cssi/SciSciGPT-SciSciNet huggingface dataset:
Quality of Electron Beam Irradiated Strawberries

Fresh ‘Tristar’ strawberries were treated by electron beam irradiation to determine the effects on postharvest quality attributes and shelf life. The intensity of red color rated by sensory panelists decreased as irradiation dosage increased from 0 to 2 kGy. Hunter ‘L’ values were higher for fruit treated with 2 kGy than for 0 and 0.5 kGy. Instron firmness values were lower for all irradiated fruit than for control fiuit. Panelists rated irradiated fruit less firm than nonirradiated fruit stored 1, 2 and 4 days. An increase in off-flavor was noted among all treatments stored 6 and 8 days. Irradiation suppressed fungi on stored berries. Irradiation doses of 1 and 2 kGy extended shelf life 2 and 4 days, respectively. Electron beam irradiation technology has excellent potential for extension of shelf life of fresh strawberry fruits.
Epidermal Growth Factor Receptor Is Not Required for Human Cytomegalovirus Entry or Signaling

Human cytomegalovirus (HCMV) can bind, fuse, and initiate gene expression in a diverse range of vertebrate cell types. This broad cellular tropism suggests that multiple receptors and/or universally distributed receptors mediate HCMV entry. Our laboratory has recently discovered that certain β1 and β3 integrin heterodimers are critical mediators of HCMV entry into permissive fibroblasts (A. L. Feire, H. Koss, and T. Compton, Proc. Natl. Acad. Sci. USA 101:15470-15475, 2004). It has also been reported that epidermal growth factor receptor (EGFR) is necessary for HCMV-mediated signaling and entry (X. Wang, S. M. Huong, M. L. Chiu, N. Raab-Traub, and E. E. Huang, Nature 424:456-461, 2003). Integrins are known to signal synergistically with growth factor receptors, and this coordination was recently reported for EGFR and β3 integrins in the context of HCMV entry (X. Wang, D. Y. Huang, S. M. Huong, and E. S. Huang, Nat. Med. 11:515-521, 2005). However, EGFR-negative cell lines, such as hematopoietic cells, are known to be infected by HCMV. Therefore, we wished to confirm a role for EGFR in HCMV entry and then examine any interaction between β1 integrins and EGFR during the entry process. Surprisingly, we were unable to detect any role for EGFR in the process of HCMV entry into fibroblast, epithelial, or endothelial cell lines. Additionally, HCMV did not activate the EGFR kinase in fibroblast cell lines. We first examined HCMV entry into two EGFR-positive or -negative cell lines but observed no increase in entry when EGFR was expressed to high levels. Physically blocking EGFR with a neutralizing antibody in fibroblast, epithelial, or endothelial cell lines or blocking EGFR kinase signaling with a chemical inhibitor in fibroblast cells did not inhibit virus entry. Lastly, we were unable to detect phosphorylation of EGFR in fibroblasts cells in response to HCMV stimulation. Our findings demonstrate that EGFR does not play a significant role in HCMV entry or signaling. These results suggest that specific integrin heterodimers either act alone as the primary entry receptors or interact in conjunction with an additional receptor(s), other than EGFR, to facilitate virus entry.
Reconstruction of three-dimensional objects in layered media: numerical experiments

We have developed a fully three-dimensional electromagnetic inverse scattering technique in a multilayered medium via the contrast source inversion. The key issues on the three-dimensional (3-D) forward and adjoint operations related to the dyadic Green's operators are briefly addressed to ensure the efficient performance of the algorithm in layered media. It is shown that it is feasible to achieve good reconstruction quality with only a few sources and a two-dimensional receiver array, provided that the signal-to-noise ratio is adequate. The effects of the interface and of the uncertainty in the background layered medium are illustrated in the simulation. The developed 3-D electromagnetic inverse scattering technique can be effectively applied to surface ground penetrating radar survey in multilayered media.
Saving power by synthesizing gated clocks for sequential circuits

Portable devices demand low power consumption to prolong battery life. Gating the clock is one strategy for saving power. The authors' technique identifies self-loops in an FSM and uses the function described by the self-loops to gate the clock. Applying these techniques to standard benchmarks achieved an average 25% less power dissipation at a cost of only 5% more area. >
Fe K-edge X-ray resonant magnetic scattering from Ba(Fe1−x Co x )2As2 superconductors

We present an X-ray resonant magnetic scattering study at the Fe-K absorption edge of the BaFe2As2 compound. The energy spec- trum of the resonant scattering, together with our calculation using the full-potential linear-augmented plane wave method with a local den- sity functional suggests that the observed resonant scattering arises from electric dipole (E1) transitions. We discuss the role of Fe K-edge X-ray resonant magnetic scattering in understanding the relationship between the structure and the antiferromagnetic transition in the doped Ba(Fe1�xCox)2As2 superconductors.
An Isoperimetric Inequality for the Torsional Rigidity of Imperfectly Bonded Fiber Reinforced Cylinders

An isoperimetric inequality for the torsional rigidity of imperfectly bonded, fiber reinforced cylinders is found. The fiber cross sections can be simply or multiply connected. The imperfect bonding conditions are given in terms of a flexible interface model.
The other rabies viruses: The emergence and importance of lyssaviruses from bats and other vertebrates

The recognition that viruses related to rabies virus cause rabies in humans has stimulated research into the relationships, geographic distribution and natural histories of these viruses. This paper reviews what is known of these fascinating viruses and the complexity of prevention and treatment of the disease they cause.
Frequency dependence of tone‐burst‐generated whole nerve action potentials

At high sound‐pressure levels, whole nerve action potentials (AP) elicited by tone burst, have been said to be generated by the click‐like action of the onset of the bursts. The contrary opinion, that the AP is frequency dependent, has also been voiced. By using high‐pass noise and tone‐on‐tone masking, tone‐burst‐elicited APs can indeed be shown to be highly frequency specific. In fact, by changing the cutoff frequency of masking noise, it is demonstrated that only a specific region on the basilar membrane, corresponding to the frequency of the tone burst, contributes to AP. As the frequency of the tone burst is changed, the masking curves shift accordingly. Tone‐on‐tone masking confirms these results by generating curves that are similar to the ones found in human psychophysical masking experiments. These findings might prove valuable in human electrocochleography where the use of high‐intensity tones is desirable for obtaining better signal‐to‐noise ratios. [Supported by grants from NIH.]
Chylothorax Complicating Repairs of the Descending and Thoracoabdominal Aorta

Background Chylothorax occurring during thoracic aortic surgery is an infrequent but serious complication. The purpose of this study was to analyze our experience with this complication and the resulting outcomes. Methods From January 1991 to July 2005, we performed 1,233 descending thoracic and thoracoabdominal aortic surgical procedures. A retrospective review was performed to analyze and identify preoperative and operative risk factors as well as management outcomes of postoperative chylothorax (PCT). Results PCT developed in five patients (0.4%). All five cases occurred with descending thoracic aortic aneurysm repair, and 80% (four of five patients) were undergoing aortic reoperation. All patients were managed successfully with no mortality. Risk factors for the development of chylothorax were descending thoracic aortic repair (p = 0.006) and thoracic aortic reoperations (p = 0.0003). Nonoperative management was successful in 60% (three of five patients). Two patients required left thoracotomy with direct ligation. Mean hospital length of stay was 35 days (range, 15 to 60 days). Mean follow-up was 33 months (range, 3 to 69 months) with no recurrence of chylothorax or additional morbidity or mortality. Conclusions Chylothorax is more likely to occur with reoperations and repairs involving the descending thoracic aorta. Although PCT is associated with longer hospital length of stay, it is not associated with increased infectious complications. Early identification and prompt treatment may decrease both early and late morbidity and mortality.
Identifying a Selective Substrate and Inhibitor Pair for the Evaluation of CYP2J2 Activity

CYP2J2, an arachidonic acid epoxygenase, is recognized for its role in the first-pass metabolism of astemizole and ebastine. To fully assess the role of CYP2J2 in drug metabolism, a selective substrate and potent specific chemical inhibitor are essential. In this study, we report amiodarone 4-hydoxylation as a specific CYP2J2-catalyzed reaction with no CYP3A4, or other drug-metabolizing enzyme, involvement. Amiodarone 4-hydroxylation enabled the determination of liver relative activity factor and intersystem extrapolation factor for CYP2J2. Amiodarone 4-hydroxylation correlated with astemizole O-demethylation but not with CYP2J2 protein content in a sample of human liver microsomes. To identify a specific CYP2J2 inhibitor, 138 drugs were screened using terfenadine and astemizole as probe substrates with recombinant CYP2J2. Forty-two drugs inhibited CYP2J2 activity by ≥50% at 30 μM, but inhibition was substrate-dependent. Of these, danazol was a potent inhibitor of both hydroxylation of terfenadine (IC50 = 77 nM) and O-demethylation of astemizole (Ki = 20 nM), and inhibition was mostly competitive. Danazol inhibited CYP2C9, CYP2C8, and CYP2D6 with IC50 values of 1.44, 1.95, and 2.74 μM, respectively. Amiodarone or astemizole were included in a seven-probe cocktail for cytochrome P450 (P450) drug-interaction screening potential, and astemizole demonstrated a better profile because it did not appreciably interact with other P450 probes. Thus, danazol, amiodarone, and astemizole will facilitate the ability to determine the metabolic role of CYP2J2 in hepatic and extrahepatic tissues.
Transdermal Permeability of N-Acetyl-D-Glucosamine

Transdermal permeation of N-acetyl-D-glucosamine (NAG), a metabolite of glucosamine was examined. Glucosamine salts are nutraceuticals used in the oral treatment of osteoarthritis. Sparse information is available regarding glucosamine and NAG transdermal or percutaneous transport and absorption. Permeability of NAG in various enhancer suspensions was evaluated by using shed snakeskin as a model membrane via Franz-type cell diffusion studies. Negligible permeability was observed for NAG in neat solutions of known membrane permeation enhancers ethanol, oleic acid, isopropyl myristate, and isopropyl palmitate, as well as from saturated solutions of NAG in water or phosphate buffer. Permeability measurements obtained from saturated solutions of NAG in DMSO and phosphate buffer solutions containing ethanol at 2%, 5%, 10%, 25%, and 50% demonstrated excellent permeation. Permeability coefficients of the phosphate buffer/ethanol solutions at 5%, 10%, and 25% were about threefold larger in value as those for saturated DMSO solution, whereas the 2% and 50% solution values were lower.
Optimal Ad Ranking for Profit Maximization

Despite the enormous commercial importance of on-line advertisements (ads), there has been little work done to clarify the basis for ranking and displaying them. Most existing methods rank ads as if the user views each of them in isolation. We will consider a more realistic user model that induces three mutual inuences between displayed ads: (i) positional bias (for viewing ads placed higher up) (ii) similar ad fatigue (which reduces interest in an ad when similar ads have already been displayed above it) and (iii) browsing impatience (which accounts for the user abandoning the ad viewing based on the ads already seen). We will show that in general, when the inter-ad similarity is taken into account, optimal ranking is NP-hard. Ignoring inter-ad similarity, we state and prove the optimal ranking function for sorting the ads that is sensitive to the other two factors. We will show that the known ad ranking strategies correspond to restricted special cases of our ranking function. We also provide simulation studies that establish the eectiveness of its generality.
Ligand-Stimulated Downregulation of the Alpha Interferon Receptor: Role of Protein Kinase D2§

Alpha interferon (IFN-α) controls homeostasis of hematopoietic stem cells, regulates antiviral resistance, inhibits angiogenesis, and suppresses tumor growth. This cytokine is often used to treat cancers and chronic viral infections. The extent of cellular responses to IFN-α is limited by the IFN-induced ubiquitination and degradation of the IFN-α/β receptor chain 1 (IFNAR1) chain of the cognate receptor. IFNAR1 ubiquitination is facilitated by the βTrcp E3 ubiquitin ligase that is recruited to IFNAR1 upon its degron phosphorylation, which is induced by the ligand. Here we report identification of protein kinase D2 (PKD2) as a kinase that mediates the ligand-inducible phosphorylation of IFNAR1 degron and enables binding of βTrcp to the receptor. Treatment of cells with IFN-α induces catalytic activity of PKD2 and stimulates its interaction with IFNAR1. Expression and kinase activity of PKD2 are required for the ligand-inducible stimulation of IFNAR1 ubiquitination and endocytosis and for accelerated proteolytic turnover of IFNAR1. Furthermore, inhibition or knockdown of PKD2 robustly augments intracellular signaling induced by IFN-α and increases the efficacy of its antiviral effects. The mechanisms of the ligand-inducible elimination of IFNAR1 are discussed, along with the potential medical significance of this regulation.
Violation of cell lineage restriction compartments in the chick hindbrain

Previous cell lineage studies indicate that the repeated neuromeres of the chick hindbrain, the rhombomeres, are cell lineage restriction compartments. We have extended these results and tested if the restrictions are absolute. Two different cell marking techniques were used to label cells shortly after rhombomeres form (stage 9+ to 13) so that the resultant clones could be followed up to stage 25. Either small groups of cells were labelled with the lipophilic dye DiI or single cells were injected intracellularly with fluorescent dextran. The majority of the descendants labelled by either technique were restricted to within a single rhombomere. However, in a small but reproducible proportion of the cases (greater than 5%), the clones expanded across a rhombomere boundary. Neither the stage of injection, the stage of analysis, the dorsoventral position, nor the rhombomere identity correlated with the boundary crossing. Judging from the morphology of the cells, both neurons and non-neuronal cells were able to expand over a boundary. These results demonstrate that the rhombomere boundaries represent cell lineage restriction barriers which are not impenetrable in normal development.
Metastatic patterns of breast cancer subtypes: What radiologists should know in the era of personalized cancer medicine

There is accumulating evidence that molecular phenotyping of breast cancer determines the timing, pattern, and outcome of metastatic disease. The most clinically relevant subtypes are hormonal-positive [oestrogen and progesterone receptor (ER/PR) positive], HER2 expressing, and triple-negative breast cancers (TNBCs). ER/PR-positive breast cancers demonstrate the best prognosis; however, metastases, in particular osseous disease, may develop much later. HER2-expressing breast cancers, although aggressive, have improved outcomes due to the advent of HER2-targeted therapies, with increased risk of central nervous system (CNS) relapses later. Finally, TNBCs present in younger women, BRCA1 mutations carriers, and carry the worst overall prognosis, with high incidence of CNS metastases, especially during the first 5 years of diagnosis. It is important for radiologists to understand the nuances of these breast cancer subtypes to predict metastatic behaviours and guide possible imaging surveillance.
MAYA MEMORY WORK

The critical role of social or collective memory in ongoing processes of societal reproduction and transformation is well acknowledged by anthropologists and is being increasingly modeled in archaeological interpretations as well. Investigating how social memory impacted the materialities and historical trajectories of the Maya civilization has great potential for advancing archaeological methodologies as well as enlarging our knowledge of the Maya. In addition to the wealth of epigraphic, ethnographic, and early historical information available for the Maya, archaeologists are examining enduring architecture, representative imagery, and even mundane artifacts that constitute a “technology of memory” for clues to the interplay of recollection and forgetting in the operation and transformation of Maya societies. This commentary reviews issues and problems in archaeological studies of social memory and addresses the specific prospects for investigating social memory among the pre-Hispanic Maya, drawing upon the analyses provided by the papers in this special section.
Erbium Fiber Amplifiers in Linear Lightwave Transmission

The invention and development of fibers doped with rare-earth element as in-line optical amplifiers [223, 224, 225, 226] were a major breakthrough that enabled great enhancement in the capability of fiber optic telecommunication networks. With their ubiquitous deployment in digital fiber-optic networks, these fiber amplifiers have met the test of time for their proven values. However, their employment in linear lightwave systems, including analog video distribution requires stringent performance specifications above and beyond those required for digital telecommunication systems. While these fiber amplifiers possess a superb carrier-to-noise ratio (CNR) – for example, Erbium fiber amplifiers (EDFA) can operate close to a 3 dB noise figure which is the quantum limit when pumped at 980 nm [209]. When coupled with a low noise laser source, EDFA is capable of delivering a CNR of 51 dB [210]. While this is satisfactory for most digital transmission systems, a more careful study is necessary for their employment in an optimized linear fiber optic distribution system. Trade-offs must be made between pump power, input signal power, and signal gain affect both amplifier performance and system cost. They are dependent on the intended function of the amplifiers (in-line versus preamplifier versus power-amplifier) and the number of stages for maximum cost-effectiveness. Preamplifiers placed before detectors generally require high gain to boost the signal into the detectors. On the other hand, for power-amplifiers located at the front portion of distribution links, a high output saturation power is paramount.
What computers do: model, connect, engage

Every 30 years there is a new wave of things that computers do. Around 1950 they began to model events in the world (simulation), and around 1980 to connect people (communication). Since 2010 they have begun to engage with the physical world in a non-trivial way (embodiment--giving them bodies). Today there are sensor networks like the Inrix traffic information system, robots like the Roomba vacuum cleaner, and cameras that can pick out faces and even smiles. But these are just the beginning. In a few years we will have cars that drive themselves, glasses that overlay the person you are looking at with their name and contact information, telepresence systems that make most business travel unnecessary, and other applications as yet unimagined. Computer systems are built on the physical foundation of hardware (steadily improving according to Moore's law) and the intellectual foundations of algorithms, abstraction and probability. Good systems use a few basic methods: approximate, incrementally change, and divide and conquer. Latency, bandwidth, availability and complexity determine performance. In the future systems will deal with uncertainty much better than today, and many of them will be safety critical and hence much more dependable.
E16. Olde Victorian Map Colouring

Let us start with the history of the arguably second most famous problem in the entire history of mathematics. It commences in Victorian London in the year 1852, when the 20-year old Francis Guthrie created The Four-Color Conjecture (4CC), and continues for 124 years, when in 1976 Kenneth Appel and Wolfgang Haken, with the assistance of John Koch and over 1200 hour of mainframe computer time converted 4CC into 4CT – The Four Color Theorem. A second proof had to wait another 20 years: in 1997 Neil Robertson, Daniel Sanders, Paul Seymour and Robin Thomas also proved 4CT. Both proofs required an essential use of computing.
Abstract W P391: Obesity Causes Endothelium Dysfunction in Rat Cerebral Parenchymal Arterioles

Obesity is a risk factor for dementia. The diameter and dilatory ability of cerebral parenchymal arterioles (PAs) regulates local perfusion to discrete neuronal populations matching nutrient delivery to neuronal demand. A mismatch in this process could lead to neuronal loss and dementia development. Thus, we hypothesized that feeding rats a high-fat (HF) diet would impair endothelium-dependent dilation and cause inward remodeling of PAs. Three-week-old male Sprague-Dawley rats were fed a HF diet for 17 weeks. Rats fed regular chow were controls. PAs branching from the middle cerebral artery were isolated and cannulated in a pressure myograph, and pressurized to 50mmHg. After the development of spontaneous myogenic tone endothelium-dependent dilation was assessed with carbachol (1nM - 100μM). PAs were then placed in 0Ca2+-PSS with 2mM EGTA+100μM sodium nitroprusside to assess of passive diameter and wall thickness. Data are means±SEM, Control vs. HF (n=3 in each group). Myogenic tone generation (% tone: 27...
Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent

Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of therapeutic agents. Pseudopterosins are group of marine diterpene glycosides that possess an array of potent biological activities in several therapeutic areas. Few studies have examined pseudopterosin effects during cellular stress and, to our knowledge, no studies have explored their ability to protect synaptic function. The present study probes pseudopterosin A (PsA) for its neuromodulatory properties during oxidative stress using the fruit fly, Drosophila melanogaster. We demonstrate that oxidative stress rapidly reduces neuronal activity, resulting in the loss of neurotransmission at a well-characterized invertebrate synapse. PsA mitigates this effect and promotes functional tolerance during oxidative stress by prolonging synaptic transmission in a mechanism that differs from scavenging activity. Furthermore, the distribution of PsA within mammalian biological tissues following single intravenous injection was investigated using a validated bioanalytical method. Comparable exposure of PsA in the mouse brain and plasma indicated good distribution of PsA in the brain, suggesting its potential as a novel neuromodulatory agent.
The Effect of Water Vapor and Oxygen in the Processing Environment on the Properties of Sputtered a-Si:H Films

A systematic study of the effect of the trace impurity of oxygen and water vapor in the processing environment on the infra-red (IR), optical and electrical properties, and defect density of sputtered a-Si:H films is reported. The results are that small contents of water introduced into the argon plasma extract H-atoms from the growth surface, thereby reducing total hydrogen content and polyhydride formation in films deposited at low substrate temperatures, <150°C. This leads to a decrease of the defect density, and hence, to improvements in the photoconductivity (Δσ) and the associated quantum efficiency-mobility-lifetime(ημτ) product.
Single time point comparisons in longitudinal randomized controlled trials: power and bias in the presence of missing data

The primary analysis in a longitudinal randomized controlled trial is sometimes a comparison of arms at a single time point. While a two-sample t-test is often used, missing data are common in longitudinal studies and decreases power by reducing sample size. Mixed models for repeated measures (MMRM) can test treatment effects at specific time points, have been shown to give unbiased estimates in certain missing data contexts, and may be more powerful than a two sample t-test. We conducted a simulation study to compare the performance of a complete-case t-test to a MMRM in terms of power and bias under different missing data mechanisms. Impact of within- and between-person variance, dropout mechanism, and variance-covariance structure were all considered. While both complete-case t-test and MMRM provided unbiased estimation of treatment differences when data were missing completely at random, MMRM yielded an absolute power gain of up to 12 %. The MMRM provided up to 25 % absolute increased power over the t-test when data were missing at random, as well as unbiased estimation. Investigators interested in single time point comparisons should use a MMRM with a contrast to gain power and unbiased estimation of treatment effects instead of a complete-case two sample t-test.
Religion and Alienation as Factors in Student Activism

In a survey of 450 University of Michigan male undergraduates in 1969, two forms of activists were identified-organization members and demonstration participants. Both types tended to be disproportionately from Jewish homes, without personal religious preference, enrolled in social science departments, and active in campus religious fellowships. Alienation was found to be multi-dimensional, involving both specific institutional alienation and more generalized feelings of alienation. The latter proved unrelated to student activism. However, activistic students were more alienated from traditional religion, college, government, and the military. The general conclusions, presented by Keniston and Flacks, that activistic students are not culturally alienated, need further specification in terms of particular areas of institutional alienation.
Finite element analysis of space grids under earthquake effect

The orthogonal and ortholaid space grids have been simplified as space joint connection system, and are analyzed by ANSYS program. By compiling the ANSYS command-flow, the natural vibration is analyzed, the earthquake action analysis of space grids is calculated by response spectrum analysis. The modes, frequencies, the values of spectrum and the maximum of truss earthquake force are obtained.
Protective effect of previous intramammary infection with Streptococcus uberis against subsequent clinical mastitis in the cow

Following challenge of 23 quarters of 17 lactating cows with 10(3) colony forming units of Streptococcus uberis 0140J, 20 (87 per cent) developed clinical mastitis. Once the disease had resolved each animal was rechallenged in two quarters, one previously challenged and one additional quarter. Of the 34 secondary quarter challenges 11 (32.2 per cent) led to clinical mastitis, a highly significant reduction over the primary challenges.
Doodling the Nerves: Surfacing Language Anxiety Experiences in an English Language Classroom

This qualitative study explored the use of doodling to surface experiences in the psychological phenomenon of language anxiety in an English classroom. It treated the doodles of 192 freshmen from a...
Testing for PL Validity

It may seem that the argument whose most sophisticated PL argument consistency form was developed in the last chapter must be valid since no possible world could be such that “All heads of horses are heads of animals” would be false. Although we can perhaps not conceive of such a world, this failure of conception is not conclusive, as we can see by returning to fundamental questions about validity. We would not, for example, consider the following argument SL valid even though its conclusion is true: Jeeves is a good butler. Therefore, Paris is the capital of France.
Experimental arts in postwar Japan: moments of encounter, engagement, and imagined return

Miryam Sas’s latest book-length study is another major contribution to the scholarship reappraising the legacy of the avant-garde arts and films in Japan from the 1960s to the 1980s. The history of...
Chromosomal defects Detected by SNP-Array-Based Karyotyping Are Independent Predictors of Survival in Acute Myeloid Leukemia (AML)

Abstract Cytogenetics is the most important predictor of outcomes in AML. Traditional metaphase cytogenetics (MC), can detect abnormalities in only 40–60% of AML patients. Whole genome scanning by single nucleotide polymorphism arrays (SNP-A) can identify somatic chromosomal changes in hematopoietic malignancies and, due to its superb resolution, may detect previously cryptic unbalanced defects, even in samples deemed “normal” or uninformative using MC. Through simultaneous detection of loss of heterozygosity (LOH) and gene copy number changes, SNP-A also facilitate the identification of somatic segmental uniparental disomy (UPD). Here we tested whether SNP-A analysis could improve the detection rate of chromosomal defects in AML and enhances the prognostic value of MC. Analyses were performed using 250K and/or 6.0 Affymetrix SNP arrays on 140 primary (p) and secondary AML (sAML) patients (newly diagnosed= 107, relapsed=15, remission= 12, persistent=6) and 116 healthy controls. Data on cytogenetic detection rate, complete remission (CR), overall survival [OS], relapse free survival [RFS], remission duration [RD], and event free survival [EFS]) rates were obtained from patients who received induction chemotherapy. We also performed Flt-3 ITD, Flt-3 TKD and NPM-1 mutation analysis and integrated the clinical outcomes with SNP-A results. For patients in whom new defects were detected, germ-line DNA was also analyzed whenever technically possible. The cytogenetic abnormality detection rate in patients with active disease was higher with SNP-A compared to MC (pAML, 75% vs 43% p=
Outcomes of HER2-positive nonmetastatic breast cancer patients with or without deleterious BRCA mutations after trastuzumab treatment.

e12550 Background: Human epidermal growth factor receptor (HER2) overexpression or amplification occurs in 20–25% of all breast cancers and is associated with an aggressive form of the disease with...
Institutional Factors for Supporting Electronic Learning Communities

This study was designed to explore how the electronic learning community (eLC) process at an established state virtual high school (SVHS) supported new and veteran online high school teachers through the communities of practice (CoP) framework. Specifically, this study focused on the institutionally-driven nature of the eLC process, using Wenger’s CoP framework to analyze institutional factors that influenced the eLC process. Case study methods, including observation, interviews, and document analysis, were used to provide a rich and dynamic analysis of the eLC process in light of what research says about preparation and support for quality online teaching. While the institutionally-driven nature of the eLC process posed some barriers to alignment with the domain and community elements of the CoP framework, case study participants expressed that the eLC process impacted their practice and connected them to colleagues with which they could collaborate and problem solve. The use of strategies such as valuing the work of eLCs, removing barriers, and connecting the eLC process to the organizational strategy served to facilitate alignment with the CoP framework and overcome some of the potential disadvantages of an institutionally-driven eLC process.
Analytics in higher education: stakeholder perspective

The application of analytics to learners and their contexts, a field known as learning analytics, is increasingly gaining research attention. However, much of the published research to date has a relatively narrow focus of targets consisting of optimising pedagogical outcomes at the level of individual learning tasks or individual courses. Drawing on stakeholder theory, we identify a broader set of constituencies in higher education and argue that learning analytics has a much broader set of potential educational applications. We present emergent insights from an ongoing action research study conducted by an Analytics Task Force at a large public university in the north-east of the USA. We identify additional stakeholders who can benefit from the application of predictive models and we define the preliminary set of questions that can be addressed through predictive analytics for each stakeholder group. Our key contribution to the field of learning analytics is the expansion of learning analytics research landscape to include new stakeholders and new focal research questions.
Alternative Long-Run Goals and the Theory of the Firm: Why Profit Maximization May Be a Better Assumption Than You Think

For several decades, economists have subjected the assumption that firms maximize profits to a barrage of criticism. Firms maximize sales (Ref. 1). Firms maximize utility of profits and sales (Ref. 2). Firms maximize just about anything but profits.† And firms that have alternative goals, we are led to believe, do not exhibit profit-maximizing behavior. In this paper, we accept the fact that firms may have goals that differ from profit maximization, but we reject the conclusion that their behavior must differ from that of a profit-maximizing firm.
Enhanced light extraction from free-standing InGaN/GaN light emitters using bio-inspired backside surface structuring

Light extraction from InGaN/GaN-based multiple-quantum-well (MQW) light emitters is enhanced using a simple, scalable, and reproducible method to create hexagonally close-packed conical nano- and micro-scale features on the backside outcoupling surface. Colloidal lithography via Langmuir-Blodgett dip-coating using silica masks (d = 170-2530 nm) and Cl2/N2-based plasma etching produced features with aspect ratios of 3:1 on devices grown on semipolar GaN substrates. InGaN/GaN MQW structures were optically pumped at 266 nm and light extraction enhancement was quantified using angle-resolved photoluminescence. A 4.8-fold overall enhancement in light extraction (9-fold at normal incidence) relative to a flat outcoupling surface was achieved using a feature pitch of 2530 nm. This performance is on par with current photoelectrochemical (PEC) nitrogen-face roughening methods, which positions the technique as a strong alternative for backside structuring of c-plane devices. Also, because colloidal lithography functions independently of GaN crystal orientation, it is applicable to semipolar and nonpolar GaN devices, for which PEC roughening is ineffective.
Introduction: The Dialectics of Early Modern Orientalism

The introduction reviews the reception of Said’s Orientalism in early modern studies and situates the volume within the critical discourse about Orientalism by early modernists across disciplines. The authors propose to re-engage with the Saidian concept of Orientalism and suggest that the Orientalism of the sixteenth and seventeenth centuries constitutes a distinct historical chapter, characterized by its rhetorical multiplicity and dialectic quality. Early modern Orientalism is best understood as an open, creative, and flexible discourse, as a style of thought rather than a system of knowledge. The authors then demonstrate how the chapters of this interdisciplinary collection relate to the proposed dialectics of early modern Orientalism and to each other, creating dialectic effects among themselves.
Role of Disulfide Bonds on DNA Packaging Forces in Bull Sperm Chromatin

Abstract Short arginine-rich proteins called protamines mediate the near crystalline DNA packaging in most vertebrate sperm cells. Protamines are synthesized during spermiogenesis and condense the paternal genome into a transcriptionally inactive state in late-stage spermatids. Protamines from eutherian mammals, including bulls and humans, also contain multiple cysteine residues that form intra- and interprotamine sulfur-sulfur bonds during the final stages of sperm maturation. Although the cross-linked protamine network is known to stabilize the resulting nucleoprotamine structure, little is known about the role of disulfide bonds on DNA condensation in the mammalian sperm. Using small angle x-ray scattering, we show that isolated bull nuclei achieve slightly lower DNA packing densities compared to salmon nuclei despite salmon protamine lacking cysteine residues. Surprisingly, reduction of the intermolecular sulfur-sulfur bonds of bull protamine results in tighter DNA packing. Complete reduction of the intraprotamine disulfide bonds ultimately leads to decondensation, suggesting that disulfide-mediated secondary structure is also critical for proper protamine function. Lastly, comparison of multiple bull collections showed some to have aberrant x-ray scattering profiles consistent with incorrect disulfide bond formation. Together, these observations shed light on the biological functions of disulfide linkages for in vivo DNA packaging in sperm chromatin.
Unified Approach to Pavement Crack and Sealed Crack Detection Using Preclassification Based on Transfer Learning

AbstractThis work focuses on solving two challenging problems in pavement crack detection: (1) noises caused by complicated pavement textures and intensity inhomogeneity cannot be removed effective...
A Proof-of-Principle Quantitative EEG Study of an Oral, Potent and Selective T-Type Calcium Modulator in Healthy Volunteers (P4.261)

Objective: To study the pharmacodynamics (PD) of CX-8998, using pharmaco-electroencephalography (phEEG) and define plasma concentrations of CX-8998 which are pharmacologically active on objective CNS parameters. Background: PhEEG concerns the description and the quantitative analysis of the effects of substances on the CNS by means of electrophysiological methods. PhEEG has demonstrated its value in the development of CNS-active compounds in many instances, and is recognized as a PD marker to study the effects of drugs on brain functions in patients and healthy volunteers. Design/Methods: A randomized, double-blind, placebo-controlled, 3-period crossover study to evaluate the PD effects of single oral doses of CX-8998 in 12 healthy young male subjects. In each treatment period, each subject received single oral doses of Treatment A (CX-8998 5 mg), Treatment B (CX-8998 18 mg) or Treatment C (placebo). Endpoints in this analysis were the alpha, beta, gamma, delta and theta frequency band power in the awake state, in the eyes closed condition, post CX-8998 (5 and 18 mg) and placebo administration, measured at 1 and 3 hours post dose. EEG data from the electrode sites were scored by blinded personnel. Results: Analysis of awake phEEG revealed statistically significant, dose-dependent changes in EEG power density spectra in the alpha frequency band. PK/PD analyses suggest that reductions of alpha power of about 25% or greater occur in a concentration–dependent manner at plasma CX-8998 concentrations greater than 200 to 300 nM. The maximal reduction in alpha band power was observed at plasma CX-8998 concentrations of approximately 700–800 nM and greater. Conclusions: These data suggest that plasma concentrations in approximately the 200–800 nM range have CNS activity and may provide therapeutic efficacy and are used for dose setting in ongoing and planned clinical trials with CX-8998. Study Supported by: Study sponsored by Merck Inc Disclosure: Dr. Papapetropoulos has nothing to disclose. Dr. Boyer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Takeda, Cavion Inc. Dr. Lee has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Karyopharm Inc, Cavion Inc.
Debate: Cisplatin plus paclitaxel in the treatment of patients with metastatic/recurrent cervical cancer

t A c e ( i Background Invasive cervical cancer was once one of the most common malignancies to affect women in the United States. Although it remains a worldwide epidemic with greater than 500,000 new cases diagnosed annually, resulting in 250,000 deaths each year, the incidence of the disease in developed countries has decreased over the preceding 60 years. In 2009, it was estimated that there were 11,270 new cases of nvasive cervical cancer and approximately 4070 deaths. The vast majority of these deaths occur among patients with untreated locally advanced and metastatic disease as well as those whose disease recurs after definitive therapy for locally advanced lesions. The reasons for the decreased incidence of invasive cervical cancer in developed nations can be attributed primarily to screening programs using cervical cytology (ie, Papanicolaou testing). Because screening is available mainly to women who have health care coverage or who are able to pay out of pocket, advanced cases of disease now occur predominantly among poor women in developed countries and throughout impoverished regions of the world. Women diagnosed with invasive disease through screening programs are most likely to be found to have early-stage, and hence, curable lesions. Although algorithms exist that incorporate high-risk human papillomavirus DNA co-testing into screening programs that use cervical cytology, the degree of impact of dual modality of screening on ortality rates from cervical cancer is unclear at the present time. imilarly, vaccines that have been licensed by the United States Food
Natural Killer Cells and Diabetes Mellitus

Diabetes mellitus has been recognized since antiquity by the classic syndrome consisting of polyuria, polydipsia, polyphagia, and glycosuria. Diabetes is a group of disorders that are associated with hyperglycemia. It is a common, serious disease of the young with a prevalence rate of 0.3% in individuals under 20 and 0.5% for individuals under 60 years of age.(1,2) Diabetes causes appreciable morbidity secondary to the complications that affect many organ systems.
From molecules to medicines: the dawn of targeted therapies for genetic epilepsies

Precision medicine is the treatment of patients with therapy targeted to their specific pathophysiology. This lofty ideal currently has limited application in clinical practice. However, new technological advances in epilepsy models and genomics suggest that the precision medicine revolution is closer than ever before. We are gaining an improved understanding of the true complexity underlying the pathophysiology of genetic epilepsies and the sources of phenotypic variation that continue to frustrate efforts at genotype–phenotype correlation. Conventional experimental models of epilepsy, such as mouse models and heterologous expression systems, have provided many of the advances in our understanding of genetic epilepsies, but fail to account for some of these complexities. Novel high-throughput models of epilepsy such as zebrafish and induced pluripotent stems cells can be combined with CRISPR–Cas9 gene editing techniques to explore the pathogenesis of a specific gene change and rapidly screen drug libraries for potential therapeutics. The knowledge gained from these models must be combined with thorough natural history studies to determine appropriate patient populations for pragmatic clinical trials. Advances in the ‘omics’, genetic epilepsy models and deep-phenotyping techniques have revolutionary translational research potential that can bring precision medicine to the forefront of clinical practice in the coming decade. New technological advances in genomics have enabled the rapid discovery of hundreds of gene mutations linked to epilepsy. This Review considers the prospects for precision medicine in genetic epilepsies, the use of conventional and novel experimental models to unpick the complex pathogenic mechanisms of these diseases and the opportunities and challenges that face basic and clinical researchers.
Noncovalent structure of SENP1 in complex with SUMO2

SUMOylation is a post-translational modification in which a small ubiquitin-like molecule (SUMO) is appended to substrate proteins and is known to influence myriads of biological processes. A delicate interplay between several families of SUMOylation proteins and their substrates ensures the proper level of SUMOylation required for normal cell function. Among the SUMO proteins, SUMO2 is known to form mono-SUMOylated proteins and engage in poly-SUMO chain formation, while sentrin-specific protease 1 (SENP1) is a key enzyme in regulating both events. Determination of the SENP1–SUMO2 interaction is therefore necessary to better understand SUMOylation. In this regard, the current paper reports the noncovalent structure of SENP1 in complex with SUMO2, which was refined to a resolution of 2.62 A with R and Rfree values of 22.92% and 27.66%, respectively. The structure shows that SENP1–SUMO2 complex formation is driven largely by polar interactions and limited hydrophobic contacts. The essential C-terminal motif (QQTGG) of SUMO2 is stabilized by a number of specific bonding interactions that enable it to protrude into the catalytic triad of SENP1 and provide the arrangement necessary for maturation of SUMO and deSUMOylation activity. Overall, the structure shows a number of structural details that pinpoint the basis of SENP1–SUMO2 complex formation.
Hospice utilization among Medicare beneficiaries dying from pancreatic cancer.

BACKGROUND Use of hospice services among patients with pancreatic cancer following pancreatic resection remains unknown. METHODS Patients with pancreatic cancer who underwent resection were identified in the Medicare Standard Analytic Files. Outcomes included overall hospice use, early hospice enrollment (≥4 weeks before death), late hospice enrollment (initiation within 3 days of death), and Medicare expenditures. RESULTS Among the 4369 deceased individuals, three-fourths of patients (n = 3252, 74.4%) used hospice at the time of death. Patients who did not use hospice were more likely to be male, have a complication on index admission and receive life sustaining treatments on subsequent admissions (P < .05). Only one-third (32.2%) of patients initiated hospice services early. Medicare expenditure during the last month of life was $10 000 lower among patients who initialized hospice services at least 1 month before death versus within 3 days of death (late: $10 581 [$5454-$17 200], early: $221 [$46-$733]; P < .001) CONCLUSION: While three-fourths of patients utilized hospice services after pancreatic resection, only one-third of patients initiated hospice services at least one-month before death. Late hospice use was associated with higher Medicare expenditures during the last month of life. Further research is needed to understand barriers to early hospice utilization.
Observational and Modeling Study of Ice Hydrometeor Radar Dual-Wavelength Ratios

AbstractThe influence of ice hydrometeor shape on the dual-wavelength ratio (DWR) of radar reflectivities at millimeter-wavelength frequencies is studied theoretically and on the basis of observati...
Pharmacology and drug interactions with HIV PrEP in transgender persons receiving gender affirming hormone therapy

Transgender persons are at increased risk of HIV infection and would benefit from pre-exposure prophylaxis (PrEP) use. However, barriers to healthcare and a lack of data regarding PrEP efficacy amo...