cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B11: Oncogenic KRAS regulates 4E-BP1, a repressor of cap-dependent translation, independently of growth factor activity

Oncogenic mutations in K-Ras often occur at high frequencies in human cancer resulting in the sustained activation of the ERK1/2 mitogen-activated protein kinase (MAPK) signaling pathway. However, the unique dependencies on upstream or downstream oncogenic signaling amongst the mutant K-Ras proteins remains elusive and often masked by the remaining wild-type allele, other Ras isoforms, or additional secondary genetic alterations. Thus, we employed an isogenic mouse embryonic fibroblast (MEFs) system devoid of H-, N-, and K-Ras alleles and reconstituted with a single Ras isoform to examine the dependencies of growth factors on K-Ras mediated control of translational regulation. Although oncogenic K-Ras G12D and G12V mutant MEF lines proliferated at twice the rate of K-Ras4b wild-type MEF cells, growth factor deprivation led to a cytostatic effect on the proliferation of all MEF lines. Analysis of signaling downstream of K-Ras revealed that phosphorylation of 4E-BP1, eIF4E, and ERK1/2 occurred in a growth factor-independent manner, which stood in contrast to the substantive effects of growth factor inhibition on AKT, p70S6K, and ribosomal protein S6 phosphorylation. Moreover, growth factor deprivation resulted in a marginal decrease of global protein synthesis with negligible effects on cap-dependent translation initiation in all K-Ras MEF cell lines. Taken together, these data suggest that oncogenic K-Ras signaling regulates 4E-BP1 phosphorylation independently of growth factor and mTORC1/2 effects. Citation Format: Jillian M. Silva, Rachel K. Bagni, Davide Ruggero, Frank McCormick. Oncogenic KRAS regulates 4E-BP1, a repressor of cap-dependent translation, independently of growth factor activity. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B11.
Coupling distributed stormwater collection and managed aquifer recharge: Field application and implications.

Groundwater is increasingly important for satisfying California's growing fresh water demand. Strategies like managed aquifer recharge (MAR) can improve groundwater supplies, mitigating the negative consequences of persistent groundwater overdraft. Distributed stormwater collection (DSC)-MAR projects collect and infiltrate excess hillslope runoff before it reaches a stream, focusing on 40-400 ha drainage areas (100-1000 ac). We present results from six years of DSC-MAR operation-including high resolution analyses of precipitation, runoff generation, infiltration, and sediment transport-and discuss their implications for regional resource management. This project generated significant water supply benefit over six years, including an extended regional drought, collecting and infiltrating 5.3 × 105 m3 (426 ac-ft). Runoff generation was highly sensitive to sub-daily storm frequency, duration, and intensity, and a single intense storm often accounted for a large fraction of annual runoff. Observed infiltration rates varied widely in space and time. The basin-average infiltration rate during storms was 1-3 m/d, with point-specific rates up to 8 m/d. Despite efforts to limit sediment load, 8.2 × 105 kg of fine-grained sediment accumulated in the infiltration basin over three years, likely reducing soil infiltration capacity. Periodic removal of accumulated material, better source control, and/or improved sediment detention could mitigate this effect in the future. Regional soil analyses can maximize DSC-MAR benefits by identifying high-infiltration capacity features and characterizing upland sediment sources. A regional network of DSC-MAR projects could increase groundwater supplies while contributing to improved groundwater quality, flood mitigation, and stakeholder engagement.
A novel stochastic wave model statistically replicating reverberation chambers

This paper presents a novel physics-oriented statistical representation for complex multipath environments, and develops a hybrid deterministic and stochastic formulation incorporating component-specific characteristics. The advancements lead to a stochastic wave model statistically replicating mode-stirred reverberation chambers, and establish an imperative design-under-chaos capability for electronic devices and systems. The research work is evaluated and validated through representative experiments.
Learning aspects of decision aids

Multiple criteria tasks often involve high levels of subjectivity and uncertainty. Decision making also is usually dynamic, with many changes in environment along with new understanding on the part of decision makers. This makes it attractive to view multiple criteria support as support to a flexible learning process. Some recent multiple criteria decision aids have sought to provide this type of support.
Beverly Murphy, AHIP, FMLA, Medical Library Association President, 2018-2019.

When I think of Beverly Murphy, AHIP, FMLA, three words come to mind: Bold, Brave, Brilliant. In every action that Beverly has undertaken as a health sciences librarian, she has demonstrated an innate ability to just “Be.” Being bold, brave, and brilliant is just what she will need to be as the Medical Library Association’s first African-American president since the association’s founding in 1898.
Ca2+-mediated activation of the skeletal-muscle ryanodine receptor ion channel

Cryo-electron micrograph studies recently have identified a Ca2+-binding site in the 2,200-kDa ryanodine receptor ion channel (RyR1) in skeletal muscle. To clarify the role of this site in regulating RyR1 activity, here we applied mutational, electrophysiological, and computational methods. Three amino acid residues that interact directly with Ca2+ were replaced, and these RyR1 variants were expressed in HEK293 cells. Single-site RyR1-E3893Q, -E3893V, -E3967Q, -E3967V, and -T5001A variants and double-site RyR1-E3893Q/E3967Q and -E3893V/E3967V variants displayed cellular Ca2+ release in response to caffeine, which indicated that they retained functionality as caffeine-sensitive, Ca2+-conducting channels in the HEK293 cell system. Using [3H]ryanodine binding and single-channel measurements of membrane isolates, we found that single- and double-site RyR1-E3893 and -E3967 variants are not activated by Ca2+. We also noted that RyR1-E3893Q/E3967Q and -E3893V/E3967V variants maintain caffeine- and ATP-induced activation and that RyR1-E3893Q/E3967Q is inhibited by Mg2+ and elevated Ca2+. RyR1-T5001A exhibited decreased Ca2+ sensitivity compared with WT-RyR1 in single-channel measurements. Computational methods suggested that electrostatic interactions between Ca2+ and negatively charged glutamate residues have a critical role in transducing the functional effects of Ca2+ on RyR1. We conclude that the removal of negative charges in the recently identified RyR1 Ca2+-binding site impairs RyR1 activation by physiological Ca2+ concentrations and results in loss of binding to Ca2+ or reduced Ca2+ affinity of the binding site.
Casimir–Polder forces in inhomogeneous backgrounds

Casimir–Polder interactions are considered in an inhomogeneous, dispersive background. We consider both the interaction between a polarizable atom and a perfectly conducting wall, and between such an atom and a plane interface separating two different inhomogeneous dielectric media. A renormalization scheme is proposed, consisting of subtracting the interaction with the local inhomogeneous medium by itself. The results are expressed in general form, and generalize the Dzyaloshinskii–Lifshitz–Pitaevskii interaction between a spatially homogeneous dielectric interface and a polarizable atom.
26. PEDIATRIC RESIDENCY LEADERSHIPS’ ATTITUDES AND CURRENT PRACTICES TOWARD PARENTING-FOCUSED CURRICULA

Background Pediatricians are uniquely well-positioned to promote strong parent-child relationships and optimal child development, however, they may be less likely to do so if they receive no formal training in this area. No study has evaluated current resident education on parenting or pediatric residency leaderships’ view on the importance of training residents on parenting. Objective To assess pediatric residency leaders’ attitudes about educating residents on parenting skills and current training and desired curricula on parenting. Methods A 21-item survey was sent to the members of the Association for Pediatric Program Directors via email in May, 2017. Results 53 of the 206 program directors (26%) and 85 of the 418 Associate Program Directors (20%) completed the survey. 100% of respondents reported it was important to train residents about parenting skills, with 58% reporting it was “very important.” However, only 11% reported training residents “very well” and 24% reported educating resident “not very well” in this area. Chi-square tests showed no significant difference in response to these two questions based on respondent's role, specialist vs generalist, or type of program. No statistically significant association was seen between the importance respondents accorded parenting education and the perceived quality of their program's training on parenting. Curricula most often used by programs included Bright Futures (91%) and Healthy Steps (28%). Among those who reported that their programs did not train residents very well on parenting, 88% reported one barrier was not having a curriculum. Desired parenting topics were discipline (95%), promoting self-regulation in children (82%), sleep training (82%), tantrums (79%), promoting language development (71%), toilet training (70%), promoting secure attachment (66%), promoting school readiness skills (64%), and promoting literacy (53%). Conclusion Pediatric leadership values training residents on parenting, however few report educating residents very well in this area, with lack of curricula as a major barrier.
Chip-Scale Whispering Gallery Mode Glass Shell Resonators for Calorimetric Biosensing Applications

In this work, we demonstrate high Q-factor chip-scale whispering gallery mode (WGM) glass microshell optical resonators thermally coupled to a microfluidic system as sensitive calorimetric biosensors. Optical resonance is induced in spherical borosilicate glass shell structures released from silicon substrate using tapered fiber and 1550 nm laser. Temperature change induced from highly selective enzymatic reactions induces thermal expansion and thermorefractive changes in the glass microshell resonators which manifest as changes in the optical resonance characteristics. As an initial proof of biosensing concept, urea-urease reaction is sensed using this system.
UNUSUAL NUMBER OF JUVENILE ARMADILLOS (DASYPUS NOVEMCINCTUS) WITH AN ADULT

The occurrence of five juvenile nine-banded armadillos (Dasypus novemcinctus) is reported from a trail-camera picture. This photo was taken as part of a larger study investigating the dynamics of a medium-sized mammal community in an urban area. While quadruplets through polyembryony are the normal number of offspring born in a litter, the occurrence of more than four juveniles with an adult is documented along with a snapshot of the interaction between two of the juveniles.
Does Progesterone Receptor Matter in the Risk of Recurrence for Patients With Ductal Carcinoma in Situ

BACKGROUND Local recurrence is a major concern in patients diagnosed with ductal carcinoma in situ (DCIS). In invasive breast cancers, estrogen receptor (ER) (+)/progesterone receptor (PR) (-) subtype is considered more aggressive with poorer prognosis as compared to ER+/PR+ tumors. It is unclear whether this holds true in DCIS. METHODS Six hundred ninety-three patients diagnosed and treated for DCIS at Froedtert and Medical College of Wisconsin Cancer Center (February 2002 to March 2015) were studied to determine if the recurrence rates were significantly different between ER+/PR- and ER+/PR+ tumors. Recurrence was defined as either noninvasive or invasive ipsilateral, contralateral, or distant disease. Probabilities of recurrences were calculated using Kaplan-Meier estimator. Cox proportional hazards model was used to evaluate the effect of prognostic factors on DCIS recurrence. RESULTS Median follow-up was 5.2 years. The 5-year recurrence-free survival (RFS) was 91% (95% CI, 88.2-93.3) while estimated 7-year RFS was 86% (95% CI, 81.9-89.2). Seventy-five patients had a recurrence during their follow-up. Patients with ER-/PR- tumors (n = 118) had a significantly higher risk of recurrence (Hazard Ratio 3.7, 95% CI, 1.9-7.2, P = 0.0001) whereas those with ER+/PR- subtype (n = 77) did not have a significant difference in recurrence risk (HR 1.75, 95% CI, 0.92-3.32, P = 0.085) when compared to ER+/PR+ tumors (n = 482). No endocrine therapy for ER+ DCIS and lumpectomy alone were also significant predictors of recurrence (P = 0.0073 and P = 0.005, respectively). CONCLUSIONS ER+/PR- subtype was not a significant predictor of recurrence in DCIS patients. This finding is in contrast to the recurrence risk seen in invasive breast cancers. Mastectomy and postlumpectomy radiation were associated with improved outcomes as was adjuvant endocrine therapy.
Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO4 ) to healthy horses. MgSO4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg2+ ). Objective data were analyzed using the Wilcoxon rank-sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg2+ increased nearly fivefold, ionized calcium (Ca2+ ) decreased by nearly 10%, and the Ca2+ to Mg2+ ratio declined more than 3.5-fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO4 .
Propensity score specification for optimal estimation of average treatment effect with binary response.

Propensity score methods are commonly used in statistical analyses of observational data to reduce the impact of confounding bias in estimations of average treatment effect. While the propensity sc...
A Preliminary Study on the Use of the Linear Regression Method for Multigroup Cross-Section Interpretation

Computational modeling and simulations are widely used for evaluation of the performance and safety features of innovative nuclear reactor designs. Multigroup-based deterministic neutronics codes a...
Epigastric Hernias in Children: A Personal Series and Systematic Review of the Literature

Epigastric hernias are relatively uncommon in children, and there is a paucity of literature on their incidence, presenting features, natural history, and surgical outcomes. A systematic review was conducted according to PRISMA guidelines. Articles describing the incidence, outcome, and interventions for pediatric epigastric hernias, both open and laparoscopic, were analyzed. Eight relevant articles published between 1975 and 2019 were included in the analysis. Of 81 children, 58% were females, 35% were symptomatic and 8% were multiple. All hernias contained preperitoneal fat only and were repaired using standard open surgery or laparoscopic techniques. No recurrences were recorded. In a personal series of 37 hernias in 36 children of median age 4 years, there were no recurrences; however, this series included two children with a recurrent or persistent epigastric hernia after surgery by others. Epigastric hernias in children are relatively uncommon. They typically contain only preperitoneal fat but more than a third are symptomatic. Standard open repair can be undertaken with minimal morbidity. Laparoscopic repair takes longer and provides a marginal cosmetic benefit.
High Responsivity Ge Phototransistor in Commercial CMOS Si-Photonics Platform for Monolithic Optoelectronic Receivers

A high-gain phototransistor (PT) is demonstrated on a commercial 90-nm CMOS Si-photonics platform. The Gummel and output characteristics, the gain, and the frequency response of the phototransistor are measured for both optical and electrical inputs. An experimental quantitative agreement has been shown between the electrical and optical performance of the PT, and the implications of having such a device for the design of monolithic optical receivers is discussed. The fabricated PT achieves high responsivity values of 53A/W and 80A/W at 1310-nm wavelength, with 1V and 4V bias voltages, respectively. An optical receiver is simulated based on the proposed PT, achieving 10GHz bandwidth and 40dB $\Omega $ transimpedance gain.
Influence of Cognitive Performance on Musculoskeletal Injury Risk: A Systematic Review:

Background:While a large number of studies have investigated the anatomic, hormonal, and biomechanical risk factors related to musculoskeletal (MSK) injury risk, there is growing evidence to sugges...
Lung Chordoma: A Discussion

Chordomas are rare neoplasms arising from remnants of the notochord. We report a case of a 61-year-old female who underwent work-up for bariatric surgery and was found to have bilateral pulmonary nodules on computed tomography scan. Video-assisted thoracoscopic wedge resections were performed, and immunohistochemical stains confirmed the diagnosis of chordoma in all lesions. Much of our current knowledge of chordomas comes from axial and extra axial, non pulmonary presentations. Surgery appears to be the best treatment option as these tumors are generally chemo resistant. However, there are limited numbers of case reports of this entity.
Debiased lasso for generalized linear models with a diverging number of covariates.

Modeling and drawing inference on the joint associations between single-nucleotide polymorphisms and a disease has sparked interest in genome-wide associations studies. In the motivating Boston Lung Cancer Survival Cohort (BLCSC) data, the presence of a large number of single nucleotide polymorphisms of interest, though smaller than the sample size, challenges inference on their joint associations with the disease outcome. In similar settings, we find that neither the debiased lasso approach (van de Geer et al., 2014), which assumes sparsity on the inverse information matrix, nor the standard maximum likelihood method can yield confidence intervals with satisfactory coverage probabilities for generalized linear models. Under this "large n, diverging p" scenario, we propose an alternative debiased lasso approach by directly inverting the Hessian matrix without imposing the matrix sparsity assumption, which further reduces bias compared to the original debiased lasso and ensures valid confidence intervals with nominal coverage probabilities. We establish the asymptotic distributions of any linear combinations of the parameter estimates, which lays the theoretical ground for drawing inference. Simulations show that the proposed refined debiased estimating method performs well in removing bias and yields honest confidence interval coverage. We use the proposed method to analyze the aforementioned BLCSC data, a large-scale hospital-based epidemiology cohort study investigating the joint effects of genetic variants on lung cancer risks.
HaPPy: hyperthread-aware power profiling dynamically

Quantifying the power consumption of individual applications co-running on a single server is a critical component for software-based power capping, scheduling, and provisioning techniques in modern datacenters. However, with the proliferation of hyperthreading in the last few generations of server-grade processor designs, the challenge of accurately and dynamically performing this power attribution to individual threads has been significantly exacerbated. Due to the sharing of core-level resources such as functional units, prior techniques are not suitable to attribute the power consumption between hyperthreads sharing a physical core. In this paper, we present a runtime mechanism that quantifies and attributes power consumption to individual jobs at fine granularity. Specifically, we introduce a hyperthread-aware power model that differentiates between the states when both hardware threads of a core are in use, and when only one thread is in use. By capturing these two different states, we are able to accurately attribute power to each logical CPU in modern servers. We conducted experiments with several Google production workloads on an Intel Sandy Bridge server. Compared to prior hyperthread-oblivious model, HaPPy is substantially more accurate, reducing the prediction error from 20.5% to 7.5% on average and from 31.5% to 9.4% in the worst case.
Flux: A Next-Generation Resource Management Framework for Large HPC Centers

Resource and job management software is crucial to High Performance Computing (HPC) for efficient application execution. However, current systems and approaches can no longer keep up with the challenges large HPC centers are facing due to ever-increasing system scales, resource and workload diversity, interplays between various resources (e.g., between compute clusters and a global file system), and complexity of resource constraints such as strict power budgeting. To address this gap, we propose Flux, an extensible job and resource management framework specifically designed to deal with the requirements of next-generation HPC centers. Flux targets an entire computing facility as one common pool of diverse sets of resources, enabling the facility to accommodate site-wide constraints (e.g., for power limits). Yet, its scalable and distributed design still offers scalable and effective scheduling strategies. This paper details the design of Flux and describes and evaluates our initial prototyping effort of the key run-time components. Our results show that our run- time prototype provides strong and predictable scalability.
Making Sense of Stories

Stories and storytelling are not new to the social sciences. In the world of qualitative research, the use and analysis of narratives date back at least to William I. Thomas and Florian Znaniecki’s work The Polish Peasant in Europe and America (1920). What has been lacking in the field is a cogent analytic framework that is at once theoretically rich and empirically sensitive. Analyzing Narrative Reality fills this role masterfully. The book challenges the journalistic impulse to see narratives as transparent and moderates the positivistic tendency to generalize stories well beyond the social context in and for which they were articulated. Instead, Analyzing Narrative Reality presents a model of narrative analysis that is sensitive to both the content and the practice of storytelling, or the whats and hows of storytelling, as the authors put it. Gubrium and Holstein’s core argument is that narrative and narration are socially embedded and ongoing practices: “Stories are assembled and told to someone, somewhere, at some time, for different purposes, and with a variety of consequences. . . . The point is that the environments of storytelling mediate the internal organization and meaning of accounts” (p. 10). And to study narratives, we must go “into the field”; indeed, the phrase is used as a chapter subheading throughout the book. Going into the field, or “narrative ethnography,” enables Gubrium and Holstein to attend to narratives in real-life situations: “Accommodating naturalistic, ethnomethodological, and conversation analytic impulses, our approach focuses on the everyday narrative activity that unfolds within situated interaction. It entails an acute awareness of myriad layers of social context that condition narrative production” (p. 24). With this broad theoretical and methodological emphasis, the authors go on to present narrative analysis in four parts. Part 1, “Narrative Reality,” sets the stage for the book, with the first two chapters reviewing alternative paradigms and rejecting them in favor of a narrative practice model. Gubrium and Holstein’s treatment of the opposition is particularly revealing of their pedagogical philosophy. They argue the merits of their own approach by offering alternative readings of other sociologists’ data.
Ecological Science and Statistical Paradigms: At the Threshold

The science of ecology is reaching a point where progress will require the development of new statistical tools and corresponding experimental approaches. In his commentary, Maurer outlines why the field has reached this threshold and suggests the statistical directions that researchers should follow in order to solve complex ecological problems.
The Effect of Acetyl-β-Methylcholine on the Structure and Function of the Eccrine Sweat Gland *

Repeated injections of large doses of acetylcholine or acetyl-jO-methylcholine administered intracutaneously result in a progressive depression of the number of active sweat glands and of the rate of sweating in the vicinity of the injection (1, 2). Thaysen and Schwartz (1) attribute the decrement of sweating to “fatigue” of the sweat gland. Collins and his associates (2) propose that the depression is due to the development of a neuroglandular block, a desensitization of receptor sites on the eccrine sweat gland by large doses of neurohumor. The facts supporting this hypothesis are: (1) the depressive action of neurohumor is blocked by atropine; (2) non-depressing doses of neurohumor can be made depressive by combining acetylcholine with the anticholinesterase agent, neostigmine; (3) depressed glands show partial recovery in about six hours when no further injections of large doses of neurohumor are given. Control experiments suggest that the depression is not due to mechanical effects of the injected fluid, injury to the glands, release of epinephrine from local chromaffin tissue, vasoconstriction, or vasodilation. Subsequent to the partial recovery there is a second depression on the day after the experiment; recovery from this depression requires about two weeks. Collins et al. (2) think that this depression may have resulted from trauma.
A novel method for the evaluation of proximal tubule epithelial cellular necrosis in the intact rat kidney using ethidium homodimer.

Ethidium homodimer is a cell-membrane impermeant nuclear fluorochrome that has been widely used to identify necrotic cells in culture. Here, we describe a novel technique for evaluating necrosis of epithelial cells in the proximal tubule that involves perfusing ethidium homodimer through the intact rat kidney. As a positive control for inducing necrosis, rats were treated with 3.5, 1.75, 0.87 and 0.43 mg/kg mercuric chloride (Hg2+, intraperitoneal), treatments which have previously been shown to rapidly cause dose-dependent necrosis of the proximal tubule. Twenty-four h after the administration of Hg2+, ethidium homodimer (5 μM) was perfused through the intact left kidney while the animal was anesthetized. The kidney was then removed, placed in embedding medium, frozen and cryosectioned at a thickness of 5 μm. Sections were permeabilized with -20°C methanol and then stained with 4',6-diamidino-2-phenylindole (DAPI) to label total nuclei. Total cell number was determined from the DAPI staining in random microscopic fields and the number of necrotic cells in the same field was determined by ethidium homodimer labeling. The Hg2+-treated animals showed a dose-dependent increase in the number of ethidium labeled cells in the proximal tubule, but not in other segments of the nephron. Other results showed that a nephrotoxic dose of gentamicin also caused a significant increase in the number of ethidium labeled cells in the proximal tubule. These results indicate that this simple and sensitive perfusion technique can be used to evaluate cellular necrosis in the proximal tubule with the three-dimensional cyto-architecture intact.
Immunomagnetic capture and colorimetric detection of malarial biomarker Plasmodium falciparum lactate dehydrogenase

We report a sensitive, magnetic bead-based colorimetric assay for Plasmodium falciparum lactate dehydrogenase (PfLDH) in which the biomarker is extracted from parasitized whole blood and purified based on antigen binding to antibody-functionalized magnetic particles. Antigen-bound particles are washed, and PfLDH activity is measured on-bead using an optimized colorimetric enzyme reaction (limit of detection [LOD] = 21.1 ± 0.4 parasites/μl). Enhanced analytical sensitivity is achieved by removal of PfLDH from the sample matrix before detection and elimination of nonspecific reductases and species that interfere with the optimal detection wavelength for measuring assay development. The optimized assay represents a simple and effective diagnostic strategy for P. falciparum malaria with time-to-result of 45 min and detection limits similar to those of commercial enzyme-linked immunosorbent assay (ELISA) kits, which can take 4-6 h. This method could be expanded to detect all species of malaria by switching the capture antibody on the magnetic particles to a pan-specific Plasmodium LDH antibody.
The video mosaic: design and preliminary research

The Video Mosaic is a collaboration portal that integrates the Davis Institute video collection capturing mathematics learning across a range of grades, schools and a span of 20+ years. We present preliminary research using the VMC for teacher professional development.
Endotracheal versus Intravenous Epinephrine in the Prehospital Treatment of Cardiac Arrest

We performed a retrospective review of the charts of 252 adult, non-traumatic, prehospital cardiac arrest patients treated over a one-year period in order to assess the effectiveness of intravenous (IV) and endotracheal (ET) administration of epinephrine (0.5–1.0 mg) (EPI) in assisting restoration of a spontaneous pulse. Patients initially receiving IV-EPI were more likely to develop a spontaneous pulse earlier than those receiving a similar dose ET (7.3% vs 0.9%; p<0.01. In those patients who received a second dose of EPI, six (2.9%) regained a spontaneous pulse; each had been treated previously with IV-EPI. None who required a third dose of EPI regained a spontaneous pulse. In total, only five (2%) patients survived to discharge. We conclude that, in our system, patients who receive the currently recommended dose of EPI to treat cardiac arrest have a poor prognosis, and that IV-EPI is associated with a higher incidence of return of a spontaneous pulse compared to those treated ET.
The Impact of High Versus Low Sedation Dosing Strategy on Cognitive Dysfunction in Survivors of Intensive Care Units: A Systematic Review and Meta-Analysis.

Background: The practice of low vs. high sedation dosing strategy may impact the cognitive and mental health function in the intensive care unit (ICU). We aim to demonstrate that high sedation strategy will result in change of mental health function in ICU patients. Methods: We performed a systemic search and meta-analysis of medical databases in MEDLINE (from 1966 to March 2013) and EMBASE (from 1980 to March 2013), as well as the Cochrane Library using the MESH terms "Intensive Care Unit," and "Mental Health, for assessing the impact of sedation on posttraumatic stress disorder (PTSD) or anxiety/depression and delirium in the mix ICU setting including cardiac surgery patients. A total of 1216 patients were included in the final analysis. Results: We included 11 studies in the final analysis and concluded that high dose sedation strategy resulted in higher incidence of cognitive dysfunction with P value of 0.009. The result for subgroup of delirium showed P = 0.11 and PTSD/depression or anxiety of P = 0.001, Heterogeneity I2 was 64%. Overall analysis was statistically significant with a P value of 0.002. Conclusion: High sedation dosing strategy will negatively affect cognitive function in critically ill patients. Large randomized trials are needed to address cognitive dysfunction in subgroup of patients with delirium.
sickle, a Novel Drosophila Death Gene in the reaper/hid/grim Region, Encodes an IAP-Inhibitory Protein

Abstract Inhibitors of apoptosis proteins (IAPs) interact with caspases and inhibit their protease activity, whereas the IAP-inhibitory proteins Smac/DIABLO in mammals and Reaper, Hid, and Grim in flies relieve IAP-mediated inhibition [1–5] to induce cell death. Here we describe the functional characterization of the novel Drosophila cell death protein Sickle (Skl), which binds to IAPs and neutralizes their apoptotic inhibitory activity. Skl exhibits no sequence homology to Reaper, Hid, Grim, or Smac/DIABLO, except within the 4 residue N-terminal IAP binding motif. Skl interacts with Drosophila and mammalian IAPs and can promote caspase activation in the presence of IAPs. Consistent with these findings, expression of Skl in Drosophila and mammalian cell lines or in Drosophila embryos induces apoptosis. Skl can also synergize with Grim to induce cell death in the Drosophila eye imaginal disc. Based on biochemical and structural data, the N terminus of Skl, like that of the mammalian Smac/DIABLO, is absolutely required for its apoptotic and caspase-promoting activities and its ability to interact with IAPs. These findings point to conservation in the structure and function of the IAP-inhibitory proteins across species and suggest the existence of other family members.
How satisfied is your patient? The service side of care delivery: part 2.

IN THE FIRST SENTENCE of the first chapter in his book Good to Great, Jim Collins draws the reader’s attention to the fact that there is a monumental difference between good and great. It takes a moment to grasp the concept that competence can actually inhibit achievement. Collins says, “The vast majority of companies never become great, precisely because the vast majority become quite good—and that is their main problem.” Think of highly successful businesses, those that have made the transition to great, and you will find a common thread. Highly successful businesses listen to customers’ needs and offer exceptional service. Successful health care organizations do the same. Listening to patients and providing exceptional service coupled with outstanding care delivery can move an organization from good to great.
Analysis of G protein α subunit mRNA abundance in preimplantation mouse embryos using a rapid, quantitative RT-PCR approach

We have developed a novel reverse transcription-polymerase chain reaction (RT-PCR)-based approach for systematically quantifying in a single experiment the abundances of many different mRNAs in preimplantation mouse embryos. With this approach, the entire mRNA population from a small number of embryos is amplified while preserving the relative abundance of each mRNA in the cDNA population. The cDNA is analyzed by quantitative hybridization to radiolabeled probes. The approach is very sensitive and provides reliable, quantitative data regarding changes in mRNA abundance. A major advantage of this method is that estimates of mRNA copy number can be obtained and compared between different mRNAs. With this approach, we analyzed the patterns of expression of nine G protein alpha subunit mRNAs (G alpha s, G alpha i, G alpha q, G alpha o, and G alpha 11-15) in oocytes, eggs, and preimplantation embryos from fertilization to the blastocyst stage. Six alpha subunit mRNAs were expressed at significant levels, all of which underwent significant temporal alterations in expression. The mRNAs encoding some alpha subunit types were expressed predominantly in the egg and 1-cell embryo, underwent sharp reductions during the 2-cell stage, and were re-expressed between the 8-cell and blastocyst stages. One alpha subunit mRNA increased in abundance at the early blastocyst stage. The possible significance of these alterations in G protein mRNA abundance to embryonic development is discussed.
Effects of environment and lifestyle on gastroesophageal reflux disease.

Background: Gastroesophageal reflux disease (GERD) is comprised of a spectrum of related disorders, including hiatal hernia, reflux disease with its associated symptoms, erosive eso
The Effect of Pregnancy and Lactation on the Disposition of [2,4,2′,4′-14C]Tetrachlorobiphenyl in the Mouse

Abstract The disposition of 150 mg/kg 2,4,2′,4′-tetrachlorobiphenyl (4-CB) administered intraperitoneally as a function of nonpregnant body weight was studied in virgin, late pregnant, and early postpartum mice and their offspring. Highest concentrations of the polychlorinated biphenyl (PCB) were observed in adipose tissue and mammary gland regardless of reproductive state. Concentrations of 4-CB equivalents in the tissues examined, however, differed among the three groups, possibly due to the alterations in lipid deposition/mobilization associated with pregnancy and lactation. Approximately 20% of 14C activity was eliminated from carcasses of virgin mice at 4 days after 4-CB administration. No significant decrease in carcass 14C content was observed during this 4-day interval in late pregnant animals. Minimal transplacental transfer of 14C activity occurred (approximately 1% of total maternal body burden) but 4-CB was rapidly eliminated in breast milk to nursing offspring. Ninety percent of total carcass 14C activity was eliminated from lactating mice over a 4-day period, approximately 75% of which could be accounted for in neonatal carcasses. This indicates milk to be the preferred route of elimination for this PCB congener in postpartum animals. Virtually all radioactivity recovered from milk comigrated with parent compound following thin-layer chromatographic analysis. A comparison between hepatic microsomal ethoxycoumarin-O-deethylase activity (ECOD) and liver concentrations of 14C activity showed that pregnant animals were less responsive to the inducing effects of 4-CB than virgin or postpartum mice. This diminution in response may be, in part, responsible for the lack of elimination of 4-CB equivalents from the late pregnant animal during the 4-day experimental period.
How to study longitudinal W 's in the TeV region

Using some new techniques we examine ways to experimentally study interactions of longitudinal {ital W} bosons in the TeV region, and to detect a heavy Higgs boson (mass {ge}1 TeV) if it exists. This is a problem that must be solved if we are eventually to fully understand and test how the SU(2){times}U(1) symmetry of the standard model is broken. To do so at a hadron collider requires methods to discriminate against large backgrounds. We use a new method based on the color properties of the signal and background, leading to a multiplicity cut, and we use analysis techniques that do not reduce the signal events by strong cuts. Our techniques do not bias {ital W} decay distributions and we conclude that it is possible to detect longitudinal {ital W} 's even in the presence of background. Results are given for how it is possible to study these matters at the Superconducting Super Collider. The use of the equivalence theorem'' between longitudinal {ital W} 's and Goldstone scalars is examined in several ways; in particular, we emphasize that in practice the equivalence does not hold numerically when the widths of heavy resonances are included in the traditional way, i.e., usingmore » the Breit-Wigner prescription. The violations are numerically large.« less
First-order transition to a metallic state in polyacetylene: A strong-coupling polaronic metal

We present a theory of the first-order transition to the metallic state in polyacetylene in terms of a crossover from a lattice of charged solitons to a regular array of polaronlike distortions. The polaronic metal is shown to have a strong indirect attractive interaction, ${\mathrm{U}}^{\mathrm{*}}$\ensuremath{\simeq}-2\ensuremath{\Delta}/3, between electrons in the half-filled, narrow, polaron subband within the Peierls energy gap (${\mathrm{E}}_{\mathrm{g}}$=2\ensuremath{\Delta}).
Optical Fiber Chemical Sensing Networks

Many industrial processes or other phenomena of interest cannot be measured with conventional instruments because they are too hot, too cold, highly radioactive, or other-wise inaccessible to direct observation. Nuclear wastes stored in underground repositories, for example, will require in-situ monitoring. A new technology that uses long distance fiber optics to transmit laser-excited fluorescence now makes it possible to remotely monitor such installations via optical fiber cables at distances up to one kilometer. The applications are listed below. - Sampling of remote locations - Multipoint sampling with single instrument - Measurements in inaccessible locations - Coping with aggressive environments - Avoiding contamination - Continuous monitoring
A planning algorithm to assess the impact of urban growth on flood expectancy / Un algorithme de planification pour évaluer l'influence de l'accroissement urbain sur la probabilité des crues

Abstract Standard engineering and planning practice regarding flood hazard delineation in the United States is based on the assumption that 1 per cent annual flood expectancy is static and that subsequent urbanization of the basin will have no significant impact on that expectancy. Research during the past three years demonstrates that this assumption is unjustified in certain settings where the hydrological response of a basin to extensive urban growth is conditioned by geological and morphometric parameters. These relationships have been synthesized into an algorithm which predicts the change in discharge corresponding to both 1 and 2 per cent exceedance probabilities on the basis of indices of urban land use changes, surficial properties of the catchment, and the configuration of the drainage network. Flood expectancy for two distinct time frames was calculated by standard statistical analyses of annual maxima. The final algorithm was developed by a stepwise multiple regression technique and utilized d...
A note on enumerative counting

Resolving an open question about the complexity of enumerative approximation, we show that if [num]SAT has a polynomial-time nk-enumerator, then P = P[num]P.
Pentobarbital induces a naloxone-reversible decrease in mesolimbic self-stimulation threshold

The effects of sodium pentobarbital and naloxone were tested on intracranial self-stimulation (ICSS) in rats implanted with electrodes in the ventral tegmental area. Threshold for ICSS was determined using a rate-independent current titration paradigm. A low dose of pentobarbital (5 mg/kg) did not have a significant effect on ICSS thresholds, while a high dose (20 mg/kg) rendered the subjects too ataxic to respond reliably in the operant task. An intermediate dose (10 mg/kg) induced a highly significant lowering of threshold (17% below saline baseline levels) without apparent deterioration in response capability. The concurrent administration of naloxone (2 mg/kg) significantly reversed the pentobarbital-induced threshold decrease, while naloxone treatment alone had no effect on the ICSS threshold.
How the Skin Can Tell Time

The mammalian central circadian pacemaker, which is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, synchronizes and entrains clocks found in peripheral tissues. Skin harbors an active circadian clock that is under the influence of the central clock. This clock, which probably operates in most-perhaps all-types of skin cells, may influence the regulation of several circadian physiological phenomena, including cell proliferation.
Crystal Structures of Substrate and Inhibitor Complexes with AmpC β-Lactamase: Possible Implications for Substrate-Assisted Catalysis

Group I β-lactamases are major resistance determinants to β-lactam antibiotics. Despite intense study, the identity of the catalytic base, the direction of hydrolytic attack, and the functional difference between β-lactam substrates and β-lactam inhibitors remain controversial. To explore these questions, we determined the X-ray crystal structures of several representative β-lactams in their acyl−adduct complexes with the group I β-lactamase AmpC. A complex with the substrate loracarbef and a deacylation-deficient mutant enzyme reveals an ordered water molecule that is consistent with β-face attack of the catalytic water in group I β-lactamases. The ring nitrogen of the substrate is placed to hydrogen-bond with this water in the position it is thought to adopt in the deacylation transition state. In complexes with the inhibitors cloxacillin and moxalactam, conformational restrictions displace the equivalent ring nitrogens, sterically blocking the formation of the presumed deacylation transition-state stru...
Directed and random biopsies of the prostate: indications based on combined results of transrectal sonography and prostate-specific antigen density determinations.

We studied the usefulness of transrectal sonography, prostate-specific antigen levels, and prostate-specific antigen density as indications for directed and random biopsies of the prostate in patients with possible prostatic cancer.A total of 141 patients with increased levels of prostate-specific antigen or abnormal findings on digital rectal examination had transrectal sonography of the prostate and determination of prostate-specific antigen density. Through sonographic visualization, all patients had biopsies of possible cancerous lesions and random biopsies of regions of the prostate that appeared normal. Histologic results were correlated with sonographic findings and determinations of prostate-specific antigen levels and prostate-specific antigen density.Adenocarcinoma was detected in 40 (28%) of the 141 patients. Transrectal sonography showed an abnormality that was determined by directed biopsy to be a carcinoma in 27 (68%) of the 40 patients. Transrectal sonography showed no carcinoma in 13 patie...
Side-Chain-Grafted Random Copolymer Brushes as Neutral Surfaces for Controlling the Orientation of Block Copolymer Microdomains in Thin Films

Random copolymers of P(S-r-MMA-r-HEMA)s with a distribution of surface reactive hydroxyl groups were synthesized to formulate neutral surface layers on a SiO2 substrate. The layers were designed to drive vertical orientation of lamellar microdomains in a top P(S-b-MMA) thin film. Copolymers with a styrene weight fraction (fSt) of 0.58 and a HEMA fraction (fHEMA) ranging from 0.01 to 0.03, with a corresponding MMA fraction (fMMA) ranging from 0.41 to 0.39, in the P(S-r-MMA-r-HEMA) copolymer showed neutral surface characteristics. The morphology of block copolymer thin films was studied by scanning electron microscopy (SEM). P(S-r-MMA-r-HEMA) copolymers prepared by both living and classical free-radical polymerizations were equally effective in demonstrating the neutrality of the surface. These side-chain-grafted random copolymer brushes showed faster grafting kinetics than the end-chain-grafted P(S-r-MMA) because of multipoint attachment to the surface. The modified surfaces had a very thin layer of random...