cssi/SciSciGPT-SciSciNet huggingface dataset:
Statistical Spectral Analysis of Time Series Arising From Stationary Stochastic Processes

We consider time series which are realizations of a stochastic process. From the time series we construct various estimates of the spectral distribution function of the process (Section 3) and we study the sampling distributions of some functionals of these estimates (Sections 4-7). We then obtain confidence regions for the spectral distribution function and various tests of hypotheses in the normal case (Sections 8-10).
Treatment of Gays in a Straight Environment: Gay Alcoholics, Drug Addicts Survive a “Straight In-patient Milieu.”

There has been considerable discussion on the need for separate treatment programs and facilities for homosexual (gay) persons who are alcoholics and/or drug addicts. Some critics feel that a heterosexual (straight) environment is not conducive for gays because of their unique problems, life style and the lack of knowledge and understanding on the part of the heterosexual staff and patients. This supposedly would result in a lower recovery rate and a reduced number of gays seeking treatment than their straight counterparts. This paper addresses these issues and indicates that gays can survive and thrive in a straight in-patient treatment milieu.
First experiences with an AI-assisted clinical evidence system to evaluate clinical consensus among clinical trial publications.

e18583Background: The ability to review the most current evidence is pressured by the volume and rapid growth of new and sometimes inconsistent medical information. IBM Watson Evidence Service (WES...
Hemiparasitic plants increase alpine plant richness and evenness but reduce arbuscular mycorrhizal fungal colonization in dominant plant species

Hemiparasitic plants increase plant biodiversity by reducing the abundance of dominant plant species, allowing for the establishment of subordinate species. Hemiparasites reduce host resources by directly removing nutrients from hosts, competing for light and space, and may indirectly reduce host resources by disrupting plant associations with symbiotic root fungi, like arbuscular mycorrhizal fungi and dark-septate endophytes. Here, we explored how a generalist hemiparasite, Castilleja, influences plant richness, evenness, community composition, and mycorrhizal colonization patterns across a ∼1,000 m elevational gradient in the North American Rocky Mountains. We hypothesized that the presence of Castilleja would be associated with increased plant richness and evenness, shaping plant community composition, and would reduce mycorrhizal colonization within dominant plant taxa. However, the magnitude of the effects would be contingent upon climate contexts, that is, elevation. Overall, we found that the presence of Castilleja was associated with an 11% increase in plant richness and a 5% increase in plant evenness, regardless of elevation. However, we found that the presence of Castilleja influenced plant composition at only two of the five sites and at the remaining three of five sites, plot pairing was the only predictor that influenced composition. Additionally, we found that the presence of Castilleja reduced mycorrhizal fungal colonization within dominant plant species by ∼20%, regardless of elevation. Taken together, our results suggest that hemiparasites regulate plant diversity, evenness, and interactions with mycorrhizal fungi independent of abiotic and biotic contexts occurring at the site, although overall effect on community composition is likely driven by site-level factors.
New leads on vitamin E succinate-induced apoptosis signaling in prostate cancer cells

Proc Amer Assoc Cancer Res, Volume 45, 2004 1390 Previously α-tocopheryl succinate (vitamin E succinate, VES) has been reported to induce caspase-mediated apoptosis in PC-3 human prostate cancer cells (Zu K and Ip C. Cancer Res. 63: 6988-95, 2003). Caspase-9 was among several initiator caspases activated by VES, suggesting that the Bcl-2 family proteins, working via the mitochondrial pathway, were likely to be involved. To assess the effect of VES on mitochondrial regulation of apoptosis, several Bcl-2 member proteins were examined by Western blotting. The results showed that VES treatment increased the expression of some pro-apoptotic proteins, such as Bax and Bak. Although the expression level of Bcl-2 and Bad was unchanged by VES, the phosphorylation status of these two proteins was modulated in a manner consistent with an enhanced apoptotic response. The finding that VES caused changes in phosphorylated Bcl-2 and Bad implies that other kinase-type signaling molecules might also be recruited in the process. Microarray analysis was therefore carried out to identify additional VES targets that may contribute to apoptosis signaling. Akt1, an important cell survival molecule, emerged as a potential candidate, since it is known to phosphorylate Bad. Western blotting analysis comfirmed that phospho-Akt1, the active form of Akt1, was reduced by VES treatment in a time- and dose-dependent manner. Phospho-Forkhead transcription factor (FKHR), another downstream target of Akt1 associated with survival, was also decreased. Interestingly, the activity of PTEN and phosphoinositide-dependent kinase 1 (PDK 1), two upstream regulators of Akt1, was not affected. Nonetheless, the regulation of phospho-Akt1 by VES offers tantalizing clues with respect to the integration of the survival pathway and the mitochondrial control of apoptosis in VES signaling. Our microarray data also provided evidence that VES was able to activate the stress-induced MAPK cascade. Western blotting analysis showed increased protein level of Apoptosis signal-regulating kinase 1 (Ask1), JNK/Erk kinase (Sek1) and its cofactor GADD45, as well as increased phosphorylation of Sek1 and JNK. Further experimentation is currently underway to assess the functional significance of JNK pathway activation in VES-induced apoptosis. In summary, our study has generated a number of new leads regarding the molecular mechanism of action of VES in apoptosis induction.
Null donors favor prepared immunologists

In this issue of Blood, Golay et al carefully examine activation and effector functions of normal neutrophils and of FcγRIIIB (CD16B)–negative neutrophils isolated from the blood of a rare null donor.1 Their work reveals, for the first time, that normal neutrophils also express FcγRIIIA (CD16A) and that the 2 receptors on neutrophils mediate distinctly different effector functions for processing antibody-opsonized substrates.
Effect of sirolimus on coagulopathy of slow-flow vascular malformations.

Background/objectives Stagnant blood flow present in slow-flow vascular malformations can lead to localized intravascular coagulopathy (LIC), measured by elevated D-dimer levels, low fibrinogen, and/or thrombocytopenia. LIC can lead to localized thrombosis and/or bleeding, resulting in pain, swelling, and functional limitations. Patients with complex vascular malformations treated with sirolimus show clinical improvement in these symptoms. We hypothesized that the clinical benefits of sirolimus may correlate with improvements in coexisting LIC. Design/methods A retrospective chart review was performed, including D-dimer, fibrinogen, and platelet count, in patients with slow-flow vascular malformations treated with sirolimus. Laboratory values were assessed at three time points (presirolimus, 1-3 months postsirolimus, and last clinic visit). Clinical response, as defined by decreased pain and swelling, was extracted from the record. Results Thirty-five patients at our vascular anomalies center had been prescribed sirolimus between 2014 and 2017. Fifteen patients (12 combined slow-flow vascular malformations and three pure venous malformations) remained after excluding patients that did not have adequate records or a venous component to their vascular malformation. Patients who did not adhere to the treatment were also excluded. All 15 had elevated D-dimer levels prior to treatment and there was a statistically significant decrease in D-dimer levels following treatment with sirolimus. Symptomatic improvement of pain and swelling was reported after 3 months of starting sirolimus in 13/15 patients. Conclusion This study suggests that sirolimus improves coagulopathy in slow-flow vascular malformations, as evidenced by reduced D-dimer levels. Improvement in LIC symptoms also correlates with sirolimus-corrected coagulopathy.
Racial discrimination and alcohol problems among African American young adults: Examining the moderating effects of racial socialization by parents and friends.

Objective Racial discrimination is a stressor that may put African Americans at risk for alcohol use and related problems. We examined whether experiences of blatant (racist events) and subtle (racial microaggressions) forms of racial discrimination were associated with alcohol consumption and alcohol problems among African American young adults, and whether childhood/adolescence racial socialization by parents and friends moderated these associations. Method The sample included 383 African American young adults (Mage = 20.65, SD = 2.28; 81% female) who completed an electronic survey in Fall, 2017. Hierarchical linear regression analyses were conducted in Mplus. Results Experiences of racist events and racial microaggressions were associated with higher levels of alcohol consumption and more alcohol problems. Racial socialization by friends, but not parents, moderated these associations. Specifically, cultural socialization by friends buffered the effect of racist events on alcohol consumption and alcohol problems, whereas promotion of mistrust by friends exacerbated the effect of racial microaggressions on alcohol problems. Conclusions Both blatant and subtle forms of racial discrimination were associated with higher risk for alcohol use or problems among African American young adults. Racial socialization by friends while growing up may play an important role in alcohol use outcomes during young adulthood. Findings highlight the importance of considering different forms of racial discrimination and emphasize the unique roles of racial socialization across different social contexts (i.e., parent and peers or friends) in relation to psychosocial outcomes among African American individuals. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Hierarchical Bayesian models for continuous and positively skewed data from small areas

There are numerous types of continuous and positively skewed data. We develop a hierarchical Bayesian generalized gamma regression model for continuous and positively skewed data. For skewed data, ...
“Righting” Conventional Wisdom: Women and Right Parties in Established Democracies

Parties are the key actors shaping women's representation in advanced parliamentary democracies. Based on traditional patterns of feminist organizing, conventional wisdom suggests that parties of the left are the strongest advocates for women. Despite the prevalence of this claim, a burgeoning body of work indicates that parties on the right can—and often do—seek to represent women. To address these competing narratives, this article offers the first large-N, party-level study of women's descriptive and substantive representation over place and time. The results suggest that party ideology continues to affect women's representation: right parties lag behind their left counterparts with respect to women's presence in elected office, and right and left parties address women differently on their platforms. At the same time, there is significant heterogeneity among right parties. Christian democrats, for example, are more likely than conservatives to adopt voluntary gender quotas and make policy claims on behalf of women. The traditional left-right distinction is thus too coarse to fully explain party behavior in these states.
Introduction to the Special Issue on Early Care and Education Collaboration

ABSTRACTThe Special Issue on Early Care and Education (ECE) collaboration presents seven articles – followed by a commentary – that describe collaborations among different ECE programs. The article...
Pancake sea ice kinematics and dynamics using shipboard stereo video

In the marginal ice zone, surface waves drive motion of sea ice floes. The motion of floes relative to each other can cause periodic collisions, and drives the formation of pancake sea ice. Additionally, the motion of floes relative to the water results in turbulence generation at the interface between the ice and ocean below. These are important processes for the formation and growth of pancakes, and likely contribute to wave energy loss. Models and laboratory studies have been used to describe these motions, but there have been no in situ observations of relative ice velocities in a natural wave field. Here, we use shipboard stereo video to measure wave motion and relative motion of pancake floes simultaneously. The relative velocities of pancake floes are typically small compared to wave orbital motion (i.e. floes mostly follow the wave orbits). We find that relative velocities are well-captured by existing phase-resolved models, and are only somewhat over-estimated by using bulk wave parameters. Under the conditions observed, estimates of wave energy loss from ice–ocean turbulence are much larger than from pancake collisions. Increased relative pancake floe velocities in steeper wave fields may then result in more wave attenuation by increasing ice–ocean shear.
Erich Meyerhoff: a man for all medical librarians

Erich Meyerhoff—recipient of the Marcia C. Noyes Award, Janet Doe Lecturer, and Fellow—was one of the Medical Library Association’s (MLA’s) most illustrious members who contributed to the welfare of MLA and its members throughout his long life. The authors review his life and significant contributions to the health sciences library profession. Erich was a friend and mentor to countless medical librarians and was truly a man for all medical librarians.
The Effect of Recombinant Tags on Citrus paradisi Flavonol-Specific 3-O Glucosyltransferase Activity

Recombinant tags are used extensively in protein expression systems to allow purification through IMAC (Immobilized Metal Affinity Chromatography), identification through Western blot, and to facilitate crystal formation for structural analysis. While widely used, their role in enzyme characterization has raised concerns with respect to potential impact on activity. In this study, a flavonol-specific 3-O glucosyltransferase (Cp3GT) from grapefruit (Citrus paradisi) was expressed in Pichia pastoris, and was assayed in its untagged form and with a C-terminal c-myc/6x His tag under various conditions to determine the effect of tags. Prior characterization of pH optima for Cp3GT obtained through expression in Escherichia coli, containing an N-terminal thioredoxin/6x His tag, indicated an optimal pH of 7–7.5, which is indicative of a normal physiological pH and agrees with other glucosyltransferase (GT) pH optima. However, characterization of Cp3GT expressed using P. pastoris with a C-terminal c-myc-6x His tag showed a higher optimal pH of 8.5–9. This suggests a possible tag effect or an effect related to physiological differences between the cell expression systems. Results testing recombinant Cp3GT expressed in Pichia with and without C-terminal tags showed a possible tag effect with regard to substrate preference and interactions with metals, but no apparent effect on enzymatic kinetics or pH optima.
The value of scientific research on the ocean's biological carbon pump.

Abstract The ocean's biological carbon pump (BCP) sequesters carbon from the surface to the deep ocean and seabed, constituting one of Earth's most valuable ecosystem services. Significant uncertainty exists surrounding the amounts and rates of organic carbon sequestered in the oceans, however. With improved understanding of BCP sequestration, especially its scale, world policymakers would be positioned to make more informed decisions regarding the mitigation of carbon emissions. Here, an analytical model of the economic effects of global carbon emissions—including scientific uncertainty about BCP sequestration—was developed to estimate the value of marine scientific research concerning sequestration. The discounted net economic benefit of a putative 20-year scientific research program to narrow the range of uncertainty around the amount of carbon sequestered in the ocean is on the order of $0.5 trillion (USD), depending upon the accuracy of predictions, the convexities of climate damage and economic output functions, and the initial range of uncertainty.
Lower Urinary Tract Symptoms

The lower urinary tract consists of interrelated structures including the bladder, urethra, smooth, and striated sphincters, pelvic floor muscles, and the prostate gland in men with a common function of providing effective urinary storage and voluntary urinary expulsion. These functions are achieved in two discrete phases of micturition [1].
The Hidden Curriculum: Strategies for Preparing Residents for Practice.

PURPOSE OF REVIEW The goal of this paper was to identify areas of importance in modern urology education that are not currently emphasized in current urological curricula. RECENT FINDINGS We identified curricular deficits in robotic surgical simulation, transgender health, leadership, business management, and social media training. Few practicing urologists feel comfortable managing transgender-specific needs, and most training programs do not adequately address transgender health. Urology programs also do not sufficiently emphasize topics in leadership, business management, or appropriate social media usage. With respect to simulation, while it is currently included in the Accreditation Council for Graduate Medical Education (ACGME) program requirements, it is currently under-utilized for training in robotic surgery. It is important for urologists to receive adequate training for the modern practice landscape. Where knowledge gaps among early practicing urologists arise, programs should adapt their curricula to address them.
Reconsidering Academic Rigor: Posing and Supporting Rigorous Course Practices at Two Research Institutions:

Background/ContextU.S. institutions of higher education have been criticized for providing limited learning gains and lacking rigor. Most understandings of academic rigor in higher education focus ...
Managing Population Health: An Ontological Framework

The science of eliminating health disparities is a component of the problem of managing population health. It is embedded in a complex system of [science/practice/policy] of/for [eliminating/decreasing/ understanding & addressing/increasing/universalizing] population [health/disease] [disparities/parities]. The system includes practices which introduce health parities (for example, vaccinating all children), policies which increase disease disparities (for example, limited reimbursement for preventive care), and 58 other components encapsulated in the ontological framework. The framework includes all the three components of translation, has symmetric objectives ranging from eliminating to universalizing, and includes the complements of both health and disparities. In this milieu, an exclusive focus on the science of eliminating health disparities would be ineffective – the approach has to be inclusive and systemic. A qualitative meta-analysis of the last 10 years’ literature reveals the biases, and the ‘bright’, ‘light’, and ‘blind’ spots in the current knowledge to manage population health. The analysis will help develop a systemic approach to the problem and thereby to systematically eliminate health disparities.
An Open-source Framework for Autonomous SoC Design with Analog Block Generation

We present the world's first autonomous mixed-signal SoC framework, driven entirely by user constraints, along with a suite of automated generators for analog blocks. The process-agnostic framework takes high-level user intent as inputs to generate optimized and fully verified analog blocks using a cell-based design methodology. Our approach is highly scalable and silicon-proven by an SoC prototype which includes 2 PLLs, 3 LDOs, 1 SRAM, and 2 temperature sensors fully integrated with a processor in a 65nm CMOS process. The physical design of all blocks, including analog, is achieved using optimized synthesis and APR flows in commercially available tools. The framework is portable across different processes and requires no-human-in-the-Ioop, dramatically accelerating design time.
Visualization of Low-Density Flows by Means of Oxygen Absorption of Ultraviolet Radiation

The high absorption of ultraviolet radiation (1,400 A.-l,500 A.) by ox3^gen has been employed to obtain photographs of several flow configurations. A vacuum spectrograph-monochromatorcamera with a 1,470 A. radiation source was adapted for installation in the low-density wind tunnel of the University of California at Berkeley. The photographs taken were of shock waves formed by flow over a sphere, a cone-cylinder, wedges, and a cylinder with axis aligned parallel to the direction of the flow. All photographs were taken at a free-stream Mach Number of ^ 3 . 9 , with a uniform jet area approximately two in. in diameter at the nozzle exit plane, and a tunnel test chamber static pressure of ^114// Hg. An analytical method of determining stream density in axially symmetric flow from the absorption of radiation as indicated by the photographs is presented. Limitations of the method are discussed.
Per-Flow Size Estimators

This chapter discusses the measurement of per-flow sizes for high-speed links. It is a particularly difficult problem because of the need to process and store a huge amount of information, which makes it difficult for the measurement module to fit in the small but fast SRAM space (in order to operate at the line speed). We provide a novel measurement function that estimates the sizes of all flows. It delivers good performance in tight memory space where other approaches no longer work. The effectiveness of the online per-flow measurement approach is analyzed and confirmed through extensive experiments based on real network traffic traces.The rest of this chapter is organized as follows: Sect. 2.1 discusses the performance metrics. Section 2.2 gives an overview of the system design. Section 2.3 discusses the state of the art. Section 2.4 presents the online data encoding module. Sections 2.5–2.6 present two offline data decoding modules. Section 2.7 discusses the problem of setting counter length. Section 2.8 addresses the problem of collecting flow labels. Section 2.9 presents the experimental results. Section 2.10 extends the estimators for large flow sizes. Section 2.11 gives the summary.
Receptor-Mediated Stimulation and Inhibition of Adenylate Cyclase

Publisher Summary This chapter discusses the stimulation of adenylate cyclase and discusses the inhibition of adenylate cyclase by receptors. Many hormones interact with cell surface receptors to transmit a stimulatory signal to the catalytic unit of adenylate cyclase through the intervention of a guanosine-5'-triphosphate (GTP) regulatory protein (termed Ns)2. The hormone binds to receptors and leads to the release of previously bound guanosine diphosphate (GDP) (an ineffective stimulator), which allows occupancy by GTP and, consequently attains a more active RsNsC complex. On hydrolysis of GTP to GDP, the complex reverts to an inactive form, which coincides with the release of hormone. Early observations on fat cell membranes indicated that GTP concentrations exceeding 1 μM reduce adenylate cyclase activity. Evidence showed that the cyclic AMP production can be decreased by a number of agents, such as adenosine and PGE, in adipocytes. Several reports demonstrated that adenylate cyclase activity could be inhibited in various broken cell preparations by, for example, muscarinic cholinergic drugs, nor- epinephrine, and opiates. Treatment of fat cell membranes (or cells prior to membrane preparation) with either trypsin or cholera toxin and NAD, or assaying in the presence of Mn2+ resulted in the abolition of the inhibitory response to GTP. In contrast, treatment of membranes with p-hydroxymercuriphenylsulfonic acid eliminated stimulation but retained inhibition by GTP.
Structural studies by nuclear magnetic resonance—XVIII : Conformational and configurational isomerism of N-alkyl imines☆

Abstract Conformations and configurations were assigned to several N-Me imines and N-alkyl acetaldimines from analyses of their 60-Mc NMR spectra. All aldimines exist exclusively in the syn configuration. Interpretation of the vicinal and long-range (across 4 and 5 and bonds) spin-spin coupling constants of N-Me aldimines led to the conclusion that I and II are the minimum energy conformations of these compounds. The ΔH° values for I ⇌ II fall between those of aldehydes, which are usually negative, and those of oximes and their O-methyl ethers, which are positive. Interpretation of the long-range (across 4 and 5 bonds) spin-spin coupling constants of N-alkyl acetaldimines led to the conclusion that III is far more stable than IV. The greater thermodynamic stabilities of the syn over the anti isomers of aldimines and III over IV have been explained in terms of nonbonded interactions across the CN double bond. The results of some of these calculations are given.
Nocturnal Behavior of the Common Loon, Gavia immer

Very little is known about nocturnal activity of Common Loons ( Gavia immer ). Knowledge of both diurnal and nocturnal behavior is needed to gain a complete understanding of their ecology. I used night vision light intensifiers to observe nocturnal behaviors of Common Loons. Results were consistent with the hypothesis that, as visual predators, loons would not forage at night and also that they would spend the majority of their time resting (92%). Loons, however, were just as active locomoting (patrolling) during the night as they were during the day. This suggests daily energy budgets need to be reexamined to incorporate this overlooked aspect of loon behavior. Lastly, loons on large lakes with multiple loon territories spent more time locomoting than loons on lakes that had just a single pair.
On Making and Breaking Contracts

This article discusses purchase agreements and the clauses affecting their termination and extension, including the question of when the contract is formed and what happens when a party is defrauded out of a contract rather into one. Also covered are ‘time is of the essence’ issues.
Generation of Deletions and Duplications Using Transposons as Portable Regions of Homology with Emphasis on Mud and Tn10 Transposons

Abstract In bacteria complementation and dominance testing requires the establishment of a diploid state for the gene of interest. In addition, it is often desirable to characterize reporter fusion constructs in strains with both the reporter fusion and an intact gene copy present in single copy. Transposons provide portable regions of homology to facilitate construction of targeted chromosomal rearrangements such as deletions and duplications. The properties of the large Mud transposons, MudA and MudB allow for the direct duplication and deletion of virtually any region of the Salmonella enterica chromosome between the points of two Mud insertions in a simple bacteriophage P22 transductional cross. Furthermore, duplication construction will be described for the generation of strains with a lac operon transcriptional fusion or lacZ gene translational fusion to any gene of interest at the join‐point of the duplication with a second intact copy of the gene of interest located in tandem single copy in the same chromosome. In addition, methods for generation of tandem chromosomal duplications using transposon Tn 10 as portable regions of homology are presented. These allow construction of strains duplicated for any gene of interest in tandem, single copy on the chromosome to allow for complementation and dominance testing for alleles for virtually any gene.
Geo-Science Related Aspects of Geopressure Energy

Geo-science related aspects of geopressure energy have been critically reviewed. Geopressure is defined as any pressure that exceeds the hydrostatic column of water extending from the reservoir zone to the land surface. The U.S. Geological Survey estimates that the thermal-mechanical energy in geopressure reservoirs in the Texas and Louisiana coasts alone is about 34,000 MW-centuries. This paper has attempted to cover reservoir geology, reservoir chemistry, and environmental consequences and ways to handle them. The importance of geology, geomechanics, and geochemistry and their synergy in exploitation strategy has been highlighted. The need for new analytical models covering the response of the geomass, consisting of rock matrix and sediment clay, and its intercoupling with the motion of the geofluids in the presence of terrestrial heat flow is stressed. The effect of reservoir geometry in the selection of reservoir well spacing has been discussed.
Abstract 1713: PDK1 and hexokinase 2 are downstream effectors of PTEN loss and regulate response to targeted therapies in multiple tumor types

Recent advances in molecular profiling of many human tumor types has enabled the development and clinical use of molecularly-targeted therapies in patients. Many tumors exhibit inactivation of PTEN which is predicted to sensitize tumor cells to PI3 kinase or AKT inhibitor therapy. However, clinical responses to PI3 kinase or AKT inhibitors are variable and not curative. Furthermore, these responses in patients do not correlate uniformly with PTEN inactivation. Therefore, we investigated whether PTEN inactivation could lead to dependence on signaling pathways and components that function independently of PI3K or AKT and that could serve as novel therapeutic targets in PTEN deficient tumors. Using multiple human tumor models including lung adenocarcinoma, lung squamous, renal cell carcinoma, and prostate adenocarcinoma that express or lack PTEN and Gene Set Enrichment Analysis, we identified alterations in numerous metabolic regulatory genes in response to PTEN inactivation, including hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1). We found that in PTEN-deficient tumor cells HK2 is upregulated and selectively localizes to the mitochondria, where it enhances glycolytic flux and inhibits apoptosis. Furthermore, we found that PDK1 is also upregulated upon PTEN inactivation and suppresses oxidative phosphorylation, upregulating glycolysis and the production of lactate. Thus, we uncovered a novel role for HK2 and PDK1 in the metabolic reprogramming that occurs as a consequence of PTEN inactivation in tumor cells. Furthermore, we found that overexpression of either HK2 or PDK1 confers resistance to targeted therapies against PI3K and other oncogenic drivers more broadly. Conversely, genetic or pharmacological suppression of HK2 or PDK1 enhances response to targeted therapy in multiple tumor cell types. Together, our data identify HK2 and PDK1 as novel molecular biomarkers and promising therapeutic targets in multiple PTEN deficient tumor types. Citation Format: Evangelos Pazarentzos, Trever G. Bivona. PDK1 and hexokinase 2 are downstream effectors of PTEN loss and regulate response to targeted therapies in multiple tumor types. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1713. doi:10.1158/1538-7445.AM2014-1713
Reticular macular lesions: a review of the phenotypic hallmarks and their clinical significance

Reticular macular lesions, also known as ‘reticular macular disease’, ‘reticular drusen’, ‘reticular pseudodrusen’, or ‘subretinal drusenoid deposits’, are a pattern of lesions commonly found in age-related macular degeneration and best visualized using at least two imaging techniques in combination. Reticular lesions have four stages of progression observable on spectral domain optical coherence tomography, but they do not show the usual signs of regression of soft drusen (calcification and pigment changes). Furthermore, reticular lesions correlate histologically with subretinal drusenoid deposits localized between the retinal pigment epithelium and the inner segment ellipsoid band. Reticular lesions are most commonly seen in older age groups of female patients with age-related macular degeneration and are usually bilateral. They are not clearly associated with known age-related macular degeneration genes and are highly associated with late-stage age-related macular degeneration and an increased mortality rate. They are also associated with alterations in the neural retina and choroid.
Pseudo-dyadic “interaction” on Amazon’s Mechanical Turk

Psychological researchers have begun to utilize Amazon’s Mechanical Turk (MTurk) marketplace as a participant pool. Although past work has established that MTurk is well suited to examining individual behavior, pseudo-dyadic interactions, in which participants falsely believe they are interacting with a partner, are a key element of social and cognitive psychology. The ability to conduct such interdependent research on MTurk would increase the utility of this online population for a broad range of psychologists. The present research therefore attempts to qualitatively replicate well-established pseudo-dyadic tasks on MTurk in order to establish the utility of this platform as a tool for researchers. We find that participants do behave as if a partner is real, even when doing so incurs a financial cost, and that they are sensitive to subtle information about the partner in a minimal-groups paradigm, supporting the use of MTurk for pseudo-dyadic research.
In vivo demonstration of the presence of specific saturable binding sites for triiodothyronine in nuclei of tadpole liver.

Abstract The binding of l -triiodothyronine (T3) by subcellular fractions of tadpole liver has been studied following in vivo administration of [125I]T3. A steady state between T3 in the nuclei and T3 in the extranuclear fraction of liver was reached 2 hr after intraperitoneal injection of a low dose of [125I]T3 into animals maintained at 25°. Saturable binding sites for T3 were not detectable in mitochondrial and microsomal fractions but were definitely present in nuclei and possibly cytosol. As determined by a loading experiment, the maximum binding capacity of the T3 binding sites in nuclei was 350 fmol/mg DNA or about 2700 molecules of T3 per nucleus. Injection of a high dose of an unlabeled iodothyronine simultaneously with a tracer dose of [125I]T3 indicated that 3′-isopropyldiiodothyronine competed most effectively for the nuclear T3 binding sites followed closely by triiodothyronine and thyroxine, while 3,5-diiodothyronine had the least competitive effect. Analysis of subnuclear fractions for distribution of radioactivity, after in vivo labeling of nuclei with a small dose of [125I]T3, indicated that 63% of the hormone was associated with chromatin. Extraction of nuclei with 0.8 M KCl removed about 50% of the macromolecular bound [125I]T3. Chromatographic analysis of the 0.8 M KCl extract on Sephadex G-200 indicated a molecular weight in the range 70–80,000 for the T3 binding macromolecule(s) in tadpole liver nuclei.
Interviewing undocumented immigrants : methodological reflections based on fieldwork in Mexico and the U.S.

This article discusses data collection methods and basic issues of research strategy in field studies of unapprehended illegal immigrants living in the United States. It suggests ways to increase the reliability and validity of interview responses. Necessary modifications in format and style of interviews are described. An annotated bibliography of recent field studies of undocumented immigrants is provided. (EXCERPT)
Degradation of dynorphin-(1–13) by membrane-bound rat brain enzymes

Abstract Under the incubation conditions of the opioid receptor binding assay, dynorphin-(1–13) is metabolized by membrane-bound exopeptidases which cleave the NH2-terminal tyrosine and the COOH-terminal lysine. Enzymatic attack, particularly that of carboxypeptidase, is extremely rapid. Following a 5 min incubation at 22°C with wellwashed brain membranes (0.5 ml; 1 g original wet weight per 100 ml), less than 50% of dynorphin-(1–13) (20 nM) remains intact. Various methods of stabilization of dynorphin-(1–13) have been examined. Degradation can be reduced, but not eliminated, by the use of metabolic inhibitors or by lowering the incubation temperature to 0°C. Substitution of an amide or methyl ester function at the carboxyl terminus of the peptide provides complete protection not only from carboxypeptidase attack but also from aminopeptidase attack. Carboxyl-substituted compounds are limited in their usefulness as stable analogues, however, since they are not resistant to hydrolysis in the presence of physiological salts.
TLINE: Software for sinusoidal steady-state analysis of transmission lines

This article describes the use of the software package TLINE, which includes three programs for the sinusoidal steady-state analysis of transmission lines. The first program provides analysis of the tandem connection of several transmission lines with the possibility of including PI, T, or L lumped-element discontinuity junctions between the transmission lines. The other two programs are related to analysis of impedance matching using single and double stubs. All analysis procedures are graphically displayed on Smith charts. Output files that include numerical values of input impedances, values of time-average powers, and reflection coefficients at various sections of a tandem transmission line system are included. The TLINE software package is used to train students on the use of the Smith chart and also to help in the teaching and demonstration of various transmission line and impedance-matching concepts.
THE STABILITY OF PLANE POISEUILLE FLOW

The problem of the stability of plane Poiseuille flow to small disturbances leads to a characteristic value problem for the Orr-Sommerfeld equation with given boundary conditions. It happens that negative values of the imaginary parts of the characteristic numbers, which indicate instability, are small, at any rate over the region here investigated, and considerable accuracy is required to establish them, while the Reynolds numbers for which they occur are large.In this paper the fourth-order differential equation is replaced by a difference system of the same order with a truncation error involving the eighth derivative, so that the error is sufficiently small with a reasonably large interval. The resulting system of linear algebraic equations is solved by direct Gaussian elimination, which avoids the difficulties due to rapid exponential growth of error for high Reynolds number which beset the standard integration procedure.The characteristic value is obtained for a range of Reynolds numbers and wavelengths of the disturbance, and the critical Reynolds number found to be 5780 for wavelength 3.062 times the width of the channel. A detailed discussion of the accuracy of the work is given for the (unstable) case of wavelength $\ensuremath{\pi}$ and Reynolds number 10 000, and a table of the profile of the disturbance is given for this case.
Microcontact printing for co-patterning cells and viruses for spatially controlled substrate-mediated gene delivery

Spatial organization of gene expression is a crucial element in the development of complex native tissues, and the capacity to achieve spatially controlled gene expression profiles in a tissue engineering construct is still a considerable challenge. To give tissue engineers the ability to design specific, spatially organized gene expression profiles in an engineered construct, we have investigated the use of microcontact printing to pattern recombinant adeno-associated virus (AAV) vectors on a two dimensional surface as a first proof-of-concept study. AAV is a highly safe, versatile, stable, and easy-to-use gene delivery vector, making it an ideal choice for this application. We tested the suitability of four chemical surfaces (–CH3, –COOH, –NH2, and –OH) to mediate localized substrate-mediated gene delivery. First, polydimethylsiloxane stamps were used to create microscale patterns of various self-assembled monolayers on gold-coated glass substrates. Next, AAV particles carrying genes of interest and human fibronectin (HFN) were immobilized on the patterned substrates, creating a spatially organized arrangement of gene delivery vectors. Immunostaining studies reveal that –CH3 and –NH2 surfaces result in the most successful adsorption of both AAV and HFN. Lastly, HeLa cells were used to analyze viral transduction and spatial localization of gene expression. We find that –CH3, –COOH, and –NH2 surfaces support complete uniform cell coverage with high gene expression. Notably, we observe a synergistic effect between HFN and AAV for substrate-mediated gene delivery. Our flexible platform should allow for the specific patterning of various gene and shRNA cassettes, resulting in spatially defined gene expression profiles that may enable the generation of highly functional tissue.
Analysis of mRNA Profiles after MEK1/2 Inhibition in Human Pancreatic Cancer Cell Lines Reveals Pathways Involved in Drug Sensitivity

Mutationally activated KRAS , detected in approximately 90% of pancreatic ductal adenocarcinomas (PDA), has proven an intractable pharmacologic target to date. Consequently, efforts to treat KRAS -mutated cancers are focused on targeting RAS-regulated signaling pathways. In mouse models, expression of BRAFV600E combined with dominant-negative TP53 elicits PDA, and pharmacologic blockade of mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibits proliferation of human PDA-derived cell lines. To better understand the role of RAF→MEK→ERK signaling on PDA cell proliferation, we assessed the consequences of MEK inhibition on global patterns of mRNA expression and tumor cell proliferation in a panel of human PDA-derived cell lines. This analysis revealed that RAF→MEK→ERK signaling regulates mRNAs involved in cell-cycle control as well as regulators of the immune system. Linear regression analysis of relative drug sensitivity and mRNA expression revealed mRNAs and pathways correlating with relative drug sensitivity of the cell lines. Mice carrying orthotopically implanted pancreas tumors that were treated with MEK inhibitor displayed reduced tumor growth, concomitant with a reduction of cells in S phase. Furthermore, analysis of tumor mRNA expression revealed PDA cell lines to display similar baseline and MEK inhibitor mRNA expression profiles in vitro and in vivo . Among the proteins subject to downregulation following MEK inhibition, we identified c-MYC as a key driver of cell proliferation downstream of RAF→MEK→ERK signaling. Indeed, in some PDA cell lines, RNA interference–mediated silencing of c-MYC expression had antiproliferative effects similar to that of MEK inhibition, thereby highlighting the importance of c-MYC in key aspects of pancreatic cancer cell maintenance. Mol Cancer Res; 10(12); 1607–19. ©2012 AACR . This article is featured in Highlights of This Issue, [p. 1511][1] [1]: /lookup/volpage/10/1511?iss=12
Ongoing movement of the hermit warbler X Townsend's warbler hybrid zone.

Background Movements of hybrid zones – areas of overlap and interbreeding between species – are difficult to document empirically. This is true because moving hybrid zones are expected to be rare, and because movement may proceed too slowly to be measured directly. Townsend's warblers (Dendroica townsendi) hybridize with hermit warblers (D. occidentalis) where their ranges overlap in Washington and Oregon. Previous morphological, behavioral, and genetic studies of this hybrid zone suggest that it has been steadily moving into the geographical range of hermit warblers, with the more aggressive Townsend's warblers replacing hermit warblers along ∼2000 km of the Pacific coast of Canada and Alaska. Ongoing movement of the zone, however, has yet to be empirically demonstrated. Methodology/Principal Findings We compared recently sampled hybrid zone specimens to those collected 10–20 years earlier, to test directly the long-standing hypothesis of hybrid zone movement between these species. Newly sampled specimens were more Townsend's-like than historical specimens, consistent with ongoing movement of the zone into the geographical range of hermit warblers. Conclusions/Significance While movement of a hybrid zone may be explained by several possible mechanisms, in this case a wealth of existing evidence suggests that movement is being driven by the competitive displacement of hermit warblers by Townsend's warblers. That no ecological differences have been found between these species, and that replacement of hermit warblers by Townsend's warblers is proceeding downward in latitude and elevation – opposite the directions of range shifts predicted by recent climate change – further support that this movement is not being driven by alternative environmental factors. If the mechanism of competitive displacement is correct, whether this process will ultimately lead to the extinction of hermit warblers will depend on the continued maintenance of the dramatic competitive asymmetry observed between the species.
The Drosophila patched gene encodes a putative membrane protein required for segmental patterning

The patched (ptc) gene is one of several segment polarity genes required for correct patterning within every segment of Drosophila. The absence of ptc gene function causes a transformation of the fate of cells in the middle part of each segment so that they form pattern elements characteristic of cells positioned around the segment border. Analysis of the mutant phenotype demonstrates that both segment and parasegment borders are included in the duplicated pattern of ptc mutants. We have cloned the ptc gene and deduced that the product is a 1286 amino acid protein with at least seven putative transmembrane alpha helices. ptc RNA is expressed in embryos in broad stripes of segmental periodicity that later split into two stripes per segment primordium. The pattern of expression does not directly predict the transformation seen in ptc mutant embryos, suggesting that ptc participates in cell interactions that establish pattern within the segment.
Social spending: Managing the social media mix

Abstract There is incessant demand for ‘proof’ of return on investment (ROI) for social media spending, and a significant degree of uncertainty among marketers with respect to allocating effort and budget to social media. In this article, we address these issues by identifying different ways that organizations use social media, highlighting important distinctions in these approaches and describing how to frame the spending decision for social media. Additionally, we identify dimensions that can be used to differentiate important types of social media in a social media mix, and relate this to tactical marketing execution. We also highlight the different nature of social objectives, the ‘backward’ process for meeting them, and the importance of establishing a social media ‘mission control’ as part of that process.
Identifying objects: five categories

Acknowledges that research on objects belonging to the categories of furniture, glass and stained glass, metalware, pottery and porcelain, or rugs and carpets involves the consultation of specific handbooks and guides. Lists, with a brief description, various decorative‐art reference books as sources for research in these categories, and offers relevant subject headings so that the New York Public Library’s catalogs can be checked for similar holdings.