, Elizabeth A. Rohn, Douglas K. Rex Department of Medicine, Indiana University Health, Indianapolis, IN Resection of large ( 2cm) sessile colorectal polyps is associated with an increased risk of complications. We performed a retrospective assessment of the impact of prophylactic closure of polypectomy sites using Microvasive Resolution clips. There were 537 sessile colorectal polyps 2cm in size removed from 482 patients. We successfully completed follow up for complications by telephone after 30 days for 474 polyps. Mean age of the 420 patients with complete follow up was 67.4 years, mean polyp size 32.3mm, and 253 polyps were 3cm in size. Location was cecum 113, ascending colon 133, transverse 114, descending 22, sigmoid 31, rectum 61. There were 183 polyps removed before clips were available. After clips became available, 161 polypectomy sites were clipped fully closed according to the judgment of the endoscopist, 39 were partly closed, and 91 were not closed because of size or inability to access for clipping. All polyps were removed using snares and low power coagulation current. In most cases submucosal injection preceded resection and argon plasma coagulation followed it.The rate of clinically significant bleeding (hospitalization, transfusion, and/or repeat colonoscopy; total of 32 polyps) was 3.1% in the fully clipped group, 7.7% in the partly clipped, and 8.8% in the non-clipped group (p .02 for fully clipped vs not clipped and .04 for any clipping vs not clipped). The rate of bleeding after clipping became available was 4.8% vs 9.8% prior to availability of clipping (p .03). The rate of hospitalization for bleeding was lower in the fully clipped (1.9%; p .01) and any clipping (3%; p 0.4) groups compared to the not-clipped (7.3%) groups. There were no significant differences in need for transfusion between the fully clipped (1.2%) vs partly clipped (0%) and not clipped (2.9%) groups. There were 7 other serious complications, including 2 perforations and 5 postpolypectomy syndromes. The rate of serious complications (bleeding, perforation, or postpolypectomy syndrome) was 5.8% after clip availability vs 12% before (p 0.1). One perforation occurred prior to clip availability and required surgery. The other occurred after clip availability and was closed with clips without surgery. Conclusions: In a retrospective study, prophylactic clipping was associated with a reduced (but not eliminated) risk of delayed bleeding and overall major complications after endoscopic resection of large colorectal polyps. These results could assist in calculating sample sizes for a prospective controlled trial of prophylactic clipping for large sessile colorectal polyps. Reductions in the cost of treating complications may offset a substantial portion of the cost of prophylactic clipping.
A PARTICLE METHOD WITH ADJUSTABLE TRANSPORT PROPERTIES : THE GENERALIZED CONSISTENT BOLTZMANN ALGORITHM

The consistent Boltzmann algorithm (CBA) for dense, hard-sphere gases is generalized to obtain the van der Waals equation of state and the corresponding exact viscosity at all densities except at the highest temperatures. A general scheme for adjusting any transport coefficients to higher values is presented.
FIELD ENHANCEMENT IN SUPERCONDUCTING TUBES

Abstract An empirical formula, f av = ( o.d. i.d. ) 0.58 , describing the behaviour of a large class of specimens, is presented as evidence of an unexpected regularity in the field enhancement effect. Some clues as to the nature of its explanation are given.
Effect of Ionizable Residues on the Folding Energy Landscape of Globular Proteins: Linking Experiment and Computation

Ionizable residues play important role in protein structure, stability and function. In globular proteins, majority of ionizable residues are located on the protein surface. We have previously used computational approach to optimized surface charge-charge interactions in several globular proteins: ubiquitin, the activation domain of human procarboxypeptidase A2 (ADA2), the fibronectin typeIII domain (TnfIII), acylphosphatase (ACP), the N-terminal domain of human U1A protein (U1A), Cdc42 GTPase, Fyn SH3 domain, and cold shock protein CspB(1-3). Biophysical studies have shown that all the designed variants have increased thermodynamic stability. Here we have measured experimentally the folding kinetics of the wild-type and designed variants of four proteins: U1A, Ten, ACP and ADA2. We have also performed native topology-based model simulations that correspond to a funneled energy landscape, but explicitly include non-native charge-charge interactions. Analysis of computer simulations provided molecular details for the experimentally observed changes in the folding rates of charge-charge optimized variants.This work was supported by grants from the National Science Foundation MCB-0110396.References:1. Gribenko, A.V., Patel, M.M., Liu, J., McCallum, S.A., Wang, C., and Makhatadze, G.I. (2009) Rational stabilization of enzymes by computational redesign of surface charge-charge interactions, Proc Natl Acad Sci USA 106, 2601-2606.2. Makhatadze, G.I., Loladze, V.V., Gribenko, A.V., and Lopez, M.M. (2004) Mechanism of thermostabilization in a designed cold shock protein with optimized surface electrostatic interactions, J Mol Biol 336, 929-942.3. Schweiker, K.L., Zarrine-Afsar, A., Davidson, A.R., and Makhatadze, G.I. (2007) Computational design of the Fyn SH3 domain with increased stability through optimization of surface charge charge interactions, Protein Sci 16, 2694-2702.4. Strickler, S.S., Gribenko, A.V., Gribenko, A.V., Keiffer, T.R., Tomlinson, J., Reihle, T., Loladze, V.V., and Makhatadze, G.I. (2006) Protein stability and surface electrostatics: a charged relationship, Biochemistry 45, 2761-2766.
Microstrip Dispersion Including Anisotropic Substrates

A perturbation-iteration solution based on potential theory is developed for determining the effective dielectric constant, characteristic impedance, and current-charge distribution on a microstrip transmission line with isotropic and anisotropic substrates. The numerical implementation of the theory is described and is suitable for use on a personal computer. Computed data for several common substrate materials are included.
Bronchial hyperresponsiveness, word descriptors, and ethnicity: women with mild asthma.

Background. Few studies have examined the ethnic differences in symptom reporting and airway hyperresponsiveness (AHR) for women with mild asthma during a methacholine (McH) challenge. Objective. The purpose of this sub-analysis was to determine: (1) whether AHR to McH varied by the ethnicity of women with mild asthma and (2) whether ethnic word descriptors (EWDs) varied by the ethnicity during induced bronchoconstriction. Methods. Specific inclusion criteria included the following: FEV1 (forced expiratory volume in 1 second) ≥ 70% predicted normal, PC30 ≤ 8 mg/McH, β2 inhaler only, and self-reported ethnicity of African American (AFAM), Mexican American–Hispanic–Latino (MexAMLat), Asian-Pacific Islander (Asian PI), or white. Serial pulmonary function testing (PFT) and Borg, visual analogue scale (VAS), and EWDs were collected. Results. A total of 44 women, mean age of 31.3 years old, with a mean baseline FEV1 of 2.85 L comprised this sub-analysis. Ethnic–racial diversity included: 12 AFAMs, 5 MexAMLat, 1...
The lysosomal-mitochondrial axis in free fatty acid–induced hepatic lipotoxicity

Impaired mitochondrial function is largely thought to be a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms resulting in mitochondrial dysfunction in NAFLD remain poorly understood. This study examined the effects of excessive accumulation of free fatty acids (FFAs) in liver cells on mitochondrial function and the role of the lysosomal-mitochondrial axis on lipotoxicity. Primary mouse hepatocytes, HepG2 and McNtcp.24 cells, were treated with varied concentrations of FFAs with different degrees of saturation for up to 24 hours. Mitochondrial function was monitored by real-time imaging, cytochrome c redistribution, and reactive oxygen species (ROS) production. The temporal relationship of lysosomal and mitochondrial permeabilization was established. Activity of the lysosomal protease cathepsin B was suppressed by genetic and pharmacological approaches. Cathepsin B– knockout mice and wild-type animals were place on a high-carbohydrate diet for 16 weeks, and mitochondrial function and liver damage were assessed. Exposure of liver cells to saturated FFAs resulted in mitochondrial depolarization, cytochrome c release, and increased ROS production. Lysosomal permeabilization and cathepsin B redistribution into the cytoplasm occurred several hours prior to mitochondrial dysfunction. Either pharmacological or genetic inhibition of cathepsin B preserved mitochondrial function. Finally, cathepsin B inactivation protected mitochondria, decreased oxidative stress, and attenuated hepatic injury in vivo. Conclusion These data strongly suggest excessive accumulation of saturated FFAs in liver cells directly induce mitochondrial dysfunction and oxidative stress. Our data further suggest this process is dependent on lysosomal disruption and activation of cathepsin B.
Stem Cells on Fire: Inflammatory Signaling in HSC Emergence

Inflammatory pathways protect the body from infection and promote healing following injury. Recent reports demonstrate the surprising involvement of these pathways during hematopoietic stem cell emergence from the hemogenic endothelium in both zebrafish and mice.
A rigorous unidirectional method for designing finite aperture diffractive optical elements

We have developed a rigorous unidirectional method for designing finite-aperture diffractive optical elements (DOE's) that employs a micro-genetic algorithm (microGA) for global optimization in conjunction with a 2-D Finite-Difference Time-Domain (FDTD) method for rigorous electromagnetic computation. The theory and implementation of this microGA-FDTD design method for normally incident TE illumination are briefly discussed. Design examples are presented, including a micro-lens, a 1-to-2 beam-fanner and a 1-to-3 beam-fanner.
Double-Walled Microspheres for Drug Delivery

Present microsphere delivery system technology consisting of a single drug dispersed within a polymer matrix has several drawbacks. One is the problem of the so-called “burst effect”. By exploiting the phenomenon of phase separation between two immiscible polymers dissolved in a mutual solvent, a double-walled microsphere could be manufactured with the second polymer coating the polymer/drug matrix. This one-step process would give a consistent coating of even very small microspheres not achievable via normal, two-step coating processes and would help to smooth out the release curve by lessening the “burst effect”. Along with solving the problem of the “burst effect”, this concept of double-walled microspheres could be used to achieve constant release of the drug over long periods of time. So far, this has only been achieved with a limited number of geometric configurations. Since every polymer has its own characteristic release rate, the release could be kept much more constant by changing the polymer type and/or properties. By combining these layers so that the release rate of one layer would complement the slowing of release due to decreased surface area or increased diffusion distances.
Extended spectrum β-lactamase–producing Klebsiella pneumoniae chronic ambulatory peritoneal dialysis peritonitis treated successfully with polymyxin B

Peritonitis is not an infrequent complication of inpatients with chronic ambulatory peritoneal dialysis (CAPD). CAPD peritonitis may be related to the catheter or secondary to perforation of an intra-abdominal viscus. The most common organisms usually associated with CAPD peritonitis are Staphylococcus aureus and Staphylococcus epidermidis (coagulase-negative staphylococci). Rarely, aerobic gram-negative bacilli have been the causative agents of CAPD peritonitis. The treatment of CAPD peritonitis usually requires removal of the peritoneal catheter and treatment with parenteral antibiotics active against the causative pathogen. We report a case of CAPD-associated peritonitis caused by an extended spectrum beta-lactamase-producing strain of Klebsiella pneumoniae. The case presented had this strain of multidrug-resistant K. pneumoniae present in blood cultures and the peritoneal fluid. Extended spectrum beta-lactamase-producing bacteria, for example, K. pneumoniae, are multidrug-resistant and sensitive to few antibiotics. This isolate was intermediately sensitive to amikacin and meropenem, but the patient did not clinically improve on these 2 antibiotics. Polymyxin B therapy was initiated after lack of clinical improvement after dialysis catheter removal and 1 week of meropenem and amikacin therapy. The patient responded rapidly to therapy with polymyxin B. Polymyxin B has a unique mechanism of action on bacterial cells and is highly active against all multidrug-resistant gram-negative organisms except Proteus species and Serratia marcescens. No toxicity was observed during therapy. Polymyxin B is being used increasingly as a therapeutic alternative to multidrug-resistant gram-negative organisms.
Circulatory Changes during Growth in the Fetal Lamb

The changes in circulation with advancing gestation were investigated in 44 fetal lambs in utero; gestational ages ranged from about 60 days to 150 days. Spinal analgesia was administered to the ewe, polyvinyl catheters were inserted into fetal vessels, and umbilical blood flow was measured by the steady-state diffusion Fick method during antipyrine infusion. Cardiac output, distribution of cardiac output, and actual organ blood flows were calculated from injections of nuclide-labeled microspheres (50µ diam) into a forelimb and into an umbilical or hindlimb vein. Umbilical Po 2 , Pco 2 and pH did not change significantly during gestation. Umbilical blood flow and total cardiac output increased in proportion to fetal weight. The proportion of the combined ventricular output distributed to the placenta decreased from about 50% in the youngest fetuses to about 40% just before term. The proportion of the cardiac output distributed to the lungs, as well as the actual flow in relation to lung weight, increased throughout gestation, with a more rapid rise after about 120 days. There was also a late increase in intestinal flow. Cerebral blood flow increased gradually throughout gestation, both as a proportion of cardiac output and in relation to brain weight. There were no significant changes in percent of cardiac output, or flow related to weight in the kidney, heart, or skin and muscular tissues. The studies suggest that, since lung blood flow is a relatively small proportion of total cardiac output, it is not important in regulating distribution of blood flow, but that the peripheral circulation in skin and muscle, which receives a large percent of fetal cardiac output, is the site where vasomotor responses may effect major redistribution of the fetal circulation.
COOPER, HERON, AND HEWARD'S APPLIED BEHAVIOR ANALYSIS (2ND ED.): CHECKERED FLAG FOR STUDENTS AND PROFESSORS, YELLOW FLAG FOR THE FIELD

At last, the field of applied behavior analysis has a beautifully crafted, true textbook that can proudly stand cover to cover and spine to spine beside any of the expensive, imposing, and ornately designed textbooks used by college instructors who teach courses in conventional areas of education or psychology. In this review, I fully laud this development, credit Cooper, Heron, and Heward for making it happen, argue that it signifies a checkered flag for students and professors, and recommend the book for classes in applied behavior analysis everywhere. Subsequently, I review its chapters, each of which could easily stand alone as publications in their own right. Finally, I supply a cautionary note, a yellow flag to accompany the well-earned checkered flag, by pointing out that, as is true with all general textbooks on applied behavior analysis, a major portion of the references involves research on persons who occupy only a tail of the normal distribution. To attain the mainstream role Skinner envisioned and most (if not all) behavior analysts desire, the field will have to increase its focus on persons who reside under the dome of that distribution.
Information Sharing and Order Variability Control Under a Generalized Demand Model

The value of information sharing and how it could address the bullwhip effect have been the subject of studies in the literature. Most of these studies used different forms of demand models, assuming that no order smoothing was used by the retailer and that the supplier has full knowledge of the retailer's demand model and order policy. In this paper, we contribute to the literature by starting with a most general demand model, coupled with a smoothing policy for order variability control. In addition, we do not require that the supplier has full knowledge of the retailer's demand model and order policy, but instead let the retailer share its projected future orders (and freely revise them as the retailer sees fit). Under such a setting, we first obtain a unifying formula for the magnitude of the bullwhip effect. The formula indicates that it is the forecast correlation over the exposure period as a whole that determines the magnitude of the bullwhip effect. We then quantify the value of information sharing and generalize the existing results in the literature. Finally, we explore the optimal smoothing parameters that could benefit the total supply chain. The resulting optimal policy resembles the postponement strategy. We find that information sharing together with order postponement improves the supply chain performance, even though the order variability may amplify in some cases.
Depth sensing indentation of nanoscale graphene platelets in nanocomposite thin films

Significant improvement of mechanical properties was observed recently in graphene platelet-epoxy nanocomposites relative to unfilled epoxy, such as an increase of the fracture toughness by 50% and dramatic decrease of fatigue crack growth rate. In this work, thin films of 0.1 wt.% of graphene platelet (GPL) – epoxy nanocomposites were fabricated and the nanoscale mechanical properties of the nanocomposite were investigated by nanoindentation. This provides information about the presence of characteristic length scales induced by the microstructure and the strength of the filler-matrix interface.
Localized multi-scale energy and vorticity analysis II. Finite-amplitude instability theory and validation

A novel localized finite-amplitude hydrodynamic stability analysis is established in a unified treatment for the study of real oceanic and atmospheric processes, which are in general highly nonlinear, and intermittent in space and time. We first re-state the classical definition using the multi-scale energy and vorticity analysis (MS-EVA) developed in Liang and Robinson [Liang, X.S., Robinson, A.R., 2005. Localized multiscale energy and vorticity analysis. I. Fundamentals. Dyn. Atmos. Oceans 38, 195–230], and then manipulate certain global operators to achieve the temporal and spatial localization. The key of the spatial localization is transfer-transport separation, which is made precise with the concept of perfect transfer, while relaxation of marginalization leads to the localization of time. In doing so the information of transfer lost in the averages is retrieved and an easy-to-use instability metric is obtained. The resulting metric is field-like (Eulerian), conceptually generalizing the classical formalism, a bulk notion over the whole system. In this framework, an instability has a structure, which is of particular use for open flow processes. We check the structure of baroclinic instability with the benchmark Eady model solution, and the Iceland–Faeroe Frontal (IFF) intrusion, a highly localized and nonlinear process occurring frequently in the region between Iceland and Faeroe Islands. A clear isolated baroclinic instability is identified around the intrusion, which is further found to be characterized by the transition from a spatially growing mode to a temporally growing mode. We also check the consistency of the MS-EVA dynamics with the barotropic Kuo model. An observation is that a local perturbation burst does not necessarily imply an instability: the perturbation energy could be transported from other processes occurring elsewhere. We find that our analysis yields a Kuo theorem-consistent mean–eddy interaction, which is not seen in a conventional Reynolds stress framework. Using the techniques of marginalization and localization, this work sets up an example for the generalization of certain geophysical fluid dynamics theories for more generic purposes.
Sorption of Brilliant Blue FCF in soils as affected by pH and ionic strength

Brilliant Blue FCF has been frequently used as a dye tracer to stain flow pathways in porous media. As an ionic organic molecule, the dye interacts in a complicated manner with the solid phase. For an adequate interpretation of stained flow pathways, the sorption characteristics of the dye need to be better understood. In this study, we investigate the suitability of Brilliant Blue FCF as a dye tracer in vadose zone hydrology. The objectives were to test the effect of aqueous solution chemistry on dye absorption spectra, and to evaluate the effect of ionic strength and type of cations on dye sorption to soils. Batch sorption studies were conducted with three different soils and different ionic strengths of the background solution. Ionic strength was adjusted with either CaCl or KCl. Sorption isotherms conformed to the Langmuir model, with the sorption capacity 2 ranging over one order of magnitude. Substantial sorption was found for the soil sample with the highest clay content and the lowest pH. Increasing ionic strength led to increased sorption of Brilliant Blue FCF. The type of background cation, Ca or K, did not influence sorption. In aqueous solution, the absorption spectrum of Brilliant Blue FCF is not sensitive to pH nor ionic strength. q 2000 Elsevier Science B.V. All rights reserved.
Substantial conformational change mediated by charge-triad residues of the death effector domain in protein-protein interactions

Protein conformational changes are commonly associated with the formation of protein complexes. The non-catalytic death effector domains (DEDs) mediate protein-protein interactions in a variety of cellular processes, including apoptosis, proliferation and migration, and glucose metabolism. Here, using NMR residual dipolar coupling (RDC) data, we report a conformational change in the DED of the phosphoprotein enriched in astrocytes, 15 kDa (PEA-15) protein in the complex with a mitogen-activated protein (MAP) kinase, extracellular regulated kinase 2 (ERK2), which is essential in regulating ERK2 cellular distribution and function in cell proliferation and migration. The most significant conformational change in PEA-15 happens at helices α2, α3, and α4, which also possess the highest flexibility among the six-helix bundle of the DED. This crucial conformational change is modulated by the D/E-RxDL charge-triad motif, one of the prominent structural features of DEDs, together with a number of other electrostatic and hydrogen bonding interactions on the protein surface. Charge-triad motif promotes the optimal orientation of key residues and expands the binding interface to accommodate protein-protein interactions. However, the charge-triad residues are not directly involved in the binding interface between PEA-15 and ERK2.
Improving child literacy in Africa: experiments with an automated reading tutor

This paper describes a research endeavor aimed at exploring the role that technology can play in improving child literacy in developing communities. An initial pilot study and subsequent four-month-long controlled field study in Ghana investigated the viability and effectiveness of an automated reading tutor in helping urban children enhance their reading skills in English. In addition to quantitative data suggesting that automated tutoring can be useful for some children in this setting, these studies and an additional preliminary pilot study in Zambia yielded useful qualitative observations regarding the feasibility of applying technology solutions to the challenge of enhancing child literacy in developing communities. This paper presents the findings, observations and lessons learned from the field studies.
War on Instagram: Framing conflict photojournalism with mobile photography apps:

This paper examines recent acclaim for professional embedded photojournalists who visually document the experience of US soldiers in Afghanistan using the popular mobile photo application Hipstamatic. These photos have stirred controversy among fellow journalists and cultural critics regarding the use of photo filters in Hipstamatic and similar app Instagram, their contribution to the de-professionalization of photojournalism, and the depiction of war as stylishly vintage. The debates about Hipstamatic and Instagram in war photography open up a whole series of enduring questions about distinctions between photography and illustration, photography and photojournalism, professional and amateur, and reporting and editorializing. In consideration of the shifting nature of digital photography, photojournalism, and specifically war photojournalism, I argue that this discourse about the use of mobile apps overlooks another important ethical issue: the implications of non-soldiers mimicking the imagined hand of t...
Dietary Phytochemicals, HDAC Inhibition, and DNA Damage/Repair Defects in Cancer Cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies.
Statistics of Earthquake Stress Drops on a Heterogeneous Fault in an Elastic Half-Space

We investigate properties of earthquake stress drops in simulations of evolving seismicity and stress field on a heterogeneous fault. The model consists of an inherently discrete strike-slip fault surrounded by a 3D elastic half-space. We consider various spatial distributions of frictional properties and analyze results generated by 150–300 model years. In all cases, the self-organized heterogeneous initial stress distributions at the times of earthquake failure lead to stress drops that are systematically lower than those predicted for a homogeneous process. In particular, the large system-sized events have stress drops that are consistently ∼25% of predictions based on the average fault strength. The type and amount of assumed spatial heterogeneity on the fault affect the stress-drop statistics of small earthquakes ( M L <5) more than those of the larger events. This produces a decrease in the range of stress drops as the earthquake magnitudes increase. The results can resolve the discrepancy between traditional estimates of stress drops and seismological observations. The general tendency for low stress drops of large events provides a rationale for reducing the statistical estimates of potential ground motion associated with large earthquakes.
An incremental step in patient safety: reducing the risks of retained foreign bodies by the use of an integrated laparotomy pad/retractor.

Retained foreign body is a recognized complication of abdominal, pelvic, and thoracic surgery and a cause of medical malpractice. Efforts to reduce its incidence include safe exposure and the use of fewer laparotomy pads. The EZ DASH is an absorbent 12-thickness laparotomy pad covering a malleable stainless steel mesh, providing both the needed retraction and a reduction in the use of individual pads. EZ DASH has been introduced into clinical use in 183 consecutive cases by specialty surgeons (colorectal, gynecology, and gynecologic oncology services) at multiple medical centers. The retractor may be shaped to the individual needs of an operating field, eg, the pelvis, and the small bowel secured behind the retractor, held in place by the tension of its mesh and the security of the abdominal wall. Positioning has been intuitive and secure, and the intraoperative use of sponges and of operating time have both been noticeably reduced. Among 183 cases, 91% of uses were felt to reduce OR time by ≤5 to ≥10 minutes. Ninety-three percent of EZ DASH cases used fewer individual laparotomy pads for small bowel retraction. Ninety-five percent of uses suggested a value added to the case by the operating surgeon with an expressed desire to use the product repeatedly. The EZ DASH is a simple method of obtaining small bowel retraction and laparotomy pad absorption with a reduction in the need for individual pads, providing excellent exposure for the operative field and reducing the risk of retained foreign body.
Cytomegalovirus disease in adult marrow transplant recipients receiving ganciclovir prophylaxis: a retrospective study.

Cytomegalovirus disease in adult marrow transplant recipients receiving ganciclovir prophylaxis: a retrospective study
Distress and the Parenting Dynamic Among BRCA1/2 Tested Mothers and Their Partners

OBJECTIVE To investigate the influence of dyadic parenting relationships on psychological distress among mothers tested for BRCA1/2 genetic mutations and their untested partners. METHODS Data were from a prospective study of mothers suspected to be at risk for hereditary breast/ovarian cancer who underwent genetic counseling and BRCA1/2 testing and their untested parenting partners (n = 109 parenting dyads). Participants completed assessments before and 1 month after genetic testing. Structural equation modeling was used to examine relationships among mothers' and partners' psychological distress, decisional conflict surrounding communication of test results to their offspring, and the parent-child communication relationship. Psychological distress was measured using items modified from the Brief Symptom Inventory. RESULTS Among mothers, greater psychological distress (B = 0.29, p < .001) and poorer parent-child communication (B = -0.12, p < .01) at baseline predicted greater distress at follow-up. Among partners, greater distress at baseline predicted greater distress at follow-up (B = 0.67, p < .001). Mother and partner decisional conflict at baseline were equally associated with the other dyad member's distress at follow-up (B = 1.17, p < .01), but not their own distress. CONCLUSIONS Our findings indicate that conflicted decision-making over family communication of hereditary breast/ovarian cancer genetic test results for one member of a parenting dyad adversely affects the other dyad member's psychological well-being. Interventions to improve outcomes for mothers who may be at-risk for hereditary breast and ovarian cancer and undergoing BRCA1/2 genetic testing should attend to mothers' and their partners' preferences regarding family communication about hereditary cancer risk.
Performance analysis of eigenportfolios for AR(1) process

In this paper, we analyze eigenportfolio returns for discrete AR(1) process. We derive closed-form expressions for Sharpe ratio and market exposure of eigenportfolios. We calculate and compare their performance for various model parameters. We validate AR(1) based covariance approximation for the market data of a basket with five stocks.
We Wear Suits and Lie to Each Other.

Objective The residency match process is stressful and costly for fourth-year medical students with significant personal and professional implications. We hypothesize that students use impression management (IM) tactics such as conforming to the perceived expectations of program directors and interviewers and to improve their chances of matching. Design After institutional review board approval, a piloted survey tool was administered to fourth-year medical students at 17 schools. Questions were divided into interviewing behavior categories—slight image creation (embellishing and tailoring), extensive image creation (constructing, inventing, and borrowing), image protection (omitting), and ingratiation (opinion conforming). Descriptive statistics are presented as percentages. Data were analyzed using chi-square test, Fischer exact test, and Bonferroni-adjusted p values where appropriate with statistical significance set at p Setting Allopathic medical schools in the United States. Participants Fourth-year medical students in the United States. Results The response rate was 21.3%. Respondents were equally male (49.7%)/female (50.3%), primarily 25 to 27-year old (65.9%) and located in the midwest (78.8%). Most attended public medical schools (73.1%). Statistically significant findings are presented in the Tables. Conclusions Fourth-year medical students feel the need, and in some instances, actually engage in IM tactics. This study demonstrates that IM tactics are used, and vary by interviewee characteristics. Program directors’ awareness of IM tactics may help improving the quality of residency interviews and therefore select more suitable candidates.
Abstract 905: Pterostilbene (PTER) suppresses breast cancer brain metastasis by targeting a c-Met mediated inflammation network

At the late stage of breast cancer, most patients develop metastatic lesions and the brain is one of the major metastatic sites. Brain metastasis profoundly affects the cognitive and sensory function as well as morbidity of patients, and the one year survival rate among these patients remains less than 20%. The result of our newly developed gene set enrichment analysis (GSEA)-based pathway screening indicates that c-Met pathway is highly activated among the patients who developed early brain metastasis. To identify a novel target of c-Met pathway in brain metastasis, we performed the microarray analysis in two brain metastatic cell lines with the expression of doxycycline-inducible sh-cMet. Our results indicate that a group of inflammatory cytokines including IL1b, IL8 and CXCL1 were significantly induced by c-Met activation. Furthermore, we found that IL1b was able to induce the secretion of HGF (hepatocyte growth factor) from tumor associated astrocytes (TAA) which in turn activates c-Met pathway in cancer cells. Our results of endothelial cell tube formation assays also strongly suggest that cMet-induced IL8 and the activation of its receptor, CXCL1, promote tumor angiogenesis which is essential for the metastatic growth of cancer cells. Natural compounds (NC) have been extensively studied for their anti-tumor effects. However, much less studies have been done on NC for the treatment/prevention of brain tumors mainly due to the obstacle of Blood-brain-barrier (BBB) permeability. To identify the NCs that can be used for treating brain metastasis, we performed pathway analysis which only focused on BBB-permeable NC. The results of GSEA indicate that Resveratrol-targeting genes were significantly enriched among those patients who developed brain metastasis compared to metastasis-free patients. Furthermore, we found that the one of derivatives of Resveratrol, Pterostilbene (PTER), showed significantly more potent activity than Resveratrol and suppressed brain metastasis in vitro and in vivo by targeting the c-Met oncogene. These findings suggest that TAA-mediated c-Met activation plays a key role in brain metastasis and that PTER is a potential therapeutic agent to treat brain metastasis by suppressing the c-Met expression. Citation Format: Fei Xing, Yin Liu, Sambad Sharma, Kerui Wu, Kounosuke Watabe. Pterostilbene (PTER) suppresses breast cancer brain metastasis by targeting a c-Met mediated inflammation network. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 905.
Next-generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance.

Background Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance. Methods Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS). Results When genes with an incidence > 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached. Conclusions In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.
G Proteins and Heart Failure

Gproteins (GTP-binding proteins) are heterodimeric protein complexes consisting of α, β, and γ subunits. G proteins transduce signals from 7-transmembrane receptors (also known as G protein–coupled receptors [GPCRs]) to effector molecules. There are 20 distinct Gα subunits (≈40 000 molecular weight), 6 distinct β subunits (≈35 000 molecular weight), and 12 γ subunits (≈8 000 molecular weight). The Gα is the major determinant of signaling selectivity, which is largely executed via one of the four major subfamilies: (1) Gα s: activation of adenylate cyclase; (2) Gα i/o: inhibition of adenylate cyclase; (3) Gαq (Gαq, Gα11, Gα14, Gα15/16): activation of phospholipase C; and (4) Gα12/13: function yet unclear.1 Why is it important to research cardiac G proteins? The answer to this question is straightforward. First, GPCRs are present in the heart, and they transduce the major (if not the most important) signaling pathways associated with cardiac remodeling, as evidenced by the action of angiotensin II, endothelin-1, and the sympathetic neurohormonal systems on cardiac remodeling. Second, substantial alteration in the expression and function of Gα proteins occurs in heart failure, eg, increase in Gαi.2 Third, there are proven benefits of specific antagonists of GPCRs, eg, angiotensin II AT1 receptors and β-adrenergic …